Medicines information services

Information on any aspect of dr ug therapy can be

obtainedfrom Regionaland DistrictMedicines Informa-

tionSer vices.Details regarding the

local

services pro-

videdwithin your Regioncan be obtained bytelephon-

ingthe following numbers.

England

Birmingham (0121)424 7298

Bristol (0117)342 2867

Ipswich (01473)704 431

Leeds (0113) 2065377

Leicester (0116)255 5779

Liverpool (0151)794 8113/4/5/7

(0151)794 8206

London

Guy’sHospital (020)7188 8750

(020)7188 3849

(020)7188 3855

NorthwickPark Hospital (020) 88692761

(020)8869 3973

Newcastle (0191)282 4631

Southampton (023)8079 6908/9

Wales

Cardiff (029)2074 2979

(029)2074 2251

Scotland

Aberdeen (01224) 552316

Dundee (01382)632 351

(01382)660 111 Extn32351

Edinburgh (0131)242 2920

Glasgow (0141) 2114407

NorthernIreland

Belfast (028) 90632032

(028)9063 3847

Republicof Ireland

Dublin Dublin473 0589

Dublin453 7941 Extn2348

UnitedKingdom MedicinesInfor mationPharma-

cistsGroup (UKMIPG) website

www.ukmi.nhs.uk

Telephonenumbers and email addresses of manu-

facturerslisted inBNF Publications areshown inthe

Indexof Manufacturers

UKTeratology Information Service

Information on drug and chemical exposures in

pregnancy

Tel:0844 892 0909

Information on drug therapy relating to dental

treatmentcan be obtained bytelephoning

Liverpool (0151)794 8206

Driverand Vehicle LicensingAgency (DVLA)

Information on the national medical guidelines of

ﬁtnessto drive is availablefrom:

www.dvla.gov.uk/medical.aspx

PatientInformation Lines

NHSDirect 08454647

PoisonsInformation Services

UKNational Poisons Information

Service

0844892 0111

Sport

Information on substances currently permitted or

prohibitedis providedin acard supplied byUK Anti-

doping.

Furtherinformation regarding medicines in sportis

availablefrom: www.ukad.org.uk

Tel:(020) 7766 7350

information@ukad.org.uk

TravelImmunisation

Up-to-date information on travel immunisation

requirementsmay be obtained from:

National Travel Health Network and Centre (for

healthcare professionals only) 0845 602 6712

(09.00–12.00and 14.00–16.30 hours weekdays)

TravelMedicine Team, Health Protection Scotland

(0141)300 1130 (14.00–16.00 hoursweekdays)

www.travax.nhs.uk(for registered users ofthe NHS

websiteTravax only)

Welsh Assembly Government (029) 2082 5397

(09.00–17.30hours weekdays)

Departmentof Health and Social Services (Belfast)

(028)9052 2118 (weekdays)

Listof Registered Medical Practitioners

Detailson whetherdoctors are registeredand holda

licence to practise medicine in the UK can be

obtainedfrom the General MedicalCouncil.

Tel:(0161) 923 6602

www.gmc-uk.org/register

BNF

March 2011

British

National

Formulary

Publishedjointly by

BMJGroup

TavistockSquare, London WC1H9JP, UK

and

Pharmaceutical Press

Pharmaceutical Press is the publishing division of the

RoyalPharmaceutical Society

1Lambeth High Street, London,SE1 7JN, UK

Societyof Great Britain 2011

ISBN:978 0 85369 9620

ISSN:0260-535X

Printedby CPI Clausen &Bosse, Leck, Germany

Typesetby Xpage

A cataloguerecord for this book is available from the

BritishLibrary.

Allrights reserved. No part of this publication may be

reproduced,stored in aretrieval system, or transmitted

inany form or byany means, without theprior written

permissionof the copyright holder.

Material published in the

British National Formu-

lary

may not be used for any form of advertising,

salesor publicitywithout prior written permission.

Eachof the classiﬁcation andthe text are protected

bycopyright and/or databaseright.

Papercopies maybe obtainedthrough anybookseller or

directfrom:

PharmaceuticalPress

c/oMacmillan Distribution (MDL)

BrunelRd

Houndmills

Basingstoke

RG216XS

Tel:+44 (0) 1256302 699

Fax:+44 (0) 1256 812521

Email:direct@macmillan.co.uk

www.pharmpress.com

Forall bulk orders ofmore than 20 copies:

Email:pharmpress@rphar ms.com

Tel:+44 (0) 207572 2266

Pharmaceutical Press also supplies the BNF in digital

formats suitable for standalone computers, intranets,

andfor use on mobile devices.

Distributionof BNFs

The UK health departments distribute BNFsto NHS

hospitals, doctors, dental surgeons, and community

pharmacies. In England, BNFs are mailedindividually

to NHS general practitioners and community pharma-

cies; contact the DH Publication Orderline for extra

copiesor changes relating tomailed BNFs.

Tel:0300 123 1002

InWales, telephone theBusiness Services Centre

Tel:(01495) 332 000

Forfurther information on the supply of copies of the

BNF to NHS organisations, see www.library.nhs.uk/

orderingbnf

TheBNF is designed asa digest for rapidreference

and it may not always include all the information

necessaryfor prescribing and dispensing. Also,less

detailis givenon areas suchas obstetrics,malignant

disease, and anaesthesia since it is expectedthat

those undertaking treatment will have specialist

knowledge and access to specialist literature.

BNF

forChildren

shouldbe consulted for detailed infor-

mationon theuse ofmedicines in children.The BNF

should be interpreted in the light of professional

knowledgeand supplemented as necessary byspe-

cialisedpublications andby reference tothe product

literature. Information is also availablefrom medi-

cinesinformation services (see inside frontcover).

Preface

The BNF is a joint publication of the British Medical

Associationand the Royal PharmaceuticalSociety. It is

published biannually under the authority of a Joint

FormularyCommittee which comprisesrepresentatives

of the two professional bodies and of the UK Health

Departments.The Dental Advisory Groupoversees the

preparationof adviceon thedrug managementof dental

andoral conditions; theGroup includes representatives

ofthe BritishDental Association.The NursePrescribers’

Advisory Group advises on the content relevant to

nurses.

TheBNF aims to provideprescribers, pharmacists and

other healthcare professionals with sound up-to-date

informationabout the use of medicines.

The BNF includes key information on the selection,

prescribing,dispensing andadministration ofmedicines.

Medicines generally prescribed in the UK are covered

and those considered less suitable for prescribing are

clearlyidentiﬁed. Littleor no informationis included on

medicinespromoted for purchase bythe public.

Informationon drugs is drawnfrom the manufacturers’

product literature, medical and pharmaceutical litera-

ture,UK healthdepartments, regulatory authorities,and

professionalbodies. Advice isconstr uctedfrom clinical

literatureand reﬂects,as faras possible,an evaluationof

theevidence from diverse sources.The BNF alsotakes

account ofauthoritative national guidelines and emer-

ging safety concerns. In addition, the editorial team

receives advice on all therapeutic areas from expert

clinicians;this ensuresthat the BNF’srecommendations

arerelevant to practice.

TheBNF is designedas a digestfor rapid referenceand

itmay not alwaysinclude all theinformation necessary

forprescribing and dispensing. Also, less detail isgiven

on areas such as obstetrics, malignant disease, and

anaesthesiasince it is expected that thoseundertaking

treatmentwill have specialist knowledgeand access to

specialist literature.

BNF forChildren

should be con-

sultedfor detailed information on theuse of medicines

inchildren. TheBNF shouldbe interpretedin thelight of

professionalknowledge andsupplemented asnecessar y

by specialised publications and by reference to the

product literature. Information is also available from

medicinesinformation services (see insidefront cover).

Itis vital to usethe most recent editionof the BNF for

makingclinical decisions. Themore important changes

forthis edition are listedon p. xvi.

Thewebsite (bnf.org)includes additional informationof

relevanceto healthcare professionals. Otherdigital for-

mats of the BNF—including intranet and versions for

mobile devices—are produced in parallel with the

printedversion.

TheBNF welcomes commentsfrom healthcarepro-

fessionals. Comments and constructive criticism

shouldbe sent to:

BritishNational Formulary,

RoyalPharmaceutical Society,

1Lambeth High Street, LondonSE1 7JN.

editor@bnf.org

Contents

Preface iii

Acknowledgements iv

Howthe BNF is constructed viii

Howto use the BNF x

Changesfor this edition xvi

Signiﬁcantchanges xvi

Dosechanges xvii

Classiﬁcationchanges xvii

Newnames xvii

Deletedpreparations xvii

Newpreparations included in this edition xviii

Guidanceon prescribing 1

Generalguidance 1

Prescriptionwriting 5

Emergencysupply of medicines 7

ControlledDrugs and drug dependence 8

Adversereactions to drugs 12

Prescribingfor children 15

Prescribingin hepatic impairment 17

Prescribingin renal impairment 17

Prescribingin pregnancy 19

Prescribingin breast-feeding 19

Prescribingin palliative care 20

Prescribingfor the elderly 24

Prescribingin dental practice 26

Drugsand sport 31

Emergencytreatment of poisoning 32

Noteson drugs and Preparations

1: Gastro-intestinal system

2: Cardiovascular system 81

3: Respiratory system 170

4: Central nervoussystem 207

5: Infections 320

6: Endocrine system 418

7: Obstetrics, gynaecology,and

urinary-tractdisorders

485

8: Malignant diseaseand immunosup-

pression

518

9: Nutrition andblood 576

10: Musculoskeletal andjoint diseases 629

11: Eye 666

12: Ear, nose,and oropharynx 685

13: Skin 700

14: Immunological productsand vac-

cines

746

15: Anaesthesia 775

Appendicesand indices

Appendix1: Interactions

800

Appendix2: Liverdisease 17

Appendix3: Renalimpairment 17

Appendix4: Pregnancy 19

Appendix5: Breast-feeding 19

Appendix6: Intravenousadditives 892

Appendix7: Borderlinesubstances 903

Appendix8: Woundmanagement products

andelasticated garments

935

Appendix9: Cautionaryand advisory labels

fordispensed medicines

957

DentalPractitioners’ Formulary 972

NursePrescribers’ Formulary 974

Non-medicalprescribing 978

Indexof manufacturers 979

Index 990

BNF 61 iii

Acknowledgements

The Joint Formulary Committee is grateful to indivi-

dualsand organisations that have providedadvice and

informationto the BNF.

Theprincipal contributors for thisedition were:

I.H.Ahmed-Jushuf, K.W.Ah-See, M.N. Badminton,

P.R.J.Barnes, D.N.Bateman, S.L.Bloom, R.J.Buckley,

I.F.Burgess, D.J.Burn, S.M.Creighton, C.E.Dearden,

D.W.Denning, R.Dinwiddie, P.Dugue, P.N.Durrington,

D.A.C. Elliman, P.Emery, M.D. Feher, B.G.Gazzard,

A.M.Geretti, A.H. Ghodse, N.J.L.Gittoes, P.J.Goadsby,

P.W.Golightly, B.G.Higgins, S.H.D.Jackson, A. Jones,

D.M.Keeling, J.R.Kirwan, P.G.Kopelman, T.H. Lee,

A.Lekkas, D.N.J.Lockwood,A.M. Lovering,M.G. Lucas,

L.Luzzatto, A.G.Marson, P.D.Mason, D.A.McArthur,

K.E.L.McColl, G.M.Mead, L.M.Melvin, E.Miller,

R.M.Mirakian, T.Murray, S.M.S. Nasser, C.Nelson-

Piercy, J.M.Neuberger, D.J.Nutt, L.P.Ormerod,

R.Patel, W.J.Penny, A.B.Provan, M.M. Ramsay,

A.S.CRice, D.J.Rowbotham,J.W.Sander, J.A.T.Sandoe,

M.Schacter, G.J.Shortland, J.Soar, S.C.E.Sporton,

S.Stephens, A.M. Szarewski, J.P.Thompson, R.P.Walt,

D.A.Warrell, J.Watkins, A.D.Weeks, A.Wilcock,

C.E.Willoughby,A.P.R.Wilson, M.M. Yaqoob.

Expert advice on the management of oral and dental

conditions was kindly provided by M. Addy,

P.Coulthard, A.Crighton, M.A.O.Lewis, J.G.Meechan,

N.D.Robb, R.A. Seymour, R. Welbury, and J.M. Zakr-

zewska. S.Kaur provided valuable advice on dental

prescribingpolicy.

Membersof the British Association of Dermatologists’

Therapy & Guidelines Subcommittee, D.A.Buckley,

L.C.Fuller, J. Hughes, S.E.Hulley, J.Lear, A.J.McDo-

nagh, J.McLelland, N.Morar, I. Nasr, S.Punjabi,

M.J.Tidman, S.E.Haveron (Secretariat), and

M.F.MohdMustapa (Secretariat) have provided valu-

ableadvice.

Members of the Advisory Committee onMalaria Pre-

vention,R.H. Behrens, P.L.Chiodini,F.Genasi, L. Good-

yer,A. Green, D.Hill, G. Kassianos, D.G.Lalloo, G.Pas-

vol, S.Patel, M.Powell, D.V.Shingadia, C.J.M. Whitty,

M.Blaze (Secretariat), and V.Smith (Secretariat) have

providedvaluable advice.

Membersof the UKOphthalmic Pharmacy Group have

alsoprovided valuable advice.

The Joint British Societies’ Coronary Risk Prediction

Chartshave been reproduced withthe kind permission

ofP.N.Durrington who has alsoprovided the BNF with

accessto the computerprogram for assessingcoronary

andstroke risk.

R.Suvarna and colleaguesat the MHRA haveprovided

valuableassistance.

Correspondents in the phar maceutical industry have

providedinformation on newproducts and commented

onproducts in the BNF.NHS Prescription Serviceshas

suppliedthe prices of productsin the BNF.

Numerousdoctors, pharmacists,nurses andothers have

sentcomments and suggestions.

The BNF has valuable access to the

Martindale

data

banksby courtesy of S.Sweetman andstaf f.

J.E.Macintyre and staff provided valuable technical

assistance.

C.Adetola, N.Bansal, H.M.N.Brady, J.J.Coleman,

S.Foad,E.H. Glover,T.Hamp, A.Holmes, J.Humphreys,

J.M.James,E. Laughton, J.Reynolds, R.G.Taljaard, and

E.J.Tong provided considerable assistance during the

productionof this edition ofthe BNF.

Xpagehave provided assistancewith typesetting devel-

opmentand related production processes.

iv BNF61

BNF Staff

ManagingEditor: Knowledge Creation

JohnMartin

BPharm,PhD, MRPharmS

AssistantEditors

LeighAnne Claase

BSc,PhD, MRPharmS

BryonyJordan

BSc,DipPharmPract, MRPharmS

ColinR. Macfarlane

BPharm,MSc, MRPharmS

PaulS. Maycock

MPharm,DipPharmPract,

MRPharmS

RachelS. M. Ryan

BPharm,MRPharmS

ShamaM. S. Wagle

BPharm,DipPharmPract,

MRPharmS

StaffEditor s

SejalAmin

BPharm,MSc, MRPharmS

AngelaK. Bennett

MPharm,DipPharmPract,

MRPharmS

ShenaS. Chauhan

BPharm,MRPharmS

SusanE. Clarke

BPharm,DipClinPharm, MRPharmS

Bele

nGranell Villen

BSc,PGDipClinPharm,

MRPharmS

ManjulaHalai

BScChem,MPharm, MRPharmS

EmmaE. Harris

MPharm,DipPharmPract,

MRPharmS

AmyE. Harvey

MPharm,PGDipCommPharm

AmberF. Lauder

BPharm,PGCertPharm, MRPharmS

AngelaM. G. McFarlane

BSc,DipClinPharm,

MRPharmS

SarahMohamad

MPharm,MRPharmS

ElizabethNix

DipPharm(NZ),MRPharmS

SanjayPatel

BPharm,MRPharmS

ClaireL. Preston

BPharm,PGDipMedMan,

MRPharmS

NirvashiRamgoolam

BPharm,MRPharmS

VinayaK. Sharma

BPharm,MSc, PGDipPIM,

MRPharmS

EditorialAssistants

RebeccaS. Bastable

BA,BTEC

CristinaLopez-Bueno

SeniorBNF Administrator

HeidiHomar

AdministrativeAssistant

ZoeDaniel

ManagingEditor: Digital Developmentand Delivery

CorneliaSchnelle

MPhil

DigitalDevelopment Editor

PhilipD. Lee

BSc,PhD

DigitalDevelopment Assistants

RobertC. Buckingham

BSc

MichelleCartwright

JenniferL. Palmer

FdSc

Terminologist

SarahPeck

BSc

Headof Publishing Services

JohnWilson

BNFPublishing Director

DuncanS. T. Enright

MA,PGCE, MInstP, FIDM

ManagingDirector, Pharmaceutical Press

RobertBolick

BA,MA

SeniorMedical Adviser

MartinJ. Kendall

OBE,MB, ChB, MD,FRCP ,FFPM

BNF 61 v

Joint Formulary

Committee

2010–2011

Chair

DerekG. Waller

BSc,MB, BS, DM,FRCP

DeputyChair

AlisonBlenkinsopp

OBE,PhD, BPharm, FRPharmS

CommitteeMembers

JeffreyK. Aronson

MA,MB ChB, DPhil,FRCP, FBPharmacolS, FFPM

AnthonyJ. Avery

BMedSci,MB ChB, DM,FRCG P

TomS.J. Elliott

BMedSci,BTech, BM,BS, MRCP,FRCPath, PhD,DSc

SueFaulding (from December 2010)

BPharm,MSc, FRPharmS

BethHird

BPharm,MSc, MRPharmS, SP, IP

W.Moira Kinnear

BSc,MSc, MRPharmS

DonalO’Donoghue

BSc,MB, ChB, FRCP

GulRoot (to September 2010)

BSc(Pharm),MRPharmS, DMS

MichaelJ. Stewart

MBChB, MD, FRCP(Ed),FRCP

RafeSuvarna

MBBS,BSc, FFPM, DAvMed, DipIMC

MarkG. Timoney

BPharm,MSc, PhD, MPSNI

ExecutiveSecretary

HeidiHomar

Dental Advisory

Group

2010–2011

Chair

DavidWray

MD,BDS, MB ChB,FDSRCPS ,FDSRCS Ed,

FMedSci

CommitteeMembers

ChristineArnold

BDS,DDPHRCS, MCDH

Barry Cockcroft

BDS,FDSRCS (Eng)

DuncanS.T. Enright

MA,PGCE, MInstP, FIDM

AmyE. Harvey

MPharm,PGDipCommPharm, MRPharmS

MartinJ. Kendall

OBE,MB, ChB, MD,FRCP, FFPM

LesleyP. Longman

BSc,BDS, FDSRCS Ed,PhD

SarahManton

BDS,FDSRCS Ed, FHEA,Ph D

JohnMartin

BPharm,PhD, MRPharmS

MichelleMoffat

BDS,MFDS RCSEd, M PaedDent RCPS, FDS(Paed

Dent)RCS Ed

RachelS.M. Ryan

BPharm,MRPharmS

Secretary

ArianneJ. Matlin

MA,MSc, PhD

ExecutiveSecretary

HeidiHomar

Adviceon dental practice

TheBritish Dental Association has contributed to

theadvice on medicines fordental practice through

itsrepresentatives on the DentalAdvisor yGroup.

vi BNF61

Nurses Prescribers’

Advisory Group

2010–2011

Chair

NickyA. Cullum (until November2010)

PhD,RGN

MollyCourtenay (from December 2010)

PhD,MSc, Cert Ed,BSc, RGN

CommitteeMembers

ShenaS. Chauhan

BPharm,MRPharmS

FionaCulley (from July 2010)

LLM,RN, BSc, CertEd

DuncanS.T. Enright

MA,PGCE, MInstP, FIDM

MichaelFanning (from November 2010)

PennyM. Franklin

RN,RCN, RSCPHN(HV), MA, PGCE

MargaretF. Helliwell

MB,BS, BSc, MFPHM,FRCP (Edin)

BryonyJordan

BSc,DipPharmPract, MRPharmS

MartinJ. Kendall

OBE,MB, ChB, MD,FRCP, FFPM

FionaLynch

BSc,MSc, RGN, RSCN

JohnMartin

BPharm,PhD, MRPharmS

ElizabethJ. Plastow

RMN,RGN, RSCPHN(HV), MSc, PGDipEd

JillM. Shearer

BSc,RGN, RM

RabinaTindale

RGN,RSCN, BSc, DipAEN,PGC E

VickyVidler

MA,RGN, RSCN

JohnWright (from November2010)

ExecutiveSecretary

HeidiHomar

BNF 61 vii

How the BNF is

constructed

The BNF is unique in bringing together authoritative,

independent guidance on best practice with clinically

validateddrug information, enabling healthcareprofes-

sionalsto select safe and effective medicines forindivi-

dualpatients.

Information in the BNF has been validated against

emergingevidence, best-practiceguidelines, and advice

froma network of clinicalexperts.

Hundreds ofchanges are made between editions, and

themost clinically signiﬁcant changes are listed at the

frontof each edition (pp.xvi–xviii)

Joint Formulary Committee

TheJoint FormularyCommittee (JFC)is responsiblefor

the content of the BNF. The JFC includes doctors

appointed by the BMJ Publishing Group, pharmacists

appointed by the Royal Pharmaceutical Society, and

representatives from the Medicines and Healthcare

productsRegulatory Agency(MHRA) andthe UKhealth

departments.The JFC decideson matters ofpolicy and

reviews amendments to the BNF in the light ofnew

evidence and exper t advice. The Committee meets

quarterlyand each member also receives proofs of all

BNFchapters for review before publication.

Editorial team

BNFstaf feditors are pharmacists with a soundunder-

standingof howdrugs are usedin clinicalpractice. Each

staff editor isresponsible for editing, maintaining, and

updatingspeciﬁc chapters of the BNF.During the pub-

licationcycle the staffeditors review information inthe

BNFagainst a varietyof sources (see below).

Amendments to thetext are drafted when the editors

are satisﬁed that any new information is reliable and

relevant. The draft amendments are passed to expert

advisers forcomment and then presented to the Joint

Formulary Committee for consideration. Additionally,

foreach edition,sections arechosen from everychapter

for thorough review. These planned reviews aim to

verify all the information in the selected sections and

to draft any amendments to reﬂect the current best

practice.

Staffeditors prepare thetext for publication andunder-

takea number of checks on the knowledge at various

stagesof the production.

Expert advisers

TheBNF uses about60 expert clinicaladvisers (includ-

ingdoctors, pharmacists, nurses,and dentists) through-

outthe UK to helpwith the productionof each edition.

The roleof these expert advisers is to review existing

text and to comment on amendments drafted by the

staff editors.These clinical experts help to ensurethat

theBNF remains reliable by:

commenting on the relevance of the text in the

contextof best clinical practicein the UK;

checking draft amendments for appropriate inter-

pretationof any new evidence;

providingexpert opinion inareas of controversy or

whenreliable evidence is lacking;

advising on areas where theBNF diverges from

summariesof product characteristics;

providingindependent advice ondrug interactions,

prescribing in hepatic impairment, renal impair-

ment, pregnancy, breast-feeding, children, the

elderly, palliative care, and the emergency treat-

mentof poisoning.

Inaddition to consultingwith regular advisers,the BNF

calls on other clinical specialists for speciﬁc develop-

mentswhen particular expertise is required.

The BNF alsoworks closely with a numberof expert

bodies that produce clinical guidelines. Drafts or pre-

publication copiesof guidelines are routinely received

forcomment and for assimilationinto the BNF.

Sourcesof BNF information

TheBNF uses a variety of sources for its information;

themain ones are shownbelow.

Summaries of product characteristics

The BNF

receivessummaries of productcharacteristics (SPCs)of

all new products as well as revised SPCs for existing

products.The SPCs are theprincipal source of product

information and are carefully processed, despite the

ever-increasingvolume of information being issued by

thepharmaceutical industry. Such processinginvolves:

verifyingthe approved names ofall relevant ingre-

dientsincluding ‘non-active’ingredients (the BNFis

committed tousing approved names and descrip-

tionsas laid down bythe Medicines Act);

comparingthe indications, cautions, contra-indica-

tions, and side-effects with similar existing drugs.

Where these are different from the expected pat-

tern, justiﬁcation is sought for their inclusion or

exclusion;

seeking independent data on the use of drugs in

pregnancyand breast-feeding;

incorporating the information into the BNF using

established criteriafor the presentation and inclu-

sionof the data;

checking interpretation of the information by two

staff editors before submitting to a senior editor;

changesrelating to doses receivean extra check;

identifyingpotential clinical problems oromissions

andseeking furtherinformation frommanufacturers

orfrom expert advisers;

carefulvalidation of any areasof divergence of the

BNFfrom the SPC before discussion by the Com-

mittee(in the light ofsupporting evidence);

constructing, with the help of expert advisers, a

commenton the role of the drug inthe context of

similardrugs.

Much of this processingis applicable to the following

sourcesas well.

Expertadvisers

Therole ofexpert clinical advisersin

providing the appropriate clinical context for all BNF

informationis discussed above.

viii BNF 61

Literature

Staff editors monitor core medical and

pharmaceutical journals.Research papers and reviews

relatingto drugtherapy arecarefully processed.W hena

differencebetween the advicein theBNF and thepaper

isnoted, the new information is assessedfor reliability

andrelevance to UKclinical practice. Ifnecessar y,new

text isdrafted and discussed with expert advisers and

theJoint FormularyCommittee. TheBNF enjoysa close

workingrelationship witha numberof national informa-

tionproviders.

Systematicreviews

TheBNF has access to various

databases of systematic reviews (including the

Cochrane Library and various web-based resources).

These are used for answering speciﬁc queries, for

reviewing existing text and for constructing new text.

Staffeditors receive training in criticalappraisal, litera-

ture evaluation, and search strategies. Reviews pub-

lished in Clinical Evidence are used tovalidate BNF

advice.

Consensus guidelines

The advice in the BNFis

checked against consensus guidelines produced by

expertbodies. A number of bodiesmake drafts or pre-

publication copies of the guidelines available to the

BNF;it is therefore possibleto ensure that aconsistent

messageis disseminated. The BNF routinelyprocesses

guidelines from the National Institute for Health and

ClinicalExcellence (NICE),the Scottish MedicinesCon-

sortium(SMC), and the Scottish Intercollegiate Guide-

linesNetwork (SIGN).

Referencesources

Textbooksand reference sources

are used to provide background information for the

review of existing text or for the construction of new

text. The BNF team works closely with the editorial

team that produces

Martindale: The Complete Drug

Reference

.The BNF hasaccess to

Martindale

informa-

tionresources and eachteam keeps the otherinformed

of signiﬁcantdevelopments and shifts in the trends of

drugusage.

Statutoryinformation

TheBNF routinely processes

relevant information from variousGovernment bodies

includingStatutory Instruments and regulations affect-

ingthe Prescriptiononly Medicines Order.Ofﬁcial com-

pendia such as the British Pharmacopoeia and its

addenda are processed routinely to ensure that the

BNF complies withthe relevant sections of the Medi-

cinesAct. The BNF itself is named as anofﬁcial com-

pendiumin the Medicines Act.

TheBNF maintainsclose links withthe HomeOf ﬁce(in

relation to controlled drug regulations) and the Medi-

cines and Healthcare products Regulatory Agency

(including the British Pharmacopoeia Commission).

Safetywarnings issued by the Commission on Human

Medicines(CHM) and guidelineson drug use issuedby

theUK healthdepartments are processedas a matterof

routine.

Relevant professional statements issued by the Royal

PharmaceuticalSociety are included in theBNF as are

guidelines from bodies such as theRoyal Collegeof

GeneralPractitioners.

TheBNF reﬂects information from theDrug Tariff, the

Scottish Drug Tariff, and the Northern Ireland Drug

Tariff.

Pricinginformation

NHSPrescription Services(from

theNHS BusinessServices Authority)provides informa-

tionon prices of medicinal products and appliancesin

theBNF.

Comments from readers

Readers of the BNF are

invited to send in comments. Numerous letters and

emails are received during the preparation of each

edition. Such feedback helps to ensure that theBNF

provides practical and clinically relevant information.

Manychanges inthe presentationand scope ofthe BNF

haveresulted from comments sentin by users.

Commentsfrom industry

Closescrutiny of theBNF

bythe manufacturers provides anadditional check and

allows them an opportunity to raise issues about the

BNF’spresentation of the role of various drugs; thisis

yetanother check on the balance of theBNF’s advice.

All comments are looked at with care and, where

necessary, additional information and expert advice

aresought.

Virtualuser groups

TheBNF has setup virtual user

groupsacross various healthcare professions (e.g.doc-

tors, pharmacists, nurses, dentists). The aim of these

groups will be to providefeedback to the editors and

publishersto ensure that BNF publicationscontinue to

servethe needs of its users.

Market research

Market research is conducted at

regularintervals to gatherfeedback on speciﬁcareas of

development, suchas dr ug interactionsor changes to

theway information is presentedin digital formats.

TheBNF is anindependent professional publication

thatis kept up-to-dateand addresses theday-to-day

prescribinginformation needs of healthcare profes-

sionals.Use of this resource throughout the health

service helps to ensure that medicines are used

safely,effectively, andappropriately.

BNF 61 ix

How to use the BNF

Inorder to achieve the safe, effective,and appropriate

useof medicines, healthcareprofessionals must beable

to use the BNF effectively, and keep up to date with

signiﬁcantchanges in eachnew edition ofthe BNF that

are relevant totheir clinical practice.

Howto Use the

BNF

is aimed as a quick refresher forall healthcare

professionals involved with prescribing, monitoring,

supplying,and administering medicines,and as alearn-

ing aid for students training to join these professions.

While

How to Use the BNF

is linked to the main

elements of rational prescribing, the generic structure

ofthis sectionmeans that itcan beadapted for teaching

andlearning in different clinical settings.

Structure of the BNF

TheContents list(on p.iii) showsthat information inthe

BNFis divided into:

Howthe BNF isConstructed

(p.viii);

Changesfor this Edition

(p.xvi);

Guidance on Prescribing

(p.1), which provides

practical information on many aspects of pre-

scribing fromwriting a prescription to prescribing

inpalliative care;

Emergency Treatmentof Poisoning

(p.32), which

providesan overview on themanagement of acute

poisoning;

Classiﬁednotes on clinical conditions, drugs, and

preparations

,these notes aredivided into 15chap-

ters,each of whichis related to aparticular system

ofthe body (e.g.chapter 2, CardiovascularSystem)

or to an aspect of medical care (e.g. chapter 5,

Infections). Each chapter is further divided into

classiﬁed sections. Each section usually begins

with

prescribing notes

followed by relevant drug

monographs

and

preparations

(see ﬁg. 1). Drugs

are classiﬁedin a section according to their phar-

macologyand therapeutic use;

Appendices and Indices

, includes 5 Appendices

(providing infor mation ondr ug interactions,intra-

venous additives, Borderline substances, wound

management, and cautionary and advisory labels

fordispensed medicines), the Dental Practitioners’

Formulary,the Nurse Prescribers’ Formulary,Non-

medical Prescribing, Index of Manufacturers, and

themain Index. Theinformation in theAppendices

should beused in conjunction with relevant infor-

mationin the chapters.

Finding information in the BNF

The BNF includes a number of aids to help access

relevantinformation:

Index

(p.990), where entriesare included in alpha-

betical order of non-proprietary drug names, pro-

prietary drug names, clinical conditions, and pre-

scribing topics. A speciﬁc entr y for ‘Dental

Prescribing’ bringstogether topics of relevance to

dental surgeons. The page reference to the drug

monograph is shown in bold type. References to

drugsin Appendices1 and 9are not includedin the

mainIndex;

Contents

(p.iii), provides a hierarchyof how infor-

mationin the BNF isorganised;

Thebeginning of eachchapter includes

aclassiﬁed

hierarchy

of how information is organised in that

chapter;

Runningheads

,located nextto thepage number on

thetop of each page, showthe section of the BNF

thatis being used;

Thumbnails

,on the outer edgeof each page, show

thechapter of the BNFthat is being used;

Cross-references

, lead to additional relevant infor-

mationin other parts of theBNF.

Finding dental information in the BNF

Extrasignposts have been added tohelp access dental

informationin the BNF:

Prescribing in Dental Practice

(p.26), includes a

contentslist dedicated to drugs and topicsof rele-

vanceto dentists, togetherwith cross-references to

theprescribing notes in theappropriate sections of

the BNF.For example, a review of this list shows

that information on the local treatment of oral

infections islocated in chapter 12 (Ear, Nose, and

Oropharynx) while information on the systemic

treatmentof these infections is found in chapter 5

(Infections). This section also includes advice on

MedicalEmergencies in DentalPractice (p.26) and

Medical Problems in Dental Practice (p.28). Gui-

danceon the preventionof endocarditis andadvice

on the management of anticoagulated patients

undergoingdental surgery can alsobe found here;

Side-headings

,in the prescribing notes, side-head-

ings facilitate the identiﬁcation of advice on oral

conditions(e.g. Dental and OrofacialPain, p. 257);

Dentalprescribing onNHS

,in thebody of theBNF,

preparationsthat canbe prescribedusing NHSform

FP10D(GP14 inScotland, WP10D inWales) canbe

identiﬁedby means of a note headed ‘Dental pre-

scribingon NHS’ (e.g. AciclovirTablets, p. 393).

Identifying effective drug treatments

Theprescribing notes in the BNFprovide an overview

of the drug management of common conditionsand

facilitate rapid appraisal of treatment options (e.g.

hypertension, p.104). For ease of use, information on

the management of certain conditions has been tabu-

lated (e.g. acute asthma, p. 173). Information is also

provided on the prevention of disease (e.g. malaria

prophylaxis for travellers, p.404). Cardiovascularrisk

predictioncharts for the primary prevention of cardio-

vasculardisease canbe found inthe glossy pagesat the

backof the BNF.

Adviceissued by the National Institute for Health and

ClinicalExcellence (NICE) isintegrated within the BNF

prescribing notes if appropriate. Summaries of NICE

technology appraisals, and relevant short guidelines,

are included in blue panels. The BNF also includes

advice issued by the Scottish Medicines Consortium

(SMC) when a medicine is restricted or not recom-

mendedfor use within NHS Scotland.

In order to select safe and effective medicines for

individual patients, information in the prescribing

notes must be used in conjunction with other pre-

x BNF61

scribing detailsabout the drugs and knowledge of the

patient’smedical and drug history.

A brief description of the clinical uses of a drug can

usuallybe found inthe Indications section ofits mono-

graph (e.g. bendroﬂumethiazide, p. 84); a cross-refer-

ence is provided to any indications for that drug that

arecovered in other sectionsof the BNF.

Thesymbol U isused to denotepreparations that are

consideredby theJoint FormularyCommittee tobe less

suitable for prescribing. Although such preparations

may not be considered as drugs of ﬁrst choice, their

usemay be justiﬁable incertain circumstances.

Drug management of medical

emergencies

Guidance on the drug management of medical emer-

genciescan be foundin the relevantBNF chapters (e.g.

treatment of anaphylaxis is included in section 3.4.3);

adviceon the management of medical emergencies in

dental practice can be found in Prescribing in Dental

Practice, p. 26. A summary of drug doses used for

MedicalEmergencies in the Community can be found

inthe glossypages at theback ofthe BNF.An algorithm

for Adult Advanced Life Support can also be found

withinthese pages.

Figure 1 Illustratesthe typical layout of a drug monograph and preparation

records in the BNF

BNF How to usethe BNF xi

DRUG NAME U

Indications

detailsof clinical uses

Cautions

detailsof precautions requiredand also

anymonitoring required

Counselling

Verbalexplanation to thepatient of spe-

ciﬁcdetails of thedrug treatment (e.g.posture when

takinga medicine)

Contra-indications

circumstanceswhen a drug

shouldbe avoided

Hepaticimpairment

adviceon the use ofa drug

inhepatic impairment

Renalimpairment

adviceon the useof a drugin

renalimpairment

Pregnancy

adviceon the use ofa drug during

pregnancy

Breast-feeding

adviceon the use ofa drug dur-

ingbreast-feeding

Side-effects

verycommon (greater than 1in 10)

andcommon (1in 100 to1 in10);

lesscommonly

(1in 1000 to1 in 100);

rarely

(1in 10 000to 1 in

1000);

veryrarely

(lessthen 1 in 10000); also

reported,frequency not known

Dose

. Doseand frequency of administration(max.

dose);

CHILDand ELDERLY detailsof dose for spe-

ciﬁcage group

. Byalternative route, dose andfrequency

ApprovedName (Non-proprietary) A

Pharmaceuticalform

,sugar-free, active ingre-

dientmg/mL, net price, packsize = basic NHS

price.Label: (as in Appendix9)

Exceptionsto the prescribingstatus are indicatedby a

noteor footnote.

ProprietaryName (Manufacturer) AD

Pharmaceuticalform

,colour, coating, active

ingredientand amount indosage form,net price,

packsize = basic NHSprice. Label: (as in

Appendix9)

Excipients

includeclinically importantexcipients

Electrolytes

clinicallysigniﬁcant quantitiesof electrolytes

Note

Speciﬁcnotes about theproduct e.g.handling

Preparations

Preparationsare included under anon-proprietary

title,if they aremarketed under sucha title, if they

arenot otherwiseprescribable under theNHS, or if

theymay be prepared extemporaneously.

Drugs

Drugsappear under pharmacopoeial orother non-

proprietary titles. When there is an

appropriate

currentmonograph

(Medicines Act1968, Section

65)preference isgiven toa nameat thehead ofthat

monograph; otherwise a British Approved Name

(BAN),if available, isused.

Thesymbol U is used to denote those prepara-

tions that are considered by the Joint Formulary

Committee to be less suitable for prescribing.

Althoughsuch preparationsmay not beconsidered

asdrugs of ﬁrstchoice, their use maybe justiﬁable

incertain circumstances.

Prescription-onlymedicinesA

This symbol has been placed against thosepre-

parationsthat are available only on aprescription

issued by an appropriate practitioner. For more

detailed information see

Medicines

Ethics and

Practice

, No. 34, London, Pharmaceutical Press,

2010(and subsequent editions asavailable).

The symbol C indicates that the preparation is

subject to the prescription requirements of the

Misuse of Drugs Act. For regulations governing

prescriptionsfor such preparations seep. 8.

Preparationsnot available for NHS

prescriptionD

This symbol has been placed against thosepre-

parationsincluded inthe BNFthat arenot prescrib-

able under the NHS. Those prescribable only for

speciﬁc disorders have a footnote specifying the

condition(s) for which the preparation remains

available. Some preparations which are not

pre-

scribable

by brand name under the NHS may

nevertheless be

dispensed

using the brand name

providingthat the prescription showsan appropri-

atenon-proprietary name.

Prices

Prices have been calculated from the basiccost

usedin pricing NHS prescriptions, see also Prices

inthe BNF, p.xiv for details.

How to usethe BNF

BNF 61 xi

Minimising harm in patients with co-

morbidities

Thedrug chosen to treat a particular conditionshould

haveminimal detrimental effects on thepatient’s other

diseases and minimise the patient’s susceptibility to

adverseef fects.To achieve this, the

Cautions

Contra-

indications

,and

Side-effects

ofthe relevantdr ugshould

be reviewed, and can usually be found in the drug

monograph. However,if a class of drugs (e.g. tetracy-

clines, p.346) share the same cautions, contra-indica-

tions, and side-effects, these are amalgamated in the

prescribingnotes whilethose uniqueto aparticular drug

in thatclass are included in its individual drug mono-

graph. Occasionally, the cautions, contra-indications,

and side-effects maybe included within a preparation

recordif they are speciﬁc to that preparation or if the

preparationis not accompanied bya monograph.

Theinformation under Cautions can be usedto assess

the risks of using a drug in a patient who has co-

morbidities that are also included in the Cautions for

that drug—if a safer alternative cannot be found, the

drugmay beprescribed while monitoringthe patientfor

adverse-effects or deterioration in the co-morbidity.

Contra-indications are far more restrictive thanCau-

tions and mean that the drug should be avoided in a

patientwith a condition thatis contra-indicated.

The impact that potential side-effects may have on a

patient’s quality of life should also be assessed. For

instance, in a patient who has difﬁculty sleeping, it

maybe preferableto avoida drug thatfrequently causes

insomnia.The prescribing notes in the BNFmay high-

lightimportant safetyconcerns anddifferences between

drugsin their ability to causecertain side-effects.

Prescribingfor patients with hepatic or

renal impairment

Drugselection should aimto minimise the potentialfor

drugaccumulation, adverse drugreactions, andexacer-

bation of pre-existing hepatic or renal disease. If it is

necessaryto prescribe drugs whose effectis altered by

hepaticor renal disease, appropriate drug doseadjust-

ments should be made, and patients should be moni-

toredadequately. Thegeneral principles for prescribing

are outlined under

Prescribingin Hepatic Impairment

(p.17) and

Prescribing in Renal Impairment

(p.17).

Information about dr ugs that should be avoided or

used with caution in hepatic disease or renal impair-

mentcan be found indrug monographs under

Hepatic

Impairment

and

Renal Impairment

(e.g. ﬂuconazole,

p.374). However, if aclass of drugs (e.g. tetracyclines,

p.346) share the same recommendations for use in

hepatic disease or renal impairment, this advice is

presented in the prescribing notes under

Hepatic

Impairment

and

Renal Impairment

and any advice

that is unique to a particular drug in that class is

includedin its individual drug monograph.

Prescribing for patients who are

pregnant or breast-feeding

Drug selection should aim to minimise harm to the

fetus,nursing infant, and mother. Theinfant should be

monitoredfor potentialside-effects of drugsused bythe

motherduring pregnancyor breast-feeding.The general

principlesfor prescribingare outlined under

Prescribing

inPregnancy

(p.19) and

Prescribingin Breast-feeding

(p.19). The prescribing notes in the BNF chapters

provide guidance on the drug treatmentof common

conditionsthat can occurduring pregnancy andbreast-

feeding(e.g. asthma, p.170). Information aboutthe use

of speciﬁc drugs during pregnancy and breast-feeding

can be found in their drug monographs under

Pregnancy

and

Breast-feeding

(e.g. ﬂuconazole,

p.374). However, if aclass of drugs (e.g. tetracyclines,

p.346) sharethe same recommendationsfor use during

pregnancyor breast-feeding,this adviceis amalgamated

in the prescribing notes under

Pregnancy

and

Breast-

feeding

whileany advice that is unique to a particular

drug in that class is included in its individual drug

monograph.

Minimising drug interactions

Drug selection should aim to minimise drug interac-

tions.If it isnecessary to prescribea potentially serious

combination of drugs, patients should be monitored

appropriately.The mechanisms underlying drug inter-

actionsare explained in Appendix1 (p. 800).

Detailsof drug interactionscan be foundin Appendix 1

of the BNF (p. 801). Drugs and their interactions are

listedin alphabetical order of thenon-proprietary drug

name,and cross-referencesto drugclasses are provided

where appropriate. Each drug or drug class is listed

twice:in the alphabetical list andalso against the drug

orclass with which itinteracts. The symbol .is placed

against interactions that are potentially serious and

where combined administration of drugs should be

avoided (or only undertaken with caution and appro-

priatemonitoring). Interactions thathave no symboldo

notusually have serious consequences.

Ifa drugor drugclass has interactions,a crossreference

towhere these can befound in Appendix 1is provided

under the Cautions of the drug monograph or pre-

scribingnotes.

Prescribing for the elderly

Generalguidance on prescribing for the elderlycan be

foundon p. 24.

Prescribing forchildren

General guidance on prescribing for children can be

foundon p.15. Fordetailed adviceon medicinesused in

children,consult

BNFfor Children

Selecting the dose

Thedrug dose is usuallylocated in the

Dose

sectionof

thedrug monograph orpreparation record.The dose of

adrug may vary according todifferent indications and

routesof administration. Ifno indication isgiven by the

dose, then that dose can beused for the conditions

speciﬁedin the Indications section of thatdr ugmono-

graph,but notfor the conditionscross-referring toother

sections of the BNF. The dose is located within the

preparation recordwhen the dose varies according to

different formulations of that drug (e.g. amphotericin,

p.378) or when a preparation has a dose different to

that in its monograph (e.g.

Sporanox

liquid, p.376).

Occasionally,drug doses may be included in the pre-

scribingnotes for practical reasons(e.g. doses of drugs

Helicobacterpylori

eradicationregimens, p. 50).The

right dose should be selected for the right indication,

routeof administration, and preparation.

xii BNF61

Doses are either expressed in terms of a deﬁnite fre-

quency(e.g. 1g 4 times daily)or in the total dailydose

format(e.g. 6g daily in 3divided doses); the totaldaily

dose should be divided into individual doses (in the

secondexample, the patient shouldreceive 2 g3 times

daily).

The doses of some drugs may need to be adjusted if

theiref fectsare altered by concomitant usewith other

drugs, orin patients with hepatic or renal impairment

(seeMinimising Drug Interactions, and Prescribing for

Patientswith Hepatic or RenalImpairment).

Dosesfor speciﬁc patient groups (e.g.the elderly) may

be included ifthey are different to the standard dose.

Dosesfor children can be identiﬁed by the terms

NEO-

NATE

,INFANT, and CHILD,and will varyaccording to their

ageor body-weight.

Conversions for imperial to metric measures can be

foundin the glossy pagesat the back of theBNF.

Selecting a suitable preparation

Patientsshould be prescribed a preparation that com-

plementstheir daily routine,and that providesthe right

dose of drug for the right indication and route of

administration.

In the BNF, preparations usually follow immediately

after the monograph for the drug which is their main

ingredient.The preparation record (see ﬁg.1) provides

informationon the type of formulation(e.g. tablet), the

amountof active drug in a solid dosage form,and the

concentration of active drug in a liquid dosage form.

The legal status is shown for prescription only medi-

cines andcontrolled drugs; any exception to the legal

status is shown by a Note immediately after the pre-

parationrecord or a footnote. Ifa proprietary prepara-

tion has a distinct colour,coating, scoring, or ﬂavour,

thisis shown in thepreparation record. Ifa proprietary

preparationincludes excipients usually speciﬁed in the

BNF(see p. 2),these are shown in the

Excipients

state-

ment,and ifit containsclinically signiﬁcant quantitiesof

electrolytes,these are usuallyshown in the

Electrolytes

statement.

Branded oral liquid preparations that do not contain

fructose, glucose, or sucrose are described as ‘sugar-

free’in the BNF.Preparations containing hydrogenated

glucosesyrup, mannitol, maltitol,sorbitol, or xylitolare

alsomarked ‘sugar-free’since there is evidencethat they

donot cause dentalcaries. Patientsreceiving medicines

containing cariogenic sugars should be advised of

appropriatedental hygiene measures toprevent caries.

Sugar-freepreparations should be used whenever pos-

sible.

Where a dr ug has several preparations, those of a

similartype may be grouped togetherunder a heading

(e.g. ‘Modiﬁed-release’ for theophylline preparations,

p.181). Where there is good evidence to show that

the preparations for a particular drug are not inter-

changeable,this is stated in a Note either in the Dose

sectionof the monograph or by the group of prepara-

tionsaffected. Whenthe doseof a drugvaries according

to different formulations of that drug,the right dose

shouldbe prescribed for thepreparation selected.

Inthe case of compound preparations, the prescribing

information of all constituents should be taken into

accountfor prescribing.

Writing prescriptions

Guidanceis provided on writing prescriptions thatwill

helpto reduce medication errors,see p. 5. Prescription

requirementsfor controlled drugs are alsospeciﬁed on

p. 8.

Administering drugs

Ifa drug canbe given parenterallyor by morethan one

route,the Dosesection inthe monographor preparation

record provides basic information on the route of

administration. Further information on administration

maybe found in themonograph or preparation record,

oftenas aNote or Counsellingadvice. Ifa class ofdrugs

(e.g. topical corticosteroids, p.708) share the same

administration advice, this may be presented in the

prescribingnotes.

Appendix 6 (p.892) provides practical information on

thepreparation of intravenousdrug infusions, including

compatibility of drugs with standard intravenousinfu-

sion ﬂuids, method of dilution or reconstitution, and

administrationrates.

Advising patients

The prescriber and the patient should agree on the

health outcomes that the patient desires and on the

strategy for achieving them (see Taking Medicines to

Best Effect, p. 1). Taking the time to explain to the

patient (and carers) the rationale and the potential

adverse effects of treatment may improve adherence.

Forsome medicines thereis a specialneed for counsel-

ling (e.g. appropriate posture during administration of

doxycycline);this is shown in

Counselling

statements,

usuallyin theCautions orDose section ofa monograph,

or within a preparation record if it is speciﬁc to that

preparation.

Patientsshould beadvised if treatmentis likely toaffect

theirability to drive oroperate machinery.

Cautionary and advisory labels that pharmacists are

recommendedto add when dispensing are included in

thepreparation record(see ﬁg.1). Details ofthese labels

canbe found in Appendix 9 (p.957); a list of products

andtheir labels is included in alphabetical order of the

non-proprietaryand proprietary drug names.

Monitoring drug treatment

Patientsshould bemonitored to ensurethey areachiev-

ingthe expected beneﬁts from drug treatment without

anyunwanted side-effects. Theprescribing notes orthe

Cautions in the drug monograph specify any special

monitoringrequirements. Further information on mon-

itoringthe plasmaconcentration of drugswith a narrow

therapeutic index can be found as a Noteunder the

Dosesection of the drug monograph.

Identifying andrepor tingadverse drug

reactions

Clinically relevant

Side-effects

for most drugs are

included in the monographs. However, if a class of

drugs (e.g. tetracyclines, p.346) share the sameside-

effects, these are presented in the prescribing notes

while those unique to a particular drug in that class

are included in its individual drug monograph. Occa-

BNF 61 xiii

sionally,side-effects may beincluded within a prepara-

tionrecord if they are speciﬁc tothat preparation or if

thepreparation is not accompaniedby a monograph.

Side-effects are generally listed in order of frequency

andarranged broadly by body systems.Occasionally a

rareside-effect might belisted ﬁrst if itis considered to

beparticularly importantbecause ofits seriousness.The

frequencyof side-effects is describedin ﬁg. 1.

An exhaustive list of side-effects is not included for

drugs thatare used by specialists (e.g. cytotoxicdrugs

anddrugs used inanaesthesia). Recognisingthat hyper-

sensitivity reactions can occur with virtually all medi-

cines,this effect is generally notlisted, unless the drug

carriesan increasedrisk ofsuch reactions.The BNFalso

omits effects that are likely to havelittle clinical con-

sequence(e.g. transient increase inliver enzymes).

Theprescribing notes in theBNF may highlight impor-

tantsafety concerns and differences between drugs in

their ability tocause certain side-ef fects.Safety warn-

ings issued by the Commission on Human Medicines

(CHM)or Medicines and Healthcare products Regula-

tory Agency(MHRA) can also be found hereor in the

drugmonographs.

AdverseReactions to Drugs (p. 12)provides advice on

preventing adverse drug reactions, and guidance on

reporting adverse drug reactions tothe MHRA. The

blacktriangle symbol Tidentiﬁes thosepreparations in

theBNF that are monitoredintensively by the MHRA.

Finding signiﬁcant changesin a new

edition

The BNF is published in March and September each

yearand includes lists ofchanges in a newedition that

arerelevant to clinical practice:

The print version includes an

Insert

that sum-

marisesthe background to several key changes. A

copyof theInsert canalso befound at bnf.orgin the

sectionon Updates under ‘What’snew in BNF?’;

Changesfor this edition

(p.xvi), provides a list of

signiﬁcant changes, dose changes, classiﬁcation

changes, new names, and new preparations that

havebeen incorporated into a newedition, as well

asa listof preparationsthat have beendiscontinued

sincethe last edition. Forease of identiﬁcation,the

marginsof these pages aremar kedin blue;

Changes to the Dental Practitioners’ Formulary

(p.973), these are locatedat the end of theDental

List;

Changesto the Appendices

,drug entries that have

been amended or introduced since the previous

editionin Appendix1 (DrugInteractions) or Appen-

dix 9 (Cautionary and Advisory Labels for Dis-

pensedMedicines) are underlined in the print ver-

sions;

E-newsletter

,the BNF& BNFC e-newsletterservice

isavailable free of charge. It alerts healthcare pro-

fessionals to details of signiﬁcant changes in the

clinicalcontent ofthese publicationsand to theway

thatthis information is delivered. Newsletters also

review clinical case studies and provide tips on

usingthese publications effectively. To sign up for

e-newslettersgo to bnf.org/newsletter. Tovisit the

e-newsletter archive, go to bnf.org/bnf/extra/

current/450066.htm

BNFUpdate

,an e-learning programme developed

incollaboration withthe Centre forPharmacy Post-

graduateEducation (CPPE),enables pharmacists to

identifyand assess how signiﬁcant changes in the

BNFaffect their clinicalpractice. Separate modules

for primary and secondary care can befound at

www.cppe.ac.uk.

Somany changes are made toeach new edition of the

BNF,that not allof them can be accommodatedin the

Insert andthe Changes section. We encourage health-

care professionals to review regularly the prescribing

informationon drugs that they encounterfrequently.

Nutrition

Appendix7 (p. 903) includes tables ofACBS-approved

enteralfeeds andnutritional supplementsbased on their

energy andprotein content. There are separate tables

forspecialised formulae for speciﬁc clinicalconditions.

Classiﬁedsections on foods for specialdiets and nutri-

tional supplements for metabolic diseases are also

included.

Wound dressings

A table on wound dressings in Appendix 8 (p.935)

allows an appropriate dressing to be selected based

onthe appearance andcondition of thewound. Further

informationabout the dressing canbe found by follow-

ingthe cross-reference tothe relevant classiﬁedsection

in the Appendix. In section (A8.2) advanced wound

contact dressings have been classiﬁed in order of

increasingabsorbency.

Unlicensed medicines

TheBNF includesunlicensed useof medicineswhen the

clinicalneed cannotbe met bylicensed medicines;such

use shouldbe supported by appropriate evidence and

experience.When the BNF recommendsan unlicensed

medicine or the ‘off-label’ use of a licensedmedicine,

thisis shown in theappropriate place by ‘[unlicensed]’.

Prices in the BNF

Basic net prices are given in the BNF to provide an

indication of relative cost. Where there is a choiceof

suitablepreparations for a particular disease or condi-

tionthe relativecost may beused inmaking a selection.

Cost-effective prescribing must, however, take into

account other factors (such as dose frequency and

duration of treatment) that affect thetotal cost.The

useof moreexpensive drugs isjustiﬁed if itwill resultin

better treatment of the patient, or a reduction of the

lengthof an illness,or the timespent in hospital. Prices

havegenerally beencalculated fromthe netcost used in

pricingNHS prescriptions in October2010. Prices gen-

erally reﬂect whole dispensing packs;prices for injec-

tionsare stated perampoule, vial, orsyringe. The price

foran extemporaneouslyprepared preparationhas been

omitted where thenet cost of the ingredients used to

makeit wouldgive a misleadinglylow impressionof the

ﬁnalprice. In Appendix8 prices statedare per dressing

orbandage.

BNF prices are not suitable for quoting to patients

seeking private prescriptions or contemplating over-

xiv BNF 61

the-counter purchases because they do not take into

accountVAT, professionalfees, and other overheads.

A fuller explanation of costs to the NHS may be

obtained from the Drug Tariff. Separate drug tariffs

are applicable to England and Wales, Scotland, and

NorthernIreland; pricesin the differenttariffs may vary.

Extra resourceson the BNF website

While theBNF website (bnf.org) hosts the digital con-

tent of the BNF proper, it also provides additional

resources such as

Frequently Asked Questions

and

onlinecalculators.

BNF prescribing practice for medical

students

Thisonline revision aid,produced in collaborationwith

Onexamination, provides clinical case studies to help

medicalstudents improve their knowledge of safe and

effectiveprescribing whileusing theBNF.Further details

aboutthis module can be found at bnf.org/bnf/extra/

current/450048.htm

Using other sourcesfor medicines

information

TheBNF isdesigned asa digestfor rapidreference. Less

detail is given on areas such as obstetrics, malignant

disease,and anaesthesia since itis expected that those

undertaking treatment will have specialist knowledge

and access to specialist literature.

BNF for Children

shouldbe consulted fordetailed information onthe use

ofmedicines inchildren. TheBNF should beinterpreted

inthe lightof professionalknowledge andsupplemented

as necessary by specialised publicationsand by refer-

enceto the productliterature. Information is alsoavail-

able from medicines information services (see inside

frontcover).

BNF 61 xv

Changes for this edition

Signiﬁcant changes

TheBNF is revisedtwice yearlyand numerous changes

are made between issues. All copiesof BNF No. 60

(September 2010) should therefore be withdrawn and

replaced by BNF No. 61 (March 2011). Signiﬁcant

changes havebeen made in the following sections for

BNFNo. 61:

Bowelcleansing preparations, section 1.6.5

Atrialﬁbrillation and atrial ﬂutter,section 2.3.1

Dronedarone[NICE guidance], section 2.3.2

Hypertensionin pregnancy, section2.5

Hypertensive crises [title ‘Accelerated or very severe

hypertension’ amended to ‘Hypertensive crises’ and

adviceupdated], section 2.5

Sitaxentan(

Thelin

)[to be withdrawn fromthe market

dueto hepatotoxicity], section 2.5.1

Heartfailure, section 2.5.5

Management of stroke [new prescribing notes on the

management of transient ischaemic attack, ischaemic

stroke,and intracerebral haemorrhage], section2.9

Clopidogrel and modiﬁed-release dipyridamole [NICE

guidance],section 2.9

Familialhypercholesterolaemia, section 2.12

Formoterol dose in children [MHRA/CHM advice],

section3.1.1.1

Fentanyl [counselling for the use of patches], section

4.7.2

Epilepsyin pregnancy, section4.8.1

Alcoholdependence, section 4.10.1

Nicotinedependence, section 4.10.2

Opioiddependence, section 4.10.3

Missedmaintenance doses in opioid dependence, sec-

tion4.10.3

Summaryof antibacterial therapy [advicereformatted],

section5.1, Table 1

Meningitis,section 5.1, Table1

Urinary-tractinfections [culture and sensitivitytesting],

section5.1.13

Treatmentof fungal infections:aspergillosis, section5.2

Treatmentof fungalinfections: invasiveor disseminated

candidiasis,section 5.2

Indinavir [application of ‘less suitable for prescribing’

symbol],section 5.3.1

Saquinavir[changes tocautions andcontra-indications],

section5.3.1

Peginterferon alfa, interferon alfa, and ribavirin for

chronichepatitis C [NICE guidance],section 5.3.3

Palivizumab[updated advice], section 5.3.5

Prophylaxisagainst malaria[recommendations forMor-

occoand Turkmenistan removed], section5.4.1

Rosiglitazone[marketing authorisationsuspended], sec-

tion6.1.2.3

Liraglutidefor the treatmentof type 2 diabetesmellitus

[NICEguidance], section 6.1.2.3

Diabeticketoacidosis, section 6.1.3

Treatmentof hypoglycaemia, section 6.1.4

Denosumabfor theprevention of osteoporoticfractures

in postmenopausal women [NICE guidance], section

6.6.2

Recurrent vulvovaginalcandidiasis [updated treatment

regimens],section 7.2.2

Combinedhormonal contraceptive interactions,section

7.3.1

Combinedoral contraceptives [preparations tabulated],

section7.3.1

Imatinibfor the adjuvant treatment of gastro-intestinal

stromaltumours [NICE guidance], section8.1.5

Imatinibfor thetreatment ofunresectable and/or meta-

static gastro-intestinal stromal tumours [NICE gui-

dance],section 8.1.5

Trastuzumabfor the treatment of HER2-positivemeta-

staticgastric cancer [NICE guidance],section 8.1.5

Bevacizumaband sunitinib: risk ofosteonecrosis of the

jaw[MHRA/CHM advice], section 8.1.5

Cautionwhen dispensing mycophenolate mofetil [new

brandavailable], section 8.2.1

Rapamune

tablets[0.5 mg tabletnot bioequivalent to

otherstrengths], section 8.2.2

Eltrombopagfor thetreatment of chronicimmune (idio-

pathic) thrombocytopenic purpura [NICE guidance],

section9.1.4

G6PD deﬁciency [rasburicase and risk of haemolysis],

section9.1.5

Calcium gluconate injection [MHRA advice], section

9.5.1

Drugsunsafe for use in acuteporphyrias, section 9.8.2

Etanercept, inﬂiximab, and adalimumab for psoriatic

arthritis[NICE guidance], section 10.1.3

Adalimumab,etanercept, inﬂiximab,rituximab,and aba-

taceptfor rheumatoid arthritisafter the failureof a TNF

inhibitor[NICE guidance], section 10.1.3

Tocilizumabfor rheumatoid arthritis [NICE guidance],

section10.1.3

Distigmine [removal of monograph for use in myas-

theniagravis], section 10.2.1

Aqueouscream [skinreactions when usedas a leave-on

emollient],section 13.2.1

Immunisationschedule, section 14.1

Haemophilustype B conjugate vaccine incomplement

deﬁciency,section 14.4

Inﬂuenzavaccines, section 14.4

Meningococcalvaccines incomplement deﬁciency,sec-

tion14.4

Adult advanced life support algorithm [Resuscitation

Council (UK) updated algorithm 2010], inside back

cover

xvi BNF 61

Dose changes

Changes in dose statements introduced into BNF No.

61:

Aciclovir [herpes simplex treatment and suppression],

p.393

AmBisome

,p. 378

Atazanavir[paediatric dose], p. 386

Benzylpenicillin,p. 333

Bisacodyl,p. 69

Cefadroxil,p. 341

Cervarix

,p. 757

Cetirizine[dose in renal impairment], p.192

Cetirizine[paediatric dose], p. 192

Co-amoxiclav[intravenous dose], p.337

Cyproterone acetate [prevention of ﬂare with initial

gonadorelinanalogue therapy], p.573

Daptomycin[dose in renal impairment],p. 357

Ethosuximide[paediatric dose], p. 283

Famciclovir,p. 394

Fersamal

,p. 578

Fluoxetine[obsessive compulsive disorder], p.241

Foradil

[dosefor children under 12years], p. 177

Fulvestrant,p. 570

Galantamine[dose in hepatic impairment], p.318

Hyoscinebutylbromide [by continuous infusion device

for bowel colic and excessive respiratory secretions],

p. 23

Hyoscinehydrobromide [by subcutaneous injectionfor

excessiverespiratory secretions], p. 21

Inﬂiximab[severe active Crohn’s disease],p. 66

Ipratropium[dose frequency forsevere acute asthmain

adults],p. 171 and p.173

Itraconazole[histoplasmosis], p. 375

Melatonin,p. 212

Meropenem,p. 346

Methoxypolyethylene glycol-epoetin beta,p. 586

Metronidazole,p. 367

Pabrinex

[Wernicke’sencephalopathy], p.616

Pancuronium,p. 789

Pantoprazole,p. 57

Phenytoinsodium, p. 297

Prednisolone [maximum dose in paediatric acute

asthma],p. 171 and p.173

Primidone[essential tremor], p. 288

Remifentanil [analgesia and sedation in ventilated,

intensive-carepatients], p. 787

Salofalk

tablets,p. 62

Saquinavir,p. 389

Seleniumsulphide [pityriasis versicolor text],p. 736

Sodiumvalproate [epilepsy], p.291

Suxamethonium[by intravenous injection], p.790

Temazepam[premedication], p. 785

Thiamine[mild deﬁciency], p. 616

Vagifem

,p. 491

Valaciclovir,p. 394

Xylometazoline[nasal spray], p. 692

Classiﬁcation changes

Classiﬁcationchanges have beenmade in the following

sectionsfor BNF No.61:

Section2.1.2 Phosphodiesterase type-3inhibitors [title

change]

Section3.3.3 Phosphodiesterase type-4inhibitors [new

sub-section]

Section 4.7.1 Non-opioid analgesics and compound

analgesicpreparations [title change]

Section4.10.1 Alcohol dependence [newsection]

Section4.10.2 Nicotine dependence [newsection]

Section4.10.3 Opioid dependence [newsection]

Section 4.10.3 Opioid substitution therapy [new sub-

section]

Section 4.10.3 Adjunctive therapy and symptomatic

treatment[new sub-section]

Section 4.10.3 Opioid-receptor antagonists [new sub-

section]

Section10.3 Drugs for the relief of soft-tissue inﬂam-

mationand topical pain relief[title change]

Section10.3.2 Rubefacients,topical NSAIDs,capsaicin,

andpoultices [title change]

Section15.1.4.1 Anxiolytics [title change]

New names

Namechanges introduced into BNFNo. 61:

Hydrocortisonemucoadhesive buccal tablets [formerly

Corlan

],p. 694

Laxido

Orange

[formerly

Laxido

],p. 71

Oilatum

Junior bath additive

[formerly

Oilatum

Junioremollient bath additive

],p. 704

Deleted preparations

Preparationslisted below have been discontinued dur-

ingthe compilation of BNFNo. 61, orare still available

but are not considered suiatable for inclusion bythe

JointFormulary Committee (see footnote).

Actinac

Andropatch

Avandamet

Avandia

Baxan

Clonidineinjection

Dexedrine

Digitoxin

Dimercaprol

Flixotide

Diskhaler

Imuderm

1.Not considered suitable for inclusion by the Joint

FormularyCommittee

BNF 61 xvii

Lidocaine5% ointment

Linola

Gamma

Loceryl

cream

Magnapen

syrup

Mixtard

Modalim

ModisalLA

Neosporin

Norvir

capsules

Octagam

PolytarAF

Premarin

vaginalcream

Premique

Cycle

Protirelin

Regainefor Men Regular Streng th

Rosiglitazone

Select-A-Jet

Dopamine

Staril

Zincsulphate eye drops

Zoleptil

Zotepine

New preparations included in this

edition

Preparations included in the relevantsections of BNF

No.61:

Adoport

[tacrolimus],p. 558

Aquamol

,p. 702

Arzip

[mycophenolatemofetil], p. 555

Bocouture

[botulinumtoxin type A], p.309

Calcichew-D

500mg/400unit caplets [calcium carb-

onatewith colecalciferol], p. 619

Capimune

[ciclosporin],p. 557

Catacrom

[sodiumcromoglycate], p. 673

ClinitasGel

[carbomers],p. 680

Cyanokit

[hydroxocobalamin],p. 39

Daxas

[roﬂumilast],p. 191

DermatonicsHeel Balm

,p. 703

Dovobet

gel[betametasone with calcipotriol], p.717

Dovonex

ointment[calcipotriol], p. 717

GenotropinGoQuick

[somatropin],p. 465

Glusartel

[glucosaminesulphate], p. 657

Gynoxin

[fenticonazole],p. 493

HumulinI KwikPen

[isophaneinsulin], p. 424

Humulin M3 KwikPen

[biphasic isophane insulin],

p.426

Hyabak

[sodiumhyaluronate], p. 681

Hylo-Care

[sodiumhyaluronate], p. 681

InsumanComb 25 SoloStar

[biphasicisophane insu-

lin],p. 426

Levact

[bendamustine],p. 524

Lodotra

[prednisone],p. 448

Lumecare

LongLasting Tear Gel

[carbomers],p. 680

Lumecare

Preservative Free Tear Drops

[hypro-

mellose],p. 680

Marol

[tramadolm/r], p. 272

Miphtel

[acetylcholinechloride], p. 682

Monofer

[ironisomaltoside 1000], p. 579

Moxivig

[moxiﬂoxacin],p. 668

Neokay

[phytomenadione],p. 621

Nexplanon

[etonorgestrel],p. 502

Nivestim

[ﬁlgrastim],p. 592

NuTRIﬂex

Omegaplus

,p. 605

NuTRIﬂex

Omegaspecial

,p. 605

OnbrezBreezhaler

[indacaterol],p. 177

Ozurdex

[dexamethasone],p. 671

PecFent

[fentanyl],p. 266

Rebif

(

Rebidose

)injection [interferonbeta-1a], p.562

Renvela

[sevelamarcarbonate], p. 613

Sativex

[

Cannabissativa

extract],p. 661

Simponi

[golimumab],p. 653

TearsNaturale

SingleDose

[hypromellose],p. 680

Tevagrastim

[ﬁlgrastim],p. 593

Tobravisc

[tobramycin],p. 669

Tracutil

,p. 607

Vimovo

[naproxenwith esomeprazole], p.639

Votrient

[pazopanib],p. 548

VPRIV

[velaglucerasealfa], p. 624

Zutectra

[hepatitisB-speciﬁc immunoglobulin], p.771

xviii BNF 61

Guidance on prescribing

General guidance

Medicines should be prescribed only when they are

necessary,and in all cases thebeneﬁt of administering

themedicine shouldbe consideredin relation tothe risk

involved. This is particularly important during

pregnancy, when the risk to both mother and fetus

mustbe considered (for further details see Prescribing

inPregnancy, p. 19).

It is important to discuss treatment options carefully

withthe patient to ensurethat the patient iscontent to

takethe medicine as prescribed (see alsoTaking Med-

icines to Best Effect, below). In particular,the patient

should be helped to distinguish the adverse effects of

prescribed drugs from the effects of the medical dis-

order.When the beneﬁcial effects of the medicine are

likely to be delayed, the patient should be advised of

this.

Taking medicines to best effect

Difﬁculties in

adherence to drug treatment occur regardless of age.

Factors contributing to poor compliance with pre-

scribedmedicines include:

prescriptionnot collected or notdispensed;

purposeof medicine not clear;

perceivedlack of efﬁcacy;

realor perceived adverse effects;

patients’perception of therisk and severityof side-

effectsmay differ from that ofthe prescriber;

instructionsfor administration not clear;

physicaldifﬁculty intaking medicines (e.g.swallow-

ingthe medicine,handling small tablets,or opening

medicinecontainers);

unattractiveformulation (e.g. unpleasant taste);

complicatedregimen.

The prescriber and the patient should agree on the

health outcomes that the patient desires and on the

strategy for achieving them (‘concordance’). The pre-

scriber should be sensitive to religious, cultural, and

personal beliefs that can affect a patient’s acceptance

ofmedicines.

Takingthe time toexplain to the patient(and relatives)

therationale and the potential adverse effectsof treat-

mentmay improve adherence. Reinforcement andela-

borationof the physician’s instructions bythe pharma-

cist and other members of the healthcare team also

helps.Advising the patient of thepossibility of alterna-

tive treatments may encourage the patient to seek

advicerather than merely abandonunacceptable treat-

ment.

Simplifying the drug regimen may help; the need for

frequent administration may reduce adherence,

althoughthere appears to be little difference in adher-

ence between once-daily and twice-daily administra-

tion. Combination products reduce the number of

drugs takenbut at the expense of the ability to titrate

individualdoses.

Biosimilarmedicines

Abiosimilar medicineis a new

biologicalproduct that issimilar to a medicinethat has

alreadybeen authorised to be marketed(the biological

referencemedicine) in the EuropeanUnion. The active

substance of a biosimilar medicine is similar, but not

identical,to the biological reference medicine. Biologi-

calproducts are different from standard chemical pro-

ductsin terms oftheir complexity andalthough theore-

ticallythere shouldbe noimportant differencesbetween

thebiosimilar and the biological reference medicinein

termsof safety or efﬁcacy, whenprescribing biological

products,it isgood practiceto use thebrand name.This

will ensure that substitution of a biosimilar medicine

doesnot occur when themedicine is dispensed.

Biosimilarmedicines have black triangle status(T, see

p.12) at the timeof initial marketing. Itis important to

reportsuspected adverse reactions to biosimilar medi-

cinesusing the Yellow Card Scheme (p.12). For biosi-

milarmedicines, adversereaction reports shouldclearly

statethe brand name ofthe suspected medicine.

Complementary and alternative medicine

increasing amount of information on complementary

and alternative medicine is becoming available. The

scope of the BNF is restricted to the discussion of

conventionalmedicines but reference is made tocom-

plementarytreatments if they affect conventionalther-

apy(e.g. interactionswith StJohn’s wort—see Appendix

1).Further information onherbal medicines isavailable

atwww.mhra.gov.uk.

Abbreviationof titles

Ingeneral, titles of drugsand

preparationsshould be written

infull

.Unofﬁcial abbre-

viations should not be used as they may be misinter-

preted.

Non-proprietarytitles

Wherenon-proprietary (‘gen-

eric’)titles aregiven, theyshould be usedin prescribing.

Thiswill enable any suitable product to be dispensed,

thereby saving delay to the patient and sometimes

expense to the health service. The onlyexception is

where there is a demonstrable difference in clinical

effect betweeneach manufacturer’s version of the for-

mulation, making it important that the patient should

alwaysreceive thesame brand; insuch cases,the brand

name or themanufacturer should be stated. Non-pro-

prietarytitles shouldnot beinvented forthe purposes of

prescribinggenerically since thiscan lead to confusion,

particularly in the case of compound and modiﬁed-

releasepreparations.

Titles used as headings for monographs maybe used

freelyin theUnited Kingdom butin othercountries may

besubject to restriction.

Manyof the non-proprietarytitles used inthis book are

titles ofmonographs in the European Pharmacopoeia,

British Pharmacopoeia, or British Pharmaceutical

Codex1973. In such casesthe preparations must com-

ply with the standard (if any) in the appropriate pub-

lication,as required by theMedicines Act (Section 65).

Proprietary titles

Names followed bythe symbol

are or have been used as proprietary names in the

United Kingdom. These names may in general be

appliedonly to products suppliedby the owners of the

trademarks.

BNF 61 1

General guidance

Marketingauthorisation and BNF advice

Ingen-

eral the

doses, indications, cautions, contra-indica-

tions,

and

side-effects

in the BNF reﬂect those in the

manufacturers’ data sheets or Summaries ofProduct

Characteristics (SPCs) which, in turn, reﬂect those in

the corresponding marketing authorisations (formerly

known as Product Licences). The BNF does not gen-

erally include proprietary medicines that are not sup-

portedby avalid Summaryof ProductCharacteristics or

whenthe marketing authorisation holder has not been

able tosupply essential information. When a prepara-

tionis available from more thanone manufacturer, the

BNFreﬂects advice that is the most clinically relevant

regardlessof any variation in the marketing authorisa-

tions.Unlicensed products can be obtained from ‘spe-

cial-order’ manufacturers or specialist importing com-

panies,see p. 988.

Wherean unlicensed drugis includedin the BNF,this is

indicatedin square brackets after the entry. When the

BNFsuggests ause (orroute) thatis outsidethe licensed

indication of a product (‘off-label’ use), this too is

indicated.Unlicensed use ofmedicines becomes neces-

sary if the clinical need cannot be met by licensed

medicines;such useshould besupported byappropriate

evidenceand experience.

The doses stated inthe BNF are intended for general

guidance and represent, unless otherwisestated, the

usual range of doses that are generally regarded as

beingsuitable for adults.

Prescribingmedicines outsidethe recommendations

oftheir marketing authorisationalters (andprobably

increases)the prescriber’sprofessional responsibility

andpotential liability.The prescriber should beable

to justify and feel competent in using such medi-

cines.

Oralsyringes

Anoral syringe is supplied whenoral

liquid medicines are prescribed in doses other than

multiples of 5mL. The oral syringe is marked in 0.5-

mLdivisions from 1 to 5mL to measure doses of less

than 5mL (other sizes of oral syringe may also be

available).It isprovided with anadaptor andan instruc-

tionleaﬂ et.The

5-mLspoon

isused for doses of 5mL

(ormultiples thereof).

Toavoid inadvertent intravenous administration of

oral liquid medicines, only an appropriate oral or

enteralsyr inge should be used to measurean oral

liquid medicine (if a medicine spoon or graduated

measurecannot be used);these syringes shouldnot

becompatible with intravenous or other parenteral

devices. Oral or enteralsyringes shouldbe clearly

labelled‘Oral’ or‘Enteral’ ina large fontsize; itis the

healthcare practitioner’s responsibility to label the

syringewith thisinformation if themanufacturer has

notdone so.

Strengthsand quantities

Thestrength or quantity

to be contained in capsules, lozenges, tablets, etc.

should be stated by the prescriber. In particular,

strengthsof liquid preparationsshould be clearlystated

(e.g.125 mg/5mL).

Ifa pharmacistreceives anincomplete prescriptionfor a

systemicallyadministered preparation and considers it

wouldnot beappropriate for thepatient to returnto the

doctor,the following procedureswill apply

(a) an attempt mustalways be made to contact the

prescriberto ascertain the intention;

(b) if the attempt issuccessful thephar macist must,

wherepracticable, subsequently arrange fordetails

ofquantity, strength where applicable, and dosage

tobe inserted by the prescriber onthe incomplete

form;

it has not proved possible to obtain the written

intention regarding an incomplete prescription,

the pharmacist may endorse the form ‘p.c.’(pre-

scriber contacted) and add details of the quantity

and strength where applicable of the preparation

supplied, and ofthe dose indicated. The endorse-

mentshould be initialledand dated bythe pharma-

cist;

(d) where the prescriber cannot be contactedand the

pharmacist has sufﬁcient information to make a

professional judgement the preparation may be

dispensed.If the quantityis missing thepharmacist

may supply sufﬁcient to complete upto 5 days’

treatment; except that where a combination pack

(i.e. a proprietary pack containing more than one

medicinal product) or oral contraceptive is pre-

scribed by name only, the smallest pack shall be

dispensed. In all cases the prescription must be

endorsed ‘p.n.c.’ (prescriber not contacted), the

quantity,the dose, and the strength(where applic-

able)of the preparationsupplied mustbe indicated,

andthe endorsement must beinitialled and dated;

(e) if the phar macist has any doubt about exercising

discretion, an incomplete prescription must be

referredback to the prescriber.

Excipients

Branded oral liquid preparations that do

notcontain

fructose

glucose

,or

sucrose

aredescribed

as ‘sugar-free’ in the BNF. Preparations containing

hydrogenatedglucose syr up,mannitol, maltitol, sorbi-

tol,or xylitol are alsomarked ‘sugar-free’ sincethere is

evidencethat they do not cause dentalcaries. Patients

receiving medicines containing cariogenic sugars

should beadvised of appropriate dental hygiene mea-

suresto prevent caries. Sugar-free preparations should

beused whenever possible.

Where information on the presence of

aspartame,

gluten

sulphites

tartrazine

arachis (peanut) oil

sesame oil

is available, this is indicated in the BNF

againstthe relevant preparation.

Information is provided on

selected excipients

in skin

preparations(section 13.1.3), invaccines (section 14.1),

and on

selected preservatives

and

excipients

in eye

dropsand injections.

Thepresence of

benzylalcohol

and

polyoxylcastor oil

(polyethoxylatedcastor oil) in injections isindicated in

theBNF.Benzyl alcohol hasbeen associatedwith a fatal

1.These recommendations are acceptablefor prescription-

only medicines (A). For items markedC see also

ControlledDrugs and Drug Dependence,p. 8.

2 Generalguidance BNF 61

General guidance

toxic syndrome in preterm neonates, and therefore,

parenteral preparations containing the preservative

should not be used in neonates. Polyoxyl castor oils,

used as vehicles in intravenous injections, have been

associatedwith severe anaphylactoid reactions.

Thepresence of

propyleneglycol

inoral or parenteral

medicinesis indicated inthe BNF; it cancause adverse

effectsif its elimination isimpaired, e.g. inrenal failure,

inneonates and young children, and inslow metaboli-

sersof thesubstance. Itmay interactwith disulﬁramand

metronidazole.

The

lactose

contentin most medicines is too small to

cause problems in most lactose-intolerant patients.

Howeverin severe lactoseintolerance, the lactosecon-

tent should be determined before prescribing. The

amount of lactose varies according to manufacturer,

product,formulation, and strength.

In the absenceof infor mationon excipients in the

BNF and in the product literature (available at

www.emc.medicines.org.uk),contact the manufac-

turer (see Indexof Manufacturers) if it is essential

tocheck details.

Extemporaneouspreparation

Aproduct should be

dispensed extemporaneously only when no product

witha marketing authorisation isavailable.

The BP direction that a preparation must be

freshly

prepared

indicatesthat it must bemade not morethan

24hours before itis issued for use.The direction thata

preparationshould be

recentlyprepared

indicatesthat

deterioration is likely if the preparationis stored for

longerthan about 4 weeksat 15–258 C.

Theterm waterused without qualiﬁcationmeans either

potable water freshly drawn direct from the public

supply and suitable for drinking or freshly boiled and

cooledpuriﬁed water. The latter should be used if the

public supply is from a local storage tank or if the

potablewater is unsuitable for aparti cular preparation

(Waterfor injections, section9.2.2).

Drugsand driving

Prescribersand other healthcare

professionalsshould advisepatients iftreatment islikely

toaffect their ability to perform skilledtasks (e.g. driv-

ing). This applies especially to drugs with sedative

effects; patients should be warned that these effects

are increasedby alcohol. General information about a

patient’sﬁtness todrive is availablefrom theDriver and

VehicleLicensing Agency at www.dvla.gov.uk.

Patents

Inthe BNF,certain drugs have beenincluded

notwithstanding the existence of actual or potential

patentrights. In sofar as suchsubstances areprotected

by Letters Patent, their inclusion in this Formulary

neitherconveys, nor implies, licenceto manufacture.

Health and safety

When handlingchemical or bio-

logicalmaterials particular attentionshould be given to

the possibility of allergy, ﬁre, explosion, radiation, or

poisoning. Substances such as corticosteroids, some

antimicrobials, phenothiazines, and many cytotoxics,

areir ritantor very potent and should be handledwith

caution. Contact with the skin and inhalation of dust

shouldbe avoided.

Safetyin the home

Patientsmust bewarned to keep

allmedicines out ofthe reach ofchildren. All soliddose

and all oral and external liquid preparations must be

dispensed in a reclosable

child-resistant container

unless:

themedicine is in an original packor patient pack

suchas to make thisinadvisable;

the patient will havedif ﬁculty in opening a child-

resistantcontainer;

aspeciﬁc requestis made thatthe product shallnot

bedispensed in a child-resistantcontainer;

no suitable child-resistant container exists for a

particularliquid preparation.

Allpatients should be advised to dispose of

unwanted

medicines

byreturning them to a supplier for destruc-

tion.

Nameof medicine

Thename of themedicine should

appear on the label unless the prescriber indicates

otherwise.

(a) The strengthis alsostated on thelabel inthe caseof

tablets,capsules, and similar preparations that are

availablein different strengths.

(b) If it is thewish of the prescriber that adescription

suchas ‘TheSedative Tablets’should appear onthe

label, the prescriber should write the desired

descriptionon the prescription form.

proprietary names or titles given in the BP, BPC,

BNF,DPF,or NPF.

(d) The name written on the label isthat used by the

prescriberon the prescription.

(e) When a prescriptionis written other than on an

NHSprescription form the name of theprescribed

preparation will be stated on the label of the dis-

pensed medicine unless the prescriber indicates

otherwise.

(f) The Council of the Royal Pharmaceutical Society

advises that the labels of dispensed medicines

should indicate the total quantity of the product

dispensedin thecontainer to whichthe label refers.

This requirement applies equally tosolid, liquid,

internal, andexternal preparations. If a product is

dispensedin morethan onecontainer, thereference

shouldbe to the amountin each container.

Non-proprietarynames of compoundpreparations

whichappear in the BNF are those that havebeen

compiledby theBritish PharmacopoeiaCommission

oranother recognisedbody; whenever possiblethey

reﬂectthe names of the activeingredients.

Prescribers should avoid creating their own com-

pound names for the purposes of generic pre-

scribing; such names do not have an approved

deﬁnitionand can be misinterpreted.

Special careshould be taken to avoid errors when

prescribing compound preparations; in particular

thehyphen in the preﬁx‘co-’ should be retained.

Specialcare should also be taken to avoidcreating

generic names for modiﬁed-release preparations

wherethe use of these names could lead toconfu-

sionbetween formulations with different lengths of

action.

BNF 61 Generalguidance 3

General guidance

EEAand Swiss prescriptions

Pharmacistscan dis-

penseprescriptions issued bydoctors anddentists from

the European Economic Area (EEA) or Switzerland

(exceptprescriptions for controlled drugs in Schedules

1to 5 or for drugs without a UK marketing authorisa-

tion).Prescriptions shouldbe written in ink orotherwise

soas to be indelible, should bedated, should state the

name of the patient, should state theaddress of the

prescriber, should contain particulars indicating

whetherthe prescriberis a doctoror dentist,and should

besigned by the prescriber.

Securityand validity of prescriptions

TheCoun-

cils of the British Medical Association and the Royal

PharmaceuticalSociety haveissued ajoint statementon

thesecurity and validity ofprescriptions.

Inparticular, prescription forms should:

notbe left unattended atreception desks;

notbe left in acar where they may bevisible; and

whennot in use, bekept in a lockeddrawer within

thesurgery and at home.

Where there is any doubt about the authenticity of a

prescription,the pharmacist shouldcontact the prescri-

ber.If this is doneby telephone, the numbershould be

obtainedfrom the directory rather than relying on the

information on the prescription for m, which may be

false.

Patient group direction (PGD)

In most cases, the

most appropriate clinical care will be provided on an

individualbasis by a prescriber to a speciﬁcindividual

patient.However, a Patient GroupDirection for supply

and administration of medicines by other healthcare

professionalscan beused where itwould beneﬁtpatient

carewithout compromising safety.

APatient GroupDirection is awritten direction relating

to the supply and administration (or administration

only)of alicensed prescription-onlymedicine bycertain

classes of healthcare professionals; the Direction is

signed by a doctor (or dentist) and by a pharmacist.

Further information on Patient Group Directions is

available in Health Service Circular HSC 2000/026

(England), HDL (2001) 7(Scotland), and WHC (2000)

116 (Wales) and at www.nelm.nhs.uk/en/

Communities/NeLM/PGDs.

NICEand Scottish Medicines Consortium

Advice

issuedby the National Institute forHealth and Clinical

Excellence(NICE) isincluded inthe BNFwhen relevant.

The BNF also includes advice issued by the Scottish

Medicines Consortium (SMC) when a medicine is

restricted or not recommended for use within NHS

Scotland. If advice within a NICE Single Technology

Appraisaldiffers from SMC advice,the Scottish Execu-

tiveexpects NHS Boards withinNHS Scotland to com-

plywith the SMCadvice. Details of theadvice together

withupdates canbe obtainedfrom www.nice.org.ukand

fromwww.scottishmedicines.org.uk.

4 Generalguidance BNF 61

General guidance

Prescription writing

Sharedcare

In its guidelines on responsibility for prescribing

(circularEL (91) 127)between hospitalsand general

practitioners,the Department ofHealth has advised

thatlegal responsibility for prescribing lieswith the

doctorwho signs the prescription.

Prescriptions

shouldbe written legibly inink or other-

wiseso asto be indelible

,should bedated, should state

the name and address of the patient, and should be

signedin inkby the prescriber

.The ageand the dateof

birthof the patientshould preferably bestated, and itis

a legal requirement in the case of prescription-only

medicinesto state the agefor children under 12 years.

Thefollowing should be noted:

(a) The unnecessary use of decimal points should be

avoided,e.g. 3mg, not 3.0mg.

Quantitiesof 1 gram or moreshould be written as

1g etc.

Quantitiesless than 1gram should be writtenin

milligrams,e.g. 500mg, not 0.5g.

Quantitiesless than 1mg should be writtenin

micrograms,e.g. 100micrograms, not 0.1mg.

Whendecimals are unavoidable azero should be

writtenin front of thedecimal point where there is

noother ﬁgure, e.g. 0.5mL, not .5mL.

Useof the decimal pointis acceptable toexpress a

range,e.g. 0.5 to 1g.

(b) ‘Micrograms’ and‘nanograms’ shouldnot beabbre-

viated.Similarly ‘units’ should notbe abbreviated.

isused in medicine

and pharmacy, and cubiccentimetre, c.c., or cm

shouldnot be used.

(d) Dose and dose frequency should be stated; in the

case of preparations to be taken ‘as required’ a

minimumdose interval should be speciﬁed.

Whendoses other than multiplesof 5 mLare pre-

scribed for

oral liquid preparations

the dose-

volume will be provided by means of an oral

syringe,see p. 2 (exceptfor preparations intended

tobe measured with apipette).

Suitablequantities:

Elixirs, Linctuses, and Paediatric Mixtures (5-

mLdose), 50, 100, or150 mL

AdultMixtures (10-mL dose), 200or 300 mL

EarDrops, Eye drops,and Nasal Drops, 10mL

(orthe manufacturer’s pack)

Eye Lotions, Gargles, and Mouthwashes,

200mL

(e) For suitable quantities of dermatological prepara-

tions,see section 13.1.2.

(f) The names of drugs and preparationsshould be

writtenclearly andnot abbreviated,using approved

titlesonly (see also advice inbox on p. 3to avoid

creatinggeneric titles formodiﬁed-release prepara-

tions).

(g) The quantity to be supplied may be stated by

indicatingthe numberof days oftreatment required

inthe box provided on NHS forms. In most cases

the exact amount will be supplied. This does not

applyto items directed to be used as required—if

the dose and frequency are not given then the

quantityto be supplied needsto be stated.

Whenseveral items are orderedon one form the

box can be marked with the number of days of

treatment provided the quantity is added for any

itemfor which the amountcannot be calculated.

(h) Although directionsshould preferably bein English

without abbreviation, it is recognised that some

Latinabbreviations are used (for details seeInside

BackCover).

(i) Medical and dental practitioners may prescribe

unlicensedmedicines (i.e. those without marketing

authorisation)or withdrawnmedicines. Theprescri-

bershould inform the patient orthe patient’s carer

thatthe product doesnot have amarketing author-

isation.

Fora sample prescription, seebelow.

1.These recommendations are acceptablefor prescription-

only medicines (A). For items markedC see also

ControlledDrugs and Drug Dependence,p. 8.

2.It is permissible to issue carbon copiesof NHS prescrip-

tionsas long asthey are signed inink.

3.Computer-generated facsimile signatures donot meet the

legalrequirement.

4.The use of capital ‘L’ in mL is a printing convention

throughoutthe BNF; both ‘mL’and ‘ml’ arerecognised SI

abbreviations.

BNF 61 Prescription writing 5

Prescription writing

Prescribing by dental surgeons

Until new pre-

scribing arrangements are in place for NHS prescrip-

tions,dental surgeons shoulduse form FP10D(GP14 in

Scotland, WP10D in Wales)to prescribe only those

items listed in the Dental Practitioners’ Formulary.

The Act and Regulations do not set any limitations

upon thenumber and variety of substances which the

dentalsurgeon mayadminister topatients inthe surgery

or may order by private prescription—provided the

relevant legal requirements are observed the dental

surgeonmay use or order whatever isrequired for the

clinicalsituation. There is no statutoryrequirement for

the dental surgeon to communicate with a patient’s

medical practitioner when prescribing for dental use.

Thereare, however,occasionswhen this wouldbe inthe

patient’s interest and such communication is to be

encouraged.For legalrequirements relating toprescrip-

tionsfor Controlled Drugs, seep. 8.

Computer-issuedprescriptions

Forcomputer-issued prescriptionsthe following advice,

based onthe recommendations of the Joint GP Infor-

mationTechnology Committee, shouldalso be noted:

1. The computermust print outthe date, thepatient’s

surname,one forename, otherinitials, and address,

andmay alsoprint out thepatient’s titleand date of

birth. The age of children under 12 years and of

adults over 60 years must be printed inthe box

available;the age of children under5 years should

beprinted in yearsand months. A facilitymay also

existto printout theage of patientsbetween 12and

60years.

2. Thedoctor’s namemust be printedat thebottom of

theprescription form; this will be the name of the

doctor responsible for the prescription(who will

normally sign it). The doctor’s surgery address,

referencenumber, and Primary Care Trust (PCT

)

are also necessary. In addition, the surgery tele-

phonenumber should be printed.

3. When prescriptions are to be signed by general

practitioner registrars,assistants, locums, or depu-

tisingdoctors, thename of thedoctor printed atthe

bottomof the formmust still be thatof the respon-

sibleprincipal.

4. Names of medicinesmust come from a dictionary

held in the computer memory, to provide a check

on the spelling and to ensure that the name is

written infull. The computer can be programmed

torecognise both the non-proprietary andthe pro-

prietaryname of a particular drug andto print out

the preferred choice, but must not print out both

names.For medicinesnot inthe dictionary,separate

checksare required—the usermust be warnedthat

no check waspossible and the entire prescription

mustbe entered in thelexicon.

5. The dictionary may contain information on the

usual doses, formulations, and pack sizes to pro-

duce standard predetermined prescriptions for

common preparations,and to provide a check on

thevalidity of an individualprescription on entry.

6. Theprescription must beprinted in Englishwithout

abbreviation;information may beentered or stored

inabbreviated form. Thedose must bein numbers,

thefrequency inwords, andthe quantityin numbers

in brackets, thus: 40mg four times daily (112). It

mustalso be possibleto prescribe byindicating the

lengthof treatment required, see(h) above.

7. The BNF recommendationsshould be followed as

in(a), (b), (c), (d),and (e) above.

8. Checks maybe incorporated to ensure that all the

information required for dispensing a particular

drug has been ﬁlled in. For instructions such as

‘as directed’ and ‘when required’, the maximum

dailydose should normally bespeciﬁed.

9. Numbersand codes usedin the systemfor organis-

ing and retrieving data mustnever appear on the

form.

10. Supplementary warnings oradvice should be writ-

tenin full,should notinterfere with theclarity ofthe

prescription itself, and should be in line with any

warnings or advice in the BNF; numerical codes

shouldnot be used.

11. A mechanism (such as printing a series of non-

speciﬁccharacters) should be incorporated tocan-

celout unused space, orwording such as‘no more

itemson this prescription’ may be added after the

last item. Otherwise the doctor should delete the

spacemanually.

12. To avoid forgery the computer may print on the

form thenumber of items to be dispensed (some-

where separate from the box for the pharmacist).

Thenumber of itemsper form needbe limited only

by the ability of the printer to produce clear and

well-demarcated instructions with sufﬁcient space

for each item anda spacer linebefore each fresh

item.

13. Handwritten alterations should only be made in

exceptional circumstances—it is preferable to

printout a new prescription. Any alterations must

bemade inthe doctor’s ownhandwriting andcoun-

tersigned; computerrecords should be updated to

fully reﬂect any alteration.Prescriptions for drugs

usedfor contraceptive purposes(but which are not

promoted as contraceptives) may need to be

marked in handwriting with the symbol , (or

endorsed inanother way to indicate that the item

isprescribed for contraceptive purposes).

14. Prescriptions for controlled drugs can beprinted

from the computer, but the prescriber’s signature

mustbe handwritten

15. The stripof paper on theside of the FP10SS

may

be used for various purposes but care should be

takento avoidincluding conﬁdential information.It

maybe advisablefor thepatient’s nameto appearat

the top, but this should be preceded by ‘conﬁden-

tial’.

16. In rural dispensing practices prescription requests

(ordetails of medicinesdispensed) will normallybe

entered in one surgery. The prescriptions (or dis-

pensedmedicines) maythen needto bedelivered to

anothersurgery or location; if possiblethe compu-

tershould hold up to10 alternatives.

17. Prescription formsthat are reprinted orissued as a

duplicateshould be labelled clearlyas such.

1.Health Board inScotland, Local Health Boardin Wales.

2.See Controlled Drugs and Drug Dependence p.8; the

prescribermay use a datestamp.

3.GP10SS in Scotland,WP10SS in Wales.

6 Prescriptionwriting BNF 61

Prescription writing

Emergency supply of medicines

Emergency supply requested by

member of the public

Pharmacistsare sometimes calledupon by membersof

thepublic to make an emergencysupply of medicines.

The Prescription Only Medicines (Human Use) Order

1997 allows exemptions from the Prescription Only

requirements for emergency supply to be made by a

person lawfullyconducting a retail pharmacy business

provided:

(a) that the pharmacist has interviewed the person

requesting the prescription-only medicine and is

satisﬁed:

(i) thatthere is immediate need for the prescrip-

tion-onlymedicine and that it is impracticable

in the circumstances to obtain a prescription

withoutundue delay;

(ii) that treatment with theprescription-only med-

icine has on a previous occasion been pre-

scribedfor the person requestingit;

(iii) asto the dose that it wouldbe appropriate for

theperson to take;

(b) that no greater quantityshall be supplied than will

provide5 days’ treatmentof phenobarbital, pheno-

barbitalsodium, orControlled Drugs inSchedules 4

or5,

or30 days’ treatment for otherprescription-

onlymedicines, except when the prescription-only

medicineis:

(i) insulin,an ointment orcream, or a preparation

forthe relief of asthmain an aerosol dispenser

whenthe smallest pack canbe supplied;

(ii) an oral contraceptivewhen a full cyclemay be

supplied;

(iii) anantibiotic in liquid form fororal administra-

tion when the smallest quantity that will

providea full course of treatment can be sup-

plied;

prescriptionbook stating:

(i) thedate of supply;

(ii) the name, quantityand, where appropriate,the

pharmaceuticalform and strength;

(iii) thename and address ofthe patient;

(iv) thenature of the emergency;

(d) that the container or package must be labelled to

show:

(i) thedate of supply;

(ii) the name, quantityand, where appropriate,the

pharmaceuticalform and strength;

(iii) thename of the patient;

(iv) thename and address ofthe pharmacy;

(v) the words ‘Emergencysupply’;

(vi) thewords ‘Keepout ofthe reach ofchildren’ (or

similarwarning);

(e) that the prescription-onlymedicine is not a sub-

stance speciﬁcally excluded from the emergency

supplyprovision, anddoes not containa Controlled

Drugspeciﬁed in Schedules1, 2, or3 to theMisuse

ofDrugs Regulations2001 except forphenobarbital

or phenobarbital sodium for the treatment of epi-

lepsy: for detailssee

Medicines, Ethics and Prac-

tice

, No. 34, London, Pharmaceutical Press, 2010

(andsubsequent editions as available).

Emergency supply requested by

prescriber

Emergencysupply of aprescription-only medicine may

also be made at the request of a doctor, a dentist, a

supplementary prescriber, a community practitioner

nurse prescriber, a nurse, pharmacist, oroptometrist

independentprescriber, or a doctoror dentist from the

EuropeanEconomic Area or Switzerland,provided:

(a) that thepharmacist issatisﬁed thatthe prescriberby

reason of some emergency is unable to furnish a

prescriptionimmediately;

(b) that the prescriber has undertaken to furnish a

prescriptionwithin 72 hours;

directionsof the prescriber requesting it;

(d) that themedicine is nota ControlledDrug speciﬁed

in Schedules 1, 2, or 3 to the Misuse of Drugs

Regulations2001 except for phenobarbital or phe-

nobarbitalsodium for thetreatment of epilepsy:for

detailssee

Medicines,Ethics and Practice

,No. 34,

London, Pharmaceutical Press, 2010 (and subse-

quenteditions as available);

(e) that anentr yshall bemade in theprescription book

stating:

(i) thedate of supply;

(ii) the name, quantityand, where appropriate,the

pharmaceuticalform and strength;

(iii) the name and address of the practitioner

requestingthe emergency supply;

(iv) thename and address ofthe patient;

(v) the date on theprescription;

(vi) when the prescription is received the entry

should be amended to include the date on

whichit is received.

Royal Pharmaceutical Society’s

guidelines

1. The pharmacist should consider the medical con-

sequencesof

not

supplyinga medicine in anemer-

gency.

2. If thephar macistis unable to make an emergency

supplyof a medicine thephar macistshould advise

thepatient how to obtainessential medical care.

For conditions that apply to supplies made at the

requestof a patientsee

Medicines,Ethics and Practice

No.34, London Pharmaceutical Press, 2010 (and sub-

sequenteditions).

1.Doctors ordentists from theEuropean EconomicArea and

Switzerland, or their patients, cannot request anemer-

gency supply of ControlledDr ugs, ordr ugs that do not

havea UK marketingauthorisation.

BNF 61 Emergency supply of medicines 7

Emergencysupply of medicines

Controlled Drugs and drug dependence

TheMisuse of Drugs Act, 1971 prohibitscertain activ-

itiesin relation to ‘Controlled Drugs’, in particular their

manufacture, supply, and possession. The penalties

applicableto offences involving the different drugsare

gradedbroadly according to the

harmfulnessattributa-

bleto a drug when it ismisuse d

andfor thispurpose the

drugsare deﬁned in the followingthree classes:

Class Aincludes: alfentanil, cocaine, diamorphine

(heroin), dipipanone, lysergide (LSD), methadone,

methylenedioxymethamfetamine (MDMA,

‘ecstasy’), morphine, opium, pethidine, phencycli-

dine, remifentanil, and class B substances when

preparedfor injection

Class Bincludes: oral ampfetamines, barbiturates,

cannabis, cannabis resin, codeine, ethylmorphine,

glutethimide, nabilone, pentazocine, phenmetra-

zine,and pholcodine

ClassC includes: certaindrugs related tothe amfe-

tamines such as benzfetamine and chlorphenter-

mine, buprenorphine, diethylpropion, mazindol,

meprobamate, pemoline, pipradrol, most benzo-

diazepines,zolpidem, androgenicand anabolicster-

oids, clenbuterol, chorionic gonadotrophin(HCG),

non-human chorionic gonadotrophin, somatotro-

pin,somatrem, and somatropin

The Misuse of Drugs Regulations 2001 deﬁne the

classes of person who are authorised to supply and

possess controlled drugs while acting in their profes-

sional capacities and lay down the conditions under

whichthese activities maybe carried out.In the regula-

tionsdrugs are dividedinto ﬁveschedules each specify-

ing the requirements governing such activities as

import, export, production, supply, possession, pre-

scribing,and record keeping whichapply to them.

Schedule 1 includes drugs such as cannabis and

lysergide which are not used medicinally. Posses-

sionand supplyare prohibitedexcept inaccordance

withHome Ofﬁce authority.

Schedule 2 includes drugs such as diamorphine

(heroin), morphine, nabilone, remifentanil, pethi-

dine, secobarbital, glutethimide, amfetamine, and

cocaineand are subject to the full controlleddr ug

requirementsrelating to prescriptions,safe custody

(exceptfor secobarbital),the need tokeep registers,

etc.(unless exempted in Schedule5).

Schedule3 includes the barbiturates(except seco-

barbital, nowSchedule 2), buprenorphine, diethyl-

propion, mazindol, meprobamate, midazolam,

pentazocine, phentermine, and temazepam. They

aresubject to thespecial prescription requirements

(except for temazepam) and to the safe custody

requirements(except for any 5,5disubstituted bar-

bituric acid (e.g.phenobarbital), mazindol, mepro-

bamate, midazolam, pentazocine, phentermine, or

any stereoisomeric form or salts of the above).

Records in registers do not need to be kept

(although thereare requirements for the retention

ofinvoices for 2 years).

Schedule 4 includes in Part I benzodiazepines

(except temazepam and midazolam, which are in

Schedule 3) and zolpidem, which are subject to

minimal control. Part II includes androgenic and

anabolicsteroids, clenbuterol,chorionic gonadotro-

phin (HCG), non-human chorionic gonadotrophin,

somatotropin, somatrem, and somatropin. Con-

trolled dr ug prescription requirements do not

apply and Schedule 4 Controlled Drugs are not

subjectto safe custody requirements.

Schedule 5 includes those preparations which,

becauseof their strength,are exempt fromvirtually

allControlled Drug requirements other thanreten-

tionof invoices for twoyears.

Prescriptions

Preparationsin Schedules2 and 3of the

Misuse of Drugs Regulations 2001 (and subsequent

amendments) are identiﬁed throughout the BNF by

the symbol C(Controlled Dr ug).The principal legal

requirementsrelating tomedical prescriptions arelisted

below(see also Department ofHealth Guidance, p. 9).

Prescriptionrequirements

Prescriptions forControlled Drugs that are subject

to prescription requirements

must be indelible,

and must be

signed

by the prescriber,

be dated,

and specify theprescriber’s

address

. The prescrip-

tionmust always state:

thename and address ofthe patient;

in the case of a preparation, the form

and

whereappropriate the strength

ofthe prepara-

tion;

either the total quantity (in both words and

ﬁgures) of the preparation,

or the number (in

both words and ﬁgures) of dosage units, as

appropriate,to besupplied; in any other case,

thetotal quantity (in bothwords and ﬁgures) of

theControlled Drug to besupplied;

thedose;

thewords ‘fordental treatmentonly’ if issuedby

adentist.

A pharmacist is not allowedto dispense a Controlled

Drugunless all theinformation required bylaw is given

onthe prescription. In the case of a prescription for a

ControlledDr ugin Schedule 2 or 3, a pharmacist can

amendthe prescription if it speciﬁes the totalquantity

only in words or in ﬁgures or if it contains minor

typographical errors, provided that such amendments

areindelible and clearly attributableto the pharmacist.

Failureto comply with the regulations concerning the

writing ofprescriptions will result in inconvenience to

patientsand delayin supplying thenecessary medicine.

Aprescription for a Controlled Drugin Schedules 2, 3,

or4 is valid for28 days from thedate stated thereon.

1.All preparations inSchedules 2 and3, except temazepam.

2.A machine-writtenprescription is acceptable. The pre-

scriber’ssignature must behandwritten.

3.The dosagefor m (e.g. tablets) must be includedon a

ControlledDrugs prescription irrespective ofwhether it is

implicit in theproprietar yname (e.g.

MST Continus

) or

whetheronly one formis available.

4.When more than one strengthof a preparation existsthe

strengthrequired must bespeciﬁed.

5.The HomeOfﬁce has advised that quantities of liquid

preparations,such as methadone oral solution,should be

writtenin millilitres.

6.The instruction ‘oneas directed’ constitutesa dose but ‘as

directed’does not.

7.The prescriber mayforward-date theprescription; thestart

datemay also bespeciﬁed in thebody of theprescription.

8 ControlledDrugs and drug dependence BNF 61

ControlledDrugs and drug dependence

Instalmentsand ‘repeats’

Aprescription mayorder

aControlled Drug to be dispensed by instalments; the

amountof instalments andthe intervals to beobserved

mustbe speciﬁed.

Instalment prescriptions must be dispensed in accor-

dancewith the directions inthe prescription. However,

theHome Ofﬁce has approved speciﬁc wordingwhich

maybe included inan instalment prescription,to cover

certainsituations; for example, if aphar macyis closed

onthe day when an instalment is due. Fordetails, see

Medicines,Ethics and Practice

,No. 34, London, Phar-

maceutical Press, 2010 (and subsequent editions as

available) or see

Drug Misuse and Dependence: UK

Guidelineson Clinical Management

(2007),available at

www.nta.nhs.uk/uploads/clinical_guidelines_2007.pdf.

Prescriptions ordering ‘repeats’ on the same form are

notpermitted for ControlledDrugs in Schedules2 or 3.

Privateprescriptions

Privateprescriptions for Con-

trolledDrugs in Schedules 2 and 3must be written on

specially designated forms provided by Primary Care

Trusts in England, Health Boardsin Scotland, Local

HealthBoards inWales, orthe Northern IrelandCentral

ServicesAgency; in addition,prescriptions mustspecify

the

prescriber’sidentiﬁcation number

.Prescriptions to

besupplied bya pharmacistin hospital areexempt from

therequirements for private prescriptions.

Department of Health guidance

Guidance (June

2006)issued bythe Departmentof Healthin England on

prescribing and dispensing of Controlled Drugs

requires:

in general, prescriptions for Controlled Drugs in

Schedules 2,3, and 4 to be limited to a supply of

upto 30 days’ treatment; exceptionally,to cover a

justiﬁable clinical need and after consideration of

anyrisk, a prescription can be issued for a longer

period, butthe reasons for the decision should be

recordedon the patient’s notes;

the patient’s identiﬁer to be shown onNHS and

privateprescriptions for Controlled Drugs inSche-

dules2 and 3.

Furtherinformation isavailable atwww.dh.gov.uk. For a

sampleprescription, see above

Dependenceand misuse

Themost serious drugsof

addiction are cocaine, diamorphine (heroin), mor-

phine, and the synthetic opioids. Forarrangements

forprescribing of diamorphine, dipipanone, or cocaine

foraddicts, see p.11.

Despitemarked reduction inthe prescribing ofamfeta-

mines,there is concernthat abuse of illicitamfetamine

andrelated compounds is widespread.

Benzodiazepines are commonly misused. However,

the misuseof barbiturates is now uncommon, in line

withdeclining medicinal use and consequent availabil-

ity.

Cannabis(Indian hemp)has noapproved medicinaluse

andcannot beprescribed bydoctors. Itsuse isillegal but

widespread. Cannabis is a mildhallucinogen seldom

accompanied by a desire to increase the dose;with-

drawalsymptoms are unusual.Lysergide (lysergic acid

diethylamide,LSD) isa muchmore potenthallucinogen;

itsuse can leadto severe psychoticstates whichcan be

life-threatening.

Thereare concernsover increasesin theavailability and

misuseof other drugs with variouslycombined halluci-

nogenic, anaesthetic, or sedative properties. These

includeketamine and gamma-hydroxybutyrate(sodium

oxybate,GHB).

Supervised consumption

Individuals prescribed

opioid substitution therapy (section 4.10.3) can take

their daily dose under the supervision of a doctor,

nurse, or pharmacist during the dose stabilisation

phase(usually the ﬁrst 3 months of treatment), after a

relapseor period ofinstability, orif there isa signiﬁcant

increase in the dose of methadone. Supervised con-

sumption should continue (in accordance with local

protocols) until the prescriber is conﬁdent that the

patientis compliant with theirtreatment.

Prescribingdrugs likely to cause dependence or

misuse

Theprescriber has threemain responsibilities:

Toavoid creatingdependence byintroducing drugs

topatients withoutsufﬁcient reason.In this context,

the proper use of the morphine-like drugs is well

understood.The dangers ofother ControlledDr ugs

areless clear becauserecognition of dependenceis

noteasy andits effects,and thoseof withdrawal,are

lessobvious.

Tosee that thepatient does not gradually increase

thedose of adrug, given forgood medical reasons,

to the point where dependence becomes more

1.A total of 14 days’ treatment by instalment of any drug

listedin Schedule 2 of the Misuse of Drugs Regulations,

buprenorphine, and diazepam may be pres cribed in

England. In

England

, forms FP10(MDA) (blue) and

FP10H(MDA) (blue) should be used.In

Scotland

, forms

GP10(peach), HBP (blue),or HBPA(pink) shouldbe used.

Wales

atotal of14 days’ treatmentby instalmentof any

drug listed in Schedules 2–5 of the Misuse of Drugs

Regulations may be prescribed. In Wales, for m

WP10(MDA)or form WP10HP(AD)should be used.

BNF 61 ControlledDrugs and drug dependence 9

ControlledDrugs and drug dependence

likely.This tendencyis seen especially withhypno-

tics and anxiolytics (for CSM advice see section

4.1).The prescriber shouldkeep a close eyeon the

amount prescribedto prevent patients from accu-

mulatingstocks. A minimal amountshould be pre-

scribedin the ﬁrst instance, or whenseeing a new

patientfor the ﬁrst time.

To avoid being used as an unwitting source of

supply for addicts. Methods include visiting more

than one doctor, fabricating stories, and forging

prescriptions.

Patients under temporary care should be given only

smallsupplies of drugs unless they present an unequi-

vocalletter from their owndoctor. Doctors shouldalso

rememberthat their ownpatients maybe attempting to

collect prescriptionsfrom other prescribers, especially

inhospitals. It is sensibleto reduce dosages steadilyor

to issue weekly or even daily prescriptions forsmall

amountsif it is apparentthat dependence is occurring.

Thestealing and misuse ofprescription forms could be

minimisedby the following precautions:

do not leave unattended if called away from the

consultingroom or atreception desks; donot leave

ina carwhere they maybe visible; whennot inuse,

keepin a locked drawer within the surgery andat

home;

draw a diagonal line across the blank part of the

formunder the prescription;

write thequantity in words and ﬁgures when pre-

scribingdrugs prone to abuse;this is obligatory for

controlleddrugs (see Prescriptions, above);

alterationsare bestavoided butif anyare madethey

should be clear and unambiguous; add initials

againstaltered items;

ifprescriptions are leftfor collectionthey should be

leftin a safe placein a sealed envelope.

Travellingabroad

Prescribeddrugs listedin Schedule

4 Part II (CDAnab) and Schedule 5 of theMisuse of

Drugs Regulations 2001 are not subject to exportor

importlicensing. However, patients intending to travel

abroadfor more than3 months carryingany amount of

drugslisted in Schedules2, 3, or4 Part I(CD Benz) will

require a personal export/import licence. Further

detailscan be obtained at

www.homeofﬁce.gov.uk/drugs/licensing/personal,

orfrom the Home Ofﬁce bycontacting

licensing_enquiry.aadu@homeofﬁce.gsi.gov.uk

(incases of emergency,telephone (020) 7035 0484).

Applications must be supported by a covering letter

fromthe prescriber and shouldgive details of:

thepatient’s name and address;

thequantities of drugs to becarried;

the strength and form in which the drugs will be

dispensed;

thecountry or countries ofdestination;

thedates oftravel to andfrom theUnited Kingdom.

Applications for licences should be sent to the Home

Ofﬁce, Drugs Licensing, Peel Building, 2 Marsham

Street, London, SW1P 4DF.Alternatively, completed

application forms can be emailed to

licensing_enquiry.aadu@homeofﬁce.gsi.gov.uk with a

scanned copy of the covering letter from the prescri-

ber.A minimumof two weeks shouldbe allowed for

processing the application.

Patientstravelling forless than 3months do notrequire

a personal export/import licence for car rying Con-

trolled Drugs, but are advised to carry a letter from

theprescribing doctor.Those travelling formore than 3

monthsare advisedto make arrangementsto havetheir

medicationprescribed by a practitioner in the country

theyare visiting.

Doctors who want to take Controlled Drugs abroad

while accompanying patients may similarly be issued

with licences. Licences are not normally issued to

doctors who want to take Controlled Drugs abroad

solelyin case a familyemergency should arise.

Personalexport/import licences do not haveany legal

status outside the UK and are issued only to comply

withthe Misuse of Drugs Act and to facilitatepassage

throughUK Customs and Excisecontrol. For clearance

inthe country to be visitedit is necessary to approach

thatcountry’s consulate in theUK.

Notiﬁcation of drug misusers

Doctors should report cases of drug misuse to their

regionalor national drug misuse database or centre—

seebelow for contacttelephone numbers. TheNational

Drugs Treatment Monitoring System (NDTMS) was

introduced in England in April 2001; regional

(NDTMS) centres replace the Regional Drug Misuse

Databases. A similar system has been introduced in

Wales.

Notiﬁcation to regional (NDTMS) or national centre

should be made when a patient starts treatment for

drug misuse.All types of problem drug misuse should

bereported including opioid, benzodiazepine,and CNS

stimulant.

Theregional (NDTMS) or nationalcentres are now the

onlynational and local source of epidemiological data

on people presenting with problemdr ug misuse; they

providevaluable informationto thoseworking withdrug

misusers and those planning services for them. The

databases cannot, however be used as a check on

multipleprescribing for drug addicts because the data

areanonymised.

Enquiriesabout the regional (NDTMS)or national cen-

tres(including information on how tosubmit data) can

bemade to one ofthe centres listed below:

ENGLAND

Eastern

Tel:(01223) 767904

Fax:(01223) 330 345

SouthEast

Tel:(01865) 334734

Fax:(01865) 334 964

London

Tel:(020) 7972 1986

Fax:(020) 7972 1998

NorthWest

Tel:(0151) 231 4533

Fax:(0151) 231 4515

NorthEast

Tel:(0191) 334 0372

Fax:(0191) 334 0391

Yorkshireand the Humber

Tel:(0113) 341 2923

Fax:(0113) 341 3082

10 Controlled Drugs and drug dependence BNF 61

ControlledDrugs and drug dependence

SouthWestern

Tel:(0117) 970 6474ext 311

Fax:(0117) 970 7021

EastMidlands

Tel:(0115) 971 2745

Fax:(0115) 971 2404

WestMidlands

Tel:(0121) 415 8556

Fax:(0121) 414 8197

SCOTLAND

Tel:(0131) 551 8715

Fax:(0131) 551 1392

WALES

Tel:(029) 2050 3343

Fax:(029) 2050 2330

InNorther nIreland, the Misuseof Drugs (Notiﬁcation

of and Supply to Addicts) (Northern Ireland) Regula-

tions1973 requiredoctors tosend particularsof persons

whomthey considerto beaddicted to certaincontrolled

drugsto the ChiefMedical Ofﬁcer ofthe Department of

Healthand Social Services. The Northern Ireland con-

tactsare:

Medicalcontact:

DrIan McMaster

C3Castle Buildings

Belfast,BT4 3FQ

Tel:(028) 9052 2421

Fax:(028) 9052 0718

ian.mcmaster@dhsspsni.gov.uk

Administrativecontact:

PublicHealth Information & ResearchBranch

Annex2

CastleBuilding

Belfast,BT4 3SQ

Tel:(028) 9052 2520

Public Health Information & Research Branch also

maintainsthe Northern Ireland Drug Misuse Database

(NIDMD)which collects detailed information on those

presentingfor treatment, on drugs misused andinject-

ing behaviour;participation is not a statutory require-

ment.

Prescribing of diamorphine (heroin),

dipipanone, and cocaine for addicts

The Misuse of Drugs (Supply to Addicts) Regulations

1997require that onlymedical practitioners whohold a

special licence issued by the Home Secretary may

prescribe, administer,or supply diamorphine, dipipan-

one (

Diconal

), or cocaine in the treatment of drug

addiction;other practitioners mustrefer anyaddict who

requires these drugs to a treatmentcentre. Whenever

possiblethe addict will be introduced by a memberof

staff fromthe treatment centre to a pharmacist whose

agreement hasbeen obtained and whose pharmacy is

conveniently sited for the patient. Prescriptions for

weekly supplies will be sent to the pharmacy by post

andwill bedispensed ona dailybasis asindicated bythe

doctor. If any alterations of the arrangements are

requestedby the addict, theportion of the prescription

affectedmust be represcribed and notmerely altered.

Generalpractitioners andother doctors donot requirea

speciallicence forprescribing diamorphine, dipipanone,

andcocaine for patients(including addicts)for

relieving

pain

fromorganic disease or injury.

Forguidance on prescription writing,see p. 8.

BNF 61 ControlledDrugs and drug dependence 11

ControlledDrugs and drug dependence

Adverse reactions to drugs

Any drug may produce unwanted or unexpected

adverse reactions. Rapid detection and recording of

adverse drug reactions is of vital importance sothat

unrecognised hazards are identiﬁed promptly and

appropriate regulatory action is taken to ensure that

medicinesare used safely.Healthcare professionalsand

coroners (see also Self-reporting below) are urged to

reportsuspected adverse drug reactions directlyto the

Medicinesand Healthcare productsRegulatory Agency

(MHRA) through the Yellow Card Schemeusing the

electronic form at www.yellowcard.gov.uk. Alterna-

tively,prepaid Yellow Cardsfor reporting are available

fromthe address belowand are alsobound in thisbook

(insideback cover).

SendYellow Cards to:

FREEPOSTYELLOW CARD

(Noother address details required)

Tel:0800 731 6789

Suspected adverse drug reactions to

any

therapeutic

agentshould be reported, including drugs

(self-medica-

tion

as wellas those

prescribed)

, bloodproducts, vac-

cines,radiographic contrastmedia, complementary and

herbalproducts.

A24-hour Freefoneservice isavailable toall parts ofthe

UK for advice and information on suspected adverse

drugreactions; contact the NationalYellow Card Infor-

mationService atthe MHRAon 0800731 6789. Outside

ofﬁce hours a telephone-answering machine will take

messages.

Thefollowing YellowCard Centrescan becontacted for

furtherinformation:

YellowCard Centre

Northwest

FreepostSW2991

70Pembroke Place

Liverpool L69 3GF

Tel:(0151) 794 8122

YellowCard Centre Wales

FreepostSW2991

UniversityHospital of

Wales

Cardiff CF4 1ZZ

Tel:(029) 2074 4181

YellowCard Centre

Northern& Yorkshire

FreepostSW2991

WolfsonUnit

ClaremontPlace

Newcastleupon

Tyne NE2 4HH

Tel:(0191) 260 6181

YellowCard Centre West

Midlands

FreepostSW2991

CityHospital

Birmingham B18 7QH

Tel:(0121) 507 5672

YellowCard Centre Scot-

land

FreepostNAT3271

CARDS,Royal Inﬁrmary

ofEdinburgh

Edinburgh EH16 4SA

Tel:(0131) 242 2919

The MHRA’s database facilitates the monitoring of

adversedrug reactions.

More detailed information on reporting anda list of

products currently under intensive monitoring can be

foundon the MHRA website:www.mhra.gov.uk.

Drug Safety Update

is a monthly newsletter from

the MHRA and the Commission on Human Medi-

cines (CHM); it is available at www.mhra.gov.uk/

drugsafetyupdate.

Self-reporting

Patients and their carers can also

report suspected adverse drug reactions to the

MHRA. Reports can be submitted directly to the

MHRA through the Yellow Card Scheme using the

electronicform atwww.yellowcard.gov.uk,by telephone

on0808 100 3352, or bydownloading the YellowCard

formfrom www.mhra.gov.uk. Alternatively,patient Yel-

low Cards are available from pharmacies and GP

surgeries. Information for patients about the Yellow

Card Scheme is available in other languages at

www.yellowcard.gov.uk.

Prescription-event monitoring

In addition to the

MHRA’sYellow CardScheme, an independent scheme

monitorsthe safety of new medicines usinga different

approach. The Drug Safety Research Unit identiﬁes

patientswho have been prescribed selected new med-

icines and collects data on clinical events in these

patients. The dataare submitted on a voluntary basis

bygeneral practitioners ongreen forms. Moreinfor ma-

tionabout the schemeand the Unit’seducational mate-

rialis available from www.dsru.org.

Newerdrugs and vaccines

Onlylimited information

is available from clinical trialson the safety of new

medicines. Further understanding about the safety of

medicines depends on the availability ofinformation

fromroutine clinical practice.

Theblack triangle symbol(T) identiﬁes newlylicensed

medicinesthat aremonitored intensively bythe MHRA.

Suchmedicines include newactive substances,biosimi-

lar medicines, medicines that have been licensed for

administrationby a new routeor drug delivery system,

or for signiﬁcant newindications which may alter the

establishedrisks and beneﬁts of thatdrug, or that con-

taina newcombination ofactive substances.There isno

standardtime forwhich products retaina blacktriangle;

safetydata are usually reviewedafter 2 years.

Spontaneous reporting is particularly valuable for

recognisingpossible newhazards rapidly.For medicines

showingthe black trianglesymbol, the MHRAasks that

allsuspected reactions (including thoseconsidered not

to be serious) are reported throughthe YellowCard

Scheme.An adversereaction should bereported evenif

it is not certain that the drug has caused it, or if the

reactionis well recognised, orif other drugs havebeen

givenat the same time.

Establisheddrugs and vaccines

Healthcareprofes-

sionals and coroners are askedto report all serious

suspected reactions to established drugs (including

over-the-counter, herbal, and unlicensed medicines

and medicines used off-label) and vaccines. Serious

reactions include those that are fatal, life-threatening,

disabling,incapacitating, or which result in or prolong

hospitalisation; they should be reported even if the

effectis wellrecognised. Examples includeanaphylaxis,

blooddisorders, endocrine disturbances, effectson fer-

tility, haemorrhage from any site, renal impairment,

jaundice, ophthalmic disorders, severe CNS effects,

severe skin reactions, reactions in pregnant women,

and any drug interactions. Reports of serious adverse

reactionsare required to enablecomparison with other

drugsof asimilar class.Reports of overdoses(deliberate

oraccidental) cancomplicate theassessment ofadverse

drug reactions, but provide important information on

thepotential toxicity of drugs.

12 Adverse reactions to drugs BNF 61

Adverse reactions to drugs

Forestablished drugs there is no need to report well-

known,relatively minor side-effects,such as drymouth

with tricyclic antidepressants or constipation with

opioids.

Adverse reactions to medical devices

Suspected

adversereactions tomedical devicesincluding dentalor

surgical materials, intra-uterine devices, and contact

lensﬂuids should bereported. Informationon reporting

thesecan be found at:www.mhra.gov.uk.

Side-effectsin the BNF

TheBNF includes clinically

relevantside-effects formost drugs; anexhaustive listis

notincluded for drugs that areused by specialists (e.g.

cytotoxicdrugs and drugs used inanaesthesia). Where

causality has not been established, side-effects in the

manufacturers’literature may beomitted from theBNF.

Recognising that hypersensitivity reactions can occur

withvirt uallyall medicines, this effect is not generally

listed,unless the drug carries anincreased risk of such

reactions.The BNF also omits effectsthat are likely to

havelittle clinical consequence (e.g. transient increase

inliver enzymes).

Side-effects are generally listed in order of frequency

andarranged broadly by body systems.Occasionally a

rareside-effect might belisted ﬁrst if itis considered to

beparticularly important because of its seriousness.

Inthe product literature thefrequency of side-effectsis

generallydescribed as follows:

Verycommon greaterthan 1 in 10

Common 1in 100 to 1 in 10

Uncommon[‘less commonly’ in

BNF]

1in 1000 to 1 in 100

Rare 1 in 10000 to 1 in 1000

Veryrare lessthan 1 in 10 000

Special problems

Delayeddrug effects

Somereactions (e.g. cancers,

chloroquine retinopathy, and retroperitoneal ﬁbrosis)

maybecome manifest months or years afterexposure.

Anysuspicion ofsuch anassociation should bereported

directlyto the MHRAthrough theYellow Card Scheme.

Theelderly

Particularvigilance is requiredto identify

adversereactions in the elderly.

Congenital abnormalities

When an infant is born

witha congenital abnormality or there is a malformed

abortedfetus doctorsare askedto consider whetherthis

mightbe an adversereaction to adrug and toreport all

drugs (including self-medication) taken during

pregnancy.

Children

Particularvigilance isrequired toidentify and

report adverse reactions in children, including those

resulting from the unlicensed use of medicines; all

suspected reactionsshould be reported directly to the

MHRA through the Yellow Card Scheme (see also

AdverseDrug Reactions in Children, p.15).

Prevention of adverse reactions

Adversereactions may be preventedas follows:

never use anydrug unless there is a good indica-

tion. If the patient is pregnant do not use a drug

unlessthe need for itis imperative;

allergy and idiosyncrasy are important causes of

adversedr ugreactions. Ask if the patient hadpre-

viousreactions;

ask if the patient is already taking other drugs

including self-medication drugs, health supple-

ments, complementary and alternative therapies

;

interactionsmay occur;

age and hepatic or renal disease may alter the

metabolism or excretion of drugs, so that much

smaller doses may be needed. Genetic factors

may also be responsible for variations inmetab-

olism, notably of isoniazid and the tricyclicanti-

depressants;

prescribe as few drugs as possible and give very

clearinstructions to theelderly orany patient likely

tomisunderstand complicated instructions;

whenever possibleuse a familiar drug; with anew

drug, beparticularly alert for adverse reactions or

unexpectedevents;

warn the patient if serious adverse reactions are

liableto occur.

Oral side-effects of drugs

Drug-induced disordersof the mouth may be dueto a

local action on the mouth or to a systemic effect

manifested by oral changes. In the latter case urgent

referral to the patient’s medical practitioner may be

necessary.

Oralmucosa

Medicamentsleft in contact with orapplied directly to

theoral mucosacan lead toinﬂammation or ulceration;

thepossibility of allergy shouldalso be borne in mind.

Aspirintablets allowed to dissolvein the sulcusfor the

treatment of toothache can lead to a white patch fol-

lowedby ulceration.

Flavouringagents, particularly essential oils,may sen-

sitise the skin, but mucosal swelling is not usually

prominent.

Theoral mucosa isparticularly vulnerable toulceration

in patients treated with cytotoxic drugs,e.g. metho-

trexate.Other drugs capable ofcausing oral ulceration

include captopril (and other ACE inhibitors), gold,

nicorandil, NSAIDs, pancreatin, penicillamine, pro-

guanil,and protease inhibitors.

Erythema multiforme or Stevens-Johnson syndrome

mayfollow the use of a wide rangeof drugs including

antibacterials, antiretrovirals, sulfonamide deriva-

tives, and anticonvulsants; the oral mucosa may be

extensivelyulcerated, with characteristic target lesions

on theskin. Oral lesions of toxic epidermal necrolysis

havebeen reported with asimilar range of drugs.

Lichenoid eruptions are associated with ACE inhi-

bitors, NSAIDs,methyldopa, chloroquine, oral anti-

diabetics,thiazide diuretics, and gold.

Candidiasis can complicate treatment with antibac-

terialsand immunosuppressants and isan occasional

side-effectof corticosteroid inhalers, see alsop. 185.

BNF 61 Adversereactions to drugs 13

Adverse reactions to drugs

Teethand Jaw

Brownstaining

ofthe teethfrequently followsthe useof

chlorhexidinemouthwash, sprayor gel, butcan readily

beremoved by polishing. Iron salts in liquid formcan

stain the enamel black. Superﬁcial staininghas been

reportedrarely with co-amoxiclav suspension.

Intrinsicstaining

ofthe teeth ismost commonlycaused

by tetracyclines.They will affect the teeth if given at

anytime from aboutthe fourth month

inutero

untilthe

age of twelve years; they are contra-indicated during

pregnancy, in breast-feeding women, and in children

under12 years. All tetracyclinescan cause permanent,

unsightly stainingin children, the colour varying from

yellowto grey.

Excessiveingestion ofﬂ uorideleads to

dentalﬂuorosis

withmottling of the enameland areas of hypoplasiaor

pitting; ﬂuoride supplements occasionally cause mild

mottling(white patches) if the doseis too large for the

child’sage (taking into account the ﬂuoride contentof

thelocal drinking water andof toothpaste).

The risk of

osteonecrosis of the jaw

is substantially

greaterfor patients receivingintravenous bisphosphon-

atesin the treatmentof cancer than forpatients receiv-

ing oral bisphosphonates for osteoporosis or Paget’s

disease.All patients receivingbisphosphonates for can-

cershould have a dental check-up (and anynecessary

remedialwork shouldbe performed)before bisphospho-

natetreatment. However, urgent bisphosphonatetreat-

ment should not be delayed,and a dental check-up

should be carried out as soon as possible in these

patients.All other patientswho are prescribed bisphos-

phonatesshould have adental examination onlyif they

havepoor dental health, see also MHRA/CHM advice

(Bisphosphonates:osteonecrosis of thejaw), p.472. For

cancer patients taking bevacizumab or sunitinib, see

also MHRA/CHMadvice (Bevacizumab and sunitinib:

riskof osteonecrosis of thejaw), p. 537.

Periodontium

Gingival overgrowth

(gingival hyperplasia) is a side-

effect of phenytoin and sometimes of ciclosporin or

of nifedipine(and some other calcium-channel block-

ers).

Thrombocytopenia

maybe drug relatedand maycause

bleedingat the gingivalmargins, which may besponta-

neousor may follow mild trauma (suchas toothbrush-

ing).

Salivaryglands

Themost commoneffect thatdrugs haveon thesalivary

glands is to

reduce ﬂow

(xerostomia). Patientswith a

persistentlydry mouthmay havepoor oralhygiene; they

areat an increased risk ofdental caries and oral infec-

tions (particularlycandidiasis). Many drugs have been

implicatedin xerostomia, particularly antimuscarinics

(anticholinergics), antidepressants (including tricyclic

antidepressants,and selective serotonin re-uptakeinhi-

bitors), alpha-blockers, antihistamines, antipsy-

chotics, baclofen, bupropion, clonidine, 5HT

ago-

nists, opioids, and tizanidine. Excessive use of

diureticscan also result inxerostomia.

Some drugs (e.g.clozapine, neostigmine) can

increase

salivaproduction

butthis israrely a problemunless the

patienthas associated difﬁculty in swallowing.

Painin thesalivary glands hasbeen reported withsome

antihypertensives (e.g. clonidine, methyldopa) and

withvinca alkaloids.

Swellingof the salivary glands canoccur with iodides,

antithyroiddrugs, phenothiazines,r itodrine,and sul-

fonamides.

Taste

There can be

decreased

taste acuity or

alteration

tastesensation. Drugs implicated include amiodarone,

calcitonin, captopril (and other ACE inhibitors), car-

bimazole,clarithromycin, gold, griseofulvin, lithium

salts, metformin, metronidazole, penicillamine,

phenindione, propafenone, protease inhibitors, ter-

binaﬁne,and zopiclone.

Defective medicines

Duringthe manufactureor distributionof amedicine

anerror oraccident may occurwhereby theﬁnished

productdoes not conformto its speciﬁcation.While

such a defectmay impair the therapeutic effect of

theproduct and couldadversely affect the healthof

apatient, itshould not beconfused with anAdverse

Drug Reaction where the product conforms to its

speciﬁcation.

TheDefective Medicines ReportCentre assists with

the investigationof problems arising from licensed

medicinalproducts thought to be defectiveand co-

ordinates anynecessar y protectiveaction. Reports

on suspect defective medicinal products should

includethe brand or the non-proprietary name,the

name of the manufacturer or supplier, the strength

anddosage form ofthe product, theproduct licence

number,the batch number or numbers of the pro-

duct,the natureof the defect,and an accountof any

action already taken in consequence. TheCentre

canbe contacted at:

TheDefective Medicines Report Centre

Medicinesand Healthcare products Regulatory

Agency

151Buckingham Palace Road

London,SW1W 9SZ

Tel:(020) 3080 6588

info@mhra.gsi.gov.uk

14 Adverse reactions to drugs BNF 61

Adverse reactions to drugs

Prescribing for children

Fordetailed advice on medicinesused for children,

consult

BNFfor Children

Children,and particularlyneonates, differ fromadults in

their response to drugs. Special care is needed in the

neonatalperiod (ﬁrst 28 days of life)and doses should

alwaysbe calculated with care. At this age,the risk of

toxicity is increased by reduced drug clearance and

differingtarget organ sensitivity.

Whenever possible,intramuscular injections should be

avoidedin children because theyare painful.

Where possible,medicines for children should be pre-

scribedwithin the terms ofthe marketing authorisation

(productlicence). However, manychildren may require

medicinesnot speciﬁcally licensed forpaediatric use.

Although medicines cannot be promoted outside the

limitsof thelicence, theMedicines Actdoes not prohibit

theuse ofunlicensed medicines.It isrecognised thatthe

informed use of unlicensed medicines orof licensed

medicinesfor unlicensed applications (‘off-label’use) is

oftennecessary in paediatric practice.

Adversedrug reactions in children

Thereporting

ofall suspected adverse drugreactions, no matterhow

minor,in children under 18 years is strongly encour-

agedthrough the YellowCard Scheme (seep. 12) even

if the intensive monitoring symbol (T) has been

removed. This is because experience in children may

stillbe limited.

Theidentiﬁcation and reportingof adverse reactions to

drugsin children is particularly importantbecause:

theaction of the drug and its pharmacokinetics in

children (especially in the very young) may be

differentfrom that in adults;

drugsare not extensively testedin children;

manydrugs are not speciﬁcally licensed foruse in

childrenand are used ‘off-label’;

suitableformulations may notbe available to allow

precisedosing in children;

thenature and courseof illnesses andadverse drug

reactionsmay differ between adultsand children.

Prescriptionwriting

Prescriptionsshould be written

accordingto theguidelines in PrescriptionWriting (p.5)

Inclusion of age is a legal requirement in the case of

prescription-onlymedicines for childrenunder 12 years

of age, but it is preferable to state the age for all

prescriptionsfor children.

It is particularly important to state the strengths of

capsules or tablets. Although liquid preparations are

particularly suitable for children, they may contain

sugarwhich encourages dental decay. Sugar-freemed-

icinesare preferred for long-term treatment.

Manychildren are able to swallow tablets or capsules

and may prefer a solid dosefor m; involvingthe child

andparents in choosing thefor mulationis helpful.

When a prescription fora liquid oral preparation is

written and the doseordered is smaller than 5 mL an

oral syringe will be supplied (for details, see p. 2).

Parents should be advised not to add any medicines

tothe infant’sfeed, since thedrug may interactwith the

milkor other liquidin it; moreover theingested dosage

may be reduced if the child does not drink all the

contents.

Parentsmust be warned to keep all medicines out of

reachof children, see Safetyin the Home, p.3.

Rare paediatric conditions

Information on substances suchas

biotin

and

sodium

benzoate

usedin rare metabolic conditions isincluded

BNF for Children

; further information can be

obtainedfrom:

AlderHey Children’s Hospital

DrugInformation Centre

Liverpool L12 2AP

Tel:(0151) 252 5381

GreatOrmond Street Hospital for Children

Pharmacy

GreatOrmond St

London WC1N 3JH

Tel:(020) 7405 9200

Dosage in children

Children’sdoses in theBNF are stated inthe individual

drugentries as far as possible,except where paediatric

useis notrecommended, informationis not available,or

thereare special hazards.

Doses are generally based on body-weight (in kilo-

grams)or the following ageranges:

ﬁrstmonth (neonate)

upto 1 year (infant)

1–5years

6–12years

Unlessthe age is speciﬁed, theter m‘child’ in the BNF

includespersons aged 12 yearsand younger.

Dosecalculation

Manychildren’s doses arestandar-

dised byweight (and therefore require multiplying by

the body-weight in kilograms to determine the child’s

dose); occasionally,the doses have been standardised

bybody surfacearea (in m

).These methodsshould be

usedrather than attempting to calculate a child’sdose

onthe basis of dosesused in adults.

Formost drugs theadult maximum dose shouldnot be

exceeded.For example ifthe dose is statedas 8mg/kg

(max. 300mg), a child weighing 10 kg should receive

80mg buta child weighing40 kgshould receive 300mg

(ratherthan 320 mg).

Youngchildren mayrequire a higher doseper kilogram

than adults because of their higher metabolic rates.

Other problems need to be considered. For example,

calculationby body-weight inthe overweight childmay

result in much higher doses being administered than

necessary;in suchcases, doseshould becalculated from

BNF 61 Prescribing for children 15

Prescribingfor children

an ideal weight, related to height and age (see inside

backcover).

Body surface area (BSA) estimates are sometimes

preferable to body-weightfor calculation of paediatric

doses since many physiological phenomena correlate

betterwith body surfacearea. Bodysurface area canbe

estimated fromweight. For more information, refer to

BNFfor Children

Where the dose for children is not stated, prescribers

shouldconsult

BNFfor Children

orseek advice from a

medicinesinformation centre.

Dosefrequency

Antibacterialsare generally given at

regular intervals throughout the day. Some ﬂ exibility

should be allowed in children to avoidwaking them

duringthe night. Forexample, the night-timedose may

begiven at the child’sbedtime.

Where new or potentiallytoxic drugs are used, the

manufacturers’recommended dosesshould be carefully

followed.

16 Prescribing for children BNF 61

Prescribingfor children

Prescribing in hepatic impairment

Liverdisease mayalter the responseto drugs in several

waysas indicatedbelow, anddrug prescribingshould be

kept to a minimum in all patients with severe liver

disease. The main problems occur in patients with

jaundice,ascites, or evidence ofencephalopathy.

Impaireddrug metabolism

Metabolismby the liver

is the main route of elimination for many drugs,but

hepatic reserve is large and liver disease has to be

severe before important changes in drug metabolism

occur.Routine liver-function tests are a poor guide to

thecapacity of theliver to metabolise drugs,and in the

individualpatient it isnot possible topredict the extent

to which the metabolism of a particular drug may be

impaired.

A few drugs, e.g. rifampicin and fusidic acid, are

excretedin the bile unchanged and can accumulatein

patients with intrahepatic or extrahepatic obstructive

jaundice.

Hypoproteinaemia

Thehypoalbuminaemia insevere

liverdisease is associatedwith reduced protein binding

and increased toxicity of some highly protein-bound

drugssuch as phenytoin and prednisolone.

Reduced clotting

Reduced hepatic synthesis of

blood-clotting factors, indicated by a prolonged

prothrombintime, increases the sensitivityto oral anti-

coagulantssuch as warfarin andphenindione.

Hepatic encephalopathy

In severe liver disease

many drugs can further impair cerebral function and

mayprecipitate hepatic encephalopathy.These include

allsedative drugs,opioid analgesics,those diuretics that

producehypokalaemia, and drugs that cause constipa-

tion.

Fluid overload

Oedema andascites in chronic liver

disease can be exacerbated bydrugs that give rise to

ﬂuidretention, e.g. NSAIDs andcorticosteroids.

Hepatotoxic drugs

Hepatotoxicity is either dose-

related or unpredictable (idiosyncratic). Drugs that

cause dose-related toxicity may do so at lower doses

in the presence of hepatic impairment than in indivi-

duals withnor mal liver function, and some drugs that

producereactions of the idiosyncratickind do so more

frequently in patients with liver disease. These drugs

shouldbe avoidedor usedvery carefullyin patientswith

liverdisease.

Where care is needed when prescribing in hepatic

impairment, this is indicated under the relevant drug

inthe BNF.

Prescribing in renal impairment

Theuse ofdrugs in patientswith reduced renalfunction

cangive rise to problemsfor several reasons:

reducedrenal excretion ofa drug orits metabolites

maycause toxicity;

sensitivityto some drugs is increasedeven if elim-

inationis unimpaired;

many side-effects are tolerated poorlyby patients

withrenal impairment;

somedrugs are noteffective when renalfunction is

reduced.

Manyof theseproblems can beavoided byreducing the

doseor by using alternativedrugs.

Principles of dose adjustment in renal

impairment

The levelof renal function below which the dose of a

drugmust be reduceddepends on theproportion ofthe

drugeliminated by renal excretionand its toxicity.

Formany drugswith onlyminor orno dose-relatedside-

effectsvery precise modiﬁcationof the dose regimenis

unnecessaryand a simplescheme for dose reductionis

sufﬁcient.

For more toxic drugs with a small safety margin or

patients at extremes of weight, dose regimens based

oncreatinine clearance(see below for details) shouldbe

used.When bothefﬁcacy andtoxicity areclosely related

toplasma-drug concentration, recommended regimens

shouldbe regarded only asa guide to initialtreatment;

subsequentdoses mustbe adjustedaccording to clinical

responseand plasma-drug concentration.

Renalfunction declines withage; many elderly patients

haverenal impairment but, becauseof reduced muscle

mass, this may not be indicated by a raised serum

creatinine.It iswise to assumeat least mildimpairment

ofrenal function when prescribingfor the elderly.

The total daily maintenance dose of a drug can be

reduced either by reducing the size of theindividual

dosesor by increasing the interval betweendoses. For

somedrugs, although the sizeof the maintenance dose

is reducedit is important to give a loading dose if an

immediate effect is required. This is because it takes

about ﬁve times the half-life of the drug to achieve

steady-state plasma concentrations. Because the

plasma half-life of drugs excreted by the kidney is

prolongedin renal impairment it can take manydoses

forthe reduced dosageto achieve atherapeutic plasma

concentration.The loading dose should usually be the

samesize as the initial dose for a patient with normal

renalfunction.

Nephrotoxic drugs should, if possible, be avoided in

patientswith renaldisease becausethe consequences of

nephrotoxicityare likely tobe more seriouswhen renal

reserveis already reduced.

Dose recommendations are based on the severityof

renalimpairment.

BNF 61 Prescribing in hepatic impairment 17

Prescribingin renal impairment

Renalfunction is measuredeither in termsof estimated

glomerular ﬁltration rate (eGFR) calculated from a

formuladerived from the Modiﬁcation ofDiet in Renal

Diseasestudy (‘MDRD formula’ that usesser umcreat-

inine,age, sex, and race (for Afro-Caribbean patients))

or it can be expressed as creatinine clearance (best

derivedfrom a 24-hour urine collection butoften calcu-

latedfrom the Cockcroft andGault formula (CG).

Cockcroftand Gault formula

EstimatedCreat-

inineClearancein

mL/minute

(140– Age)  Weight Constant

Serumcreatinine

Agein years

Weightin kilograms; use ideal body-weight

Serumcreatinine in micromol/litre

Constant= 1.23 for men; 1.04 for women

Theserum-creatinine concentration is sometimes used

instead asa measure of renal function but it is only a

roughguide to drug dosing.

Important

Renal function in adults is increasingly being

reportedon the basisof estimated glomerular ﬁltra-

tionrate (eGFR) normalised to a bodysurface area

of1.73 m

andderived fromthe Modiﬁcation ofDiet

in Renal Disease (MDRD) formula. However, pub-

lishedinformation onthe effectsof renal impairment

on drug elimination is usuallystated in terms of

creatinine clearance as a surrogate for glomerular

ﬁltrationrate (GFR).

Theinformation ondosage adjustment inthe BNFis

expressedin terms of eGFR, rather than creatinine

clearance, for most drugs (see exceptions below:

ToxicDrugs andPatients at Extremes ofWeight).

Althoughthe twomeasures of renalfunction are not

interchangeable,in practice, for mostdr ugsand for

most patients(over 18 years) of average build and

height, eGFR (MDRD ‘formula’) can be used to

determinedosage adjustments inplace ofcreatinine

clearance.An individual’sabsolute glomerular ﬁltra-

tionrate canbe calculatedfrom theeGFR as follows:

GFR

Absolute

= eGFR  (individual’s body surface

area/1.73)

Toxic drugs

For potentially toxic drugs with a

smallsafety margin,creatinine clearance (calculated

from the Cockcroft and Gault formula) should be

usedto adjust drug dosages in addition to plasma-

drugconcentration and clinical response.

Patients at extremes of weight

In patients at

bothextremes of weight (BMI ofless than 18.5kg/

or greater than 30 kg/m

) the absolute glom-

erular ﬁltration rateor creatinine clearance (calcu-

latedfrom the Cockcroft andGault formula) should

beused to adjust drug dosages.

In theBNF, values for eGFR, creatinine clearance (for

toxicdr ugs),or another measure of renal function are

included where possible.However, where such values

arenot available,the BNF reﬂectsthe terms usedin the

publishedinformation.

Chronic kidney disease in adults:UK guidelinesfor

identiﬁcation,management and referral (March 2006)

deﬁnerenal function as follows:

Degreeof impairment eGFRmL/minute/1.73m

Normal- Stage 1 Morethan 90 (with other

evidenceof kidney damage)

Mild- Stage 2 60–89 (with other evidence

ofkidney damage)

Moderate

-Stage 3 30–59

Severe- Stage 4 15–29

Establishedrenal failure -

Stage5

Lessthan 15

1.NICE clinical guideline 73 (September 2008)—Chronic

kidneydisease: Stage 3A eGFR 45–59, Stage 3B eGFR 30–

Dialysis

For prescribing in patients on continuous ambula-

tory peritoneal dialysis (CAPD) or haemodialysis,

consultspecialist literature.

Drugprescribing should be kept tothe minimum in all

patientswith severe renal disease.

If even mild renal impairment is considered likely on

clinical grounds, renal function should be checked

beforeprescribing any drug which requires dosemod-

iﬁcation.

Wherecare is neededwhen prescribing inrenal impair-

ment, this is indicated under the relevant drug in the

BNF.

18 Prescribing in renal impairment BNF 61

Prescribingin renal impairment

Prescribing in pregnancy

Drugscan have harmful effects onthe embryo or fetus

atany timeduring pregnancy.It isimportant tobear this

inmind when prescribing for awoman of

childbearing

age

orfor men

trying

father

achild.

Duringthe

ﬁrsttrimester

drugscan produce congenital

malformations(teratogenesis), and the period of great-

est risk is from the third to the eleventh week of

pregnancy.

Duringthe

second

and

thirdtrimesters

drugscan affect

the growth or functional development of the fetus, or

theycan have toxic effectson fetal tissues.

Drugs given shortly before term or during labour can

haveadverse effects on labour or onthe neonate after

delivery.

Notall the damagingeffects of intrauterineexposure to

drugsare obviousat birth,some mayonly manifest later

in life.Such late-onset effects include malignancy, e.g.

adenocarcinomaof the vagina after pubertyin females

exposedto diethylstilbestrol in the womb,and adverse

effects on intellectual, social, and functional develop-

ment.

TheBNF identiﬁes drugs which:

may have harmful effects in pregnancy and indi-

catesthe trimester of risk

arenot known to behar mfulin pregnancy

Theinformation is based on human data,but informa-

tion from

animal

studies has been included for some

drugswhen its omission might bemisleading.

Where care isneeded when prescribing in pregnancy,

thisis indicated under therelevant drug in the BNF.

Drugsshould be prescribedin pregnancy onlyif the

expected beneﬁt to the mother is thought to be

greaterthan therisk tothe fetus,and alldrugs should

be avoided if possible during the ﬁrst trimester.

Drugs which have been extensively used in

pregnancyand appear to be usually safeshould be

prescribed in preference to new or untried drugs;

andthe smallest effective doseshould be used.

Few drugs have been shown conclusively to be

teratogenicin humans, but no drug is safe beyond

alldoubt in early pregnancy. Screening procedures

areavailable when there is a known risk ofcertain

defects.

Absenceof information does not implysafety.

Itshould be noted that the BNF provides indepen-

dent advice and may not always agree with the

productliterature.

Information on drugs and pregnancy is also avail-

ablefrom the UK TeratologyInformation Service.

Tel:0844 8920909 (08:30–17:00 Monday toFriday)

Fax:(0191) 260 6193

Outside of these hours, urgent enquiries only

www.uktis.org

Prescribing in breast-feeding

Breast-feeding is beneﬁcial; the immunological and

nutritional valueof breast milk to the infant is greater

thanthat of formula feeds.

Although there is concern that drugs taken by the

mothermight affect the infant, thereis very little infor-

mationon this. In theabsence of evidence ofan effect,

thepotential forharm to theinfant canbe inferred from:

theamount of drugor activemetabolite of thedrug

deliveredto the infant (dependent on the pharma-

cokineticcharacteristics of thedrug in themother);

theefﬁciency of absorption, distribution, andelim-

inationof the drug by theinfant (infant pharmaco-

kinetics);

the nature of the effect of the drug on the infant

(pharmacodynamic properties of the drug in the

infant).

Theamount of drug transferred inbreast milk is rarely

sufﬁcient toproduce a discernible effect on the infant.

This applies particularly to drugs that are poorly

absorbedand need to be given parenterally. However,

thereis a theoretical possibility thata small amount of

drugpresent inbreast milkcan inducea hypersensitivity

reaction.

Aclinical effect can occur in the infantif a pharmaco-

logically signiﬁcant quantity of the drug is present in

milk.For somedrugs (e.g.ﬂuvastatin), theratio between

theconcentration in milk and that in maternal plasma

may be high enough to expose the infant to adverse

effects.Some infants,such as thoseborn prematurelyor

who have jaundice, are at a slightly higher risk of

toxicity.

Some drugs inhibit the infant’s sucking reﬂex (e.g.

phenobarbital) while others can affect lactation (e.g.

bromocriptine).

TheBNF identiﬁes drugs:

that should be used with caution or are contra-

indicatedin breast-feeding;

that can be given to the mother during breast-

feedingbecause theyare presentin milk inamounts

whichare too small tobe harmful to the infant;

thatmight be present inmilk in signiﬁcant amount

butare not known tobe harmful.

Wherecare is needed when prescribingin breast-feed-

ing,this isindicated under therelevant drug inthe BNF.

Formany drugs insufﬁcient evidenceis available to

provide guidance and it is advisable to administer

onlyessential drugs toa mother during breast-feed-

ing. Because of the inadequacy of information on

drugsin breast-feeding,absence of informationdoes

notimply safety.

BNF 61 Prescribingin pregnancy 19

Prescribingin breast-feeding

Prescribing in palliative care

Palliativecare is theactive total care ofpatients whose

diseaseis not responsiveto curative treatment.Control

ofpain, of othersymptoms, and ofpsychological, social

andspiritual problems,is paramount toprovide thebest

quality of life for patientsand their families. Careful

assessment of symptoms and needs of the patient

shouldbe undertaken by amultidisciplinary team.

Specialistpalliative careis availablein mostareas asday

hospice care,home-care teams (often known as Mac-

millan teams), in-patient hospice care, and hospital

teams.Many acute hospitals andteaching centres now

haveconsultative, hospital-based teams.

Hospice care of terminally ill patients has shown the

importanceof symptom control and psychosocial sup-

port of the patient and family. Families should be

includedin the care ofthe patient if they wish.

Many patients wish to remain at home with their

families.Although some families may at ﬁrst be afraid

of caring for the patient at home, support can be

provided by community nursing services, social ser-

vices, voluntary agencies and hospices together with

thegeneral practitioner.The familymay bereassured by

the knowledge that the patient will be admitted to a

hospitalor hospice if thefamily cannot cope.

Drug treatment

The numberof dr ugsshould be as

fewas possible, foreven the takingof medicine maybe

aneffort. Oral medication is usuallysatisfactory unless

thereis severe nausea and vomiting, dysphagia,weak-

ness, or coma, when parenteral medication may be

necessary.

Pain

Analgesicsare moreef fectivein preventingpain than in

therelief ofestablished pain;it isimportant that theyare

givenregularly.

Paracetamol(p. 259)or a NSAID(section 10.1.1)given

regularly will often make the use of opioid analgesics

unnecessary. A NSAID may also control the pain of

bonesecondaries

;if necessary, ﬂurbiprofen orindome-

tacincan be given rectally.Radiotherapy, bisphosphon-

ates (section6.6.2), and radioactive isotopes of stron-

tium (

Metastron

availablefrom GE Healthcare) may

alsobe useful for pain dueto bone metastases.

An opioid analgesic (section 4.7.2) such as codeine

(p.264), alone or in combination with a non-opioid

analgesic at adequate dosage, may be helpful in the

controlof moderate painif non-opioid analgesics alone

are not sufﬁcient. Alternatively,tramadol (p. 271) can

beconsidered for moderate pain. If thesepreparations

donot control the pain, morphine (p.268) is the most

useful opioid analgesic. Alternatives to morphine,

including hydromor phone (p. 267), methadone

(p.267), oxycodone(p. 269), andtransdermal fentanyl

(seebelow and p. 265) arebest initiated by those with

experience in palliative care. Initiation of an opioid

analgesic should not be delayed by concern over a

theoretical likelihood of psychological dependence

(addiction).

Equivalentsingle doses of opioid analgesics

Theseequivalences areintended only as an approximate

guide;patients should be carefully monitored after any

changein medication and dose titration may be required

Analgesic Dose

Morphinesalts (oral) 10mg

Diamorphinehydrochloride (intramuscular) 3mg

Hydromorphonehydrochloride 1.3mg

Oxycodone(oral) 5mg

Oralroute

Morphine(p. 268) isgiven

bymouth

asan

oralsolution oras standard (‘immediaterelease’) tablets

regularly every 4 hours, the initial dose depending

largely on the patient’sprevious treatment. A dose of

5–10mg is enoughto replace a weakeranalgesic (such

as paracetamol), but10–20 mg or more is required to

replacea strong one(comparable to morphine itself).If

theﬁrst dose ofmor phineis no moreeffective than the

previousanalgesic, thenext doseshould beincreased by

30–50%,the aim being to choose the lowestdose that

preventspain. Thedose should beadjusted with careful

assessment of the pain,and the use of adjuvant anal-

gesics (such as NSAIDs) should also be considered.

Although morphine in a dose of 5–20 mg is usually

adequatethere should be no hesitation in increasingit

stepwiseaccording to response to100 mg oroccasion-

ally up to 500 mg or higher ifnecessar y. It may be

possibleto omit the overnight doseif double the usual

doseis given at bedtime.

When the pain iscontrolled and the patient’s 24-hour

morphinerequirement is established,the dailydose can

begiven as a

modiﬁed-releasepreparation

ina single

doseor in two divideddoses.

Preparations suitable for twice-daily administration

include

Morphgesic

tablets (p.268),

MST Con-

tinus

tablets or suspension (p. 269), and

Zomorph

capsules(p. 269).

MXL

capsules(p. 269) allowadmin-

istration of the total daily morphine requirement as a

singledose.

The starting dose of modiﬁed-releasemor phine pre-

parations designed for twice daily administration is

usually10–20 mg every 12 hours ifno other analgesic

(oronly paracetamol) hasbeen taken previously,but to

replacea weakeropioid analgesic (suchas co-codamol)

the starting dose is usually 20–30mg every 12 hours.

Increments should be made to the dose, not to the

frequency of administration, which should remain at

every12 hours.

Theeffective dose ofmodiﬁed-release preparations can

alternativelybe determined by giving the oral solution

ofmorphine every 4 hoursin increasing dosesuntil the

pain has been controlled, and then transferring the

patient to the same total 24-hour dose of morphine

givenas the modiﬁed-release preparation (dividedinto

two portions for 12-hourly administration). The ﬁrst

doseof the modiﬁed-release preparation is given with,

orwithin 4 hours of, the last doseof the oral solution.

Thepatient should be monitored closely for treatment

efﬁcacyand side-effects.

If pain occurs between regular doses of morphine

(‘breakthrough pain’), an additional dose (‘rescue

dose’)should be given. An additional doseshould also

20 Prescribing in palliative care BNF 61

Prescribingin palliative care

begiven 30 minutes beforean activity thatcauses pain

(e.g. wound dressing). Morphine, as oral solution or

standard formulation tablets, should be prescribed for

breakthroughpain. Thestandard doseof a strongopioid

forbreakthrough pain is usually one-tenth toone-sixth

ofthe regular 24hour total dailydose, repeatedevery 4

hoursif necessary(review painmanagement ifanalgesic

required more frequently). Each patient should be

assessed onan individual basis. Fentanyl lozenges are

alsolicensed for breakthrough pain.

Oxycodone(p. 269)can beused inpatients whorequire

anopioid but cannottolerate morphine. Ifthe patient is

already receiving an opioid, oxycodone should be

started at a dose equivalent to the current analgesic

(seeEquivalent SingleDoses ofOpioid Analgesics table,

p.20).

Levomepromazine(p. 220) is licensed totreat pain in

palliativecare, andmay beof beneﬁtin somepatients. It

should bereser ved for usein conjunction with strong

opioidanalgesics indistressed patients withsevere pain

unresponsiveto other measures.

Parenteral route

If the patient becomes unable to

swallow,the equivalentintramuscular doseof morphine

ishalf theoral solutiondose; in thecase ofthe modiﬁed-

releasetablets it ishalf the total 24-hourdose (which is

thendivided into 6portions to be givenevery 4 hours).

Diamorphine (p. 264) is preferred for injection

because,being moresoluble, itcan be givenin asmaller

volume. The equivalent intramuscular (or subcuta-

neous) dose is approximately a third of the oral dose

ofmorphine.

Subcutaneousinfusion

ofdiamorphine via

continuousinfusion devicecan beuseful (for details,see

p.23).

If the patientcan resume taking medicines by mouth,

then oral morphine may be substituted for subcuta-

neousinfusion ofdiamorphine. Seetable ofapproximate

equivalentdoses of morphine anddiamor phine,p. 24.

Rectal route

Morphine (p.269) is also available for

rectal administration

as suppositories; alternatively

oxycodone(p. 269) suppositories can be obtained on

specialorder.

Transdermal route

Transdermal preparations of

fentanyl and buprenorphine are available (section

4.7.2);they are notsuitable for acutepain or inpatients

whose analgesic requirements are changing rapidly

because the long time to steady state prevents rapid

titrationof thedose. Prescribers shouldensure thatthey

arefamiliar withthe correctuse of transdermalprepara-

tions(see underFentanyl, p.265) because inappropriate

usehas caused fatalities.

Thefollowing 24-hourdoses of morphineby mouthare

considered to be approximately equivalent to the

fentanylpatches shown:

Morphinesalt 45 mgdaily : fentanyl ‘12’patch

Morphinesalt 90 mgdaily : fentanyl ‘25’patch

Morphinesalt 180 mgdaily : fentanyl ‘50’patch

Morphinesalt 270 mgdaily : fentanyl ‘75’patch

Morphinesalt 360 mgdaily : fentanyl ‘100’patch

Morphine (as oral solution or standard formulation

tablets)is given for breakthroughpain.

Gastro-intestinalpain

Thepain of

bowelcolic

may

be reduced byloperamide 2–4 mg 4 times daily.Hyo-

scine hydrobromide(section 4.6) may also be helpful,

givensublingually at a doseof 300 micrograms3 times

dailyas

Kwells

tablets.For the dose bysubcutaneous

infusion,see p. 23).

Gastricdistension pain due topressure on thestomach

maybe helped by apreparation incorporating an anta-

cidwith an antiﬂatulent (section1.1.1) and aprokinetic

suchas domperidone 10mg 3times daily beforemeals.

Muscle spasm

The pain of muscle spasm can be

helpedby a musclerelaxant such asdiazepam 5–10mg

dailyor baclofen 5–10mg 3 times daily.

Neuropathic pain

Patients with neuropathic pain

(section 4.7.3) may beneﬁt from a trial of a tricyclic

antidepressant for several weeks. An anticonvulsant

maybe addedor substituted ifpain persists; gabapentin

and pregabalin (both section 4.8.1) are licensed for

neuropathic pain. Ketamine is sometimes used under

specialist supervision for neuropathic pain that

respondspoorly to opioid analgesics.

Paindue to ner ve compression may be reduced by a

corticosteroidsuch asdexamethasone 8mg daily,which

reduces oedema around the tumour, thus reducing

compression.

Nerveblocks can beconsidered when painis localised

to a speciﬁc area. Transcutaneous electrical nerve

stimulation(TENS) may also help.

Miscellaneous conditions

Unlicensedindications or routes

Several recommendations in this section involve

unlicensedindications or routes.

Anorexia

Anorexia may be helped by prednisolone

15–30mg dailyor dexamethasone 2–4mg daily.

Bowelcolic and excessive respiratory secretions

Bowelcolic andexcessive respiratorysecretions maybe

reducedby asubcutaneous injection ofhyoscine hydro-

bromide 400 micrograms, hyoscine butylbromide

20mg, or glycopyrronium200 micrograms.These anti-

muscarinics are generally given every 4hour s when

required,but hourly use is occasionallynecessary, par-

ticularly in excessive respiratory secretions. If symp-

tomspersist, they can be given regularly via a contin-

uousinfusion device,see p.23. Care isrequired toavoid

thediscomfort of dry mouth.

Capillarybleeding

Capillarybleeding can betreated

withtranexamic acid(section 2.11)by mouth; treatment

isusually discontinued oneweek after the bleedinghas

stopped, or, if necessary, it can be continued at a

reduceddose. Alternatively,gauze soakedin tranexamic

acid 100mg/mL or adrenaline(epinephrine) solution

1mg/mL (1in 1000)can beapplied tothe affected area.

VitaminK may be usefulfor the treatment andpreven-

tion of bleeding associated with prolonged clotting in

liverdisease. In severe chronic cholestasis, absorption

of vitamin K may be impaired; either parenteral or

water-solubleoral vitamin Kshould beconsidered (sec-

tion9.6.6).

BNF 61 Prescribingin palliative care 21

Prescribingin palliative care

Constipation

Constipationis avery common causeof

distressand is almost invariableafter administration of

anopioid analgesic.It shouldbe preventedif possibleby

theregular administration oflaxatives; a faecalsoftener

with a peristaltic stimulant (e.g. co-danthramer) or

lactulose solution with a senna preparation should be

used(section 1.6.2and section 1.6.3).Methylnaltrexone

(section 1.6.6) is licensed for the treatment of opioid-

inducedconstipation.

Convulsions

Patientswith cerebral tumours or urae-

mia may be susceptible toconvulsions. Prophylactic

treatment with phenytoin or carbamazepine (section

4.8.1) should be considered. When oral medication is

nolonger possible,diazepam assuppositories 10–20mg

every 4 to 8 hours, or phenobarbital by injection 50–

200mg twice dailyis continued asprophylaxis. For the

use of midazolam by subcutaneous infusion using a

continuousinfusion device, see below.

Drymouth

Drymouth maybe relievedby goodmouth

care and measures such as chewingsugar-free gum,

suckingice or pineapple chunks, orthe use of artiﬁcial

saliva(section 12.3.5);dry mouth associated with candi-

diasiscan be treatedby oral preparationsof nystatin or

miconazole (section 12.3.2); alternatively, ﬂuconazole

canbe given by mouth(section 5.2.1). Dry mouth may

be caused by certain medications including opioids,

antimuscarinic drugs (e.g. hyoscine), antidepressants

and some antiemetics; if possible, an alternative pre-

parationshould be considered.

Dysphagia

A corticosteroidsuch as dexamethasone

8mg dailymay help, temporarily,if there isan obstruc-

tiondue to tumour. Seealso Dry Mouth, above.

Dyspnoea

Breathlessnessat rest may be relieved by

regularoral morphinein carefullytitrated doses,starting

at5 mgevery 4 hours.Diazepam 5–10 mgdaily may be

helpfulfor dyspnoea associatedwith anxiety.A cortico-

steroid,such as dexamethasone 4–8mg daily,may also

behelpful if there is bronchospasm or partial obstruc-

tion.

Fungatingtumours

Fungatingtumours can be trea-

tedby regulardressing andantibacterial drugs;systemic

treatment with metronidazole (section 5.1.11) is often

requiredto reduce malodour buttopical metronidazole

(section13.10.1.2) is also used.

Hiccup

Hiccupdue togastric distensionmay behelped

bya preparation incorporating anantacid with an anti-

ﬂatulent (section 1.1.1). If this fails, metoclopramide

10mg every6 to 8 hoursby mouth orby subcutaneous

orintramuscular injectioncan beadded; if thisalso fails,

baclofen 5mg twice daily, or nifedipine 10 mg three

times daily, or chlorpromazine (section 4.2.1) can be

tried.

Hypercalcaemia

seesection 9.5.1.2

Insomnia

Patients with advanced cancer may not

sleep because of discomfort, cramps, night sweats,

joint stiffness, or fear. There should be appropriate

treatment of these problems before hypnotics are

used. Benzodiazepines, such as temazepam (section

4.1.1),may be useful.

Intractablecough

Intractablecough may berelieved

bymoist inhalationsor by regularadministration of oral

morphine in an initial dose of 5 mg every 4 hours.

Methadonelinctus should be avoided because it has a

longduration of action andtends to accumulate.

Nausea and vomiting

Nausea and vomiting are

commonin patients with advanced cancer.Ideally, the

cause should bedeter mined beforetreatment with an

antiemetic(section 4.6) is started.

Nausea and vomiting may occur with opioid therapy

particularlyin the initialstages but canbe prevented by

giving an antiemetic such as haloperidol or metoclo-

pramide.An antiemeticis usually necessaryonly forthe

ﬁrst 4 or5 days and therefore combined preparations

containingan opioid withan antiemetic are notrecom-

mended because they lead to unnecessary antiemetic

therapy (and associated side-effects when used long-

term).

Metoclopramidehas aprokinetic action andis usedin a

dose of10 mg 3 times daily by mouthfor nausea and

vomiting associated with gastritis, gastric stasis, and

functionalbowel obstruction.Drugs withantimuscarinic

effects antagonise prokinetic drugs and, if possible,

shouldnot be used concurrently.

Haloperidolis usedby mouthin an initialdose of1.5 mg

onceor twice daily(can be increasedif necessary to5–

10mg dailyin divideddoses) for mostmetabolic causes

ofvomiting (e.g. hypercalcaemia, renalfailure).

Cyclizineis given ina dose of50 mgup to 3times daily

by mouth. It is used for nausea and vomiting due to

mechanicalbowel obstruction, raised intracranial pres-

sure,and motion sickness.

Antiemetictherapy should bereviewed every 24hours;

it maybe necessary to substitute the antiemetic or to

addanother one.

Levomepromazinecan be used if ﬁrst-line antiemetics

areinadequate; itis givenby mouthin adose of6–50 mg

daily(6-mg tablets availablefrom ‘special-order’ manu-

facturersor specialist importing companies,see p. 988)

in 1–2 divided doses. For the doseby subcutaneous

infusion, see p.23. Dexamethasone8–16 mg daily by

mouthcan be used asan adjunct.

Forthe administration of antiemetics by subcutaneous

infusionusing a continuous infusiondevice, see below.

For the treatment of nausea and vomiting associated

withcancer chemotherapy, seesection 8.1.

Pruritus

Pruritus,even when associatedwith obstruc-

tivejaundice, often responds to simple measures such

asapplication of emollients(section 13.2.1). Inthe case

of obstructive jaundice, further measures include

administrationof colestyramine (section 1.9.2).

Raised intracrani al pressure

Headache due to

raised intracranial pressure often responds to a high

doseof a corticosteroid,such as dexamethasone 16mg

dailyfor 4 to 5 days, subsequently reduced to 4–6mg

dailyif possible;dexamethasone should begiven before

6p.m. toreduce the risk ofinsomnia.

Restlessnessand confusion

Restlessnessand con-

fusion mayrequire treatment with haloperidol 1–3 mg

bymouth every8 hours. Levomepromazineis alsoused

occasionallyfor restlessness. For the dose by subcuta-

neousinfusion using a continuous infusion device, see

p.23.

22 Prescribing in palliative care BNF 61

Prescribingin palliative care

Continuousinfusion devices

Althoughdr ugscan usually be administered

bymouth

to control the symptoms of advanced cancer, the par-

enteral route may sometimes be necessary. Repeated

administrationof

intramuscularinjections

canbe difﬁ-

cult in a cachectic patient. This has led to the use of

portable continuous infusion devices, such as syringe

drivers, to give a

continuous subcutaneous infusion

whichcan provide goodcontrol of symptomswith little

discomfortor inconvenience to thepatient.

Syringedriver rate settings

Staff using syringe drivers should be adequately

trainedand different ratesettings should beclearly

identiﬁed and differentiated; incorrect use of

syringe drivers is a common cause of medication

errors.

Indicationsfor the parenteral route are:

the patient is unable to take medicines by mouth

owingto

nauseaand vomiting, dysphagia, severe

weakness,

coma;

thereis

malignantbowel obstruction

inpatients for

whomfurther surgeryis inappropriate (avoidingthe

needfor anintravenous infusionor for insertionof a

nasogastrictube);

occasionallywhen thepatient

doesnot wish

totake

regularmedication by mouth.

Bowel colic and excessive respiratory secretions

Hyoscinehydrobromide effectively reduces respiratory

secretions and is sedative (but occasionally causes

paradoxical agitation); it is given in a

subcutaneous

infusiondose

of1.2–2.4 mg/24hours.

Hyoscinebutylbromide is used for bowel colic andfor

excessive respiratory secretions, and is less sedative

than hyoscine hydrobromide. Hyoscine butylbromide

is given in a

subcutaneous infusion dose

of 60–

300mg/24hours for bowel colic and 20–120mg/

24hours for excessive respiratory secretions (impor-

tant: these doses of

hyoscine butylbromide

must not

be confused with the much lower dose of

hyoscine

hydrobromide

,above).

Glycopyrronium0.6–1.2 mg/24hours by subcutaneous

infusionmay also be used.

Convulsions

Ifa patienthas previouslybeen receiving

an antiepileptic drug

has a primary or secondary

cerebraltumour

isat riskof convulsion (e.g.owing to

uraemia) antiepileptic medication should not be

stopped.Midazolam is thebenzodiazepine antiepileptic

ofchoice for

continuoussubcutaneous infusion

,and itis

giveninitially in a doseof 20–40 mg/24hours.

Nausea and vomiting

Haloperidol is given in a

subcutaneousinfusion dose

of2.5–10 mg/24hours.

Levomepromazineis given in a

subcutaneousinfusion

dose

of 5–25mg/24 hours but sedation can limit the

dose.

Cyclizine is particularly likely to precipitate if mixed

with diamorphine or other drugs (see under Mixing

andCompatibility, below); itis given ina

subcutaneous

infusiondose

of150 mg/24hours.

Metoclopramidecan causeskin reactions;it isgiven ina

subcutaneousinfusion dose

of30–100 mg/24hours.

Octreotide(section 8.3.4.3), whichstimulates waterand

electrolyteabsorption andinhibits watersecretion inthe

smallbowel, can beused by subcutaneousinfusion in a

doseof 250–500 micrograms/24hours to reduceintes-

tinal secretions and to reduce vomiting due to bowel

obstruction. Doses of 750 micrograms/24 hours, and

occasionallyhigher, are sometimes required.

Pain control

Diamorphine is the preferred opioid

since its high solubility permits a large dose to be

givenin asmall volume (seeunder Mixingand Compat-

ibility,below). The tableon p. 24 shows approximate

equivalentdoses of morphine anddiamor phine.

Restlessness and confusion

Haloperidol haslittle

sedative effect; it is given in a

subcutaneous infusion

dose

of5–15 mg/24hours.

Levomepromazinehas a sedative effect;it is given ina

subcutaneousinfusion dose

of12.5–200 mg/24hours.

Midazolamis a sedative and an antiepileptic that may

beused in addition to an antipsychotic drug in aver y

restless patient; it is givenin a

subcutaneous infusion

dose

of20–100 mg/24hours.

Mixingand compatibility

Thegeneral principlethat

injections should be given into separate sites (and

should not be mixed) does not apply to the use of

syringedrivers in palliative care. Providedthat there is

evidence of compatibility, selected injections can be

mixed in syringe drivers. Not all types of medication

can be used in a subcutaneous infusion. Inparticular,

chlorpromazine, prochlorperazine, and diazepam are

contra-indicated as they cause skin reactions at the

injection site;to a lesser extent cyclizine and levome-

promazinealso sometimes cause localirritation.

Intheory injections dissolvedin water forinjections are

morelikely tobe associatedwith pain(possibly owingto

theirhypotonicity). Theuse of physiologicalsaline (sod-

iumchloride 0.9%) however increasesthe likelihood of

precipitationwhen more than one drug is used; more-

over subcutaneous infusion rates are so slow (0.1–

0.3mL/hour) that pain is not usually a problemwhen

wateris used as adiluent.

Diamorphinecan be given bysubcutaneous infusion in

a strength of up to 250mg/mL; up to a strength of

40mg/mL either

waterfor injections

physiological

saline

(sodium chloride 0.9%) is a suitable diluent—

abovethat strength only

waterfor injections

isused (to

avoidprecipitation).

Thefollowing can be mixedwith

diamorphine

Cyclizine

Hyoscinehydrobromide

Dexamethasone

Levomepromazine

Haloperidol

Metoclopramide

Hyoscinebutylbromide Midazolam

1.Cyclizine may precipitateat concentrations above10 mg/

inthe presence of sodium chloride0.9%

asthe

concentration of diamorphine relative to cyclizine in-

creases; mixtures of diamorphine and cyclizine are also

likelyto precipitate after24 hours.

2.Special care is needed to avoid precipitationof dexa-

methasonewhen preparing it.

3.Mixtures of haloperidol and diamorphine are likely to

precipitate after 24 hours if haloperidol concentration is

above2 mg/mL.

4.Under some conditions infusions containing metoclopra-

mide become discoloured; such solutions should be

discarded.

BNF 61 Prescribingin palliative care 23

Prescribingin palliative care

Subcutaneous infusion solution should be monitored

regularlyboth to checkfor precipitation (anddiscolora-

tion) andto ensure that the infusion is running at the

correctrate.

Problemsencountered with syringe drivers

The

followingare problems that may be encountered with

syringedrivers and the actionthat should be taken:

ifthe subcutaneous infusionruns

tooquickly

check

therate setting and thecalculation;

ifthe subcutaneous infusion runs

tooslowly

check

thestart button, the battery,the syringe driver, the

cannula,and make sure that theinjection site isnot

inﬂamed;

ifthere is an

injectionsite reaction

makesure that

thesite does not need tobe changed—ﬁrmness or

swelling at the site of injection is not in itself an

indication forchange, but pain or obvious inﬂam-

mationis.

Equivalentdoses of morphine sulphate and

diamorphinehydrochloride given over 24

hours

Theseequivalences are approximate only andshould

beadjusted according to response

MORPHINE

PARENTERAL

DIAMORPHINE

Oral

morphine

sulphate

Subcutaneous

infusionof

morphinesulphate

Subcutaneous

infusionof

diamorphine

hydrochloride

over24 hours over 24 hours over24 hours

30mg 15mg 10 mg

60mg 30mg 20 mg

90mg 45mg 30 mg

120mg 60 mg 40mg

180mg 90 mg 60mg

240mg 120mg 80mg

360mg 180mg 120mg

480mg 240mg 160mg

600mg 300mg 200mg

780mg 390mg 260mg

960mg 480mg 320mg

1200mg 600mg 400mg

Ifbreakthrough pain occurs give a subcutaneous (pre-

ferable)or intramuscular injection equivalent to one-

tenthto one-sixth of the total 24-hour subcutaneous

infusiondose. It is kinder to give an intermittent bolus

injectionsubcutaneously—absorption is smoother so

thatthe risk of adverse effects at peak absorption is

avoided(an even better method is to use a subcuta-

neousbutterﬂy needle).

Tominimise the risk of infection no individual subcu-

taneousinfusion solution should be used for longer

than24 hours.

Prescribing for the elderly

Oldpeople, especially thevery old, requirespecial care

andconsideration fromprescribers.

Medicinesfor Older

People

,a component documentof the NationalService

Framework for Older People,

describes how to max-

imisethe beneﬁtsof medicines andhow to avoidexces-

sive,inappropriate, orinadequate consumption of med-

icinesby older people.

Appropriate prescribing

Elderly patients often

receivemultiple drugs for their multiple diseases. This

greatlyincreases the riskof drug interactions aswell as

adversereactions, and mayaffect compliance (seeTak-

ing medicines to best effect under General guidance).

The balance of beneﬁt and harm of somemedicines

maybe alteredin theelderly. Therefore,elderly patients’

medicinesshould be reviewed regularly andmedicines

whichare not of beneﬁtshould be stopped.

Non-pharmacologicalmeasures may bemore appropri-

atefor symptoms such asheadache, sleeplessness, and

lightheadednesswhen associatedwith socialstress as in

widowhood,loneliness, and family dispersal.

In some cases prophylactic drugs are inappropriate if

they are likely to complicate existing treatment or

introduceunnecessary side-effects, especiallyin elderly

patientswith poorprognosis orwith poor overallhealth.

However,elderly patients should not be denied medi-

cineswhich may help them, such as anticoagulants or

antiplatelet drugs for atrial ﬁbrillation, anti-

hypertensives,statins, and drugs forosteoporosis.

Form of medicine

Frail elderly patients may have

difﬁcultyswallowing tablets; if left in themouth, ulcer-

ationmay develop. Theyshould always be encouraged

totake their tablets or capsuleswith enough ﬂuid, and

whilstin an upright position to avoid the possibilityof

oesophagealulceration. Itcan be helpfulto discusswith

thepatient thepossibility of takingthe drugas a liquidif

available.

Manifestationsof ageing

Inthe very old, manifes-

tations of normal ageingmay be mistaken for disease

andlead to inappropriate prescribing. Inaddition, age-

related muscle weakness and difﬁculty in maintaining

balance shouldnot be confused with neurological dis-

ease.Disorders such as lightheadednessnot associated

withpostural or postprandial hypotension are unlikely

tobe helped by drugs.

Sensitivity

Thenervous system of elderly patientsis

moresensitive to many commonlyused drugs, such as

1.Department of Health. National Service Framework for

OlderPeople. London:Department ofHealth, March 2001.

24 Prescribing for the elderly BNF 61

Prescribingfor theelderly

opioidanalgesics, benzodiazepines, antipsychotics, and

antiparkinsoniandr ugs,all of which mustbe used with

caution.Similarly, other organs may alsobe more sus-

ceptibleto theeffects ofdrugs suchas antihypertensives

andNSAIDs.

Pharmacokinetics

Pharmacokinetic changes can markedly increase the

tissueconcentration of a drug in theelderly, especially

indebilitated patients.

The most important effect of age is reduced renal

clearance. Many aged patients thus

excrete drugs

slowly

, and are

highly susceptible to nephrot oxic

drugs

. Acute illness can lead to rapid reduction in

renalclearance, especially if accompanied bydehydra-

tion.Hence, apatient stabilised ona drugwith a narrow

marginbetween the therapeuticand thetoxic dose (e.g.

digoxin) can rapidly develop adverse ef fects in the

aftermath of a myocardial infarction or a respiratory-

tractinfection. The hepatic metabolism oflipid soluble

drugs isreduced in elderly patients because there is a

reduction in liver volume. This is important fordrugs

witha narrow therapeutic window.

Adverse reactions

Adversereactions oftenpresent inthe elderly ina vague

and non-speciﬁc fashion.

Confusion

is often the pre-

senting symptom (caused by almost any of the com-

monlyused drugs). Other common manifestations are

constipation

(with antimuscarinics and many tran-

quillisers)and postural

hypotension

and

falls

(withdiur-

eticsand many psychotropics).

Hypnotics

Manyhypnotics with long half-lives have

serioushangover effects, including drowsiness, unstea-

dygait, slurred speech, and confusion. Hypnotics with

shorthalf-lives should beused but theytoo can present

problems(section 4.1.1). Shortcourses of hypnoticsare

occasionally useful for helping a patient through an

acuteillness or some other crisisbut every effort must

bemade to avoid dependence.Benzodiazepines impair

balance,which can result infalls.

Diuretics

Diureticsare overprescribed in old ageand

shouldnot be usedon a long-termbasis to treatsimple

gravitational oedema which will usually respond to

increased movement, raising the legs, and support

stockings.A few days of diuretic treatmentmay speed

the clearing of the oedema but it should rarely need

continueddrug therapy.

NSAIDs

Bleeding associated with aspirin and other

NSAIDsis more common in the elderlywho are more

likelyto have a fatal or serious outcome. NSAIDs are

alsoa special hazardin patients withcardiac disease or

renalimpairment which mayagain place older patients

atparticular risk.

Owing to the

increasedsuscep tibility of the elderly

the

side-effectsof NSAIDs

thefollowing recommenda-

tionsare made:

for

osteoarthritis,soft-tissue lesions

,and

backpain

ﬁrst try measures such as weight reduction (if

obese),warmth, exercise,and useof awalking stick;

for

osteoarthritis,soft-tissue lesions, back pain

,and

painin rheumatoidarthrit is

,paracetamol shouldbe

used ﬁrst and can often provide adequate pain

relief;

alternatively,a low-dose NSAID (e.g. ibuprofen up

to1.2 g daily)may be given;

forpain relief wheneither drug isinadequate, para-

cetamolin a full dose plusa low-dose NSAID may

begiven;

ifnecessary, theNSAID dosecan beincreased oran

opioidanalgesic given with paracetamol;

donot give two NSAIDsat the same time.

For advice on prophylaxis of NSAID-induced peptic

ulcers if continuedNSAID treatment is necessary, see

section1.3.

Other drugs

Other drugs which commonlycause

adverse reactions are

antiparkinsonian drugs, anti-

hypertensives, psychotropics

, and

digoxin

. The usual

maintenance dose of digoxin in very old patients is

125micrograms daily (62.5 micrograms in those with

renal disease); lower doses are often inadequate but

toxicityis commonin thosegiven 250micrograms daily.

Drug-inducedblood disorders aremuch more common

inthe elderly.Therefore drugs witha tendency tocause

bone marrow depression (e.g.

co-trimoxazole, mian-

serin

)should be avoided unless there is no acceptable

alternative.

Theelderly generallyrequire a lowermaintenance dose

warfarin

than younger adults;once again, theout-

comeof bleeding tends tobe more serious.

Guidelines

Alwaysconsider whether a drugis indicated at all.

Limitrange

Itis a sensible policyto prescribe froma

limitedrange ofdrugs andto bethoroughly familiarwith

theireffects in the elderly.

Reduce dose

Dosage should generally be substan-

tiallylower than foryounger patients and itis common

tostart with about 50% of theadult dose. Some drugs

(e.g. long-acting antidiabetic drugs such as gliben-

clamide)should be avoided altogether.

Review regularly

Review repeatprescriptions regu-

larly.In many patientsit may be possible tostop some

drugs, provided that clinical progress is monitored. It

maybe necessary to reducethe dose of somedrugs as

renalfunction declines.

Simplify regimens

Elderly patients beneﬁt from

simple treatment regimens. Only drugs with a clear

indicationshould be prescribed andwhenever possible

givenonce or twicedaily. In particular,regimens which

callfor a confusing arrayof dosage intervals should be

avoided.

Explain clearly

Writefull instructions on every pre-

scription (

including

repeat prescriptions) so that con-

tainers can be properly labelled with full directions.

Avoid imprecisions like ‘as directed’. Child-resistant

containersmay be unsuitable.

Repeatsand disposal

Instruct patientswhat to do

whendrugs run out,and alsohow todispose of anythat

are no longer necessary. Try to prescribe matching

quantities.

Ifthese guidelines arefollowed mostelderly people will

copeadequately withtheir own medicines.If not thenit

isessential to enrol the help of a thirdparty, usually a

relativeor a friend.

BNF 61 Prescribingfor the elderly 25

Prescribingfor theelderly

Prescribing in dental practice

Thefollowing isa listof topics ofparticular relevanceto

dentalsurgeons.

Adviceon the drug management ofdental and oral

conditions has been integrated into the BNF.For

ease of access, guidance on such conditions is

usually identiﬁed by means of a relevant heading

(e.g.Dental andOrofacial Pain) in the appropriate

sectionsof the BNF.

Generalguidance

Prescribingby dental surgeons, p.6

Oralside-effects of drugs, p.13

Medicalemergencies in dental practice,below

Medicalproblems in dental practice,p. 28

Drug managementof dental and oralconditions

Dentaland orofacial pain, p.257

Neuropathicpain, p. 272

Non-opioidanalgesics and compound analgesic

preparations,p. 257

Opioidanalgesics, p. 263

Non-steroidalanti-inﬂammator ydrugs, p. 631

Oralinfections

Bacterialinfections, p. 321

Phenoxymethylpenicillin,p. 333

Broad-spectrumpenicillins (amoxicillin and

ampicillin),p. 336

Cephalosporins(cefalexin and cefradine),

p.341

Tetracyclines,p. 347

Macrolides(clarithromycin, erythromycin and

azithromycin),p. 352

Clindamycin,p. 354

Metronidazole,p. 367

Fusidicacid p. 735

Fungalinfections, p. 695

Localtreatment, p. 695

Systemictreatment, p. 373

Viralinfections

Herpeticgingivostomatitis, local treatment,

p.696

Herpeticgingivostomatitis, systemictreatment,

p.392 and p.696

Herpeslabialis, p. 739

Anaesthetics,anxiolytics and hypnotics

Anaesthesia,sedation, and resuscitationin dental

practice,p. 776

Hypnotics,p. 208

Peri-operativeanxiolytics, p.783

Localanaesthesia, p. 794

Oralulceration and inﬂammation, p.693

Mouthwashes,gargles and dentifrices, p.697

Dry mouth,p. 698

Minerals

Fluorides,p. 613

Aromaticinhalations, p. 203

Nasaldecongestants, p. 691

DentalPractitioners’ Formulary, p.972

Changesto Dental Practitioners’ Formulary,p. 973

Medical emergencies in dental practice

Thissection provides guidelineson the managementof

the more common medical emergencies which may

arisein dental practice. Dentalsurgeons and their staff

should be familiar with standard resuscitation proce-

dures,but inall circumstancesit isadvisable tosummon

medical assistance as soon as possible. For an algo-

rithm ofthe procedure for cardiopulmonary resusci-

tation,see inside back cover.

Thedr ugsrefer redto in this sectioninclude:

Adrenaline Injection (Epinephrine Injection), adr-

enaline 1 in 1000, (adrenaline 1 mg/mL as acid

tartrate),1-mL amps

AspirinDispersible Tablets 300mg

GlucagonInjection, glucagon (as hydrochloride), 1-

unitvial (with solvent)

Glucose(for administration by mouth)

GlycerylTrinitrate Spray

MidazolamBuccal Liquid, midazolam10 mg/mL

MidazolamInjection, midazolam (as hydrochloride)

2mg/mL, 5-mL amps,or 5mg/mL, 2-mL amps

Oxygen

SalbutamolAerosol Inhalation,salbutamol 100micr-

ograms/meteredinhalation

Adrenalinsufﬁciency

Adrenal insufﬁciency may follow prolonged therapy

with corticosteroids and can persist for years after

stopping. A patient with adrenal insufﬁciency may

become hypotensiveunder the stress of a dental visit

(important:see also p. 444 for details ofcorticosteroid

coverbefore dental surgical procedures under general

anaesthesia).

Management

Laythe patient ﬂat

Giveoxygen (see section 3.6)

Transferpatient urgently to hospital

Anaphylaxis

Asevere allergic reactionmay follow oralor parenteral

administration of a drug. Anaphylactic reactions in

dentistry may follow the administration of a drug or

contactwith substancessuch as latexin surgical gloves.

Ingeneral, the more rapidthe onset ofthe reaction the

moreprofound it tends to be. Symptoms maydevelop

withinminutes and rapid treatmentis essential.

Anaphylactic reactions may also be associated with

additives

and

excipients

in foods and medicines (see

Excipients, p.2). Reﬁned arachis (peanut) oil, which

maybe present in somemedicinal products, is unlikely

tocause an allergic reaction—neverthelessit is wise to

checkthe full formula of preparations which maycon-

tain allergenic fats or oils (including those for topical

application,parti cularlyif they are intended for use in

themouth or for applicationto the nasal mucosa).

26 Prescribing in dental practice BNF 61

Prescribingin dental practice

Symptomsand signs

Paraesthesia,ﬂushing, and swelling offace

Generaliseditching, especially of handsand feet

Bronchospasm and laryngospasm (with wheezing

anddifﬁculty in breathing)

Rapid weakpulse together with fall in blood pres-

sureand pallor; ﬁnally cardiacarrest

Management

First-line treatment includes securing the airway,

restoration of blood pressure (laying the patient ﬂat

and raising the feet, or in the recovery position if

unconsciousor nauseous and at risk of vomiting), and

administration of adrenaline (epinephrine) injection

(section 3.4.3). This is given intramuscularly in a

doseof 500 micrograms (0.5mL adrenaline injection 1

in1000); a dose of 300micrograms (0.3 mLadrenaline

injection1 in 1000) may be appropriatefor

immediate

self-administration

.The doseis repeated ifnecessary at

5-minute intervals according to blood pressure,pulse,

andrespiratory function. Oxygenadministration is also

ofprimary importance (see section 3.6).Arrangements

should be made to transfer the patient to hospital

urgently.

Forfurther details on the management of anaphy-

laxisincluding details ofpaediatric doses of adrena-

line,see p. 197

Asthma

Patientswith asthma may have an attack while at the

dentalsurger y.Most attacks will respond to 2puf fsof

the patient’s short-acting beta

agonistinhaler such as

salbutamol 100 micrograms/puff; further puffs are

required ifthe patient does not respond rapidly. If the

patient is unable to use the inhaleref fectively,further

puffs should be given through a large-volume spacer

device(or,if not available,througha plasticor paper cup

witha hole inthe bottomfor the inhalermouthpiece). If

theresponse remains unsatisfactory, or if further dete-

riorationoccurs, then the patientshould be transferred

urgently to hospital. Whilst awaiting transfer, oxygen

(section 3.6)should be given with salbutamol 5 mg or

terbutaline10 mg bynebuliser; if anebuliser is unavail-

able, then 2–10 puffs of salbutamol 100 micrograms/

metered inhalation should be given (preferably by a

large-volume spacer), and repeated every 10–20 min-

utesif necessary.If asthmais part ofa more generalised

anaphylacticreaction, anintramuscular injectionof adr-

enaline (as detailedunder Anaphylaxis above) should

begiven.

Fora tabledescribing themanagement of acuteasthma,

seep. 173

Patientswith severe chronic asthma or whose asthma

has deteriorated previouslyduring a dental procedure

may requirean increase in their prophylactic medica-

tionbefore adental procedure.This shouldbe discussed

withthe patient’s medicalpractitioner and may include

increasingthe dose of inhaledor oral corticosteroid.

Cardiacemergencies

Ifthere is a history of

angina

thepatient will probably

carryglycer yltrinitrate spray or tablets(or isosorbide

dinitrate tablets) and should be allowed to use them.

Hospital admission is not necessary if symptoms are

mildand resolve rapidlywith the patient’sown medica-

tion.See also Coronary Artery Diseaseon p. 29.

Arrhythmias

maylead to asudden reduction incardiac

output with loss of consciousness. Medical assistance

shouldbe summoned. For advice on pacemaker inter-

ference,see also Pacemakers,p. 29.

Thepain of

myocardialinfarction

issimilar to that of

anginabut generally more severeand more prolonged.

Forgeneral advicesee also CoronaryArtery Disease on

p. 29

Symptomsand signs of myocardialinfarction

Progressive onset of severe, crushing pain across

front of chest; pain may radiate towards the

shoulderand down arm, or into neck and jaw

Skinbecomes pale and clammy

Nauseaand vomiting are common

Pulsemay be weak andblood pressure may fall

Breathlessness

Initialmanagement of myocardial infarction

Callimmediately for medical assistance and an ambu-

lance,as appropriate.

Allowthe patient to restin the position that feelsmost

comfortable; in the presence of breathlessness this is

likely to be sitting position, whereas the syncopal

patientshould be laid ﬂat; often an intermediate posi-

tion(dictated by the patient) will be most appropriate.

Oxygenmay be administered (seesection 3.6).

Sublingualglyceryl trinitratemay relievepain. Intramus-

cular injection of drugs should be avoided because

absorptionmay be too slow (particularly when cardiac

output isreduced) and pain relief is inadequate. Intra-

muscularinjection alsoincreases the riskof local bleed-

inginto the muscleif thepatient is givena thrombolytic

drug.

Reassure the patient as much as possible to relieve

further anxiety.If available, aspirin in a single dose of

300mg should begiven. A note(to say that aspirinhas

been given) should be sent with the patient to the

hospital. Forfurther details on the initial management

ofmyocardial infarction, see p.156.

Ifthe patientcollapses and losesconsciousness attempt

standard resuscitation measures. For an algorithm of

theprocedure for cardiopulmonary resuscitation,see

insideback cover.

Epilepticseizures

Patientswith epilepsy must continuewith their normal

dosage of anticonvulsant drugs when attending for

dental treatment. It is not uncommon for epileptic

patientsnot to volunteer the information that they are

epilepticbut there shouldbe little difﬁculty inrecognis-

inga tonic-clonic (grand mal)seizure.

Symptomsand signs

Theremay be a briefwarning (but variable)

Suddenloss of consciousness,the patient becomes

rigid, falls,may give a cry, and becomes cyanotic

(tonicphase)

After 30 seconds,there are jerking movements of

thelimbs; the tongue maybe bitten (clonic phase)

There may be frothing from mouth and urinary

incontinence

Theseizure typicallylasts afew minutes;the patient

maythen become ﬂaccid but remain unconscious.

Aftera variable timethe patient regains conscious-

nessbut may remain confusedfor a while

BNF 61 Prescribing in dental practice 27

Prescribingin dental practice

Management

Duringa convulsion tryto ensure thatthe patient isnot

atrisk from injurybut make noattempt to putanything

in the mouth or between the teeth (in mistaken belief

thatthis will protect thetongue). Give oxygen (section

3.6)to support respiration ifnecessar y.

Donot attempt to restrainconvulsive movements.

After convulsive movements have subsided place the

patient inthe coma (recovery) position and check the

airway.

Afterthe convulsionthe patientmay be confused(‘post-

ictal confusion’) and may need reassurance and sym-

pathy.The patient should not be sent home until fully

recovered.Seek medicalattention ortransfer thepatient

tohospital if itwas theﬁrst episode ofepilepsy, or if the

convulsionwas atypical, prolonged (or repeated), or if

injuryoccurred.

Medicationshould only be given if convulsiveseizures

areprolonged (convulsivemovements lasting 5minutes

orlonger) or repeated rapidly.

Eithermidazolam buccal liquidor midazolam injection

solution can be givenby the buccal route [unlicensed

use]in a singledose of 10mg. Forfurther details onthe

management of status epilepticus, including details of

paediatricdoses of midazolam, seep. 296.

Focalseizures similarly need verylittle active manage-

ment (in an automatism only a minimum amountof

restraintshould beapplied to preventinjury). Again,the

patientshould beobserved untilpost-ictal confusionhas

completelyresolved.

Hypoglycaemia

Insulin-treated diabetic patients attending for dental

treatmentunder local anaesthesia should inject insulin

and eatmeals as normal. If food is omitted the blood

glucosewill fall to an abnormally low level (hypoglyc-

aemia). Patients can often recognise the symptoms

themselves and this state responds to sugar in water

or a few lumpsof sugar. Children may not have such

prominentchanges but may appearunduly lethargic.

Symptomsand signs

Shakingand trembling

Sweating

‘Pinsand needles’ in lipsand tongue

Hunger

Palpitation

Headache(occasionally)

Doublevision

Difﬁcultyin concentration

Slurringof speech

Confusion

Changeof behaviour; truculence

Convulsions

Unconsciousness

Management

Initially glucose 10–20g is given by mouth either in

liquid form or as granulated sugar or sugar lumps.

Approximately 10g of glucose is available fromnon-

diet versions of

Lucozade

Energy Original

55mL,

Coca-Cola

100mL,

Ribena

Blackcurrant

18mL (to

be diluted), 2 teaspoons sugar,and also from 3 sugar

lumps

. If necessary this may be repeated in 10–15

minutes.

Ifglucose cannot be givenby mouth, if itis ineffective,

orif thehypoglycaemia causesunconsciousness, gluca-

gon1 mg (1unit) should be givenby intramuscular (or

subcutaneous) injection; a child under 8 years or of

body-weight under 25 kg should be given 500 micr-

ograms. Once the patient regains consciousness oral

glucoseshould be administeredas above.If glucagon is

ineffective or contra-indicated, the patient should be

transferred urgentlyto hospital. The patient must also

beadmitted tohospital ifhypoglycaemia iscaused byan

oralantidiabetic drug.

Syncope

Insufﬁcient bloodsupply to the brain results in loss of

consciousness. The commonest cause is a vasovagal

attackor simplefaint (syncope) dueto emotional stress.

Symptomsand signs

Patientfeels faint

Lowblood pressure

Pallorand sweating

Yawningand slow pulse

Nauseaand vomiting

Dilatedpupils

Musculartwitching

Management

Laythe patient asﬂ atas is reasonablycomfortable

and, in the absence of associated breathlessness,

raisethe legs to improvecerebral circulation

Loosenany tight clothing aroundthe neck

Onceconsciousness isregained, givesugar in water

ora cup of sweettea

Other possiblecauses

Postural hypotension can be a consequence of rising

abruptlyor of standing upright for toolong; antihyper-

tensive drugs predisposeto this. When rising, suscep-

tiblepatients should take their time.Management is as

fora vasovagal attack.

Understressful circumstances,some patientshyperven-

tilate.This givesrise tofeelings offaintness but doesnot

usuallyresult in syncope. In mostcases reassurance is

allthat isnecessary; rebreathingfrom cuppedhands ora

bagmay be helpful butcalls for careful supervision.

Adrenalinsufﬁciency or arrhythmias areother possible

causesof syncope, see p.26 and p.29.

Medical problems in dental practice

Individuals presenting at the dental surgery may also

suffer from an unrelated medical condition; this may

requiremodiﬁcation to the managementof their dental

condition.If thepatient hassystemic diseaseor is taking

othermedication, the matter mayneed to bediscussed

with thepatient’s general practitioner or hospital con-

sultant.

For advice on adrenal insufﬁciency, anaphylaxis,

asthma, cardiacemergencies, epileptic seizures, hypo-

glycaemiaand syncopesee under MedicalEmergencies

inDental Practice.

1.Proprietary products of quick-acting carbohydrate (e.g.

GlucoGel

Dextrogel

Hypo-Fit

) are available on

prescription for the patient to keep to hand in caseof

hypoglycaemia

28 Prescribing in dental practice BNF 61

Prescribingin dental practice

Allergy

Patientsshould be asked about any history of allergy;

thosewith a history of atopicallergy (asthma, eczema,

hayfever, etc.)are atspecial risk.Those witha historyof

asevere allergy orof anaphylactic reactionsare at high

risk—itis essential to conﬁrmthat they are notallergic

toany medication, or toany dental materials orequip-

ment(including latex gloves). See also Anaphylaxison

p.26.

Arrhythmias

Patients,especially those who suffer from heart failure

or who have sustained amyocardial infarction, may

have irregular cardiac rhythm. Atrial ﬁbrillation is a

common arrhythmia even in patients with normal

hearts and is of little concern except that dental sur-

geons should be aware that such patients may be

receiving anticoagulant therapy.The patient’s medical

practitioner should be askedwhether any special pre-

cautions are necessary. Premedication (e.g. with tem-

azepam) may be useful in some instances for very

anxiouspatients.

Seealso Cardiac emergencies,p. 27 and DentalAnaes-

thesia,p. 794.

Cardiacprostheses

Foran account of the risk of infective endocarditis in

patients with prosthetic heart valves, see Infective

Endocarditis, below. For advice on patients receiving

anticoagulants,see Thromboembolic disease, below.

Coronaryartery disease

Patientsare vulnerable for atleast 4 weeks following a

myocardialinfarction or following anysudden increase

in the symptoms of angina. It would be advisable to

check with the patient’s medical practitioner before

commencingtreatment. See also Cardiac Emergencies

onp. 27.

Treatmentwith low-dose aspirin(75 mgdaily), clopido-

grel, or dipyridamole should not be stopped routinely

norshould thedose bealtered beforedental procedures.

AWorking Partyof the BritishSociety for Antimicrobial

Chemotherapy has not recommended antibiotic

prophylaxis for patients following coronary artery

bypasssurgery.

Cyanoticheart disease

Patientswith cyanotic heart disease areat risk in the

dentalchair, particularly ifthey have pulmonary hyper-

tension.In such patients a syncopal reactionincreases

the shuntaway from the lungs, causing more hypoxia

whichworsens the syncopal reaction—a vicious circle

that may prove fatal. The advice of the cardiologist

shouldbe sought onany patient withcongenital cyano-

ticheart disease. Treatment in hospital ismore appro-

priatefor some patients withthis condition.

Hypertension

Patients with hypertension are likely to be receiving

antihypertensivedrugs such as those described insec-

tion2.5. Their bloodpressure may fall dangerouslylow

undergeneral anaesthesia,see alsounder DentalAnaes-

thesiaon p. 794.

Immunosuppressionand indwelling

intraperitonealcatheters

SeeTable 2, section 5.1

Infectiveendocarditis

While almost any dental procedure can cause bacter-

aemia, there is noclear association with the develop-

ment of infective endocarditis. Routine daily activities

suchas tooth brushingalso produce a bacteraemiaand

maypresent agreater risk ofinfective endocarditis than

asingle dental procedure.

Antibacterialprophylaxis andchlorhexidine mouthwash

arenot recommendedfor theprevention ofendocarditis

inpatients undergoing dentalprocedures. Suchprophy-

laxis may expose patients to the adverse effects of

antimicrobials when the evidence of beneﬁt has not

beenproven.

Reduction of oral bacteraemia

Patientsat risk of

endocarditis

shouldbe advised tomaintain the highest

possible standards of oral hygiene in order to reduce

the:

needfor dental extractions orother surgery;

chancesof severe bacteraemia if dental surgery is

needed;

possibilityof ‘spontaneous’ bacteraemia.

Postoperative care

Patientsat risk of endocarditis

should be warned to report to the doctor or dental

surgeon any unexplained illness that develops after

dental treatment. Any infection in patients at risk of

endocarditis

shouldbe investigatedpromptly and trea-

tedappropriately to reduce therisk of endocarditis.

Patients on anticoagulant therapy

For general

adviceon dental surgeryin patients receiving oralanti-

coagulanttherapy seeThromboembolic Disease,below.

Jointprostheses

SeeTable 2, section 5.1

Pacemakers

Pacemakers prevent asystole or severe bradycardia.

Someultrasonic scalers, electronic apex locators,elec-

tro-analgesicdevices, and electrocautery devicesinter-

ferewith the normal functionof pacemakers (including

shielded pacemakers) and should not be used. The

manufacturer’sliterature shouldbe consulted whenever

possible.If severe bradycardiaoccurs in apatient ﬁtted

with a pacemaker, electrical equipment should be

switched off and the patient placed supine with the

legs elevated. If the patient loses consciousness and

the pulse remains slowor is absent, cardiopulmonar y

resuscitation (see inside back cover) may be needed.

Callimmediately for medical assistance and an ambu-

lance,as appropriate.

1.Patients at risk of endocarditis include those with valve

replacement,acquired valvular heartdisease with stenosis

or regurgitation, structural congenital heart disease (in-

cludingsurgically corrected or palliated structural condi-

tions, but excluding isolated atrial septal defect, fully

repaired ventricular septal defect, fully repaired patent

ductus arteriosus, and closure devices considered to be

endothelialised), hypertrophic cardiomyopathy,or a pre-

viousepisode of infectiveendocarditis

BNF 61 Prescribing in dental practice 29

Prescribingin dental practice

AWorking Partyof the BritishSociety for Antimicrobial

Chemotherapy does not recommend antibacterial

prophylaxisfor patients with pacemakers.

Thromboembolicdisease

Patients receiving a heparin or an oral anticoagulant

such as warfarin, acenocoumarol (nicoumalone),

phenindione, dabigatran etexilate, or rivaroxaban

maybe liable to excessive bleeding after extraction of

teethor other dental surgery.Often dental surgery can

be delayed until the anticoagulant therapy has been

completed.

Fora patientrequiring long-term therapy withwarfarin,

the patient’smedical practitioner shouldbe consulted

andthe International NormalisedRatio (INR) shouldbe

assessed 72 hours before the dental procedure. This

allowssufﬁcient timefor dose modiﬁcationif necessary.

In those with an unstable INR (including those who

require weekly monitoringof their INR, or those who

havehad some INR measurements greater than 4.0 in

thelast 2months), theINR should beassessed within24

hoursof the dental procedure.Patients requiring minor

dentalprocedures (including extractions) who have an

INR below 4.0 may continue warfarin without dose

adjustment. There is no need to check the INR for a

patientrequiring a non-invasive dentalprocedure.

Ifpossible, asingle extractionshould bedone ﬁrst;if this

goeswell further teeth maybe extracted at subsequent

visits(two orthree at atime). Measuresshould be taken

to minimise bleeding during and after the procedure.

Thisincludes the useof suturesand a haemostaticsuch

as oxidised cellulose, collagen sponge or resorbable

gelatinsponge. Scaling androot planing should initially

berestricted to alimited area toassess the potentialfor

bleeding.

Fora patient on long-term warfarin, the advice of the

clinician responsible for the patient’s anticoagulation

shouldbe sought if:

theINR isunstable, or ifthe INRis greater than4.0;

thepatient has thrombocytopenia, haemophilia, or

otherdisorders of haemostasis, or suffers fromliver

impairment,alcoholism, or renal failure;

thepatient is receivingantiplatelet drugs, cytotoxic

drugsor radiotherapy.

Intramuscular injections are

contra-indicated

patients on anticoagulant therapy, and in those with

anydisorder of haemostasis.

Alocal anaesthetic containinga vasoconstrictor should

begiven byinﬁltration, orby intraligamentaryor mental

nerve injection if possible. If regional nerve blocks

cannot be avoided the local anaesthetic should be

givencautiously using an aspiratingsyringe.

Drugs whichhave potentially serious interactions with

anticoagulantsinclude aspirinand otherNSAIDs, carba-

mazepine,imidazole and triazole antifungals (including

miconazole),er ythromycin,clarithromycin, and metro-

nidazole;for details ofthese and otherinteractions with

anticoagulants, see Appendix 1 (dabigatranetexilate,

heparins, phenindione, rivaroxaban, and coumarins).

Althoughstudies have failedto demonstrate aninterac-

tion,common experiencein anticoagulant clinicsis that

the INR can be altered following a course of an oral

broad-spectrumantibiotic, such as ampicillin or amox-

icillin.

Informationon the treatmentof patients who takeanti-

coagulants is available at www.npsa.nhs.uk/

patientsafety/alerts-and-directives/alerts/

anticoagulant

Liverdisease

Liverdisease may alterthe response to drugsand drug

prescribing should be kept to a minimum in patients

withsevere liver disease. Problemsare likely mainly in

patients with

jaundice

ascites

, or evidence of

encephalopathy

For guidance on prescribing for patients with hepatic

impairment, see p. 17. Where care is needed when

prescribing in hepatic impairment, this is indicated

underthe relevant drug in theBNF.

Renalimpairment

Theuse ofdrugs in patientswith reduced renalfunction

cangive riseto manyproblems. Manyof theseproblems

canbe avoided by reducingthe dose or by usingalter-

nativedrugs.

Special care is required in renal transplantation and

immunosuppressedpatients; if necessary such patients

shouldbe referred to specialists.

For guidance on prescribing in patients with renal

impairment, see p. 17. Where care is needed when

prescribingin renal impairment, this isindicated under

therelevant drug in the BNF.

Pregnancy

Drugs taken during pregnancy can be harmful to the

fetus and should be prescribed only if the expected

beneﬁtto the mother is thought tobe greater than the

riskto the fetus; alldrugs should be avoidedif possible

duringthe ﬁrst trimester.

For guidance on prescribing in pregnancy, see p. 19.

Where care isneeded when prescribing in pregnancy,

thisis indicated under therelevant drug in the BNF.

Breast-feeding

Somedr ugstaken by the mother whilst breast-feeding

canbe transferredto the breastmilk, andmay affect the

infant.

Forguidance onprescribing inbreast-feeding, see p.19.

Wherecare is needed when prescribingin breast-feed-

ing,this isindicated under therelevant drug inthe BNF.

30 Prescribing in dental practice BNF 61

Prescribingin dental practice

Drugs and sport

UK Anti-Doping advises that athletes are personally

responsibleshould a prohibited substance be detected

in their body.An advice card listing examples of per-

mittedand prohibited substances isavailable from:

UKAnti-Doping

OceanicHouse

1aCockspur Street

LondonSW1Y 5BG

Tel:(020) 7766 7350

information@ukad.org.uk

www.ukad.org.uk

A similar card detailing classes of drugs and doping

methods prohibited in football is available from the

FootballAssociation. Thiscontains information speciﬁc

tothe Football AssociationDoping Control Regulations

including the Football Association’spolicy on social

drugs. Further information is available at

www.thefa.com.

GeneralMedical Council’s advice

Doctorswho prescribe orcollude inthe provision of

drugsor treatment with the intentionof improperly

enhancingan individual’sperformance in sportcon-

travenethe GMC’sguidance,and suchactions would

usually raise a question of a doctor’s continued

registration. This does not preclude the provision

ofany careor treatmentwhere thedoctor’s intention

isto protect or improvethe patient’s health.

BNF 61 Drugs and sport 31

Drugs and sport

Emergency treatment of

poisoning

Thesenotes provide onlyan overview of thetreatment

ofpoisoning, andit is stronglyrecommended thateither

TOXBASEor the UKNational Poisons Information

Service (see below)be consulted when there is doubt

aboutthe degree of riskor about management.

Hospital admission

Patients who have features of

poisoning should generally be admitted to hospital.

Patients who have taken poisons with delayed action

should also be admitted, even if they appear well.

Delayed-actionpoisons include aspirin, iron, paraceta-

mol, tricyclic antidepressants, and co-phenotrope

(diphenoxylatewith atropine,

Lomotil

);the effects of

modiﬁed-releasepreparations are also delayed. A note

ofall relevantinformation, includingwhat treatmenthas

beengiven, should accompany thepatient to hospital.

Further information and advice

TOXBASE,the primary clinical toxicology databaseof

theNational PoisonsInformation Service,is availableon

the internet toregistered users at www.toxbase.org (a

backupsite isavailable atwww.toxbasebackup.org ifthe

mainsite cannot be accessed). It provides information

aboutroutine diagnosis, treatment,and management of

patients exposed to drugs, household products, and

industrialand agricultural chemicals.

Specialistinfor mationand advice on the treatment

ofpoisoning is availableday and night fromthe UK

NationalPoisons Information Service on the fol-

lowingnumber:

Tel:0844 892 0111

Advice on laborator y analytical services can be

obtainedfrom TOXBASE or fromthe National Poisons

InformationService.

Helpwith identifying capsules or tablets maybe avail-

ablefrom a regional medicines infor mationcentre (see

insidefront cover) or (out of hours) from the National

PoisonsInformation Service.

General care

It is often impossible to establish with certainty the

identityof the poison and the size of the dose.This is

notusually important becauseonly a fewpoisons (such

as opioids, paracetamol, and iron) have speciﬁc anti-

dotes;few patientsrequire active removalof thepoison.

In most patients, treatment is directed at managing

symptoms as they arise. Nevertheless,knowledge of

thetype andtiming ofpoisoning canhelp in anticipating

thecourse of events.All relevant informationshould be

soughtfrom the poisonedindividual and fromcarers or

parents. However, such information should be inter-

preted with care because it may not be completeor

entirelyreliable. Sometimes symptomsarise from other

illnesses and patients should be assessed carefully.

Accidentsmay involvedomestic andindustrial products

(the contents of which are not generally known). The

NationalPoisons Information Service shouldbe con-

sulted when there is doubt about any aspectof sus-

pectedpoisoning.

Respiration

Respiration is often impaired in unconscious patients.

Anobstr uctedairway requires immediate attention. In

the absence of trauma, the airway should be opened

withsimple measures suchas chin liftor jaw thrust. An

oropharyngealor nasopharyngeal airwaymay be useful

in patients with reduced consciousness to prevent

obstruction,provided ventilationis adequate.Intubation

andventilation should be consideredin patients whose

airway cannot be protected or who have respiratory

acidosis because of inadequate ventilation; such

patientsshould be monitored ina critical care area.

Most poisons that impair consciousness also depress

respiration.Assisted ventilation(either mouth-to-mouth

or using a bag-valve-mask device) may be needed.

Oxygen is not a substitute for adequate ventilation,

althoughit should begiven inthe highest concentration

possiblein poisoningwith carbon monoxideand irritant

gases.

Blood pressure

Hypotensionis common in severe poisoningwith cen-

tralnervous system depressants. Asystolic blood pres-

sureof lessthan 70mmHg maylead toirreversible brain

damageor renal tubular necrosis. Hypotension should

becorrected initiallyby tilting downthe headof the bed

and administration of either sodium chloride intra-

venousinfusion or a colloidal infusion.Vasoconstrictor

sympathomimetics (section 2.7.2) are rarelyrequired

and their use may be discussed with the National

PoisonsInformation Service.

Fluid depletion without hypotension is common after

prolonged coma and after aspirin poisoning due to

vomiting,sweating, and hyperpnoea.

Hypertension, often transient, occurs less frequently

than hypotension in poisoning; it may be associated

with sympathomimetic drugs such as amfetamines,

phencyclidine,and cocaine.

Heart

Cardiacconduction defects and arrhythmias canoccur

in acute poisoning, notably with tricyclic antidepres-

sants, some antipsychotics, and some antihistamines.

Arrhythmiasoften respond to correction of underlying

hypoxia, acidosis, or other biochemical abnormalities,

but ventricular arrhythmias that cause serious hypo-

tension require treatment (section 2.3.1). If the QT

intervalis prolonged,specialist advice shouldbe sought

becausethe use of someanti-arrhythmic drugs may be

inappropriate.Supraventricular arrhythmias areseldom

life-threateningand drugtreatment isbest withhelduntil

thepatient reaches hospital.

32 BNF 61

Emergencytreatment of poisoning

Body temperature

Hypothermia maydevelop in patients of any age who

havebeen deeply unconsciousfor some hours, particu-

larlyfollowing overdose with barbiturates or phenothi-

azines. It may be missed unless core temperature is

measuredusing alow-reading rectal thermometeror by

someother means.Hypothermia should bemanaged by

prevention of further heat loss and appropriate re-

warmingas clinically indicated.

Hyperthermia can develop in patients taking CNS

stimulants; children and the elderly are also at risk

when taking therapeutic doses of drugs with anti-

muscarinic properties. Hyperthermia is initially mana-

gedby removing all unnecessary clothing and using a

fan. Spongingwith tepid water will promote evapora-

tion.Advice shouldbe soughtfrom the NationalPoisons

Information Service on the management of severe

hyperthermia resulting from conditions such as the

serotoninsyndrome.

Both hypothermia and hyperthermia require urgent

hospitalisationfor assessmentandsuppor tivetreatment.

Convulsions

Singleshort-lived convulsionsdo not requiretreatment.

Ifconvulsions areprotracted or recurfrequently, loraze-

pam4 mg or diazepam(preferably as emulsion) 10mg

should be given by slow intravenous injection into a

large vein (section 4.8.2). Benzodiazepines should not

begiven by the intramuscular route for convulsions.If

theintravenous route isnot readily available,diazepam

canbe administered as a rectal solutionor midazolam

[unlicensed use] can be given by the buccal route

(section4.8.2).

Removal and elimination

Prevention of absorption

Given by mouth, activated charcoal can bind many

poisons in the gastro-intestinal system, thereby

redu-

cingtheir absorption

.The sooner it is given themore

effectiveit is, but it maystill be effective up to 1hour

after ingestion of the poison—longer in the case of

modiﬁed-release preparations or of drugs with anti-

muscarinic(anticholinergic) properties. Itis particularly

usefulfor the prevention of absorption of poisons that

aretoxic in small amounts,such as antidepressants.

Forthe useof charcoal inactive eliminationtechniques,

seebelow.

Active elimination techniques

Repeated doses of activated charcoal by mouth

enhancethe elimination

ofsome drugs after they have

been absorbed; repeated doses aregiven after over-

dosagewith:

Carbamazepine

Dapsone

Phenobarbital

Quinine

Theophylline

The usual dose of activated charcoal in adults and

childrenover 12 years of age is 50g initially then 50g

every4 hours. Vomitingshould be treated (e.g.with an

antiemetic drug) since it mayreduce the efﬁcacy of

charcoal treatment. In cases of intolerance, the dose

maybe reduced and the frequencyincreased (e.g. 25g

every 2 hours

12.5g every hour) but this may

compromiseefﬁcacy.

Inchildren under 12 yearsof age, activated charcoalis

givenin a doseof 1g/kg (max. 50g) every 4hours; the

dosemay bereduced and thefrequency increasedif not

tolerated.

Othertechniques intendedto enhancethe eliminationof

poisonsafter absorption areonly practicable inhospital

and are only suitable for a small number of severely

poisonedpatients. Moreover, they only applyto a lim-

itednumber of poisons. Examplesinclude:

haemodialysis for ethylene glycol,lithium, metha-

nol, phenobarbital, salicylates, and sodium val-

proate;

alkalinisationof the urine forsalicylates.

Removal from the gastro-intestinal

tract

Gastric lavage is rarely required; for substances that

cannot be removed effectively by other means (e.g.

iron),it should be considered only if a life-threatening

amounthas been ingested within the previous hour.It

shouldbe carriedout onlyif the airwaycan beprotected

adequately.Gastric lavageis contra-indicatedif a corro-

sive substance or a petroleum distillate has been

ingested, but it may occasionally be considered in

patientswho have ingesteddrugs that arenot adsorbed

bycharcoal, suchas iron orlithium. Induction of

emesis

(e.g. with ipecacuanha) is not recommended because

thereis noevidence thatit affects absorptionand itmay

increasethe risk of aspiration.

Wholebowel irrigation

(bymeans of abowel cleansing

preparation) has been used in poisoning with certain

modiﬁed-release or enteric-coated formulations, in

severepoisoning with ironand lithiumsalts, and ifillicit

drugs are carried in the gastro-intestinal tract (‘body-

packing’). However, it is not clear that the procedure

improves outcome and advice should be sought from

theNational Poisons Information Service.

CHARCOAL,ACTIVATED

Indications

reductionof absorption of poisons inthe

gastro-intestinalsystem; see also activeelimination

techniques,above

Cautions

drowsyor comatose patient (riskof aspira-

tion,ensure airway protected); reducedgastro-intes-

tinalmotility (risk of obstruction);not for poisoning

withpetroleum distillates, corrosive substances,

alcohols,malathion, andmetal saltsincluding ironand

lithiumsalts

Side-effects

blackstools

Dose

. Reductionof absorption, ADULTand CHILD over 12

years,50 g;

CHILDunder 12 years, 1g/kg (max. 50g)

. Activeelimination, see notes above

Note

Activatedcharcoal dosesin BNFmay differfrom those

inproduct literature. Suspensionor reconstituted powder

maybe mixedwith softdrinks (e.g.caffeine-free dietcola) or

fruitjuices to maskthe taste

Actidose-Aqua

Advance(Alliance)

Oralsuspension

,activated charcoal1.04 g/5mL, net

price50-g pack (240mL) = £8.69

BNF 61 Emergencytreatment of poisoning 33

Emergencytreatment of poisoning

Carbomix

(Beacon)

Powder

,activated charcoal, net price25-g pack =

£8.50,50-g pack = £11.90

Charcodote

(TEVAUK)

Oralsuspension

,activated charcoal 1g/5 mL,net

price50-g pack = £11.88

Speciﬁc drugs

Alcohol

Acuteintoxication with alcohol (ethanol)is common in

adultsbut also occurs inchildren. The features include

ataxia, dysarthria, nystagmus, and drowsiness, which

mayprogress to coma, with hypotension and acidosis.

Aspiration of vomit is a special hazard and hypoglyc-

aemiamay occur in childrenand some adults. Patients

are managed supportively,with particular attention to

maintaininga clear airway andmeasures to reduce the

riskof aspiration ofgastric contents. Theblood glucose

ismeasured and glucose givenif indicated.

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

Analgesics (non-opioid)

Aspirin

Themain features of salicylate poisoning are

hyperventilation,tinnitus, deafness, vasodilatation, and

sweating.Coma isuncommon but indicatesvery severe

poisoning. The associated acid-base disturbances are

complex.

Treatmentmust bein hospital, whereplasma salicylate,

pH, and electrolytes can be measured; absor ption of

aspirinmay be slow and theplasma-salicylate concen-

trationmay continue torise for severalhours, requiring

repeated measurement. Plasma-salicylate concentra-

tion may not correlate with clinical severity in the

young and the elderly, and clinical and biochemical

assessmentis necessary. Generally,the clinical severity

of poisoningis less below a plasma-salicylate concen-

trationof 500 mg/litre (3.6mmol/litre), unless there is

evidenceof metabolic acidosis. Activated charcoalcan

begiven within 1 hourof ingesting more than125 mg/

kgof aspirin. Fluidlosses should be replacedand intra-

venous sodium bicarbonate may be given (ensuring

plasma-potassiumconcentration is withinthe reference

range)to enhanceurinary salicylateexcretion (optimum

urinarypH 7.5–8.5).

Plasma-potassium concentration should be corrected

before giving sodium bicarbonate as hypokalaemia

maycomplicate alkalinisation of theurine.

Haemodialysis is the treatment of choice for severe

salicylate poisoning and should be considered when

the plasma-salicylate concentration exceeds 700mg/

litre(5.1 mmol/litre)or inthe presenceof severemetab-

olicacidosis.

NSAIDs

Mefenamicacid has important consequences

inoverdosage becauseit cancause convulsions,which if

prolongedor recurrent require treatment, seep. 33.

Overdosage with ibuprofen may cause nausea, vomi-

ting, epigastric pain, and tinnitus, but more serious

toxicityis veryuncommon. Activated charcoalfollowed

by symptomatic measures are indicated if more than

400mg/kg hasbeen ingestedwithin thepreceding hour.

Paracetamol

In cases of intravenous paracetamol poisoning

contact the National Poisons Information Service

foradvice on risk assessmentand management.

Single or repeated doses totalling as little as 10–15 g

(20–30 tablets) or 150mg/kg of paracetamol ingested

within24 hoursmay cause severehepatocellular necro-

sis and, much less frequently, renal tubular necrosis.

Patients at

high-risk

of liver damage, including those

takingenzyme-inducing drugsor who aremalnourished

(see p.35), may develop liver toxicity with as little as

75mg/kg ofparacetamol (equivalent to approx.5 g(10

tablets) in a 70-kg patient) taken within 24 hours.

Nauseaand vomiting, theonly early featuresof poison-

ing,usually settle within 24 hours. Persistence beyond

thistime, often associated with the onset of right sub-

costal pain and tenderness, usuallyindicates develop-

mentof hepatic necrosis.Liver damage is maximal3–4

days after ingestion and may lead to encephalopathy,

haemorrhage, hypoglycaemia, cerebral oedema, and

death.

Therefore,despite a lackof signiﬁcant early symptoms,

patients who have taken an overdose of paracetamol

shouldbe transferred to hospital urgently.

Administrationof activated charcoal should beconsid-

ered if paracetamol in excess of 150mg/kg or 12 g,

whichever is the smaller (or in excess of 75mg/kg

for those considered to be at

highrisk

, see below),is

thoughtto havebeen ingested withinthe previous hour.

Acetylcysteine protectsthe liver if infused up to, and

possiblybeyond, 24hours ofingesting paracetamol.It is

mosteffective if givenwithin 8 hours ofingestion, after

whicheffectiveness declines.In patientswho present 8–

36 hours after a potentiallytoxic ingestion, acetylcys-

teinetreatment should commence immediately even if

plasma-paracetamol concentrations are not yet avail-

able;if morethan 24 hourshave elapsedsince ingestion

advice should be sought from the National Poisons

Information Service. Giving acetylcysteine by mouth

[unlicensedroute] isan alternative ifintravenous access

isnot possible—contact the National PoisonsInforma-

tionService for advice.In remote areas,methionine by

mouthis an alternativeonly if acetylcysteinecannot be

given promptly.Once the patient reaches hospital the

need to continue treatment with the antidote will be

assessed from the plasma-paracetamol concentration

(relatedto the time fromingestion).

Patientsat risk of liver damageand therefore requiring

treatmentcan be identiﬁed froma single measurement

ofthe plasma-paracetamolconcentration, related tothe

time fromingestion, provided this time interval is not

less than 4 hours; earlier samples maybe misleading.

The concentration is plotted on a paracetamol treat-

ment graph, with a reference line (‘normal treatment

line’)joining plots of200 mg/litre(1.32 mmol/litre)at 4

hours and 6.25mg/litre (0.04 mmol/litre) at 24 hours

(see p. 35). Those whose plasma-paracetamol concen-

tration isabove the

normaltreatm entline

are treated

withacetylcysteine byintravenous infusion(or, ifacetyl-

cysteine is not available, with methionine by mouth,

provided the overdose has been taken within 10–12

hours

and

thepatient is not vomiting).

34 Emergency treatment ofpoisoning BNF61

Emergencytreatment of poisoning

Patientsat

high-risk

ofliver damage include those:

taking liver enzyme-inducing drugs (e.g. carba-

mazepine,phenobarbital, phenytoin, primidone,rif-

ampicin, rifabutin, efavirenz, nevirapine, alcohol

andSt John’s wort);

whoare malnourished (e.g. in anorexiaor bulimia,

cystic ﬁbrosis,hepatitis C, in alcoholism, or those

whoare HIV-positive);

whohave not eaten fora few days.

These patients can develop toxicity at lower plasma-

paracetamolconcentration and should betreated if the

concentration is above the

high-risk treatment line

(whichjoins plots that are at 50% of the plasma-para-

cetamolconcentrations of the normal treatmentline).

The prognostic accuracy of plasma-paracetamol con-

centration taken after 15 hours is uncertain, but a

concentrationabove the relevant treatmentline should

beregarded as carrying a seriousrisk of liver damage.

Patientswhose plasma-paracetamolconcentrations are abovethe normal treatmentline shouldbe treated with

acetylcysteineby intravenousinfusion (or,if acetylcysteine cannotbe used,with methionineby mouth, provided

theoverdose has beentaken within 10–12hours and the patientis not vomiting).

Patientsat high-risk ofliver damage includethose:

. taking liver enzyme-inducingdrugs (e.g. carbamazepine, phenobarbital,phenytoin, primidone, rif-

ampicin,rifabutin, efavirenz, nevirapine, alcohol,St John’s wort);

. who aremalnourished (e.g.in anorexiaor bulimia,cystic ﬁbrosis,hepatitis C,in alcoholism,or thosewho

areHIV-positive);

. who have noteaten for a fewdays.

Thesepatients shouldbe treatedif their plasma-paracetamolconcentration isabove thehigh-risk treatment

line.

The prognostic accuracy after 15 hours is uncertain but a plasma-paracetamol concentration above the

relevanttreatment line should beregarded as carrying aserious risk of liverdamage.

Graphreproduced courtesyof University ofWales Collegeof MedicineTherapeutics and ToxicologyCentre

BNF 61 Emergencytreatment of poisoning 35

Emergencytreatment of poisoning

Theplasma-paracetamol concentration maybe difﬁcult

tointer pretwhen paracetamol has been ingested over

severalhours. Ifthere is doubtabout timing orthe need

fortreatment then thepatient should betreated withan

antidote.

ACETYLCYSTEINE

Indications

paracetamoloverdosage, seenotes above

Cautions

asthma(see side-effects below butdo not

delayacetylcysteine treatment)

Side-effects

hypersensitivity-likereactions managed

byreducing infusion rateor suspending untilreaction

settled(rash also managed bygiving antihistamine;

acuteasthma managed by givingnebulised short-

actingbeta

agonist)—contactthe National Poisons

InformationService if reaction severe

Dose

. Byintravenous infusion, ADULTand CHILD, initially

150mg/kg (max. 16.5g) over 15minutes, then

50mg/kg (max. 5.5g) over 4hours then 100mg/kg

(max.11 g) over16 hours

Administration

Diluterequisite dosein glucoseintravenous

infusion5% as follows:

ADULT

and

CHILD

over12 years,

initially200 mLgiven over 15minutes, then 500mL over4

hours,then 1litreover 16hours ;

CHILD

under12 years,body-

weightover 20kg, initially 100mL givenover 15 minutes,

then250 mLover 4hours, then500 mLover 16hours;

CHILD

body-weightunder 20kg, initially 3mL/kg givenover 15

minutes,then 7mL/kg over4 hours,then 14mL/kg over16

hours

Note

Manufactureralso recommends other infusion ﬂuids,

butglucose 5% ispreferable

Acetylcysteine(Non-proprietary) A

Injection

,acetylcysteine 200 mg/mL,net price 10-

mLamp = £1.96

Parvolex

(UCBPharma) A

Injection

,acetylcysteine 200 mg/mL,net price 10-

mLamp = £2.25

METHIONINE

Indications

paracetamoloverdosage, seenotes above

Hepaticimpairment

mayprecipitate coma

Side-effects

nausea,vomiting, drowsiness, irritability

Dose

. ADULTandCHILD over6 yearsinitially 2.5g, followedby

3further doses of 2.5g every 4 hours,

CHILDunder 6

yearsinitially 1 g,followed by 3further doses of 1g

every4 hours

Methionine(Pharma Nord)

Tablets

,f/c, methionine 500mg, net price 20-tab

pack= £9.95

Withparacetamol (co-methiamol)

Section4.7.1

Analgesics (opioid)

Opioids (narcotic analgesics) cause coma, respiratory

depression, and pinpoint pupils. The speciﬁc antidote

naloxoneis indicated if there is coma or bradypnoea.

Since naloxone has a shorter duration of action than

manyopioids, close monitoringand repeated injections

are necessary according to the respiratory rate and

depth of coma. When repeated administration of nal-

oxoneis required, it can be given by continuous intra-

venousinfusion insteadand therate ofinfusion adjusted

according to vital signs. The effects of some opioids,

such as buprenorphine, are only partially reversed by

naloxone. Dextropropoxyphene and methadone have

verylong durations of action; patients mayneed to be

monitoredfor long periods followinglarge overdoses.

Naloxonereverses the opioidef fectsof dextropropoxy-

phene; the long duration of action of dextropropoxy-

phenecalls for prolongedmonitoring and further doses

of naloxone may be required. Norpropoxyphene, a

metaboliteof dextropropoxyphene,also has cardiotoxic

effects which may require treatment with sodium

bicarbonate,or magnesium sulphate, or both; arrhy-

thmiasmay occur for upto 12 hours.

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

NALOXONEHYDROCHLORIDE

Indications

overdosagewith opioids; reversal of

opioid-inducedrespiratory depression andreversal of

neonatalrespiratory depression resultingfrom opioid

administrationto mother during labour(section

15.1.7)

Cautions

physicaldependence on opioids; cardiac

irritability;naloxone is short-acting, seenotes above

Pregnancy

section15.1.7

Breast-feeding

section15.1.7

Dose

. Byintravenous injection, 0.4–2mg; if no response

repeatat intervals of 2–3minutes to a max.of 10mg

(thenreview diagnosis);further dosesmay berequired

ifrespiratory function deteriorates;

CHILD10 micr-

ograms/kg;if no response givesubsequent dose of

100micrograms/kg (then reviewdiagnosis); further

dosesmay be required ifrespiratory function dete-

riorates

. Bysubcutaneous

intramuscularinjection, ADULT

andCHILD dose as forintravenous injection but use

onlyif intravenous route notfeasible (onset of action

slower)

. Bycontinuous intravenous infusionusing an infusion

pump,rate adjustedaccording toresponse (initial rate

maybe setat 60% ofinitial intravenousinjection dose

(seeabove) and infused over1 hour)

Important

Dosesused in acuteopioid overdosagemay not

beappropriate for themanagement of opioid-inducedresp-

iratorydepression and sedationin those receivingpalliative

careand in chronicopioid use; seealso section 15.1.7for

managementof postoperative respiratorydepression

Naloxone(Non-proprietary) A

Injection

,naloxone hydrochloride 20micrograms/

mL,net price 2-mL amp= £5.50; 400micrograms/

mL,1-mL amp = £4.10;1 mg/mL, 2-mLpreﬁlled

syringe= £8.36

Minijet

Naloxone(UCB Pharma) A

Injection

,naloxone hydrochloride 400micrograms/

mL,net price1-mL disposablesyringe =£20.40, 2-mL

disposablesyringe =£12.96, 5-mL disposable syringe

=£12.68

1.A restriction does notapply where administration isfor

savinglife in emergency

36 Emergency treatment ofpoisoning BNF61

Emergencytreatment of poisoning

Antidepressants

Tricyclic and related antidepressants

Tricyclic

andrelated antidepressants cause dry mouth, coma of

varyingdegree, hypotension,hypothermia, hyperreﬂex-

ia,extensor plantar responses, convulsions,respirator y

failure, cardiac conduction defects, and arrhythmias.

Dilatedpupils and urinary retention alsooccur. Metab-

olicacidosis maycomplicate severe poisoning;delirium

withconfusion, agitation, andvisual and auditoryhallu-

cinationsare common during recovery.

Assessment in hospital is strongly advised in case of

poisoning by

tricyclicand related antidepressants

but

symptomatic treatment can be given before transfer.

Supportive measures to ensure a clear airway and

adequate ventilation during transfer are mandatory.

Intravenous lorazepam or intravenous diazepam (pre-

ferably in emulsion form) may be required to treat

convulsions.Activated charcoal given within 1 hourof

theoverdose reduces absorption of thedrug. Although

arrhythmiasare worrying, somewill respond tocor rec-

tionof hypoxiaand acidosis. Theuse ofanti-ar rhythmic

drugs isbest avoided, but intravenous infusion ofsod-

iumbicarbonate canarrest arrhythmiasor prevent them

in those with an extended QRS duration. Diazepam

givenby mouth is usually adequate tosedate delirious

patientsbut large doses maybe required.

Selectiveserotonin re-uptake inhibitors (SSRIs)

Symptomsof poisoningby selectiveserotonin re-uptake

inhibitors include nausea, vomiting, agitation, tremor,

nystagmus, drowsiness, and sinus tachycardia; con-

vulsionsmay occur. Rarely,severe poisoning results in

theserotonin syndrome, with marked neuropsychiatric

effects, neuromuscular hyperactivity, and autonomic

instability;hyperthermia, rhabdomyolysis, renal failure,

andcoagulopathies may develop.

Managementof SSRIpoisoning is supportive.Activated

charcoal given within 1 hourof the overdose reduces

absorptionof the drug.Convulsions can betreated with

lorazepam,diazepam, or buccalmidazolam [unlicensed

use](see p. 33). Contactthe National Poisons Informa-

tionService forthe management ofhyperthermia or the

serotoninsyndrome.

Antimalarials

Overdosage with quinine, chloroquine, or hydroxy-

chloroquine is extremely hazardous and difﬁcult to

treat.Urgent advicefrom the NationalPoisons Informa-

tion Service is essential. Life-threatening features

include arrhythmias (which can have a very rapid

onset)and convulsions (which canbe intractable).

Beta-blockers

Therapeuticoverdosages with beta-blockersmay cause

lightheadedness, dizziness, and possibly syncope as a

resultof bradycardiaand hypotension;heart failure may

beprecipitated orexacerbated. Thesecomplications are

mostlikely inpatients withconduction systemdisorders

or impaired myocardial function. Bradycardia is the

most common arrhythmia caused by beta-blockers,

but sotalol may induce ventricular tachyarrhythmias

(sometimesof the torsade depointes type). Theef fects

ofmassive overdosage can varyfrom one beta-blocker

to another; propranolol overdosage in particular may

causecoma and convulsions.

Acutemassive overdosage

mustbe managedin hospital

andexpert adviceshould be obtained.Maintenance ofa

clearairway and adequateventilation is mandatory.An

intravenous injection of atropine isrequired to treat

bradycardia (3 mg for an adult, 40micrograms/kg

(max. 3mg) for a child). Cardiogenic shock unrespon-

siveto atropine is probably best treated with anintra-

venous injection of glucagon 2–10 mg (

CHILD 50–

150micrograms/kg, max.10 mg)[unlicensed indication

anddose] inglucose 5%(with precautionsto protect the

airwayin case of vomiting)followed by an intravenous

infusion of 50 micrograms/kg/hour. If glucagon is not

available,intravenous isoprenaline (availablefrom ‘spe-

cial-order’ manufacturers or specialist importing com-

panies, see p. 988) is an alternative. A cardiac pace-

makercan be used toincrease the heart rate.

Calcium-channelblockers

Featuresof calcium-channel blocker poisoning include

nausea, vomiting, dizziness, agitation, confusion, and

coma in severe poisoning. Metabolic acidosis and

hyperglycaemia may occur. Verapamil and diltiazem

havea profoundcardiac depressanteffect causinghypo-

tension and arrhythmias, including complete heart

blockand asystole. The dihydropyridine calcium-chan-

nel blockers cause severe hypotension secondary to

profoundperipheral vasodilatation.

Activatedcharcoal should be considered if the patient

presents within 1 hour of overdosagewith a calcium-

channel blocker; repeated doses of activated charcoal

are considered if a modiﬁed-release preparation is

involved.In patients withsigniﬁcant features ofpoison-

ing, calcium chloride or calcium gluconate (section

9.5.1.1)is givenby injection; atropine is givento correct

symptomatic bradycardia. In severe cases, an insulin

and glucose infusion may berequired in the manage-

ment of hypotension and myocardial failure. Forthe

management of hypotension, the choice of inotropic

sympathomimetic dependson whether hypotension is

secondary to vasodilatation or to myocardial depres-

sion—advice should be soughtfrom the National Poi-

sonsInformation Service.

Hypnotics and anxiolytics

Benzodiazepines

Benzodiazepinestaken alonecause

drowsiness, ataxia, dysarthria, nystagmus,and occa-

sionally respiratory depression, and coma. Activated

charcoal can be given within 1 hour of ingesting a

signiﬁcant quantity of benzodiazepine, provided the

patientis awakeand theairway is protected.Benzodiaz-

epines potentiate the effects of other central nervous

system depressants taken concomitantly.Use of the

benzodiazepineantagonist ﬂumazenil [unlicensed indi-

cation] can be hazardous, particularly in mixed over-

dosesinvolving tricyclicantidepressants orin benzodia-

zepine-dependentpatients. Flumazenil mayprevent the

needfor ventilation, particularlyin patients with severe

respiratorydisorders; itshould beused on expertadvice

only and not as a diagnostic test in patients with a

reducedlevel of consciousness.

BNF 61 Emergencytreatment of poisoning 37

Emergencytreatment of poisoning

Iron salts

Iron poisoning in childhoodis usually accidental. The

symptomsare nausea, vomiting,abdominal pain, diarr-

hoea,haematemesis, and rectal bleeding. Hypotension

and hepatocellular necrosis can occur later. Coma,

shock, and metabolic acidosis indicate severe poison-

ing.

Advice should be sought from the National Poisons

InformationSer viceif a signiﬁcant quantityof iron has

beeningested within the previoushour.

Mortality is reducedby intensive and speciﬁc therapy

withdesferrioxamine, which chelatesiron. The serum-

iron concentration is measured as an emergency and

intravenousdesferrioxamine given to chelate absorbed

ironin excess of theexpected iron binding capacity.In

severetoxicity intravenous desferrioxamine shouldbe

given

immediately

withoutwaiting for the result ofthe

serum-ironmeasurement.

DESFERRIOXAMINE MESILATE

(DeferoxamineMesilate)

Indications

ironpoisoning; chronic iron overload

(section9.1.3)

Cautions

section9.1.3

Renalimpairment

section9.1.3

Pregnancy

section9.1.3

Breast-feeding

section9.1.3

Side-effects

section9.1.3

Dose

. Bycontinuous intravenous infusion, ADULTand CHILD

upto 15 mg/kg/hour,reduced after 4–6 hours;max.

80mg/kg in 24hours (in severe cases,higher doses

onadvice from the NationalPoisons Information

Service)

Preparations

Section9.1.3

Lithium

Mostcases of lithiumintoxication occur as acomplica-

tion of long-term therapy and are caused by reduced

excretion of the drug because of a variety of factors

including dehydration, deterioration of renal function,

infections,and co-administrationof diureticsor NSAIDs

(or other drugs that interact). Acute deliberate over-

dosesmay also occur with delayedonset of symptoms

(12hours or more) owing to slowentry of lithium into

the tissues and continuing absorption from modiﬁed-

releaseformulations.

The early clinical features are non-speciﬁc and may

include apathy and restlessness which could be con-

fused with mental changes arising fromthe patient’s

depressive illness. Vomiting, diarrhoea, ataxia, weak-

ness, dysarthria, muscle twitching, and tremor may

follow.Severe poisoningis associated withconvulsions,

coma,renal failure, electrolyte imbalance,dehydration,

andhypotension.

Therapeutic serum-lithium concentrations are within

therange of 0.4–1mmol/litre; concentrations inexcess

of 2 mmol/litre are usually associated with serious

toxicity and such cases may need treatment with

haemodialysisif neurological symptomsor renal failure

are present. Inacute overdosage much higher serum-

lithiumconcentrations may bepresent without features

of toxicity and all that is usually necessary is to take

measures to increase urine output (e.g. by increasing

ﬂuid intake but avoiding diuretics). Otherwise, treat-

ment is supportive with special regardto electrolyte

balance, renal function, and control of convulsions.

Gastriclavage maybe considered ifit canbe performed

within1 hour of ingesting signiﬁcant quantities of lith-

ium. Whole-bowel irrigation should be considered for

signiﬁcantingestion, but advice should besought from

theNational Poisons Information Service,p. 32.

Phenothiazines and relateddrugs

Phenothiazinescause less depression of consciousness

and respiration than other sedatives. Hypotension,

hypothermia, sinus tachycardia, and arrhythmias may

complicate poisoning. Dystonic reactions can occur

with therapeutic doses (particularly with prochlorper-

azineand triﬂuoperazine),and convulsionsmay occurin

severecases. Arrhythmiasmay respond tocorrection of

hypoxia,acidosis, and otherbiochemical abnormalities,

but specialist advice should be sought if ar rhythmias

result from a prolonged QTinter val; the use of some

anti-arrhythmic drugs can worsen such arrhythmias.

Dystonic reactions are rapidly abolished byinjection

of drugs such as procyclidine(section 4.9.2) or diaze-

pam(section 4.8.2, emulsion preferred).

Atypical antipsychoticdrugs

Features of poisoning by atypical antipsychotic drugs

(section 4.2.1) include drowsiness, convulsions, extra-

pyramidal symptoms,hypotension, and ECG abnor m-

alities(including prolongation ofthe QT interval).Man-

agementis supportive. Activatedcharcoal can begiven

within 1 hour of ingesting a signiﬁcant quantity of an

atypicalantipsychotic drug.

Stimulants

Amfetamines

Amfetaminescause wakefulness,exces-

siveactivity, paranoia, hallucinations,and hypertension

followedby exhaustion,convulsions, hyperthermia, and

coma.The early stages can be controlledby diazepam

or lorazepam; advice should be sought from the

National Poisons Information Service (p. 32) on the

management of hypertension. Later, tepid sponging,

anticonvulsants, and artiﬁcial respiration may be

needed.

Cocaine

Cocaine stimulatesthe central nervous sys-

tem, causing agitation, dilated pupils, tachycardia,

hypertension,hallucinations, hyperthermia, hypertonia,

and hyperreﬂexia; cardiac effects include chest pain,

myocardialinfarction, and arrhythmias.

Initial treatment of cocaine poisoninginvolves intra-

venousadministration of diazepam to controlagitation

andcooling measures forhyperther mia(see Body tem-

perature, p.33); hypertension and cardiac effects

requirespeciﬁc treatment and expert advice shouldbe

sought.

38 Emergency treatment ofpoisoning BNF61

Emergencytreatment of poisoning

Ecstasy

Ecstasy (methylenedioxymethamfetamine,

MDMA) may cause severe reactions, even at doses

thatwere previously tolerated.The mostserious effects

are delirium, coma, convulsions,ventricular arrhyth-

mias,hyperthermia, rhabdomyolysis,acute renalfailure,

acutehepatitis, disseminated intravascularcoagulation,

adult respiratory distress syndrome, hyperreﬂexia,

hypotensionand intracerebral haemorrhage; hyponatr-

aemiahas also been associatedwith ecstasy use.

Treatment of methylenedioxymethamfetamine poison-

ing is supportive, with diazepam to control severe

agitationor persistentconvulsions andclose monitoring

including ECG.Self-induced water intoxication should

beconsidered in patients withecstasy poisoning.

‘Liquid ecstasy’ is a term used for sodium oxybate

(gamma-hydroxybutyrate,GHB), which isa sedative.

Theophylline

Theophyllineand related drugs are oftenprescribed as

modiﬁed-releaseformulations andtoxicity cantherefore

bedelayed. They causevomiting (which maybe severe

and intractable), agitation, restlessness, dilated pupils,

sinus tachycardia, and hyperglycaemia. More serious

effects are haematemesis, convulsions, and supraven-

tricular and ventricular arrhythmias. Severe hypokal-

aemiamay develop rapidly.

Repeated doses of activated charcoal can be used to

eliminate theophylline even if more than 1 hour has

elapsed after ingestion and especially if a modiﬁed-

release preparation has been taken (see also under

Active Elimination Techniques, p. 33). Ondansetron

(section4.6) may be effective for severe vomiting that

isresistant to other antiemetics[unlicensed indication].

Hypokalaemia is corrected by intravenous infusion of

potassiumchloride and may beso severe as to require

60mmol/hour (high doses require ECG monitoring).

Convulsionsshould becontrolled byintravenous admin-

istration of lorazepam or diazepam (see Convulsions,

p.33). Sedation with diazepam may be necessary in

agitatedpatients.

Provided the patient does not suffer fromasthma, a

short-actingbeta-blocker (section 2.4) can be adminis-

teredintravenously toreverse severetachycardia, hypo-

kalaemia,and hyperglycaemia.

Other poisons

Consulteither theNational Poisons InformationService

dayand night or TOXBASE,see p. 32.

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

Cyanides

Oxygen should be administered to patients with cya-

nidepoisoning. The choice of antidotedepends on the

severity of poisoning, certainty of diagnosis, and the

cause.Dicobalt edetate is the antidote of choicewhen

there is a strong clinical suspicion of severecyanide

poisoning. Dicobalt edetate itself is toxic, associated

withanaphylactoid reactions, and is potentially fatal if

administered in the absence of cyanide poisoning.A

regimenof sodium nitritefollowed bysodium thiosul-

phate isan alternative if dicobalt edetate is not avail-

able.

Hydroxocobalamin(

Cyanokit

—noother preparation

ofhydroxocobalamin is suitable) canbe considered for

use invictims of smoke inhalation who show signs of

signiﬁcantcyanide poisoning.

DICOBALTEDETATE

Indications

severepoisoning with cyanides

Cautions

owingto toxicity tobe used onlyfor deﬁnite

cyanidepoisoning whenpatient tendingto lose,or has

lost,consciousness; notto be usedas aprecautionary

measure

Side-effects

hypotension,tachycardia, and vomiting;

anaphylactoidreactions includingfacial andlar yngeal

oedemaand cardiac abnormalities

Dose

. Byintravenous injection,ADULT 300mg over 1minute

(5minutes if condition lessserious) followed imme-

diatelyby 50mL ofglucose intravenous infusion50%;

ifresponse inadequate asecond dose of bothmay be

given,but risk of cobalttoxicity;

CHILDconsult the

NationalPoisons Information Service

DicobaltEdetate (Non-proprietary) A

Injection

,dicobalt edetate 15mg/mL, net price 20-

mL(300-mg) amp = £13.75

HYDROXOCOBALAMIN

Indications

seenotes above

Side-effects

gastro-intestinaldisturbances, transient

hypertension,peripheral oedema, dyspnoea, throat

disorders,hot ﬂush, dizziness,headache, restlessness,

memoryimpairment, red coloration of urine,lym-

phocytopenia,eye disorders,pustular rashes,pruritus,

reversiblered coloration of skinand mucous mem-

branes

Dose

. Byintravenous infusion, ADULT5 gover 15 minutes;a

seconddose of 5g can be givenover 15 minutes–2

hoursdepending on severityof poisoning andpatient

stability;

CHILD70 mg/kg(max. 5g) over15 minutes;a

seconddose of70 mg/kg(max. 5g) can begiven over

15minutes–2 hours depending onseverity of pois-

oningand patient stability

Cyanokit

(SwedishOrphan) TA

Intravenousinfusion

,powder for reconstitution,

hydroxocobalamin,net price2 2.5-g vials= £772.00

Note

Deepred colour of hydroxocobalamin may interferewith

laboratorytests (see Side-effects,above)

SODIUM NITRITE

Indications

poisoningwith cyanides (used incon-

junctionwith sodium thiosulphate)

Side-effects

ﬂushingand headache due to vasodila-

tation

1.A restriction does notapply where administration isfor

savinglife in emergency

BNF 61 Emergencytreatment of poisoning 39

Emergencytreatment of poisoning

Dose

. Byintravenous injection over 5–20minutes (as sod-

iumnitrite injection 30mg/mL), 300 mg;

CHILD4–

10mg/kg (max. 300mg)

SodiumNitrite A

Injection

,sodium nitrite 3% (30mg/mL) inwater for

injections

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.988

SODIUM THIOSULPHATE

Indications

inconjunction with sodium nitritefor

cyanidepoisoning

Dose

. Byintravenous injection over 10minutes (as sodium

thiosulphateinjection 500 mg/mL),12.5 g; dosemay

berepeated in severe cyanidepoisoning if dicobalt

edetatenot available;

CHILD400 mg/kg (max.12.5 g);

dosemay be repeated insevere cyanide poisoning if

dicobaltedetate not available

SodiumThiosulphate A

Injection

,sodium thiosulphate 50% (500mg/mL) in

waterfor injections

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.988

Ethylene glycol and methanol

Fomepizole (available from ‘special-order’ manufac-

turersor specialist importing companies, see p.988) is

thetreatment of choice for ethyleneglycol and metha-

nol(methyl alcohol)poisoning. Ifnecessary, ethanol(by

mouthor byintravenous infusion) canbe used, butwith

caution.Advice on thetreatment of ethyleneglycol and

methanol poisoning should be obtained from the

National Poisons Information Service. It is important

to start antidote treatment promptly in cases ofsus-

pectedpoisoning with these agents.

Heavy metals

Heavymetal antidotes include succimer (DMSA)[unli-

censed],unithiol (DMPS) [unlicensed], sodium calcium

edetate,and dimercaprol. Dimercaprol in the manage-

mentof heavy metalpoisoning has beensuperseded by

otherchelating agents. Inall cases ofheavy metal pois-

oning, the adviceof the National Poisons Information

Serviceshould be sought.

SODIUM CALCIUMEDETATE

(SodiumCalciumedetate)

Indications

leadpoisoning

Renalimpairment

usewith caution in mildimpair-

ment;avoid in moderate tosevere impairment—

contactthe National PoisonsInfor mationService for

advice

Side-effects

nausea,diarrhoea, abdominal pain, pain

atsite of injection, thrombophlebitisif given too

rapidly,renal damage particularlyin overdosage;

hypotension,lacrimation, myalgia, nasal congestion,

sneezing,malaise, thirst, fever,chills, headache, and

zincdepletion also reported

Dose

. Byintravenous infusion, ADULTand CHILD 40mg/kg

twicedaily for up to5 days; if necessary,a second

coursecan be given atleast 7 days after theﬁrst

course,a thirdcourse canbe givenat least7 daysafter

thesecond course

Ledclair

(Durbin)A

Injection

,sodium calcium edetate 200mg/mL, net

price5-mL amp = £7.29

Noxious gases

Carbon monoxide

Carbon monoxide poisoning is

usually due to inhalation of smoke, car exhaust, or

fumescaused by blocked ﬂues or incompletecombus-

tionof fuel gases in conﬁnedspaces.

Immediatetreatment of carbon monoxide poisoning is

essential.The person should bemoved to fresh air,the

airway cleared, and high-ﬂow oxygen 100% adminis-

teredthrough a tight-ﬁtting mask with an inﬂated face

seal.Artiﬁcial respiration should be givenas necessary

and continued until adequate spontaneous breathing

starts, or stopped only after persistent and efﬁcient

treatment of cardiac arrest has failed. The patient

should be admitted to hospitalbecause complications

may arise after a delay of hours or days. Cerebral

oedema mayoccur in severe poisoning and is treated

withan intravenous infusionof mannitol(section 2.2.5).

Referral for hyperbaric oxygen treatment should be

discussedwith theNational PoisonsInformation Service

ifthe patientis pregnant orin casesof severepoisoning,

suchas if thepatient is orhas been unconscious,or has

psychiatricor neurological features other than a head-

ache,or has myocardialischaemia or anar rhythmia,or

hasa bloodcarboxyhaemoglobin concentrationof more

than20%.

Sulphur dioxide, chlorine, phosgene, ammonia

Allof these gasescan cause upperrespiratory tract and

conjunctivalirritation. Pulmonary oedema, with severe

breathlessnessand cyanosis may develop suddenly up

to 36 hours after exposure. Death may occur. Patients

are kept under observation and those who develop

pulmonaryoedema are given oxygen.Assisted ventila-

tionmay be necessary in themost serious cases.

CS Spray

CSspray,which is usedfor riotcontrol, irritates theeyes

(hence ‘tear gas’) and the respiratory tract; symptoms

normally settle spontaneously within 15 minutes. If

symptomspersist, the patient should be removed to a

well-ventilatedarea, and theexposed skin washed with

soapand water afterremoval of contaminatedclothing.

Contact lenses should be removed and rigid ones

washed(soft ones shouldbe discarded). Eyesymptoms

should be treated by irrigating the eyes with physio-

logical saline (or water if saline is not available)and

advice sought from an ophthalmologist. Patients with

1.A restriction does notapply where administration isfor

savinglife in emergency

40 Emergency treatment ofpoisoning BNF61

Emergencytreatment of poisoning

features of severe poisoning, particularly respiratory

complications,should beadmitted to hospitalfor symp-

tomatictreatment.

Nerve agents

Treatmentof nerveagent poisoningis similarto organo-

phosphorus insecticide poisoning (see below), but

advicemust be soughtfrom the National PoisonsInfor-

mationSer vice. The risk of cross-contamination issig-

niﬁcant; adequate decontamination and protective

clothingfor healthcarepersonnel are essential.In emer-

gencies involving the release of nerve agents, kits

(‘NAASpods’) containing pralidoximecan be obtained

throughthe AmbulanceService fromthe NationalBlood

Service(or the Welsh Blood Servicein South Wales or

designatedhospital pharmaciesin Northern Irelandand

Scotland—seeTOXBASE forlist of designatedcentres).

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

Pesticides

Organophosphorus insecticides

Organophos-

phorusinsecticides are usually supplied as powdersor

dissolvedin organic solvents. Allare absorbed through

the bronchiand intact skin as well as through the gut

and inhibit cholinesterase activity, thereby prolonging

and intensifying the effects of acetylcholine.Toxicity

betweendif ferentcompounds varies considerably, and

onsetmay be delayed afterskin exposure.

Anxiety, restlessness, dizziness, headache, miosis,

nausea, hypersalivation, vomiting, abdominal colic,

diarrhoea,bradycardia, and sweating are commonfea-

turesof organophosphoruspoisoning. Muscle weakness

andfasciculation may developand progress togeneral-

ised ﬂaccid paralysis, including the ocular and respir-

atorymuscles. Convulsions, coma, pulmonary oedema

withcopious bronchial secretions, hypoxia, and arrhy-

thmias occur in severe cases. Hyperglycaemia and

glycosuriawithout ketonuria mayalso be present.

Furtherabsorption ofthe organophosphorus insecticide

shouldbe prevented by movingthe patient to freshair,

removing soiled clothing, and washingcontaminated

skin. In severe poisoning it is vital to ensurea clear

airway,frequent removalof bronchial secretions,and

adequate ventilation and oxygenation; gastric lavage

may be considered provided that the airway is pro-

tected.Atr opinewill reverse the muscarinic effects of

acetylcholineand is given byintravenous injection in a

doseof 2mg (20micrograms/kg (max. 2mg) in achild)

asatropine sulphateevery 5to 10 minutes(according to

theseverity ofpoisoning) untilthe skinbecomes ﬂushed

anddry, the pupilsdilate, and bradycardia isabolished.

Pralidoxime chloride, a cholinesterase reactivator, is

used as an adjunct to atropinein moderate or severe

poisoning.It improvesmuscle tonewithin 30 minutesof

administration.Pralidoxime chloride is continued until

the patient has not required atropine for 12 hours.

Pralidoximechloride can be obtained from designated

centres, the names of which are held by the National

PoisonsInformation Service (see p.32).

PRALIDOXIME CHLORIDE

Indications

adjunctto atropine in thetreatment of

poisoningby organophosphorus insecticide orner ve

agent

Cautions

myastheniagravis

Contra-indications

poisoningwith carbamates or

withorganophosphorus compounds without anti-

cholinesteraseactivity

Renalimpairment

usewith caution

Side-effects

drowsiness,dizziness, disturbances of

vision,nausea, tachycardia, headache, hyperventila-

tion,and muscular weakness

Dose

. Byintravenous infusion, ADULTand CHILD initially

30mg/kg over 20minutes, followed by8 mg/kg/

hour;usual max. 12g in 24 hours

Note

Theloading dose may be administered by intravenous

injection(diluted to aconcentration of 50mg/mL withwater

forinjections) over atleast 5 minutesif pulmonary oedemais

presentor if itis not practicalto administer anintravenous

infusion;pralidoxime chloride dosesin BNF maydiffer from

thosein product literature

Pralidoximechloride A

Injection

,powder for reconstitution, pralidoxime

chloride1 g/vial

Availableas

Protopam

(fromdesignated centres fororgano-

phosphorusinsecticide poisoning orfrom the NationalBlood

Service(or WelshAmbulance Services forMid West andSouth

EastWales)—see TOXBASEfor list ofdesignated centres)

Arestriction does notapply where administration isfor

savinglife in emergency

Snake bitesand animal stings

Snakebites

Envenomingfrom snake bite isuncom-

mon in the UK. Many exoticsnakes are kept, some

illegally,but theonly indigenous venomoussnake is the

adder (

Vipera berus

). The bite may cause local and

systemic effects. Local effects include pain, swelling,

bruising, and tender enlargement of regional lymph

nodes. Systemic effects include early anaphylactic

symptoms(transient hypotension with syncope, angio-

edema,urticaria, abdominal colic,diarrhoea, and vomi-

ting), with later persistent or recurrent hypotension,

ECG abnormalities, spontaneous systemic bleeding,

coagulopathy,adult respiratory distress syndrome,and

acute renal failure. Fatal envenoming is rarebut the

potential for severe envenoming must not be under-

estimated.

Early anaphylactic symptoms should be treatedwith

adrenaline (epinephrine) (section 3.4.3). Indications

forantivenom treatment include

systemicenvenoming

especiallyhypotension (see above),ECG abnormalities,

vomiting,haemostatic abnormalities, and marked local

envenomingsuch that after bites on the hand or foot,

swelling extends beyond the wrist or ankle within 4

hours of the bite. For both adults andchildren, the

contentsof one vial(10 mL)of European viper venom

antiserum (available from Movianto) isgiven

byintra-

venousinjection

over10–15 minutes or

byintravenous

infusion

over30 minutes afterdiluting in sodium chlor-

ide intravenous infusion 0.9% (use 5mL diluent/kg

body-weight). The dose can be repeated after 1–2

hours if symptoms of

systemic envenoming

persist.

However,for those patients who present withclinical

featuresof

severeenvenoming

(e.g.shock, ECGabnorm-

alities,or localswelling that hasadvanced from thefoot

BNF 61 Emergencytreatment of poisoning 41

Emergencytreatment of poisoning

toabove the kneeor from the handto above theelbow

within 2 hours of the bite), an initialdose of2 vials

(20mL) ofthe antiserum isrecommended; if symptoms

systemic envenoming

persist contact the National

PoisonsInformation Service.Adrenaline (epinephrine)

injectionmust be immediately tohand for treatment of

anaphylacticreactions to the antivenom (for the man-

agementof anaphylaxis, see section3.4.3).

Antivenom is available for bites by certain foreign

snakes and spiders, stings by scorpions and ﬁsh. For

information on identiﬁcation, management, and for

supplyin anemergency, telephonethe National Poisons

InformationService. Whenever possible the TOXBASE

entry should be read, and relevant information col-

lected, before telephoning the National Poisons Infor-

mationService (see p. 32).

Insect stings

Stings from ants,wasps, hornets, and

bees cause local pain and swelling but seldom cause

severedirect toxicity unlessmany stings areinﬂicted at

the same time. If the sting is in the mouth or on the

tongue local swelling may threaten the upper airway.

The stings from these insects are usually treated by

cleaning the area with a topical antiseptic. Bee stings

shouldbe removed asquickly as possible.Anaphylactic

reactions require immediate treatment with intramus-

cularadrenaline (epinephrine);self-administered intra-

muscularadrenaline (e.g.

EpiPen

)is the best ﬁrst-aid

treatmentfor patients with severe hypersensitivity. An

inhaled bronchodilator should be used for asthmatic

reactions. For the management of anaphylaxis, see

section3.4.3. A short course of an oralantihistamine

or a topical corticosteroid may help to reduce

inﬂammation andrelieve itching. A vaccine containing

extractsof bee andwasp venom can beused to reduce

the risk of anaphylaxis and systemic reactions in

patientswith systemic hypersensitivity to bee or wasp

stings(section 3.4.2).

Marinestings

Thesevere painof weeverﬁsh (

Trachi-

nus vipera

) and Portuguese man-o’-warstings canbe

relieved by immersing the stung area immediately in

uncomfortably hot, but not scalding, water (not more

than 458C). People stung by jellyﬁsh and Portuguese

man-o’-war around the UK coast should be removed

from the sea as soon as possible. Adherent tentacles

should be lifted off carefully (wearing gloves or using

tweezers)or washed off with seawater. Alcoholicsolu-

tions, including suntan lotions, should not be applied

because they can cause further discharge of stinging

hairs.Ice packs will reducepain and a slurry of baking

soda (sodium bicarbonate), but not vinegar, may be

usefulfor treating stings fromUK species.

42 Emergency treatment ofpoisoning BNF61

Emergencytreatment of poisoning

1 Gastro-intestinal system

1.1 Dyspepsia and gastro-oeso-

phagealreﬂux disease

1.1.1

Antacidsand simeticone 44

1.1.2 Compound alginates and pro-

prietaryindigestion preparations

1.2 Antispasmodics and otherdrugs

alteringgut motility

1.3 Antisecretory drugsand mucosal

protectants

1.3.1

-receptorantagonists 51

1.3.2 Selective antimuscarinics 53

1.3.3 Chelates and complexes 53

1.3.4 Prostaglandin analogues 54

1.3.5 Proton pump inhibitors 54

1.4 Acute diarrhoea 57

1.4.1

Adsorbentsand bulk-forming

drugs

1.4.2 Antimotility drugs 58

1.5 Chronic bowel disorders 59

1.5.1

Aminosalicylates 61

1.5.2 Corticosteroids 64

1.5.3 Drugs affecting the immune

response

1.5.4 Food allergy 66

1.6 Laxatives 67

1.6.1

Bulk-forminglaxatives 67

1.6.2 Stimulant laxatives 68

1.6.3 Faecal softeners 70

1.6.4 Osmotic laxatives 71

1.6.5 Bowel cleansing preparations 73

1.6.6 Peripheral opioid-receptor

antagonists

1.6.7 5HT

-receptoragonists 75

1.7 Local preparations for analand

rectaldisorders

1.7.1

Soothinghaemorrhoidal pre-

parations

1.7.2 Compound haemorrhoidal pre-

parationswith corticosteroids

1.7.3 Rectal sclerosants 77

1.7.4 Management of anal ﬁssures 77

1.8 Stoma care 77

1.9 Drugs affecting intestinal secre-

tions

1.9.1

Drugsaffecting biliary composi-

tionand ﬂow

1.9.2 Bile acid sequestrants 78

1.9.3 Aprotinin 79

1.9.4 Pancreatin 79

Thischapter also includes advice on the drug man-

agementof the following:

Clostridiumdifﬁcile

infection,p. 60

constipation,p. 67

Crohn’sdisease, p. 59

diverticulardisease, p. 61

foodallergy, p. 66

Helicobacterpylori

infection,p. 49

irritablebowel syndrome, p. 61

NSAID-associatedulcers, p. 50

ulcerativecolitis, p. 59

1.1

Dyspepsia and gastro-

oesophageal reﬂux

disease

1.1.1 Antacids and simeticone

1.1.2 Compound alginates and proprietary

indigestionpreparations

Dyspepsia

Dyspepsiacovers upper abdominal pain, fullness, early

satiety,bloating, and nausea. It can occur with gastric

andduodenal ulceration (section 1.3) and gastriccancer

butmost commonly it is of uncertain origin.

Urgentendoscopic investigation is required if dyspepsia

isaccompanied by ‘alarm features’ (e.g. bleeding, dys-

phagia, recur rent vomiting, or weight loss). Urgent

investigation should also be considered for patients

over55 years with unexplained, recent-onset dyspepsia

thathas not responded to treatment.

Patients with dyspepsia should be advisedabout life-

style changes (see Gastro-oesophagealreﬂux disease,

below).Some medications may cause dyspepsia—these

should be stopped, if possible. Antacids mayprovide

somesymptomatic relief.

Ifsymptoms persist in

uninvestigateddyspepsia

,treat-

mentinvolves a proton pump inhibitor (section1.3.5)

for 4 weeks. A proton pump inhibitor can be used

intermittentlyto control symptoms long ter m. Patients

withuninvestigated dyspepsia, who do not respond to

an initial trial with a proton pump inhibitor, should be

tested for

Helicobacter pylori

and given eradication

therapy (section 1.3) if

H. pylori

is present. Alterna-

tively,particularly in populations where

H.pylori

infec-

tion is more likely, the ‘test and treat’ strategy for

pylori

can be used before a trial with a proton pump

inhibitor.

BNF 61 43

Gastro-intestinalsystem

H.pylori

ispresent in patients with

functional(inves-

tigated, non-ulcer) dyspepsia

, eradication therapy

should be provided. If symptoms persist, treatment

witheither a pr otonpump inhibitor (section 1.3.5) or

ahistamine H

-receptorantagonist (section1.3.1) can

begiven for 4 weeks. These antisecretory drugs can be

used intermittently to control symptoms long ter m.

However, most patients with functionaldyspepsia do

notbeneﬁt symptomatically from

H.pylori

eradication

therapyor antisecretory drugs.

Gastro-oesophageal reﬂuxdisease

Gastro-oesophageal reﬂux disease (includingnon-ero-

sive gastro-oesophageal reﬂ ux and erosive oeso-

phagitis) is associated with heartburn, acidregurgita-

tion, and sometimes, dif ﬁculty in swallowing

(dysphagia); oesophageal inﬂ ammation (oesophagitis),

ulceration,and stricture formation may occur and there

isan association with asthma.

Themanagement of gastro-oesophageal reﬂux disease

includesdrug treatment, lifestyle changes and, in some

cases,surgery. Initial treatmentis guided by the severity

ofsymptoms and treatment is then adjusted according

to response. The extent of healing depends on the

severityof the disease, the treatment chosen, and the

durationof therapy.

Patientswith gastro-oesophageal reﬂux disease should

beadvised about lifestyle changes (avoidance of excess

alcohol and of aggravating foods such asfats); other

measuresinclude weight reduction, smoking cessation,

andraising the head of the bed.

For

mild symptoms

of gastro-oesophageal reﬂux dis-

ease, initial management may include the use of

antacids and alginates. Alginate-containing antacids

canform a ‘raft’that ﬂoats on the surface of thestomach

contentsto reduce reﬂux and protect the oesophageal

mucosa. Histamine H

-receptor antagonists (section

1.3.1) may relieve symptoms and permit reduction in

antacid consumption. However, proton pump inhi-

bitors (section 1.3.5) provide moreef fective relief of

symptoms than H

-receptor antagonists. When symp-

tomsabate, treatment is titrated down to a level which

maintainsremission (e.g. by giving treatment inter mit-

tently).

For

severesymptoms

ofgastro-oesophageal reﬂux dis-

easeor for patients with a proven or severe pathology

(e.g.

oesophagitis,oesophageal ulceration, oesophago-

pharyngeal reﬂux, Barrett’s oesophagus

), initial man-

agementinvolves the use of a proton pump inhibitor

(section1.3.5); patients need to be reassessed if symp-

toms persist despite treatment for 4–6 weeks witha

proton pump inhibitor. When symptoms abate, treat-

mentis titrated down to a level which maintains remis-

sion (e.g. by reducing the dose of the proton pump

inhibitoror by giving it intermittently, or by substituting

treatment with a histamine H

-receptor antagonist).

However,for endoscopically conﬁrmed

erosive, ulcer-

ative

, or

stricturing

disease, or

Barrett’s oesophagus

treatmentwith a proton pump inhibitor usually needsto

bemaintained at the minimum effective dose.

Aprokinetic drug suchas metoclopramide (section4.6)

may improve gastro-oesophageal sphincter function

andaccelerate gastric emptying.

Children

Gastro-oesophageal reﬂux disease is com-

mon in infancy but most symptoms resolve without

treatmentbetween 12 and 18 months of age. In infants,

mildor moderate reﬂux without complications can be

managed initially by changing the frequency and

volumeof feed; a feed thickener or thickened formula

feedcan be used (with adviceof a dietitian—see Appen-

dix 7 for suitable products). If necessary, a suitable

alginate-containingpreparation can be used instead of

thickened feeds. For older children, life-stylechanges

similar to those for adults (see above) may be helpful

followed if necessary by treatment with an alginate-

containingpreparation.

Childrenwho do not respond to these measures or who

have problems such as respiratory disorders or sus-

pectedoesophagitis need to be referred to hospital; an

-receptorantagonist (section 1.3.1) may be neededto

reduceacid secretion. If the oesophagitis is resistant to

-receptorblockade, the proton pump inhibitor ome-

prazole(section 1.3.5) can be tried.

1.1.1

Antacids and simeticone

Antacids(usually containing aluminium or magnesium

compounds) can often relieve symptoms in

ulcerdys-

pepsia

and in

non-erosive gastro-oesophageal reﬂux

(seealso section 1.1); they are also sometimes used in

functional (non-ulcer) dyspepsia but the evidence of

beneﬁt is uncertain. Antacids are best given when

symptoms occur or are expected, usually between

mealsand at bedtime, 4 or more times daily; additional

dosesmay be requiredup to once an hour.Conventional

dosese.g. 10mL 3 or 4 times dailyof liquid magnesium–

aluminiumantacids promote ulcer healing, but less well

than antisecretory drugs (section 1.3); proof of a rela-

tionship between healing and neutralising capacityis

lacking. Liquid preparations are more effective than

tabletpreparations.

Aluminium-and magnesium-containing antacids(e.g.

aluminium hydroxide, and magnesium carbonate,

hydroxide and trisilicate), being relatively insoluble in

water,are long-acting if retained in the stomach. They

are suitable for most antacid purposes. Magnesium-

containingantacids tend to be laxative whereas alumin-

ium-containingantacids may be constipating; antacids

containingboth magnesium and aluminium may reduce

these colonic side-effects. Aluminium accumulation

doesnot appear to be a risk if renal function is normal.

Theacid-neutralising capacity of preparations that con-

tainmore than one antacid may be the same as simpler

preparations. Complexes such ashydrotalcite confer

nospecial advantage.

Sodium bicarbonate should no longer be prescribed

alonefor the relief of dyspepsia but it is present as an

ingredient in many indigestion remedies. However,it

retains a place in the management of urinary-tract

disorders (section 7.4.3) and acidosis (section 9.2.1.3

and section 9.2.2). Sodium bicarbonate should be

avoidedin patients on salt-restricted diets.

Bismuth-containingantacids (unless chelates) are not

recommended because absorbed bismuth can be neu-

rotoxic,causing encephalopathy; they tend to be con-

stipating. Calcium-containing antacids (section 1.1.2)

44 1.1.1 Antacids and simeticone BNF 61

Gastro-intestinalsystem

caninduce rebound acid secretion: with modest doses

theclinical signiﬁcance is doubtful, but prolonged high

dosesalso cause hypercalcaemia and alkalosis, and can

precipitatethe milk-alkali syndrome.

Simeticone(activated dimeticone) is added to an anta-

cidas an antifoaming agent to relieve ﬂatulence. These

preparations may be useful for therelief of hiccup in

palliativecare. Alginates, added as protectants, may be

usefulin gastro-oesophageal reﬂux disease (section 1.1

andsection 1.1.2). The amount of additional ingredient

or antacid in individual preparations varies widely, as

doestheir sodium content, so that preparationsmay not

befreely interchangeable.

Seealso section 1.3 for dr ugs used in the treatment of

pepticulceration.

Hepaticimpairment

Inpatients with ﬂuid retention,

avoid antacids containing large amounts of sodium.

Avoid antacids that cause constipation because this

can precipitate coma. Avoid antacids containing

magnesium salts in hepaticcoma if there is arisk of

renalfailure.

Renal impairment

In patients with ﬂuid retention,

avoid antacids containing large amounts of sodium.

Thereis a risk of accumulation and aluminium toxicity

withantacids containing aluminium salts. Absorption of

aluminiumfrom aluminium saltsis increased by citrates,

whichare contained in many effervescent preparations

(such as effer vescent analgesics). Antacids containing

magnesiumsalts should beavoided or used at a reduced

dosebecause there is an increased risk of toxicity.

Interactions

Antacidsshould preferably not be taken

atthe same time as other drugs since they may impair

absorption.Antacids may also damage enteric coatings

designedto prevent dissolution in the stomach.See also

Appendix1 (antacids, calcium salts).

Low Na

Thewords ‘low Na

’added after some preparations

indicate a sodium content of less than 1 mmol per

tabletor 10-mL dose.

Aluminium- and magnesium-

containing antacids

ALUMINIUM HYDROXIDE

Indications

dyspepsia;hyperphosphataemia (section

9.5.2.2)

Cautions

seenotes above; interactions: Appendix 1

(antacids)

Contra-indications

hypophosphataemia;neonates

andinfants

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Side-effects

seenotes above

Aluminium-onlypreparations

Alu-Cap

(Meda)

Capsules

,green/red, dried aluminium hydroxide

475mg (low Na

).Net price 120-cap pack = £3.75

Dose

antacid,1 capsule 4 times daily and at bedtime; CHILD not

recommendedfor antacid therapy

Co-magaldrox

Co-magaldroxis a mixture of aluminium hydroxide and

magnesiumhydroxide; the proportions are expressed in the

form

where

and

arethe strengths in milligrams per unit

doseof magnesium hydroxide and aluminium hydroxide

respectively

Maalox

(Sanoﬁ-Aventis)

Suspension

,sugar-free, co-magaldrox 195/220

(magnesiumhydroxide 195 mg, dried aluminium

hydroxide220 mg/5mL (low Na

)).Net price 500 mL

=£2.79

Dose

ADULTand CHILD over14 years, 10–20mL 20–60 minutes

aftermeals and at bedtime or when required

Mucogel

(Chemidex)

Suspension

,sugar-free, co-magaldrox 195/220

(magnesiumhydroxide 195 mg, dried aluminium

hydroxide220 mg/5mL (low Na

)).Net price 500 mL

=£1.71

Dose

ADULTand CHILD over12 years, 10–20mL 3 times daily,

20–60minutes after meals, and at bedtime or when required

MAGNESIUM CARBONATE

Indications

dyspepsia

Cautions

seenotes above; interactions: Appendix1

(antacids)

Contra-indications

hypophosphataemia

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; magnesium

carbonatemixture has a high sodium content

Side-effects

diarrhoea;belching due to liberated car-

bondioxide

AromaticMagnesium Carbonate Mixture, BP

(AromaticMagnesium Carbonate Oral Suspen-

sion)

Oralsuspension

,light magnesium carbonate 3%,

sodiumbicarbonate 5%, in a suitable vehicle con-

tainingaromatic cardamom tincture. Contains about

6mmol Na

/10mL. Net price 200 mL = 66p

Dose

10mL 3 times daily in water

For preparations also containing aluminium, see

aboveand section 1.1.2.

MAGNESIUM TRISILICATE

Indications

dyspepsia

Cautions

seeunder Magnesium Carbonate

Contra-indications

seeunder Magnesium Carbonate

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; magnesium tri-

silicatemixture has a high sodium content

Side-effects

diarrhoea,belching due to liberated car-

bondioxide; silica-based renal stones reported on

long-termtreatment

MagnesiumTrisilicate Tablets, Compound,BP

Tablets

,magnesium trisilicate 250 mg, dried alumin-

iumhydroxide 120 mg

Dose

1–2tablets chewed when required

MagnesiumTrisilicate Mixture, BP

(MagnesiumTrisilicate Oral Suspension)

Oralsuspension

,5% each of magnesium trisilicate,

lightmagnesium carbonate, and sodium bicarbonate

ina suitable vehicle with a peppermint ﬂavour. Con-

tainsabout 6 mmol Na

/10mL

Dose

10–20mLin water 3 times daily or as required; CHILD 5–12

years,5–10 mL in water 3 times daily or as required

For preparations also containing aluminium, see

aboveand section 1.1.2.

BNF 61 1.1.1 Antacidsand simeticone 45

Gastro-intestinalsystem

Aluminium-magnesium complexes

HYDROTALCITE

Aluminiummagnesium carbonate hydroxide

hydrate

Indications

dyspepsia

Cautions

seenotes above; interactions: Appendix1

(antacids)

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Side-effects

seenotes above

Withsimeticone

AltacitePlus

seebelow

Antacid preparations containing

simeticone

AltacitePlus

(Peckforton)

Suspension

,sugar-free, co-simalcite 125/500 (sime-

ticone125 mg, hydrotalcite 500 mg)/5mL (low Na

Netprice 500 mL = £2.79

Dose

10mL between meals and at bedtime when required;

CHILD8–12 years 5 mL between meals and at bedtim e when

required

Asilone

(Thornton& Ross)

Suspension

,sugar-free, dried aluminium hydroxide

420mg, simeticone 135 mg, light magnesium oxide

70mg/5mL (low Na

).Net price 500 mL = £1.95

Dose

ADULTandCHILD over12 years,5–10 mL after meals and at

bedtimeor when requi red up to 4 times daily

MaaloxPlus

(Sanoﬁ-Aventis)

Suspension

,sugar-free, dried aluminium hydroxide

220mg, simeticone 25 mg, magnesium hydroxide

195mg/5mL (low Na

).Net price 500 mL = £2.79

Dose

5–10mL4 times daily (after meals and atbedtim e)or when

required;CHILD under 12 years see

BNFfor Children

Simeticone alone

Simeticone (activated dimeticone) is an antifoaming

agent. It is licensed for infantile colic but evidence of

beneﬁtis uncer tain.

Dentinox

(DDD)U

Colicdrops

(=emulsion), simeticone 21 mg/2.5-mL

dose.Net price 100 mL = £1.73

Dose

colicor wind pains, NEONATE andINFANT 2.5mL with or

aftereach feed (max. 6 doses in 24hour s);may be added to bottle

feed

Note

The brand name

Dentinox

is also used for other

preparationsincluding teething gel

Infacol

(Forest)U

Liquid

,sugar-free, simeticone 40 mg/mL (low Na

Netprice 50 mL = £2.26. Counselling, use of dropper

Dose

colicor wind pains, NEONATE andINFANT 0.5–1mL before

feeds

1.1.2

Compound alginates and

proprietary indigestion

preparations

Alginatetaken in combination with an antacid increases

the viscosity of stomach contents and can protect the

oesophageal mucosa from acid reﬂux. Some alginate-

containing preparations form a viscous gel (‘raft’) that

ﬂoats on the surface of the stomach contents, thereby

reducingsymptoms of reﬂux.

Antacids may damage enteric coatings designed to

prevent dissolution in the stomach. For interactions,

seeAppendix 1 (antacids, calcium salts).

Alginate raft-forming oral suspensions

The following preparations contain sodium alginate,

sodiumbicarbonate, and calciumcarbonate in a suitable

ﬂavouredvehicle, and conform to the speciﬁcation for

AlginateRaft-forming Oral Suspension, BP.

Acidex

(Pinewood)

Liquid

,sugar-free, sodium alginate 250 mg, sodium

bicarbonate133.5 mg, calcium carbonate 80 mg/

5mL. Contains about 3 mmol Na

/5mL. Net price

500mL (aniseed- or peppermint-ﬂavour) = £2.30

Dose

10–20mLafter meals and at bedtime; CHILD 6–12years 5–

10mL after meals and at bedtime

Peptac

(IVAX)

Suspension

,sugar-free, sodium bicarbonate

133.5mg, sodium alginate 250mg, calcium carbonate

80mg/5mL. Contains 3.1 mmol Na

/5mL. Net price

500mL (aniseed- or peppermint-ﬂavoured) = £2.16

Dose

10–20mLafter meals and at bedtime; CHILD 6–12years 5–

10mL after meals and at bedtime

Othercompound alginate preparations

Gastrocote

(Actavis)

Tablets

,alginic acid 200 mg, dried aluminium hydro-

xide80 mg, magnesium trisilicate 40 mg, sodium

bicarbonate70 mg. Contains about 1 mmol Na

tablet.Net price 100-tab pack = £3.51

Cautions diabetes mellitus (high sugar content)

Dose

ADULTandCHILD over 6 years, 1–2 tablets chewed 4 times

daily(after meals and at bedtime)

Liquid

,sugar-free, peach-coloured, dried aluminium

hydroxide80 mg, magnesium trisilicate 40 mg, sod-

iumalginate 220 mg, sodium bicarbonate 70 mg/

5mL. Contains 2.13 mmol Na

/5mL. Net price

500mL = £2.67

Dose

5–15mL 4 times daily (after meals and at bedtime); CHILD

6–12years, 5–10 mL 4 times daily (after meals a nd at bedtime)

Gaviscon

Advance(Reckitt Benckiser)

Tablets

,sugar-free, sodium alginate 500 mg, potas-

siumbicarbonate 100 mg. Contains 2.25 mmol Na

1mmol K

/tablet.Net price 60-tabpack (peppermint-

ﬂavoured)= £3.07

Excipients

includeaspartame (section 9.4.1)

Dose

ADULTand CHILD over12 years, 1–2 tablets to be chewed

aftermeals and at bedtime; CHILD 6–12 years, 1 tablet to be

chewedafter meals and at bedtime (under medical advice only)

Suspension

,sugar-free, aniseed- or peppermint ﬂa-

vour,sodium alginate 500 mg, potassium bicarbonate

46 1.1.2 Compound alginates and proprietary indigestion preparations BNF 61

Gastro-intestinalsystem

100mg/5mL. Contains 2.3 mmol Na

,1 mmol K

5mL, net price 250 mL = £2.56, 500 mL = £5.12

Dose

ADULTandCHILD over12 years,5–10 mL after meals and at

bedtime;CHILD 2–12 years, 2.5–5mL after meals and at bedtime

(undermedical advice only)

GavisconInfant

(ReckittBenckiser)

Oralpowder

,sugar-free, sodium alginate 225 mg,

magnesiumalginate 87.5 mg, with colloidal silica and

mannitol/dose.Contains 0.92 mmol Na

/dose.Net

price30 doses = £2.46

Dose

INFANTbody-weight under 4.5kg, 1 ‘dose’ mixed with

feeds(or water in breast-fed infants) when required (max. 6 times

in24 hours); body-weight over 4.5 kg, 2 ‘doses’ mixed with feeds

(orwater in breast-fed infants) when required (max. 6 times in 24

hours);CHILD 2 ‘doses’ in water after each meal (max. 6 times in

24hours)

Note

Notto be used in preterm neonat es, or where excessive

waterloss likely (e.g. feve r, diarrhoea, vomiting, high room tem-

perature),or if intestin al obstruction. Not to be used with other

preparationscontaining thickening agents

Important

Eachhalf of the dual-sachet is identiﬁed as ‘one dose’.

Toavoid errors prescribe with directions in terms of ‘dose’

Topal

(Fabre)

Tablets

,alginic acid 200 mg, dried aluminium hydro-

xide30 mg, light magnesium carbonate 40 mg with

lactose220 mg, sucrose 880 mg, sodium bicarbonate

40mg (low Na

).Net price 42-tab pack = £1.67

Cautions diabetes mellitus (high sugar content)

Dose

ADULTandCHILD over12 years,1–3 tablets chewed 4 times

daily(after meals and at bedtime)

1.2

Antispasmodics and

other drugs altering gut

motility

Drugsin this section include antimuscariniccompounds

and drugs believed to be direct relaxants of intestinal

smoothmuscle. The smooth muscle relaxant properties

of antimuscarinic and other antispasmodic drugs may

beuseful in

irritablebowel syndrome

andin

diverticular

disease

The dopamine-receptor antagonists metoclopramide

and domperidone (section 4.6) stimulate transit in the

gut.

Antimuscarinics

Antimuscarinics (formerly termed ‘anticholinergics’)

reduceintestinal motility.They are used forthe manage-

mentof

irritablebowel syndrome

and

diverticulardis-

ease

.However, their value has not been established and

response varies. Other indications for antimuscarinic

drugs include arrhythmias (section 2.3.1), asthma and

airwaysdisease (section 3.1.2), motion sickness (section

4.6),parkinsonism (section 4.9.2), urinar y incontinence

(section7.4.2), mydriasis and cycloplegia (section 11.5),

premedication (section 15.1.3) andas an antidote to

organophosphoruspoisoning (p. 41).

Antimuscarinics that are used for gastro-intestinal

smoothmuscle spasm include the tertiar y amines atro-

pine sulphate and dicycloverine hydrochloride and

thequaternar y ammonium compounds propantheline

bromideand hyoscine butylbromide. The quaternary

ammoniumcompounds are less lipid soluble than atro-

pineand are less likely to cross the blood–brain bar rier;

theyare also less well absorbed from the gastro-intes-

tinaltract.

Dicycloverine hydrochloride has amuch less marked

antimuscarinicaction than atropine and may also have

somedirect action on smooth muscle. Hyoscine butyl-

bromide is advocated as a gastro-intestinal antispas-

modic,but it is poorly absorbed; the injection is useful

in endoscopy and radiology.Atropine andthe bella-

donna alkaloids are outmoded treatments, any clinical

virtuesbeing outweighed by atropinic side-ef fects.

Cautions

Antimuscarinicsshould be used with caution

inDown’s syndrome, in children and inthe elderly; they

shouldalso be used with caution in gastro-oesophageal

reﬂux disease, diarrhoea, ulcerative colitis, autonomic

neuropathy,acute myocardial infarction, hypertension,

conditions characterised by tachycardia (including

hyperthyroidism,cardiac insufﬁciency, cardiacsurger y),

pyrexia,and in individuals susceptible to angle-closure

glaucoma.Interactions: Appendix 1 (antimuscarinics).

Contra-indications

Antimuscarinicsare contra-indi-

catedin myasthenia gravis(but may be used todecrease

muscarinic side-effects of anticholinesterases—section

10.2.1), paralytic ileus, pyloric stenosis, toxic megaco-

lon,and prostatic enlargement.

Side-effects

Side-effects of antimuscarinics include

constipation,transient bradycardia (followed by tachy-

cardia,palpitation and arrhythmias), reduced bronchial

secretions,urinary urgency and retention, dilatation of

the pupils with loss of accommodation, photophobia,

drymouth, ﬂushing and dryness of the skin. Side-effects

that occur occasionally include confusion (particularly

in the elderly), nausea, vomiting, and giddiness;very

rarely,angle-closure glaucoma may occur.

ATROPINESULPHATE

Indications

symptomaticrelief of gastro-intestinal

disorderscharacterised by smooth muscle spasm;

mydriasisand cycloplegia (section 11.5); premedi-

cation(section 15.1.3); see also notes above

Cautions

seenotes above

Contra-indications

seenotes above

Pregnancy

notknown to be harmful; manufacturer

advisescaution

Breast-feeding

smallamount present in milk—man-

ufactureradvises caution

Side-effects

seenotes above

Dose

. 0.6–1.2mg at night

Atropine(Non-proprietary) AU

Tablets

,atropine sulphate 600 micrograms. Net price

28-tabpack = £17.59

DICYCLOVERINEHYDROCHLORIDE

(Dicyclominehydrochloride)

Indications

symptomaticrelief of gastro-intestinal

disorderscharacterised by smooth muscle spasm

Cautions

seenotes above

BNF 61 1.2 Antispasmodicsand other drugs altering gut motility 47

Gastro-intestinalsystem

Contra-indications

seenotes above; also infants

under6 months

Pregnancy

notknown to be harmful; manufacturer

advisesuse only if essential

Breast-feeding

avoid—presentin milk; apnoea

reportedin infant

Side-effects

seenotes above

Dose

. 10–20mg 3 times daily; INFANT 6–24 months 5–10mg

3–4times daily, 15 minutes before feeds;

CHILD2–12

years10 mg 3 times daily

Merbentyl

(Sanoﬁ-Aventis)A

Tablets

,dicycloverine hydrochloride 10 mg, net price

100-tabpack = £4.84; 20 mg (

Merbentyl20

),84-tab

pack= £8.14

Syrup

,dicycloverine hydrochloride 10 mg/5 mL, net

price120 mL = £1.77

Note

Dicycloverinehydrochloride can be sold to the public

providedthat max. single dose is 10 mg and max. daily dose

is60 mg

Compoundpreparations

Kolanticon

(Peckforton)

Gel

,sugar-free, dicycloverine hydrochloride 2.5 mg,

driedaluminium hydroxide 200 mg, light magnesium

oxide100 mg, simeticone 20 mg/5 mL, net price

200mL = £2.21, 500 mL = £3.35

Dose

ADULTand CHILD over12 years, 10–20mL every 4 hours

whenrequired

HYOSCINE BUTYLBROMIDE

Indications

symptomaticrelief of gastro-intestinal or

genito-urinarydisorders characterised by smooth

musclespasm; bowel colic and excessive respiratory

secretions(see Prescribing in Palliative Care, p. 23)

Cautions

seenotes above

Contra-indications

seenotes above

Pregnancy

manufactureradvises use only if potential

beneﬁtoutweighs risk

Breast-feeding

amounttoo small to be harmful

Side-effects

seenotes above

Dose

. Bymouth (but poorly absorbed, see notes above),

smoothmuscle spasm, 20 mg 4 times daily;

CHILD6–

12years, 10 mg 3 times daily

Irritablebowel syndrome, 10 mg 3 times daily,

increasedif required up to 20 mg 4 times daily

. Byintramuscular

slowintravenous injection, acute

spasmand spasm in diagnostic procedures, 20 mg

repeatedafter 30 minutes if necessary (may be

repeatedmore frequently in endoscopy),max. 100 mg

daily;

CHILD2–18 years see

BNFfor Children

Buscopan

(BoehringerIngelheim) A

Tablets,

coated,hyoscine butylbromide 10 mg, net

price56-tab pack = £2.25

Note

Hyoscine butylbromide tablets canbe sold to the

publicfor medically conﬁr med irritable bowel syndrome,

providedsingle dose doesnot exceed 20 mg, daily dosedoes

notexceed 80mg, and pack does not contain a total of more

than240 mg

Injection

,hyoscine butylbromide 20 mg/mL, net

price1-mL amp = 22p

PROPANTHELINEBROMIDE

Indications

symptomaticrelief of gastro-intestinal

disorderscharacterised by smooth muscle spasm;

urinaryfrequency (section 7.4.2); gustator y sweating

(section6.1.5)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

manufactureradvises caution

Renalimpairment

manufactureradvises caution

Pregnancy

manufactureradvises avoid unless essen-

tial

Breast-feeding

maysuppress lactation

Side-effects

seenotes above

Dose

. ADULTand CHILD over12 years, 15 mg 3 times daily at

least1 hour before meals and 30 mg at night, max.

120mg daily

Pro-Banthine

(Archimedes)A

Tablets

,pink, s/c, propantheline bromide 15 mg, net

price112-tab pack = £14.40. Label: 23

Other antispasmodics

Alverine, mebeverine, and peppermint oil are

believed to be direct relaxants of intestinal smooth

muscle and may relieve pain in

irritable bowel

syndrome

and

diverticular disease

. They have no ser-

iousadverse ef fects but, like all antispasmodics, should

beavoided in paralytic ileus. Peppermint oil occasion-

allycauses heartburn.

ALVERINECITRATE

Indications

adjunctin gastro-intestinal disorders

characterisedby smooth muscle spasm; dysmenor r-

hoea

Contra-indications

paralyticileus

Pregnancy

usewith caution

Breast-feeding

manufactureradvises avoid—limited

informationavailable

Side-effects

nausea;headache, dizziness; pruritus,

rash;hepatitis also reported

Dose

. ADULTand CHILD over 12 years, 60–120 mg 1–3 times

daily

Spasmonal

(Norgine)

Capsules

,alverine citrate 60 mg (blue/grey), net

price100-cap pack = £9.47; 120 mg (

Spasmonal

Forte

,blue/grey), 60-cap pack = £10.94

MEBEVERINE HYDROCHLORIDE

Indications

adjunctin gastro-intestinal disorders

characterisedby smooth muscle spasm

Cautions

avoidin acute porphyria (section 9.8.2.)

Contra-indications

paralyticileus

Pregnancy

notknown to be harmful; manufacturers

advisecaution

Side-effects

allergicreactions (including rash, urti-

caria,angioedema) reported

48 1.2 Antispasmodics and other drugs altering gut motility BNF 61

Gastro-intestinalsystem

Dose

. ADULTand CHILD over 10 years 135–150 mg 3 times

dailypreferably 20 minutes before meals;

CHILDunder

10years see

BNFfor Children

MebeverineHydrochloride (Non-proprietary) A

Tablets

,mebeverine hydrochloride 135 mg, net price

100-tabpack = £4.21

Oralsuspension

,mebeverine hydrochloride (as

mebeverineembonate) 50mg/5 mL, net price 300mL

=£137.00

Mebeverinehydrochloride can be sold to the public for

symptomaticrelief of irritable bowel syndrome provided

thatmax. single dose is 135mg and max. daily dose is

405mg; for uses other than symptomatic relief of irritable

bowelsyndrome provided that max. single dose is 100 mg

andmax. daily dose is 300 mg

Colofac

(Solvay)A

Tablets

,s/c, mebeverine hydrochloride 135 mg, net

price100-tab pack = £7.52

Modiﬁedrelease

Colofac

MR(Solvay) A

Capsules

,m/r, mebeverine hydrochloride 200 mg,

netprice 60-cap pack = £6.67. Label: 25

Dose

irritablebowel syndrome, 1 capsule twice daily preferably

20minutes beforemeals; CHILD 12–18years see

BNFforChildren

Compoundpreparations

Fybogel

Mebeverine(Reckitt Benckiser) A

Granules

,buff, effervescent, ispaghula husk 3.5 g,

mebeverinehydrochloride 135 mg/sachet, net price

10sachets = £2.50. Label: 13, 22, counselling, see

below

Excipients

includeaspartame (section 9.4.1)

Electrolytes

2.5mmol/sachet

Dose

irritablebowel syndrome, ADULT andCHILD over 12 years,

1sachetin water, morning and evening 30minutes before food; an

additionalsachet may also be taken before the midday meal if

necessary

Counselling

Preparationsthat swell in contact with liquid should

alwaysbe carefully swallowedwith water and should not be taken

immediatelybefore going to bed

10-sachetpack can be sold to the public

PEPPERMINT OIL

Indications

reliefof abdominal colic and distension,

particularlyin irritable bowel syndrome

Cautions

sensitivityto menthol

Pregnancy

notknown to be harmful

Breast-feeding

signiﬁcantlevels of menthol in breast

milkunlikely

Side-effects

heartburn,perianal irritation; rarely,

allergicreactions (including rash, headache, brady-

cardia,muscle tremor, ataxia)

Localirritation

Capsulesshould not be broken or chewed

becausepeppermint oil may irritate mouth or oesophagus

Dose

. Seepreparations

Colpermin

(McNeil)

Capsules

,m/r, e/c, light blue/dark blue, blue band,

peppermintoil 0.2 mL. Net price 100-cap pack =

£12.05.Label: 5, 22, 25

Excipients

includearachis (peanut) oil

Dose

ADULTand CHILD over15 years, 1–2 capsules, swallowed

wholewith water, 3 times daily for up to 3 months if necessary

Mintec

(Almirall)

Capsules

,e/c, green/ivory, peppermint oil 0.2 mL.

Netprice 84-cap pack = £7.04. Label: 5, 22, 25

Dose

ADULTover 18 years, 1–2 capsules swallowed whole with

water,3 times daily before meals for up to 2–3 months if neces-

sary

Motility stimulants

Metoclopramide and domperidone (section 4.6) are

dopaminereceptor antagonists which stimulate gastric

emptyingand small intestinal transit, and enhance the

strengthof oesophageal sphincter contraction. They are

used in some patientswith

functional dyspepsia

that

hasnot responded to a proton pump inhibitor or a H

receptor antagonist. Metoclopramide is also used to

speed the transit of barium during intestinal follow-

through examination, and as accessor y treatment for

gastro-oesophagealreﬂux disease

.For themanagement

of gastroparesis in patients withdiabetes, see section

6.1.5. Metoclopramide and domperidone are useful in

non-speciﬁcand in cytotoxic-induced nausea and vomi-

ting. Metoclopramide and occasionally domperidone

can cause acute dystonic reactions, particularly in

youngwomen and children—for further details of this

andother side-effects, see section 4.6.

1.3

Antisecretory drugs and

mucosal protectants

1.3.1 H

-receptorantagonists

1.3.2 Selective antimuscarinics

1.3.3 Chelates and complexes

1.3.4 Prostaglandin analogues

1.3.5 Proton pump inhibitors

Pepticulceration commonly involves the stomach, duo-

denum, and lower oesophagus; after gastric surgery it

involvesthe gastro-enterostomy stoma.

Healingcan be promotedby general measures, stopping

smokingand taking antacids and by antisecretory drug

treatment, but relapse is common when treatment

ceases. Nearly all duodenal ulcers and most gastric

ulcers not associated with NSAIDs are caused by

Helicobacterpylori

Themanagement of

H.pylori

infectionand of NSAID-

associatedulcers is discussed below.

Helicobacter pylori infection

Eradication of

Helicobacter pylori

reduces recurrence

ofgastric and duodenalulcers and the risk of rebleeding.

Italso causes regression of mostlocalised gastric muco-

sa-associatedlymphoid-tissue (MALT) lymphomas. The

presenceof

H.pylori

shouldbe conﬁrmed before star t-

ing eradication treatment. Acid inhibition combined

with antibacterial treatment ishighly effectivein the

eradicationof

H.pylori

; reinfection is rare. Antibiotic-

associatedcolitis is an uncommon risk.

Forinitial treatment, a one-week triple-therapy regimen

thatcomprises a proton pump inhibitor, clarithromycin,

BNF 61 1.3 Antisecretory drugs and mucosal protectants 49

Gastro-intestinalsystem

and

either

amoxicillin

metronidazole can be used.

However,if a patient has been treated with metronid-

azolefor other infections, aregimen containing a proton

pump inhibitor, amoxicillin and clarithromycin is pre-

ferred for initial therapy. If a patient has been treated

witha macrolide for otherinfections, a regimen contain-

inga proton pump inhibitor, amoxicillin and metronid-

azole is preferred for initial therapy. These regimens

eradicate

H. pylori

in about 85% of cases. There is

usually no need to continue antisecretory treatment

(with a proton pump inhibitor or H

-receptor antago-

nist), however, if the ulcer is large, or complicated by

haemorrhage or perforation, then antisecretory treat-

ment is continued for a further 3 weeks. Treatment

failure usually indicates antibacterial resistance or

poorcompliance. Resistance toamoxicillin is rare. How-

ever,resistance to clarithromycin and metronidazole is

commonand can develop during treatment.

Two-weektriple-therapy regimens offer the possibility

ofhigher eradication rates compared to one-week regi-

mens,but adverse ef fects are common and poor com-

plianceis likely to offset any possible gain.

Two-weekdual-therapy regimens using a proton pump

inhibitor and a single antibacterial are licensed, but

producelow rates of

H.pylori

eradicationand are not

recommended.

Tinidazoleis also used occasionally for

H.pylori

eradi-

cation as an alternative to metronidazole; tinidazole

should be combined with antisecretory drugs and

otherantibacterials.

Atwo-week regimen comprising a proton pump inhibi-

tor (e.g. omeprazole 20 mg twice daily)

plus

tripotass-

ium dicitratobismuthate 120 mg four times daily,

plus

tetracycline500 mg four times daily,

plus

metronidazole

400–500mg three times daily can be used for eradica-

tionfailure. Alternatively, the patient can be referred for

endoscopyand treatment basedon the results of culture

andsensitivity testing.

Forthe role of

H.pylori

eradicationtherapy in patients

starting or taking a NSAID, see NSAID-associated

Ulcers, below. For

H. pylori

eradication in patients

withdyspepsia, see also section 1.1.

Testfor Helicobacter pylori

C-Ureabreath test kits are available for the diagnosis

of gastro-duodenal infection with

Helicobacter pylori

The test involves collection ofbreath samples before

and after ingestion of an oral solution of

C-urea; the

samplesare sent for analysis by an appropriate labora-

tory.Thetest should not be performed within 4weeks of

treatment with an antibacterial or within 2 weeksof

treatment with an antisecretory drug.A speciﬁc

C-

urea breath test kit for children is available(

Helico-

bacter Test INFAI for children of the age 3–11

However,the appropriatenessof testing for

H. pylori

infectionin children has not been established.

diabactUBT

(MDE)A

Tablets

C-urea50 mg, net price 1 kit (including 1

tablet,4 breath-sample containers, straws) = £21.25

(analysisincluded), 10-kit pack (hosp. only) = £74.50

(analysisnot included)

HelicobacterTest INFAI

(Infai)A

Oralpowder

C-urea75 mg,net price 1 kit (including

4breath-sample containers, straws) = £19.20 (spec-

trometricanalysis included), 1 kit (including 2 breath

bags)= £14.20 (spectroscopic analysis not included),

50-testset = £855.00 (spectrometric analysis

included);45 mg (

HelicobacterTest INFAI for chil-

drenof the age3–11

),1 kit (including 4 breath-

samplecontainers, straws) = £19.20 (spectrometric

analysisincluded)

Pylobactell

(Torbet)A

Solubletablets

C-urea100 mg, net price 1 kit

(including6 breath-sample containers, 30-mL mixing

andadministration vial, straws) = £20.75 (analysis

included)

NSAID-associated ulcers

Gastro-intestinalbleeding and ulceration can occurwith

NSAID use (section 10.1.1). The risk of serious upper

gastro-intestinal side-effects varies betweenindividual

NSAIDs(see CSM advice, p. 632). Whenever possible,

theNSAID should be withdrawn if an ulcer occurs.

Recommendedregimens for Helicobacter pylori eradication inadults

Antibacterial

Pricefor 7-day course

Acidsuppressant

Amoxicillin Clarithromycin Metronidazole

Esomeprazole

1g twicedaily 500mg twicedaily — £15.10

20mg twicedaily

— 250mgtwice daily 400 mgtwice daily £13.32

Lansoprazole

1g twicedaily 500mg twicedaily — £6.97

30mg twicedaily

1g twicedaily — 400mg twicedaily £3.77

— 250mgtwice daily 400 mgtwice daily £5.19

Omeprazole

1g twicedaily 500mg twicedaily — £6.81

20mg twicedaily

500mg 3times daily

—

400mg 3times daily £3.62

— 250mgtwice daily 400 mgtwice daily £5.03

Pantoprazole

1g twicedaily 500mg twicedaily

—

£7.26

40mg twicedaily

— 250mgtwice daily 400 mgtwice daily £5.48

Rabeprazole

1g twicedaily 500mg twicedaily

—

£15.63

20mg twicedaily

— 250mgtwice daily 400 mgtwice daily £13.85

50 1.3 Antisecretory drugs and mucosal protectants BNF 61

Gastro-intestinalsystem

Patients at high risk of developing gastro-intestinal

complications with a NSAID includethose aged over

65years, those with a history of peptic ulcer disease or

serious gastro-intestinal complication, those taking

other medicines that increase the risk of gastro-intes-

tinalside-effects, or those with serious co-morbidity. In

thoseat risk of ulceration, a proton pump inhibitor can

be considered for protectionagainst gastric and duo-

denal ulcers associated with non-selective NSAIDs; a

-receptorantagonist such as ranitidine given at twice

theusual dose or misoprostol are alternatives.Colic and

diarrhoea may limit the dose of misoprostol. A combi-

nationof a cyclo-oxygenase-2 selective inhibitor with a

proton pump inhibitor may be more appropriatefor

thosewith a history of upper gastro-intestinal bleeding

or3 or more risk factors for gastro-intestinal ulceration,

butsee NSAIDs and Cardiovascular Events, p. 631.

NSAIDuse and

H.pylori

infectionare independent risk

factorsfor gastro-intestinal bleeding and ulceration. In

patientsalready taking aNSAID, eradication of

H.pylori

isunlikely to reduce the riskof NSAID-induced bleeding

orulceration. However, in patients with dyspepsia or a

historyof gastric or duodenal ulcer, who are

H.pylori

positive,and who areabout to start long-term treatment

with a non-selective NSAID, eradication of

H. pylori

mayreduce the overall risk of ulceration.

Ifthe

NSAIDcan be discontinued

ina patient who has

developed an ulcer, aproton pump inhibitor usually

produces the most rapid healing; alternatively, the

ulcer can be treated with a H

-receptor antagonist or

misoprostol.

treatmentwith a non-selective NSAIDneeds to con-

tinue

,the following options are suitable:

Treat ulcer with aproton pump inhibitorand on

healing continue the proton pump inhibitor(dose

notnormally reduced because asymptomatic ulcer

recurrencemay occur);

Treat ulcer with aproton pump inhibitorand on

healingswitch to misoprostol for maintenance ther-

apy (colic and diarrhoea may limit the dose of

misoprostol);

Treatulcer with a proton pump inhibitorand switch

non-selectiveNSAID to a cyclo-oxygenase-2 selec-

tive inhibitor, but see NSAIDs and Cardiovascular

Events,p. 631; on healing, continuation of the pro-

ton pump inhibitor in patients with a history of

upper gastro-intestinal bleeding may provide

furtherprotection against recurrence.

treatmentwith acyclo-oxygenase-2 selectiveinhibitor

needs to continue

, treat ulcer with a proton pump

inhibitor; on healing continuation of the proton pump

inhibitor in patients with a history of upper gastro-

intestinal bleeding may provide further protection

againstrecurrence.

1.3.1

-receptor antagonists

Histamine H

-receptor antagonists heal

gastric and

duodenal ulcers

by reducing gastric acidoutput as a

resultof histamine H

-receptorblockade; they are also

usedto relieve symptoms of

gastro-oesophagealreﬂux

disease

(section1.1). H

-receptorantagonists should not

normally be used for

Zollinger-Ellison syndrome

because proton pump inhibitors (section 1.3.5) are

moreeffective.

Maintenancetreatment with low doses for the preven-

tionof peptic ulcer disease has largely been replaced in

Helicobacter pylori

positive patients by eradication

regimens(section 1.3).

-receptor antagonists are used for the treatmentof

functionaldyspepsia

(section1.1). H

-receptorantago-

nists may be used for the treatment of

uninvestigated

dyspepsia

inpatients without alarm features.

-receptorantagonist therapy can promote healing of

NSAID-associated ulcers

(particularly duodenal) (sec-

tion1.3).

Treatmentwith a H

-receptorantagonist has not been

shownto be beneﬁcial in haematemesis and melaena,

butprophylactic use reduces the frequency of bleeding

from

gastroduodenal erosions in hepatic coma

, and

possibly in other conditions requiring intensive care.

-receptor antagonists also reduce the risk of

acid

aspiration

inobstetric patients at delivery (Mendelson’s

syndrome).

Cautions

-receptorantagonists might mask symp-

toms of gastric cancer; particular care is required in

patientspresenting with ‘alarm features’ (see p. 43), in

such cases gastric malignancy should be ruled out

beforetreatment.

Side-effects

Side-effects of the H

-receptor antago-

nists include diarrhoea, headache, and dizziness. Rash

(including erythema multiforme and toxic epidermal

necrolysis) occurs less frequently. Other side-effects

reported rarely or very rarely include hepatitis, chole-

static jaundice, bradycardia, psychiatric reactions

(including confusion, depression, and hallucinations)

particularlyin the elderly or the very ill, blood disorders

(includingleucopenia, thrombocytopenia, and pancyto-

penia), art hralgia, and myalgia. Gynaecomastia and

impotence occur occasionally with cimetidine and

there are isolated reports with the other H

-receptor

antagonists.

Interactions

Cimetidine retards oxidative hepatic

drugmetabolism by binding to microsomal cytochrome

P450. It should be avoided in patients stabilised on

warfarin, phenytoin, and theophylline (or aminophyl-

line), but other interactions (see Appendix 1) may be

of less clinical relevance.Famotidine, nizatidine, and

ranitidinedo not share the drug metabolism inhibitory

propertiesof cimetidine.

CIMETIDINE

Indications

benigngastric and duodenal ulceration,

stomalulcer, reﬂux oesophagitis, other conditions

wheregastric acid reduction is beneﬁcial (see notes

aboveand section 1.9.4)

Cautions

seenotes above; interactions: Appendix 1

(histamineH

-antagonists)and notes above

Hepaticimpairment

increasedrisk of confusion;

reducedose

Renalimpairment

reducedose; 200 mg 4 times daily

ifeGFR 30–50 mL/minute/1.73 m

;200 mg 3 times

dailyif eGFR 15–30 mL/minute/1.73m

;200 mg

twicedaily if eGFR less than 15 mL/minute/1.73m

;

occasionalrisk of confusion

Pregnancy

manufactureradvises avoid unless essen-

tial

Breast-feeding

signiﬁcantamount present in milk—

notknown to be harmful but manufacturer advises

avoid

BNF 61 1.3.1 H

-receptor antagonists 51

Gastro-intestinalsystem

Side-effects

seenotes above; also malaise;

lesscom-

monly

tachycardia;

rarely

interstitialnephritis;

very

rarely

pancreatitis,galactorrhoea, vasculitis, alopecia

Dose

. 400mg twice daily (with breakfast and at night)

800mg at night (benign gastric and duodenal ulcer-

ation)for at least 4 weeks (6 weeks in gastric ulcer-

ation,8 weeks in NSAID-associated ulceration); when

necessarythe dose may be increased to 400 mg 4

timesdaily;

INFANTunder 1 year 20 mg/kg daily in

divideddoses has been used;

CHILD1–12 years, 25–

30mg/kg daily in divideddoses; max. 400 mg 4 times

daily

Maintenance,400 mg at night

400mg morning and

night

. Reﬂuxoesophagitis, 400 mg 4 times daily for 4–8

weeks

. Prophylaxisof stress ulceration, 200–400mg every 4–

6hours

. Gastricacid reduction (prophylaxis of acid aspiration;

donot use syrup), obstetrics 400 mgat start of labour,

thenup to 400 mg every 4 hours if required (max.

2.4g daily); surgical procedures 400 mg 90–120 min-

utesbefore induction of general anaesthesia

. Short-bowelsyndrome, 400 mg twice daily (with

breakfastand at bedtime) adjusted according to

response

. Toreduce degradation of pancreatic enzyme supple-

ments,0.8–1.6 g daily in 4 divided doses 1–1½ hours

beforemeals

Cimetidine(Non-proprietary) A

Tablets

,cimetidine 200 mg, net price 60-tab pack =

£9.08;400 mg, 60-tab pack = £7.61; 800 mg, 30-tab

pack= £22.86

Oralsolution

,cimetidine 200 mg/5mL, net price

300mL = £14.56

Excipients

mayinclude propylene glycol (see Excipients, p.2)

Cimetidinecan be sold to the public for adults and children

over16 years (provided packs do not contain more than 2

weeks’supply) for the short-term symptomatic relief of

heartburn,dyspepsia, and hyperacidity (max. single dose

200mg, max. daily dose 800 mg), and for the prophylactic

managementof nocturnal heartburn (single night-time dose

100mg)

Tagamet

(Chemidex)A

Tablets

,all green, f/c, cimetidine 200 mg, net price

120-tabpack = £19.58; 400 mg, 60-tab pack =£22.62;

800mg, 30-tab pack = £22.62

Syrup

,orange, cimetidine 200 mg/5mL. Net price

600mL = £28.49

Excipients

includepropylene glycol 10%, (see Excipients, p.2)

FAMOTIDINE

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(histamineH

-antagonists)and notes above

Renalimpairment

usenormal dose every 36–48

hoursor use half normal dose if eGFR less than

50mL/minute/1.73m

;seizures reported very rarely

Pregnancy

manufactureradvises avoid unless poten-

tialbeneﬁt outweighs risk

Breast-feeding

presentin milk—not known to be

harmfulbut manufacturer advises avoid

Side-effects

seenotes above; also constipation;

less

commonly

drymouth, nausea, vomiting, ﬂatulence,

tastedisorders, anorexia, fatigue;

veryrarely

chest

tightness,interstitial pneumonia, seizures, paraes-

thesia

Dose

. Benigngastric and duodenal ulceration, treatment,

40mg at night for 4–8 weeks; maintenance (duodenal

ulceration),20 mg at night

. Reﬂuxoesophagitis, 20–40 mg twice daily for 6–

12weeks; maintenance, 20 mg twice daily

CHILDnot recommended

Famotidine(Non-proprietary) A

Tablets

,famotidine 20 mg, net price 28-tab pack =

£4.47;40 mg, 28-tab pack = £5.64

Famotidinecan be sold to the public for adults and children

over16 years (provided packs do not contain more than 2

weeks’supply) for the short-term symptomatic relief of

heartburn,dyspepsia, and hyperacidity, and for the preven-

tionof these symptoms when associated with consumption

offood or drink includingwhen they cause sleep disturbance

(max.single dose 10 mg, max. daily dose 20 mg)

Pepcid

(MSD)A

Tablets

,f/c, famotidine 20 mg (beige), net price 28-

tabpack = £13.37; 40 mg (brown), 28-tab pack =

£25.40

NIZATIDINE

Indications

seeunder Dose

Cautions

seenotes above; also avoid rapid intra-

venousinjection (risk of arrhythmias and postural

hypotension);interactions: Appendix 1 (histamine

-antagonists)and notes above

Hepaticimpairment

manufactureradvises caution

Renalimpairment

usehalf normal dose if eGFR 20–

50mL/minute/1.73m

;use one-quarter normal dose

ifeGFR less than 20 mL/minute/1.73 m

Pregnancy

manufactureradvises avoid unless essen-

tial

Breast-feeding

amounttoo small to be harmful

Side-effects

seenotes above; also sweating;

rarely

nausea,fever, vasculitis, hyperuricaemia

Dose

. Bymouth, benign gastric, duodenal or NSAID-asso-

ciatedulceration, treatment, 300 mg in the evening

150mg twice daily for 4–8 weeks; maintenance,

150mg at night

Gastro-oesophagealreﬂux disease, 150–300 mg twice

dailyfor up to 12 weeks

. Byintravenous infusion, for short-term use in peptic

ulceras alterna tive to oral route (for hospital inpati-

ents),by intermittent intravenous infusionover 15

minutes,100 mg 3 times daily,

bycontinuous

intravenousinfusion, 10 mg/hour; max. 480 mg daily

CHILDnot recommended

Nizatidine(Non-proprietary) A

Capsules

,nizatidine 150 mg, net price 30-cap pack =

£12.04;300 mg, 30-cap pack = £14.28

Nizatidinecan be sold to the public for the prevention and

treatmentof symptoms of food-related heartbur n and meal-

inducedindigestion in adults and children over 16 years;

max.single dose 75 mg, max. daily dose 150mg for max. 14

days

Axid

(Flynn)A

Capsules

,nizatidine 150 mg (pale yellow/dark yel-

low),net price 28-cap pack (hosp. only) = £6.87, 30-

cappack = £7.97; 300 mg (pale yellow/brown), 30-

cappack = £15.80

Injection

,nizatidine 25 mg/mL. For dilution and use

asan intravenous infusion. Net price 4-mL amp =

£1.14

52 1.3.1 H

-receptor antagonists BNF61

Gastro-intestinalsystem

RANITIDINE

Indications

seeunder Dose, other conditions where

reductionof gastric acidity is beneﬁcial (see notes

aboveand section 1.9.4)

Cautions

seenotes above; also acute porphyria;

interactions:Appendix 1 (histamine H

-antagonists)

andnotes above

Renalimpairment

usehalf normal dose if eGFR less

than50 mL/minute/1.73 m

Pregnancy

manufactureradvises avoid unless essen-

tial,but not known to be harmful

Breast-feeding

signiﬁcantamount present in milk,

butnot known to be harmful

Side-effects

seenotes above;

lesscommonly

blurred

vision;also reported pancreatitis, involuntary move-

mentdisorders, interstitial nephritis, alopecia

Dose

. Bymouth, benign gastric and duodenal ulceration,

chronicepisodic dyspepsia,

ADULTand CHILD over 12

years,150 mg twice daily

300mg at night for 4–8

weeksin benign gastric and duodenal ulceration, up

to6 weeks in chronic episodic dyspepsia, and up to 8

weeksin NSAID-associated ulceration (in duodenal

ulcer300 mg can be given twice daily for 4 weeks to

achievea higher healing rate);

CHILD3–12 years,

(benigngastric and duodenal ulceration) 2–4 mg/kg

(max.150 mg) twice daily for 4–8 weeks

Prophylaxisof NSAID-associated gastric or duodenal

ulcer[unlicensed dose],

ADULTand CHILD over 12

years,300 mg twice daily

Gastro-oesophagealreﬂux disease,

ADULTand CHILD

over12 years, 150 mg twice daily

300mg at night

forup to 8 weeks or if necessar y 12 weeks (moderate

tosevere, 600 mg daily in 2–4 divided doses for up to

12weeks); long-ter m treatment of healed gastro-

oesophagealreﬂux disease, 150 mg twice daily;

CHILD

3–12years, 2.5–5 mg/kg (max. 300 mg) twice daily

Gastricacid reduction (prophylaxis of acid aspiration)

inobstetrics,

ADULTandCHILD over12 years, by mouth,

150mg atonset of labour, then every 6 hours; surgical

procedures,by intramuscular

slowintravenous

injection,50 mg 45–60 minutes before induction of

anaesthesia(intravenous injection diluted to 20 mL

andgiven over at least 2 minutes), or by mouth,

150mg 2 hours before induction of anaesthesia and

alsowhen possible on the preceding evening

. Byintramuscular injection, 50 mg every 6–8 hour s

. Byslow intravenous injection,

ADULTand CHILD over

12years, 50 mg diluted to 20 mL and given over at

least2 minutes; may be repeated every 6–8 hours

. Prophylaxisof stress ulceration [unlicensed dose],

ADULTand CHILD over 12 years, by slow intravenous

injectionover at least 2 minutes, 50 mg diluted to

20mL every 8 hours (may be changed to 150 mg

twicedaily by mouth when oral feeding commences)

Ranitidine(Non-proprietary) A

Tablets

,ranitidine (as hydrochloride) 150 mg, net

price60-tab pack = £1.97; 300 mg, 30-tab pack =

£2.17

Brandsinclude

Ranitic

Effervescenttablets

,ranitidine (as hydrochloride)

150mg, net price 60-tab pack = £18.04; 300 mg, 30-

tabpack = £17.03. Label: 13

Excipients

mayinclude sodium (check with supplier)

Oralsolution

,ranitidine (as hydrochloride) 75 mg/

5mL, net price 100 mL = £7.44, 300 mL = £19.61

Excipients

mayinclude alcohol (check with supplier)

Note

Ranitidine can be sold to the public for adults and

childrenover 16 years (provided packs do not contain more

than2 weeks’ supply) for the short-term symptomatic relief of

heartburn,dyspepsia, and hyperacidity, and for the prevention

ofthese symptoms when associated with consumption of food

ordrink (max. single dose 75 mg, max. daily dose 300 mg)

Injection

,ranitidine (as hydrochloride) 25 mg/mL,

netprice 2-mL amp = 54p

Zantac

(GSK)A

Tablets

,f/c, ranitidine (as hydrochloride) 150 mg, net

price60-tab pack = £1.30; 300 mg, 30-tab pack =

£1.30

Syrup

,sugar-free, ranitidine (as hydrochloride)

75mg/5mL, net price 300 mL = £20.76

Excipients

includealcohol 8%

Injection

,ranitidine (as hydrochloride) 25 mg/mL,

netprice 2-mL amp = 57p

1.3.2

Selective antimuscarinics

Pirenzepine is a selective antimuscarinic drug which

was used for the treatment of gastric and duodenal

ulcers.It has been discontinued.

1.3.3

Chelates and complexes

Tripotassiumdicitratobismuthate isa bismuth chelate

effectivein healing gastric and duodenal ulcers. For the

role of tripotassium dicitratobismuthate in a

Helico-

bacter pylori

eradication regimen for those who have

notresponded to ﬁrst-line regimens, see section 1.3.

The bismuth content of tripotassium dicitratobismuth-

ateis low but absorption has been reported; encephalo-

pathy(described with older high-dose bismuth prepara-

tions)has not been reported.

Sucralfatemay act by protectingthe mucosa from acid-

pepsin attack in gastric and duodenal ulcers. It is a

complexof aluminium hydroxide andsulphated sucrose

but has minimal antacid properties. It should be used

with caution in patients underintensive care (impor-

tant:reports of bezoar formation, seeBezoar Formation

below)

TRIPOTASSIUM

DICITRATOBISMUTHATE

Indications

benigngastric and duodenal ulceration;

seealso

Helicobacterpylori

infection,section 1.3

Cautions

seenotes above; interactions: Appendix 1

(tripotassiumdicitratobismuthate)

Renalimpairment

avoidin severe impairment

Pregnancy

manufactureradvises avoid on theoretical

grounds

Breast-feeding

noinformation available

Side-effects

maydarken tongue and blacken faeces;

lesscommonly

nausea,vomiting, diarrhoea, consti-

pation,rash, and pruritus reported

BNF 61 1.3.2 Selective antimuscarinics 53

Gastro-intestinalsystem

De-Noltab

(Astellas)

Tablets

,f/c, tripotassium dicitratobismuthate120 mg,

netprice 112-tab pack= £5.09. Counselling,see below

Electrolytes

2mmol/tablet

Dose

2tablets twice daily

1tablet 4 times daily; taken for 28

daysfollowed by further 28 days if necessar y; maintenance not

indicatedbut course may be repeated after interval of 1 month;

CHILDnot recommended

Counselling

Tobe swallowed with half a glass of water; twice-

dailydosage to be taken 30 minutes before breakfast and main

eveningmeal; four-times-daily dosage to be taken as follows: one

dose30 minutes before breakfast, midday meal and main evening

meal,and one dose 2 hours after main evening meal; milk should

notbe drunk by itself during treatment but small quantities may

betaken in tea or coffee or on cereal; antacids, fruit, or fruit juice

shouldnot be taken half an hour before or after a dos e; may

darkentongue and blacken faeces

SUCRALFATE

Indications

seeunder Dose

Cautions

administrationof sucralfate and enteral

feedsshould be separated by 1 hour; interactions:

Appendix1 (sucralfate)

Bezoar formation

Followingreports of bezoar formation

associatedwith sucralfate, caution is advised in seriously ill

patients,especially those receiving concomitant enteral

feedsor those with predisposing conditions such as delayed

gastricemptying

Renalimpairment

usewith caution; aluminium is

absorbedand may accumulate

Pregnancy

noevidence of harm; absor ption from

gastro-intestinaltract negligible

Breast-feeding

amountprobably too small to be

harmful

Side-effects

constipation;

lessfrequently

diarrhoea,

nausea,indigestion, ﬂ atulence, gastric discomfort,

backpain, dizziness, headache, drowsiness, bezoar

formation(see above), dry mouth and rash

Dose

. Benigngastric and duodenal ulceration and chronic

gastritis,

ADULTandCHILD over 15years, 2 g twice daily

(onrising and at bedtime)

1g 4 times daily 1 hour

beforemeals andat bedtime, taken for 4–6weeks or in

resistantcases up to 12 weeks; max. 8 g daily

. Prophylaxisof stress ulceration,

ADULTand CHILD over

15years, 1 g 6 times daily; max. 8 g daily

CHILDunder 15 years see

BNFfor Children

Antepsin

(Chugai)A

Tablets

,scored, sucralfate 1g, net price 50-tab pack =

£5.77.Label: 5

Note

Crushedtablets may be dispersed in water

Suspension

,sucralfate, 1 g/5 mL, net price 250 mL

(aniseed-and caramel-ﬂavoured) = £5.77. Label: 5

1.3.4

Prostaglandin analogues

Misoprostol, a synthetic prostaglandin analogue has

antisecretoryand protective properties,promoting heal-

ing of

gastric and duodenal ulcers

. It can prevent

NSAID-associatedulcers, its usebeing most appropriate

forthe frail or very elderly from whom NSAIDs cannot

bewithdrawn.

Forcomment on the use of misoprostol to induce abor-

tionor labour [unlicensed indications], seesection 7.1.1.

MISOPROSTOL

Indications

seenotes above and under Dose

Cautions

conditionswhere hypotension might preci-

pitatesevere complications (e.g. cerebrovascular dis-

ease,cardiovascular disease)

Contra-indications

planningpregnancy (important:

seeWomen of Childbearing Age, and also Pregnancy,

below)

Women of childbearing age

Manufacturer advises that

misoprostolshould not be used in women of childbearing

ageunless the patient requires non-steroidal anti-inﬂamm-

atory(NSAID) therapy and is at high risk of complications

fromNSAID-inducedulceration. In such patients itis advised

thatmisoprostol should only be used if the patient takes

effectivecontraceptive measures

andhas been advised ofthe

risksof takingmisoprostol if pregnant

Pregnancy

avoid—potentuterine stimulant (has been

usedto induce abortion) and may be teratogenic;

important:see also Women of Childbearing Age,

above

Breast-feeding

noinformation available—manufac-

tureradvises avoid

Side-effects

diarrhoea(may occasionally be severe

andrequire withdrawal, reduced by giving single

dosesnot exceeding 200 micrograms and by avoiding

magnesium-containingantacids); also reported:

abdominalpain, dyspepsia, ﬂatulence, nausea and

vomiting,abnormal vaginal bleeding (including inter-

menstrualbleeding, menorrhagia, and postmenopau-

salbleeding), rashes, dizziness

Dose

. Benigngastric and duodenal ulceration and NSAID-

associatedulceration,

ADULTover 18 years, 800 micr-

ogramsdaily (in 2–4 divided doses) with breakfast (or

mainmeals) and at bedtime; treatment should be

continuedfor at least 4 weeks and may be continued

forup to 8 weeks if required

. Prophylaxisof NSAID-induced gastric and duodenal

ulcer,

ADULTover 18 years, 200 micrograms 4 times

daily(if not tolerated, reduced to 200 micrograms2–3

timesdaily, but less effective)

Cytotec

(Pharmacia)A

Tablets

,scored, misoprostol 200 micrograms, net

price60-tab pack = £10.03. Label: 21

Withdiclofenac or naproxen

Section10.1.1

1.3.5

Proton pump inhibitors

Protonpump inhibitors inhibit gastric acid secretion by

blockingthe hydrogen-potassiumadenosine triphospha-

taseenzyme system (the ‘proton pump’) of the gastric

parietalcell. Proton pump inhibitors are ef fective short-

term treatments for

gastric

and

duodenalulce rs

; they

arealso used in combination with antibacterials for the

eradicationof

Helicobacterpylori

(seep. 50 for speciﬁc

regimens). Following endoscopic treatment of severe

pepticulcer bleeding, an intravenous, high-dose proton

pump inhibitor reduces the risk of rebleeding and the

needfor surgery.Proton pump inhibitors can be usedfor

the treatment of

dyspepsia

and

gastro-oesophageal

reﬂuxdisease

(section1.1).

Protonpump inhibitors are also used for the prevention

andtreatment of NSAID-associatedulcers (see p. 50). In

patientswho need tocontinue NSAID treatment after an

54 1.3.4 Prostaglandin analogues BNF 61

Gastro-intestinalsystem

ulcer has healed, the dose of proton pump inhibitor

shouldnormally not be reduced because asymptomatic

ulcerdeterioration may occur.

A proton pump inhibitorcan be used to reduce the

degradationof pancreatic enzyme supplements (section

1.9.4)in patients with cystic ﬁbrosis. They can also be

used to control excessive secretion of gastric acidin

Zollinger–Ellison syndrome

; high doses are often

required.

Cautions

Protonpump inhibitors may mask the symp-

toms of gastric cancer; particular care is required in

those presenting with ‘alarm features’ (see p.43), in

such cases gastric malignancy should be ruled out

beforetreatment.

Side-effects

Side-effects of the proton pump inhi-

bitors include gastro-intestinal disturbances (including

nausea,vomiting, abdominal pain,ﬂ atulence,diar rhoea,

constipation),and headache. Less frequent side-ef fects

includedry mouth, peripheral oedema, dizziness, sleep

disturbances,fatigue, paraesthesia, arthralgia, myalgia,

rash,and pr uritus. Other side-effects reported rarely or

veryrarely include taste disturbance, stomatitis, hepat-

itis, jaundice, hypersensitivity reactions (including

anaphylaxis,bronchospasm), fever, depression, halluci-

nations,confusion, gynaecomastia, interstitial nephritis,

hyponatraemia, blood disorders (including leucopenia,

leucocytosis, pancytopenia, thrombocytopenia), visual

disturbances, sweating, photosensitivity, alopecia, Ste-

vens-Johnsonsyndrome, and toxic epider mal necroly-

sis.By decreasinggastric acidity, protonpump inhibitors

may increase the risk of gastro-intestinal infections

(including

Clostridiumdifﬁcile

infection).

ESOMEPRAZOLE

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(protonpump inhibitors)

Hepaticimpairment

insevere hepatic impairment

max.20 mg daily(

CHILD1–12 years max. 10mg daily);

forsevere peptic ulcer bleeding in severe hepatic

impairment,initial intravenous infusion of80 mg, then

bycontinuous intravenous infusion, 4 mg/hour for 72

hours

Renalimpairment

manufactureradvises caution in

severerenal insufﬁciency

Pregnancy

manufactureradvises caution—no infor-

mationavailable

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

seenotes above

Dose

. Bymouth duodenal ulcer associated with

Helico-

bacterpylori

,see eradication regimens on p. 50

NSAID-associatedgastric ulcer,

ADULTover 18 years,

20mg once daily for 4–8 weeks; prophylaxis in

patientswith an increased risk of gastroduodenal

complicationswho require continued NSAID treat-

ment,20 mg daily

Gastro-oesophagealreﬂux disease (in the presence of

erosivereﬂux oesophagitis),

ADULTand CHILD over 12

years,40 mg once daily for 4 weeks, continued for

further4 weeks if not fully healed or symptoms

persist;maintenance 20 mg daily;

CHILD1–12 years,

body-weight10–20 kg, 10 mg once daily for 8 weeks;

body-weightover 20 kg, 10–20 mg once daily for 8

weeks

Symptomatictreatment of gastro-oesophageal reﬂux

disease(in the absence of oesophagitis),

ADULTand

CHILDover 12 years, 20 mg once daily for up to 4

weeks,then 20 mg daily when required;

CHILD1–12

years,body-weight over 10 kg, 10mg once daily for

upto 8 weeks

Zollinger–Ellisonsyndrome,

ADULTover 18 years,

initially40 mg twice daily, adjusted according to

response;usual range 80–160 mg daily (above 80 mg

in2 divided doses)

. Byintravenous injection overat least 3 minutes

intravenousinfusion,

ADULTover 18 years, gastro-

oesophagealreﬂux disease, 40 mg once daily; symp-

tomaticreﬂux disease without oesophagitis, treat-

mentof NSAID-associated gastric ulcer,prevention of

NSAID-associatedgastric or duodenal ulcer, 20 mg

daily;continue until oral administration possible

. Severepeptic ulcer bleeding (following endoscopic

treatment),

ADULTover 18 years, initial intravenous

infusionof 80 mg over 30 minutes, then by continu-

ousintravenous infusion 8mg/hour for 72 hours,

thenby mouth 40mg once daily for 4 weeks

Nexium

(AstraZeneca)A

Tablets

,f/c, esomeprazole (as magnesium trihydrate)

20mg (light pink), net price 28-tab pack = £18.50;

40mg (pink), 28-tab pack = £25.19. Counselling,

administration

Counselling

Donot chewor crush tablets, swallow whole

dispersein water

Granules

,yellow, e/c, esomeprazole (as magnesium

trihydrate)10 mg/sachet, net price 28-sachet pack =

£25.19.Label: 25, counselling, administration

Counselling

Dispersethe contentsof each sachet in approx.

15mLwater. Stir and leave to thicken for a few minutes; stir

againbefore administration and use within 30 minutes; rinse

containerwith 15 mL water to obtain full dose; can be

administeredthrough nasogastric or gastric tube

Injection

,powder for reconstitution, esomeprazole

(assodium salt), net price 40-mg vial = £3.13

Withnaproxen

Section10.1.1

LANSOPRAZOLE

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(protonpump inhibitors)

Hepaticimpairment

usehalf normal dose in moder-

ateto severe liver disease

Pregnancy

manufactureradvises avoid

Breast-feeding

avoidunless essential—present in

milkin

animal

studies

Side-effects

seenotes above; also glossitis, pan-

creatitis,anorexia, restlessness, tremor, impotence,

petechiae,and pur pura;

veryrarely

colitis,raised

serumcholesterol or triglycerides

Dose

. Benigngastric ulcer, 30 mg daily in the morning for 8

weeks

. Duodenalulcer, 30 mg daily in the morning for 4

weeks;maintenance 15 mg daily

. NSAID-associatedduodenal or gastric ulcer, 30 mg

oncedaily for4 weeks, continued for further4 weeks if

notfully healed; prophylaxis, 15–30 mg once daily

. Eradicationof

Helicobacterpylori

associatedwith

duodenalulcer or ulcer-like dyspepsia, see eradica-

tionregimens on p. 50

BNF 61 1.3.5 Proton pump inhibitors 55

Gastro-intestinalsystem

. Zollinger-Ellisonsyndrome (and other hypersecretory

conditions),initially 60 mg once daily adjusted

accordingto response; daily doses of 120 mg or more

givenin two divided doses

. Gastro-oesophagealreﬂux disease, 30 mg daily in the

morningfor 4 weeks, continued for further 4 weeks if

notfully healed; maintenance 15–30 mg daily

. Acid-relateddyspepsia, 15–30 mg daily in the morn-

ingfor 2–4 weeks

CHILDunder 18 years see

BNFfor Children

Note

Lansoprazole doses in BNF may differ from those in

productliterature

Lansoprazole(Non-proprietary) A

Capsules

,enclosing e/c granules, lansoprazole

15mg, net price 28-cap pack = £1.44; 30 mg, 28-cap

pack= £2.23. Label: 5, 22, 25

Dentalprescribing onNHS

Lansoprazolecapsules may be

prescribed

Zoton

(Wyeth)A

FasTab

(=orodispersible tablet), lansoprazole

15mg, net price 28-tab pack = £2.99; 30 mg, 28-tab

pack= £5.50. Label: 5, 22, counselling, administration

Excipients

includeaspartame (section 9.4.1)

Counselling

Tabletsshould be placed on the tongue, allowed to

disperseand swallowed, or may be swallowed whole with a glass

ofwater.Alter natively,tablets can be dispersed in a small amount

ofwater and administered by an oral syringe or nasogastric tube

OMEPRAZOLE

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(protonpump inhibitors)

Hepaticimpairment

notmore than 20 mg daily

shouldbe needed

Pregnancy

notknown to be harmful

Breast-feeding

presentin milk but not known to be

harmful

Side-effects

seenotes above; also agitation and

impotence

Dose

. Bymouth, benign gastric and duodenal ulcers, 20 mg

oncedaily for 4 weeks in duodenal ulceration or 8

weeksin gastric ulceration; in severe or recurrent

casesincrease to 40 mg daily; maintenance for

recurrentduodenal ulcer, 20 mg once daily; preven-

tionof relapse in duodenal ulcer, 10 mg daily

increasingto 20 mg once daily if symptoms return

NSAID-associatedduodenal or gastric ulcer and gas-

troduodenalerosions, 20 mg once daily for 4 weeks,

continuedfor further 4 weeks if not fully healed;

prophylaxisin patients with a histor y of NSAID-

associatedduodenal or gastric ulcers, gastroduodenal

lesions,or dyspeptic symptoms who require contin-

uedNSAID treatment, 20 mg once daily

Duodenalor benign gastric ulcer associated with

Helicobacterpylori

,see eradication regimens on

p. 50

Zollinger–Ellisonsyndrome, initially60 mg once daily;

usualrange 20–120 mg daily (above 80 mg in 2

divideddoses)

Gastricacid reduction during general anaesthesia

(prophylaxisof acid aspiration), 40 mg on the pre-

cedingevening then 40 mg 2–6 hours before surgery

Gastro-oesophagealreﬂux disease, 20 mg once daily

for4 weeks, continued for further 4–8 weeks if not

fullyhealed; 40 mg once daily has been given for 8

weeksin gastro-oesophageal reﬂux disease refractory

toother treatment; maintenance 20 mg once daily

Acidreﬂux disease (long-term management), 10 mg

dailyincreasing to 20 mg once daily if symptoms

return

Acid-relateddyspepsia, 10–20 mg once daily for 2–4

weeksaccording to response

Severeulcerating reﬂux oesophagitis,

CHILDover 1

year,body-weight 10–20 kg, 10 mg once daily

increasedif necessar y to 20 mg once daily for 4–12

weeks;body-weight over 20 kg, 20 mg once daily

increasedif necessar y to 40 mg once daily for 4–12

weeks;to be initiated by hospital paediatrician

. Byintravenous injection over 5 minutes

byintra-

venousinfusion over 20–30 minutes, prophylaxis of

acidaspiration, 40 mg completed 1 hour before sur-

gery

Benigngastric ulcer, duodenal ulcer and gastro-

oesophagealreﬂux, 40 mg once daily until oral

administrationpossible

. Majorpeptic ulcer bleeding (following endoscopic

treatment)[unlicensed indication], initial intravenous

infusionof 80 mg over 40–60 minutes, then by con-

tinuousintravenous infusion, 8mg/hour for 72 hours

(thenchange to oral therapy)

Counselling

Swallowwhole,

disperse

MUPS

tablets in

water,

mixcapsule contents or

MUPS

tabletswith fruit

juiceor yoghurt. Preparationsconsisting of an e/c tablet within

acapsule should not be opened

Omeprazole(Non-proprietary) A

Capsules

,enclosing e/c granules, omeprazole 10mg,

netprice 28-cap pack = £1.81; 20 mg, 28-cap pack =

£1.92;40 mg, 7-cap pack = £1.95, 28-cap pack =

£21.65.Counselling, administration

Dental prescribingon NHS

Gastro-resistantomeprazole

capsulesmay be prescribed

Capsules

,enclosing e/c tablet, omeprazole 10 mg,

netprice 28-cap pack = £1.81; 20 mg, 28-cap pack =

£1.92.Counselling, administration

Brandsinclude

Mepradec

Dental prescribingon NHS

Gastro-resistantomeprazole

capsulesmay be prescribed

Tablets

,e/c, omeprazole 10 mg, net price 28-tab

pack=£5.84; 20 mg, 28-tab pack= £5.71; 40 mg,7-tab

pack= £5.15. Label: 25

Intravenousinfusion

,powder for reconstitution,

omeprazole(as sodium salt), net price 40-mg vial =

£5.18

Omeprazole10 mg tablets can be sold to the public for the

short-termrelief of reﬂux-like symptoms (e.g. heartburn) in

adultsover 18 years, max. daily dose 20 mg for max. 4

weeks,and a pack size of 28 tablets

Losec

(AstraZeneca)A

MUPS

(multiple-unitpellet system = dispersible

tablets),f/c, omeprazole 10 mg (light pink), net price

28-tabpack = £7.75; 20 mg (pink), 28-tab pack =

£11.60;40 mg (red-brown), 7-tab pack = £5.80.

Counselling,administration

Capsules

,enclosing e/c granules, omeprazole 10 mg

(pink),net price 28-cap pack = £7.75; 20 mg (pink/

brown),28-cap pack = £11.60; 40 mg (brown), 7-cap

pack= £5.80. Counselling, administration

Intravenousinfusion

,powder for reconstitution,

omeprazole(as sodium salt), net price 40-mg vial =

£5.41

Injection

,powder for reconstitution, omeprazole (as

sodiumsalt), net price 40-mg vial (with solvent) =

£5.41

Withketoprofen

Section10.1.1

56 1.3.5 Proton pump inhibitors BNF 61

Gastro-intestinalsystem

PANTOPRAZOLE

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(protonpump inhibitors)

Hepaticimpairment

max.20 mg daily in severe

impairmentand cirrhosis—monitor liver function

(discontinueif deterioration)

Renalimpairment

max.oral dose 40 mg daily

Pregnancy

manufactureradvises avoid unless poten-

tialbeneﬁt outweighs risk—fetotoxic in

animals

Breast-feeding

manufactureradvises avoid unless

potentialbeneﬁt outweighs risk—small amount pre-

sentin milk in

animal

studies

Side-effects

seenotes above; also hyperlipidaemia,

weightchanges

Dose

. Bymouth, benign gastric ulcer, ADULT over18 years,

40–80mg daily in the morning for 4 weeks,continued

forfurther 4 weeks if not fully healed

Gastro-oesophagealreﬂux disease,

ADULTand CHILD

over12 years, 20–80 mg daily in the morning for 4

weeks,continued for further 4 weeks if not fully

healed;maintenance 20 mg daily, increased to 40 mg

dailyif symptoms return

Duodenalulcer,

ADULTover 18 years, 40–80 mg daily

inthe mor ning for 2 weeks, continued for further 2

weeksif not fully healed

Duodenalulcer associated with

Helicobacterpylori

seeeradication regimens on p. 50

Prophylaxisof NSAID-associated gastric or duodenal

ulcerin patients with an increased risk of gastroduo-

denalcomplications who require continued NSAID

treatment,

ADULTover 18 years, 20 mg daily

Zollinger–Ellisonsyndrome (and other hypersecre-

toryconditions),

ADULTover 18 years, initially 80 mg

oncedaily adjusted according to response (

ELDERLY

max.40 mg daily); daily doses above80 mg given in 2

divideddoses

. Byintravenous injection overat least 2 minutes

intravenousinfusion,

ADULTover 18 years, duodenal

ulcer,gastric ulcer, and gastro-oesophageal reﬂux,

40mg daily until oral administration can be resumed

Zollinger–Ellisonsyndrome (and other hypersecre-

toryconditions),

ADULTover 18 years, initially 80 mg

(160mg if rapid acid control required) then 80 mg

oncedaily adjustedaccording to response; daily doses

above80 mg given in 2 divided doses

Pantoprazole(Non-proprietary) A

Tablets

,e/c, pantoprazole 20 mg, net price 28-tab

pack= £1.79; 40 mg, 28-tab pack = £2.82. Label: 25

Note

Pantoprazole20mg tablets can be soldto the public for

theshort-term treatment of reﬂux symptoms(e.g. heartburn)

inadults over 18 years, max. daily dose 20 mg for max. 4

weeks

Protium

(Nycomed)A

Injection

,powder for reconstitution, pantoprazole (as

sodiumsalt), net price 40-mg vial = £5.11

RABEPRAZOLE SODIUM

Indications

seeunder Dose

Cautions

seenotes above; interactions: Appendix 1

(protonpump inhibitors)

Hepaticimpairment

manufactureradvises caution in

severehepatic dysfunction

Pregnancy

manufactureradvises avoid—no informa-

tionavailable

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

seenotes above; also cough, inﬂuenza-

likesyndrome, and rhinitis;

lesscommonly

chestpain

andnervousness;

rarely

anorexiaand weight gain

Dose

. Benigngastric ulcer, 20 mg daily in the morning for 6

weeks,continued forfurther 6 weeks if notfully healed

. Duodenalulcer, 20 mg daily in the morning for 4

weeks,continued forfurther 4 weeks if notfully healed

. Gastro-oesophagealreﬂux disease, 20 mg once daily

for4–8 weeks; maintenance 10–20 mg daily; symp-

tomatictreatment in the absence of oesophagitis,

10mg daily for up to 4 weeks, then 10 mg daily when

required

. Duodenaland benign gastric ulcer associated with

Helicobacterpylori

,see eradication regimens on

p. 50

. Zollinger–Ellisonsyndrome, initially 60 mg once daily

adjustedaccording to response (max. 120 mg daily);

dosesabove 100 mg daily given in 2 divided doses

CHILDnot recommended

Pariet

(Janssen-Cilag, Eisai) A

Tablets

,e/c, rabeprazole sodium 10 mg (pink), net

price28-tab pack = £11.56; 20 mg (yellow), 28-tab

pack= £19.55. Label: 25

1.4

Acute diarrhoea

1.4.1 Adsorbents and bulk-forming drugs

1.4.2 Antimotility drugs

Thepriority in acute diarrhoea, as in gastro-enteritis, is

theprevention or reversal of ﬂuid and electrolyte deple-

tion.This is particularly important in infants and in frail

and elderly patients. Fordetails of oral rehydration

preparations, see section 9.2.1.2. Severe depletion of

ﬂuid and electrolytes requires immediate admission to

hospitaland urgent replacement.

Antimotilitydrugs (section 1.4.2) relieve symptoms of

acutediar rhoea. They are used in the management of

uncomplicated acute diarrhoea in adults; ﬂuid and

electrolyte replacement may be necessar y in caseof

dehydration. However, antimotility drugs are not

recommendedfor acute diarrhoea in young children.

Antispasmodics(section 1.2) areoccasionally of value in

treatingabdominal cramp associated with diarrhoea but

they should not be used for primarytreatment. Anti-

spasmodics and antiemetics should be avoided in

young children with gastro-enteritisbecause they are

rarelyeffective and have troublesome side-ef fects.

Antibacterialdrugs are generally unnecessary in simple

gastro-enteritisbecause the complaint usually resolves

quicklywithout them, andinfective diarrhoeas in the UK

often have a viral cause. Systemicbacterial infection

does,however,need appropriate systemic treatment; for

drugs used in campylobacter enteritis, shigellosis, and

salmonellosis,see Table 1, section 5.1. Ciproﬂoxacin is

occasionally used for prophylaxis against travellers’

diarrhoea,but routine use is not recommended. Lacto-

bacilluspreparations have not been shown to be effec-

tive.

BNF 61 1.4 Acute diarrhoea 57

Gastro-intestinalsystem

Colestyramine (section 1.9.2), binds unabsorbedbile

saltsand provides symptomatic relief of diarrhoea fol-

lowingileal disease or resection.

1.4.1

Adsorbents and bulk-

forming drugs

Adsorbents such as kaolin are notrecommended for

acute diarrhoeas

. Bulk-for ming dr ugs, such as isp-

aghula, methylcellulose, and sterculia (section 1.6.1)

are useful in controlling diarrhoea associated with

diverticulardisease.

KAOLIN, LIGHT U

Indications

diarrhoeabut see notes above

Cautions

interactions:Appendix 1 (kaolin)

KaolinMixture, BP U

(KaolinOral Suspension)

Oralsuspension

,light kaolin or light kaolin (natural)

20%,light magnesium carbonate 5%, sodium bicarb-

onate5% in a suitable vehicle with a peppermint

ﬂavour.

Dose

10–20mL every 4 hours

1.4.2

Antimotility drugs

Antimotility drugs have arole in the managementof

uncomplicated

acute diarrhoea

in adults but not in

youngchildren; see also section 1.4. However, insevere

cases,ﬂuid and electrolyte replacement(section 9.2.1.2)

areof primary importance.

For comments on the role of antimotility drugs in

chronicbowel disorders

see section 1.5. For their role

stomacare

seesection 1.8.

Loperamide can be used for faecal incontinence [unli-

censedindication] after the underlying cause of incont-

inencehas been addressed.

CODEINEPHOSPHATE

Indications

seenotes above; cough suppression (sec-

tion3.9.1); pain (section 4.7.2)

Cautions

section4.7.2; tolerance and dependence

mayoccur with prolonged use; interactions: Appen-

dix1 (opioid analgesics)

Contra-indications

section4.7.2; also conditions

whereinhibition of peristalsis should be avoided,

whereabdominal distension develops, or in acute

diarrhoealconditions such as acute ulcerative colitis

orantibiotic-associated colitis

Hepaticimpairment

section4.7.2

Renalimpairment

section4.7.2

Pregnancy

section4.7.2

Breast-feeding

section4.7.2

Side-effects

section4.7.2

Dose

. Acutediarrhoea, ADULTand CHILD over12 years, 30mg

3–4times daily (range 15–60 mg)

Preparations

Section4.7.2

CO-PHENOTROPE

Amixture of diphenoxylate hydrochloride and atro-

pinesulphate in the mass proportions 100 parts to 1

partrespectively

Indications

adjunctto rehydration in acute diar rhoea

(butsee notes above); control of faecal consistency

aftercolostomy or ileostomy (section 1.8)

Cautions

section4.7.2; also young children are parti-

cularlysusceptible to overdosageand symptoms may

bedelayed and observation is needed for at least 48

hoursafter ingestion; presence of subclinical doses of

atropinemay give rise to atropine side-effects in

susceptibleindividuals or in overdosage (section 1.2);

interactions:Appendix 1 (antimuscarinics, opioid

analgesics)

Contra-indications

section4.7.2 and also see under

Antimuscarinics(section 1.2)

Hepaticimpairment

section4.7.2; also avoid in

jaundice

Renalimpairment

section4.7.2

Pregnancy

section4.7.2 and also see under Atropine

Sulphate(section 1.2)

Breast-feeding

maybe present in milk

Side-effects

section4.7.2 and also see under Anti-

muscarinics(section 1.2); also abdominal pain, ano-

rexia,and fever

Dose

. Seepreparations

Co-phenotrope(Non-proprietary) A

Tablets

,co-phenotrope 2.5/0.025 (diphenoxylate

hydrochloride2.5 mg, atropine sulphate 25 micr-

ograms),net price 100 = £8.95

Brandsinclude

Lomotil

Dose

initially4 tablets, followed by 2 tablets every 6 hours until

diarrhoeacontrolled; CHILD under 4 years see

BNFfor Children

4–9years 1 tablet 3 times daily,9–12 years 1 tablet 4 times daily,

12–16years 2 tablets 3 times daily, but see also notes above

Note

Co-phenotrope2.5/0.025 can besold to the public for adults

andchildren over 16 years (provided packs do not contain more

than20 tablets) as an adjunct to rehydration in acute diarrhoea

(max.daily dose 10 tablets)

LOPERAMIDEHYDROCHLORIDE

Indications

symptomatictreatment of acute diarr-

hoea;adjunct to rehydration in acute diarrhoea in

adultsand children over4 years (but see notes above);

chronicdiarrhoea in adults only

Cautions

seenotes above; interactions: Appendix 1

(loperamide)

Contra-indications

conditionswhere inhibition of

peristalsisshould be avoided, where abdominal dis-

tensiondevelops, or in conditions such as active

ulcerativecolitis or antibiotic-associated colitis

Hepaticimpairment

riskof accumulation—manufac-

tureradvises caution

Pregnancy

manufacturersadvise avoid—no informa-

tionavailable

Breast-feeding

amountprobably too small to be

harmful

Side-effects

abdominalcramps, dizziness, drowsi-

ness,and skin reactions including ur ticaria; paralytic

ileusand abdominal bloating also reported

Dose

. Acutediarrhoea, 4 mg initially followed by 2 mg after

eachloose stool for up to 5 days; usual dose 6–8 mg

daily;max. 16 mg daily;

CHILDunder 4 years not

58 1.4.1 Adsorbents and bulk-forming drugs BNF 61

Gastro-intestinalsystem

recommended;4–8 years, 1 mg 3–4 times daily for up

3days only

;8–12 years,2 mg 4 times dailyfor up to

5days

. Chronicdiarrhoea in adults, initially, 4–8 mg daily in

divideddoses, subsequently adjusted according to

responseand given in 2 divided doses for mainte-

nance;max. 16 mg daily;

CHILDunder 18 years see

BNFfor Children

. Faecalincontinence [unlicensed indication], initially

500micrograms daily,adjusted accordingto response;

max.16 mg daily in divided doses

Loperamide(Non-proprietary) A

Capsules

,loperamide hydrochloride 2 mg, net price

30-cappack = £1.07

Tablets

,loperamide hydrochloride 2mg, net price 30-

tabpack = £2.15

Brandsinclude

Norimode

Note

Loperamidecan be sold to the public, provided it is licensed

andlabelled for the treatment of acute diarrhoea in adults and

childrenover 12 years of age, or for acute diarrhoea associated with

irritablebowel syndrome (afterinitial diagnosis by a doctor) in adults

over18 years of age

Imodium

(Janssen-Cilag)A

Capsules

,green/grey, loperamide hydrochloride

2mg. Net price 30-cap pack = £1.09

Syrup

,sugar free, red, loperamide hydrochloride

1mg/5mL. Net price 100 mL = £1.17

Compoundpreparations

Imodium

Plus(McNeil)

Caplets

(=tablets), loperamide hydrochloride 2 mg,

simeticone125 mg, net price 6-tab pack = £2.27, 12-

tabpack = £3.58

Dose

acutediarrhoea with abdominal colic, initially 2 caplets

(CHILD12–18 years 1 caplet) then 1 caplet after each loose stool;

max.4 caplets daily for up to 2 days; CHILD under 12 years not

recommended

MORPHINE

Indications

seenotes above; cough in terminal dis-

ease(section 3.9.1); pain (section 4.7.2)

Cautions

seenotes above and under Mor phine Salts

(section4.7.2)

Contra-indications

seenotes above and under Mor-

phineSalts (section 4.7.2)

Hepaticimpairment

section4.7.2

Renalimpairment

section4.7.2

Pregnancy

section4.7.2

Breast-feeding

seeunder Morphine Salts (section

4.7.2)

Side-effects

seenotes above and under Morphine

Salts(section 4.7.2); sedation and the risk of depend-

enceare g reater

Dose

. Seepreparation

Kaolinand Morphine Mixture, BP U

(Kaolinand Morphine Oral Suspension)

Oralsuspension

,light kaolin or light kaolin (natural)

20%,sodium bicarbonate 5%, and chloroform and

morphinetincture 4% in a suitable vehicle. Contains

anhydrousmorphine 550–800 micrograms/10 mL.

Dose

ADULTand CHILD over12 years, 10mL every 6 hours in

water

1.5

Chronic bowel disorders

Once tumours are ruled out individual symptoms of

chronicbowel disorders need speciﬁc treatment includ-

ingdietary manipulation as well as drug treatment and

themaintenance of a liberal ﬂuid intake.

Inﬂammatory bowel disease

Chronicinﬂammatory bowel diseases include

ulcerative

colitis

and

Crohn’s disease

. Effective management

requires drug therapy, attention to nutrition, and in

severeor chronic active disease, surger y.

Aminosalicylates (balsalazide, mesalazine, olsalazine,

and sulfasalazine), corticosteroids (hydrocortisone,

beclometasone, budesonide, and prednisolone), and

drugs that affect the immune response are used in

thetreatment of inﬂammatory bowel disease.

Treatmentof acute ulcerativecolitis and Crohn’s

disease

Acutemild to moderate disease affecting the

rectum(proctitis) or the recto-sigmoid is treatedinitially

with local application of an aminosalicylate (section

1.5.1); alternatively, a local corticosteroid can be used

butit is less effective. A combination of a local amino-

salicylate and a local corticosteroid can be used for

proctitisthat doesnot respond to a local aminosalicylate

alone. Foam preparations and suppositories are espe-

ciallyuseful when patients have difﬁculty retaining liq-

uidenemas.

Diffuseinﬂammatory bowel disease ordisease that does

not respond to local therapy requiresoral treatment.

Milddisease affecting the proximal colon canbe treated

withan oral aminosalicylate alone; a combination of a

localand an oralaminosalicylate can be used in proctitis

or distal colitis. Refractory or moderate inﬂammator y

boweldisease usually requires adjunctive use of an oral

corticosteroidsuch as prednisolone (section 1.5.2) for

4–8weeks. Modiﬁed-release budesonide is licensed for

Crohn’sdisease affecting the ileum and the ascending

colon; it causes fewer systemic side-effectsthan oral

prednisolonebut may be less effective. Beclometasone

dipropionate by mouth islicensed as an adjunct to

mesalazinefor mild to moderate ulcerative colitis, but it

is not known whether it is as effective as other corti-

costeroids.

Severe inﬂammatory bowel disease or disease that is

notresponding to an oral corticosteroid requires hospi-

tal admission and treatment with an intravenous

corticosteroid (such as hydrocortisone or methyl-

prednisolone,section 6.3.2); other therapy may include

intravenousﬂuid and electrolyte replacement, and pos-

sibly parenteral nutrition. Specialist supervision is

requiredfor patients who fail to respond adequately to

these measures. Patients with severe ulcerative colitis

that has not responded to intravenous corticosteroids,

maybeneﬁt from a shor t course of intravenous ciclos-

porin [unlicensed indication] (section 1.5.3). Patients

withunresponsive or chronically active Crohn’s disease

may beneﬁt from azathioprine (section 1.5.3),

mercaptopurine (section 1.5.3), or once-weekly

methotrexate (section 1.5.3) [all unlicensed indica-

tions];these dr ugs have a slower onset of action.

Inﬂiximab (section 1.5.3) is licensed for the manage-

mentof severe active Crohn’s disease and severe ulcer-

ative colitis in patients whose condition has not

BNF 61 1.5 Chronicbowel disorders 59

Gastro-intestinalsystem

respondedadequately to treatmentwith a corticosteroid

and a conventional drug that af fects the immune

response,or who are intolerant of them.

NICEguidance

Inﬂiximaband adalimumab for Crohn’s

disease(May 2010)

Inﬂiximab or adalimumab is recommended for the

treatmentof severe active Crohn’s disease that has

not responded to conventionaltherapy (including

corticosteroids and other drugs affecting the

immune response) or when conventional therapy

cannot be used because of intoleranceor contra-

indications;inﬂiximab can also be used in a similar

wayin children over 6years of age. In adults over 18

years of age,inﬂ iximab is recommended for the

treatment of ﬁstulating Crohn’s disease that has

not responded to conventionaltherapy (including

antibacterials, drainage, and other drugs affecting

theimmune response)or when conventional therapy

cannot be used because of intoleranceor contra-

indications.

Inﬂiximab or adalimumab should be given as a

plannedcourse of treatment for 12 months or until

treatment failure, whichever is shorter.Treatment

shouldbe continued beyond 12 months only if there

is evidence of active disease—in these cases the

need for treatment should be reviewed at least

annually.If the disease relapses after stopping treat-

ment, adalimumab or inﬂiximab can be restarted

(but see Hypersensitivity Reactions under Inﬂixi-

mab,p. 66).

NICEguidance

Inﬂiximabfor subacute manifestations of

ulcerativecolitis (April 2008)

Inﬂiximabis not recommended for the treatment of

subacute manifestations of moderate to severe

activeulcerative colitis that wouldnor mallybe man-

agedin an outpatient setting.

NICEguidance

Inﬂiximabfor acute exacerbations of

ulcerativecolitis (December 2008)

Inﬂiximab is recommended as an option for the

treatment of acute exacerbationsof severe ulcer-

ativecolitis when treatment with ciclosporin is con-

tra-indicatedor inappropriate.

Adalimumab (section 1.5.3) is licensed forthe treat-

mentof severe active Crohn’s disease in patients whose

condition has not respondedadequately to treatment

with a corticosteroid and a conventional drug that

affects the immune response, or who are intolerant of

them. For inducing remission, adalimumabshould be

usedin combination with a corticosteroid, but it may be

givenalone if a corticosteroid is inappropriate or is not

tolerated. Adalimumab may also be usedfor Crohn’s

disease in patients who have relapsed while taking

inﬂiximab or who cannot tolerateinﬂ iximab because

ofhypersensitivity reactions.

Maintenance of remission of acute ulcerative

colitis and Crohn’s disease

Smoking cessation

(section 4.10.2) reduces the risk of relapse in Crohn’s

disease and should be encouraged. Aminosalicylates

areefﬁcacious in the maintenance of remission of ulcer-

ativecolitis, but there is no evidence of efﬁcacy in the

maintenanceof remission of Crohn’s disease. Corticos-

teroids are not suitable for maintenance treatment

because of their side-effects. In resistant or frequently

relapsingcases either azathioprine (section1.5.3) [unli-

censed indication] or mercaptopurine (section 1.5.3)

[unlicensed indication], given underclose supervision

maybe helpful. Methotrexate (section 1.5.3) is tried in

Crohn’sdisease if azathioprine or mercaptopurine can-

notbe used [unlicensed indication]. Maintenance ther-

apy with inﬂiximab should be considered for patients

withCrohn’sdisease or ulcerative colitis who respond to

theinitial induction course of inﬂiximab; ﬁxed-interval

dosingis superior to inter mittent dosing. Adalimumab

islicensed for maintenance therapy in Crohn’s disease.

FistulatingCrohn’s disease

Treatmentmay not be

necessary for simple,asymptomatic perianal ﬁstulas.

Metronidazole (section 5.1.11) or ciproﬂoxacin (sec-

tion 5.1.12) can improve symptoms of ﬁstulating

Crohn’s disease but complete healing occurs rarely

[unlicensed indication]. Metronidazole by mouth is

used at a dose of 10–20 mg/kg daily in divided doses

(usualdose 400–500mg 3 times daily); it is usuallygiven

for 1 month but no longer than 3 months because of

concernsabout peripheral neuropathy. Ciproﬂoxacin by

mouth is given at a dose of 500 mg twice daily. Other

antibacterials should be givenif speciﬁcally indicated

(e.g.sepsis associated with ﬁstulas andperianal disease)

and for managing bacterial overgrowth in the small

bowel. Fistulas may also requiresurgical exploration

andlocal drainage.

Either azathioprine or mercaptopur ine is used as a

second-linetreatment for ﬁstulating Crohn’sdisease and

continued for maintenance [unlicensed indication].

Inﬂiximabis used for ﬁstulating Crohn’s disease refrac-

toryto conventional treatments; ﬁxed-interval dosing is

superior to intermittent dosing.Maintenance therapy

withinﬂ iximab should be considered for patients who

respond to the initial induction course of inﬂiximab.

Adalimumab can be used if there is intolerance to

inﬂiximab[unlicensed indication]

Adjunctivetreatment of inﬂammatorybowel dis-

ease

Dueattention should be paid to diet; high-ﬁbre or

low-residuediets should be used as appropriate.

Antimotilitydrugs such as codeine and loperamide, and

antispasmodicdrugs may precipitate paralytic ileus and

megacolonin active ulcerative colitis; treatment of the

inﬂammationis more logical. Laxativesmay be required

inproctitis. Diarrhoea resulting from the loss of bile-salt

absorption(e.g. in terminal ileal disease or bowel resec-

tion)may improve with colestyramine (section 1.9.2),

whichbinds bile salts.

Clostridium difﬁcile infection

Clostridiumdifﬁcile

infectionis caused by colonisation

ofthe colon with

Clostridiumdifﬁcile

andproduction of

toxin.It often follows antibiotic therapyand is usually of

acuteonset, but may become chronic. It is a particular

hazardof ampicillin, amoxicillin, co-amoxiclav, second-

and third-generation cephalosporins, clindamycin, and

quinolones, but few antibiotics are free of this side-

effect. Oral metronidazole (see section 5.1.11) or oral

vancomycin (see section 5.1.7) are used as speciﬁc

treatment;vancomycin may be preferred for very sick

patients. Metronidazole can be given by intravenous

infusionif oral treatment is inappropriate.

60 1.5 Chronic bowel disorders BNF 61

Gastro-intestinalsystem

Diverticular disease

Diverticular disease is treated with a high-ﬁbre diet,

bran supplements, and bulk-for ming drugs (section

1.6.1).Antispasmodics mayprovide symptomatic relief

whencolic is aproblem (section 1.2). Antibacterials are

used only when thediverticula in the intestinal wall

becomeinfected. Antimotility drugs which slow intes-

tinal motility, e.g. codeine, diphenoxylate,and loper-

amide could possibly exacerbate the symptoms of

diverticulardisease and are contra-indicated.

Irritable bowel syndrome

Irritable bowel syndrome can present with pain,con-

stipation,or diarrhoea. In some patients there may be

important psychological aggravating factors which

respondto reassurance and possibly speciﬁc treatment

e.g.with an antidepressant.

The ﬁbre intake of patients with irritable bowel

syndromeshould be reviewed. If an increase in dietary

ﬁbre is required, soluble ﬁbre (e.g. ispaghula husk,

sterculia,or oats) is recommended; insoluble ﬁbre (e.g.

bran)may exacerbate symptoms and its use should be

discouraged. A laxative (section 1.6) can beused to

treat constipation. An osmotic laxative, such as a

macrogol, is preferred; lactulosemay cause bloating.

Stimulant laxatives should be avoided or used only

occasionally. Loperamide (section 1.4.2) mayrelieve

diarrhoea and antispasmodic drugs (section 1.2) may

relieve pain. Opioids with a central action, such as

codeine,are better avoided because of the risk of dep-

endence.

Atr icyclicantidepressant (section 4.3.1) can be used

forabdominal pain ordiscomfort [unlicensed indication]

inpatients who have not responded to laxatives, loper-

amide,or antispasmodics. Low doses of a tricyclic anti-

depressantare used (e.g. amitriptyline, initially 5–10 mg

eachnight, increased if necessar y in steps of 10 mg at

intervalsof at least2 weeks to max. 30mg each night). A

selectiveserotonin reuptake inhibitor (section 4.3.3)

may be considered in those who do not respond to a

tricyclicantidepressant [unlicensed indication].

Malabsorption syndromes

Individual conditions need speciﬁc management and

also general nutritional consideration. Coeliac disease

(glutenenteropathy) usuallyneeds a gluten-free diet and

pancreaticinsuf ﬁciency needs pancreatin supplements

(section1.9.4)

For further information on foods for special diets

(ACBS),see Appendix 7.

1.5.1

Aminosalicylates

Sulfasalazineis a combination of 5-aminosalicylic acid

(‘5-ASA’)and sulfapyridine; sulfapyridine acts only as a

carrierto the colonic site of action but still causes side-

effects. In the newer aminosalicylates, mesalazine (5-

aminosalicylicacid), balsalazide (aprodrug of 5-amino-

salicylic acid) and olsalazine (a dimer of 5-aminosali-

cylic acid which cleaves in the lower bowel), the sul-

phonamide-related side-effects of sulfasalazine are

avoided,but 5-aminosalicylic acid alone can still cause

side-effects including blood disorders (see recommen-

dation below) and lupus-like syndrome also seen with

sulfasalazine.

Cautions

Renalfunction should be monitored before

starting an oral aminosalicylate, at 3 months of treat-

ment, and then annually during treatment(more fre-

quentlyin renal impairment). Blood disorders can occur

withaminosalicylates (see recommendation below).

Blooddisorders

Patients receiving aminosalicylates should be

advised to report any unexplained bleeding, br uis-

ing, pur pura, sore throat, fever or malaise that

occurs during treatment. A blood count should be

performed and the dr ug stopped immediately if

thereis suspicion of a blood dyscrasia.

Contra-indications

Aminosalicylates should be

avoidedin salicylate hypersensitivity.

Side-effects

Side-effects of the aminosalicylates

include diarrhoea, nausea, vomiting, abdominal pain,

exacerbation of symptoms of colitis, headache, hyper-

sensitivityreactions (including rash and urticaria); side-

effects that occur rarely include acute pancreatitis,

hepatitis, myocarditis, pericarditis, lung disorders

(includingeosinophilia and ﬁbrosing alveolitis), periph-

eral neuropathy, blood disorders (including agranulo-

cytosis,aplastic anaemia, leucopenia, methaemoglobin-

aemia, neutropenia, and thrombocytopenia—seealso

recommendation above), renal dysfunction (interstitial

nephritis,nephrotic syndrome), myalgia, arthralgia, skin

reactions (including lupus erythematosus-like

syndrome,Stevens-Johnson syndrome), alopecia.

BALSALAZIDE SODIUM

Indications

treatmentof mild to moderate ulcerative

colitisand maintenance of remission

Cautions

seenotes above; also history of asthma;

interactions:Appendix 1 (aminosalicylates)

Blooddisorders

Seerecommendation above

Contra-indications

seenotes above

Hepaticimpairment

avoidin severe impairment

Renalimpairment

manufactureradvises avoid in

moderateto severe impairment

Pregnancy

manufactureradvises avoid

Breast-feeding

monitorinfant for diarrhoea

Side-effects

seenotes above; also cholelithiasis

Dose

. Acuteattack, 2.25 g 3 times daily until remission

occursor for up to max. 12 weeks

. Maintenance,1.5 g twice daily, adjusted according to

response(max. 6 g daily)

CHILDunder 18 years see

BNFfor Children

Colazide

(Almirall)A

Capsules

,beige, balsalazide sodium 750 mg. Net

price130-cap pack = £30.42. Label: 21, 25, counsel-

ling,blood disorder symptoms (see recommendation

above)

BNF 61 1.5.1 Aminosalicylates 61

Gastro-intestinalsystem

MESALAZINE

Indications

treatmentof mild to moderate ulcerative

colitisand maintenance of remission; see also under

preparations

Cautions

seenotes above; elderly; interactions:

Appendix1 (aminosalicylates)

Blooddisorders

Seerecommendation above

Contra-indications

seenotes above

Hepaticimpairment

avoidin severe impairment

Renalimpairment

usewith caution; avoid if eGFR

lessthan 20 mL/minute/1.73 m

Pregnancy

negligiblequantities cross placenta

Breast-feeding

diarrhoeareported but negligible

amountsdetected in breast milk; monitor infant for

diarrhoea

Side-effects

seenotes above

Dose

. Seeunder preparations, below

Note

The delivery characteristics of oral mesalazinepre-

parationsmay vary; these preparations should not be con-

sideredinterchangeable

Asacol

(WarnerChilcott) A

Foamenema

,mesalazine 1 g/metered application,

netprice 14-application canister with disposable

applicatorsand plastic bags = £26.72. Counselling,

blooddisorder symptoms (see recommendation

above)

Excipients

includedisodium edetate, hydroxybenzoates (parabens),

polysorbate20, sodium metabisulphite

Dose

acuteattack affecting the rectosigmoid region, 1 metered

application(mesalazine 1 g) into the rectum daily for 4–6 weeks;

acuteattack affecting the descending colon, 2 metered applica-

tions(mesalazine 2 g) once daily for 4–6 weeks; CHILD 12–18

years,see

BNFfor Children

Suppositories

,mesalazine 250 mg, net price 20-sup-

pospack = £4.82; 500 mg, 10-suppos pack = £4.82.

Counselling,blood disorder symptoms (see recom-

mendationabove)

Dose

acuteattack or maintenance, by rectum0.75–1.5 g daily in

divideddoses, with last dose at bedtime; CH ILD12–18 years, see

BNFfor Children

Asacol

MR(Warner Chilcott) A

Tablets

,red, e/c, mesalazine 400mg, net price 90-tab

pack= £29.41, 120-tab pack = £39.21. Label: 5, 25,

counselling,blood disorder symptoms (see recom-

mendationabove)

Dose

ulcerativecolitis, acute attack, 2.4 g daily in divided doses;

maintenanceof remission of ulcerative colitis and Crohn’s ileo-

colitis,1.2–2.4 g daily in divided doses; CHILD 12–18 years, see

BNFfor Children

Tablets

,red-brown, e/c, mesalazine800 mg, net price

180-tabpack = £117.62. Label: 5, 25, counselling,

blooddisorder symptoms (see recommendation

above)

Dose

ADULTover 18 years, ulcerative colitis, acute attack, 2.4–

4.8g daily in divided doses; maintenance of remission of ulcer-

ativecolitis and Crohn’s ileo-colitis, up to 2.4 g daily in divided

doses

Note

Preparations that lower stool pH (e.g. lactulose) may

preventrelease of mesalazine

Ipocol

(Sandoz)A

Tablets

,e/c, mesalazine 400 mg, net price 120-tab

pack= £41.62. Label: 5, 25, counselling, blood dis-

ordersymptoms (see recommendation above)

Dose

acuteattack, 2.4 g daily in divided doses; maintenance,

1.2–2.4g daily in divided doses; CHILD 12–18years, see

BNFfor

Children

Note

Preparationsthat lowerstool pH (e.g. lactulose) may prevent

releaseof mesalazine

Mesren

MR(IVAX) A

Tablets

,red-brown, e/c, mesalazine400 mg, net price

90-tabpack =£19.50, 120-tab pack = £26.00. Label: 5,

25,counselling, blood disorder symptoms (see

recommendationabove)

Dose

ADULTand CHILD over12 years, ulcerative colitis, acute

attack,2.4 g daily in divided doses; maintenance of rem ission of

ulcerativecolitis and Crohn’sileo-colitis, 1.2–2.4 g daily in divided

doses

Mezavant

XL(Shire) A

Tablets

,m/r, red-brown, e/c, mesalazine 1.2 g, net

price60-tab pack = £62.44. Label: 21, 25, counselling,

blooddisorder symptoms (see recommendations

above)

Dose

ADULTover18 years,acute attack, 2.4 g once daily,increase

ifnecessary to 4.8g once daily (review treatment at 8 weeks);

maintenance,2.4 g once daily

Pentasa

(Ferring)A

Tablets

,m/r, scored, mesalazine 500 mg (grey), net

price100-tab pack = £24.21. Counselling, adminis-

tration,see dose, blood disorder symptoms (see

recommendationabove)

Dose

ADULTandCHILD over15 years,acute attack, up to 4g daily

in2–3 divided doses; maintenance, 2 g once daily; tablets may be

dispersedin water, but should not be chewed; CHILD 5–15years

see

BNFfor Children

Granules

,m/r, pale grey-brown, mesalazine 1 g/

sachet,net price 50-sachet pack = £28.82; 2g/sachet,

60-sachetpack = £72.05. Counselling, administration,

seedose, blood disorder symptoms (see recommen-

dationabove)

Dose

acuteattack, up to 4 g daily in 2–4 divided doses; main-

tenance,2g once daily; granules should be placed on tongue and

washeddown with water or orange juice without chewing; CHILD

5–18years see

BNFfor Children

Retentionenema

,mesalazine 1 g in 100-mL pack.

Netprice 7 enemas = £17.73. Counselling, blood

disordersymptoms (see recommendation above)

Dose

byrectum ADULTandCHILD over 12 years, 1 enema at

bedtime

Suppositories

,mesalazine 1 g. Net price 28-suppos

pack= £40.01. Counselling, blood disordersymptoms

(seerecommendation above)

Dose

byrectum ulcerative proctitis, ADULTand CHILD over15

years,acuteattack, 1 g daily for2–4 weeks; maintenance, 1 gdaily;

CHILD12–15 years see

BNFfor Children

Salofalk

(DrFalk) A

Tablets

,e/c, yellow, mesalazine 250 mg. Net price

100-tabpack =£16.19. Label: 5, 25, counselling,blood

disordersymptoms (see recommendation above)

Dose

acuteattack, 0.5–1 g 3 times daily; maintenance, 500 mg

threetimes daily; CHILD 12–18 years see

BNFfor Children

Granules

,m/r, grey, e/c, vanilla-ﬂavoured, mesal-

azine500 mg/sachet, net price 100-sachet pack =

£28.74;1 g/sachet, 50-sachet pack = £28.74; 1.5 g/

sachet,60-sachet pack = £48.85. Label: 25, counsel-

ling,administration, see dose, blood disorder symp-

toms(see recommendation above)

Excipients

includeaspartame (section 9.4.1)

Dose

acuteattack, 1.5–3g once daily (preferably in the morning)

0.5–1g3 times daily; maintenance, 500 mg 3times daily; CHILD

6–18years see

BNFfor Children

Counselling

granulesshould be placed on tongue and washed

downwith water without chewing

Note

Preparationsthat lowerstool pH (e.g. lactulose) may prevent

releaseof mesalazine

62 1.5.1 Aminosalicylates BNF 61

Gastro-intestinalsystem

Suppositories

,mesalazine 500 mg. Net price 30-

suppospack = £14.81. Counselling, blood disorder

symptoms(see recommendation above)

Dose

ADULTand CHILD over15 years, acute attack, by rectum,

0.5–1g2–3 times daily adjusted according to response; CHILD 12–

15years see

BNFfor Children

Enema

,mesalazine 2 g in 59-mL pack. Net price 7

enemas= £29.92. Counselling, blood disorder symp-

toms(see recommendation above)

Dose

acuteattack

maintenance,by rectum, 2g daily at bed-

time;CHILD 12–18 years see

BNFfor Children

Rectalfoam

,mesalazine 1 g/meteredapplication, net

price14-application canister with disposable appli-

catorsand plastic bags = £30.17. Counselling, blood

disordersymptoms (see recommendation above)

Excipients

includecetostearyl alcohol, disodium edetate, polysorbate

60,propylene glycol, sodium metabisulphite

Dose

mildulcerative colitis affecting sigmoid colon and rectum,

ADULTand CHILD over12 years, 2metered applications (mesal-

azine2 g) into the rectum at bedtime or in 2 divided doses

OLSALAZINE SODIUM

Indications

treatmentof mild ulcerative colitis and

maintenanceof remission

Cautions

seenotes above; interactions: Appendix 1

(aminosalicylates)

Blooddisorders

Seerecommendation above

Contra-indications

seenotes above

Renalimpairment

usewith caution; manufacturer

advisesavoid in signiﬁcant impairment

Pregnancy

manufactureradvises avoid unless poten-

tialbeneﬁt outweighs risk

Breast-feeding

monitorinfant for diarrhoea

Side-effects

seenotes above; watery diarrhoea com-

mon;also reported, tachycardia, palpitation, pyrexia,

blurredvision, and photosensitivity

Dose

. ADULTand CHILD over 12 years, acute attack, 1 g daily

individed doses after meals increased if necessary

over1 week to max. 3 g daily (max. single dose 1 g);

maintenance,500 mg twice daily after meals

CHILDunder 12 years see

BNFfor Children

Dipentum

(UCBPharma) A

Capsules

,brown, olsalazine sodium 250 mg. Net

price112-cap pack = £19.77. Label: 21, counselling,

blooddisorder symptoms (see recommendation

above)

Tablets

,yellow, scored, olsalazine sodium 500 mg.

Netprice 60-tab pack =£21.18. Label: 21, counselling,

blooddisorder symptoms (see recommendation

above)

SULFASALAZINE

(Sulphasalazine)

Indications

treatmentof mild to moderate and severe

ulcerativecolitis and maintenanceof remission; active

Crohn’sdisease; rheumatoid arthritis (section 10.1.3)

Cautions

seenotes above; also history of allergy or

asthma;G6PD deﬁciency (section 9.1.5); slow acety-

latorstatus; risk of haematological and hepatic toxi-

city(differential white cell, red cell, and platelet

countsinitially and at monthly inter vals for ﬁrst 3

months;liver function tests at monthly intervals for

ﬁrst3 months); maintain adequate ﬂuid intake; upper

gastro-intestinalside-effects common over 4 g daily;

acuteporphyria (section 9.8.2); interactions: Appen-

dix1 (aminosalicylates)

Blooddisorders

Seerecommendation above

Contra-indications

seenotes above; also sulphona-

midehypersensitivity; child under 2 years of age

Hepaticimpairment

usewith caution

Renalimpairment

riskof toxicity, including cr ystal-

luria,in moderate impairment—ensure high ﬂuid

intake;avoid in severe impairment

Pregnancy

theoreticalrisk of neonatal haemolysis in

thirdtrimester; adequate folate supplements should

begiven to mother

Breast-feeding

smallamounts in milk (1 report of

bloodydiarrhoea); theoretical risk of neonatal hae-

molysisespecially in G6PD-deﬁcient infants

Side-effects

seenotes above; also cough, insomnia,

dizziness,fever, blood disorders (including Heinz

bodyanaemia, megaloblastic anaemia), proteinuria,

tinnitus,stomatitis, taste disturbances, and pruritus;

lesscommonly

dyspnoea,depression, convulsions,

vasculitis,and alopecia; also reported loss of appetite,

hypersensitivityreactions (including exfoliative

dermatitis,epidermal necrolysis, photosensitivity,

anaphylaxis,serum sickness), ataxia, hallucinations,

asepticmeningitis, oligosper mia, crystalluria, distur-

bancesof smell, and parotitis; yellow-orange disco-

lorationof skin,urine, and other body ﬂuids; somesoft

contactlenses may be stained

Dose

. Bymouth, acute attack 1–2 g 4 times daily (but see

cautions)until remission occurs (if necessary corti-

costeroidsmay also be given), reducing to a main-

tenancedose of 500 mg 4 times daily;

CHILD2–12

yearssee

BNFfor Children

. Byrectum, in suppositories, alone or in conjunction

withoral treatment 0.5–1 g morning and night after a

bowelmovement;

CHILD5–12 years see

BNFfor

Children

Sulfasalazine(Non-proprietary) A

Tablets

,sulfasalazine 500 mg, net price 112 = £6.74.

Label:14, counselling, blood disorder symptoms (see

recommendationabove), contact lenses may be

stained

Tablets

,e/c, sulfasalazine 500 mg. Net price 112-tab

pack= £14.46. Label: 5, 14, 25, counselling, blood

disordersymptoms (see recommendation above),

contactlenses may be stained

Brandsinclude

SulazineEC

Suspension

,sulfasalazine 250 mg/5 mL, net price

500mL = £29.50. Label: 14, counselling, blood dis-

ordersymptoms (see recommendation above), con-

tactlenses may be stained

Excipients

mayinclude alcohol

Salazopyrin

(Pharmacia)A

Tablets

,yellow, scored, sulfasalazine 500 mg, net

price112-tab pack = £6.97. Label: 14, counselling,

blooddisorder symptoms (see recommendation

above),contact lenses may be stained

EN-Tabs

(=tablets e/c), yellow, f/c, sulfasalazine

500mg, net price 112-tab pack = £8.43. Label: 5, 14,

25,counselling, blood disorder symptoms (see

recommendationabove), contact lenses may be

stained

Suppositories

,yellow, sulfasalazine500 mg, net price

10= £3.30. Label: 14, counselling, blood disorder

symptoms(see recommendation above), contact

lensesmay be stained

BNF 61 1.5.1 Aminosalicylates 63

Gastro-intestinalsystem

1.5.2

Corticosteroids

Forthe role of corticosteroids in acute ulcerative colitis

andCrohn’s disease, see Inﬂ ammatory Bowel Disease,

p.59.

BECLOMETASONEDIPROPIONATE

Indications

adjunctto aminosalicylates in acute mild

tomoderate ulcerative colitis; asthma (section 3.2);

allergicand vasomotor rhinitis (section 12.2.1); oral

ulceration[unlicensed indication] (section 12.3.1)

Cautions

section6.3.2; interactions: Appendix 1

(corticosteroids)

Contra-indications

section6.3.2

Hepaticimpairment

manufactureradvises avoid in

severeimpairment—no information available

Pregnancy

section6.3.2

Breast-feeding

section6.3.2

Side-effects

section6.3.2; also nausea, constipation,

headache,and drowsiness

Dose

. 5mg in the morning; max. duration of treatment 4

weeks;

CHILDsafety and efﬁcacy not established

Clipper

(Chiesi)A

Tablets

,m/r, ivory, beclometasone dipropionate

5mg, net price 30-tab pack = £56.56. Label: 25

BUDESONIDE

Indications

seepreparations

Cautions

section6.3.2; for autoimmune hepatitis,

monitorliver function tests every 2 weeks for 1

month,then at least every 3 months; interactions:

Appendix1 (corticosteroids)

Contra-indications

section6.3.2

Hepaticimpairment

section6.3.2

Pregnancy

section6.3.2

Breast-feeding

section6.3.2

Side-effects

section6.3.2

Dose

. Seepreparations

Budenofalk

(DrFalk) A

Capsules

,pink, enclosing e/c granules, budesonide

3mg, net price 100-cap pack = £75.05. Label: 5, 10,

steroidcard, 22, 25

Dose

mildto moderate Crohn’s disease affecting ileum or

ascendingcolon, chronic diarrhoea due to c ollagenous colitis,

ADULTover18 years, 3 mg 3 times daily for up to 8 weeks; reduce

dosefor the last 2 weeks of treatment (see also section 6.3.2);

CHILD12–18 years see

BNFfor Children

Autoimmunehepatitis, ADULT over18 years, induction of remis-

sion,3 mg 3 times daily; maintenance, 3 mg twice daily

Rectalfoam

,budesonide 2 mg/metered application,

netprice 14-application canister with disposable

applicatorsand plastic bags = £57.11

Excipients

includecetyl alcohol, disodium edetate, propylene glycol,

sorbicacid

Dose

ulcerativecolitis affecting sigmoid colon and rectum, by

rectum,ADULT over18 years, 1 metered application (budesonide

2mg) once daily for up to 8 weeks

Entocort

(AstraZeneca)A

CRCapsules

,grey/pink, enclosing e/c, m/rgranules,

budesonide3 mg, net price 100-cap pack = £99.00.

Label:5, 10, steroid card, 25

Note

Dispensein original container (contains desiccant)

Dose

mildto moderate Crohn’s disease affecting the ileum or

ascendingcolon, 9 mg once daily in the morning for up to 8

weeks;reduce dose for the last 2–4 weeks of treatment (see also

section6.3.2); CHILD 12–18 years see

BNFfor Children

Enema

,budesonide 2 mg/100mL when dispersible

tabletreconstituted in isotonic saline vehicle, net

pricepack of 7 dispersible tablets and bottles of

vehicle= £33.00

Dose

ulcerativecolitis involving rectal and recto-sigmoid dis-

ease,by rectum, 1 enema at bedtime for 4 weeks; CHILD 12–18

yearssee

BNFfor Children

HYDROCORTISONE

Indications

ulcerativecolitis, proctitis, proctosigmoi-

ditis

Cautions

section6.3.2; systemic absorption may

occur;prolonged use should be avoided

Contra-indications

intestinalobstruction, bowel per-

foration,recent intestinal anastomoses, extensive ﬁs-

tulas;untreated infection

Side-effects

section6.3.2; also local irritation

Dose

. Byrectum see preparations

Colifoam

(Meda)A

Foam

inaerosol pack, hydrocortisone acetate 10%,

netprice 14-application canister with applicator =

£9.28

Excipients

includecetyl alcohol, hydroxybenzoates (parabens), propy-

leneglycol

Dose

initially1 metered applicat ion (125 mg hydrocortisone

acetate)inserted into the rectum once or twice daily for 2–3

weeks,thenonce on alternate days; CHILD 2–18years see

BNFfor

Children

PREDNISOLONE

Indications

ulcerativecolitis, and Crohn’s disease;

otherindications, see section 6.3.2, see also prepara-

tions

Cautions

section6.3.2; systemic absorption may

occurwith rectal preparations; prolonged use should

beavoided

Contra-indications

section6.3.2; intestinal obstruc-

tion,bowel perforation,recent intestinal anastomoses,

extensiveﬁstulas; untreated infection

Hepaticimpairment

section6.3.2

Renalimpairment

section6.3.2

Pregnancy

section6.3.2

Breast-feeding

section6.3.2

Side-effects

section6.3.2

Dose

. Bymouth, initially 20–40 mg daily (up to 60 mg daily

insome cases), preferably taken in the morning after

breakfast;continued until remission occurs, followed

byreducing doses

. Byrectum, see preparations

Oralpreparations

Section6.3.2

64 1.5.2 Corticosteroids BNF 61

Gastro-intestinalsystem

Rectalpreparations

Predenema

(Chemidex)A

Retentionenema

,prednisolone 20 mg (as sodium

metasulphobenzoate)in 100-mL single-dose dispo-

sablepack. Net price 1 (standard tube) = 71p, 1 (long

tube)= £1.21

Dose

ulcerativecolitis, by rectum, ADULT andCHILD over12

years,initially 20 mg at bedtime for 2–4 weeks, continued if good

response

Predfoam

(Forest)A

Foam

inaerosol pack, prednisolone 20 mg (as meta-

sulphobenzoatesodium)/metered application, net

price14-application canister with disposable appli-

cators= £6.32

Excipients

includecetostearyl alcohol, disodium edetate, polysorbate

20,sorbic acid

Dose

proctitisand distal ulcerative colitis, 1 metered application

(20mgpred nisolone) inserted into the rectum once or twice daily

for2 weeks,continued for further 2 weeks if good response; CHILD

notrecommended

Predsol

(UCBPharma) A

Retentionenema

,prednisolone 20 mg (as sodium

phosphate)in 100-mL single-dose disposable packs

ﬁttedwith a nozzle. Net price 7 = £6.00

Dose

rectaland rectosigmoidal ulcerative colitis and Crohn’s

disease,by rectum, initially 20mg at bedtime for 2–4 weeks,

continuedif good res ponse; CHILD notrecommended

Suppositories

,prednisolone 5 mg (as sodium phos-

phate).Net price 10 = £1.35

Dose

ADULTand CHILD proctitisand rectal complications of

Crohn’sdisease,by rectum, 5mg inserted night and morning after

abowel movement

1.5.3

Drugs affecting the

immune response

For the role of azathioprine, ciclospor in, mercapto-

purine,and methotrexate in the treatment of inﬂamm-

atorybowel disease, see p. 59.

Folicacid (section 9.1.2) should be given to reduce the

possibilityof methotrexate toxicity [unlicensed indica-

tion].Folic acid is usually given at a dose of 5 mg once

weekly on a differentday tothe methotrexate;alter-

nativeregimens may be used in some settings.

AZATHIOPRINE

Indications

seeunder Inﬂammatory Bowel Disease,

p.59; autoimmune conditions and prophylaxis of

transplantrejection (section 8.2.1); rheumatoid arth-

ritis(section 10.1.3); severe refractory eczema (sec-

tion13.5.3)

Cautions

section8.2.1

Contra-indications

section8.2.1

Hepaticimpairment

section8.2.1

Renalimpairment

section8.2.1

Pregnancy

section8.2.1

Breast-feeding

section8.2.1

Side-effects

section8.2.1

Dose

. Severeacute Crohn’s disease, maintenance of remis-

sionof Crohn’s disease or ulcerative colitis [unli-

censedindications],

ADULTover 18 years, by mouth,

2–2.5mg/kg daily; some patients may respond to

lowerdoses

Preparations

Section8.2.1

CICLOSPORIN

(Cyclosporin)

Indications

severeacute ulcerative colitis refractory

tocorticosteroid treatment [unlicensed indication];

transplantationand graft-versus-host disease,

nephroticsyndrome (section 8.2.2); rheumatoid arth-

ritis(section 10.1.3); atopic dermatitis and psoriasis

(section13.5.3)

Cautions

section8.2.2

Hepaticimpairment

section8.2.2

Renalimpairment

section8.2.2

Pregnancy

seeImmunosuppresant therapy, p. 553

Breast-feeding

section8.2.2

Side-effects

section8.2.2

Dose

. Bycontinuous intravenous infusion, ADULTover 18

years,2 mg/kg daily over 24 hours; dose adjusted

accordingto blood-ciclosporin concentration and

response

Preparations

Section8.2.2

MERCAPTOPURINE

(6-Mercaptopurine)

Indications

seeunder Inﬂammatory Bowel disease,

p.59; acute leukaemias and chronic myeloid leuk-

aemia(section 8.1.3)

Cautions

section8.1.3

Hepaticimpairment

section8.1.3

Renalimpairment

section8.1.3

Pregnancy

section8.1.3

Breast-feeding

section8.1.3

Side-effects

section8.1.3

Dose

. Severeacute Crohn’s disease, maintenance of remis-

sionof Crohn’s disease or ulcerative colitis [unli-

censedindications],

ADULTover18 years, by mouth,1–

1.5mg/kg daily; some patients may respond to lower

doses

Preparations

Section8.1.3

METHOTREXATE

Indications

seeunder Inﬂammatory Bowel Disease,

p.59; malignant disease (section 8.1.3); rheumatoid

arthritis(section 10.1.3); psoriasis (section 13.5.3)

Cautions

section10.1.3

Contra-indications

section10.1.3

Hepaticimpairment

section10.1.3

Renalimpairment

section10.1.3

Pregnancy

section10.1.3

Breast-feeding

section10.1.3

Side-effects

section10.1.3

BNF 61 1.5.3 Drugs affecting the immune response 65

Gastro-intestinalsystem

Dose

. Byintramuscular injection, severe Crohn’s disease

[unlicensedindication],

ADULTover18 years, induction

ofremission, 25 mg onceweekly; maintenance, 15 mg

onceweekly

. Bymouth, maintenance of remission of severe

Crohn’sdisease [unlicensed indication],

ADULTover18

years,10–25 mg once weekly

Important

Notethat the above dose is a weekly dose. To avoid

errorwith low-dose methotrexate, it is recommended

that:

thepatient is carefully advised of the dose andfrequency

and the reason for taking methotrexateand any other

prescribedmedicine (e.g. folic acid);

onlyone strength of methotrexate tablet (usually 2.5mg) is

prescribedand dispensed;

theprescription and the dispensing label clearly show the

doseand frequency of methotrexate administration;

thepatient is warned to report immediately the onset of

anyfeature of blood disorders (e.g. sore throat, bruising,

and mouth ulcers), liver toxicity (e.g. nausea, vomiting,

abdominal discomfort, and dark urine), and respiratory

effects(e.g. shortness of breath).

Preparations

Section10.1.3

Cytokinemodulators

Inﬂiximab and adalimumab are monoclonal anti-

bodies which inhibit the pro-inﬂammatory cytokine,

tumour necrosis factor alpha. They should be used

under specialist supervision. Adequate resuscitation

facilitiesmust be available when inﬂ iximab is used.

ADALIMUMAB

Indications

seeunder Inﬂammatory Bowel Disease,

p.60; ankylosing spondylitis, psoriatic arthritis, rheu-

matoidarthritis, juvenile idiopathic arthritis, (section

10.1.3);psoriasis (section 13.5.3)

Cautions

section10.1.3

Contra-indications

section10.1.3

Pregnancy

section10.1.3

Breast-feeding

section10.1.3

Side-effects

section10.1.3

Dose

. Bysubcutaneous injection, severe active Crohn’s

disease,

ADULTover 18 years, initially 80 mg, then

40mg 2 weeks after initial dose

acceleratedregi-

men,initially 160mg in 4 divided dosesover 1–2 days,

then80 mg 2 weeks after initial dose; maintenance,

40mg on alternate weeks, increased if necessary to

40mg weekly; review treatment if no response within

12weeks of initial dose

Preparations

Section10.1.3

INFLIXIMAB

Indications

seeunder Inﬂammatory Bowel Disease,

p.59; ankylosing spondylitis, rheumatoid arthritis

(section10.1.3); psoriasis (section 13.5.3)

Cautions

seesection 10.1.3; also history of dysplasia

orcolon carcinoma

Hypersensitivity reactions

Risk of delayed hypersensi-

tivityif drug-free interval exceeds 16 weeks

Contra-indications

seesection 10.1.3

Pregnancy

section10.1.3

Breast-feeding

section10.1.3

Side-effects

seesection 10.1.3; also hepatosplenic T-

celllymphoma

Dose

. Byintravenous infusion, severe active Crohn’s dis-

ease,

ADULTover 18 years, initially 5 mg/kg, then

5mg/kg 2 weeks after initial dose; then if the condi-

tionhas responded, maintenance 5 mg/kg 6 weeks

afterinitial dose, then 5 mg/kg every 8 weeks;

CHILD

6–18years, initially 5 mg/kg, then 5 mg/kg 2 weeks

and6 weeks after initial dose, then 5 mg/kg every 8

weeks;interval between maintenance doses adjusted

accordingto response; discontinue if no response

within10 weeks of initial dose

FistulatingCrohn’s disease,

ADULTover 18 years,

initially5 mg/kg, then 5 mg/kg 2 weeks and 6 weeks

afterinitial dose, then if condition has responded,

consultproduct literature for guidance on further

doses;

CHILDunder 18 years, see

BNFfor Children

Severeactive ulcerative colitis, ADULT over18 years,

initially5 mg/kg, then 5 mg/kg 2 weeks and 6 weeks

afterinitial dose, then 5 mg/kg every 8 weeks; dis-

continueif no response 14 weeks after initial dose

Preparations

Section10.1.3

1.5.4

Food allergy

Allergywith classical symptoms of vomiting, colic and

diarrhoea caused by speciﬁc foods such as shellﬁsh

shouldbe managed by strict avoidance. The condition

should be distinguished from symptoms of occasional

foodintolerance in those with irritable bowel syndrome.

Sodiumcromoglicate may be helpful as an adjunct to

dietaryavoidance.

SODIUM CROMOGLICATE

(Sodiumcromoglycate)

Indications

foodallergy (in conjunction with dietary

restriction);asthma (section 3.3.1); allergic con-

junctivitis(section 11.4.2); allergic rhinitis (section

12.2.1)

Pregnancy

notknown to be harmful

Breast-feeding

unlikelyto be present in milk

Side-effects

occasionalnausea, rashes, and joint pain

Dose

. 200mg4 times daily before meals;may be increased if

necessaryafter 2–3 weeksto a max. of 40 mg/kgdaily

andthen reduced according to response;

CHILD2–14

years100 mg 4 times daily before meals; may be

increasedif necessar y after 2–3 weeks to a max. of

40mg/kg daily and then reduced according to

response

Counselling

Capsules may be swallowed whole or the

contentsdissolved in hot water and diluted with cold water

beforetaking

Nalcrom

(Sanoﬁ-Aventis)A

Capsules

,sodium cromoglicate 100 mg. Net price

100-cappack = £59.75. Label: 22, counselling, see

doseabove

66 1.5.4 Food allergy BNF 61

Gastro-intestinalsystem

1.6

Laxatives

1.6.1 Bulk-forming laxatives

1.6.2 Stimulant laxatives

1.6.3 Faecal softeners

1.6.4 Osmotic laxatives

1.6.5 Bowel cleansing preparations

1.6.6 Peripheral opioid-receptor

antagonists

1.6.7 5HT

-receptoragonists

Before prescribing laxatives it is important to be sure

thatthe patient

constipatedand that the constipation

not

secondary to an underlying undiagnosed com-

plaint.

Itis also important for those who complain of constipa-

tionto understand that bowel habit can vary consider-

ably in frequency withoutdoing harm. Some people

tendto consider themselves constipated if they do not

havea bowel movement each day.A useful deﬁnition of

constipationis the passage of hard stoolsless frequently

thanthe patient’s own normal pattern and this can be

explainedto the patient.

Misconceptionsabout bowel habits have led to exces-

sivelaxative use. Abuse may lead to hypokalaemia.

Thus, laxatives should generally be avoided except

where straining will exacerbate a condition (such as

angina) or increasethe risk of rectal bleeding as in

haemorrhoids. Laxatives are also of value in

drug-

induced constipation

, for the expulsion of

parasites

afteranthelmintic treatment, and toclear the alimentary

tractbefore

surgeryand radiological procedures

.Pro-

longed treatment of constipation is sometimes neces-

sary.

For the role of laxatives in thetreatment ofirritable

bowelsyndrome,see p. 61. For the preventionof opioid-

inducedconstipation in palliative care, see p. 22.

Children

Laxativesshould be prescribed by a health-

care professional experienced inthe management of

constipationin children. Delays of greater than 3 days

betweenstools may increase the likelihood of pain on

passinghard stools leading to anal ﬁssure, anal spasm

andeventually to a learned response to avoid defaeca-

tion.

infants

, increased intake of ﬂ uids, particularly fruit

juicecontaining sorbitol (e.g.pr une,pear, or apple), may

besufﬁcient to soften the stool. In infants under 1 year

ofage with mild constipation, lactulose (section 1.6.4)

canbe used to soften the stool; either an oral prepara-

tioncontaining macrogols or, rarely,g lycerolsupposi-

toriescan be used to clear faecal impaction. The infant

should be referred to a hospital paediatric specialist if

thesemeasures fail.

The diet of

children over 1 year of age

should be

reviewedto ensure that it includes an adequate intake

of ﬁbre and ﬂuid. An osmotic laxative containing

macrogols(section 1.6.4) can also be used, particularly

in children with chronic constipation; lactulose isan

alternativein children who cannot tolerate a macrogol.

Ifthere is an inadequate response to the osmotic laxa-

tive,a stimulant laxative (section1.6.2) can be added.

Treatment of faecal impaction may initially increase

symptoms of soiling andabdominal pain.In children

over 1 year of age with faecal impaction, an oral pre-

parationcontaining macrogols (section1.6.4) is used to

clear faecal mass andto establish and maintain soft

well-formedstools. If disimpaction does not occur after

2 weeks, a stimulantlaxative (section 1.6.2)can be

added. If the impacted mass is not expelled following

treatment with macrogols and a stimulant laxative,a

sodium citrateenema can be administered. Although

rectaladministration of laxatives may be effective, this

routeis frequently distressing for thechild and may lead

topersistence of withholding. A phosphateenema may

be administered under specialistsupervision ifdisim-

pactiondoes not occur after a sodium citrate enema; a

bowelcleansing preparation(section 1.6.5) is an alter-

native. Manual evacuation under anaesthetic maybe

necessaryif disimpaction does not occur after oral and

rectaltreatment, or if the child is afraid.

Long-termregular use of laxatives is essential to main-

tainwell-formed stools and prevent recurrence of faecal

impaction;intermittent use may provoke relapses.

For children with chronic constipation, it maybe

necessary to exceed the licensed doses of some

laxatives.Parents and carers of children should be

advised to adjust thedose oflaxative in orderto

establish a regular pattern of bowel movements in

whichstools are soft, well-formed, and passed with-

outdiscomfort.

Laxatives should be administered at a time that

produces an effect that is likelyto ﬁtin withthe

child’stoilet routine.

Pregnancy

If dietary and lifestyle changes fail to

control constipation in pregnancy,moderate doses of

poorlyabsorbed laxatives may be used. A bulk-forming

laxativeshould be tried ﬁrst. An osmotic laxative, such

aslactulose, can also be used. Bisacodyl or senna may

besuitable, if a stimulant ef fect is necessary.

The laxatives that follow have been divided into 5

maingroups (sections 1.6.1–1.6.5). This simple clas-

siﬁcationdisguises the fact that some laxatives have

acomplex action.

1.6.1

Bulk-forming laxatives

Bulk-forming laxatives relieve constipation by increas-

ing faecal mass which stimulates peristalsis; patients

should be advised thatthe full ef fect may take some

daysto develop.

Bulk-forming laxatives are of particular valuein those

withsmall hard stools,but should not be required unless

ﬁbre cannot be increased in the diet. A balanced diet,

includingadequate ﬂuid intake and ﬁbre is of value in

preventingconstipation.

Bulk-forminglaxatives are useful in the management of

patientswith

colostomy

ileostomy

haemorrhoids

anal

ﬁssure

chronicdiarrhoea associated with diverticular

disease

irritable bowel syndrome

, and as adjuncts in

ulcerative colitis

(section 1.5). Adequate ﬂuid intake

must be maintained to avoid intestinal obstruction.

Unprocessed wheat bran, taken with food or fruit

juice, is a most effective bulk-forming preparation.

BNF 61 1.6 Laxatives 67

Gastro-intestinalsystem

Finelyground bran, though more palatable, has poorer

water-retaining properties, but can be taken as bran

bread or biscuits in appropriately increased quantities.

Oatbran is also used.

Methylcellulose,ispaghula, and sterculia areuseful in

patientswho cannot tolerate bran. Methylcellulose also

actsas a faecal softener.

ISPAGHULAHUSK

Indications

seenotes above

Cautions

adequateﬂuid intake should be maintained

toavoid intestinal obstruction—it may be necessary

tosupervise elderly or debilitated patients or those

withintestinal nar rowing or decreased motility

Contra-indications

difﬁcultyin swallowing, intestinal

obstruction,colonic atony, faecal impaction

Side-effects

ﬂatulence,abdominal distension, gastro-

intestinalobstruction or impaction; hypersensitivity

reported

Dose

. Seepreparations below

Counselling

Preparationsthat swell in contact with liquid

shouldalways be carefully swallowed with water and should

notbe taken immediately before going to bed

Fibrelief

(Manx)

Granules

,sugar- and gluten-free, ispaghula husk

3.5g/sachet (natural or orange ﬂavour), net price 10

sachets= £1.23, 30 sachets = £2.07. Label: 13, coun-

selling,see above

Excipients

includeaspartame (section 9.4.1)

Dose

ADULTandCHILD over 12 years, 1–6 sachets daily in water

in1–3 divided doses, preferably after meals

Fybogel

(ReckittBenckiser)

Granules

,buff, effervescent, sugar- and gluten-free,

ispaghulahusk 3.5 g/sachet (low Na

),net price 30

sachets(plain, lemon, or orange ﬂavour) = £1.84.

Label:13, counselling, see above

Excipients

includeaspartame 16 mg/sachet (see section 9.4.1)

Dose

1sachet or 2 level 5-mL spoonfuls in water twice daily

preferablyafter meals; CHILD (butsee section 1.6)2–12 years ½–1

level5-mL spoonful in water, twice daily preferably after meals

(CHILD2–6 years on specialist practitioner’s advice only)

Isogel

(Potters)

Granules

,brown, sugar- and gluten-free, ispaghula

husk90%. Net price 200 g = £2.67. Label: 13, coun-

selling,see above

Dose

constipation,2 level 5-mLsp oonfulsin water once or twice

daily,preferably at mealtimes; CHILD (but see section 1.6) 2–12

years,1 level 5-mL spoonful in water once or twice daily, pre-

ferablyat mealtimes

Diarrhoea(section 1.4.1), 1 level 5-mL spoonful 3 times daily

Note

Maybe difﬁcult to obtain

IspagelOrange

(LPC)

Granules

,beige, effer vescent, sugar- and gluten-free,

ispaghulahusk 3.5 g/sachet, net price 30 sachets =

£2.10.Label: 13, counselling, see above

Excipients

includeaspartame (section 9.4.1)

Dose

1sachet in water 1–3 times daily, preferably after meals;

CHILD(but see sect ion 1.6) 2–12 years see

BNFfor Children

Regulan

(Procter& Gamble)

Powder

,beige, sugar- and gluten-free, ispaghula husk

3.4g/5.85-g sachet (orange or lemon/lime ﬂavour).

Netprice 30 sachets = £2.44. Label: 13, counselling,

seeabove

Excipients

includeaspartame (section 9.4.1)

Dose

1sachet in 150 mL water 1–3 times daily, preferably after

meals;CHILD (but see section 1.6) 2–6 years, see

BNFfor

Children

;6–12 years2.5–5 mL in water 1–3 times daily,preferably

aftermeals

METHYLCELLULOSE

Indications

seenotes above

Cautions

seeunder Ispaghula Husk

Contra-indications

seeunder Ispaghula Husk; also

infectivebowel disease

Side-effects

seeunder Ispaghula Husk

Dose

. Seepreparations below

Counselling

Preparationsthat swell in contact with liquid

shouldalways be carefully swallowed with water and should

notbe taken immediately before going to bed

Celevac

(Amdipharm)

Tablets

,pink, scored, methylcellulose ‘450’ 500 mg,

netprice 112-tab pack= £3.22. Counselling,see above

anddose

Dose

constipationand diarrhoe a, 3–6 tablets twice daily; in

constipationthe dose should be taken with at least 300 mL liquid;

indiarrhoea, ileostomy,and colostomy control, avoid liquid intake

for30 minutes before and after dose; CHILD 7–12 years see

BNF

forChildren

STERCULIA

Indications

seenotes above

Cautions

seeunder Ispaghula Husk

Contra-indications

seeunder Ispaghula Husk

Side-effects

seeunder Ispaghula Husk

Dose

. Seeunder preparations below

Counselling

Preparationsthat swell in contact with liquid

shouldalways be carefully swallowed with water and should

notbe taken immediately before going to bed

Normacol

(Norgine)

Granules

,coated, gluten-free, sterculia 62%. Net

price500 g = £5.94; 60  7-g sachets = £4.99.

Label:25, 27, counselling, see above

Dose

1–2heaped 5-mLspoonfuls, or the contents of 1–2 sachets,

washeddown without chewing with plenty of liquid once or twice

dailyafter meals; CHILD (butsee section 1.6) 6–12 years half adult

dose

NormacolPlus

(Norgine)

Granules

,brown, coated, gluten-free, sterculia 62%,

frangula(standardised) 8%. Net price 500 g = £6.34;

60 7 g sachets = £5.34. Label: 25, 27, counselling,

seeabove

Dose

constipationand after haemorrhoidectomy, 1–2 heaped 5-

mLspoonfuls

thecontents of 1–2 sachets washed down with-

outchewing with plenty of liquid once or twice daily after mea ls;

CHILD6–12 years see

BNFfor Children

1.6.2

Stimulant laxatives

Stimulantlaxatives include bisacodyl, sodium picosul-

fate,and members of the anthraquinone group,senna

and dantron. The indications for dantron arelimited

(see below) by its potential carcinogenicity (based on

rodent

carcinogenicity studies) and evidence of geno-

toxicity.Powerfulstimulants such ascascara (an anthra-

quinone)and castor oilare obsolete. Docusate sodium

probably acts both asa stimulant andas a softening

agent.

Stimulantlaxatives increase intestinal motility andoften

cause abdominal cramp; they should be avoided in

intestinalobstr uction. Excessive use of stimulant laxa-

tives can cause diar rhoea and related effects suchas

hypokalaemia; however, prolonged use may be justiﬁ-

ablein some circumstances (see section 1.6 for the use

ofstimulant laxatives in children).

68 1.6.2 Stimulant laxatives BNF 61

Gastro-intestinalsystem

Glycerolsuppositories actas a rectal stimulant byvirtue

ofthe mildly irritant action of glycerol.

The parasympathomimetics bethanechol, distigmine,

neostigmine,and pyridostigmine (see section 7.4.1 and

section10.2.1) enhance parasympathetic activity in the

gutand increase intestinal motility.They are rarely used

fortheir gastro-intestinal effects. Organic obstruction of

thegut must ﬁrst be excluded and they should not be

usedshortly after bowel anastomosis.

BISACODYL

Indications

seeunder Dose

Cautions

seenotes above

Contra-indications

seenotes above, acute surgical

abdominalconditions, acute inﬂammatory bowel

disease,severe dehydration

Pregnancy

seePregnancy, p. 67

Side-effects

seenotes above; nausea and vomiting;

colitisalso reported;

suppositories

,local ir ritation

Dose

. Constipation,by mouth,5–10 mg at night, increasedif

necessaryto max. 20 mg at night;

CHILD(but see

section1.6) 4–18 years 5–20 mg once daily, adjusted

accordingto response

Byrectum in suppositories, 10 mg in the morning;

CHILD(but see section 1.6) 2–18 years 5–10 mg once

daily,adjusted according to response

. Beforeradiological proceduresand surgery, by mouth,

10mg in themor ningand 10 mg in the evening on the

daybefore procedure, and by rectumin suppositories,

10mg 1–2 hours before procedure the following day;

CHILD4–18 years see

BNFfor Children

Note

tablets act in 10–12 hours; suppositories act in 20–60

minutes

Bisacodyl(Non-proprietary)

Tablets

,e/c, bisacodyl 5 mg. Net price 100 = £3.27.

Label:5, 25

Suppositories

,bisacodyl 10 mg. Net price 12 =£1.11

Paediatricsuppositories

,bisacodyl 5mg. Net price 5

=94p

Note

Thebrand name

Dulcolax

D(Boehringer Ingelheim) is

usedfor bisacodyl table ts, net price 10-tab pack = 74p;

suppositories(10 mg), 10 =£1.57; paediatric suppos itories (5mg),

5= 94p

Thebrand names

Dulcolax

PicoLiquid

and

Dulcolax

Pico

Perles

areused for sodium picosulfate preparations

DANTRON

(Danthron)

Indications

onlyfor constipation in terminally ill

patientsof all ages

Cautions

seenotes above;

rodent

studiesindicate

potentialcarcinogenic risk; avoid prolonged contact

withskin (as in incontinent patientsor infants wearing

nappies)—riskof ir ritation and excoriation

Contra-indications

Seenotes above

Pregnancy

manufacturersof co-danthramer and co-

danthrusateadvise avoid—no information available

Breast-feeding

manufacturersof co-danthramer and

co-danthrusateadvise avoid—limited information

available

Side-effects

seenotes above; urine may be coloured

red

Dose

. Seeunder preparations

Withpoloxamer ‘188’ (as co-danthramer)

Note

Co-danthramer suspension 5 mL = one co-danthramer

capsule,but strong co-danthramer suspension 5 mL = two

strongco-danthramer capsules

Co-danthramer(Non-proprietary) A

Capsules

,co-danthramer 25/200 (dantron 25 mg,

poloxamer‘188’ 200 mg). Net price 60-cap pack =

£12.86.Label: 14, (urine red)

Dose

1–2capsules at bedtime; CHILD 1capsule at bedtime

(restrictedindications, see notes above)

Strongcapsules

,co-danthramer 37.5/500 (dantron

37.5mg, poloxamer ‘188’ 500 mg). Net price 60-cap

pack= £15.55. Label: 14, (urine red)

Dose

ADULTand CHILD over12 years, 1–2 capsules at bedtime

(restrictedindications, see notes above)

Suspension

,co-danthramer 25/200 in 5mL (dantron

25mg, poloxamer ‘188’ 200 mg/5 mL). Net price

300mL = £11.27, 1 litre = £37.57. Label: 14, (urine

red)

Dose

5–10mL at night; CHILD 2.5–5mL (restricted indications,

seenotes above)

Brandsinclude

Codalax

Danlax

Strongsuspension

,co-danthramer 75/1000 in 5 mL

(dantron75 mg, poloxamer ‘188’ 1g/5 mL). Net price

300mL = £30.13. Label: 14, (urine red)

Dose

ADULTand CHILD over12 years, 5mL at night (restricted

indications,see notes above)

Brandsinclude

CodalaxForte

Withdocusate sodium (as co-danthrusate)

Co-danthrusate

(Non-proprietary)A

Capsules

,co-danthrusate 50/60 (dantron 50 mg,

docusatesodium 60 mg). Net price 63-cap pack =

£15.87.Label: 14, (urine red)

Dose

1–3capsules at night; CHILD 6–12 years 1 capsule at night

(restrictedindications, see notes above)

Brandsinclude

Normax

Suspension

,yellow, co-danthrusate 50/60 (dantron

50mg, docusate sodium 60 mg/5 mL). Net price

200mL = £8.75. Label: 14, (urine red)

Dose

5–15mL at night; CHILD 6–12 years 5 mL at night

(restrictedindications, see notes above)

Brandsinclude

Normax

DOCUSATESODIUM

(Dioctylsodium sulphosuccinate)

Indications

constipation,adjunct in abdominal radi-

ologicalprocedures

Cautions

seenotes above; do not give with liquid

parafﬁn;rectal preparations not indicated if

haemorrhoidsor anal ﬁssure

Contra-indications

seenotes above

Pregnancy

notknown to be harmful—manufacturer

advisescaution

Breast-feeding

presentin milk following oral admin-

istration—manufactureradvises caution; rectal

administrationnot known to be harmful

Side-effects

seenotes above

Dose

. Bymouth, chronic constipation, up to 500 mg daily in

divideddoses;

CHILD(but see section 1.6) 6 months–2

years12.5 mg 3 times daily, adjusted according to

response(use paediatric solution); 2–12 years 12.5–

25mg 3 times daily, adjusted according to response

(usepaediatric oral solution)

Note

Oralpreparations act within 1–2 days

Withbarium meal, ADULT andCHILD over 12 years,

400mg

BNF 61 1.6.2 Stimulant laxatives 69

Gastro-intestinalsystem

Dioctyl

(UCBPharma)

Capsules

,yellow/white, docusate sodium 100 mg,

netprice 30-cap pack = £1.92, 100-cap pack = £6.40

Docusol

(Typharm)

Adultoral solution

,sugar-free, docusate sodium

50mg/5mL, net price 300 mL = £5.49

Paediatricoral solution

,sugar-free, docusate sodium

12.5mg/5mL, net price 300 mL = £5.29

Rectalpreparations

NorgalaxMicro-enema

(Norgine)

Enema

,docusate sodium 120 mg in 10-g single-dose

disposablepacks. Net price 10-g unit = 57p

Dose

ADULTand CHILD (butsee section 1.6) over 12 years, 10-g

unit

GLYCEROL

(Glycerin)

Indications

constipation

Dose

. Seebelow

GlycerolSuppositories, BP

(GlycerinSuppositories)

Suppositories

,gelatin 140 mg, glycerol 700 mg, pur-

iﬁedwater to 1g, net price 12 =£1.27 (1 g),£1.29 (2 g),

£1.48(4 g)

Dose

1suppository moistened with water before use, when

required.The usual sizes are for INFANT under 1 year, small (1-g

mould),CHILD 1–12years medium (2-g mould), ADULTand CHILD

over12 years, large (4-g mould)

SENNA

Indications

constipation

Cautions

seenotes above

Contra-indications

seenotes above

Pregnancy

seePregnancy, p. 67

Breast-feeding

notknown to be harmful

Side-effects

seenotes above

Dose

. Seeunder preparations

Note

Actsin 8–12 hours

Senna(Non-proprietary)

Tablets

,total sennosides (calculated as sennoside B)

7.5mg. Net price 60 = £1.47

Dose

2–4tablets, usually at night; initialdos esho uldbe low then

graduallyincreased; CHILD (but see section 1.6) 2–6 years see

BNFfor Children

;6–18 years 1–4 tablets once daily, adjusted

accordingto response

Note

Lowerdose on packs on sale to the public

Brandsinclude

Senokot

Manevac

(HFAHealthcare)

Granules

,coated, senna fruit 12.4%, ispaghula 54.2%,

netprice 400 g = £7.45. Label: 25, counselling,

administration

Excipients

includesucrose 800 mg per level 5-mL spoonful of granules

Dose

ADULTand CHILD over12 years, 1–2 level 5-mL spoonfuls

atnight with at least 150 mL water,fr uit juice, milk or warm drink

Counselling

Preparationsthat swell in contact with liquid should

alwaysbe carefully swallowed with wateror appropriate ﬂ uid and

shouldnot be taken immediately before going to bed

Senokot

(ReckittBenckiser)

Tablets

D,see above

Syrup

,sugar-free, brown, total sennosides (calculated

assennoside B) 7.5 mg/5mL, net price 500 mL =

£2.69

Dose

10–20mL, usually at bedtime; CHILD (but see section 1.6)

1month–2years see

BNFforChildren

,2–4 years 2.5–10mL once

daily,adjustedaccording to response; 4–18 years 2.5–20mL once

daily,adjusted according to response

Note

Lowerdose on packs on sale to the public

SODIUM PICOSULFATE

(Sodiumpicosulphate)

Indications

constipation;bowel evacuation before

abdominalradiological and endoscopic procedures

onthe colon, and surgery (section 1.6.5); acts within

6–12hours

Cautions

seenotes above; active inﬂ ammatory bowel

disease(avoid if fulminant)

Contra-indications

seenotes above; severe dehydra-

tion

Pregnancy

seePregnancy, p. 67

Breast-feeding

notknown to be present in milk but

manufactureradvises avoid unless potential beneﬁt

outweighsrisk

Side-effects

seenotes above

Dose

. 5–10mg at night;CHILD (but see section 1.6)1 month–

4years 2.5–10 mg once daily, adjusted according to

response;4–18 years 2.5–20 mg once daily, adjusted

accordingto response

Note

Sodiumpicosulfate dosesin BNF may differ from those

inproduct literature

SodiumPicosulfate (Non-proprietary)

Elixir

,sodium picosulfate 5 mg/5mL, net price

100mL = £1.85

Note

The brand name

Dulcolax

Pico Liquid

(Boehringer

Ingelheim)is used for sodium picosulfate elixir 5mg/5 mL

Dulcolax

Pico(Boehringer Ingelheim)

Perles

(=capsules), sodium picosulfate 2.5 mg, net

price20-cap pack = £1.93, 50-cap pack = £2.73

Note

Thebrand name

Dulcolax

isalso usedfor bisacodyl tablets

andsuppositories

Bowelcleansing preparations

Section1.6.5

Other stimulant laxatives

Unstandardised preparations of cascara, frangula, rhu-

barb, and senna should beavoided astheir laxative

action is unpredictable. Aloes, colocynth, and jalap

should be avoided as they have a drastic purgative

action.

1.6.3

Faecal softeners

Liquidparaf ﬁn, the traditional lubricant, has disadvan-

tages(see below). Bulklaxatives (section 1.6.1) and non-

ionic surfactant ‘wetting’ agents e.g. docusate sodium

(section 1.6.2) also have softening properties. Such

drugsare useful for oral administration in the manage-

mentof haemorrhoids and anal ﬁssure; glycerol(section

1.6.2)is useful for rectal use.

Enemascontaining arachis oil (ground-nut oil, peanut

oil)lubricate and soften impacted faeces and promote a

bowelmovement.

ARACHIS OIL

Indications

seenotes above

Dose

. Seebelow

70 1.6.3 Faecal softeners BNF 61

Gastro-intestinalsystem

ArachisOil Enema (Non-proprietary)

Enema

,arachis (peanut) oil in 130-mL single-dose

disposablepacks. Net price 130 mL = £7.98

Dose

tosoften impacted faeces, 130 mL; the enema should be

warmedbefore use; CHILD (butsee section 1.6) under 3 years not

recommended;over 3 years reduce adult dose in proportion to

body-weight(medical supervision only), see

BNFfor Children

LIQUID PARAFFINU

Indications

constipation

Cautions

avoidprolonged use; contra-indicated in

childrenunder 3 years

Side-effects

analseepage of parafﬁn and consequent

analirritation after prolonged use, granulomatous

reactionscaused by absorption of small quantities of

liquidparafﬁn (especially from the emulsion), lipoid

pneumonia,and interference with the absorption of

fat-solublevitamins

Dose

. Seeunder preparation

LiquidParafﬁn Oral Emulsion, BPU

Oralemulsion

,liquid paraf ﬁn 5mL, vanillin 5 mg,

chloroform0.025 mL, benzoic acid solution 0.2 mL,

methylcellulose-20200 mg, saccharin sodium

500micrograms, water to 10 mL

Dose

ADULTover 18 years, 10–30 mL at night when required

Counselling

Shouldnot betaken immediately before going to bed

1.6.4

Osmotic laxatives

Osmoticlaxatives increase the amount of water in the

largebowel, either by drawing ﬂuid from the body into

thebowel or by retaining the ﬂ uid they were adminis-

teredwith.

Lactuloseis a semi-synthetic disaccharide which is not

absorbedfrom the gastro-intestinal tract. It produces an

osmoticdiarrhoea of low faecal pH,and discourages the

proliferation of ammonia-producing organisms. It is

thereforeuseful in the treatment of

hepaticencephalo-

pathy

Macrogolsare inert polymers of ethylene glycol which

sequesterﬂuid in the bowel; giving ﬂuid with macrogols

mayreduce the dehydrating effect sometimes seen with

osmoticlaxatives.

Saline purgatives such asmagnesium hydroxide are

commonly abused but are satisfactor y for occasional

use; adequate ﬂuid intake should be maintained.

Magnesiumsalts areuseful where rapid bowel evacua-

tionis required. Sodium saltsshould be avoidedas they

maygive rise to sodium and water retention in suscep-

tibleindividuals. Phosphate enemasare useful inbowel

clearancebefore radiology, endoscopy, and surgery.

LACTULOSE

Indications

constipation(may take up to 48 hours to

act),hepatic encephalopathy (portal systemic

encephalopathy)

Cautions

lactoseintolerance; interactions: Appendix

1(lactulose)

Contra-indications

galactosaemia,intestinal obstr uc-

tion

Pregnancy

notknown to be harmful; see also

Pregnancy,p. 67

Side-effects

nausea(can be reduced by administra-

tionwith water, fruit juice or with meals), vomiting,

ﬂatulence,cramps, and abdominal discomfort

Dose

. Seeunder preparations below

Lactulose(Non-proprietary)

Solution

,lactulose 3.1–3.7g/5 mL with otherketoses.

Netprice 300-mL pack = £2.10, 500-mL pack = £2.59

Dose

constipation,initially 15mL twice daily, adjusted according

toresponse; CHILD (butsee section 1.6) under 1year 2.5 mL twice

daily,adjusted according to response; 1–5 years 2.5–10 mL twice

daily,adjusted according to response; 5–18 years 5–20 mL twice

daily,adjusted according to response

Hepaticencephalopathy, 30–50 mL 3 times daily, subsequently

adjustedto produce 2–3 soft stools daily; CHILD 12–18years see

BNFfor Children

Note

Lactulosedoses in BNF may differ from those in product

literature

Brandsinclude

Duphalac

Lactugal

Regulose

MACROGOLS

(Polyethyleneglycols)

Indications

seepreparations below

Cautions

discontinueif symptoms of ﬂ uid and

electrolytedisturbance; see also preparations below

Contra-indications

intestinalperforation or obstruc-

tion,paralytic ileus, severe inﬂammatory conditions

ofthe intestinal tract (such as Crohn’s disease, ulcer-

ativecolitis, and toxic megacolon), see also prepara-

tionsbelow

Pregnancy

manufacturersadvice use only if essen-

tial—noinformation available

Breast-feeding

manufacturersadvice use only if

essential—noinformation available

Side-effects

abdominaldistension and pain, nausea,

ﬂatulence

Dose

. Seepreparations below

MacrogolOral Powder, Compound (Non-proprietary)

Oralpowder

,macrogol ‘3350’ (polyethylene glycol

‘3350’)13.125 g, sodium bicarbonate 178.5 mg, sod-

iumchloride 350.7 mg, potassium chloride 46.6 mg/

sachet,net price 20-sachet pack = £4.45, 30-sachet

pack= £6.68. Label: 13

Brandsinclude

Laxido

Orange

Molaxole

Cautions patients with cardiovascular impairment should not

takemore than 2 sachets in any 1 hour

Dose

chronicconstipation, ADULT andCHILD over 12 years, 1–3

sachetsdaily in divided doses usually for up to 2 weeks; contents

ofeach sachet dissolved in half a glass (approx. 125 mL) of water;

maintenance,1–2 sachets daily

Faecalimpaction, ADULTand CHILD over 12 years, 8 sachets daily

dissolvedin 1 litre of water and drunk within 6 hours, usually for

max.3 days

Afterreconstitution the solution should be kept in a refrigerator

anddiscarded if unuse d after 6 hours

Movicol

(Norgine)

Oralpowder

,macrogol ‘3350’ (polyethylene glycol

‘3350’)13.125 g, sodium bicarbonate 178.5 mg, sod-

iumchloride 350.7 mg, potassium chloride 46.6 mg/

sachet,net price 20-sachet pack (lime and lemon

ﬂavour)= £4.45, 30-sachet pack (lime- and lemon- or

chocolate-or plain-ﬂavoured) = £6.68, 50–sachet

pack(lime- and lemon- or plain-ﬂavoured) = £11.13.

Label:13

Note

Amountof potassium chloride varies according to ﬂ avour

Movicol

asfollows: plain-ﬂavour (sugar-free) = 50.2 mg/

sachet;lime and lemon ﬂavour = 46.6 mg/sachet;

BNF 61 1.6.4 Osmotic laxatives 71

Gastro-intestinalsystem

chocolateﬂavour = 31.7 mg/sachet. 1 sachet when reconstituted

with125 mL water provides K

5.4mmol/litre

Cautions patients with cardiovascular impairment should not

takemore than 2 sachets in any 1 hour

Dose

chronicconstipation, ADULT andCHILD over 12 years, 1–3

sachetsdaily in divided doses usually for up to 2 weeks; contents

ofeach sachet dissolved in half a glass (approx. 125 mL) of water;

maintenance,1–2 sachets daily

Faecalimpaction, ADULTand CHILD over 12 years, 8 sachets daily

dissolvedin 1 litre of water and drunk within 6 hours, usually for

max.3 days

Afterreconstitution the solution should be kept in a refrigerator

anddiscarded if unuse d after 6 hours

Movicol

-Half(Norgine)

Oralpowder

,sugar-free, macrogol ‘3350’ (polyethy-

leneglycol ‘3350’) 6.563 g, sodium bicarbonate

89.3mg, sodium chloride 175.4 mg, potassium chlor-

ide23.3 mg/sachet, net price 20-sachet pack (lime

andlemon ﬂ avour) = £2.67, 30-sachet pack = £4.01.

Label:13

Cautions patients with cardiovascular impairment should not

takemore than 4 sachets in any 1 hour

Dose

chronicconstipation, ADULT andCHILD over 12 years, 2–

6sachetsdaily in divided doses usually for up to 2 weeks; content

ofeach sachet dissolved in quarter of a glass (approx. 60–65mL)

ofwater; maintenance, 2–4 sachets daily

Faecalimpaction,ADULT andCHILD over12years, 16 sachets daily

dissolvedin 1 litre of water and drunk within 6 hours, usually for

max.3 days

Afterreconstitution the solution should be kept in a refrigerator

anddiscarded if unuse d after 6 hours

Movicol

PaediatricPlain (Norgine) A

Oralpowder

,sugar-free, macrogol ‘3350’ (polyethy-

leneglycol ‘3350’) 6.563 g, sodium bicarbonate

89.3mg, sodium chloride 175.4 mg, potassium chlor-

ide25.1 mg/sachet, net price 30-sachet pack = £4.45.

Label:13

Cautions

withhigh doses

,impaired gag reﬂex, reﬂux oeso-

phagitis,impaired consciousness

Contra-indications cardiovascularimpair ment; renal impairment

Dose

chronicconstipation and prevention of faecal impaction,

CHILDunder 2 years see

BNFfor Children

;2–6 years 1 sachet

daily,adjusted according to response (max. 4 sachets daily); 6–12

years2 sachets daily, adjusted according to response (max. 4

sachetsdaily)

Faecalimpaction,CHILD under5 years see

BNFforChildren

;5–12

years4 sachets on ﬁrst day then increased in steps of 2 sachets

dailyto 12 sachets daily (taken in divided doses over 12 hour s

eachday until impaction resolves); content of each sachet dis-

solvedin quarter of a glass (approx. 60–65 mL) of water

Afterreconstitution the solution should be kept in a refrigerator

anddiscarded if unuse d after 24 hours

MAGNESIUM SALTS

Indications

seeunder preparations below

Cautions

elderlyand debilitated; see also notes above;

interactions:Appendix 1 (antacids)

Contra-indications

acutegastro-intestinal conditions

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidor reduce dose; increased

riskof toxicity

Side-effects

colic

Dose

. Seepreparations

Magnesiumhydroxide

MagnesiumHydroxide Mixture, BP

Aqueoussuspension containing about 8% hydrated

magnesiumoxide. Do not store in cold place

Dose

constipation,30–45 mL with water at bedtime when

required;CHILD 3–12years, 5–10 mL with water at bedtime when

required

Magnesiumhydroxide with liquid parafﬁn

LiquidParafﬁn and Magnesium HydroxideOral

Emulsion,BP U

Oralemulsion

,25% liquid parafﬁn in aqueous sus-

pensioncontaining 6% hydrated magnesium oxide

Dose

constipation,5–20 mL when required

Note

Liquidparafﬁn and magnesium hydroxide preparations on

saleto the public include:

Milpar

Magnesiumsulphate

MagnesiumSulphate

Label:13, 23

Dose

rapidbowel evacuation(acts in 2–4 hours) 5–10 g in aglass

ofwater preferably before breakfast

Note

Magnesiumsulphate is on sale to the public as Epsom Salts

Bowelcleansing preparations

Section1.6.5

PHOSPHATES(RECTAL)

Indications

rectaluse in constipation; bowel evacua-

tionbefore abdominal radiological procedures, endo-

scopy,and surgery

Cautions

elderlyand debilitated;

withenema

electrolytedisturbances, congestive heart failure,

ascites,uncontrolled hypertension,maintain adequate

hydration

Contra-indications

acutegastro-intestinal conditions

(includinggastro-intestinal obstruction, inﬂammator y

boweldisease, and conditions associated with

increasedcolonic absor ption)

Renalimpairment

useenema with caution

Side-effects

localirritation;

withenema

,electrolyte

disturbances

Dose

. Seeunder preparations

Carbalax

(Chemidex)

Suppositories

,sodium acid phosphate (anhydrous)

1.3g, sodium bicarbonate 1.08 g, net price 12 = £2.01

Dose

constipation,ADULT andCHILD over 12 years, 1 supposi-

tory,inserted 30 minutes before evacuation required; moisten

withwater before use

Fleet

Ready-to-useEnema (Casen-Fleet)

Enema

,sodium acid phosphate 21.4 g, sodium phos-

phate9.4 g/118 mL, net price 133-mL pack (delivers

118mL dose) with standard tube = 57p

Dose

ADULTand CHILD (butsee section 1.6) over 12 years,

118mL;CH ILD3–12 years, on doctor’s advice only (under 3 years

notrecommended)

PhosphatesEnema BP Formula B

Enema

,sodium dihydrogen phosphate dihydrate

12.8g, disodium phosphate dodecahydrate 10.24 g,

puriﬁedwater, freshly boiled and cooled, to 128 mL.

Netprice 128 mL with standard tube = £2.98, with

longrectal tube = £3.98

Dose

128mL; CHILD (butsee section 1.6) over 3 years, reduced

accordingto body weight see

BNFfor Children

SODIUM CITRATE(RECTAL)

Indications

rectaluse in constipation

Cautions

elderlyand debilitated; see also notes above

Contra-indications

acutegastro-intestinal conditions

Dose

. Seeunder preparations

MicoletteMicro-enema

(Pinewood)

Enema

,sodium citrate 450 mg, sodium lauryl sul-

phoacetate45 mg, glycerol 625 mg, together with

potassiumsorbate and sorbitol in a viscous solution,

72 1.6.4 Osmotic laxatives BNF 61

Gastro-intestinalsystem

in5-mL single-dose disposable packs with nozzle.Net

price5 mL = 38p

Dose

ADULTand CHILD over3 years, 5–10mL (but see section

1.6)

MicralaxMicro-enema

(UCBPharma)

Enema

,sodium citrate 450 mg, sodium alkylsul-

phoacetate45 mg, sorbic acid 5 mg, together with

glyceroland sorbitol in a viscous solution in 5-mL

single-dosedisposable packs with nozzle. Net price

5mL = 41p

Dose

ADULTand CHILD over3 years, 5mL (but see section 1.6)

RelaxitMicro-enema

(Crawford)

Enema

,sodium citrate 450 mg, sodium lauryl sul-

phate75 mg, sorbic acid 5 mg, together with glycerol

andsorbitol in a viscous solution in 5-mL single-dose

disposablepacks with nozzle. Net price 5 mL = 32p

Dose

ADULTandCHILD (butsee section 1.6)5 mL (insert only half

nozzlelength in c hild under 3 years)

1.6.5

Bowel cleansing

preparations

Bowel cleansing preparations are used before colonic

surgery, colonoscopy, or radiological examination to

ensure the bowel is free of solid contents. Theyare

nottreatments for constipation.

Cautions

Renal function should be measured before

startingtreatment. Bowel cleansing preparations should

beused with caution in patients with ﬂ uid and electro-

lyte disturbances. Hypovolaemia should be corrected

beforeadministration of bowel cleansing preparations.

Adequatehydration should be maintained during treat-

ment.Bowel cleansing preparationsshould be used with

cautionin colitis (avoid if acute severe colitis), in chil-

dren,in the elderly,or in those who aredebilitated. They

should also be used with caution inpatients with an

impairedgag reﬂex, reduced levels of consciousness, or

possibility of regurgitation or aspiration. Other oral

drugs should notbe taken one hour beforeor after

administrationof bowel cleansing preparations because

absorptionmay be impaired.

Contra-indications

Bowelcleansing preparations are

contra-indicated in patients with gastro-intestinal

obstruction or perforation, gastric retention, acute

severecolitis, or toxic megacolon.

Side-effects

Side-effectsof bowel cleansing prepara-

tionsinclude nausea, vomiting, abdominal pain (usually

transient—reduced by taking more slowly), and abdo-

minal distention. Less frequent side-effects include

headache,dizziness, dehydration, and electrolytedistur-

bances.

MACROGOLS

Indications

seenotes above

Cautions

seenotes above; also heart failure; acute

inﬂammatory bowel disease

Contra-indications

seenotes above

Pregnancy

manufacturersadvise use only if essen-

tial—noinformation available

Breast-feeding

manufacturersadvise use only if

essential—noinformation available

Side-effects

seenotes above; also fatigue, sleep dis-

turbances,and anal discomfort

Dose

. Seepreparations

Klean-Prep

(Norgine)

Oralpowder

,sugar-free, macrogol ‘3350’ (polyethy-

leneglycol ‘3350’) 59 g, anhydrous sodium sulphate

5.685g, sodium bicarbonate 1.685 g, sodium chloride

1.465g, potassium chloride 743 mg/sachet, net price

4sachets = £8.23. Label: 10, patient information

leaﬂet,13, counselling

Excipients

includeaspartame (section 9.4.1)

Electrolytes

1sachet when reconstituted with 1litre of water provides

125mmol,K

10mmol,Cl



35mmol,HCO



20mmol

Dose

bowelevacuation before surger y,colono scopy,or radi-

ologicalexamination, a glass (approx. 250 mL) of reconstituted

solutionevery 10–15 minutes, or by nasogastric tube 20–30 mL/

minute,starting on the day before procedure until 4litres have

beenconsumed; alternatively, administration may be divided into

two(2litres of reconstituted solution taken on the evening before

procedureand 2 litres of reconstituted solution taken on the

morningof procedure). Treatment can be stopped if bowel

motionsbecome watery and clear. To facilitate gastric emptying,

domperidoneor metoclopramide may be given 30 minutes before

starting;CHILD 12–18 years see

BNFfor Children

Counselling

1sachet should be reconstituted with1 litre of water.

Flavouringsuch as clear fruit cordials may be added if required.

Solidfood should not be taken for at least 2 hours before starting

treatment.After reconstitution the solution should be kept in a

refrigeratorand discarded if unused after 24 hours

Moviprep

(Norgine)

Oralpowder

,lemon- or orange-ﬂavoured,

SachetA

(containingmacrogol ‘3350’ (polyethylene glycol

‘3350’)100 g, anhydrous sodium sulphate 7.5 g, sod-

iumchloride 2.691 g, potassium chloride 1.015 g) and

SachetB

(containingascorbic acid 4.7 g, sodium

ascorbate5.9 g), net price 4-sachet pack (2 each of

sachetA and B) = £9.87. Label: 10, patient informa-

tionleaﬂet, 13, counselling, see below

Excipients

includeaspartame (section 9.4.1)

Electrolytes

1pair of sachets (A+B) when reconstituted with 1 litre of

waterprovides Na

181.6mmol(Na

56.2mmolabsorbable), K

14.2mmol,Cl



59.8mmol

Contra-indications G6PD deﬁciency

Renalimpairment cautionif eGFR less than 30mL/minute/

1.73m

Dose

bowelevacuation for surgery, colonoscopy or radiological

examination,ADULT over18 years, 2 litres of recon stituted solu-

tionon the evening before procedure

1litre of reconstituted

solutionon the evening before procedure and 1litre of reconsti-

tutedsolution early on the morning of procedure; treatment

shouldbe completed at least 1 hour before colonoscopy

Counselling

Onepairof sachets (A and B) should bereconstituted

in1litre of water and taken over 1–2 hours. Solid food should not

betaken during treatment until procedure completed. 1litre of

otherclear ﬂuid should alsobe taken during treatment. Treatment

canbe stopped if bowel motions become watery and clear

MAGNESIUM CITRATE

Reconstitutionof a sachet containing 11.57 g magnesium

carbonateand 17.79 g anhydrous citric acid produces a solu-

tioncontaining magnesium citrate

Indications

seepreparations

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidif eGFR less than 30 mL/

minute/1.73m

—riskof hyper magnesaemia

Pregnancy

caution

Breast-feeding

caution

Side-effects

seenotes above

Dose

. Seepreparations

BNF 61 1.6.5 Bowel cleansing preparations 73

Gastro-intestinalsystem

Citramag

(Sanochemia)

Oralpowder

,sugar-free, effer vescent, magnesium

carbonate11.57 g, anhydrous citric acid 17.79 g/

sachet,net price 10-sachet pack (lemon and lime

ﬂavour)= £17.20. Label: 10, patient information

leaﬂet,13, counselling, see below

Electrolytes

2þ

118mmol/sachet

Dose

bowelevacuation for surgery, colonoscopy or radiological

examination,on day before procedure, 1 sachet at 8 a.m. and 1

sachetbetween 2 and 4 p.m.; CHILD 5–10 years one-third adult

dose;over 10 years and frail ELDERLY one-halfadult dose

Counselling

Onesachet should be reconstituted with 200 mL of

hotwater; the solution should be allowed to cool for approx. 30

minutesbefore drinking. Low residue or ﬂuid only diet (e.g. water,

fruitsquash, clear soup, black tea or coffee) recommended before

procedure(according to prescriber’sadvice) and copious intake of

clearﬂuids recommende d until procedure

PHOSPHATES(ORAL)

Indications

seepreparations

Cautions

seenotes above; also cardiac disease (avoid

incongestive cardiac failure)

Contra-indications

seenotes above; also ascites;

congestivecardiac failure

Hepaticimpairment

usewith caution in cirrhosis;

avoidin ascites

Renalimpairment

avoidif eGFR less than 60 mL/

minute/1.73m

Pregnancy

caution

Breast-feeding

caution

Side-effects

seenotes above; also chest pain, arrhy-

thmias,asthenia, and renal failure

Dose

. Seepreparations

OsmoPrep

(TMC)

Tablets

,monobasic sodium phosphate monohydrate

1.102g, disodium phosphate 398 mg, net price 32-tab

pack= £8.50. Label: 10, patient information leaﬂet,

counselling,see below

Electrolytes

13.6mmol,Mg

2þ

0.34mmol,phosphate 10.8mmol/

tablet

Dose

bowelevacuation before diagnostic procedure, ADULTover

18years, 4tablets ever y15 minutes until a total of 20 tablets have

beenconsumed onthe evening before procedure, then onthe next

day(starting 3–5 hours before procedure) 4 tablets every 15

minutesuntil a total of 12 tablets have been consumed; do not

repeatcourse within 7 days

Counselling

On the day before procedure, a light, low-ﬁbre

breakfastmay be cons umed in the morning, clear liquid diet

recommendedafter 12 noon. Each dose of 4 tablets to be taken

with250 mL clear liquid. Copious intake of water or other clear

liquidsrecommended during treatment

FleetPhospho-soda

(Casen-Fleet)

Oralsolution

,sugar-free, sodium dihydrogen phos-

phatedihydrate 24.4 g, disodium phosphate dodeca-

hydrate10.8 g/45mL. Net price 2  45-mL bottles =

£4.79.Label: 10, patient information leaﬂet, counsel-

ling

Electrolytes

217mmol,phosphate 186mmol/45 mL

Dose

bowelevacuation before colonic surgery, colonoscopy or

radiologicalexamination, ADULTover 18 years, 45mL diluted with

halfa glass (120 mL) of cold water, followed by one full glass

(240mL) of cold water

Timingof doses is dependent on the time of the procedure

Formorning procedure, ﬁrst dose should be taken at 7 a.m. and

secondat 7 p.m. on day before the procedure

Forafternoon procedure, ﬁrst dose should be taken at 7 p.m. on

daybefore and second dose at 7 a.m. on day of the procedure

Actswithin half to 6 hours of ﬁrst dose

Counselling

Intakeof solid food should be stopped for at least 6

hoursbefore starting treatment and until procedure completed.

Copiousintake of water or other clear ﬂ uids (e.g. clear soup,

strainedfruit juice without pulp, black tea or coffee) recom-

mendeduntil midnight before morning procedure and until 8 a.m.

beforeafternoon procedure. At least one glass (approx 240mL) of

wateror other clear ﬂuid should also be taken immediately before

eachdose

SODIUM PICOSULFATEWITH

MAGNESIUM CITRATE

Indications

seepreparations

Cautions

seenotes above; also recentgastro-intestinal

surgery;cardiac disease (avoid in congestive cardiac

failure)

Contra-indications

seenotes above; also gastro-

intestinalulceration; ascites; congestive cardiac fail-

ure

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidif eGFR less than 30 mL/

minute/1.73m

—riskof hyper magnesaemia

Pregnancy

caution

Breast-feeding

caution

Side-effects

seenotes above; also anal discomfort,

sleepdisturbances, fatigue, and rash

Dose

. Seepreparations

CitraFleet

(Casen-Fleet)

Oralpowder

,sodium picosulfate 10 mg/sachet, with

magnesiumcitrate, net price 2-sachet pack (lemon-

ﬂavoured)= £3.25. Label: 10, patient information

leaﬂet,13, counselling, see below

Electrolytes

5mmol,Mg

2þ

86mmol/sachet

Dose

bowelevacuation on day before radiological examination,

endoscopy,orsurgery, ADULTover 18 years, 1 sachet before8 a.m.

then1 sachet 6–8 hours later

Actswithin 3 hour s of ﬁrst dose

Counselling

One sachet should be reconstituted with 150 mL

(approx.half a glass) of cold water; patients should be warned

thatheat is generated during reconstitution and that the solution

shouldbe allowed to cool before drinking. Low residue diet

recommendedon the day before procedure and copious intake of

wateror other clear ﬂuids recommended during treatment

Picolax

(Ferring)

Oralpowder

,sugar-free, sodium picosulfate 10 mg/

sachet,with magnesium citrate, net price 20-sachet

pack= £33.90. Label: 10, patient information leaﬂet,

13,counselling, see below

Electrolytes

5mmol,Mg

2þ

87mmol/sachet

Dose

bowelevacuation on day before radiological procedure,

endoscopy,or surgery, ADULT andCHILD over 9 years, 1 sachet

before8 a.m. then 1 sachet 6–8 hours later; CHILD 1–2years,

quartersachet before 8 a.m. then quarter sachet 6–8 hours later;

2–4years, half sachet before 8 a.m. then half sachet 6–8 hour s

later;4–9 years, 1 sachet before 8 a.m. then half sachet 6–8 hours

later

Actswithin 3 hour s of ﬁrst dose

Counselling

One sachet should be reconstituted with 150 mL

(approx.half a glass) of cold water; patients should be warned

thatheat is generated during reconstitution and that the solution

shouldbe allowed to cool before drinking. Low residue diet

recommendedon the day before procedure and copious intake of

wateror other clear ﬂuids recommended during treatment

1.6.6

Peripheral opioid-

receptor antagonists

Methylnaltrexoneis a peripherallyacting opioid-recep-

tor antagonist that is licensed for the treatment of

opioid-inducedconstipation in patients receiving pallia-

tive care, when response to other laxatives is inade-

74 1.6.6 Peripheral opioid-receptor antagonists BNF61

Gastro-intestinalsystem

quate; it should be used as an adjunct to existing

laxative therapy. Methylnaltrexone does notalter the

centralanalgesic effect of opioids. For the prevention of

opioid-inducedconstipation in palliative care, see p. 22.

METHYLNALTREXONEBROMIDE

Indications

opioid-inducedconstipation in terminally

illpatients, when response to other laxatives is

inadequate

Cautions

diverticulardisease; faecal impaction;

patientswith colostomy or peritoneal catheter

Contra-indications

gastro-intestinalobstruction;

acutesurgical abdominal conditions

Hepaticimpairment

manufactureradvises avoid in

severehepatic impairment—no infor mation available

Renalimpairment

ifeGFR less than 30 mL/minute/

1.73m

,reduce dose as follows: body-weight under

62kg, 75 micrograms/kg on alternate days; body-

weight62–114 kg, 8 mg on alternate days; body-

weightover 114 kg, 75 micrograms/kg on alternate

days

Pregnancy

toxicityat high doses in

animal

studies—

manufactureradvises avoid unless essential

Breast-feeding

manufactureradvises use only if

potentialbeneﬁt outweighs risk—present in milk in

animal

studies

Side-effects

abdominalpain, nausea, diarrhoea,

ﬂatulence;dizziness; injection site reactions, hyper-

hidrosis;also reported gastro-intestinal perforation

Dose

. Bysubcutaneous injection,ADULTover 18 years, body-

weightunder 38 kg, 150 micrograms/kg on alternate

days;body-weight 38–62 kg, 8 mg on alternate days;

body-weight62–114 kg, 12 mg on alternate days;

body-weightover 114 kg, 150 micrograms/kg on

alternatedays; may be given less frequently depend-

ingon response; 2 consecutive dosesmay be given 24

hoursapart if no response to treatment on the pre-

cedingday; rotate sites of injection; max. duration of

treatment4 months

Note

Mayact within 30–60 minutes

Relistor

(Wyeth)TA

Injection

,methylnaltrexone bromide 20 mg/mL, net

price0.6-mL vial = £21.05, 7-vial pack (with syringes

andneedles) = £147.35

1.6.7

5HT

-receptor agonists

Prucalopride is a selective serotonin 5HT

-receptor

agonistwith prokinetic properties. It is licensed for the

treatmentof chronic constipationin women, when other

laxativeshave failed to provide an adequate response.

Headache and gastro-intestinal symptoms (including

abdominal pain, nausea, anddiarrhoea) arethe most

frequentside-effects. The side-effects generally occur at

thestart of treatment and are usually transient.

PRUCALOPRIDE

Indications

chronicconstipation in women when

otherlaxatives fail to provide an adequate response

Cautions

historyof arrhythmias or ischaemic heart

disease;concomitant use with drugs that prolong QT

interval;severe, unstable chronic illness

Contra-indications

intestinalperforation or obstruc-

tion;severe inﬂ ammatory conditions of the intestinal

tract(such as Crohn’s disease, ulcerative colitis, and

toxicmegacolon)

Hepaticimpairment

max.1 mg daily in severe

impairment

Renalimpairment

max.1 mg daily if eGFR less than

30mL/minute/1.73m

Pregnancy

manufactureradvises avoid and recom-

mendseffective contraception during treatment

Breast-feeding

manufactureradvises avoid—present

inmilk

Side-effects

nausea,vomiting, abdominal pain, dys-

pepsia,ﬂatulence, diarrhoea, rectal bleeding; head-

ache,dizziness, fatigue; polyuria;

lesscommonly

anorexia,palpitation, tremor, and fever

Dose

. ADULTover 18 years, 2mg once daily; ELDERLY over65

years,initially 1 mg once daily, increased if necessary

to2 mg once daily

Note

Reviewtreatment if no response after 4 weeks

Resolor

(Movetis)TA

Tablets

,f/c, prucalopride (as succinate) 1 mg (white),

netprice 28-tab pack = £38.69; 2 mg (pink), 28-tab

pack= £59.52

1.7

Local preparations for

anal and rectal disorders

1.7.1 Soothing haemorrhoidal preparations

1.7.2 Compound haemorrhoidal

preparationswith corticosteroids

1.7.3 Rectal sclerosants

1.7.4 Management of anal ﬁssures

Analand perianal pruritus,soreness, and excoriation are

best treated by application of bland ointments and

suppositories (section 1.7.1). These conditions occur

commonly in patients suf fering from haemorrhoids,

ﬁstulas, and proctitis. Cleansing with attention to any

minorfaecal soiling, adjustmentof the diet to avoid hard

stools, the use of bulk-for ming materials such as bran

(section 1.6.1) and ahigh residue dietare helpful. In

proctitis these measures may supplement treatment

withcorticosteroids or sulfasalazine (see section 1.5).

When necessary, topical preparations containing local

anaesthetics(section 1.7.1) or corticosteroids (section

1.7.2) are used, provided perianal thrush has been

excluded.Perianal thrush is treated with a topical anti-

fungalpreparation (section 13.10.2).

Forthe management of

analﬁssures

,see section 1.7.4.

1.7.1

Soothing haemorrhoidal

preparations

Soothingpreparations containing mild astringents such

asbismuth subgallate, zinc oxide, and hamamelis may

givesymptomatic relief in haemorrhoids. Many proprie-

tary preparations also contain lubricants, vaso-

constrictors,or mild antiseptics.

Localanaesthetics are used to relieve pain associated

with

haemorrhoids

and

pruritusani

butgood evidence

BNF 61 1.6.7 5HT

-receptor agonists 75

Gastro-intestinalsystem

is lacking. Lidocaine ointment (section 15.2) isused

before emptying the bowelto relieve pain associated

with

analﬁssure

.Alternative local anaesthetics include

tetracaine, cinchocaine (dibucaine), and pramocaine

(pramoxine), but they are more ir ritant. Local anaes-

thetic ointments can be absorbed through the rectal

mucosa therefore excessive application should be

avoided,parti cularly in infants and children. Prepara-

tions containing local anaesthetics should be used for

shortperiods only (nolonger than a few days) sincethey

maycause sensitisation of the anal skin.

1.7.2

Compoundhaemorrhoidal

preparations with

corticosteroids

Corticosteroids are often combined with localanaes-

theticsand soothing agentsin preparations for haemorr-

hoids.They are suitable for occasional shor t-term use

after exclusion of infections, such as herpes simplex;

prolongeduse can cause atrophy of the anal skin. See

section13.4 for general comments on topical corticos-

teroidsand section 1.7.1 for comment on local anaes-

thetics.

Children

Haemorrhoids in children are rare.Treat-

ment is usually symptomatic and the use ofa locally

appliedcream is appropriate for short periods; however,

local anaesthetics can cause stinging initially and this

mayaggravate the child’s fear of defaecation.

Anugesic-HC

(Pﬁzer)A

Cream

,benzyl benzoate 1.2%, bismuth oxide 0.875%,

hydrocortisoneacetate 0.5%, Peru balsam 1.85%,

pramocainehydrochloride 1%,zinc oxide 12.35%. Net

price30 g (with rectal nozzle) = £3.71

Dose

applynight and morning and after a bowel movement; do

notuse for longer than 7 days; CHILD notrecommended

Suppositories

,buff, benzyl benzoate 33 mg, bismuth

oxide24 mg, bismuth subgallate 59 mg, hydrocorti-

soneacetate 5 mg, Peru balsam 49 mg, pramocaine

hydrochloride27 mg, zinc oxide 296 mg, net price 12

=£2.69

Dose

insert1 suppository night and morning and after a bowel

movement;do not use for longer than 7 days; CHILD not recom-

mended

Anusol-HC

(McNeil)A

Ointment

,benzyl benzoate 1.25%, bismuth oxide

0.875%,bismuth subgallate 2.25%, hydrocortisone

acetate0.25%, Peru balsam 1.875%, zinc oxide

10.75%.Net price 30 g (with rectal nozzle) = £3.29

Dose

applynight and morning and after a bowel movement; do

notuse for longer than 7 days; CHILD notrecommended

Note

Aproprietary brand (

AnusolPlus HC

ointment)is on sale

tothe public

Suppositories

,benzyl benzoate 33mg, bismuth oxide

24mg, bismuth subgallate 59 mg, hydrocortisone

acetate10 mg, Perubalsam 49 mg, zinc oxide 296mg.

Netprice 12 = £2.31

Dose

insert1 suppository night and morning and after a bowel

movement;do not use for longer than 7 days; CHILD not recom-

mended

Note

Aproprietary brand (

AnusolPlus HC

suppositories)is on

saleto the public

Perinal

(Dermal)

Sprayapplication

,hydrocortisone 0.2%, lidocaine

hydrochloride1%. Net price 30-mL pack = £6.11

Dose

ADULTand CHILD over14 years, spray once over the

affectedarea up to 3 times daily;do not use for longer than 7 days

withoutmedical advice; CHILD under 14 years on medical advice

only

ProctofoamHC

(Meda)A

Foam

inaerosol pack, hydrocortisone acetate 1%,

pramocainehydrochloride 1%. Net price 21.2-g pack

(approx.40 applications) with applicator = £5.06

Dose

haemorrhoidsand proctitis, 1 applicatorful (4–6 mg

hydrocortisoneacetate, 4–6 mg pramocaine hydrochloride) by

rectum2–3 times daily and after each bowel movement (max. 4

timesdaily); do not use for longer than 7 days; CHILD not

recommended

Proctosedyl

(Sanoﬁ-Aventis)A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,hydrocortisone 0.5%. Net price 30 g = £10.34

(withcannula)

Dose

applymorning and night and after a bowel movement,

externallyor by rectum; do not use for longer than 7 days

Suppositories

,cinchocaine (dibucaine) hydro-

chloride5 mg, hydrocortisone 5 mg. Net price 12 =

£4.66

Dose

insert1 suppository night and morning and after a bowel

movement;do not use for longer than 7 days

Scheriproct

(BayerSchering) A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,prednisolone hexanoate 0.19%.Net price 30 g =

£2.94

Dose

applytwice daily for5–7 days (3–4 times daily on 1st day if

necessary),then once daily for a few days after symptoms have

cleared

Suppositories

,cinchocaine (dibucaine) hydro-

chloride1 mg, prednisolone hexanoate 1.3 mg. Net

price12 = £1.38

Dose

insert1 suppository daily after a bowel movement, for 5–7

days(in severe cases initially 2–3 times daily)

Ultraproct

(Meadow)A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,ﬂuocortolone caproate 0.095%, ﬂ uocortolone

pivalate0.092%, net price 30 g (with rectal nozzle) =

£4.57

Dose

applytwice daily for5–7 days (3–4 times daily on 1st day if

necessary),then once daily for a few days after symptoms have

cleared

Suppositories

,cinchocaine (dibucaine) hydro-

chloride1 mg, ﬂuocortolone caproate 630 micr-

ograms,ﬂuocortolone pivalate 610 micrograms, net

price12 = £2.15

Dose

insert1 suppository daily after a bowel movement, for 5–7

days(in severe cases initially 2–3 times daily) then 1 suppositor y

everyother day for 1 week

Uniroid-HC

(Chemidex)A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,hydrocortisone 0.5%. Net price 30 g (with

applicator)= £4.23

Dose

ADULTandCHILD over12 years, apply twice daily and after

abowel movement, externally or by rectum; do not use forlonger

than7 days; CHILD under 12 years on medical advice only

Suppositories

,cinchocaine (dibucaine) hydro-

chloride5 mg, hydrocortisone 5 mg. Net price 12 =

£1.91

Dose

ADULTandCHILD over 12 years, insert 1 suppository twice

dailyand after a bowel movement; do not use for longer than 7

days

76 1.7.2 Compound haemorrhoidal preparations with corticosteroids BNF61

Gastro-intestinalsystem

Xyloproct

(AstraZeneca)A

Ointment

(water-miscible),aluminium acetate 3.5%,

hydrocortisoneacetate 0.275%, lidocaine 5%, zinc

oxide18%, net price 20 g (with applicator) = £2.26

Dose

applyseveral times daily; short-term use only

1.7.3

Rectal sclerosants

Oily phenol injection is used to inject haemor rhoids

particularlywhen unprolapsed.

PHENOL

Indications

seenotes above

Side-effects

irritation,tissue necrosis

OilyPhenol Injection, BP A

phenol5% in a suitable ﬁxed oil. Net price 5-mL amp

=£4.65

Dose

2–3mL into the submucosal layer at the base of the pile;

severalinjections may be given at different sites, max. total

injected10 mL at any one time

1.7.4

Management of anal

ﬁssures

The management of

anal ﬁssures

requires stool soft-

eningby increasing dietary ﬁbre in the form of bran or

byusing a bulk-forming laxative.Short-ter muse of local

anaesthetic preparations may help (section 1.7.1). If

these measures are inadequate, the patient should be

referredfor specialist treatment in hospital. The use of a

topical nitrate (e.g. glyceryl trinitrate 0.4% ointment)

maybe considered. Before considering surgery, topical

diltiazem2% may be used twice daily [unlicensed indi-

cation]in patients with chronic anal ﬁssures unrespon-

siveto topical nitrates.

The

ScottishMed icinesConsortium

(p.4) has advised

(January 2008) that glyceryl trinitrate 0.4% ointment

(

Rectogesic

)is not recommended for use within NHS

Scotland for the relief of pain associated with chronic

analﬁssure.

GLYCERYLTRINITRATE

Indications

analﬁssure; angina, left ventricular failure

(section2.6.1); extravasation (section 10.3)

Cautions

section2.6.1

Contra-indications

section2.6.1

Hepaticimpairment

section2.6.1

Renalimpairment

section2.6.1

Pregnancy

section2.6.1

Breast-feeding

section2.6.1

Side-effects

section2.6.1; also diarrhoea, bur ning,

itching,and rectal bleeding

Dose

. Seepreparations

Rectogesic

(ProStrakan)A

Rectalointment

,glyceryl trinitrate 0.4%, net price

30g = £34.80

Excipients

includelanolin, propylene glycol

Dose

ADULTover18 years,apply 2.5 cm of ointment toanal canal

every12 hours until pain stops; max. duration of use 8 weeks

Note

2.5cm of ointment contains glyceryl trinitrate 1.5mg; dis-

cardtube 8 weeks after ﬁrst opening

1.8

Stoma care

Prescribingfor patients with stomacalls for special care.

The following is a brief account of some of the main

pointsto be borne in mind.

Enteric-coated

and

modiﬁed-release

preparations are

unsuitable, particularly in patients with an ileostomy,

as there maynot be sufﬁcient release of the active

ingredient.

Laxatives

Enemas and washouts should not be pre-

scribedfor patients with anileostomy as they may cause

rapidand severe loss of water and electrolytes.

Colostomy patients may suffer fromconstipation and

wheneverpossible should be treated by increasing ﬂuid

intake or dietar y ﬁbre. Bulk-forming drugs (section

1.6.1) should be tried. If they are insufﬁcient, as small

a dose as possibleof senna (section 1.6.2) shouldbe

used.

Antidiarrhoeals

Drugssuch as loperamide, codeine

phosphate, or co-phenotrope (diphenoxylate with

atropine) are effective. Bulk-forming drugs (section

1.6.1)may be tried but it is often difﬁcult to adjust the

doseappropriately.

Antibacterials should not be given for an episode of

acutediarrhoea.

Antacids

Thetendency to diarrhoea from magnesium

salts or constipation from aluminium salts may be

increasedin these patients.

Diuretics

Diuretics should be used with caution in

patientswith an ileostomy as they may become exces-

sivelydehydrated and potassium depletion may easily

occur.It is usually advisable to use a potassium-spar-

ingdiuretic (see section 2.2.3).

Digoxin

Patientswith a stoma are particularly suscep-

tibleto hypokalaemia if on digoxin therapy and potas-

siumsupplements or a potassium-sparing diuretic may

beadvisable (for comment see section 9.2.1.1).

Potassium supplements

Liquid formulations are

preferredto modiﬁed-release formulations (see above).

Analgesics

Opioidanalgesics (see section 4.7.2) may

cause troublesome constipation in colostomy patients.

Whena non-opioid analgesicis required paracetamol is

usually suitable but anti-inﬂammator y analgesics may

causegastric ir ritation and bleeding.

Ironpreparations

Ironpreparations may cause loose

stoolsand sore skin in these patients. If this is trouble-

someand if iron is deﬁnitely indicated an intramuscular

iron preparation (see section9.1.1.2) should be used.

Modiﬁed-release preparations should be avoided for

thereasons given above.

Careof stoma

Patientsare usually given advice about

theuse of

cleansingagents

protectivecreams

lotions

deodorants

,or

sealants

whilstin hospital, either by the

surgeon or by stoma care nurses. Voluntary organisa-

tionsoffer help and suppor t to patients with stoma.

BNF 61 1.7.3 Rectal sclerosants 77

Gastro-intestinalsystem

1.9

Drugs affecting intestinal

secretions

1.9.1 Drugs affecting biliary composition

andﬂow

1.9.2 Bile acid sequestrants

1.9.3 Aprotinin

1.9.4 Pancreatin

1.9.1

Drugs affecting biliary

composition and ﬂow

Theuse of laparoscopic cholecystectomy and of endo-

scopicbiliary techniques has limitedthe place of the bile

acidur sodeoxycholicacid in gallstone disease. Urso-

deoxycholicacid issuitable for patients with unimpaired

gall bladder function, small or medium-sizedradiolu-

centstones, and whose mild symptoms are not amen-

ableto other treatment; it should be used cautiously in

thosewith liver disease (but see below). Patients should

begiven dietary advice (including avoidance of exces-

sivecholesterol and calories) and they require radiolo-

gicalmonitoring. Long-term prophylaxismay be needed

after complete dissolution of the gallstoneshas been

conﬁrmed because they may recur in up to 25% of

patientswithin one year of stopping treatment.

Ursodeoxycholic acid is alsoused in primary biliary

cirrhosis; liver tests improvein most patients but the

effecton overall survival is uncertain.

URSODEOXYCHOLIC ACID

Indications

seeunder Dose and under preparations

Cautions

seenotes above; interactions: Appendix 1

(ursodeoxycholicacid)

Contra-indications

radio-opaquestones, non-func-

tioninggall bladder, inﬂammatory diseases and other

conditionsof the smallintestine, colon and liver which

interferewith entero-hepatic circulation of bile salts

Hepaticimpairment

avoidin chronic liver disease

(butused in primary biliar y cirrhosis)

Pregnancy

noevidence of harm but manufacturer

advisesavoid

Breast-feeding

notknown to be harmful but manu-

factureradvises avoid

Side-effects

nausea,vomiting, diarrhoea; gallstone

calciﬁcation;pruritus

Dose

. Dissolutionof gallstones, 8–12mg/kg daily as a single

doseat bedtime

intwo divided doses, for up to 2

years;treatment is continued for 3–4 months after

stonesdissolve

. Primarybiliary cirrhosis, see under

Ursofalk

UrsodeoxycholicAcid (Non-proprietary) A

Tablets

,ursodeoxycholic acid 150 mg, net price 60-

tabpack = £20.48. Label: 21

Capsules

,ursodeoxycholic acid 250 mg,net price 60-

cappack = £38.86. Label: 21

Destolit

(Norgine)A

Tablets

,scored, ursodeoxycholic acid 150 mg, net

price60-tab pack = £17.67. Label: 21

Urdox

(Wockhardt)A

Tablets

,f/c, ursodeoxycholic acid 300 mg, net price

60-tabpack = £26.50. Label: 21

Ursofalk

(DrFalk) A

Capsules

,ursodeoxycholic acid 250 mg,net price 60-

cappack = £30.17, 100-cap pack = £31.88. Label: 21

Suspension

,sugar-free, ursodeoxycholic acid

250mg/5mL, net price 250 mL = £26.98. Label: 21

Dose

primarybiliary cir rhosis, 10–15 mg/kg daily as a single

dailydose or in 2–4 divided doses

Dissolutionof gallstones, see Dose, above

Ursogal

(Galen)A

Tablets

,scored, ursodeoxycholic acid 150 mg, net

price60-tab pack = £17.05. Label: 21

Capsules

,ursodeoxycholic acid 250 mg,net price 60-

cappack = £30.50. Label: 21

Otherpreparations for biliarydisorders

A terpene mixture (

Rowachol

) raises biliary choles-

terol solubility. It is not considered to be a useful

adjunct.

Rowachol

(Rowa)AU

Capsules

,green, e/c, borneol 5 mg, camphene 5 mg,

cineole2 mg, menthol 32 mg, menthone 6mg, pinene

17mg in olive oil. Net price 50-cap pack = £7.35.

Label:22

Dose

1–2capsules 3 times daily before food (but see notes

above)

Interactions:Appendix 1 (

Rowachol

)

1.9.2

Bile acid sequestrants

Colestyramine is an anion-exchange resin that is not

absorbed from the gastro-intestinal tract. It relieves

diarrhoeaand pruritus by forming an insoluble complex

withbile acids in the intestine. Colestyramine can inter-

ferewith the absorption of a number of drugs. Colestyr-

amine is also used in hypercholesterolaemia (section

2.12).

COLESTYRAMINE

(Cholestyramine)

Indications

pruritusassociated with partial biliar y

obstructionand primary biliary cirrhosis; diar rhoea

associatedwith Crohn’s disease, ileal resection,

vagotomy,diabetic vagal neuropathy, and radiation;

hypercholesterolaemia(section 2.12)

Cautions

section2.12

Contra-indications

section2.12

Pregnancy

section2.12

Breast-feeding

section2.12

Side-effects

section2.12

Dose

. Pruritus,4–8 g daily in a suitable liquid; CHILD 1–18

yearssee

BNFfor Children

. Diarrhoea,initially 4g daily increased by 4g at weekly

intervalsto 12–24 g daily in a suitable liquid in 1–4

78 1.9 Drugs affecting intestinal secretions BNF 61

Gastro-intestinalsystem

divideddoses, then adjusted as required; max. 36 g

daily;

CHILD1–18 years see

BNFfor Children

Counselling

Otherdr ugs should be taken at least 1 hour

beforeor 4–6 hours after colestyramine to reduce possible

interferencewith absorption

Note

Thecontents of each sachet should be mixed with at

least150 mL of water or other suitable liquid such as fruit

juice,skimmed milk, thin soups, and pulpy fruits with a high

moisturecontent

Preparations

Section2.12

1.9.3

Aprotinin

Aprotininis no longer used for the treatment of acute

pancreatitis.

1.9.4

Pancreatin

Supplementsof pancreatin are given by mouth to com-

pensate for reduced or absent exocrine secretion in

cystic ﬁbrosis, and following pancreatectomy, gastrec-

tomy,or chronic pancreatitis. They assist the digestion

of starch, fat, and protein. Pancreatin may also be

necessaryif a tumour (e.g. pancreatic cancer) obstructs

outﬂowfrom the pancreas.

Pancreatinis inactivated by gastric acid therefore pan-

creatinpreparations are best taken with food (or imme-

diatelybefore or after food). Gastric acid secretion may

be reduced by giving cimetidine or ranitidine an hour

beforehand (section 1.3). Concurrent use of antacids

alsoreduces gastric acidity.Enteric-coated preparations

delivera higher enzyme concentration inthe duodenum

(provided the capsule contents are swallowed whole

without chewing). Higher-strength preparations are

alsoavailable (impor tant:see CSM advice below).

Since pancreatin is also inactivated by heat, excessive

heatshould be avoided if preparations are mixed with

liquidsor food; theresulting mixtures should not be kept

formore than one hour.

Dosage is adjusted according to size, number, and

consistencyof stools, so that the patient thrives; extra

allowancewill be needed if snacks are taken between

meals.

Pancreatin can irritate the perioral skin and buccal

mucosa if retained in the mouth, and excessive doses

can cause perianal ir ritation. The most frequent side-

effectsare gastro-intestinal, including nausea, vomiting,

andabdominal discomfort; hyperuricaemia and hyper-

uricosuria have been associated with very high doses.

Hypersensitivityreactions occur occasionally and may

affectthose handling the powder.

PANCREATIN

Indications

seeabove

Cautions

seeabove and (for higher-strength prepara-

tions)see below

Pregnancy

notknown to be harmful

Side-effects

seeabove and (for higher-strength pre-

parations)see below

Dose

. Seepreparations

Creon

10000 (Solvay)

Capsules

,brown/clear, enclosing buf f-coloured e/c

granulesof pancreatin (pork), providing: protease

600units, lipase 10000 units, amylase 8000 units. Net

price100-cap pack = £12.93. Counselling, see dose

Dose

ADULTand CHILD initially1–2 capsules with each meal

eithertaken whole or contents mixed with ﬂuid or soft food (then

swallowedimmediately without chewing)

Creon

Micro(Solvay)

Gastro-resistantgranules

,brown, pancreatin (por k),

providing:protease 200 units, lipase 5000 units, amy-

lase3600 units per 100 mg, net price 20 g = £31.50

Counselling,see dose

Dose

ADULTand CHILD initially100 mg with each meal either

takenwhole or mixed with acidic ﬂ uid or soft food (then swal-

lowedimmediately without chewing)

Nutrizym10

(MerckSerono)

Capsules

,red/yellow, enclosing e/c minitablets of

pancreatin(pork), providing minimum of: protease

500units, lipase 10 000units, amylase 9000 units. Net

price100 = £14.47. Counselling, see dose

Dose

ADULTand CHILD 1–2capsules with meals and 1 capsule

withsnacks, swallowed whole or contents taken with water or

mixedwith soft food (then swallowed immediately without

chewing);higher doses may be required according to response

Pancrex

(Paines& Byrne)

Granules

,pancreatin (pork), providing minimum of:

protease300 units, lipase 5000 units, amylase

4000units/g. Net price 300 g = £20.39. Label: 25,

counselling,see dose

Dose

ADULTandCHILD 5–10g just before meals washed down or

mixedwith a little milk or water

PancrexV

(Paines& Byrne)

Capsules

,pancreatin (pork), providing minimum of:

protease430 units, lipase 8000 units, amylase

9000units. Net price 300-cap pack = £15.80. Coun-

selling,see dose

Dose

ADULTandCHILD over1 year 2–6 capsules with each meal,

swallowedwhole or sprinkled on food; INFANT up to 1 year

contentsof 1–2 capsules mixed with feeds

Capsules‘125’

,pancreatin (por k), providing mini-

mumof: protease 160units, lipase 2950 units,amylase

3300units, net price 300-cap pack = £9.72. Counsel-

ling,see dose

Dose

NEONATEcontents of 1–2 capsules mixed with feeds

Tablets

,e/c, pancreatin (pork), providing minimum

of:protease 110 units, lipase 1900 units, amylase

1700units. Net price 300-tab pack = £4.51. Label: 5,

25,counselling, see dose

Dose

ADULTand CHILD 5–15tablets before each meal

Tabletsforte

,e/c, pancreatin (pork), providing mini-

mumof: protease 330units, lipase 5600 units,amylase

5000units. Net price 300-tab pack = £13.74. Label: 5,

25,counselling, see dose

Dose

ADULTand CHILD 6–10tablets before each meal

Powder

,pancreatin (pork), providing minimum of:

protease1400 units, lipase 25 000 units, amylase

30000units/g. Net price 300 g = £24.28. Counselling,

seedose

Dose

ADULTand CHILD over1 month, 0.5–2 g before each meal,

washeddown or mixed with liquid; NEONATE 250–500mg with

eachfeed

BNF 61 1.9.3 Aprotinin 79

Gastro-intestinalsystem

Higher-strengthpreparations

The high-strength pancreatin preparations

Nutrizym

and

PancreatinHL

havebeen associated with

the development of large bowel strictures (ﬁbrosing

colonopathy) in children with cystic ﬁbrosis aged

between 2 and 13 years. No associationwas found

with

Creon

25000

and

Creon

40000

.The follow-

ingis recommended:

Pancrease HL

and

Nutrizym 22

should not be

used in children aged 15 years or less with cystic

ﬁbrosis;

the total dose ofpancreatic enzyme supplements

used in patients with cystic ﬁbrosis should not

usuallyexceed 10 000 units of lipase per kg body-

weightdaily;

ifa patient on any pancreatin preparation develops

newabdominal symptoms (or any change in exist-

ing abdominal symptoms) the patient should be

reviewed to exclude the possibility of colonic

damage.

Possiblerisk factors are gender (boys at greater risk

thangirls), more severe cystic ﬁbrosis, and concomi-

tant use of laxatives.The peak age for developing

ﬁbrosingcolonopathy is between 2 and 8 years.

Counselling

Itis important toensure adequate hydration at all

timesin patients receiving higher-strength pancreatin pre-

parations.

Creon

25000 (Solvay)A

Capsules

,orange/clear, enclosing brown-coloured

e/cpellets of pancreatin (pork), providing: protease

(total)1000 units, lipase 25 000 units, amylase

18000units, net price 100-cap pack = £28.25. Coun-

selling,see above and under dose

Dose

ADULTandCHILD initially1 capsule with meals either taken

wholeor contents mixed with ﬂuid or soft food (then swallowed

immediatelywithout chewing)

Creon

40000 (Solvay)A

Capsules

,brown/clear, enclosing brown-coloured

e/cgranules of pancreatin (pork), providing: protease

(total)1600 units, lipase 40 000 units, amylase

25000units, net price 100-cap pack = £60.00. Coun-

selling,see above and under dose

Dose

ADULTand CHILD initially1–2 capsules with meals either

takenwhole or conten ts mixed with ﬂuid or soft food (then

swallowedimmediately without chewing)

Nutrizym22

(MerckSerono) A

Capsules

,red/yellow, enclosing e/c minitablets of

pancreatin(pork), providing minimum of: protease

1100units, lipase 22 000units, amylase 19 800 units.

Netprice 100-cap pack = £33.33. Counselling, see

aboveand under dose

Dose

ADULTand CHILD over15 years, 1–2 capsules with meals

and1 capsule with snacks, swallowed whole or contents taken

withwater or mixed with soft food (then swallowed immediately

withoutchewing)

PancreaseHL

(Janssen-Cilag)A

Capsules

,enclosing light brown e/c minitablets of

pancreatin(pork), providing minimum of: protease

1250units, lipase 25 000units, amylase 22 500 units.

Netprice 100 = £31.70. Counselling, see above and

underdose

Dose

ADULTand CHILD over15 years, 1–2 capsules during each

mealand 1 caps ule with snacks swallowed whole or contents

mixedwith slightly acidic liquid or soft food (then swallowed

immediatelywithout chewing)

80 1.9.4 Pancreatin BNF 61

Gastro-intestinalsystem

2 Cardiovascular system

2.1 Positive inotropic drugs 81

2.1.1

Cardiacglycosides 81

2.1.2 Phosphodiesterase type-3 inhi-

bitors

2.2 Diuretics 83

2.2.1

Thiazidesand related diuretics 84

2.2.2 Loop diuretics 86

2.2.3 Potassium-sparing diuretics and

aldosteroneantagonists

2.2.4 Potassium-sparing diureticswith

otherdiuretics

2.2.5 Osmotic diuretics 89

2.2.6 Mercurial diuretics 90

2.2.7 Carbonic anhydrase inhibitors 90

2.2.8 Diuretics with potassium 90

2.3 Anti-arrhythmic drugs 90

2.3.1

Managementof arrhythmias 90

2.3.2 Drugs for arrhythmias 92

2.4 Beta-adrenoceptor blocking

drugs

2.5 Hypertension and heart failure 104

2.5.1

Vasodilatorantihypertensive

drugs

107

2.5.2 Centrally actingantihypertensive

drugs

110

2.5.3 Adrenergic neurone blocking

drugs

111

2.5.4 Alpha-adrenoceptor blocking

drugs

112

2.5.5 Drugs affecting the renin-angio-

tensinsystem

114

2.5.5.1 Angiotensin-converting enzyme

inhibitors

115

2.5.5.2 Angiotensin-II receptor antago-

nists

121

2.5.5.3 Renin inhibitors 124

2.6 Nitrates, calcium-channel block-

ers,and other antianginal drugs

124

2.6.1

Nitrates 125

2.6.2 Calcium-channel blockers 128

2.6.3 Other antianginal drugs 134

2.6.4 Peripheral vasodilators and

relateddrugs

135

2.7 Sympathomimetics 137

2.7.1

Inotropicsympathomimetics 137

2.7.2 Vasoconstrictor sympatho-

mimetics

138

2.7.3 Cardiopulmonary resuscitation 139

2.8 Anticoagulants and protamine 139

2.8.1

Parenteralanticoagulants 140

2.8.2 Oral anticoagulants 146

2.8.3 Protamine sulphate 149

2.9 Antiplatelet drugs 149

2.10 Stable angina, acute coronary

syndromes,and ﬁbrinolysis

154

2.10.1

Managementof stable angina

andacute coronary syndromes

154

2.10.2 Fibrinolytic drugs 157

2.11 Antiﬁbrinolytic drugs and

haemostatics

159

2.12 Lipid-regulating drugs 161

2.13 Local sclerosants 169

Thischapter also includes adviceon the drug man-

agementof the following:

angina,p. 154

arrhythmias,p. 90

cardiovasculardisease risk, p.104 and p. 161

heartfailure, p. 114

hypertension,p. 104

myocardialinfarction, p. 154

phaeochromocytoma,p. 113

stroke,p. 150

2.1

Positive inotropic drugs

2.1.1 Cardiac glycosides

2.1.2 Phosphodiesterase type-3 inhibitors

Positiveinotropic drugs increase the force of contrac-

tion of the myocardium; for sympathomimetics with

inotropicactivity see section 2.7.1.

2.1.1

Cardiac glycosides

Digoxinis acardiac glycosidethat increasesthe forceof

myocardialcontraction andreduces conductivity within

theatrioventricular (AV) node.

Digoxin is most useful for controlling ventricular

responsein persistent and permanent atrial ﬁbrillation

andatrial ﬂutter(section 2.3.1). Forreference tothe role

ofdigoxin in heart failure,see section 2.5.5.

BNF 61 81

Cardiovascularsystem

For management of atrial ﬁbrillation the maintenance

doseof digoxincan usuallybe determined bythe ventri-

cularrate atrest, whichshould not usuallybe allowedto

fallpersistently below 60 beatsper minute.

Digoxinis nowrarely usedfor rapidcontrol of heartrate

(seesection 2.3for the managementof supraventricular

arrhythmias). Even with intravenous administration,

response may take many hours; persistence of tachy-

cardiais therefore not an indication for exceeding the

recommended dose. The intramuscular route is not

recommended.

Inpatients with heart failurewho are in sinus rhythm a

loadingdose is notrequired, and a satisfactoryplasma-

digoxinconcentration can beachieved over aperiod of

abouta week.

Digoxinhas along half-lifeand maintenancedoses need

tobe given onlyonce daily (althoughhigher doses may

bedivided to avoid nausea); renalfunction is the most

importantdeterminant of digoxin dosage.

Unwantedeffects depend both on theconcentration of

digoxin in the plasma and on the sensitivity of the

conducting system or of the myocardium, which is

often increased in heart disease. It can sometimes be

difﬁcultto distinguish betweentoxic effects andclinical

deteriorationbecause symptomsof bothare similar.The

plasma concentration alone cannot indicate toxicity

reliably,but thelikelihood of toxicity increasesprogres-

sively through the range 1.5to 3 micrograms/litre for

digoxin.Digoxin shouldbe used withspecial care inthe

elderly,who may beparticularly susceptible to digitalis

toxicity.

Regular monitoring of plasma-digoxin concentration

during maintenancetreatment is not necessary unless

problemsare suspected. Hypokalaemiapredisposes the

patient to digitalis toxicity; it is managed by giving a

potassium-sparing diuretic or, if necessary, potassium

supplementation.

Iftoxicity occurs, digoxinshould be withdrawn;serious

manifestations require urgent specialist management.

Digoxin-speciﬁcantibody fragments are availablefor

reversalof life-threatening overdosage (see below).

DIGOXIN

Indications

heartfailure (see also section2.5.5),

supraventriculararrhythmias (particularly atrial

ﬁbrillationand atrial ﬂutter; see alsosection 2.3.2)

Cautions

recentmyocardial infarction; sick sinus

syndrome;thyroid disease;reduce dose inthe elderly;

severerespiratory disease; hypokalaemia, hypo-

magnesaemia,hypercalcaemia, and hypoxia (riskof

digitalistoxicity); monitor serum electrolytesand

renalfunction; avoidrapid intravenous administration

(riskof hypertension and reducedcoronary ﬂow);

interactions:Appendix 1 (cardiac glycosides)

Contra-indications

intermittentcomplete heartblock,

seconddegree AV block; supraventriculararrhyth-

miasassociated with accessory conductingpathways

e.g.Wolff-Parkinson-White syndrome; ventricular

tachycardiaor ﬁbrillation; hypertrophic cardiomyo-

pathy(unless concomitant atrial ﬁbrillation and heart

failure—butuse with caution); myocarditis;constric-

tivepericarditis (unless to controlatrial ﬁbrillation or

improvesystolic dysfunction—but use withcaution)

Renalimpairment

reducedose and monitor plasma-

digoxinconcentration; toxicity increased byelectro-

lytedisturbances

Pregnancy

mayneed dosage adjustment

Breast-feeding

amounttoo small to behar mful

Side-effects

seenotes above; also nausea,vomiting,

diarrhoea;ar rhythmias,conduction disturbances;

dizziness;blurred or yellow vision;rash, eosinophilia;

lesscommonly

depression;

veryrarely

anorexia,

intestinalischaemia and necrosis, psychosis,apathy,

confusion,headache, fatigue, weakness, gynaeco-

mastiaon long-term use, andthrombocytopenia

Dose

. Rapiddigitalisation, for atrial ﬁbrillationor ﬂutter, by

mouth,0.75–1.5 mg over24 hours in divideddoses

. Maintenance,for atrialﬁbrillation orﬂutter, bymouth,

accordingto renal function andinitial loading dose;

usualrange 125–250 microgramsdaily

. Heartfailure (for patientsin sinus rhythm),by mouth,

62.5–125micrograms once daily

. Emergencyloading dose, for atrialﬁbrillation or ﬂut-

ter,by intravenous infusion (butrarely necessary),

0.75–1mg over atleast 2 hours (seealso Cautions)

thenmaintenance doseby mouthon thefollowing day

Note

Theabove doses mayneed to be reducedif digoxin (or

anothercardiac glycoside) hasbeen given inthe preceding 2

weeks.Digoxin doses inthe BNF maydiffer from thosein

productliterature. Forplasma concentrationmonitoring, blood

shouldideally be takenat least 6hours after adose

Digoxin(Non-proprietary) A

Tablets

,digoxin 62.5 micrograms,net price 28-tab

pack= £2.03; 125micrograms, 28-tab pack= £1.12;

250micrograms, 28-tabpack = £1.13

Injection

,digoxin 250 micrograms/mL,net price 2-

mLamp = 70p

Paediatricinjection

,digoxin 100 micrograms/mL

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.988

Lanoxin

(Aspen)A

Tablets

,digoxin 125 micrograms,net price 500-tab

pack= £8.09; 250micrograms (scored), 500-tabpack

=£8.09

Injection

,digoxin 250 micrograms/mL,net price 2-

mLamp = 66p

Lanoxin-PG

(Aspen)A

Tablets

,blue, digoxin62.5 micrograms,net price500-

tabpack = £8.09

Elixir

,yellow, digoxin 50micrograms/mL. Do not

dilute,measure withpipette. Net price60 mL= £5.35.

Counselling,use of pipette

Digoxin-speciﬁc antibody

Digoxin-speciﬁcantibody fragments areindicated for

thetreatment ofknown orstrongly suspecteddigoxin or

other cardiac glycoside overdosage when measures

beyond the withdrawal of the cardiac glycoside and

correction of any electrolyte abnormalities are felt to

benecessary (see also notes above).

Digibind

(GSK)A

Injection

,powder forpreparation ofinfusion, digoxin-

speciﬁcantibody fragments (F(ab)) 38mg, net price

pervial = £93.97 (hosp.and poisons centres only)

Dose

consultproduct literature

82 2.1.1 Cardiac glycosides BNF61

Cardiovascularsystem

2.1.2

Phosphodiesterase type-

3 inhibitors

Enoximoneand milrinoneare phosphodiesterasetype-

3inhibitors that exert most of theiref fecton the myo-

cardium. Sustained haemodynamic beneﬁt has been

observedafter administration, but there isno evidence

ofany beneﬁcial effect on survival.

ENOXIMONE

Indications

congestiveheart failure where cardiac

outputreduced and ﬁlling pressuresincreased

Cautions

heartfailure associated with hypertrophic

cardiomyopathy,stenotic or obstructivevalvular dis-

easeor other outlet obstruction;monitor blood pres-

sure,heart rate, ECG, centralvenous pressure, ﬂuid

andelectrolyte status, renal function,platelet count,

hepaticenzymes; avoid extravasation; interactions:

Appendix1 (phosphodiesterase type-3 inhibitors)

Hepaticimpairment

dosereduction may be required

Renalimpairment

considerdose reduction

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risk

Breast-feeding

manufactureradvises caution—no

informationavailable

Side-effects

ectopicbeats; less frequently ventricular

tachycardiaor supraventricular arrhythmias (more

likelyin patients with pre-existingarrhythmias);

hypotension;also headache, insomnia, nauseaand

vomiting,diarrhoea; occasionally, chills,oliguria,

fever,urinary retention; upper andlower limb pain

Dose

. Byslow intravenous injection (ratenot exceeding

12.5mg/minute), diluted beforeuse, initially 0.5–

1mg/kg, then 500micrograms/kg every 30minutes

untilsatisfactory response or total of3 mg/kg given;

maintenance,initial dose of upto 3 mg/kgmay be

repeatedevery 3–6 hoursas required

. Byintravenous infusion, initially 90micrograms/kg/

minuteover 10–30minutes, followed bycontinuous or

intermittentinfusion of 5–20micrograms/kg/minute

Totaldose over 24hours should notusually exceed

24mg/kg

Perfan

(INCA-Pharm)A

Injection

,enoximone 5 mg/mL.For dilution before

use.Net price 20-mL amp= £15.02

Excipients

includealcohol, propyleneglycol

Note

Plasticapparatus should be used;crystal formation if

glassused

MILRINONE

Indications

short-termtreatment ofsevere congestive

heartfailure unresponsive to conventionalmainte-

nancetherapy (not immediately aftermyocardial

infarction);acute heart failure, includinglow output

statesfollowing heart surgery

Cautions

seeunder Enoximone; also correct hypo-

kalaemia;interactions: Appendix 1 (phosphodi-

esterasetype-3 inhibitors)

Renalimpairment

reducedose andmonitor response

ifeGFR less than 50mL/minute/1.73 m

—consult

productliterature for details

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risk

Breast-feeding

manufactureradvises caution—no

informationavailable

Side-effects

ectopicbeats, ventricular tachycardia,

supraventriculararrhythmias (more likely inpatients

withpre-existing arrhythmias), hypotension; head-

ache;

lesscommonly

ventricularﬁbrillation, chest

pain,tremor, hypokalaemia, thrombocytopenia;

very

rarely

bronchospasm,anaphylaxis, and rash

Dose

. Byintravenous injection over 10minutes, either

undilutedor diluted before use,50 micrograms/kg

followedby intravenous infusion ata rate of 375–

750nanograms/kg/minute, usuallyfor upto 12hours

followingsurgery or for 48–72hours in congestive

heartfailure; max. daily dose1.13 mg/kg

Primacor

(Sanoﬁ-Aventis)A

Injection

,milrinone (as lactate) 1mg/mL, net price

10-mLamp = £16.61

2.2

Diuretics

2.2.1 Thiazides and related diuretics

2.2.2 Loop diuretics

2.2.3 Potassium-sparing diuretics and

aldosteroneantagonists

2.2.4 Potassium-sparing diuretics with

otherdiuretics

2.2.5 Osmotic diuretics

2.2.6 Mercurial diuretics

2.2.7 Carbonic anhydrase inhibitors

2.2.8 Diuretics with potassium

Thiazides (section 2.2.1) are used to relieve oedema

dueto chronic heartfailure (section 2.5.5)and, in lower

doses,to reduce blood pressure.

Loop diuretics (section 2.2.2) are used in pulmonary

oedema due to left ventricular failure and in patients

withchronic heart failure (section2.5.5).

Combination diuretic therapy may be effective in

patients with oedema resistant to treatment with one

diuretic.Vigorous diuresis, particularly with loop diur-

etics,may induce acutehypotension; rapid reductionof

plasmavolume should be avoided.

Elderly

Lowerinitial doses ofdiuretics should beused

inthe elderly because they are particularlysusceptible

to the side-effects. The dose should then be adjusted

according to renal function. Diuretics should not be

usedcontinuously on a long-term basis totreat simple

gravitational oedema (which will usually respond to

increased movement, raising the legs, and support

stockings).

Potassium loss

Hypokalaemia canoccur with both

thiazide and loop diuretics. The risk of hypokalaemia

dependson theduration ofaction as wellas thepotency

andis thus greater with thiazides thanwith an equipo-

tentdose of a loopdiuretic.

Hypokalaemia is dangerous in severe cardiovascular

diseaseand in patients also being treated withcardiac

glycosides.Often theuse of potassium-sparingdiuretics

(section2.2.3) avoids the need to take potassium sup-

plements.

Inhepatic failure,hypokalaemia caused bydiuretics can

precipitate encephalopathy, particularly in alcoholic

BNF 61 2.1.2 Phosphodiesterase type-3 inhibitors 83

Cardiovascularsystem

cirrhosis; diuretics can also increase the risk of hypo-

magnesaemiain alcoholic cirrhosis, leadingto arrhyth-

mias.Spironolactone, apotassium-sparing diuretic (sec-

tion2.2.3), is chosen for oedemaarising from cirrhosis

ofthe liver.

Potassiumsupplements or potassium-sparing diuretics

are seldom necessary when thiazides are used in the

routine treatment of hypertension (see also section

9.2.1.1).

2.2.1

Thiazides and related

diuretics

Thiazides and related compounds are moderately

potent diuretics; they inhibit sodium reabsorption at

thebeginning of the distal convolutedtubule. They act

within1 to2 hours oforal administrationand mosthave

aduration of action of 12to 24 hours; theyare usually

administeredearly in the day so thatthe diuresis does

notinterfere with sleep.

In the management of

hypertension

a low dose of a

thiazide, e.g. bendroﬂ umethiazide 2.5 mg daily, pro-

ducesa maximal or near-maximal blood pressure low-

ering effect, with very littlebiochemical disturbance.

Higher doses cause more marked changes in plasma

potassium, sodium,uric acid, glucose, and lipids, with

littleadvantage inblood pressure control.For reference

tothe useof thiazidesin chronicheart failuresee section

2.5.5.

Bendroﬂumethiazide iswidely used for mild or mod-

erate heart failure and for hypertension—alone in the

treatment ofmild hypertension or with other drugs in

moresevere hypertension.

Chlortalidone, a thiazide-related compound, has a

longer duration of action than the thiazides and may

begiven on alternatedays to control oedema.It is also

usefulif acute retention isliable to be precipitatedby a

more rapid diuresis or if patients dislike the altered

patternof micturition caused byother diuretics.

Other thiazide diuretics (including benzthiazide, clop-

amide, cyclopenthiazide, hydrochlorothiazide, and

hydroﬂumethiazide)do not offer anysigniﬁcant advan-

tageover bendroﬂumethiazide or chlortalidone.

Metolazone is particularly ef fective when combined

with a loop diuretic (even in renal failure); profound

diuresiscan occur and the patient should therefore be

monitoredcarefully.

Xipamide and indapamide are chemically related to

chlortalidone. Indapamide is claimed to lower blood

pressure with less metabolic disturbance, particularly

lessaggravation of diabetes mellitus.

Cautions

See also section 2.2. Thiazides and related

diuretics can exacerbate diabetes, gout, and systemic

lupuserythematosus. Electrolytes shouldbe monitored,

particularlywith high doses, long-term use, or inrenal

impairment.Thiazides and relateddiuretics should also

beused withcaution in nephroticsyndrome, hyperaldo-

steronism, and malnourishment; interactions: Appen-

dix1 (diuretics)

Contra-indications

Thiazides and related diuretics

should be avoided in refractory hypokalaemia, hypo-

natraemiaand hypercalcaemia,symptomatic hyperuric-

aemia,and Addison’s disease.

Hepaticimpairment

Thiazidesand related diuretics

shouldbe usedwith caution inmild tomoderate impair-

mentand avoidedin severeliver disease.Hypokalaemia

may precipitate coma, although hypokalaemia can be

preventedby using apotassium-sparing diuretic. There

is an increased risk of hypomagnesaemia in alcoholic

cirrhosis.

Renalimpairment

Thiazidesand relateddiuretics are

ineffective ifeGFR is less than 30 mL/minute/1.73m

and should be avoided; metolazone remains effective

butwith a risk ofexcessive diuresis.

Pregnancy

Thiazidesand related diureticsshould not

be used to treat gestational hypertension. They may

cause neonatal thrombocytopenia, bone marrow sup-

pression, jaundice,electrolyte disturbances, and hypo-

glycaemia; placental perfusion may also be reduced.

Stimulation of labour, uterine inertia, and meconium

staininghave also been reported.

Breast-feeding

Theamount of bendroﬂumethiazide,

chlortalidone, cyclopenthiazide, and metolazone pre-

sent in milk is too small to be harmful; large doses

maysuppress lactation. For indapamide and xipamide

seeindividual drugs.

Side-effects

Side-effectsof thiazides andrelated diur-

eticsinclude mildgastro-intestinal disturbances, postur-

al hypotension, altered plasma-lipid concentrations,

metabolicand electrolyte disturbances including hypo-

kalaemia(see also notes above), hyponatraemia,hypo-

magnesaemia, hypercalcaemia, hyperglycaemia,hypo-

chloraemic alkalosis, hyperuricaemia, and gout. Less

common side-effects include blood disorders such as

agranulocytosis, leucopenia, and thrombocytopenia,

and impotence. Pancreatitis, intrahepatic cholestasis,

cardiacarrhythmias, headache, dizziness, paraesthesia,

visual disturbances, and hypersensitivity reactions

(including pneumonitis, pulmonary oedema, photo-

sensitivity,and severeskin reactions)have also been

reported.

BENDROFLUMETHIAZIDE

(Bendroﬂuazide)

Indications

oedema,hypertension (see also notes

above)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above

Dose

. Oedema,initially 5–10mg daily in themorning

alternatedays; maintenance 5–10mg 1–3 times

weekly

. Hypertension,2.5 mg dailyin the morning; higher

dosesrarely necessary (see notes above)

Bendroﬂumethiazide(Non-proprietary) A

Tablets

,bendroﬂumethiazide 2.5 mg,net price 28 =

79p;5 mg, 28= 86p

Brandsinclude

Aprinox

84 2.2.1 Thiazides and related diuretics BNF 61

Cardiovascularsystem

CHLORTALIDONE

(Chlorthalidone)

Indications

ascitesdue to cirrhosis in stablepatients

(underclose supervision), oedema due tonephrotic

syndrome,hypertension (see also notesabove), mild

tomoderate chronic heart failure;diabetes insipidus

(seesection 6.5.2)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above;also

rarely

jaundiceand

allergicinterstitial nephritis

Dose

. Oedema,up to 50mg daily

. Hypertension,25 mg dailyin the morning, increased

to50 mg dailyif necessary (but seenotes above)

. Heartfailure, 25–50mg daily in the morning,

increasedif necessary to100–200 mgdaily (reduceto

lowesteffective dose for maintenance)

Hygroton

(Alliance)A

Tablets

,yellow, scored, chlortalidone 50mg, netprice

28-tabpack = £1.64

CYCLOPENTHIAZIDE

Indications

oedema,hypertension (see also notes

above);heart failure

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also

rarely

depression

Dose

. Heartfailure, 250–500micrograms daily in the

morningincreased if necessary to1 mg daily(reduce

tolowest effective dose for maintenance)

. Hypertension,initially 250 microgramsdaily in the

morning,increased if necessary to500 micrograms

daily(but see notes above)

. Oedema,up to 500micrograms daily for ashort

period

Navidrex

(Goldshield)A

Tablets

,scored, cyclopenthiazide 500micrograms,

netprice 28-tab pack =£1.27

Excipients

includegluten

Note

Maybe difﬁcult toobtain

INDAPAMIDE

Indications

essentialhypertension

Cautions

seenotes above; also acutepor phyria (sec-

tion9.8.2)

Contra-indications

seenotes above; also hypersensi-

tivityto sulfonamides

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

presentin milk—manufacturer

advisesavoid

Side-effects

seenotes above;also palpitation,diuresis

withdoses above 2.5mg daily

Dose

. 2.5mg dailyin the morning

Indapamide(Non-proprietary) A

Tablets

,s/c, indapamide 2.5mg, net price 28-tab

pack= £1.27, 56-tab pack= £2.01

Natrilix

(Servier)A

Tablets

,f/c, indapamide 2.5mg. Net price 30-tab

pack= £3.40, 60-tab pack= £6.80

Modiﬁedrelease

EthibideXL

(Genus)A

Tablets

,m/r, indapamide 1.5mg, net price30-tab

pack= £4.05. Label: 25

Dose

hypertension,1 tablet daily,preferably inthe morning

NatrilixSR

(Servier)A

Tablets

,m/r, indapamide 1.5mg, net price30-tab

pack= £3.40. Label: 25

Dose

hypertension,1 tablet daily,preferably inthe morning

METOLAZONE

Indications

oedema,hypertension (see also notes

above)

Cautions

seenotes above; also acutepor phyria (sec-

tion9.8.2)

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also chills,chest pain

Dose

. Oedema,5–10 mg dailyin the morning, increasedif

necessaryto 20 mgdaily in resistant oedema,max.

80mg daily

. Hypertension,initially 5 mgdaily in the morning;

maintenance5 mg onalternate days

Metenix5

(Sanoﬁ-Aventis)A

Tablets

,blue, metolazone 5mg, net price 100-tab

pack= £18.20

XIPAMIDE

Indications

oedema,hypertension (see also notes

above)

Cautions

seenotes above; also acutepor phyria (sec-

tion9.8.2)

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

noinformation available

Side-effects

seenotes above

Dose

. Oedema,initially 40mg daily in the morning,

increasedto 80 mgin resistant cases; maintenance

20mg in themorning

. Hypertension,20 mg dailyin the morning

Diurexan

(Meda)A

Tablets

,scored, xipamide 20mg, net price 140-tab

pack= £19.46

BNF 61 2.2.1 Thiazides and related diuretics 85

Cardiovascularsystem

2.2.2

Loop diuretics

Loop diuretics are used in pulmonary oedema dueto

left ventricularfailure; intravenous administration pro-

duces relief of breathlessness and reduces pre-load

soonerthan would be expected fromthe time of onset

ofdiuresis. Loop diureticsare also usedin patients with

chronicheart failure. Diuretic-resistant oedema(except

lymphoedema and oedema due to peripheral venous

stasisor calcium-channelblockers) canbe treatedwith a

loopdiuretic combined witha thiazide or relateddiure-

tic (e.g. bendroﬂumethiazide 5–10 mg daily or meto-

lazone5–20 mg daily).

Ifnecessary, a loopdiuretic can be addedto antihyper-

tensive treatment to achieve better control of blood

pressure in those with resistant hypertension, or in

patientswith impaired renal functionor heart failure.

Loopdiuretics inhibit reabsorption from the ascending

limb of the loop of Henle

in the renal tubule and are

powerfuldiuretics.

Furosemide and bumetanide are similarin activity;

bothact within 1 hour of oraladministration and diur-

esisis completewithin 6hours sothat, if necessary,they

canbe given twice in one day withoutinterfering with

sleep.Following intravenousadministration they havea

peakef fectwithin 30 minutes. The diuresis associated

withthese drugs is dose related.

Torasemidehas properties similar to those of furose-

mideand bumetanide, andis indicated for oedemaand

forhypertension.

Cautions

Hypovolaemia and hypotension should be

corrected before initiation of treatment with loop diur-

etics;electrolytes shouldbe monitoredduring treatment

(see also Potassium Loss, section 2.2). Loop diuretics

can exacerbate diabetes (but hyperglycaemia is less

likely than with thiazides) and gout. If there is an

enlargedprostate, urinaryretention can occur,although

thisis less likelyif small dosesand less potent diuretics

areused initially; anadequate urinary output shouldbe

established before initiating treatment; interactions:

Appendix1 (diuretics).

Contra-indications

Loopdiuretics should beavoided

insevere hypokalaemia, severe hyponatraemia,anuria,

comatoseand precomatose states associatedwith liver

cirrhosis, and in renal failure due to nephrotoxic or

hepatotoxicdrugs.

Hepaticimpairment

Hypokalaemiainduced by loop

diuretics may precipitate hepatic encephalopathy and

coma—potassium-sparingdiuretics can beused to pre-

ventthis.

Renalimpairment

Highdoses of loop diuretics may

occasionallybe needed;high dosesor rapid intravenous

administration can cause tinnitus and deafness; high

doses of bumetanide can also cause musculoskeletal

pain.

Pregnancy

Furosemideand bumetanideshould notbe

used to treat gestational hypertension because of the

maternalhypovolaemia associated with thiscondition.

Side-effects

Side-effectsof loopdiuretics includemild

gastro-intestinal disturbances, pancreatitis, hepatic

encephalopathy, postural hypotension, temporary

increase inser um-cholesteroland triglyceride concen-

tration, hyperglycaemia (less common than with thi-

azides),acute urinaryretention, electrolytedisturbances

(including hyponatraemia, hypokalaemia (see section

2.2), hypocalcaemia, hypochloraemia, and hypo-

magnesaemia), metabolic alkalosis, blood disorders

(includingbone-marrow depression,thrombocytopenia,

and leucopenia), hyperuricaemia, visual disturbances,

tinnitusand deafness(usually withhigh parenteraldoses

andrapid administration, andin renal impairment),and

hypersensitivity reactions(including rash, photosensit-

ivity,and pruritus).

FUROSEMIDE

(Frusemide)

Indications

oedema(see notes above); resistant

hypertension(see notes above)

Cautions

seenotes above;also hypoproteinaemiamay

reducediuretic effectand increase riskof side-effects;

hepatorenalsyndrome; intravenous administration

rateshould notusually exceed4 mg/minute,however

singledoses ofup to80 mgmay beadministered more

rapidly

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above;also lower rateof

infusionmay be necessary

Pregnancy

seenotes above

Breast-feeding

amounttoo small to beharmful; may

inhibitlactation

Side-effects

seenotes above; also intrahepatic

cholestasisand gout

Dose

. Bymouth, oedema, initially 40mg in themorning;

maintenance20–40 mg daily;

CHILDunder 18 years

see

BNFfor Children

Resistantoedema, 80–120 mgdaily

Resistanthypertension, 40–80 mgdaily

. Byintramuscular injection

slowintravenous

injection(rate of administration,see Cautionsabove),

initially20–50 mg,increased if necessary in stepsof

20mg notless than every2 hours; dosesgreater than

50mg by intravenousinfusion only; max. 1.5g daily;

CHILDunder 18 years see

BNFfor Children

Furosemide(Non-proprietary) A

Tablets

,furosemide 20mg, netprice 28 =81p; 40mg,

28= 84p; 500mg, 28 =£4.05

Brandsinclude

Rusyde

Oralsolution

,sugar-free, furosemide, net price

20mg/5mL, 150 mL= £13.97; 40mg/5 mL,150 mL

=£18.19; 50mg/5 mL, 150mL =£19.35

Brandsinclude

Frusol

(containsalcohol 10%)

Injection

,furosemide 10mg/mL, netprice 2-mL amp

=30p, 5-mL amp =38p, 25-mL amp= £2.50

Lasix

(Sanoﬁ-Aventis)A

Injection

,furosemide 10mg/mL, netprice 2-mL amp

=75p

Note

Large-volumefurosemide injections also available; brands

include

Minijet

BUMETANIDE

Indications

oedema(see notes above)

Cautions

seenotes above

Contra-indications

seenotes above

86 2.2.2 Loop diuretics BNF 61

Cardiovascularsystem

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

noinformation available; may inhibit

lactation

Side-effects

seenotes above; also gynaecomastia,

breastpain, musculoskeletal pain (associatedwith

highdoses in renal failure)

Dose

. Bymouth, 1 mgin the morning, repeatedafter 6–8

hoursif necessary; severecases, 5mg daily increased

by5 mg every12–24 hours according toresponse;

ELDERLY,500micrograms daily may besufﬁcient

. Byintravenous injection, 1–2mg, repeated after 20

minutesif necessary;

ELDERLY,500micrograms daily

maybe sufﬁcient

. Byintravenous infusion, 2–5mg over 30–60minutes;

ELDERLY,500micrograms daily may besufﬁcient

. Byintramuscular injection, 1mg initially then

adjustedaccording to response;

ELDERLY,500micr-

ogramsdaily may be sufﬁcient

Bumetanide(Non-proprietary) A

Tablets

,bumetanide 1 mg,net price 28-tab pack=

£1.12;5 mg, 28-tabpack = £4.33

Oralliquid

,bumetanide 1mg/5 mL,net price150 mL

=£128.00

Injection

,bumetanide 500micrograms/mL, net price

4-mLamp = £1.79

Burinex

(LEO)A

Tablets

,scored, bumetanide 1mg, net price 28-tab

pack= £1.52; 5mg, 28 =£9.67

TORASEMIDE

Indications

oedema(see notes above), hypertension

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

manufactureradvises avoid—toxicity in

animal

studies

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

seenotes above; also dry mouth;

rarely

limbparaesthesia

Dose

. Oedema,5 mg oncedaily, preferably inthe morning,

increasedif required to 20mg once daily;usual max.

40mg daily

. Hypertension,2.5 mg daily,increased if necessaryto

5mg once daily

Torasemide(Non-proprietary) A

Tablets

,torasemide 5 mg,net price 28-tab pack=

£10.36;10 mg, 28-tabpack = £13.71

Torem

(Meda)A

Tablets

,torasemide 2.5 mg,net price 28-tab pack=

£3.78;5 mg (scored),28-tab pack = £5.53;10 mg

(scored),28-tab pack = £8.14

2.2.3

Potassium-sparing

diuretics and aldosterone

antagonists

Amiloride and triamterene on their own are weak

diuretics. They cause retention of potassium and are

thereforegiven withthiazide or loopdiuretics asa more

effective alternative to potassium supplements. See

section2.2.4 for compound preparationswith thiazides

orloop diuretics.

Potassiumsupplements must not be given with potas-

sium-sparing diuretics.Administration of a potassium-

sparingdiuretic to a patient receivingan ACE inhibitor

oran angiotensin-II receptor antagonistcan also cause

severehyperkalaemia.

AMILORIDEHYDROCHLORIDE

Indications

oedema;potassium conservation when

usedas an adjunct tothiazide or loop diuretics for

hypertension,congestive heart failure, orhepatic

cirrhosiswith ascites

Cautions

monitorelectrolytes; diabetes mellitus;

elderly;interactions: Appendix 1 (diuretics)

Contra-indications

hyperkalaemia;anuria; Addison’s

disease

Renalimpairment

monitorplasma-potassium con-

centration(high risk of hyperkalaemiain renal

impairment);manufacturers advise avoid insevere

impairment

Pregnancy

notused to treat gestationalhypertension

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

includegastro-intestinal disturbances,

drymouth, rashes, confusion, posturalhypotension,

hyperkalaemia,hyponatraemia

Dose

. Usedalone, initially 10mg daily

5mg twice daily,

adjustedaccording to response; max.20 mg daily

. Withother diuretics, congestiveheart failure and

hypertension,initially 5–10 mgdaily; cirrhosis with

ascites,initially 5mg daily

Amiloride(Non-proprietary) A

Tablets

,amiloride hydrochloride 5mg, net price 28-

tabpack = 96p

Oralsolution

,sugar-free, amiloride hydrochloride

5mg/5mL, net price 150mL = £39.73

Brandsinclude

Amilamont

(Excipientsinclude propyleneglycol,

seeExcipients, p.2)

Compoundpreparations with thiazide orloop

diuretics

Section2.2.4

TRIAMTERENE

Indications

oedema,potassium conservation with

thiazideand loop diuretics

Cautions

seeunder Amiloride Hydrochloride; may

causeblue ﬂuorescence of urine

Contra-indications

seeunder Amiloride Hydro-

chloride

Renalimpairment

monitorplasma-potassium con-

centration(high risk of hyperkalaemiain renal

BNF 61 2.2.3 Potassium-sparing diuretics and aldosterone antagonists 87

Cardiovascularsystem

impairment);manufacturers advise avoid insevere

impairment

Pregnancy

notused to treat gestationalhypertension

Breast-feeding

presentin milk—manufacturer

advisesavoid

Side-effects

includegastro-intestinal disturbances,

drymouth, rashes; slight decrease inblood pressure,

hyperkalaemia,hyponatraemia; photosensitivity and

blooddisorders also reported; triamterenefound in

kidneystones

Dose

. Initially150–250 mgdaily, reducing to alternatedays

after1 week; taken individed doses after breakfast

andlunch; lower initial dosewhen given with other

diuretics

Counselling

Urinemay look slightlyblue in somelights

Dytac

(Goldshield)A

Capsules

,maroon, triamterene 50mg, net price 30-

cappack = £17.35 Label:14, (see above), 21

Compoundpreparations with thiazides orloop

diuretics

Section2.2.4

Aldosterone antagonists

Spironolactonepotentiates thiazideor loopdiuretics by

antagonising aldosterone; it is a potassium-sparing

diuretic.Spironolactone is of value in the treatment of

oedema and ascites caused by cir rhosis of the liver;

furosemide (section 2.2.2) can be used as an adjunct.

Lowdoses of spironolactoneare beneﬁcial inmoderate

tosevere heart failure, seesection 2.5.5.

Spironolactone is also used in primary hyperaldo-

steronism(Conn’s syndrome).It is givenbefore surgery

orif surgery is not appropriate, in the lowest effective

dosefor maintenance.

Eplerenone is licensed for useas an adjunct in left

ventricular dysfunction with evidence of heart failure

aftera myocardial infarction(see also section 2.5.5and

section2.10.1).

Potassiumsupplements mustnot be given with aldo-

steroneantagonists.

EPLERENONE

Indications

adjunctin stable patients withleft ventri-

culardysfunction with evidence ofheart failure, fol-

lowingmyocardial infarction (start therapywithin 3–

14days of event)

Cautions

measureplasma-potassium concentration

beforetreatment, during initiation, andwhen dose

changed;elderly; interactions:Appendix 1 (diuretics)

Contra-indications

hyperkalaemia;concomitant use

ofpotassium-sparing diuretics or potassium supple-

ments

Hepaticimpairment

avoidin severe liver disease

Renalimpairment

increasedrisk of hyperkalaemia—

closemonitoring required; avoid ifeGFR less than

50mL/minute/1.73m

Pregnancy

manufactureradvises caution—no infor-

mationavailable

Breast-feeding

manufactureradvises use only if

potentialbeneﬁt outweighs risk

Side-effects

diarrhoea,nausea; hypotension; dizzi-

ness;hyperkalaemia; rash;

lesscommonly

ﬂatulence,

vomiting,atrial ﬁbrillation, postural hypotension,

arterialthrombosis, dyslipidaemia, pharyngitis, head-

ache,insomnia, gynaecomastia, pyelonephritis,

hyponatraemia,dehydration, eosinophilia, asthenia,

malaise,back pain, leg cramps,impaired renal func-

tion,azotaemia, sweating and pruritus

Dose

. Initially25 mgonce daily,increased within4 weeks to

50mg once daily;

CHILDnot recommended

Inspra

(Pﬁzer)TA

Tablets

,yellow, f/c, eplerenone25 mg, netprice 28-

tabpack = £42.72; 50mg, 28-tabpack = £42.72

SPIRONOLACTONE

Indications

oedemaand ascites in cirrhosis ofthe

liver,malignant ascites, nephroticsyndrome, conges-

tiveheart failure (section 2.5.5);primar yhyperaldo-

steronism

Cautions

potentialmetabolic productscarcinogenic in

rodents

;elderly; monitor electrolytes (discontinueif

hyperkalaemia);acute porphyria (section 9.8.2);

interactions:Appendix 1 (diuretics)

Contra-indications

hyperkalaemia,hyponatraemia;

anuria;Addison’s disease

Renalimpairment

monitorplasma-potassium con-

centration(high risk of hyperkalaemiain renal

impairment);avoid if rapidly deterioratingor severe

impairment

Pregnancy

feminisationof male fetus in

animal

stu-

dies

Breast-feeding

metabolitespresent in milk, but

amountprobably too small tobe harmful

Side-effects

gastro-intestinaldisturbances, hepato-

toxicity;malaise, headache, confusion, drowsiness,

dizziness;gynaecomastia, benign breast tumour,

breastpain, menstrualdisturbances, changesin libido;

hypertrichosis,hyperkalaemia (discontinue), hypo-

natraemia,acute renal failure, hyperuricaemia,

leucopenia,agranulocytosis, thrombocytopenia; leg

cramps;alopecia, hirsutism, rash, andStevens-John-

sonsyndrome

Dose

. 100–200mg daily,increased to 400mg if required;

CHILDunder 18 years, see

BNFfor Children

. Heartfailure, see section 2.5.5

Spironolactone(Non-proprietary) A

Tablets

,spironolactone 25 mg,net price 28 =£1.50;

50mg, 28 =£2.11; 100mg, 28 =£2.46. Label: 21

Oralsuspensions

,spironolactone 5 mg/5mL,

10mg/5mL, 25 mg/5mL, 50mg/5 mL,and 100mg/

5mL. Label: 21

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.988

Aldactone

(Pharmacia)A

Tablets

,f/c, spironolactone 25mg (buff), net price

100-tabpack = £8.89; 50mg (white), 100-tabpack =

£17.78;100 mg (buff),28-tab pack = £9.96.Label: 21

Withthiazides or loop diuretics

Section2.2.4

88 2.2.3 Potassium-sparing diuretics and aldosterone antagonists BNF 61

Cardiovascularsystem

2.2.4

Potassium-sparing

diuretics with other

diuretics

Althoughit is preferable to prescribe thiazides(section

2.2.1) and potassium-sparing diuretics (section 2.2.3)

separately,the use of ﬁxed combinationsmay be justi-

ﬁedif compliance isa problem. Potassium-sparingdiur-

eticsare not usually necessaryin the routine treatment

of hypertension, unless hypokalaemia develops. For

interactions,see Appendix 1 (diuretics).

Amiloridewith thiazides

Co-amilozide

(Non-proprietary)A

Tablets

,co-amilozide 2.5/25 (amiloridehydro-

chloride2.5 mg,hydrochlorothiazide 25mg), netprice

28-tabpack = £3.73

Brandsinclude

Moduret25

Dose

hypertension,initially 1tablet daily,increased if necessary

tomax. 2 tabletsdaily

Congestiveheart failure, initially1 tabletdaily, increased if

necessaryto max. 4tablets daily

Oedemaand ascitesincir rhosisofthe liver,initially 2tablets daily,

increasedif necessary tomax. 4 tabletsdaily; reduce formain-

tenanceif possible

Tablets

,co-amilozide 5/50 (amiloridehydrochloride

5mg, hydrochlorothiazide50 mg), netprice 28 =

£1.14

Brandsinclude

Amil-Co

Moduretic

Dose

hypertension,initially ½tablet daily,increasedif necessary

tomax. 1 tabletdaily

Congestiveheart failure, initially½ tabletdaily, increased if

necessaryto max. 2tablets daily

Oedemaand ascitesin cirrhosisof theliver, initially1 tabletdaily,

increasedif necessary tomax. 2 tabletsdaily; reduce formain-

tenanceif possible

Navispare

(Goldshield)A

Tablets

,f/c, orange, amiloride hydrochloride2.5 mg,

cyclopenthiazide250 micrograms,net price 28-tab

pack= £2.70

Excipients

includegluten

Dose

hypertension,1–2 tabletsin the morning

Amiloridewith loop diuretics

Co-amilofruse

(Non-proprietary)A

Tablets

,co-amilofruse 2.5/20 (amiloridehydro-

chloride2.5 mg, furosemide20 mg),net price 28-tab

pack= £1.18, 56-tab pack= £1.83

Brandsinclude

FrumilLS

Dose

oedema,1 tablet inthe morning

Tablets

,co-amilofruse 5/40 (amiloridehydrochloride

5mg, furosemide40 mg), netprice 28-tab pack =

£1.17,56-tab pack = £1.42

Brandsinclude

Frumil

Dose

oedema,1–2 tabletsin the morning

Tablets

,co-amilofruse 10/80 (amiloridehydro-

chloride10 mg, furosemide80 mg),net price 28-tab

pack= £11.51

Dose

oedema,1 tablet inthe morning

Amiloridewith bumetanide (Non-proprietary) A

Tablets

,amiloride hydrochloride 5mg, bumetanide

1mg, net price28-tab pack =£29.60

Dose

oedema,1–2 tabletsdaily

Triamterenewith thiazides

Counselling

Urinemay look slightlyblue in somelights

Co-triamterzide(Non-proprietary) A

Tablets

,co-triamterzide 50/25 (triamterene 50mg,

hydrochlorothiazide25 mg),net price 30-tab pack =

95p.Label: 14, (see above),21

Dose

hypertension,1 tablet dailyafter breakfast, increasedif

necessary,max. 4daily

Oedema,2 tablets daily(1 afterbreakf astand 1after midday

meal)increased to 3daily ifnecessar y(2 afterbreakf astand 1

aftermidday meal);usual maintenancein oedema,1 dailyor 2on

alternatedays; max. 4daily

Brandsinclude

Triam-Co

Dyazide

(Goldshield)A

Tablets

,peach, scored, co-triamterzide 50/25

(triamterene50 mg, hydrochlorothiazide25 mg),net

price30-tab pack = 95p.Label: 14, (see above),21

Dose

hypertension,1 tablet dailyafter breakfast, increasedif

necessary,max. 4daily

Oedema,2 tablets daily(1 afterbreakf astand 1after midday

meal)increased to 3daily ifnecessar y(2 afterbreakf astand 1

aftermidday meal);usual maintenancein oedema,1 dailyor 2on

alternatedays; max. 4daily

Kalspare

(DHPHealthcare) A

Tablets

,orange, f/c, scored, triamterene50 mg,

chlortalidone50 mg, netprice 28-tab pack =£9.90.

Label:14, (see above), 21

Dose

hypertension,oedema, 1–2tablets in themorning

Triamterenewith loop diuretics

Counselling

Urinemay look slightlyblue in somelights

Frusene

(Orion)A

Tablets

,yellow, scored, triamterene50 mg, furose-

mide40 mg,net price 56-tab pack= £4.34. Label:14,

(seeabove)

Dose

oedema,½–2 tabletsdaily in themorning

Spironolactonewith thiazides

Co-ﬂumactone

(Non-proprietary)AU

Tablets

,co-ﬂumactone 25/25 (hydroﬂumethiazide

25mg, spironolactone25 mg), netprice 100-tab pack

=£20.23

Brandsinclude

Aldactide25

Dose

congestiveheart failure, initially4 tabletsdaily; range 1–8

tabletsdaily (but notrecommended because spironolactone

generallygiven inlower dose)

Tablets

,co-ﬂumactone 50/50 (hydroﬂumethiazide

50mg, spironolactone50 mg),net price28-tab pack=

£10.70

Brandsinclude

Aldactide50

Dose

congestiveheart failure, initially2 tabletsdaily; range 1–4

tabletsdaily (but notrecommended because spironolactone

generallygiven inlower dose)

Spironolactonewith loop diuretics

Lasilactone

(Sanoﬁ-Aventis)A

Capsules

,blue/white, spironolactone 50mg, furose-

mide20 mg, netprice 28-cap pack =£7.97

Dose

resistantoedema, 1–4capsules daily

2.2.5

Osmotic diuretics

Mannitolis anosmotic diuretic thatcan beused to treat

cerebraloedema and raised intra-ocular pressure.

BNF 61 2.2.4 Potassium-sparing diuretics with other diuretics 89

Cardiovascularsystem

MANNITOL

Indications

seenotes above; glaucoma (section11.6)

Cautions

extravasationcauses inﬂammation and

thrombophlebitis;monitor ﬂuid and electrolytebal-

ance,serum osmolality, andpulmonar yand renal

function;assess cardiac function beforeand during

treatment;interactions: Appendix 1 (mannitol)

Contra-indications

severecardiac failure; severe

pulmonaryoedema; intracranial bleeding (except

duringcraniotomy); anuria; severe dehydration

Renalimpairment

usewith caution in severeimpair-

ment

Pregnancy

manufactureradvises avoid unless essen-

tial—noinformation available

Breast-feeding

manufactureradvises avoid unless

essential—noinformation available

Side-effects

lesscommonly

hypotension,thrombo-

phlebitis,ﬂuid and electrolyte imbalance;

rarely

dry

mouth,thirst, nausea, vomiting, oedema,raised

intracranialpressure, arrhythmia, hypertension,

pulmonaryoedema, chest pain, headache,con-

vulsions,dizziness, chills, fever,urinary retention,

focalosmotic nephrosis, dehydration, cramp,blurred

vision,rhinitis, skin necrosis, andhypersensitivity

reactions(including urticaria and anaphylaxis);

very

rarely

congestiveheart failure and acuterenal failure

Dose

. Cerebraloedema and raisedintra-ocular pressure, by

intravenousinfusion over30–60 minutes,0.25–2 g/kg

repeatedif necessary 1–2 times after4–8 hours

Note

Formannitol 20%, anin-line ﬁlter isrecommended (15-

micronﬁlters have beenused)

Mannitol(Baxter) A

Intravenousinfusion

,mannitol 10%, net price500-

Viaﬂex

bag= £2.26, 500-mL

Viaﬂo

bag=

£2.15;20%, net price 250-mL

Viaﬂex

bag= £3.27,

250-mL

Viaﬂo

bag= £3.27,500-mL

Viaﬂex

bag=

£3.29,500-mL

Viaﬂo

bag= £3.12

2.2.6

Mercurial diuretics

Mercurial diuretics are effective but are now almost

neverused because of their nephrotoxicity.

2.2.7

Carbonic anhydrase

inhibitors

The carbonic anhydrase inhibitor acetazolamide is a

weakdiuretic andis little usedfor its diureticeffect. Itis

used for prophylaxis against mountain sickness [unli-

censedindication] but is not a substitutefor acclimati-

sation.

Acetazolamideand eye drops ofdorzolamide and brin-

zolamideinhibit the formation of aqueoushumour and

areused in glaucoma (section11.6).

2.2.8

Diuretics with potassium

Many patients on diuretics do not need potassium

supplements (section 9.2.1.1). For many of those who

do,the amount of potassiumin combined preparations

maynot beenough, andfor this reasontheir use isto be

discouraged.

Diuretics with potassium and potassium-sparing diur-

eticsshould not usually begiven together.

Counselling

Modiﬁed-release potassium tablets should be

swallowedwhole with plentyof ﬂuid duringmeals while

sittingor standing

Diumide-KContinus

(Teofarma)AU

Tablets

,white/orange, f/c, furosemide40 mg, potas-

sium8 mmol formodiﬁed release, net price30-tab

pack= £3.00. Label: 25,27, counselling, see above

Neo-NaClex-K

(Goldshield)AU

Tablets

,pink/white, f/c,bendroﬂumethiazide 2.5mg,

potassium8.4 mmol formodiﬁed release, net price

100tab-pack = £8.99. Label:25, 27, counselling, see

above

2.3

Anti-arrhythmic drugs

2.3.1 Management of arrhythmias

2.3.2 Drugs for arrhythmias

2.3.1

Management of

arrhythmias

Managementof an arrhythmia requiresprecise diagno-

sisof thetype of arrhythmia,and electrocardiographyis

essential;underlying causessuch asheart failure require

appropriatetreatment.

Ectopic beats

If ectopicbeats are spontaneous and

the patient has a normal heart, treatment is rarely

required andreassurance to the patient will often suf-

ﬁce.If they are particularly troublesome,beta-blockers

are sometimes effective and may be safer than other

suppressantdrugs.

Atrial ﬁbrillation

All patients with atrial ﬁbrillation

should be assessedfor their risk of stroke and throm-

boembolism, and thromboprophylaxis given if neces-

sary (seebelow). Atrial ﬁbrillation can be managed by

eithercontrolling the ventricular rate or by attempting

torestore and maintain sinusrhythm.

All haemodynamically unstable patients with acute-

onsetatrial ﬁbrillation shouldundergo electrical cardio-

version. Intravenous amiodarone, or alternatively ﬂe-

cainide,can be usedin non-life-threatening cases when

electricalcardioversion is delayed. Ifurgent ventricular

rate control is required, a beta-blocker, verapamil, or

amiodaronecan be given intravenously.

Inhaemodynamically stable patients, a rhythm-control

treatmentstrategy is preferred for patients withparox-

ysmal atrial ﬁbrillation; rate-control is preferred for

those with permanent atrial ﬁbrillation. For patients

withpersistent atrial ﬁbrillation, the treatment strategy

shouldbe based oncriteria such asage, co-morbidities,

presenceof symptoms, andthe relativeadvantages and

disadvantagesof each treatment.

Ventricularrate can be controlled with a beta-blocker

(section 2.4), or diltiazem [unlicensed indication], or

verapamil.Digoxin is usually onlyeffective for control-

ling the ventricular rate at rest, and should therefore

90 2.2.6 Mercurial diuretics BNF61

Cardiovascularsystem

onlybe used as monotherapy inpredominantly seden-

tary patients. When a single drug fails toadequately

control the ventricular rate, patients should receive

digoxinwith either a beta-blocker, diltiazem, or verap-

amil.If ventricular functionis diminished, thecombina-

tionof a beta-blocker (that is licensed for use in heart

failure)and digoxin is preferred (see section2.5.5, and

interactions:Appendix 1 (cardiacglycosides)). Digoxin

is alsoused when atrial ﬁbrillation is accompanied by

congestiveheart failure.

Sinus rhythm can be restored by electrical cardio-

version,or pharmacological cardioversion with an oral

or intravenous anti-arrhythmic drug e.g. ﬂecainide or

amiodarone.If necessary,sotalol or amiodarone canbe

started 4 weeks before electrical cardioversion to

increase success of the procedure. If atrial ﬁbrillation

hasbeen present formore than 48hours, cardioversion

shouldnot be attempteduntil the patienthas been fully

anticoagulated(see section 2.8.2)for at least3 weeks;if

thisis not possible, parenteral anticoagulation (section

2.8.1)should be commenced and aleft atrial thrombus

ruled out immediately before cardioversion; oral anti-

coagulation should be given after cardioversion and

continued for at least 4 weeks. For atrial ﬁbrillation of

over48 hours duration, electrical cardioversion is pre-

ferredto pharmacological methods.If drug treatmentis

required to maintain sinus rhythm,a beta-blocker is

used. If a standard beta-blocker is not appropriate or

isineffective, an oralanti-arrhythmic drug suchas sota-

lol(section 2.4),ﬂecainide, propafenone,or amiodarone,

isrequired.

In symptomatic paroxysmal atrial ﬁbrillation, ventri-

cularrhythm is controlled witha beta-blocker. Alterna-

tively, if symptoms persist or a beta-blocker is not

appropriate,an oral anti-arrhythmic drug suchas sota-

lol,ﬂecainide, propafenone,or amiodaronecan begiven

(see also Paroxysmal Supraventricular Tachycardia

below,and Supraventricular Ar rhythmias). In selected

patients withinfrequent episodes of symptomatic par-

oxysmalatrial ﬁbrillation, sinusrhythm can be restored

usingthe ‘pill-in-the-pocket’ approach;this involves the

patient taking oral ﬂecainide or propafenone to self-

treatan episode of atrialﬁbrillation when it occurs.

Allpatients withatrial ﬁbrillation shouldbe assessed for

theirrisk ofstroke andthe needfor thromboprophylaxis.

Anticoagulants(section 2.8)are indicated forthose with

a history of ischaemic stroke, transient ischaemic

attacks, or thromboembolic events, and those with

valvedisease, heart failure, or impaired leftventricular

function;anticoagulants should beconsidered for those

withcardiovascular disease, diabetes, hypertension, or

thyrotoxicosis, and in the elderly. Anticoagulants are

also indicated during cardioversion procedures (see

above).Aspirin (section 2.9) is lesseffective than warf-

arin at preventing emboli, but may beappropriate if

thereare noother risk factorsfor stroke,or if warfarinis

contra-indicated.

Atrialﬂutter

Likeatrial ﬁbrillation, treatment options

foratrial ﬂutterinvolve either controllingthe ventricular

rateor attemptingto restoreand maintain sinusrhythm.

However,atrial ﬂ utter generally responds less well to

drugtreatment than atrial ﬁbrillation.

Control of the ventricular rate is usually an interim

measure pending restoration of sinus rhythm. Ventri-

cularrate can becontrolled byadministration of abeta-

blocker(section 2.4), diltiazem [unlicensed indication],

orverapamil (section 2.6.2); anintravenous beta-block-

er or verapamilis preferred for rapid control. Digoxin

(section 2.1.1) can be added if rate control remains

inadequate, and may be particularly useful in those

withheart failure.

Conversion to sinus rhythm can be achieved byelec-

tricalcardioversion (bycardiac pacingor directcurrent),

pharmacological cardioversion,or catheter ablation. If

theduration of atrialﬂutter is unknown, orit has lasted

for over 48 hours, cardioversion should not be

attempteduntil thepatient hasbeen fullyanticoagulated

(see section 2.8.2) for at least 3 weeks; ifthis isnot

possible, parenteral anticoagulation (section 2.8.1)

shouldbe commenced and a left atrialthrombus ruled

out immediately before cardioversion; oral anti-

coagulation should be given after cardioversion and

continuedfor at least 4weeks.

Directcurrent cardioversion is usuallythe treatment of

choicewhen rapid conversionto sinus rhythmis neces-

sary (e.g.when atrial ﬂutter is associated with haemo-

dynamiccompromise); catheterablation is preferredfor

the treatment of recurrent atrial ﬂutter. There is a

limited role for anti-arrhythmic drugs astheir use is

not always successful. Flecainide or propafenone can

slow atrial ﬂutter, resulting in 1:1 conduction to the

ventricles, and should therefore be prescribed in con-

junctionwith a ventricularrate controlling drugsuch as

a beta-blocker, diltiazem [unlicensed indication], or

verapamil. Amiodarone can be used when other drug

treatmentsare contra-indicated or ineffective.

All patientsshould be assessed for their risk of stroke

and the need for thromboprophylaxis; the choice of

anticoagulantis based on thesame criteria as for atrial

ﬁbrillation(see notes above).

Paroxysmal supraventricular tachycardia

This

willoften terminate spontaneously or withreﬂex vagal

stimulation such as a Valsalvamanoeuvre, immersing

theface inice-cold water,or carotidsinus massage;such

manoeuvresshould beperformed withECG monitoring.

Ifthe effects of reﬂexvagal stimulation are transientor

ineffective,or if thearrhythmia is causingsevere symp-

toms, intravenousadenosine (section 2.3.2) shouldbe

given. If adenosine is ineffective or contra-indicated,

intravenousverapamil (section 2.6.2) is an alternative,

butit shouldbe avoidedin patientsrecently treated with

beta-blockers(see p. 133).

Failureto terminateparoxysmal supraventricular tachy-

cardiawith reﬂ ex vagalstimulation or drug treatment

maysuggest anarrhythmia of atrialorigin, such asfocal

atrialtachycardia or atrial ﬂutter.

Treatmentwith direct current cardioversion is needed

in haemodynamically unstable patients or when the

above measures have failed to restore sinus rhythm

(andan alternative diagnosis hasnot been found).

Recurrent episodes of paroxysmal supraventricular

tachycardia can be treated by catheter ablation, or

prevented with drugs such as diltiazem, verapamil,

beta-blockersincluding sotalol (section 2.4), ﬂecainide,

orpropafenone (section 2.3.2).

Arrhythmias after myocardial infarction

patientswith a paroxysmal tachycardiaor rapid irregu-

larity ofthe pulse it is best not to administer an anti-

arrhythmic until an ECG record has been obtained.

Bradycardia,particularly ifcomplicated byhypotension,

BNF 61 2.3.1 Management of arrhythmias 91

Cardiovascularsystem

shouldbe treated with 500micrograms of atropinesul-

phate given intravenously; the dose may be repeated

every3–5 minutes if necessary upto a maximum total

doseof 3mg. Ifthere isa riskof asystole,or ifthe patient

is unstableand has failed to respond to atropine, adr-

enaline should be given by intravenous infusion ina

doseof 2–10micrograms/minute, adjustedaccording to

response.

Forfurther advice, referto the most recentrecommen-

dations of the Resuscitation Council (UK) available at

www.resus.org.uk.

Ventriculartachycardia

Pulselessventricular tachy-

cardiaor ventricular ﬁbrillation should be treated with

immediatedeﬁbrillation (seeCardiopulmonar yResusci-

tation,section 2.7.3).

Patientswith unstablesustained ventriculartachycardia,

whocontinue to deteriorate with signs of hypotension

orreduced cardiacoutput, should receivedirect current

cardioversionto restore sinusrhythm. If thisfails, intra-

venous amiodarone(section 2.3.2) should be adminis-

teredand direct current cardioversionrepeated.

Patientswith sustained ventriculartachycardia who are

haemodynamically stable can be treated with intra-

venous anti-arrhythmic drugs. Amiodarone isthe pre-

ferred drug. Flecainide, propafenone (section 2.3.2),

and, although less ef fective, lidocaine (section 2.3.2)

haveall beenused. Ifsinus rhythmis notrestored, direct

current cardioversionor pacing should be considered.

Catheter ablation is an alternative if cessation of the

arrhythmia is not urgent. Non-sustained ventricular

tachycardiacan be treated witha beta-blocker (section

2.4).

All patients presenting with ventricular tachycardia

shouldbe referred to aspecialist. Following restoration

of sinus rhythm, patients who remain at highrisk of

cardiac arrest will require maintenance therapy. Most

patientswill betreated with animplantable cardioverter

deﬁbrillator. Beta-blockers or sotalol (in place of a

standardbeta-blocker), or amiodarone (in combination

witha standardbeta-blocker), canbe used inaddition to

the devicein some patients; alternatively, they can be

used alone when use ofan implantable cardioverter

deﬁbrillatoris not appropriate.

Torsadede pointes

isa form of ventriculartachycardia

associated with a long QT syndrome (usually dr ug-

induced, but other factors including hypokalaemia,

severe bradycardia, and genetic predisposition are

also implicated). Episodes are usually self-limiting, but

are frequentlyrecur rentand can cause impairment or

lossof consciousness. If not controlled,the arrhythmia

can progress to ventricular ﬁbrillation and sometimes

death. Intravenous infusion of magnesium sulphate

(section 9.5.1.3) is usually effective. A beta-blocker

(but not sotalol) and atrial (or ventricular) pacing can

beconsidered. Anti-arrhythmicscan further prolongthe

QTinterval, thus worsening thecondition.

2.3.2

Drugs for arrhythmias

Anti-arrhythmic drugs can be classiﬁed clinically into

those that act on supraventricular ar rhythmias (e.g.

verapamil), those that act on both supraventricular

and ventricular arrhythmias (e.g. amiodarone), and

thosethat acton ventriculararrhythmias (e.g.lidocaine).

Anti-arrhythmic dr ugscan also be classiﬁed according

totheir effectson the electricalbehaviour ofmyocardial

cells during activity (the Vaughan Williams classiﬁca-

tion) although this classiﬁcation is of less clinical sig-

niﬁcance:

ClassI: membrane stabilising drugs (e.g.lidocaine,

ﬂecainide)

ClassII: beta-blockers

ClassIII: amiodarone; sotalol (alsoClass II)

ClassIV: calcium-channelblockers (includes verap-

amilbut not dihydropyridines)

Cautions

Thenegative inotropic effects of anti-arrhy-

thmicdrugs tend to be additive.Therefore special care

should betaken if two or more are used, especially if

myocardial function is impaired. Most drugs that are

effective in countering arrhythmias can alsoprovoke

themin some circumstances; moreover, hypokalaemia

enhancesthe arrhythmogenic(pro-ar rhythmic)effect of

manydrugs.

Supraventricular arrhythmias

Adenosineis usually thetreatment of choice fortermi-

nating paroxysmal supraventricular tachycardia. As it

hasa veryshort duration ofaction (half-lifeonly about8

to 10 seconds, but prolonged in those taking dipyrid-

amole),most side-effects are short lived.Unlike verap-

amil,adenosine canbe used aftera beta-blocker.Verap-

amilmay be preferable toadenosine in asthma.

Dronedaroneis a multi-channel blocking anti-arrhyth-

mic drug; it is licensed for use in clinically stable

patientswith previous or current non-permanent atrial

ﬁbrillation,to prevent recur renceor tolower the ventri-

cularrate.

The

ScottishMed icinesConsortium

(p.4) has advised

(August2010) that dronedarone (

Multaq

)is accepted

for restricteduse within NHS Scotland for the preven-

tion of recurrence of atrial ﬁbrillation in patients in

whomconventional ﬁrst-line anti-arrhythmic drugs are

ineffective,contra-indicated, or nottolerated; treatment

shouldbe initiated on specialistadvice only.

NICEguidance

Dronedaronefor the treatment of non-

permanentatrial ﬁbrillation (August 2010)

Dronedaroneis an option for thetreatment of non-

permanentatrial ﬁbrillation only inpatients who:

arenot controlled on ﬁrst-line therapy (usually

includingbeta-blockers), and

donot have unstable New YorkHeart Associa-

tionclass III or IVheart failure, and

haveat leastone cardiovascular riskfactor from

thefollowing:

hypertension managed byat least two dif-

ferentdrug classes

diabetesmellitus

previoustransient ischaemic attack, stroke,

orsystemic embolism

leftatrial diameter 50mm

leftventricular ejection fraction <40%

age70 years

92 2.3.2 Drugs for arrhythmias BNF 61

Cardiovascularsystem

Oral administration of a cardiac glycoside (such as

digoxin, section 2.1.1) slows the ventricular response

incases of atrial ﬁbrillation and atrial ﬂutter. However,

intravenous infusion of digoxin is rarely effective for

rapidcontrol of ventricular rate.Cardiac glycosides are

contra-indicated in supraventricular arrhythmias asso-

ciatedwith accessory conducting pathways(e.g. Wolff-

Parkinson-Whitesyndrome).

Verapamil(section 2.6.2) is usuallyeffective for supra-

ventricular tachycardias. An initial intravenous dose

(important: serious beta-blocker interaction hazard,

see p.133) may be followed by oral treatment; hypo-

tension may occur with large doses. It should not be

used for tachyarrhythmias where the QRScomplex is

wide (i.e. broad complex) unless a supraventricular

origin has been established beyond reasonable doubt.

It is also contra-indicated in atrial ﬁbrillation or atrial

ﬂutter associatedwith accessory conducting pathways

(e.g.Wolff-Parkinson-White syndrome).It shouldnot be

used in children with arrhythmias without specialist

advice;some supraventricularar rhythmiasin childhood

can be accelerated byverapamil with dangerous con-

sequences.

Intravenous administration of a beta-blocker (section

2.4)such as esmolol or propranolol, can achieverapid

controlof the ventricular rate.

Drugs for bothsupraventricular and ventricular arrhy-

thmiasinclude amiodarone, beta-blockers (seep. 98),

disopyramide, ﬂ ecainide, procainamide (available

from‘special-order’ manufacturers orspecialist import-

ingcompanies, seep. 988),and propafenone,see below

underSupraventricular and VentricularAr rhythmias.

ADENOSINE

Indications

rapidreversion to sinus rhythmof parox-

ysmalsupraventricular tachycardias, includingthose

associatedwith accessory conducting pathways(e.g.

Wolff-Parkinson-Whitesyndrome); aidto diagnosis of

broador narrow complex supraventriculartachy-

cardias

Cautions

monitorECG and have resuscitationfacil-

itiesavailable; atrial ﬁbrillation orﬂutter with acces-

sorypathway (conduction down anomalouspathway

mayincrease); ﬁrst-degree AV block;bundle branch

block;left maincoronar yartery stenosis;uncor rected

hypovolaemia;stenotic valvular heart disease;left to

rightshunt; pericarditis; pericardial effusion;auto-

nomicdysfunction; stenotic carotid arterydisease

withcerebrovascular insufﬁciency; recentmyocardial

infarction;heart failure; heart transplant (seebelow);

interactions:Appendix 1 (adenosine)

Contra-indications

second-or third-degree AV block

andsick sinus syndrome (unlesspacemaker ﬁtted);

longQT syndrome; severehypotension; decompen-

satedheart failure; chronic obstructive lungdisease

(includingasthma)

Pregnancy

largedoses may produce foetaltoxicity;

manufactureradvises use only ifessential

Breast-feeding

noinformation available—unlikely to

bepresent in milk owingto short half-life

Side-effects

nausea;arrhythmia (discontinue if asys-

toleor severe bradycardia occur),sinus pause, AV

block,ﬂushing, angina (discontinue), dizziness;dys-

pnoea;headache;

lesscommonly

metallictaste; pal-

pitation,hyperventilation, weakness, blurred vision,

sweating;

veryrarely

transientworsening of intracra-

nialhypertension, bronchospasm, injection-site reac-

tions;

alsoreported

vomiting,syncope, hypotension

(discontinueif severe), cardiac arrest,respirator y

failure(discontinue), and convulsions

Dose

. Byrapid intravenous injection intocentral or large

peripheralvein, 6 mgover 2 seconds withcardiac

monitoring;if necessary followed by12 mg after1–2

minutes,and then by 12mg after afurther 1–2 min-

utes;increments should not begiven if high levelAV

blockdevelops at any particulardose

Important

Patientswith a hearttransplant are verysensi-

tiveto effectsof adenosineand should receiveinitial doseof

3mg over2 seconds,followed ifnecessary by6 mgafter 1–2

minutes,and then by12 mgafter a further1–2 minutes.

Also,if essentialto givewith dipyridamolereduce adenosine

doseto a quarterof the usualdose

Note

Adenosinedoses in theBNF may differfrom those in

productliterature

Adenocor

(Sanoﬁ-Aventis)A

Injection

,adenosine 3mg/mL inphysiological saline,

netprice 2-mL vial =£4.45 (hosp. only)

Note

Intravenous infusion of adenosine (

Adenoscan

, Sanoﬁ-

Aventis)maybe usedin conjunctionwith radionuclidemyocardial

perfusionimaging in patientswho cannot exerciseadequately or

forwhom exerciseis inappropriate—consult productliterature

DRONEDARONE

Indications

seenotes above

Cautions

heartfailure (avoid in patientswith a recent

historyof moderate heart failure,or with a signiﬁ-

cantlyreduced left ventricular function);correct

hypokalaemiaand hypomagnesaemia before starting

andduring treatment; measure serum creatinine7

daysafter initiation; interactions: Appendix1 (dro-

nedarone)

Contra-indications

second-or third-degree AV block

andsick sinus syndrome (unlesspacemaker ﬁtted);

bradycardia;prolonged QT interval; haemodynami-

callyunstable patients(including thosewith moderate

orsevere heart failure)

Hepaticimpairment

avoidin severe impairment

Renalimpairment

avoidif eGFR less than30 mL/

minute/1.73m

Pregnancy

manufactureradvises avoid—toxicity in

animal

studies

Breast-feeding

manufactureradvises avoid—present

inmilk in

animal

studies

Side-effects

gastro-intestinaldisturbances; QT-inter-

valprolongation, bradycardia; fatigue, asthenia; rash,

pruritus;raised serum creatinine;

lesscommonly

taste

disturbance;erythema, eczema, dermatitis, photo-

sensitivity

Dose

. Bymouth, 400 mgtwice daily

Multaq

(Sanoﬁ-Aventis)TA

Tablets

,f/c, dronedarone (as hydrochloride)400 mg,

netprice 20-tab pack= £22.50, 60-tabpack =£67.50.

Label:21

Supraventricular and ventricular

arrhythmias

Amiodarone is used in the treatment of arrhythmias,

particularlywhen other drugs areineffective or contra-

indicated.It can beused for paroxysmal supraventricu-

BNF 61 2.3.2 Drugs for arrhythmias 93

Cardiovascularsystem

lar,nodal and ventriculartachycardias, atrial ﬁbrillation

and ﬂutter, and ventricular ﬁbrillation. It can also be

usedfor tachyarrhythmiasassociated withWolff-Parkin-

son-Whitesyndrome. It should be initiated only under

hospitalor specialist supervision. Amiodarone may be

givenby intravenous infusion aswell as bymouth, and

has the advantage of causing little or no myocardial

depression.Unlike oral amiodarone, intravenous amio-

daroneacts relatively rapidly.

Intravenous injection of amiodarone can be used in

cardiopulmonary resuscitation for ventricular ﬁbrilla-

tion or pulseless tachycardia unresponsive to other

interventions(section 2.7.3).

Amiodarone has a very long half-life (extending to

several weeks)and only needs to be given once daily

(buthigh dosescan cause nauseaunless divided). Many

weeks or months may be required to achieve steady-

stateplasma-amiodarone concentration; this isparticu-

larly important when drug interactions are likely (see

alsoAppendix 1).

Most patients taking amiodarone develop corneal

microdeposits(rever sibleon withdrawal of treatment);

these rarely interfere with vision, but drivers may be

dazzled by headlights at night. However, if vision is

impairedor if optic neuritis or opticneuropathy occur,

amiodaronemust be stopped to preventblindness and

expert advice sought. Because of the possibility of

phototoxic reactions, patients should be advised to

shield the skin from light during treatment and for

several months after discontinuing amiodarone; a

wide-spectrum sunscreen (section 13.8.1) to protect

against both long-wave ultraviolet and visible light

shouldbe used.

Amiodaronecontains iodine andcan cause disordersof

thyroid function; both hypothyroidism and hyper-

thyroidism may occur. Clinical assessment alone is

unreliable, and laboratory tests should be performed

before treatmentand ever y6 months. Thyroxine (T4)

maybe raisedin the absenceof hyperthyroidism; there-

foretri-iodothyronine (T3), T4, and thyroid-stimulating

hormone(thyrotrophin, TSH)should all bemeasured. A

raisedT3 and T4 witha very low orundetectable TSH

concentrationsuggests the development of thyrotoxic-

osis. The thyrotoxicosis may be ver y refractory, and

amiodaroneshould usually be withdrawn at least tem-

porarilyto help achievecontrol; treatmentwith carbim-

azolemay be required. Hypothyroidism canbe treated

with replacement therapy without withdrawing amio-

daroneif it is essential;careful supervision is required.

Pneumonitis should always be suspected if new or

progressiveshortness of breath or coughdevelops in a

patient taking amiodarone. Fresh neurological symp-

toms should raise the possibility of peripheral neuro-

pathy.

Amiodaroneis also associated with hepatotoxicity and

treatmentshould bediscontinued ifsevere liverfunction

abnormalitiesor clinical signs of liverdisease develop.

Beta-blockers actas anti-arrhythmic drugs principally

byattenuating the effectsof the sympatheticsystem on

automaticity and conductivity within the heart, for

details see section 2.4. For special reference to the

roleof sotalol in ventriculararrhythmias, see p. 98.

Disopyramidecan be givenby intravenous injectionto

controlarrhythmias after myocardial infarction(includ-

ing those not responding to lidocaine), but it impairs

cardiac contractility. Oral administration of disopyr-

amide is useful, but it has an antimuscarinic effect

which limits its use in patients susceptible to angle-

closureglaucoma or with prostatichyperplasia.

Flecainide belongs to the same generalclass as lido-

caine and may be of value for serious symptomatic

ventricular arrhythmias. It may also beindicated for

junctional re-entry tachycardias and for paroxysmal

atrial ﬁbrillation. However, it can precipitate serious

arrhythmias in a small minority of patients (including

thosewith otherwise normal hearts).

Propafenoneis used forthe prophylaxis and treatment

ofventricular arrhythmias and alsofor some supraven-

tricular arrhythmias. It has complex mechanisms of

action,including weak beta-blocking activity (therefore

cautionis needed in obstructive airwaysdisease—con-

tra-indicatedif severe).

Drugs for supraventricular arrhythmias include aden-

osine, cardiac glycosides, and verapamil;see above

under Supraventricular Arrhythmias. Drugs for ventri-

cularar rhythmiasinclude lidocaine; see under Ventri-

cularArrhythmias, p. 96.

Mexiletine and procainamide are both available from

‘special-order’ manufacturers or specialist importing

companies,see p. 988. Mexiletine canbe used for life-

threatening ventricular ar rhythmias; procainamide is

given by intravenous injection to control ventricular

arrhythmias.

AMIODARONE HYDROCHLORIDE

Indications

seenotes above (should beinitiated in

hospitalor under specialist supervision)

Cautions

liver-functionand thyroid-function tests

requiredbefore treatment and thenever y 6 months

(seenotes above for testsof thyroid function); hypo-

kalaemia(measure serum-potassium concentration

beforetreatment); chest x-ray requiredbefore treat-

ment;heart failure; elderly; severebradycardia and

conductiondisturbances in excessive dosage;intra-

venoususe may cause moderateand transient fall in

bloodpressure (circulatory collapse precipitatedby

rapidadministration or overdosage) orsevere hepa-

tocellulartoxicity (monitor transaminases closely);

administrationby central venous catheterrecom-

mendedif repeatedor continuous infusionrequired—

infusionvia peripheral veins maycause pain and

inﬂammation;ECG monitoring and resuscitation

facilitiesmust be available duringintravenous use;

acuteporphyria (section 9.8.2); interactions:Appen-

dix1 (amiodarone)

Contra-indications

(exceptin cardiac arrest) sinus

bradycardia,sino-atrial heartblock; unlesspacemaker

ﬁttedavoid in severe conductiondisturbances or

sinusnode disease; thyroid dysfunction;iodine sen-

sitivity;avoid

intravenoususe

insevere respiratory

failure,circulatory collapse, or severearterial hypo-

tension;avoid bolus injection incongestive heart

failureor cardiomyopathy

Pregnancy

possiblerisk of neonatalgoitre; use only if

noalternative

Breast-feeding

avoid;present in milk insigniﬁcant

amounts;theoretical risk of neonatalhypothyroidism

fromrelease of iodine

Side-effects

nausea,vomiting, taste disturbances,

raisedserum transaminases (may requiredose

reductionor withdrawalif accompaniedby acute liver

disorders),jaundice; bradycardia (see Cautions);

94 2.3.2 Drugs for arrhythmias BNF 61

Cardiovascularsystem

pulmonarytoxicity (including pneumonitis and ﬁbro-

sis);tremor, sleep disorders; hypothyroidism,hyper-

thyroidism;reversible corneal microdeposits (some-

timeswith nightglare); phototoxicity, persistent slate-

greyskin discoloration (see alsonotes above), injec-

tion-sitereactions;

lesscommonly

onsetor worsening

ofarrhythmia, conduction disturbances (seeCau-

tions),peripheral neuropathy and myopathy(usually

reversibleon withdrawal);

veryrarely

chronicliver

diseaseincluding cirrhosis, sinus arrest, broncho-

spasm(in patients with severerespirator yfailure),

ataxia,benign intracranial hypertension, headache,

vertigo,epididymo-orchitis, impotence,haemolytic or

aplasticanaemia, thrombocytopenia, rash (including

exfoliativedermatitis), hypersensitivity including

vasculitis,alopecia, impaired vision dueto optic

neuritisor optic neuropathy (includingblindness),

anaphylaxison rapid injection, alsohypotension,

respiratorydistress syndrome, sweating, andhot

ﬂushes

Dose

. Bymouth, 200mg 3times daily for1 weekreduced to

200mg twice dailyfor a further week;maintenance,

usually200 mg dailyor the minimum requiredto

controlthe arrhythmia

. Byintravenous infusion(see Cautions above),initially

5mg/kg over 20–120minutes with ECG monitoring;

subsequentinfusion given if necessaryaccording to

responseup to max. 1.2g in 24hours

. Ventricularﬁbrillation or pulseless ventriculartachy-

cardiarefractory to deﬁbrillation, section 2.7.3

Amiodarone(Non-proprietary) A

Tablets

,amiodarone hydrochloride 100mg, net price

28-tabpack = £1.75; 200mg, 28-tabpack = £2.22.

Label:11

Injection

,amiodarone hydrochloride 30mg/mL, net

price10-mL preﬁlled syringe =£19.60

Excipients

mayinclude benzylalcohol (avoidin neonates unlessno

saferalternative available,see Excipients,p. 2)

Sterileconcentrate

,amiodarone hydrochloride

50mg/mL, netprice 3-mL amp= £1.33,6-mL amp =

£2.86.For dilution and useas an infusion

Excipients

mayinclude benzylalcohol (avoidin neonates unlessno

saferalternative available,see Excipients,p. 2)

CordaroneX

(Sanoﬁ-Aventis)A

Tablets

,scored, amiodarone hydrochloride 100mg,

netprice 28-tab pack =£4.28; 200mg, 28-tab pack=

£6.99.Label: 11

Sterileconcentrate

,amiodarone hydrochloride

50mg/mL, net price3-mL amp = £1.33.For dilution

anduse as an infusion

Excipients

includebenzyl alcohol(avoid inneonates unless nosafer

alternativeavailable, seeExcipients, p.2)

DISOPYRAMIDE

Indications

ventriculararrhythmias, especially after

myocardialinfarction; supraventricular arrhythmias

Cautions

monitorfor hypotension, hypoglycaemia,

ventriculartachycardia, ventricular ﬁbrillation ortor-

sadede pointes (discontinueif occur); atrial ﬂutteror

atrialtachycardia with partial block,bundle branch

block,heart failure (avoid ifsevere); prostatic enlar-

gement;susceptibility to angle-closure glaucoma;

avoidin acutepor phyria(section 9.8.2);interactions:

Appendix1 (disopyramide)

Contra-indications

second-and third-degree heart

blockand sinus node dysfunction(unless pacemaker

ﬁtted);cardiogenic shock; severe uncompensated

heartfailure

Hepaticimpairment

half-lifeprolonged—may need

dosereduction

Renalimpairment

reducedose by increasing dose

interval;adjust according to response;avoid sus-

tained-releasepreparation

Pregnancy

mayinduce labourif usedin thirdtrimester

Breast-feeding

presentin milk—use only ifessential

andmonitor infant for antimuscariniceffects

Side-effects

ventriculartachycardia, ventricular

ﬁbrillationor torsade de pointes (usuallyassociated

withprolongation of QRS complexor QT interval—

seeCautions above), myocardial depression,hypo-

tension,AV block; antimuscarinicef fectsinclude dry

mouth,blurred vision, urinary retention, andvery

rarelyangle-closure glaucoma; gastro-intestinal irri-

tation;psychosis, cholestaticjaundice, hypoglycaemia

alsoreported (see Cautions above)

Dose

. Bymouth, 300–800 mgdaily in divided doses

. Byslow intravenousinjection, 2mg/kg over atleast 5

minutesto a max. of150 mg, withECG monitoring,

followedimmediately

either

by200 mg bymouth,

then200 mg every8 hours for 24 hours

400micrograms/kg/hour by intravenousinfusion;

max.300 mg inﬁrst hour and 800mg daily

Disopyramide(Non-proprietary) A

Capsules

,disopyramide (as phosphate) 100mg, net

price84 = £24.38; 150mg, 84= £32.57

Rythmodan

(Sanoﬁ-Aventis)A

Capsules

,disopyramide 100 mg(green/beige), net

price84-cap pack = £14.14;150 mg,84-cap pack =

£18.76

Injection

,disopyramide (as phosphate) 10mg/mL,

netprice 5-mL amp =£2.61

Modiﬁedrelease

RythmodanRetard

(Sanoﬁ-Aventis)A

Tablets

,m/r, scored, f/c,disopyramide (as phos-

phate)250 mg, netprice 60-tab pack =£27.72.

Label:25

Dose

250–375mg every12 hours

FLECAINIDE ACETATE

Indications

capsules,tablets, and injection:

AVnodal

reciprocatingtachycardia, arrhythmias associated

withaccessory conducting pathways (e.g.Wolff-Par-

kinson-Whitesyndrome), disabling symptoms ofpar-

oxysmalatrial ﬁbrillation in patientswithout left

ventriculardysfunction (arrhythmias of recentonset

willrespond more readily)

Immediate-releasetablets only:

symptomaticsus-

tainedventricular tachycardia,disabling symptoms of

prematureventricular contractions or non-sustained

ventriculartachycardia in patients resistantto or

intolerantof other therapy

Injectiononly:

ventriculartachyarrhythmias resistant

toother treatment

Cautions

patientswith pacemakers (especially those

whomay be pacemaker dependentbecause stimula-

tionthreshold may riseappreciably); atrial ﬁbrillation

followingheart surgery; elderly (accumulationmay

occur);ECG monitoring and resuscitationfacilities

BNF 61 2.3.2 Drugs for arrhythmias 95

Cardiovascularsystem

mustbe available during intravenoususe; interac-

tions:Appendix 1 (ﬂecainide)

Contra-indications

heartfailure; abnormal left

ventricularfunction; history of myocardialinfarction

andeither asymptomatic ventricular ectopicsor

asymptomaticnon-sustained ventricular tachycardia;

long-standingatrial ﬁbrillation where conversionto

sinusrhythm not attempted; haemodynamicallysig-

niﬁcantvalvular heart disease; avoidin sinus node

dysfunction,atrial conduction defects,second-degree

orgreater AV block, bundlebranch block or distal

blockunless pacing rescue available

Hepaticimpairment

avoid(or reduce dose)in severe

liverdisease

Renalimpairment

reduceinitial oral dose tomax.

100mg dailyor reduce intravenous dose by50%, if

eGFRless than 35mL/minute/1.73 m

Pregnancy

usedin pregnancy to treatmaternal and

fetalarrhythmias in specialist centres; toxicity

reportedin

animal

studies;infant hyperbilirubinaemia

alsoreported

Breast-feeding

signiﬁcantamount presentin milk but

notknown to be harmful

Side-effects

oedema,pro-arrhythmic effects; dys-

pnoea;dizziness, asthenia, fatigue, fever;visual dis-

turbances;

rarely

pneumonitis,hallucinations,

depression,confusion, amnesia, dyskinesia, con-

vulsions,peripheral neuropathy;

alsoreported

gastro-

intestinaldisturbances, anorexia,hepatic dysfunction,

ﬂushing,syncope, drowsiness, tremor,vertigo, head-

ache,anxiety, insomnia, ataxia,paraesthesia, anae-

mia,leucopenia, thrombocytopenia, cornealdeposits,

tinnitus,increased antinuclear antibodies, hyper-

sensitivityreactions (including rash, urticaria,and

photosensitivity),increased sweating

Dose

. Bymouth (initiated under directionof hospital con-

sultant),ventricular arrhythmias, initially 100mg

twicedaily (max. 400mg daily usually reservedfor

rapidcontrol or in heavilybuilt patients), reduced

after3–5 days to thelowest dose that controls

arrhythmia

Supraventriculararrhythmias, 50 mgtwice daily,

increasedif required to max.300 mg daily

. Byslow intravenous injection (inhospital), 2 mg/kg

over10–30 minutes, max. 150mg, with ECGmoni-

toring;followed if required byinfusion at a rateof

1.5mg/kg/hour for 1hour, subsequentlyreduced to

100–250micrograms/kg/hour for upto 24 hours;

max.cumulative dose in ﬁrst24 hours, 600mg;

transferto

oral

treatment,as above

Flecainide(Non-proprietary) A

Tablets

,ﬂecainide acetate 50mg, net price 60-tab

pack= £6.04; 100mg, 60-tab pack= £8.95

Tambocor

(3M)A

Tablets

,ﬂecainide acetate 50mg, net price 60-tab

pack= £11.57;100 mg(scored), 60-tab pack= £16.53

Injection

,ﬂecainide acetate 10mg/mL, net price15-

mLamp = £4.40

Modiﬁedrelease

Tambocor

XL(Meda) A

Capsules

,m/r, grey/pink, ﬂecainideacetate 200 mg,

netprice 30-cap pack =£14.77. Label: 25

Dose

supraventriculararrhythmias, 200mg once daily

Note

Notto be used tocontrol arrhythmias in acute situations;

patientsstabilised on 200mg dailyimmediate-release ﬂecainide

maybe transferred to

Tambocor

PROPAFENONEHYDROCHLORIDE

Indications

ventriculararrhythmias; paroxysmal

supraventriculartachyarrhythmias which include

paroxysmalatrial ﬂutteror ﬁbrillationand paroxysmal

re-entranttachycardias involving the AVnode or

accessorypathway, where standardtherapy ineffec-

tiveor contra-indicated

Cautions

heartfailure; elderly; pacemaker patients;

potentialfor conversion of paroxysmalatrial ﬁbrilla-

tionto atrial ﬂutter with 2:1or 1:1 conduction block;

greatcaution in obstructive airwaysdisease owing to

beta-blockingactivity (contra-indicated if severe);

interactions:Appendix 1 (propafenone)

Driving

Mayaffect performance ofskilled tasks e.g.driving

Contra-indications

uncontrolledcongestive heart

failure,cardiogenic shock (except arrhythmia

induced),severe bradycardia, electrolyte distur-

bances,severe obstructive pulmonary disease,

markedhypotension; myasthenia gravis; unlessade-

quatelypaced avoid in sinusnode dysfunction, atrial

conductiondefects, second degree orgreater AV

block,bundle branch block ordistal block

Hepaticimpairment

reducedose

Pregnancy

manufactureradvises avoid—no informa-

tionavailable

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

gastro-intestinaldisturbances, dry

mouth,bitter taste, anorexia, jaundice,cholestasis,

hepatitis;chest pain, bradycardia, sino-atrial,atrio-

ventricular,or intraventricular blocks,hypotension

(includingpostural hypotension), dizziness, syncope,

pro-arhythmiceffects; anxiety, confusion,ataxia,

restlessness,headache, sleep disorders, paraesthesia,

fatigue,seizures, extrapyramidal symptoms; impo-

tence,reduced sperm count; blooddisorders; lupus

syndrome;blurred vision; hypersensitivity (including

skinreactions)

Dose

. Body-weight70 kgand over, initially 150mg 3 times

dailyafter foodunder direct hospitalsuper visionwith

ECGmonitoring and blood pressurecontrol (if QRS

intervalprolonged by morethan 20%, reducedose or

discontinueuntil ECG returns tonor mallimits); may

beincreased at intervals of atleast 3 days to300 mg

twicedaily and, if necessary,to max. 300mg 3 times

daily;body-weight under 70kg, reduce dose;

ELDERLY

mayrespond to lower doses

Arythmol

(Abbott)A

Tablets

,f/c, propafenone hydrochloride150 mg, net

price90-tab pack = £7.37;300 mg,60-tab pack =

£9.34.Label: 21, 25, counselling,driving

Ventriculararrhythmias

Intravenouslidocaine can beused for the treatmentof

ventricular tachycardia in haemodynamically stable

patients (section2.3.1), and ventricular ﬁbrillation and

pulseless ventricular tachycardia in cardiac arrest

refractory to deﬁbrillation (section 2.7.3), however itis

nolonger the anti-arrhythmic drug ofﬁrst choice.

Drugs for bothsupraventricular and ventricular arrhy-

thmias include amiodarone, beta-blockers, disopyr-

amide,ﬂecainide, procainamide (available from ‘spe-

cial-order’ manufacturers or specialist importing

96 2.3.2 Drugs for arrhythmias BNF 61

Cardiovascularsystem

companies, see p.988), andpropafenone, seeabove

underSupraventricular and VentricularAr rhythmias.

Mexiletine is available from ‘special-order’ manufac-

turersor specialistimporting companies (seep. 988) for

treatmentof life-threatening ventricular arrhythmias.

LIDOCAINE HYDROCHLORIDE

(Lignocainehydrochloride)

Indications

ventriculararrhythmias, especially after

myocardialinfarction; eye (section 11.7);local

anaesthesia(section 15.2)

Cautions

lowerdoses incongestive cardiacfailure and

followingcardiac surgery; monitor ECGand have

resuscitationfacilities available; elderly;interactions:

Appendix1 (lidocaine)

Contra-indications

sino-atrialdisorders, all grades of

atrioventricularblock, severe myocardial depression;

acuteporphyria (section 9.8.2)

Hepaticimpairment

caution—increasedrisk of side-

effects

Renalimpairment

possibleaccumulation oflidocaine

andactive metabolite; caution insevere impairment

Pregnancy

crossesthe placenta but notknown to be

harmfulin

animal

studies—useif beneﬁt outweighs

risk

Breast-feeding

presentin milk but amounttoo small

tobe harmful

Side-effects

dizziness,paraesthesia, or drowsiness

(particularlyif injection too rapid);other CNS effects

includeconfusion, respiratory depression andcon-

vulsions;hypotension and bradycardia (maylead to

cardiacarrest);

rarely

hypersensitivityreactions

includinganaphylaxis

Dose

. Byintravenous injection, in patientswithout gross

circulatoryimpairment, 100 mgas a bolusover a few

minutes(50 mg inlighter patients or those whose

circulationis severely impaired), followedimmedi-

atelyby infusion of 4mg/minute for 30minutes,

2mg/minute for 2hours, then 1mg/minute; reduce

concentrationfurther if infusioncontinued beyond 24

hours(ECG monitoring and specialistadvice for

infusion)

Note

Following

intravenousinjection

lidocainehas a short

durationof action (lastingfor 15–20 minutes).If an

intra-

venousinfusion

isnot immediately availablethe initial

intravenousinjection

of50–100 mgcan be repeatedif

necessaryonce or twiceat intervals ofnot less than 10

minutes

Lidocaine(Non-proprietary) A

Injection1%

,lidocaine hydrochloride10 mg/mL,net

price2-mL amp =21p; 5-mL amp= 26p; 10-mLamp

=39p; 20-mL amp =78p

Injection2%

,lidocaine hydrochloride20 mg/mL,net

price2-mL amp =32p; 5-mL amp= 31p; 10-mLamp

=60p; 20-mL amp =80p

Infusion

,lidocaine hydrochloride 0.1% (1mg/mL)

and0.2% (2 mg/mL)in glucose intravenous infusion

5%.500-mL containers

Minijet

Lignocaine(UCB Pharma) A

Injection

,lidocaine hydrochloride 1% (10mg/mL),

netprice 10-mL disposable syringe= £8.48; 2%

(20mg/mL), 5-mL disposablesyringe = £8.18

2.4

Beta-adrenoceptor

blocking drugs

Beta-adrenoceptorblocking drugs (beta-blockers)block

the beta-adrenoceptors in theheart, peripheralvascu-

lature,bronchi, pancreas, and liver.

Many beta-blockers are now available and in general

theyare all equally effective. Thereare, however,dif fer-

encesbetween them, which mayaf fectchoice in treat-

ingparticular diseases or individualpatients.

Intrinsicsympathomimetic activity (ISA,partia lagonist

activity) represents the capacity of beta-blockers to

stimulate as well as to block adrenergic receptors.

Oxprenolol, pindolol, acebutolol, and celiprolol

have intrinsic sympathomimetic activity; they tend to

causeless bradycardiathan the otherbeta-blockers and

mayalso cause less coldnessof the extremities.

Somebeta-blockers arelipid solubleand someare water

soluble.Atenolol, celiprolol, nadolol, and sotalol are

themost water-soluble; they areless likely to enterthe

brain, and may therefore cause less sleep disturbance

and nightmares. Water-soluble beta-blockers are

excretedby the kidneys and dosage reduction is often

necessaryin renal impairment.

Beta-blockerswith a relatively short duration ofaction

haveto begiven two orthree timesdaily. Manyof these

are,however, availablein modiﬁed-releaseformulations

sothat administration oncedaily is adequatefor hyper-

tension. For angina twice-daily treatment may some-

timesbe needed even witha modiﬁed-release formula-

tion. Some beta-blockers,such as atenolol, bisoprolol,

carvedilol, celiprolol,and nadolol, have an intrinsically

longerduration ofaction andneed tobe givenonly once

daily.

Beta-blockersslow the heart andcan depress the myo-

cardium; they are contra-indicated in patients with

second- or third-degree heart block. Beta-blockers

should also be avoided in patients with worsening

unstable heart failure; care is required when initiating

abeta-blocker inthose withstable heart failure(see also

section2.5.5). Sotalolmay prolong theQT interval,and

itoccasionally causes life-threateningventricular arrhy-

thmias(impor tant:particular care is required to avoid

hypokalaemiain patients taking sotalol).

Labetalol, celiprolol, car vedilol, and nebivolol are

beta-blockersthat have, in addition,an arteriolar vaso-

dilatingaction, by diverse mechanisms,and thus lower

peripheral resistance. There is no evidence that these

drugshave importantadvantages overother beta-block-

ersin the treatment ofhypertension.

Beta-blockerscan precipitatebronchospasm andshould

thereforeusually beavoided inpatients with ahistory of

asthma.When there isno suitable alternative,it maybe

necessaryfor a patient with well-controlled asthma,or

chronicobstructive pulmonary disease (without signiﬁ-

cant reversible airways obstruction), to receive treat-

mentwith abeta-blocker fora co-existingcondition (e.g.

heartfailure or following myocardialinfarction). In this

situation, a cardioselective beta-blocker should be

selectedand initiated at a lowdose by a specialist; the

patientshould be closelymonitored for adverseeffects.

Atenolol,bisoprolol, metoprolol, nebivolol, and (toa

lesserextent) acebutolol, have less effect onthe beta

(bronchial)receptor s and are, therefore, relatively

car-

BNF 61 2.4 Beta-adrenoceptor blocking drugs 97

Cardiovascularsystem

dioselective

,but they are not

cardiospeciﬁc

.They have

alesser effect on airways resistance but are not freeof

thisside-effect.

Beta-blockersare also associatedwith fatigue, coldness

ofthe extremities(may be lesscommon withthose with

ISA,see above),and sleepdisturbances withnightmares

(may be less common with the water-soluble beta-

blockers,see above).

Beta-blockers can affect carbohydrate metabolism,

causing hypoglycaemia or hyperglycaemia in patients

with or without diabetes; they can also interfere with

metabolicand autonomic responses to hypoglycaemia,

therebymasking symptoms such as tachycardia. How-

ever,beta-blockers arenot contra-indicated indiabetes,

although thecardioselective beta-blockers (see above)

may be prefer red. Beta-blockers should be avoided

altogetherin those with frequentepisodes of hypoglyc-

aemia.Beta-blockers, especially whencombined with a

thiazide diuretic, should be avoided for the routine

treatment of uncomplicated hypertension in patients

with diabetes or in those at high risk of developing

diabetes.

Pregnancy

Beta-blockers may cause intra-uterine

growthrestriction, neonatal hypoglycaemia,and brady-

cardia; the risk is greater in severe hypertension.The

useof labetalol in maternal hypertension isnot known

to be harmful, except possibly in the ﬁrst trimester.

Information on the safety of carvedilol during

pregnancyis lacking. If beta-blockersare used close to

delivery,infants should be monitoredfor signs of beta-

blockade (and alpha-blockade with labetalol orcar ve-

dilol).For the treatment of hypertension in pregnancy,

seesection 2.5.

Breast-feeding

Infantsshould be monitored asthere

isa risk of possible toxicity due to beta-blockade(and

alpha-blockade with labetalol or carvedilol), but the

amount of most beta-blockers present in milk is too

smallto affectinfants. Acebutolol,atenolol, nadolol,and

sotalolare presentin milkin greater amountsthan other

beta-blockers.The manufacturersof celiprolol, esmolol,

andnebivolol advise avoidance ifbreast-feeding.

Hypertension

Themode of actionof beta-blockers in

hypertensionis notunderstood, but theyreduce cardiac

output, alter baroceptor reﬂex sensitivity, and block

peripheral adrenoceptors. Somebeta-blockers depress

plasmarenin secretion.It ispossible that acentral effect

mayalso partly explain theirmode of action.

Beta-blockersare effective for reducing bloodpressure

but other antihypertensives (section 2.5) are usually

more effective for reducing the incidence of stroke,

myocardial infarction, and cardiovascular mortality,

especially in the elderly. Other antihypertensives are

therefore preferred for routine initial treatment of

uncomplicatedhypertension.

Ingeneral, the dose ofa beta-blocker does not haveto

behigh; for example, atenololis given in adose of 25–

50mg daily and it is rarely necessary to increase the

doseto 100 mg.

Beta-blockers canbe used to control the pulse rate in

patients with

phaeochromocytoma

(section 2.5.4).

However, they should never be used alone as beta-

blockadewithout concurrent alpha-blockade may lead

to a hypertensive crisis. For this reason phenoxybenz-

amine should always be used together with the beta-

blocker.

Angina

By reducing cardiac work beta-blockers

improve exercise tolerance and relieve symptoms in

patientswith

angina

(forfurther details onthe manage-

ment ofstable angina and acute coronary syndromes,

see section 2.10.1). As with hypertension there is no

good evidence of the superiority of any one drug,

although occasionally a patient will respond better to

one beta-blocker than to another. There is some evi-

dencethat sudden withdrawal maycause an exacerba-

tionof anginaand thereforeg radualreduction ofdose is

preferablewhen beta-blockers areto be stopped.There

isa riskof precipitatingheart failure whenbeta-blockers

and verapamil are used together in established

ischaemicheart disease (important: see p.133).

Myocardial infarction

For advice on the manage-

mentof ST-segmentelevation myocardialinfarction and

non-ST-segment elevation myocardial infarction, see

section 2.10.1. Several studies have shown that some

beta-blockers can reduce the recurrence rate of

myo-

cardialinfarction

.However, uncontrolled heart failure,

hypotension, bradyarrhythmias, and obstructive air-

ways disease render beta-blockers unsuitablein some

patientsfollowing amyocardial infarction.Atenolol and

metoprolol may reduce early mortality after intra-

venous and subsequent oral administration in the

acutephase, while acebutolol, metoprolol, proprano-

lol,and timolol have protective value when started in

theearly convalescent phase. The evidence relatingto

other beta-blockers is less convincing; somehave not

been tested in trials of secondary prevention. Sudden

cessation of abeta-blocker can cause a rebound wor-

seningof myocardial ischaemia.

Arrhythmias

Beta-blockers act as

anti-arrhythmic

drugs

principallyby attenuating the effectsof the sym-

patheticsystem onautomaticity andconductivity within

theheart. Theycan be usedin conjunction withdigoxin

tocontrol the ventricular response in atrial ﬁbrillation,

especiallyin patients withthyrotoxicosis. Beta-blockers

are alsouseful in the management of supraventricular

tachycardias, and are used to control those following

myocardialinfarction (see above).

Esmololis arelatively cardioselectivebeta-blocker with

aver yshort duration of action, used intravenously for

the short-term treatment of supraventricular arrhyth-

mias,sinus tachycardia, orhypertension, particularly in

theperi-operative period. It may also be usedin other

situations, such as acute myocardial infarction, when

sustainedbeta-blockade might be hazardous.

Sotalol, a non-cardioselective beta-blocker with addi-

tional class III anti-arrhythmic activity, is used for

prophylaxis in paroxysmal supraventricular arrhyth-

mias. It also suppresses ventricular ectopic beats and

non-sustained ventricular tachycardia. It has been

shownto be moreef fectivethan lidocaine inthe termi-

nationof spontaneoussustained ventricular tachycardia

dueto coronarydisease or cardiomyopathy.However,it

mayinduce torsade de pointesin susceptible patients.

Heart failure

Beta-blockers may produce beneﬁt in

heart failure by blocking sympathetic activity.

Bisoprolol and carvedilol reduce mortality in any

grade of stable heart failure; nebivolol is licensed for

stablemild to moderateheart failurein patients over70

98 2.4 Beta-adrenoceptor blocking drugs BNF 61

Cardiovascularsystem

years. Treatment should be initiated by those experi-

encedin themanagement ofheart failure(section 2.5.5).

Thyrotoxicosis

Beta-blockersare used in pre-opera-

tive preparation for thyroidectomy. Administration of

propranolol can reverse clinical symptoms of

thyro-

toxicosis

within4 days. Routine tests of increased thy-

roid function remain unaltered. The thyroid gland is

renderedless vascular thusmaking surgery easier (sec-

tion6.2.2).

Otheruses

Beta-blockershave been usedto alleviate

some symptoms of

anxiety

; probably patients with

palpitation, tremor,and tachycardia respond best (see

alsosection 4.1.2 and section 4.9.3). Beta-blockers are

also used in the

prophylaxis of migraine

(section

4.7.4.2).Betaxolol, carteolol, levobunolol,metipranolol,

and timolol are used topically in

glaucoma

(section

11.6).

PROPRANOLOLHYDROCHLORIDE

Indications

seeunder Dose

Cautions

seenotes above; also avoidabrupt with-

drawalespecially in ischaemic heartdisease; ﬁrst-

degreeAV block; portal hypertension(risk of dete-

riorationin liver function); diabetes;histor yof

obstructiveairways disease (introducecautiously and

monitorlung function—see notesabove); myasthenia

gravis;symptoms of hypoglycaemia andthyrotoxic-

osismay be masked(also see notesabove); psoriasis;

historyof hypersensitivity—may increase sensitivity

toallergens and result inmore serious hypersensi-

tivityresponse, also may reduceresponse to adrena-

line(epinephrine) (see also section3.4.3); interac-

tions:Appendix 1 (beta-blockers), important:

verapamilinteraction, see also p.133

Contra-indications

asthma(but see notes above),

uncontrolledheart failure, Prinzmetal’sangina,

markedbradycardia, hypotension, sick sinus

syndrome,second- or third- degreeAV block,

cardiogenicshock, metabolic acidosis, severeper-

ipheralarterial disease; phaeochromocytoma (apart

fromspeciﬁc use with alpha-blockers,see also notes

above)

Bronchospasm

Beta-blockers,including those considered

tobe cardioselective, shouldusually be avoidedin patients

witha history ofasthma or bronchospasm.However, when

thereis noalternative, a cardioselectivebeta-blocker canbe

givento these patientswith caution andunder specialist

supervision.

Hepaticimpairment

reduceoral dose

Renalimpairment

manufactureradvises caution—

dosereduction may be required

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also gastro-intestinal

disturbances;bradycardia, heart failure, hypotension,

conductiondisorders, peripheral vasoconstriction

(includingexacerbation of intermittent claudication

andRaynaud’s phenomenon); bronchospasm(see

above),dyspnoea; headache, fatigue, sleepdistur-

bances,paraesthesia, dizziness, vertigo,psychoses;

sexualdysfunction; purpura, thrombocytopenia;

visualdisturbances; exacerbation of psoriasis,alo-

pecia;

rarely

rashesand dry eyes (reversibleon

withdrawal);overdosage: see EmergencyTreatment

ofPoisoning, p. 37

Dose

. Bymouth, hypertension, initially 80mg twice daily,

increasedat weekly intervals asrequired; mainte-

nance160–320 mg daily

Prophylaxisof variceal bleeding inportal hyper-

tension,initially 40mg twicedaily, increasedto 80mg

twicedaily accordingto heartrate; max.160 mgtwice

daily

Phaeochromocytoma(only with an alpha-blocker),

60mg dailyfor 3days beforesurgery

30mg dailyin

patientsunsuitable for surgery

Angina,initially 40 mg2–3 times daily;maintenance

120–240mg daily

Arrhythmias,hypertrophic cardiomyopathy,anxiety

tachycardia,and thyrotoxicosis (adjunct),10–40 mg

3–4times daily

Anxietywith symptomssuch as palpitation,sweating,

tremor,40 mgonce daily, increasedto 40 mg3 times

dailyif necessary

Prophylaxisafter myocardialinfarction, 40mg 4times

dailyfor 2–3days, then80 mgtwice daily,beginning 5

to21 days after infarction

Essentialtremor, initially 40mg 2–3times daily;

maintenance80–160 mg daily

Migraineprophylaxis, 80–240mg daily in divided

doses

. Byintravenous injection, arrhythmias andthyrotoxic

crisis,1 mg over1 minute; if necessaryrepeat at 2-

minuteintervals; max. total dose 10mg (5mg in

anaesthesia)

Note

Excessive bradycardiacan be counteredwith intra-

venousinjection of atropinesulphate 0.6–2.4mg in divided

dosesof 600micrograms; for overdosagesee Emergency

Treatmentof Poisoning,p. 37

Propranolol(Non-proprietary) A

Tablets

,propranolol hydrochloride 10mg, net price

28= 92p;40 mg,28 =93p; 80mg, 56= £1.54;160 mg,

56= £4.02. Label: 8

Brandsinclude

Angilol

Oralsolution

,propranolol hydrochloride 5mg/5mL,

netprice 150 mL= £12.50; 10mg/5 mL,150 mL =

£16.45;50 mg/5mL, 150mL = £19.98. Label:8

Brandsinclude

Syprol

Inderal

(AstraZeneca)A

Injection

,propranolol hydrochloride 1mg/mL, net

price1-mL amp = 21p

Modiﬁedrelease

Note

Modiﬁed-releasepreparations canbe usedfor once daily

administration

Half-InderalLA

(AstraZeneca)A

Capsules

,m/r, lavender/pink, propranololhydro-

chloride80 mg, netprice 28-cap pack =£5.40.

Label:8, 25

Note

Modiﬁed-release capsules containing propranolol hydro-

chloride80 mgalso available; brandsinclude

BedranolSR

HalfBeta Prograne

Inderal-LA

(AstraZeneca)A

Capsules

,m/r, lavender/pink, propranololhydro-

chloride160 mg, net price 28-cap pack =£1.91.

Label:8, 25

Note

Modiﬁed-release capsules containing propranolol hydro-

chloride160 mgalso available; brandsinclude

BedranolSR

BetaPrograne

Slo-Pro

BNF 61 2.4 Beta-adrenoceptor blocking drugs 99

Cardiovascularsystem

ACEBUTOLOL

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

halvedose if eGFR 25–50mL/

minute/1.73m

;use quarter dose ifeGFR less than

25mL/minute/1.73m

;do not administer morethan

oncedaily

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Hypertension,initially 400 mgonce daily

200mg

twicedaily, increased after2 weeks to 400mg twice

dailyif necessary

. Angina,initially 400mg once daily

200mg twice

daily;300 mg 3times dailyin severe angina; up to

1.2g daily hasbeen used

. Arrhythmias,0.4–1.2 g dailyin 2–3 divided doses

Sectral

(Sanoﬁ-Aventis)A

Capsules

,acebutolol (as hydrochloride) 100mg

(buff/white),net price 84-cap pack =£14.97; 200mg

(buff/pink),56-cap pack = £19.18.Label: 8

Tablets

,f/c, acebutolol 400mg (as hydrochloride),

netprice 28-tab pack =£18.62. Label: 8

ATENOLOL

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

max.50 mg daily(10 mg onalter-

natedays

intravenously

)if eGFR 15–35mL/minute/

1.73m

;max. 25mg daily or 50mg onalternate days

(10mg every 4days

intravenously

)if eGFR less than

15mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Bymouth, hypertension,25–50 mgdaily (higherdoses

rarelynecessary)

Angina,100 mg dailyin 1 or 2doses

Arrhythmias,50–100 mg daily

Migraineprophylaxis [unlicensed],50–200 mgdaily in

divideddoses

. Byintravenous injection,arrhythmias, 2.5mg ata rate

of1 mg/minute, repeatedat 5-minute intervals toa

max.of 10 mg

Note

Excessive bradycardiacan be counteredwith intra-

venousinjection of atropinesulphate 0.6–2.4mg in divided

dosesof 600micrograms; for overdosagesee Emergency

Treatmentof Poisoning,p. 37

. Byintravenous infusion, arrhythmias, 150micr-

ograms/kgover 20minutes, repeated every 12hours

ifrequired

Earlyintervention within 12 hours ofmyocardial

infarction(section 2.10.1), by intravenousinjection

over5 minutes, 5mg, then by mouth,50 mg after15

minutes,50 mg after12 hours, then 100mg daily

Atenolol(Non-proprietary) A

Tablets

,atenolol 25mg, net price 28-tabpack = 83p;

50mg, 28-tabpack =86p; 100 mg,28-tab pack= 91p.

Label:8

Tenormin

(AstraZeneca)A

‘25’tablets

,f/c, atenolol25 mg,net price28-tab pack

=£1.16. Label: 8

LStablets

,orange, f/c, scored, atenolol50 mg,net

price28-tab pack = £2.04.Label: 8

Tablets

,orange, f/c, scored, atenolol100 mg, net

price28-tab pack = £3.46.Label: 8

Syrup

,sugar-free, atenolol 25mg/5 mL,net price

300mL =£8.55. Label: 8

Injection

,atenolol 500micrograms/mL, net price10-

mLamp = 96p (hosp.only)

Withdiuretic

Co-tenidone

(Non-proprietary)A

Tablets

,co-tenidone 50/12.5 (atenolol50 mg,chlor-

talidone12.5 mg), netprice 28-tab pack =£1.77; co-

tenidone100/25 (atenolol 100mg, chlortalidone

25mg), 28-tab pack= £1.57. Label: 8

Dose

hypertension,1 tablet daily(but see alsounder Dose

above)

Kalten

(BPC100) A

Capsules

,red/ivory, atenolol 50mg, co-amilozide

2.5/25(anhydrous amiloride hydrochloride2.5 mg,

hydrochlorothiazide25 mg),net price 28-cap pack =

£12.17.Label: 8

Dose

hypertension,1 capsule daily

Tenoret50

(AstraZeneca)A

Tablets

,brown, f/c, co-tenidone 50/12.5(atenolol

50mg, chlortalidone12.5 mg),net price28-tab pack=

£1.15.Label: 8

Dose

hypertension,1 tablet daily

Tenoretic

(AstraZeneca)A

Tablets

,brown, f/c, co-tenidone 100/25(atenolol

100mg, chlortalidone25 mg),net price 28-tabpack =

£1.25.Label: 8

Dose

hypertension,1 tablet daily(but see alsounder Dose

above)

Withcalcium-channel blocker

Note

Onlyindicated when calcium-channel blocker or beta-

blockeralone proves inadequate.For prescribing information

onnifedipine see section2.6.2

Beta-Adalat

(BayerSchering) A

Capsules

,reddish-brown, atenolol 50mg, nifedipine

20mg (m/r),net price 28-cap pack= £9.00. Label: 8,

Dose

hypertension,1 capsule daily,increased ifnecessary to

twicedaily; ELDERLY,1 daily

Angina,1 capsule twicedaily

Tenif

(AstraZeneca)A

Capsules

,reddish-brown, atenolol 50mg, nifedipine

20mg (m/r),net price28-cap pack =£10.63. Label:8,

Dose

hypertension,1 capsule daily,increased ifnecessary to

twicedaily; ELDERLY,1 daily

Angina,1 capsule twicedaily

100 2.4 Beta-adrenoceptorblocking drugs BNF 61

Cardiovascularsystem

BISOPROLOLFUMARATE

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride;

ensureheart failure not worseningbefore increasing

dose

Contra-indications

seeunder Propranolol Hydro-

chloride;also acute or decompensatedheart failure

requiringintravenous inotropes; sino-atrial block

Hepaticimpairment

max.10 mg dailyin severe

impairment

Renalimpairment

reducedose if eGFR lessthan

20mL/minute/1.73m

(max.10 mg daily)

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride;

also

lesscommonly

depression,muscle weakness,and

cramp;

rarely

hypertriglyceridaemia,syncope, and

hearingimpairment;

veryrarely

conjunctivitis

Dose

. Hypertensionand angina, usually 10mg once daily

(5mg maybe adequatein some patients);max. 20mg

daily

. Adjunctin heart failure (section2.5.5), initially

1.25mg oncedaily (inthe morning) for1 weekthen, if

welltolerated, increased to 2.5mg once dailyfor 1

week,then 3.75 mgonce daily for 1week, then 5mg

oncedaily for 4 weeks,then 7.5 mgonce daily for 4

weeks,then 10mg once daily; max. 10mg daily

BisoprololFumarate (Non-proprietary) A

Tablets

,bisoprolol fumarate 5mg, net price 28-tab

pack= £1.08; 10mg, 28-tab pack= £1.14. Label: 8

Cardicor

(MerckSerono) A

Tablets

,f/c, bisoprolol fumarate 1.25mg (white), net

price28-tab pack =£4.90; 2.5mg (scored, white), 28-

tabpack = £3.40; 3.75mg (scored, off-white),28-tab

pack= £4.90; 5mg (scored,light yellow), 28-tabpack

=£5.90; 7.5mg (scored, yellow),28-tab pack =£5.90;

10mg (scored,orange), 28-tab pack =£5.90. Label: 8

Emcor

(MerckSerono) A

LSTablets

,yellow, f/c, scored,bisoprolol fumarate

5mg, net price28-tab pack =£11.30. Label: 8

Tablets

,orange, f/c, scored, bisoprololfumarate

10mg, net price28-tab pack =£12.68. Label: 8

CARVEDILOL

Indications

hypertension;angina; adjunctto diuretics,

digoxin,or ACE inhibitors insymptomatic chronic

heartfailure

Cautions

seeunder Propranolol Hydrochloride;

monitorrenal function during dose titrationin

patientswith heart failure whoalso have renal

impairment,low blood pressure, ischaemicheart

disease,or diffuse vascular disease

Contra-indications

seeunder Propranolol Hydro-

chloride;acute or decompensated heartfailure

requiringintravenous inotropes

Hepaticimpairment

avoid

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

posturalhypotension, dizziness, head-

ache,fatigue, gastro-intestinal disturbances,brady-

cardia;occasionally diminishedperipheral circulation,

peripheraloedema and painful extremities,dry

mouth,dry eyes, eye irritationor disturbed vision,

impotence,disturbances of micturition, inﬂuenza-like

symptoms;rarely angina, AVblock, exacerbation of

intermittentclaudication or Raynaud’s phenomenon;

allergicskin reactions,exacerbation ofpsoriasis, nasal

stufﬁness,wheezing, depressed mood, sleepdistur-

bances,paraesthesia, heart failure, changesin liver

enzymes,thrombocytopenia, leucopenia also

reported

Dose

. Hypertension,initially 12.5 mgonce daily, increased

after2 days to usualdose of 25mg once daily; if

necessarymay be further increased atintervals of at

least2 weeks tomax. 50mg daily insingle or divided

doses;

ELDERLYinitial dose of12.5 mg dailymay

providesatisfactory control

. Angina,initially 12.5mg twice daily,increased after 2

daysto 25 mgtwice daily

. Adjunctin heart failure (section2.5.5) initially

3.125mg twice daily(with food), dose increasedat

intervalsof at least 2 weeksto 6.25mg twice daily,

thento 12.5mg twice daily,then to25 mgtwice daily;

increaseto highest dose tolerated,max. 25 mgtwice

dailyin patients with severeheart failure or body-

weightless than 85kg and 50mg twice daily in

patientsover 85 kg

Carvedilol(Non-proprietary) A

Tablets

,carvedilol 3.125 mg,net price 28-tab pack=

£1.10;6.25 mg, 28-tabpack = £1.25;12.5 mg, 28-tab

pack= £1.37; 25mg, 28-tab pack= £1.84. Label: 8

Eucardic

(Roche)A

Tablets

,scored, carvedilol 3.125mg (pink), net price

28-tabpack = £7.13; 6.25mg (yellow),28-tab pack =

£7.92;12.5 mg (peach),28-tab pack = £8.81;25 mg,

28-tabpack = £11.00. Label:8

CELIPROLOLHYDROCHLORIDE

Indications

mildto moderate hypertension

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

reducedose by half ifeGFR 15–

40mL/minute/1.73m

;avoid if eGFR lessthan

15mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

headache,dizziness, fatigue, nausea and

somnolence;also bradycardia, bronchospasm;

depressionand pneumonitis reported rarely

Dose

. 200mg once dailyin the morning, increasedto

400mg once dailyif necessary

Celiprolol(Non-proprietary) A

Tablets

,celiprolol hydrochloride200mg, netprice 28-

tabpack = £4.53; 400mg, 28-tabpack = £24.24.

Label:8, 22

Celectol

(Winthrop)A

Tablets

,f/c, scored, celiprolol hydrochloride200 mg

(yellow),net price 28-tab pack= £19.83; 400mg, 28-

tabpack = £39.65. Label:8, 22

BNF 61 2.4 Beta-adrenoceptor blocking drugs 101

Cardiovascularsystem

ESMOLOLHYDROCHLORIDE

Indications

short-termtreatment of supraventricular

arrhythmias(including atrial ﬁbrillation, atrial ﬂutter,

sinustachycardia); tachycardia andhypertension in

peri-operativeperiod

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

manufactureradvises caution

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride;

alsoon infusion venous irritationand thrombophleb-

itis

Dose

. Byintravenous infusion, usually withinrange 50–

200micrograms/kg/minute (consult productlitera-

turefor detailsof dose titrationand dosesduring peri-

operativeperiod)

Brevibloc

(Baxter)A

Injection

,esmolol hydrochloride10 mg/mL,net price

10-mLvial = £7.79, 250-mLinfusion bag =£89.69

LABETALOLHYDROCHLORIDE

Indications

hypertension(including hypertension in

pregnancy,hypertension with angina,and hyper-

tensionfollowing acute myocardial infarction);

hypertensivecrises (see section 2.5);controlled

hypotensionin anaesthesia

Cautions

seeunder Propranolol Hydrochloride; inter-

fereswith laboratory tests for catecholamines;liver

damage(see below)

Liverdamage

Severehepatocellular damagereported after

bothshort-term and long-termtreatment. Appropriate

laboratorytesting needed atﬁrst symptom of liverdys-

functionand iflaboratory evidenceofdamage (orif jaundice)

labetalolshould be stoppedand not restarted

Contra-indications

seeunder Propranolol Hydro-

chloride

Hepaticimpairment

avoid—severehepatocellular

injuryreported

Renalimpairment

dosereduction may be required

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

posturalhypotension (avoid upright

positionduring and for 3hours after intravenous

administration),tiredness, weakness, headache,

rashes,scalp tingling, difﬁculty inmicturition, epi-

gastricpain, nausea, vomiting; liverdamage (see

above);rarely lichenoid rash

Dose

. Bymouth, initially 100mg (50mg in elderly) twice

dailywith food, increased atintervals of 14 days to

usualdose of200 mgtwice daily;up to800 mgdaily in

2divided doses (3–4 divideddoses if higher); max.

2.4g daily

. Byintravenous injection,50 mgover atleast 1minute,

repeatedafter 5minutes if necessary; max.total dose

200mg

Note

Excessive bradycardiacan be counteredwith intra-

venousinjection of atropinesulphate 0.6–2.4mg in divided

dosesof 600micrograms; for overdosagesee Emergency

Treatmentof Poisoning,p. 37

. Byintravenous infusion, 2mg/minute until satisfac-

toryresponse then discontinue; usual totaldose 50–

200mg, (notrecommended forphaeochromocytoma,

seeunder Phaeochromocytoma, section 2.5.4)

Hypertensionof pregnancy, 20mg/hour, doubled

every30 minutes; usual max. 160mg/hour

Hypertensionfollowing myocardialinfarction, 15mg/

hour,gradually increased to max.120 mg/hour

LabetalolHydrochloride (Non-proprietary) A

Tablets

,f/c, labetalol hydrochloride 100mg, net

price,56 = £7.85;200 mg, 56= £11.49; 400mg, 56 =

£20.60.Label: 8, 21

Trandate

(UCBPharma) A

Tablets

,all orange,f/c, labetalolhydrochloride 50mg,

netprice 56-tab pack =£3.64; 100mg, 56-tab pack=

£4.01;200 mg, 56-tabpack = £6.51;400 mg, 56-tab

pack= £9.05. Label: 8,21

Injection

,labetalol hydrochloride5 mg/mL, netprice

20-mLamp = £2.04

METOPROLOLTARTRATE

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Hepaticimpairment

reducedose in severe impair-

ment

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Bymouth, hypertension, initially 100mg daily,

increasedif necessary to 200mg daily in1–2 divided

doses;max. 400 mgdaily (but high dosesrarely

necessary)

Angina,50–100 mg 2–3times daily

Arrhythmias,usually 50 mg2–3 times daily;up to

300mg daily individed doses if necessary

Migraineprophylaxis, 100–200mg daily in divided

doses

Hyperthyroidism(adjunct), 50 mg4 times daily

. Byintravenous injection, arrhythmias, upto 5 mgat

rate1–2 mg/minute, repeatedafter 5minutes if

necessary,total dose 10–15mg

Note

Excessive bradycardiacan be counteredwith intra-

venousinjection of atropinesulphate 0.6–2.4mg in divided

dosesof 600micrograms; for overdosagesee Emergency

Treatmentof Poisoning,p. 37

Insurgery, by slow intravenousinjection 2–4 mgat

inductionor tocontrol arrhythmias developing during

anaesthesia;2-mg dosesmay berepeated to amax. of

10mg

Earlyintervention within 12 hours ofinfarction, by

intravenousinjection 5mg every 2minutes to a max.

of15 mg, followedafter 15 minutes by50 mgby

mouthevery 6 hours for 48hours; maintenance

200mg daily individed doses

MetoprololTartrate (Non-proprietary) A

Tablets

,metoprolol tartrate 50mg, net price 28=

£1.31,56 = £1.74; 100mg, 28= £1.59, 56 =£2.51.

Label:8

Betaloc

(AstraZeneca)A

Injection

,metoprolol tartrate 1mg/mL, net price 5-

mLamp = 42p

Lopresor

(Novartis)A

Tablets

,f/c, scored, metoprololtartrate 50mg (pink),

netprice 56-tab pack =£2.57; 100 mg(blue), 56-tab

pack= £6.68. Label: 8

102 2.4 Beta-adrenoceptorblocking drugs BNF 61

Cardiovascularsystem

Modiﬁedrelease

LopresorSR

(Recordati)A

Tablets

,m/r, yellow,f/c, metoprolol tartrate 200 mg,

netprice 28-tab pack =£9.80. Label: 8, 25

Dose

hypertension,200 mgdaily; angina, 200–400mg daily;

migraineprophylaxis, 200mg daily

NADOLOL

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Hepaticimpairment

manufactureradvises caution

Renalimpairment

increasedosage interval if eGFR

lessthan 50 mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Hypertension,initially 80 mgonce daily, increasedin

incrementsof up to 80mg at weeklyintervals if

required;max. 240 mgdaily (higher doses rarely

necessary)

. Angina,initially 40mg oncedaily, increasedat weekly

intervalsif required; usual max.160 mg daily(rarely

upto 240 mgmay be required)

. Arrhythmias,initially 40mg once daily, increasedat

weeklyintervals up to 160mg if required;reduce to

40mg if bradycardiaoccurs

. Migraineprophylaxis, initially 40mg once daily,

increasedin 40 mgincrements at weekly intervals

accordingto response; usual maintenancedose 80–

160mg once daily

. Thyrotoxicosis(adjunct), 80–160mg once daily

Corgard

(Sanoﬁ-Aventis)A

Tablets

,blue, scored, nadolol80 mg, netprice 28-tab

pack= £5.00. Label: 8

NEBIVOLOL

Indications

essentialhypertension; adjunct in stable

mildto moderate heart failurein patients over 70

years

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride;also acute or decompensatedheart failure

requiringintravenous inotropes

Hepaticimpairment

noinformation available—man-

ufactureradvises avoid

Renalimpairment

for

hypertension

,initially 2.5 mg

oncedaily,increased to5 mgonce dailyif required;for

heartfailure

,manufacturer advises avoid ifserum

creatininegreater than 250micromol/litre

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride;

alsooedema and depression

Dose

. Hypertension,5 mg daily;ELDERLY initially 2.5mg

daily,increased if necessary to5 mgdaily

. Adjunctin heart failure (section2.5.5), initially

1.25mg once daily,then if toleratedincreased at

intervalsof 1–2 weeks to2.5 mg oncedaily, then to

5mg once daily,then to max.10 mg oncedaily

Nebivolol(Non-proprietary) A

Tablets

,nebivolol (as hydrochloride) 5mg, netprice

28-tabpack = £3.98. Label:8

Nebilet

(Menarini)A

Tablets

,scored, nebivolol(as hydrochloride)5mg, net

price28-tab pack = £9.23.Label: 8

Note

Alsoavailable as

Hypoloc

OXPRENOLOLHYDROCHLORIDE

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Hepaticimpairment

reducedose

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Hypertension,80–160 mg dailyin 2–3 divided doses,

increasedas required; max. 320mg daily

. Angina,80–160 mg dailyin 2–3 divided doses;max.

320mg daily

. Arrhythmias,40–240 mg daily in 2–3 divided doses;

max.240 mg daily

. Anxietysymptoms (short-term use), 40–80mg daily

in1–2 divided doses

Oxprenolol(Non-proprietary) A

Tablets

,coated, oxprenolol hydrochloride 20mg, net

price56 =£1.86; 40mg, 56=£3.73; 80mg, 56 =£6.20;

160mg, 20 =£2.36. Label: 8

Trasicor

(Amdipharm)A

Tablets

,f/c, oxprenololhydrochloride 20mg (contain

gluten),net price 56-tabpack =£1.86; 40 mg(contain

gluten),56-tab pack = £3.73;80 mg (yellow),56-tab

pack= £6.20. Label: 8

Modiﬁedrelease

Slow-Trasicor

(Amdipharm)A

Tablets

,m/r, f/c, oxprenololhydrochloride 160 mg,

netprice 28-tab pack =£7.50. Label: 8, 25

Dose

hypertension,angina, initially 160mg oncedaily; if

necessarymay be increasedto max. 320mg daily

Withdiuretic

Trasidrex

(Goldshield)A

Tablets

,red, s/c, co-prenozide 160/0.25(oxprenolol

hydrochloride160 mg(m/r), cyclopenthiazide

250micrograms), net price28-tab pack =£10.66.

Label:8, 25

Dose

hypertension,1 tablet daily,increased ifnecessary to 2

dailyas asingle dose

PINDOLOL

Indications

seeunder Dose

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

mayadversely affect renal func-

tionin severe impairment—manufacturer advises

avoid

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

BNF 61 2.4 Beta-adrenoceptor blocking drugs 103

Cardiovascularsystem

Dose

. Hypertension,initially 5mg 2–3 times daily

15mg

oncedaily, increased asrequired at weekly intervals;

usualmaintenance 15–30 mgdaily; max. 45mg daily

. Angina,2.5–5 mg upto 3 times daily

Pindolol(Non-proprietary) A

Tablets

,pindolol 5mg, netprice 100-tabpack =£7.81.

Label:8

Visken

(Amdipharm)A

Tablets

,scored, pindolol 5mg, net price 56-tabpack

=£5.85; 15mg, 28-tab pack =£8.79. Label: 8

Withdiuretic

Viskaldix

(Amdipharm)A

Tablets

,scored, pindolol 10mg, clopamide 5mg, net

price28-tab pack = £6.70.Label: 8

Dose

hypertension,1 tablet dailyin themor ning,increased if

necessaryto 2 daily;max. 3 daily

SOTALOLHYDROCHLORIDE

Indications

life-threateningarrhythmias including

ventriculartachyarrhythmias; symptomatic non-sus-

tainedventricular tachyarrhythmias; prophylaxis of

paroxysmalatrial tachycardia or ﬁbrillation,paroxys-

malAV re-entrant tachycardias(both nodal and

involvingaccessory pathways), and paroxysmal

supraventriculartachycardia after cardiac surgery;

maintenanceof sinus rhythm followingcardioversion

ofatrial ﬁbrillation or ﬂutter

Cautions

seeunder Propranolol Hydrochloride; cor-

recthypokalaemia, hypomagnesaemia, or other

electrolytedisturbances; severe or prolongeddiar r-

hoea;interactions: Appendix 1 (beta-blockers),

important:verapamil interaction see also p.133

Contra-indications

seeunder Propranolol Hydro-

chloride;congenital or acquired longQT syndrome;

torsadede pointes; renal failure

Renalimpairment

usehalf normal dose if eGFR30–

60mL/minute/1.73m

;use one-quarter normaldose

ifeGFR 10–30 mL/minute/1.73m

;avoid if eGFR

lessthan 10 mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride;

arrhythmogenic(pro-arrhythmic) effect (torsade de

pointes—increasedrisk in women)

Dose

. Bymouth with ECG monitoringand measurement of

correctedQT interval, arrhythmias, initially80 mg

dailyin 1–2 divided dosesincreased gradually at

intervalsof 2–3 days tousual dose of 160–320mg

dailyin 2 divided doses;higher doses of 480–640mg

dailyfor life-threatening ventricular arrhythmias

underspecialist supervision

Sotalol(Non-proprietary) A

Tablets

,sotalol hydrochloride 40mg, net price 56=

£1.29;80 mg,56 =£1.91; 160 mg,28 =£2.32. Label: 8

Beta-Cardone

(UCBPharma) A

Tablets

,scored, sotalol hydrochloride 40mg (green),

netprice 56-tab pack =£1.29; 80 mg(pink), 56-tab

pack= £1.91; 200mg, 28-tab pack= £2.40. Label: 8

Sotacor

(Bristol-MyersSquibb) A

Tablets

,scored, sotalol hydrochloride 80mg, net

price28-tab pack = £3.06.Label: 8

TIMOLOLMALEATE

Indications

seeunder Dose; glaucoma (section11.6)

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Hepaticimpairment

dosereduction may be neces-

sary

Renalimpairment

manufactureradvises caution—

dosereduction may be required

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Dose

. Hypertension,initially 10 mgdaily in 1–2 divided

doses;gradually increasedif necessary tomax. 60mg

daily,usual maintenance dose10–30 mg daily(doses

above30 mg dailygiven in divided doses)

. Angina,initially 5mg twice daily increased ifneces-

saryby 10mg dailyevery 3–4 days;max. 30mg twice

daily

. Prophylaxisafter myocardial infarction, initially5 mg

twicedaily,increased after 2days to10 mgtwice daily

iftolerated

. Migraineprophylaxis, 10–20mg daily in 1–2 divided

doses

Betim

(Meda)A

Tablets

,scored, timolol maleate 10mg, net price30-

tabpack = £2.08. Label:8

Withdiuretic

Timololwith amiloride and hydrochlorothiazide

(Non-proprietary)A

Tablets

,scored, timolol maleate 10mg, amiloride

hydrochloride2.5 mg,hydrochlorothiazide 25mg, net

price28-tab pack = £29.87.Label: 8

Dose

hypertension,1–2 tablets daily

Prestim

(Meda)A

Tablets

,scored, timolol maleate 10mg, bendroﬂu-

methiazide2.5 mg, net price 30-tab pack =£3.49.

Label:8

Dose

hypertension,1–2 tablets daily;max. 4 daily

2.5

Hypertension and heart

failure

Hypertension

Lowering raised blood pressure

decreases the risk of stroke, coronary events, heart

failure, and renal impairment. Advice on antihyper-

tensive therapy in this section takes into account the

recommendations of the JointBritish Societies (JBS2:

BritishSocieties’ guidelines onprevention of cardiovas-

culardisease in clinicalpractice.

Heart

2005;91 (Suppl

V):v1–v52).

Possible causes of hypertension (e.g. renal disease,

endocrine causes), contributor y factors, risk factors,

andthe presence ofany complications ofhypertension,

such as left ventricular hypertrophy, should be estab-

lished. Patients should be given advice on lifestyle

104 2.5 Hypertensionand heart failure BNF61

Cardiovascularsystem

changesto reduceblood pressureor cardiovascularrisk;

these include smoking cessation, weight reduction,

reduction of excessive intake of alcohol, reduction of

dietarysalt, reductionof total andsaturated fat,increas-

ingexercise, and increasing fruitand vegetable intake.

Thresholdsand targets for treatment

Thefollow-

ingthresholds for treatment

arerecommended:

Severe hypertension with acute target-organ

damage,

severe hypertension (systolic blood

pressure 180 mmHg

diastolic 110 mmHg)

withoutacute target-organ damage, treat promptly

(seeHypertensive crises, p.106)

When the initial blood pressure is systolic 160–

179mmHg

diastolic 100–109mmHg,

and

the

patient has cardiovascular complications, target-

organ damage (e.g. left ventricular hypertrophy,

renal impairment) or diabetes mellitus (type 1 or

2),conﬁrm over3–4 weeksthen treatif thesevalues

aresustained;

When the initial blood pressure is systolic 160–

179mmHg

diastolic 100–109mmHg, but the

patient has

cardiovascular complications, no

target-organdamage, orno diabetes,advise lifestyle

changes,reassess weekly initiallyand treat if these

valuesare sustained on repeatmeasurements over

4–12weeks;

When the initial blood pressure is systolic 140–

159mmHg

diastolic 90–99mmHg

and

the

patient has cardiovascular complications, target-

organ damage or diabetes, conﬁrm within 12

weeksand treat if thesevalues are sustained;

When the initial blood pressure is systolic 140–

159mmHg

diastolic90–99 mmHg and

cardi-

ovascular complications, no target-organ damage,

or no diabetes, advise lifestyle changes and reas-

sessmonthly; treat persistent mild hypertensionif

the 10-year cardiovascular disease risk is 20% or

more.

Atarget systolic blood pressure <140mmHg

and

dia-

stolicblood pressure <90 mmHgis suggested. Alower

targetsystolic blood pressure< 130mmHg

and

diasto-

licblood pressure <80mmHg should beconsidered for

those with established atherosclerotic cardiovascular

disease, diabetes, or chronic renal failure. In some

individuals it may not be possible to reduce blood

pressure below the suggested targets despite the use

ofappropriate therapy.

Drugtreatment of hypertension

Responseto drug

treatment for hypertension may be af fected by the

patient’sage and ethnicbackground. An ACEinhibitor

(section2.5.5.1) or anangiotensin-II receptor antago-

nist(section 2.5.5.2)may be themost appropriateinitial

drug in younger Caucasians; however a beta-blocker

may be considered if an ACEinhibitor or an angio-

tensin-IIreceptor antagonist is not tolerated oris con-

tra-indicated (see also Hypertension in Pregnancy,

p.106). Afro-Caribbean patients andthose agedover

55years respond lesswell to ACEinhibitors and angio-

tensin-IIreceptor antagonists,therefore a thiazide(sec-

tion2.2.1) ora calcium-channel blocker(section 2.6.2)

maybe chosen for initialtreatment.

Beta-blockers, especially when combined with a thia-

zide diuretic, should be avoided for the routine treat-

ment of uncomplicated hypertension in patients with

diabetesor in those athigh risk ofdeveloping diabetes.

Asingle antihypertensivedrug isoften notadequate and

other antihypertensive drugs are usually added in a

step-wisemanner until control is achieved.Unless it is

necessary to lower the blood pressure urgently, an

intervalof at least 4weeks should be allowedto deter-

mineresponse.

Whentwo antihypertensive drugs are needed, an ACE

inhibitor

anangiotensin-II receptorantagonist canbe

combined with

either

a thiazide

a calcium-channel

blocker.

Ifcontrol is inadequate with 2 drugs, a thiazide

and

calcium-channelblocker can be added.The addition of

an alpha-blocker (section 2.5.4), spironolactone,

anotherdiuretic, ora beta-blocker shouldbe considered

in resistant hypertension. In patients with

primary

hyperaldosteronism

, spironolactone (section 2.2.3) is

effective.

Other measures to reduce cardiovascular risk

Aspirin (section 2.9)in a dose of 75 mgdaily reduces

therisk of cardiovascularevents and myocardialinfarc-

tion. Unduly high blood pressure must becontrolled

beforeaspirin is given. Unless contra-indicated,aspirin

isrecommended for all patients withestablished cardi-

ovasculardisease. Useof aspirin in primaryprevention,

inthose with orwithout diabetes,is of unprovenbeneﬁt

(seealso section 2.9).

Lipid-regulatingdrugs can also be of beneﬁt incardio-

vascular disease or in those whoare at high risk of

developingcardiovascular disease (section 2.12).

Hypertensionin the elderly

Beneﬁtfrom antihyper-

tensivetherapy is evidentup to atleast 80 yearsof age,

butit isprobably inappropriateto applya strict agelimit

whendeciding on drug therapy.Patients who reach 80

yearsof age whiletaking antihypertensive drugsshould

continuetreatment, provided that it continues tobe of

beneﬁtand does not cause signiﬁcantside-effects. The

thresholdsfor treatmentare diastolicpressure averaging

90mmHg

systolic pressure averaging

160mmHg over 3 to 6 months’obser vation(despite

appropriate lifestyle interventions). Treatment with a

low dose of a thiazide or a dihydropyridinecalcium-

channel blocker is effective. An ACE inhibitor (or an

angiotensin-II receptor antagonist) (section 2.5.5) can

beadded if necessary.

Isolated systolic hypertension

Isolated systolic

hypertension (systolic pressure 160mmHg, diastolic

pressure <90mmHg) isassociated with an increased

cardiovascular disease risk, particularly in those aged

over 60 years. Systolic blood pressure averaging

160mmHg orhigher over3 to 6months (despiteappro-

priatelifestyle interventions)should be loweredin those

over60 years, even if diastolic hypertension isabsent.

Treatmentwith a low dose of a thiazide or a dihydro-

pyridine calcium-channelblocker is effective. An ACE

inhibitor(or an angiotensin-IIreceptor antagonist) (sec-

1.Thresholds and targets for treatment based on blood

pressuremeasured in clinic maynot apply to ambulatory

or home blood-pressure monitoring, which usually give

lowervalues.

2.Cardiovascular disease risk may be determined from the

chartissued by theJoint British Societies(

Heart

2005;91

(Suppl V): v1–v52)—see inside back cover. The Joint

British Societies’ ‘Cardiac Risk Assessor’ computer pro-

gramme may also be used to determine cardiovascular

diseaserisk.

BNF 61 2.5Hypertension and heart failure 105

Cardiovascularsystem

tion 2.5.5) can be added if necessary. Patients with

severe postural hypotension should not receive blood

pressurelowering drugs.

Isolated systolic hypertension in younger patients is

uncommon but treatment may be indicated in those

witha threshold systolicpressure of 160mmHg (orless

ifat increasedrisk ofcardiovascular disease,see above).

Hypertensionin diabetes

Forpatients withdiabetes,

the aim should be to maintain systolic pressure

<130mmHg and diastolic pressure <80mmHg. How-

ever, in some individuals, it may not be possible to

achievethis levelof controldespite appropriate therapy.

Mostpatients requirea combinationof antihypertensive

drugs.

Hypertension iscommon in type 2 diabetes, and anti-

hypertensive treatment prevents macrovascular and

microvascularcomplications. In type1 diabetes, hyper-

tension usually indicates the presence of diabetic

nephropathy. An ACE inhibitor (or an angiotensin-II

receptor antagonist) may have a speciﬁc role in the

management of diabetic nephropathy (section 6.1.5);

in patients with type 2 diabetes, an ACE inhibitor (or

an angiotensin-II receptor antagonist) can delay pro-

gressionof microalbuminuria to nephropathy.

Hypertension in renal disease

The threshold for

antihypertensive treatment in patients with renal

impairment or persistent proteinuria is a systolic

bloodpressure  140mmHg

adiastolic blood pres-

sure 90 mmHg. Optimalblood pressure is a systolic

blood pressure <130 mmHg and a diastolic pressure

<80mmHg, or lower if proteinuriaexceeds 1 g in 24

hours.An ACE inhibitor (or an angiotensin-II receptor

antagonist)should be considered for patientswith pro-

teinuria; however,ACE inhibitors should be used with

cautionin renal impairment, see section 2.5.5.1. Thia-

zidediuretics may beineffective and highdoses of loop

diuretics may be required. A dihydropyridine calcium

channelblocker can be added.

Hypertensionin pregnancy

Hypertensivecomplica-

tionsin pregnancycan behazardous forboth themother

andthe fetus, and areassociated with a signiﬁcant risk

ofmorbidity and mortality; complications canoccur in

pregnant women with pre-existing chronic hyper-

tension, or in those who develop hypertension in the

latterhalf of pregnancy.

Labetalol(section 2.4)is widelyused for treatinghyper-

tension in pregnancy. Methyldopa (section 2.5.2) is

consideredsafe for use in pregnancy. Modiﬁed-release

preparations of nifedipine [unlicensed] are also used,

butsee section2.6.2 (p. 132)for warningson use during

pregnancy.

Thefollowing advicetakes into accountthe recommen-

dations ofNICE Clinical Guideline 107 (August 2010),

Hypertensionin Pregnancy.

Pregnant women with chronic hypertension who are

already receiving antihypertensive treatment should

have their drug therapy reviewed. In uncomplicated

chronic hypertension, a target blood pressure of

<150/100mmHg is recommended; women with tar-

get-organdamage as a result of chronic hypertension,

and in women with chronic hypertension who have

givenbirth, a target bloodpressure of <140/90mmHg

is advised. Long-term antihypertensive treatment

should be reviewed 2 weeks following the birth.

Women managed with methyldopa during pregnancy

should discontinuetreatment and restart their original

antihypertensivemedication within 2 daysof the birth.

Pregnant women are at high riskof developing pre-

eclampsiaif they have chronickidney disease, diabetes

mellitus,autoimmune disease, chronichypertension, or

if they have had hypertension during a previous

pregnancy; these women are advised to take aspirin

(section2.9) in a dose of 75mg once daily [unlicensed

indication]from week 12of pregnancy until thebaby is

born.Women with morethan one moderate risk factor

(ﬁrst pregnancy, aged 40 years, pregnancy interval

>10 years, BMI 35 kg/m

at ﬁrst visit, multiple

pregnancy,or familyhistory ofpre-eclampsia) fordevel-

oping pre-eclampsia are also advised to take aspirin

75mg once daily[unlicensed indication] from week 12

ofpregnancy until the babyis born.

Womenwith pre-eclampsia orgestational hypertension

who present with a blood pressure over 150/

100mmHg, should receive initial treatmentwith oral

labetalol to achieve a target blood pressure of

<150mmHg systolic, and diastolic 80–100mmHg. If

labetalolis unsuitable, methyldopa or modiﬁed-release

nifedipinemay be considered. Womenwith gestational

hypertensionor pre-eclampsiawho havebeen managed

withmethyldopa during pregnancy should discontinue

treatment within 2 days of the birth. Women with a

bloodpressure of160/110 mmHgwho require critical

care during pregnancy or after birth should receive

immediate treatment with either oral or intravenous

labetalol, intravenous hydralazine (section 2.5.1), or

oral modiﬁed-release nifedipine to achieve a target

blood pressure of <150mmHg systolic,and diastolic

80–100mmHg.

For use of magnesium sulphate in pre-eclampsia and

eclampsia,see section 9.5.1.3.

Hypertensivecrises

Ifblood pressure isreduced too

quicklyin themanagement of hypertensivecrises, there

isa risk of reduced organ perfusion leading to cerebral

infarction,blindness, deteriorationin renalfunction, and

myocardialischaemia.

hypertensive emergency

is deﬁned as severe hyper-

tension with acute damage to the target organs(e.g.

signs of papilloedema or retinal haemorrhage, or the

presenceof clinical conditions such as acute coronary

syndromes, acute aortic dissection, acutepulmonar y

oedema, hypertensive encephalopathy, acute cerebral

infarction,intracerebral or subarachnoid haemorrhage,

eclampsia,or rapidly progressing renalfailure); prompt

treatmentwith intravenous antihypertensive therapy is

generallyrequired. Over the ﬁrstfew minutes orwithin

2hours, blood pressure shouldbe reduced by 20–25%.

When intravenous therapy is indicated, treatment

optionsinclude sodium nitroprusside [unlicensed](sec-

tion 2.5.1), labetalol (section 2.4), glyceryl trinitrate

(section 2.6.1), phentolamine (section 2.5.4), hydral-

azine (section 2.5.1), or esmolol (section 2.4); choice

of drug is dependent on concomitant conditions and

clinicalstatus of the patient.

Severehypertension (bloodpressure 180/110mmHg)

without acute target-organ damage is deﬁned as a

hypertensiveurgency

;blood pressureshould bereduced

graduallyover 24–48 hours with oral antihypertensive

therapy,suchas labetalol, orthe calcium-channelblock-

106 2.5 Hypertensionand heart failure BNF61

Cardiovascularsystem

ers(section 2.6.2) amlodipine, felodipine, orisradipine.

Useof sublingual nifedipine isnot recommended.

Foradvice on short-term management ofhypertensive

episodes in phaeochromocytoma, see under Phaeo-

chromocytoma,section 2.5.4.

2.5.1

Vasodilator

antihypertensive drugs

Vasodilators have a potent hypotensiveef fect, espe-

cially when used in combination with abeta-blocker

anda thiazide.Impor tant:for awarning on thehazards

ofa very rapid fallin blood pressure, see Hypertensive

crises,p. 106.

Diazoxide has been used by intravenous injection in

hypertensive emergencies, however alternative treat-

mentsare preferred (see section 2.5)

Hydralazineis given by mouth as an adjunctto other

antihypertensives forthe treatment of resistant hyper-

tension but is rarely used; when used alone it causes

tachycardiaand ﬂuid retention. The incidence of side-

effects islower if the dose is kept below 100mg daily,

butsystemic lupus erythematosus shouldbe suspected

ifthere isunexplained weight loss,arthritis, orany other

unexplainedill health.

Sodium nitroprusside [unlicensed] is given by intra-

venous infusion to control severe hypertensive emer-

gencieswhen parenteral treatment isnecessar y.

Minoxidil should be reserved for the treatment of

severehypertension resistant to other drugs. Vasodila-

tationis accompanied by increasedcardiac output and

tachycardiaand thepatients developﬂuid retention. For

thisreason the additionof a beta-blockerand a diuretic

(usually furosemide, in high dosage) are mandatory.

Hypertrichosis is troublesome and renders this drug

unsuitablefor women.

Prazosin,doxazosin, and terazosin (section 2.5.4) have

alpha-blockingand vasodilator properties.

Ambrisentan, bosentan, iloprost, sildenaﬁl, sitaxen-

tan, and tadalaﬁl are licensed for the treatment of

pulmonary arterial hypertension and should be used

under specialist supervision. Epoprostenol (section

2.8.1)can be used in patients withprimar ypulmonary

hypertensionresistant to other treatments. Bosentanis

alsolicensed toreduce the numberof new digitalulcers

in patientswith systemic sclerosis and ongoing digital

ulcerdisease.

The

ScottishMed icinesConsortium

(p.4) has advised

(November2005) that iloprost (

Ventavis

)is accepted

for restricted use within NHS Scotland in patients in

whom bosentan is ineffective or not tolerated, and

shouldonly be prescribed byspecialists in the Scottish

PulmonaryVascular Unit.

The

ScottishMed icinesConsortium

(p.4) has advised

(October2008) that ambrisentan (

Volibris

)should be

prescribedonly byspecialists in theScottish Pulmonary

VascularUnit or other similarspecialists.

The

ScottishMed icinesConsortium

(p.4) has advised

(January 2010) that sildenaﬁl (

Revatio

) should be

prescribedonly byspecialists in theScottish Pulmonary

VascularUnit or other similarspecialists.

Sitaxentan

Sitaxentan (

Thelin

) is to be withdrawn from

worldwidemarkets due to severe, sometimes fatal,

hepatotoxicity; the beneﬁts of treatment with

sitaxentan no longer outweigh the risks. Patients

currently takingsitaxentan are advised not to stop

until their treatment has been reviewed by their

prescriber;patients should beswitched to asuitable

alternative as soon as possible. Patients with

abnormal liver function tests at the time of

sitaxentan discontinuation should be monitored

regularly until liver enzymes return to within the

normalrange.

AMBRISENTAN

Indications

pulmonaryarterial hypertension

Cautions

notto be initiated insigniﬁcant anaemia;

monitorhaemoglobin concentration or haematocrit

after1 monthand 3 monthsof startingtreatment, and

periodicallythereafter (reduce dose ordiscontinue

treatmentif signiﬁcant decrease inhaemoglobin

concentrationor haematocritobserved); monitorliver

functionbefore treatment, and monthlythereafter—

discontinueif liver enzymes raised signiﬁcantlyor if

symptomsof liver impairment develop

Hepaticimpairment

avoidin severe impairment

Renalimpairment

usewith caution ifeGFR less than

30mL/minute/1.73m

Pregnancy

avoid(teratogenic in

animal

studies);

excludepregnancy before treatment andensure

effectivecontraception during treatment; monthly

pregnancytests advised

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

abdominalpain, constipation; palpita-

tion,ﬂushing, peripheral oedema; upper respiratory-

tractdisorders; headache; anaemia;

lesscommonly

hypersensitivityreactions (including angioedemaand

rash)

Dose

. ADULTover 18years, 5 mgonce daily, increasedif

necessaryto 10 mgonce daily

Volibris

(GSK)TA

Tablets

,f/c, ambrisentan 5mg (pale pink), netprice

30-tabpack = £1618.08; 10mg (dark pink),30-tab

pack= £1618.08

BOSENTAN

Indications

pulmonaryarterial hypertension; sys-

temicsclerosis with ongoing digitalulcer disease (to

reducenumber of new digitalulcers)

Cautions

notto be initiated ifsystemic systolic blood

pressureis below 85mmHg; monitor haemoglobin

beforeand during treatment (monthlyfor ﬁrst 4

months,then 3-monthly); avoid abruptwithdrawal;

monitorliver function before treatment,at monthly

intervalsduring treatment, and 2 weeksafter dose

increase(reduce dose or suspendtreatment if liver

enzymesraised signiﬁcantly)—discontinue if symp-

tomsof liver impairment; interactions: Appendix1

(bosentan)

Contra-indications

acuteporphyria (section 9.8.2)

Hepaticimpairment

avoidin moderate and severe

impairment

BNF 61 2.5.1 Vasodilatorantihypertensive drugs 107

Cardiovascularsystem

Pregnancy

avoid(teratogenic in

animal

studies);

effectivecontraception required during andfor at

least3 months after administration(hor monal

contraceptionnot considered effective); monthly

pregnancytests advised

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

gastro-intestinaldisturbances, dry

mouth,rectal haemorrhage, hepatic impairment (see

Cautions,above); ﬂushing, hypotension, palpitation,

oedema,chest pain; dyspnoea; headache,dizziness,

fatigue;back pain and painin extremities; anaemia;

hypersensitivityreactions (including rash, pruritus,

andanaphylaxis)

Dose

. Pulmonaryarterial hypertension, initially 62.5mg

twicedaily increased after 4weeks to 125mg twice

daily;max. 250 mgtwice daily;

CHILDunder 12 years

see

BNFfor Children

. Systemicsclerosis with ongoing digitalulcer disease,

initially62.5 mgtwice dailyincreased after 4weeks to

125mg twice daily

Tracleer

(Actelion)TA

Tablets

,f/c, orange, bosentan (asmonohydrate)

62.5mg, net price56-tab pack =£1510.21; 125 mg,

56-tabpack = £1510.21

DIAZOXIDE

Indications

hypertensiveemergency including severe

hypertensionassociated with renal disease(but no

longerrecommended—see section 2.5); hypoglyc-

aemia(section 6.1.4)

Cautions

ischaemicheart disease; interactions:

Appendix1 (diazoxide)

Renalimpairment

dosereduction may be required

Pregnancy

prolongeduse may produce alopecia,

hypertrichosis,and impaired glucose tolerancein

neonate;inhibits uterine activity duringlabour

Side-effects

tachycardia,hypotension, hyperglyc-

aemia,sodium and water retention;

rarely

cardiome-

galy,hyperosmolar non-ketotic coma,leucopenia,

thrombocytopenia,and hirsuitism

Dose

. Byrapid intravenous injection(less than 30seconds),

1–3mg/kg tomax. singledose of 150mg (seebelow);

maybe repeated after 5–15minutes if required

Note

Single doses of 300mg have been associatedwith

anginaand with myocardialand cerebral infarction

Eudemine

(Goldshield)AU

Injection

,diazoxide 15mg/mL, net price20-mL amp

=£30.00

Tablets

,see section 6.1.4

HYDRALAZINE HYDROCHLORIDE

Indications

moderateto severe hypertension

(adjunct);heart failure (with long-actingnitrate, but

seesection 2.5.5); hypertensive emergencies(includ-

ingduring pregnancy) (see section2.5)

Cautions

coronaryartery disease (may provoke

angina,avoid after myocardial infarctionuntil stabi-

lised),cerebrovascular disease; occasionally blood

pressurereduction toorapid even withlow parenteral

doses;manufacturer advisestest forantinuclear factor

andfor proteinuria every 6 monthsand check acet-

ylatorstatus before increasing doseabove 100 mg

daily,but evidence ofclinical value unsatisfactory;

interactions:Appendix 1 (hydralazine)

Contra-indications

idiopathicsystemic lupus erythe-

matosus,severe tachycardia,high outputheart failure,

myocardialinsufﬁciency due to mechanicalobstruc-

tion,cor pulmonale,dissecting aorticaneurysm; acute

porphyria(section 9.8.2)

Hepaticimpairment

reducedose

Renalimpairment

reducedose if eGFR lessthan

30mL/minute/1.73m

Pregnancy

neonatalthrombocytopenia reported, but

riskshould be balanced againstrisk of uncontrolled

maternalhypertension; manufacturer advises avoid

beforethird trimester

Breast-feeding

presentin milk but notknown to be

harmful;monitor infant

Side-effects

tachycardia,palpitation, ﬂushing, hypo-

tension,ﬂuid retention,gastro-intestinal disturbances;

headache,dizziness; systemic lupus erythematosus-

likesyndrome after long-term therapywith over

100mg daily(or less inwomen andin slow acetylator

individuals)(see also notes above);rarely rashes,

fever,peripheral neuritis, polyneuritis,paraesthesia,

arthralgia,myalgia, increased lacrimation, nasalcon-

gestion,dyspnoea, agitation, anxiety,anorexia; blood

disorders(including leucopenia, thrombocytopenia,

haemolyticanaemia), abnormal liver function,jaun-

dice,raised plasma creatinine, proteinuriaand hae-

maturiareported

Dose

. Bymouth, hypertension, 25mg twice daily,increased

tousual max. 50mg twice daily (seenotes above)

Heartfailure (initiated in hospital)25 mg 3–4times

daily,increased every 2days if necessary; usual

maintenancedose 50–75 mg4 times daily

. Byslow intravenous injection, hypertensiveemer-

genciesand hypertension with renalcomplications,

5–10mg diluted with10 mL sodiumchloride 0.9%;

maybe repeated after 20–30minutes (see Cautions)

. Byintravenous infusion, hypertensive emergencies

andhypertension with renal complications,initially

200–300micrograms/minute; maintenance usually

50–150micrograms/minute

Hydralazine(Non-proprietary) A

Tablets

,hydralazine hydrochloride 25mg, net price

56= £9.32; 50mg, 56 =£16.84

Apresoline

(Amdipharm)A

Tablets

,yellow,s/c, hydralazinehydrochloride 25mg,

netprice 84-tab pack =£3.38

Excipients

includegluten

Injection

,powder for reconstitution, hydralazine

hydrochloride,net price 20-mg amp= £2.22

ILOPROST

Indications

idiopathicor familial pulmonary arterial

hypertension

Cautions

unstablepulmonary hypertension with

advancedright heart failure; hypotension(do not

initiateif systolic blood pressurebelow 85 mmHg);

acutepulmonary infection; chronic obstructive

pulmonarydisease; severe asthma; interactions:

Appendix1 (iloprost)

Contra-indications

unstableangina; within 6 months

ofmyocardial infarction; decompensated cardiac

failure(unless under close medicalsuper vision);

108 2.5.1 Vasodilatorantihypertensive drugs BNF61

Cardiovascularsystem

severearrhythmias; congenital or acquired heart-

valvedefects; within 3 monthsof cerebrovascular

events;pulmonary veno-occlusivedisease; conditions

whichincrease risk of bleeding

Hepaticimpairment

eliminationreduced—initially

2.5micrograms no morefrequently than every 3

hours(max. 6 times daily),adjusted according to

response(consult product literature)

Pregnancy

manufactureradvises avoid (toxicity in

animal

studies);effective contraception mustbe used

duringtreatment

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

vasodilatation,hypotension, syncope,

cough,headache, throat or jawpain; nausea, vomi-

ting,diarrhoea, chest pain,dyspnoea, bronchospasm,

andwheezing also reported

Dose

. Byinhalation of nebulised solution,initial dose

2.5micrograms increasedto 5micrograms for second

dose,if tolerated maintainat 5 micrograms6–9 times

dailyaccording toresponse; reduceto 2.5micrograms

6–9times daily if higherdose not tolerated;

CHILD8–

18years see

BNFfor Children

Ventavis

(BayerSchering) A

Nebulisersolution

,iloprost (as trometamol)

10micrograms/mL, net price30  1-mL (10micr-

ogram)unit-dose vials = £400.19,168  1-mL =

£2241.08.For use with

Prodose

Dor

Venta-Neb

Dnebuliser

MINOXIDIL

Indications

severehypertension, in addition toa

diureticand a beta-blocker

Cautions

seenotes above; angina; after myocardial

infarction(until stabilised); lower dosesin dialysis

patients;acute porphyria(section 9.8.2);interactions:

Appendix1 (vasodilator antihypertensives)

Contra-indications

phaeochromocytoma

Renalimpairment

usewith caution in signiﬁcant

impairment

Pregnancy

avoid—possibletoxicity includingreduced

placentalperfusion; neonatal hirsutism reported

Breast-feeding

presentin milk but notknown to be

harmful

Side-effects

sodiumand waterretention; weight gain,

peripheraloedema, tachycardia, hypertrichosis;

reversiblerise in creatinine andblood urea nitrogen;

occasionally,gastro-intestinal disturbances, breast

tenderness,rashes

Dose

. Initially5 mg(ELDERLY, 2.5mg) daily, in1–2 divided

doses,increased in stepsof 5–10mg at intervals ofat

least3 days; max.100 mg daily(seldom necessary to

exceed50 mg daily)

Loniten

(Pharmacia)A

Tablets

,scored, minoxidil 2.5mg, net price 60-tab

pack= £8.88; 5mg, 60-tab pack= £15.83; 10mg, 60-

tabpack = £30.68

SILDENAFIL

Indications

pulmonaryarterial hypertension; erectile

dysfunction(section 7.4.5)

Cautions

hypotension(avoid ifsystolic blood pressure

below90 mmHg);intravascular volumedepletion; left

ventricularoutﬂow obstruction; cardiovascular dis-

ease;autonomic dysfunction; pulmonary veno-

occlusivedisease; anatomical deformation ofthe

penis,predisposition to priapism; bleedingdisorders

oractive peptic ulceration; considergradual with-

drawal;interactions: Appendix 1 (sildenaﬁl)

Contra-indications

recenthistory of stroke or myo-

cardialinfarction, history of non-arteriticanterior

ischaemicoptic neuropathy; hereditary degenerative

retinaldisorders; avoid concomitant useof nitrates

Hepaticimpairment

for

pulmonaryhypertension

,if

usualdose not tolerated, reduce

oral

doseto 20 mg

twicedaily,or reduce

intravenous

doseto 10mg twice

daily;manufacturer advises avoid insevere impair-

ment

Renalimpairment

for

pulmonaryhypertension

,if

usualdose not tolerated, reduce

oral

doseto 20 mg

twicedaily,or reduce

intravenous

doseto 10mg twice

daily

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risk—no evidence ofhar m in

ani-

mal

studies

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

gastro-intestinaldisturbances, dry

mouth;ﬂushing, oedema; bronchitis, cough;head-

ache,migraine, night sweats, paraesthesia,insomnia,

anxiety,tremor, vertigo; fever,inﬂuenza-like symp-

toms;anaemia; back and limbpain, myalgia; visual

disturbances,retinal haemorrhage, photophobia,

painfulred eyes;nasal congestion, epistaxis;cellulitis,

alopecia;

lesscommonly

gynaecomastia,priapism;

alsoreported

rash,retinal vascularocclusion andnon-

arteriticanterior ischaemic optic neuropathy(dis-

continueif sudden visual impairment),and sudden

hearingloss (advise patient toseek medical help)

Dose

. Bymouth, 20 mg3 times daily; CHILDunder 18 years

see

BNFfor Children

. Byintravenous injection, when oralroute not appro-

priate,10 mg threetimes daily

Revatio

(Pﬁzer)TA

Tablets

,f/c, sildenaﬁl(as citrate),20 mg,net price 90-

tabpack = £373.50

Injection

,sildenaﬁl (as citrate), 800micrograms/mL,

netprice 50-mL vial =£45.28

Viagra

(Pﬁzer)AD

Section7.4.5 (erectile dysfunction)

SITAXENTANSODIUM

Indications

pulmonaryarterial hypertension (but see

notesabove)

Cautions

testliver function before treatmentand

monitormonthly during treatment (discontinue

treatmentif liver enzymes signiﬁcantly raised);mea-

surehaemoglobin concentration before treatment,

after1–3 months, thenevery 3 months; interactions:

Appendix1 (sitaxentan)

Hepaticimpairment

avoid

Pregnancy

avoidunless essential—toxicity in

animal

studies;manufacturer advises effective contraception

duringtreatment

BNF 61 2.5.1 Vasodilatorantihypertensive drugs 109

Cardiovascularsystem

Breast-feeding

manufactureradvises avoid—present

inmilk in

animal

studies

Side-effects

gastro-intestinaldisturbances; peripheral

oedema,ﬂushing; headache, insomnia, fatigue,dizzi-

ness;decreased haemoglobin,prolonged prothrombin

time,increased INR; muscle cramp; nasalcongestion,

epistaxis

Dose

. ADULTover 18years 100 mgonce daily

Thelin

(Encysive)TA

Tablets

,f/c, yellow-orange, sitaxentansodium

100mg, net price28-tab pack =£1540.00

Note

Allorders of Thelin should be based ona prescription

froma specialistin Pulmonary ArterialHypertension, whohas

receivedappropriate training aspart of theProgrammed

Accessto SitaxentanSodium (PASS)scheme.Orders should be

placedwith Polarspeedat 01525 217211

SODIUM NITROPRUSSIDE

Indications

hypertensiveemergencies (see section

2.5);controlled hypotension in anaesthesia;acute or

chronicheart failure

Cautions

hypothyroidism,hyponatraemia, ischaemic

heartdisease, impaired cerebral circulation,elderly;

hypothermia;monitor blood pressure andblood-cya-

nideconcentration and if treatmentexceeds 3 days,

alsoblood-thiocyanate concentration; avoid sudden

withdrawal—terminateinfusion over 15–30 minutes;

protectinfusion from light; interactions:Appendix 1

(sodiumnitroprusside)

Contra-indications

severevitamin B

deﬁciency;

Leber’soptic atrophy; compensatory hypertension

Hepaticimpairment

usewith caution; avoid in

hepaticfailure—cyanide or thiocyanate metabolites

mayaccumulate

Renalimpairment

avoidprolonged use—cyanide or

thiocyanatemetabolites may accumulate

Pregnancy

avoidprolonged use—potential for accu-

mulationof cyanide in fetus

Breast-feeding

noinformation available; caution

adviseddue to thiocyanate metabolite

Side-effects

associatedwith over rapid reduction in

bloodpressure (reduce infusion rate):headache, diz-

ziness,nausea, retching,abdominal pain,perspiration,

palpitation,anxiety, retrosternal discomfort;occa-

sionallyreduced platelet count, acutetransient phle-

bitis

Cyanide

Side-effects causedby excessive plasma concen-

trationof the cyanidemetabolite include tachycardia,

sweating,hyperventilation, arrhythmias, markedmetabolic

acidosis(discontinue and giveantidote, see p.39)

Dose

. Hypertensiveemergencies, by intravenous infusion,

initially0.5–1.5 micrograms/kg/minute,then

increasedin steps of 500nanograms/kg/minute

every5 minutes within range 0.5–8micrograms/kg/

minute(lower doses if alreadyreceiving other anti-

hypertensives);stop if response unsatisfactorywith

max.dose in 10 minutes

Note

Lowerinitial dose of 300 nanograms/kg/minutehas

beenused

. Maintenanceof blood pressureat 30–40% lowerthan

pretreatmentdiastolic blood pressure, 20–400micr-

ograms/minute(lower doses for patientsbeing trea-

tedwith other antihypertensives)

. Controlledhypotension in surgery,by intravenous

infusion,max. 1.5 micrograms/kg/minute

. Heartfailure, by intravenous infusion,initially 10–

15micrograms/minute, increasedever y5–10 min-

utesas necessary; usual range 10–200micrograms/

minutenormally for max. 3 days

SodiumNitroprusside (Non-proprietary) A

Intravenousinfusion

,powder for reconstitution,

sodiumnitroprusside 10 mg/mL

Availablefrom ‘special-order’ manufacturersor spe-

cialistimporting companies, see p.988

TADALAFIL

Indications

pulmonaryarterial hypertension; erectile

dysfunction(section 7.4.5)

Cautions

hypotension(avoid ifsystolic blood pressure

below90 mmHg); aorticand mitral valve disease;

pericardialconstriction; congestive cardiomyopathy;

leftventricular dysfunction; life-threatening arrhyth-

mias;coronary artery disease; uncontrolled hyper-

tension;pulmonary veno-occlusive disease; predis-

positionto priapism; anatomical deformationof the

penis;hereditary degenerative retinal disorders;

interactions:Appendix 1 (tadalaﬁl)

Contra-indications

acutemyocardial infarction in

past90 days; history ofnon-arteritic anterior

ischaemicoptic neuropathy;avoid concomitantuse of

nitrates

Hepaticimpairment

initially20 mgonce daily inmild

tomoderate impairment; avoid insevere impairment

Renalimpairment

initially20 mgonce dailyin mildto

moderateimpairment, increased to 40mg once daily

iftolerated; avoid in severeimpairment

Pregnancy

manufactureradvises avoid

Breast-feeding

manufactureradvises avoid—present

inmilk in

animal

studies

Side-effects

nausea,vomiting, dyspepsia, gastro-

oesophagealreﬂux, chest pain, palpitation, ﬂushing,

hypotension,nasopharyngitis, epistaxis, headache,

myalgia,back and limb pain,increased uterine

bleeding,blurred vision, facial oedema,rash;

less

commonly

tachycardia,hypertension, seizures,

amnesia,priapism, hyperhidrosis;

alsoreported

unstableangina, arrhythmia, myocardial infarction,

stroke,hearing loss, non-arteritic anteriorischaemic

opticneuropathy, retinal vascularocclusion, visual

ﬁelddefect, Stevens-Johnson syndrome

Dose

. ADULTover 18years, 40 mgonce daily

Adcirca

(Lilly)TA

Tablets

,f/c, tadalaﬁl20 mg (orange),net price56-tab

pack= £491.22

2.5.2

Centrally acting

antihypertensive drugs

Methyldopa is a centrally acting antihypertensive; it

may be used for the management of hypertension in

pregnancy.Side-effects areminimised ifthe dailydose is

keptbelow 1 g.

Clonidinehas thedisadvantage that suddenwithdrawal

oftreatment may cause severerebound hypertension.

Moxonidine,a centrallyacting drug,is licensedfor mild

tomoderate essential hypertension. It mayhave a role

when thiazides, calcium-channel blockers, ACE inhi-

bitors, and beta-blockers are not appropriate or have

failedto control blood pressure.

110 2.5.2 Centrallyacting antihypertensive drugs BNF 61

Cardiovascularsystem

CLONIDINEHYDROCHLORIDE U

Indications

hypertension;migraine (section 4.7.4.2);

menopausalﬂushing (section 6.4.1.1)

Cautions

mustbe withdrawngradually toavoid severe

reboundhypertension; Raynaud’s syndromeor other

occlusiveperipheral vascular disease; historyof

depression;interactions: Appendix 1 (clonidine)

Driving

Drowsinessmay affectperfor mance of skilledtasks

(e.g.driving); effects ofalcohol may beenhanced

Pregnancy

maylower fetal heart rate,but risk should

bebalanced against risk ofuncontrolled maternal

hypertension;avoid intravenous injection

Breast-feeding

manufactureradvises avoid—present

inmilk

Side-effects

drymouth, sedation, depression, ﬂuid

retention,bradycardia, Raynaud’s phenomenon,

headache,dizziness, euphoria, nocturnalunrest, rash,

nausea,constipation, rarely impotence

Dose

. Bymouth, 50–100 micrograms3 times daily,

increasedevery second orthird day; usual max.dose

1.2mg daily

Catapres

(BoehringerIngelheim) AU

Tablets

,scored, clonidine hydrochloride 100micr-

ograms,net price 100-tab pack= £5.32; 300micr-

ograms,100-tab pack =£12.39. Label: 3, 8

Dixarit

Section4.7.4.2

METHYLDOPA

Indications

hypertension

Cautions

monitorblood counts and liver-function

beforetreatment and at intervalsduring ﬁrst 6–12

weeksor if unexplained feveroccurs; history of

depression;positive direct Coombs’test in upto 20%

ofpatients (may affect bloodcross-matching); inter-

ferencewith laboratory tests;interactions: Appendix

1(methyldopa)

Driving

Drowsinessmay affectperfor mance of skilledtasks

(e.g.driving); effects ofalcohol may beenhanced

Contra-indications

depression,phaeochromocytoma;

acuteporphyria (section 9.8.2)

Hepaticimpairment

manufactureradvises caution in

historyof liver disease; avoidin active liver disease

Renalimpairment

startwith small dose; increased

sensitivityto hypotensive and sedativeeffect

Pregnancy

notknown to be harmful

Breast-feeding

amounttoo small to behar mful

Side-effects

gastro-intestinaldisturbances, dry

mouth,stomatitis, sialadenitis; bradycardia, exacer-

bationof angina, postural hypotension,oedema;

sedation,headache, dizziness, asthenia, myalgia,

arthralgia,paraesthesia, nightmares, mild psychosis,

depression,impaired mental acuity,parkinsonism,

Bell’spalsy; hepatitis, jaundice;pancreatitis; haemo-

lyticanaemia; bone-marrow depression, leucopenia,

thrombocytopenia,eosinophilia; hypersensitivity

reactionsincluding lupus erythematosus-like

syndrome,drug fever,myocarditis, pericarditis;rashes

(includingtoxic epidermal necrolysis); nasalconges-

tion,failure of ejaculation, impotence,decreased libi-

do,gynaecomastia, hyperprolactinaemia, amenor-

rhoea

Dose

. Initially250 mg2–3 timesdaily,increased gradually at

intervalsof at least 2 days,max. 3g daily;

ELDERLY

initially125 mgtwice daily, increasedg radually,max.

2g daily

Methyldopa(Non-proprietary) A

Tablets

,coated, methyldopa (anhydrous)125 mg,net

price56-tab pack = £16.29;250 mg,56-tab pack =

£8.26;500 mg, 56-tabpack = £11.49.Label: 3, 8

Aldomet

(Iroko)A

Tablets

,all yellow, f/c,methyldopa (anhydrous)

250mg, net price60 = £6.15;500 mg, 30= £4.55.

Label:3, 8

MOXONIDINE

Indications

mildto moderate essential hypertension

Cautions

avoidabrupt withdrawal (if concomitant

treatmentwith beta-blocker has tobe stopped, dis-

continuebeta-blocker ﬁrst, then moxonidineafter a

fewdays); severe coronary arterydisease; unstable

angina;ﬁrst-degree AV block;moderate heart failure;

interactions:see Appendix 1 (moxonidine)

Contra-indications

conductiondisorders (sick sinus

syndrome,sino-atrial block, second- orthird-degree

AVblock); bradycardia; severeheart failure

Renalimpairment

max.single dose 200micrograms

andmax. daily dose 400micrograms if eGFR30–

60mL/minute/1.73m

;avoid if eGFR lessthan

30mL/minute/1.73m

Pregnancy

manufactureradvises avoid—no informa-

tionavailable

Breast-feeding

presentin milk—manufacturer

advisesavoid

Side-effects

drymouth, diarrhoea, nausea, vomiting,

dyspepsia,dizziness, somnolence, insomnia, back

pain,rash, pruritus;

lesscommonly

bradycardia,tin-

nitus,angioedema, oedema, nervousness, neckpain

Dose

. 200micrograms oncedaily in the morning,increased

ifnecessary after 3 weeksto 400micrograms daily in

1–2divided doses; max. 600micrograms daily in2

divideddoses (max. single dose400 micrograms)

Moxonidine(Non-proprietary) A

Tablets

,f/c, moxonidine 200micrograms, net price

28-tabpack =£3.76; 300micrograms, netprice 28-tab

pack=£4.82; 400micrograms, netprice 28-tabpack =

£5.01.Label: 3

Physiotens

(Solvay)A

Tablets

,f/c, moxonidine 200micrograms (pink), net

price28-tab pack = £9.72;300 micrograms(red), 28-

tabpack =£11.49; 400 micrograms(red), 28-tab pack

=£13.26. Label: 3

2.5.3

Adrenergic neurone

blocking drugs

Adrenergicneurone blocking drugs preventthe release

of noradrenaline from postganglionic adrenergic neu-

rones.These drugsdo notcontrol supineblood pressure

and may cause postural hypotension. For this reason

theyhave largely fallenfrom use,but may benecessar y

withother therapy in resistanthypertension.

BNF 61 2.5.3 Adrenergicneurone blocking drugs 111

Cardiovascularsystem

Guanethidine,which alsodepletes thenerve endings of

noradrenaline, is licensed for rapid control of blood

pressure,however alternative treatments are preferred

(seesection 2.5).

GUANETHIDINE MONOSULPHATE

Indications

hypertensivecrisis (but no longer recom-

mended—seesection 2.5)

Cautions

coronaryor cerebral arteriosclerosis,

asthma,history of peptic ulceration; interactions:

Appendix1 (adrenergic neurone blockers)

Contra-indications

phaeochromocytoma,heart fail-

ure

Renalimpairment

reducedose if eGFR 40–65mL/

minute/1.73m

;avoid if eGFR lessthan 40 mL/min-

ute/1.73m

Pregnancy

posturalhypotension and reduced utero-

placentalperfusion; should not beused to treat

hypertensionin pregnancy

Side-effects

posturalhypotension, failure of ejacula-

tion,ﬂuid retention, nasal congestion, headache,

diarrhoea,drowsiness

Dose

. Byintramuscular injection,10–20 mg,repeated after3

hoursif required

Ismelin

(Amdipharm)AU

Injection

,guanethidine monosulphate10 mg/mL,net

price1-mL amp = £1.56

2.5.4

Alpha-adrenoceptor

blocking drugs

Prazosinhas post-synaptic alpha-blocking and vasodi-

lator properties and rarelycauses tachycardia. It may,

however,reduce bloodpressure rapidly after the ﬁrst

dose andshould be introduced with caution. Doxazo-

sin, indoramin,and terazosin have properties similar

tothose of prazosin.

Alpha-blockerscan be usedwith otherantihypertensive

drugsin thetreatment of resistanthypertension (section

2.5).

Prostatic hyperplasia

Alfuzosin, doxazosin, indor-

amin,prazosin, tamsulosin, and terazosinare indicated

forbenign prostatic hyperplasia (section7.4.1).

DOXAZOSIN

Indications

hypertension(see notes above); benign

prostatichyperplasia (section 7.4.1)

Cautions

carewith initial dose(postural hypotension);

pulmonaryoedema due to aortic or mitral stenosis;

cataractsurgery (risk of intra-operativeﬂ oppyiris

syndrome);heart failure; interactions: Appendix1

(alpha-blockers)

Driving

Mayaffect performance ofskilled tasks e.g.driving

Contra-indications

historyof hypotension; mono-

therapyin overﬂow bladder oranuria

Hepaticimpairment

usewith caution; manufacturer

advisesavoid in severe impairment—noinfor mation

available

Pregnancy

noevidence of teratogenicity; manufac-

turersadvise use only whenpotential beneﬁt out-

weighsrisk

Breast-feeding

accumulatesin milk—manufacturer

advisesavoid

Side-effects

seesection 7.4.1; also dyspnoea,cough-

ing;fatigue, vertigo, paraesthesia, sleepdisturbance,

anxiety;inﬂuenza-like symptoms; backpain, myalgia;

lesscommonly

weightchanges, angina, myocardial

infarction,hypoaesthesia, tremor, agitation, micturi-

tiondisturbance, epistaxis, arthralgia, tinnitus,and

gout;

veryrarely

cholestasis,hepatitis, jaundice,

bradycardia,arrhythmias, bronchospasm,hot ﬂushes,

gynaecomastia,abnormal ejaculation, leucopenia,

thrombocytopenia,and alopecia

Dose

. Hypertension,1 mg daily,increased after 1–2weeks

to2 mgonce daily,andthereafter to 4mg oncedaily,if

necessary;max. 16 mgdaily

Doxazosin(Non-proprietary) A

Tablets,

doxazosin(as mesilate) 1mg, net price 28-

tabpack =93p; 2mg, 28-tab pack= 99p;4 mg,28-tab

pack= £1.39. Counselling,initial dose, driving

Brandsinclude

Doxadura

Cardura

(Pﬁzer)A

Tablets

,doxazosin (asmesilate) 1mg, netprice 28-tab

pack= £10.56; 2mg, 28-tab pack= £14.08. Counsel-

ling,initial dose, driving

Modiﬁed-release

Doxazosin

(Non-proprietary)A

Tablets

,m/r, doxazosin (as mesilate)4 mg,net price

28-tabpack = £6.33. Label:25, counselling, initial

dose,driving

Dose

hypertension,benign prostatic hyperplasia,4 mgonce

daily,increased to8 mgonce daily after4 weeks ifnecessary

Brandsinclude

Doxadura

Raporsin

Slocinx

Cardura

XL(Pﬁzer) A

Tablets

,m/r, doxazosin (as mesilate)4 mg,net price

28-tabpack = £5.70; 8mg, 28-tabpack = £9.98.

Label:25, counselling, driving, initialdose

Dose

hypertension,benign prostatic hyperplasia,4 mgonce

daily,increased to8 mgonce daily after4 weeks ifnecessary

INDORAMIN

Indications

hypertension(see notes above); benign

prostatichyperplasia (section 7.4.1)

Cautions

avoidalcohol (enhances rate andextent of

absorption);control incipient heart failure before

initiatingindoramin; elderly; Parkinson’sdisease

(extrapyramidaldisorders reported); epilepsy (con-

vulsionsin

animal

studies);history of depression;

cataractsurgery (risk of intra-operativeﬂ oppyiris

syndrome);interactions: Appendix1 (alpha-blockers)

Driving

Drowsinessmay affectperfor mance of skilledtasks

(e.g.driving); effects ofalcohol may beenhanced

Contra-indications

establishedheart failure

Hepaticimpairment

manufactureradvises caution

Renalimpairment

manufactureradvises caution

Pregnancy

noevidence of teratogenicity; manufac-

turersadvise use only whenpotential beneﬁt out-

weighsrisk

Breast-feeding

noinformation available

Side-effects

seesection 7.4.1; also sedation;

less

commonly

fatigue,weight gain, failure ofejaculation;

112 2.5.4 Alpha-adrenoceptorblocking drugs BNF61

Cardiovascularsystem

alsoreported extrapyramidal disorders, urinaryfre-

quency,and incontinence

Dose

. Hypertension,initially 25mg twicedaily, increasedby

25–50mg daily atintervals of 2 weeks;max. daily

dose200 mg in2–3 divided doses

Baratol

(Amdipharm)A

Tablets

,blue, f/c, indoramin (ashydrochloride)

25mg, net price84-tab pack =£9.00. Label: 2

Doralese

Section7.4.1 (prostatic hyperplasia)

PRAZOSIN

Indications

hypertension(see notes above); conges-

tiveheart failure (but seesection 2.5.5); Raynaud’s

syndrome(see also section 2.6.4);benign prostatic

hyperplasia(section 7.4.1)

Cautions

ﬁrstdose may cause collapsedue to hypo-

tension(therefore should betaken on retiringto bed);

elderly;cataract surgery(risk ofintra-operative ﬂoppy

irissyndrome); interactions: Appendix 1(alpha-

blockers)

Driving

Mayaffect performance ofskilled tasks e.g.driving

Contra-indications

notrecommended for congestive

heartfailure dueto mechanicalobstruction (e.g.aortic

stenosis)

Hepaticimpairment

initially500 micrograms daily;

increasedwith caution

Renalimpairment

initially500 micrograms dailyin

moderateto severe impairment; increased withcau-

tion

Pregnancy

noevidence of teratogenicity; manufac-

turersadvise use only whenpotential beneﬁt out-

weighsrisk

Breast-feeding

amountprobably too small tobe

harmful

Side-effects

seesection 7.4.1; also dyspnoea;ner-

vousness;urinary frequency;

lesscommonly

insom-

nia,paraesthesia, sweating, arthralgia, eyedisorders,

tinnitus,and epistaxis;

rarely

pancreatitis,ﬂushing,

vasculitis,bradycardia, hallucinations, worseningof

narcolepsy,gynaecomastia, urinaryincontinence, and

alopecia

Dose

. Hypertension(see notes above),500 micrograms 2–3

timesdaily for 3–7days, the initialdose on retiringto

bedat night (to avoidcollapse, see Cautions);

increasedto 1 mg2–3 times daily fora further 3–7

days;further increased if necessary tomax. 20 mg

dailyin divided doses

. Congestiveheart failure (but seesection 2.5.5),

500micrograms 2–4 timesdaily (initial dose atbed-

time,see above), increasing to4 mg dailyin divided

doses;maintenance 4–20 mgdaily in divided doses

(butrarely used)

. Raynaud’ssyndrome (but efﬁcacy notestablished, see

section2.6.4), initially 500micrograms twice daily

(initialdose at bedtime, seeabove) increased, if

necessary,after 3–7 days tousual maintenance 1–

2mg twice daily

Prazosin(Non-proprietary) A

Tablets

,prazosin (as hydrochloride) 500micrograms,

netprice 56-tab pack =£2.51; 1 mg,56-tab pack =

£3.23;2 mg,56-tab pack =£4.39; 5mg, 56-tab pack=

£8.75.Counselling, initial dose, driving

Hypovase

(Pﬁzer)A

Tablets

,prazosin (as hydrochloride) 500micrograms,

netprice 60-tab pack =£2.69; 1 mg,scored, 60-tab

pack= £3.46. Counselling,initial dose, driving

TERAZOSIN

Indications

mildto moderate hypertension(see notes

above);benign prostatic hyperplasia (section7.4.1)

Cautions

ﬁrstdose may cause collapsedue to hypo-

tension(within 30–90 minutes, thereforeshould be

takenon retiring to bed)(may also occur withrapid

doseincrease); cataract surgery (risk ofintra-opera-

tiveﬂoppy iris syndrome); interactions:Appendix 1

(alpha-blockers)

Driving

Mayaffect performance ofskilled tasks e.g.driving

Pregnancy

noevidence of teratogenicity; manufac-

turersadvise use only whenpotential beneﬁt out-

weighsrisk

Breast-feeding

noinformation available

Side-effects

seesection 7.4.1;

alsoreported

weight

gain,dsypnoea, paraesthesia,ner vousness,decreased

libido,thrombocytopenia, back pain, andpain in

extremities

Dose

. Hypertension,1 mg atbedtime (compliance with

bedtimedose important, seeCautions); dose doubled

after7 days if necessary; usualmaintenance dose 2–

10mg once daily;more than 20mg daily rarely

improvesefﬁcacy

Terazosin(Non-proprietary) A

Tablets

,terazosin (as hydrochloride) 2mg, net price

28-tabpack =£2.16; 5mg,28-tab pack =£2.58;10 mg,

28-tabpack = £7.88.Counselling, initial dose, driving

Hytrin

(Amdipharm)A

Tablets

,terazosin (as hydrochloride) 2mg (yellow),

netprice 28-tab pack= £2.29;5 mg (tan),28-tab pack

=£4.29; 10mg (blue), 28-tab pack =£8.57; starter

pack(for hypertension)of 7 1-mg tabs with21 2-

mgtabs = £13.00. Counselling,initial dose, driving

Phaeochromocytoma

Long-term management of phaeochromocytoma

involves surgery. However, surger y should not take

place until there is adequate blockade of both alpha-

and beta-adrenoceptors; the optimal choice of drug

therapy remains unclear. Alpha-blockers are used in

the short-term management of hypertensive episodes

inphaeochromocytoma. Once alpha blockadeis estab-

lished, tachycardia can be controlled by the cautious

additionof abeta-blocker (section2.4); acardioselective

beta-blockeris preferred.

Phenoxybenzamine,a powerfulalpha-blocker, isef fec-

tivein the management of phaeochromocytoma but it

has manyside-effects. Phentolamine is a short-acting

alpha-blocker used mainly during surgery of phaeo-

chromocytoma; its use for the diagnosis of phaeo-

chromocytoma has beensuper seded by measurement

ofcatecholamines in blood andurine.

Metirosine (available from ‘special-order’ manufac-

turers or specialist importing companies, see p.988)

inhibits the enzyme tyrosine hydroxylase, andhence

the synthesis of catecholamines. It is rarely used in

thepre-operative managementof phaeochromocytoma,

and long term in patientsunsuitable for surgery; an

BNF 61 2.5.4 Alpha-adrenoceptor blocking drugs 113

Cardiovascularsystem

alpha-adrenoceptorblocking drugmay alsobe required.

Metirosineshould not be usedto treat essential hyper-

tension.

PHENOXYBENZAMINE

HYDROCHLORIDE

Indications

hypertensiveepisodes in phaeochromo-

cytoma

Cautions

elderly;congestive heart failure; severe

ischaemicheart disease (seealso Contra-indications);

cerebrovasculardisease (avoid ifhistor yof cerebro-

vascularaccident); monitor blood pressureregularly

duringinfusion; carcinogenic in

animals

;avoid in

acuteporphyria (section 9.8.2); avoidextravasation

(irritantto tissues)

Contra-indications

historyof cerebrovascular acci-

dent;during recovery period after myocardialinfarc-

tion(usually 3–4 weeks); avoidinfusion in hypovol-

aemia

Renalimpairment

usewith caution

Pregnancy

hypotensionmay occur in newborn

Breast-feeding

maybe present in milk

Side-effects

posturalhypotension with dizziness and

markedcompensatory tachycardia, lassitude, nasal

congestion,miosis, inhibition of ejaculation;rarely

gastro-intestinaldisturbances; decreased sweating

anddry mouth after intravenousinfusion; idiosyn-

craticprofound hypotension within fewminutes of

startinginfusion; convulsions following rapidintra-

venousinfusion also reported

Dose

. Seeunder preparations

Phenoxybenzamine(Goldshield) A

Injectionconcentrate

,phenoxybenzamine hydro-

chloride50 mg/mL. Tobe diluted beforeuse, net

price2-mL amp = £57.14(hosp. only)

Dose

intravenousinfusion

(preferablythrough large vein),

adjunctin severe shock(but rarelyused) and phaeochromo-

cytoma,1 mg/kgdaily overat least2 hours; donot repeatwithin

24hours (intensive carefacilities needed)

Caution

Owingto riskof contact sensitisationhealthcare profes-

sionalsshould avoidcontam inationof hands

Dibenyline

(Goldshield)A

Capsules

,red/white, phenoxybenzamine hydro-

chloride10 mg, netprice 30-cap pack =£10.84

Dose

phaeochromocytoma,10 mgdaily, increasedby 10mg

daily;usual dose 1–2mg/kg dailyin 2divided doses

PHENTOLAMINE MESILATE

Indications

hypertensiveepisodes due to phaeo-

chromocytomae.g. during surgery; diagnosisof

phaeochromocytoma(but see notes above)

Cautions

monitorblood pressure (avoid inhypo-

tension),heart rate; gastritis, pepticulcer; elderly;

interactions:Appendix 1 (alpha-blockers)

Contra-indications

hypotension;history of myo-

cardialinfarction; coronary insufﬁciency, angina,or

otherevidence of coronary artery disease

Renalimpairment

manufactureradvises caution—no

informationavailable

Pregnancy

usewith caution—may cause marked

decreasein maternal blood pressurewith resulting

fetalanoxia

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

posturalhypotension, tachycardia, dizzi-

ness,ﬂushing; nausea and vomiting,diar rhoea,nasal

congestion;also acute or prolonged hypotension,

angina,chest pain, arrhythmias

Dose

. Hypertensiveepisodes, by intravenous injection,2–

5mg repeated ifnecessary

. Diagnosisof phaeochromocytoma, consult product

literature

Rogitine

(Alliance)A

Injection

,phentolamine mesilate 10mg/mL, net

price1-mL amp = £1.53

Excipients

includesulphites

2.5.5

Drugs affecting the renin-

angiotensin system

2.5.5.1 Angiotensin-convertin genzyme

inhibitors

2.5.5.2 Angiotensin-II receptor antagonists

2.5.5.3 Renin inhibitors

Heart failure

Drug treatment of heart failure associated with a

reducedleft ventricularejection fraction(left ventricular

systolicdysfunction) iscovered below;optimal manage-

ment of heart failure with a preserved left ventricular

ejectionfraction has not beenestablished..

The treatment of chronic heart failure aims to relieve

symptoms,improve exercise tolerance,reduce the inci-

denceof acute exacerbations,and reduce mortality.An

ACEinhibitor, titrated to a ‘target dose’ (or the max-

imum tolerated dose if lower), together with abeta-

blocker,form thebasis of treatmentfor allpatients with

heartfailure due toleft ventricular systolic dysfunction.

An ACEinhibitor (section 2.5.5.1) is generally advised

forpatients with asymptomatic left ventricular systolic

dysfunction or symptomatic heart failure. An angio-

tensin-IIreceptor antagonist (section 2.5.5.2) maybe

a useful alternative for patients who,because of side-

effectssuch as cough,cannot tolerate ACEinhibitors; a

relatively high dose of the angiotensin-II receptor

antagonistmay be required toproduce beneﬁt. Cande-

sartan, an angiotensin-II receptorantagonist, can also

beadded to ACE inhibitor and beta-blockertherapy in

patients withmild to moderate heart failure who con-

tinueto remain symptomatic.

Thebeta-blockers bisoprololand carvedilol(section 2.4)

areof valuein anygrade ofstable heartfailure dueto left

ventricularsystolic dysfunction; nebivolol (section 2.4)

is licensed for stable mild to moderate heart failure in

patients over 70 years. Beta-blocker treatment should

bestarted by those experienced inthe management of

heartfailure, ata very lowdose and titratedvery slowly

over a period of weeks or months. Symptoms may

deteriorateinitially, calling for adjustment of concomi-

tanttherapy.

The aldosterone antagonist spironolactone (section

2.2.3)can be considered for patients withmoderate to

severe heart failure who are already taking an ACE

inhibitor and a beta-blocker; low doses of spirono-

lactone (usually 25 mg daily) reduce symptoms and

mortalityin these patients. If spironolactonecannot be

114 2.5.5 Drugsaffecting the renin-angiotensin system BNF61

Cardiovascularsystem

used,eplerenone (section 2.2.3) may beconsidered for

the management of heart failure after an acute myo-

cardialinfarction with evidence of left ventricular sys-

tolicdysfunction. Close monitoringof serum creatinine,

eGFR, and potassium is necessary, particularly follow-

ing any change in treatment or any change in the

patient’sclinical condition.

Patients who cannot tolerate an ACE inhibitor oran

angiotensin-IIreceptor antagonist, orin whom theyare

contra-indicated, may be given isosorbide dinitrate

(section 2.6.1) with hydralazine (section 2.5.1), but

this combination may be poorly tolerated. In patients

ofAfrican orCaribbean origin, andthose withmoderate

to severe heart failure, the combination of isosorbide

dinitrateand hydralazinemay be consideredin addition

tostandard therapy with an ACE inhibitor and abeta-

blocker,if necessary.

Digoxin (section 2.1.1) improves symptoms of heart

failure andexercise tolerance and reduces hospitalisa-

tiondue to acute exacerbations but itdoes not reduce

mortality.Digoxin is reservedfor patients with worsen-

ingor severeheart failure dueto left ventricularsystolic

dysfunctionwho remainsymptomatic despitetreatment

withan ACEinhibitor anda beta-blockerin combination

with either analdosterone antagonist, candesartan, or

isosorbidedinitrate with hydralazine.

Patientswith ﬂuid overloadshould also receiveeither a

loopor a thiazide diuretic (with saltor ﬂuid restriction

whereappropriate). A thiazide diuretic (section 2.2.1)

maybe of beneﬁtin patients withmild heart failureand

good renal function; however, thiazide diuretics are

ineffective in patients with poor renal function (eGFR

less than 30mL/minute/1.73m

, see Renal Impair-

ment,section 2.2.1) and a loopdiuretic (section 2.2.2)

isprefer red.If diuresis with a single diuretic is insufﬁ-

cient, a combination of a loop diuretic and a thiazide

diuretic maybe tried; addition of metolazone (section

2.2.1)may also beconsidered but the resultingdiuresis

maybe profoundand careis neededto avoidpotentially

dangerouselectrolyte disturbances.

2.5.5.1

Angiotensin-convertingenzyme

inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhi-

bitors)inhibit the conversion of angiotensinI to angio-

tensinII. They have many uses and aregenerally well

tolerated. The main indications of ACE inhibitors are

shownbelow.

Heartfailure

ACEinhibitors are used inall grades of

heart failure, usually combined with a beta-blocker

(section2.5.5). Potassium supplements and potassium-

sparingdiuretics shouldbe discontinued beforeintrodu-

cingan ACE inhibitor because of the risk of hyperkal-

aemia.However, a low dose ofspironolactone may be

beneﬁcialin severe heart failure(section 2.5.5) andcan

be used withan ACE inhibitor provided serum potas-

sium is monitored carefully.Profound ﬁrst-dose hypo-

tensionmay occur when ACEinhibitors are introduced

to patients with heart failure who are already taking a

highdose ofa loop diuretic(e.g. furosemide80 mgdaily

or more). Temporary withdrawal of the loop diuretic

reducesthe risk, but may cause severe reboundpulm-

onaryoedema. Therefore, for patientson high dosesof

loop diuretics, the ACE inhibitor may need to be

initiated under specialist supervision, see below. An

ACE inhibitor can be initiated in the community in

patients whoare receiving a low dose of a diuretic or

who are not otherwise at risk of serious hypotension;

nevertheless,care isrequired and avery lowdose ofthe

ACEinhibitor is given initially.

Hypertension

An ACE inhibitor may be the most

appropriate initial drug for hypertension in younger

Caucasian patients; Afro-Caribbean patients, those

agedover 55 years,and those withprimary aldosteron-

ismrespond less well (see section 2.5). ACE inhibitors

are particularly indicated for hypertension in patients

withtype 1 diabeteswith nephropathy (seealso section

6.1.5).They may reduce bloodpressure very rapidly in

some patients particularly in those receivingdiuretic

therapy (see Cautions, below); the ﬁrst dose should

preferablybe given at bedtime.

Diabetic nephropathy

Forcomment on the role of

ACEinhibitors in the management of diabetic nephro-

pathy,see section 6.1.5.

Prophylaxis of cardiovascular events

ACE inhi-

bitorsare used inthe early and long-termmanagement

of patients whohave had a myocardial infarction, see

section 2.10.1.ACE inhibitors may also have a role in

preventingcardiovascular events.

Initiationunder specialist supervision

ACEinhi-

bitors should be initiated under specialist supervision

andwith carefulclinical monitoring inthose withsevere

heartfailure or in those:

receiving multiple or high-dose diuretic therapy (e.g.

morethan 80mg of furosemidedaily or itsequivalent);

withhypovolaemia;

with hyponatraemia (plasma-sodium concentration

below130 mmol/litre);

with hypotension (systolic blood pressure below

90mmHg);

withunstable heart failure;

receivinghigh-dose vasodilator therapy;

knownrenovascular disease.

Renaleffects

Renalfunction and electrolytes should

bechecked beforestarting ACE inhibitors(or increasing

the dose) and monitored during treatment (more fre-

quentlyif features mentionedbelow present); hyperkal-

aemiaand other side-effectsof ACEinhibitors are more

commonin those with impaired renalfunction and the

dose may need to be reduced (see Renal impairment

belowand under individual drugs).Although ACE inhi-

bitorsnow havea specialisedrole insome formsof renal

disease, including chronic kidney disease, they also

occasionallycause impairment of renal function which

may progress and become severe in other circum-

stances (atparticular risk are the elderly). A specialist

should be involved if renal function is signiﬁcantly

reducedas a result oftreatment with an ACEinhibitor.

Concomitanttreatment with NSAIDs increasesthe risk

of renal damage, and potassium-sparing diuretics (or

potassium-containingsalt substitutes) increase the risk

ofhyperkalaemia.

Inpatients withsevere bilateral renalartery stenosis (or

severestenosis ofthe artery supplyinga singlefunction-

ingkidney), ACEinhibitors reduceor abolishglomerular

ﬁltrationand are likelyto cause severe andprogressive

renal failure. They are therefore not recommended in

BNF 61 2.5.5 Drugsaffecting the renin-angiotensin system 115

Cardiovascularsystem

patientsknown to have theseforms of critical renovas-

culardisease.

ACEinhibitor treatment is unlikely to havean adverse

effect onoverall renal function in patients with severe

unilateralrenal artery stenosis and a normalcontralat-

eral kidney, but glomerular ﬁltration is likely to be

reduced(or even abolished) in theaf fectedkidney and

thelong-term consequences are unknown.

ACE inhibitors are therefore best avoided in patients

with knownor suspected renovascular disease, unless

theblood pressure cannotbe controlled byother drugs.

IfACE inhibitors areused, they shouldbe initiated only

under specialistsuper vision andrenal function should

bemonitored regularly.

ACE inhibitors should also be used with particular

caution in patients who may have undiagnosed and

clinically silent renovascular disease. This includes

patientswith peripheral vascular disease or those with

severegeneralised atherosclerosis.

Cautions

ACEinhibitors needto be initiatedwith care

in patientsreceiving diuretics (important: see Conco-

mitant diuretics, below); ﬁrst doses can cause hypo-

tensionespecially in patients takinghigh doses of diur-

etics,on a low-sodium diet, ondialysis, dehydrated, or

withheart failure (seeabove). They shouldalso beused

withcaution in peripheral vascular disease or general-

ised atherosclerosis owing to risk of clinically silent

renovasculardisease; for usein pre-existing renovascu-

lar disease, see Renal Effects above. The risk of

agranulocytosisis possibly increasedin collagen vascu-

lar disease (blood counts recommended). ACE inhi-

bitorsshould be used with carein patients with severe

orsymptomatic aorticstenosis (riskof hypotension)and

in hypertrophic cardiomyopathy.They should also be

used with care(or avoided) in those with a history of

idiopathic or hereditary angioedema. If jaundice or

marked elevations of hepatic enzymes occur during

treatment thenthe ACE inhibitor should be discontin-

ued—riskof hepatic necrosis (see alsoHepatic impair-

ment, below). Interactions: Appendix 1 (ACE inhi-

bitors).

Anaphylactoid reactions

To prevent anaphylactoid

reactions, ACE inhibitors should be avoided during

dialysis with high-ﬂux polyacrylonitrile membranes

and during low-density lipoprotein apheresis with

dextran sulphate; they should alsobe withheld before

desensitisationwith wasp or beevenom.

Concomitantdiuretics

ACEinhibitors cancause aver y

rapidfall inblood pressure involume-depleted patients;

treatment should therefore be initiated with very low

doses. If the dose of diuretic is grea ter than 80mg

furosemideor equivalent, the ACE inhibitor should be

initiated underclose supervision and in some patients

thediuretic dosemay needto be reducedor thediuretic

discontinuedat least 24 hoursbeforehand (may not be

possiblein heart failure—riskof pulmonary oedema). If

high-dose diuretic therapy cannot be stopped, close

observation is recommended after administration of

the ﬁrst dose of ACEinhibitor, for at least 2 hours or

untilthe blood pressure hasstabilised.

Contra-indications

ACE inhibitors are contra-indi-

catedin patients withhypersensitivity toACE inhibitors

(includingangioedema).

Hepaticimpairment

Useof prodrugs such ascilaza-

pril, enalapril, fosinopril,imidapril, moexipril, perindo-

pril, quinapril,ramipril, and trandolapril requires close

monitoringin patients with impairedliver function

Renal impairment

ACE inhibitors should be used

with caution and the response monitored (see Renal

effects above); hyperkalaemia and other side effects

morecommon; the dose may need to bereduced, see

individualdrugs.

Pregnancy

ACE inhibitors should be avoided in

pregnancyunless essential. They may adversely affect

fetal and neonatal blood pressure control and renal

function; skull defects and oligohydramnios have also

beenreported.

Breast-feeding

Informationon the use of ACE inhi-

bitorsin breast-feeding is limited. Cilazapril, fosinopril,

imidapril,lisinopril, moexipril, perindopril,ramipril, and

trandolapril are not recommended; alternative treat-

mentoptions, withbetter established safetyinformation

duringbreast-feeding, areavailable. Captopril,enalapril,

andquinapril should be avoided in the ﬁrstfew weeks

afterdelivery, particularlyin preterm infants, dueto the

riskof profound neonatalhypotension; if essential,they

maybe used in mothers breast-feeding older infants—

theinfant’s blood pressure shouldbe monitored.

Side-effects

ACEinhibitors cancause profoundhypo-

tension(see Cautions) andrenal impairment (seeRenal

effects above), and a persistent dry cough. They can

also cause angioedema (onset may be delayed; higher

incidence reported in Afro-Caribbean patients), rash

(which may be associated with pruritus and urticaria),

pancreatitis,and upperrespiratory-tract symptomssuch

as sinusitis, rhinitis, and sore throat. Gastro-intestinal

effects reported with ACE inhibitors include nausea,

vomiting,dyspepsia, diarrhoea, constipation,and abdo-

minalpain. Altered liverfunction tests,cholestatic jaun-

dice,hepatitis, fulminant hepatic necrosis, and hepatic

failurehave been reported—discontinue if marked ele-

vationof hepatic enzymes orjaundice. Hyperkalaemia,

hypoglycaemia,and blooddisorders includingthrombo-

cytopenia, leucopenia, neutropenia, and haemolytic

anaemia have also been reported. Other reported

side-effects include headache, dizziness, fatigue,

malaise,taste disturbance,paraesthesia, bronchospasm,

fever, serositis, vasculitis, myalgia, arthralgia, positive

antinuclearantibody, raised erythrocyte sedimentation

rate,eosinophilia, leucocytosis, and photosensitivity.

Combination products

Products incorporating an

ACE inhibitor with a thiazide diuretic or a calcium-

channel blocker are available for the management of

hypertension.Use ofthese combinationproducts should

bereser vedfor patients whose blood pressure hasnot

respondedadequately to asingle antihypertensive drug

andwho have beenstabilised on the individualcompo-

nentsof the combination inthe same proportions.

CAPTOPRIL

Indications

mildto moderate essential hypertension

aloneor with thiazide therapyand severe hyper-

tensionresistant to other treatment;congestive heart

failurewith left ventricular dysfunction(adjunct—see

section2.5.5); following myocardial infarction,see

116 2.5.5 Drugsaffecting the renin-angiotensin system BNF61

Cardiovascularsystem

dose;diabetic nephropathy(microalbuminuria greater

than30 mg/day) intype 1 diabetes

Cautions

seenotes above

Contra-indications

seenotes above

Renalimpairment

seenotes above; reduce dose;

max.initial dose 25mg daily (do notexceed 100 mg

daily)if eGFR20–40 mL/minute/1.73m

;max. initial

dose12.5 mg daily(do not exceed 75mg daily) if

eGFR10–20 mL/minute/1.73m

;max. initial dose

6.25mg daily (donot exceed 37.5mg daily) if eGFR

lessthan 10 mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; tachycardia, serum

sickness,weight loss, stomatitis,maculopapular rash,

photosensitivity,ﬂushing and acidosis

Dose

. Hypertension,used alone, initially 12.5mg twice

daily;if used inaddition to diuretic(see notes above),

orin elderly,initially 6.25mg twice daily(ﬁr stdose at

bedtime);usual maintenance dose 25mg twice daily;

max.50 mgtwice daily (rarely3 times daily insevere

hypertension)

. Heartfailure (adjunct), initially 6.25–12.5mg 2–3

timesdaily underclose medicalsupervision (seenotes

above),increased gradually at intervalsof at least 2

weeksup to max. 150mg daily individed doses if

tolerated

. Prophylaxisafter infarctionin clinicallystable patients

withasymptomatic or symptomatic leftventricular

dysfunction(radionuclide ventriculography or echo-

cardiographyundertaken before initiation), initially

6.25mg, starting asearly as 3 daysafter infarction,

thenincreased over several weeksto 150mg daily (if

tolerated)in divided doses

. Diabeticnephropathy, 75–100mg daily in divided

doses;if further blood pressure reductionrequired,

otherantihypertensives may be usedin conjunction

withcaptopril; in severe renalimpair ment,initially

12.5mg twice daily(if concomitant diuretic therapy

required,loop diuretic rather thanthiazide should be

chosen)

Captopril(Non-proprietary) A

Tablets

,captopril 12.5 mg,net price 56-tab pack=

£1.51;25 mg,56-tab pack =£1.56; 50mg, 56-tabpack

=£1.96

Brandsinclude

Ecopace

Kaplon

Capoten

(Squibb)A

Tablets

,captopril 25 mg,net price 28-tab pack=

£5.26;50 mg (scored),56-tab pack = £17.96

Withdiuretic

Note

Formild to moderate hypertension in patientsstabi-

lisedon theindividual components inthe sameproportions.

Forprescribing information onthiazides, see section2.2.1

Co-zidocapt(Non-proprietary) A

Tablets

,co-zidocapt 12.5/25 (hydrochlorothiazide

12.5mg, captopril 25mg), netprice 28-tab pack =

£14.10

Brandsinclude

Capto-co

Tablets

,co-zidocapt 25/50 (hydrochlorothiazide

25mg, captopril 50mg), net price 28-tab pack =

£14.00

Brandsinclude

Capto-co

Capozide

(Squibb)A

LStablets

,scored, co-zidocapt 12.5/25 (hydro-

chlorothiazide12.5 mg,captopril 25mg), netprice 28-

tabpack = £10.05

Tablets

,scored, co-zidocapt 25/50 (hydrochloro-

thiazide25 mg,captopril 50mg), netprice 28-tabpack

=£7.02

CILAZAPRIL

Indications

essentialhypertension; congestive heart

failure(adjunct—see section 2.5.5)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above; max. dose

500micrograms daily inliver cirrhosis; manufacturer

advisesavoid in ascites

Renalimpairment

seenotes above; max. initialdose

500micrograms once daily(do not exceed 2.5mg

oncedaily) if eGFR10–40 mL/minute/1.73m

;avoid

ifeGFR less than 10mL/minute/1.73 m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also

lesscommonly

dry

mouth,decreased appetite, angina, tachycardia,pal-

pitation,ﬂushing, dyspnoea, impotence, excessive

sweating;

rarely

glossitis,bronchitis, interstitial lung

disease,gynaecomastia, peripheral neuropathy,Ste-

vens-Johnsonsyndrome, toxic epidermal necrolysis

Dose

. Hypertension,initially 1 mgonce daily (reduced to

500micrograms daily ifused in addition todiuretic

(seenotes above), or incardiac decompensation, in

severehypertension, in volume depletion,in the

elderly,or in renalimpair ment),then adjusted

accordingto response; usual maintenancedose 2.5–

5mg once daily;max. 5 mgdaily

. Heartfailure (adjunct), initially 500micrograms once

dailyunder close medical supervision (seenotes

above),increased at weekly intervalsto 1–2.5 mg

oncedaily if tolerated; max.5 mg oncedaily

Vascace

(Roche)A

Tablets

,f/c, cilazapril 500micrograms (white), net

price30-tab pack =£3.68; 1 mg(yellow), 30-tab pack

=£6.07; 2.5mg (pink), 28-tab pack =£7.20; 5mg

(brown),28-tab pack =£12.51

ENALAPRIL MALEATE

Indications

hypertension;symptomatic heart failure

(adjunct—seesection 2.5.5); prevention ofsympto-

maticheart failure in patientswith asymptomatic left

ventriculardysfunction

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; max. initialdose

2.5mg dailyif eGFR lessthan 30mL/minute/1.73 m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also dyspnoea;depres-

sion,asthenia; blurred vision;

lesscommonly

dry

mouth,peptic ulcer, anorexia, ileus;arrhythmias,

palpitation,ﬂushing; confusion, nervousness, drowsi-

ness,insomnia, vertigo; impotence; musclecramps;

tinnitus;alopecia, sweating; hyponatraemia;

rarely

BNF 61 2.5.5 Drugsaffecting the renin-angiotensin system 117

Cardiovascularsystem

stomatitis,glossitis, Raynaud’s syndrome,pulmonary

inﬁltrates,allergic alveolitis, dream abnormalities,

gynaecomastia,Stevens-Johnson syndrome, toxic

epidermalnecrolysis, exfoliative dermatitis, pemphi-

gus;

veryrarely

gastro-intestinalangioedema

Dose

. Hypertension,used alone, initially 5mg oncedaily; if

usedin addition to diuretic(see notes above), or in

renalimpairment, lowerinitial dosesmay be required;

usualmaintenance dose 20mg once daily; max.

40mg once daily

. Heartfailure (adjunct), asymptomatic leftventricular

dysfunction,initially 2.5 mgonce daily under close

medicalsupervision (see notes above), increased

graduallyover 2–4 weeks to10–20 mg twicedaily if

tolerated

EnalaprilMaleate (Non-proprietary) A

Tablets

,enalapril maleate 2.5mg, net price 28-tab

pack= £1.05; 5mg, 28-tabpack = 96p;10 mg, 28-tab

pack= £1.05; 20mg, 28-tab pack= £1.24

Brandsinclude

Ednyt

Innovace

(MSD)A

Tablets

,enalapril maleate 2.5mg, net price 28-tab

pack= £5.35; 5mg (scored), 28-tab pack= £7.51;

10mg (red),28-tab pack =£10.53; 20mg (peach), 28-

tabpack = £12.51

Withdiuretic

Note

Formild to moderatehypertension in patientsstabilised

onthe individual componentsin the sameproportions. For

prescribinginformation on thiazides,see section 2.2.1

Innozide

(MSD)A

Tablets

,yellow, scored, enalaprilmaleate 20 mg,

hydrochlorothiazide12.5 mg,net price 28-tab pack=

£12.82

Note

Non-proprietary tabletscontaining enalapril maleate

(20mg) andhydrochlorothiazide (12.5mg) are available

FOSINOPRIL SODIUM

Indications

hypertension;congestive heart failure

(adjunct—seesection 2.5.5)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; chest pain;musculo-

skeletalpain

Dose

. Hypertension,initially 10 mgdaily, increased if

necessaryafter 4 weeks; usualdose range 10–40mg

(dosesover 40 mgnot shown to increaseefﬁcacy); if

usedin addition to diureticsee notes above

. Heartfailure (adjunct), initially 10mg once daily

underclose medical supervision (see notesabove),

increasedgradually to 40mg once daily iftolerated

Fosinoprilsodium (Non-proprietary) A

Tablets

,fosinopril sodium 10mg, net price 28-tab

pack= £2.18; 20mg, 28-tab pack= £2.53

IMIDAPRIL HYDROCHLORIDE

Indications

essentialhypertension

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; initial dose

2.5mg daily ifeGFR 30–80 mL/minute/1.73m

;

avoidif eGFR less than30 mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; dry mouth, glossitis,

ileus;bronchitis, dyspnoea; sleep disturbances,

depression,confusion, blurred vision, tinnitus,impo-

tence

Dose

. Initially5 mgdaily before food; if usedin addition to

diuretic(see notes above), inelderly, in patients with

heartfailure, angina or cerebrovasculardisease, or in

renalor hepatic impairment, initially 2.5mg daily;if

necessaryincrease dose at intervals ofat least 3

weeks;usual maintenance dose 10mg once daily;

max.20 mg daily(elderly, 10mg daily)

Tanatril

(Chiesi)A

Tablets

,scored, imidapril hydrochloride 5mg, net

price28-tab pack= £6.40;10 mg,28-tab pack= £7.22;

20mg, 28-tab pack= £8.67

LISINOPRIL

Indications

hypertension(but see notes above);

symptomaticheart failure (adjunct—see section

2.5.5);short-term treatment following myocardial

infarctionin haemodynamically stable patients;renal

complicationsof diabetes mellitus

Cautions

seenotes above

Contra-indications

seenotes above

Renalimpairment

seenotes above;max. initial doses

5–10mg daily ifeGFR 30–80 mL/minute/1.73m

(max.40 mgdaily); 2.5–5mg dailyif eGFR10–30 mL/

minute/1.73m

(max.40 mg daily);2.5 mg dailyif

eGFRless than 10mL/minute/1.73 m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also

lesscommonly

tachycardia,palpitation, cerebrovascular accident,

myocardialinfarction, Raynaud’s syndrome,confu-

sion,mood changes, vertigo, sleepdisturbances,

asthenia,impotence;

rarely

drymouth, gynaecomas-

tia,alopecia, psoriasis;

veryrarely

allergicalveolitis,

pulmonaryinﬁltrates, profuse sweating, pemphigus,

Stevens-Johnsonsyndrome, and toxic epider mal

necrolysis

Dose

. Hypertension,initially 10 mgonce daily; if usedin

additionto diuretic (see notesabove) or in cardiac

decompensationor in volumedepletion, initially 2.5–

5mg oncedaily; usual maintenance dose20 mgonce

daily;max. 80 mgonce daily

. Heartfailure (adjunct), initially 2.5mg once daily

underclose medical supervision (see notesabove);

increasedin steps no greaterthan 10 mgat intervals

ofat least 2 weeksup to max. 35mg once dailyif

tolerated

. Prophylaxisafter myocardialinfarction, systolicblood

pressureover 120 mmHg,5 mgwithin 24 hours, fol-

lowedby further5 mg24 hours later,then 10mg after

afurther 24 hours, andcontinuing with 10mg once

dailyfor 6 weeks (orcontinued if heart failure);sys-

118 2.5.5 Drugsaffecting the renin-angiotensin system BNF61

Cardiovascularsystem

tolicblood pressure 100–120mmHg, initially 2.5mg

oncedaily, increased tomaintenance dose of 5mg

oncedaily

Note

Should not be started after myocardial infarction if

systolicblood pressure lessthan 100mmHg; temporarily

reducemaintenance dose to5 mgand if necessary 2.5mg

dailyif systolic bloodpressure 100mmHg or lessduring

treatment;withdraw if prolongedhypotension occurs (sys-

tolicblood pressure lessthan 90mmHg for morethan 1

hour)

. Renalcomplications ofdiabetes mellitus, initially2.5–

5mg oncedaily adjustedaccording toresponse; usual

doserange 10–20 mgonce daily

Lisinopril(Non-proprietary) A

Tablets,

lisinopril(as dihydrate) 2.5mg, net price28-

tabpack = 87p; 5mg, 28-tab pack= 93p; 10mg, 28-

tabpack = £1.01; 20mg, 28-tabpack = £1.19

Zestril

(AstraZeneca)A

Tablets

,lisinopril (as dihydrate) 2.5mg, net price28-

tabpack = £1.78; 5mg (pink), 28-tabpack = £1.31;

10mg (pink), 28-tabpack = £2.05; 20mg (pink), 28-

tabpack = £2.17

Withdiuretic

Note

Formild to moderatehypertension in patientsstabilised

onthe individual componentsin the sameproportions. For

prescribinginformation on thiazides,see section 2.2.1

CaracePlus

(MSD)A

Carace10 Plus tablets

,blue, lisinopril 10mg,

hydrochlorothiazide12.5 mg,net price 28-tab pack=

£10.10

Carace20 Plus tablets

,yellow, scored, lisinopril

20mg, hydrochlorothiazide12.5 mg, netprice 28-tab

pack= £11.43

Lisicostad

(Genus)A

Lisicostad10/12.5 mg tablets

,scored, lisinopril (as

dihydrate)10 mg,hydrochlorothiazide 12.5mg, net

price28-tab pack = £10.99

Lisicostad20/12.5 mg tablets

,scored, lisinopril (as

dihydrate)20 mg,hydrochlorothiazide 12.5mg, net

price28-tab pack = £11.99

Zestoretic

(AstraZeneca)A

Zestoretic10 tablets

,peach, lisinopril (as dihydrate)

10mg, hydrochlorothiazide12.5 mg, netprice 28-tab

pack= £2.27

Zestoretic20 tablets

,lisinopril (as dihydrate)20 mg,

hydrochlorothiazide12.5 mg,net price 28-tab pack=

£3.84

MOEXIPRIL HYDROCHLORIDE

Indications

essentialhypertension

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above; initial dose

3.75mg once dailyin hepatic cirrhosis

Renalimpairment

seenotes above; ifeGFR less than

40mL/minute/1.73m

,initial dose 3.75mg once

dailytitrated to max. 15mg once daily

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; arrhythmias, angina,

chestpain, syncope, cerebrovascular accident,myo-

cardialinfarction; appetite and weightchanges; dry

mouth,photosensitivity, ﬂushing, nervousness,mood

changes,anxiety, drowsiness, sleepdisturbance, tin-

nitus,inﬂuenza-like syndrome, sweating anddys-

pnoea

Dose

. Monotherapy,initially 7.5mg once daily; ifused in

additionto diuretic(see notes above),with nifedipine,

orin elderly, initially3.75 mg oncedaily; usual range

7.5–30mg once daily;doses above 30mg daily not

shownto increase efﬁcacy

Perdix

(UCBPharma) A

Tablets

,f/c, pink, scored, moexiprilhydrochloride

7.5mg, net price28-tab pack =£6.04; 15 mg,28-tab

pack= £6.96

PERINDOPRIL ERBUMINE

Indications

hypertension(but see notes above);

symptomaticheart failure (adjunct—see section

2.5.5);prophylaxis of cardiac eventsfollowing myo-

cardialinfarction or revascularisation instable cor-

onaryarter ydisease

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; max. initialdose

2mg once dailyif eGFR 30–60mL/minute/1.73 m

;

2mg oncedaily on alternatedays ifeGFR 15–30 mL/

minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above;also asthenia,mood and

sleepdisturbances

Dose

. Hypertension,initially 4mg oncedaily in themorning

for1 month, subsequently adjustedaccording to

response;if used in additionto diuretic (see notes

above),in elderly, inrenal impairment, in cardiac

decompensation,or involume depletion,initially 2mg

oncedaily; max. 8mg daily

. Heartfailure (adjunct), initially2 mgonce daily in the

morningunder close medical supervision (seenotes

above),increased after at least2 weeks tomax. 4 mg

oncedaily if tolerated

. Followingmyocardial infarction orrevascularisation,

initially4 mgonce dailyin themorning increasedafter

2weeks to 8mg once daily iftolerated;

ELDERLY2 mg

oncedaily for1 week,then 4mg oncedaily for1 week,

thereafterincreased to 8mg once daily iftolerated

Perindopril(Non-proprietary) A

Tablets

,perindopril erbumine (=

tert

-butylamine)

2mg, netprice 30-tabpack =£1.72; 4mg, 30-tabpack

=£1.81; 8mg, 30-tab pack =£1.94. Label: 22

PERINDOPRIL ARGININE

Indications

seeunder PerindoprilErbumine andnotes

above

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; max. initialdose

2.5mg oncedaily ifeGFR 30–60mL/minute/1.73 m

;

2.5mg once dailyon alternate days ifeGFR 15–

30mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

BNF 61 2.5.5 Drugsaffecting the renin-angiotensin system 119

Cardiovascularsystem

Side-effects

seeunder Perindopril Erbumine and

notesabove

Dose

. Hypertension,initially 5mg oncedaily in themorning

for1 month, subsequently adjustedaccording to

response;if used in additionto diuretic (see notes

above),in elderly, inrenal impairment, in cardiac

decompensation,or in volume depletion,initially

2.5mg once daily;max. 10 mgdaily

. Heartfailure (adjunct), initially 2.5mg once dailyin

themorning under close medicalsuper vision(see

notesabove), increased after 2weeks to max. 5mg

oncedaily if tolerated

. Followingmyocardial infarction orrevascularisation,

initially5 mgonce dailyin themorning increasedafter

2weeks to 10mg once daily iftolerated;

ELDERLY

2.5mg oncedaily for1 week, then5 mgonce dailyfor

1week, thereafter increased to10 mg oncedaily if

tolerated

Coversyl

Arginine(Servier) A

Tablets

,f/c, perindopril arginine 2.5mg (white), net

price30-tab pack = £8.27;5 mg(light green, scored),

30-tabpack = £9.36; 10mg (green), 30-tabpack =

£11.02.Label: 22

Perindoprilarginine with diuretic

Note

Forhypertension not adequatelycontrolled by perindo-

prilalone. For prescribinginformation on indapamide,see

section2.2.1

Coversyl

ArgininePlus (Servier) A

Tablets

,f/c, perindopril arginine 5mg, indapamide

1.25mg, net price30-tab pack =£12.65. Label: 22

QUINAPRIL

Indications

essentialhypertension; congestive heart

failure(adjunct—see section 2.5.5)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; max. initialdose

2.5mg once dailyif eGFR less than40 mL/minute/

1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; asthenia, chestpain,

oedema,ﬂatulence, nervousness, depression, insom-

nia,blurred vision, impotence, andback pain

Dose

. Hypertension,initially 10 mgonce daily; with a

diuretic(see notes above), inelderly, or in renal

impairmentinitially 2.5 mgdaily; usual maintenance

dose20–40 mgdaily insingle or2 divideddoses; upto

80mg daily hasbeen given

. Heartfailure (adjunct), initialdose 2.5mg daily under

closemedical supervision (see notes above),

increasedgradually to 10–20mg daily in 1–2divided

dosesif tolerated; max. 40mg daily

Quinapril(Non-proprietary) A

Tablets

,quinapril (as hydrochloride) 5mg, net price

28-tabpack = £2.05; 10mg, 28-tabpack = £1.91;

20mg, 28-tab pack= £2.39; 40mg, 28-tab pack=

£2.81

Brandsinclude

Quinil

Accupro

(Pﬁzer)A

Tablets

,f/c, quinapril (as hydrochloride)5 mg

(brown),net price28-tab pack= £8.60;10 mg(brown),

28-tabpack = £8.60; 20mg (brown),28-tab pack =

£10.79;40 mg (red-brown),28-tab pack =£9.75

Withdiuretic

Note

Forhypertension in patientsstabilised on the individual

componentsin the sameproportions. For prescribinginfor-

mationon thiazides, seesection 2.2.1

Accuretic

(Pﬁzer)A

Tablets

,pink, f/c,scored, quinapril(as hydrochloride)

10mg, hydrochlorothiazide12.5 mg, netprice 28-tab

pack= £11.75

RAMIPRIL

Indications

hypertension;symptomatic heart failure

(adjunct—seesection 2.5.5); following myocardial

infarctionin patients with clinicalevidence of heart

failure;prevention ofcardiovascular eventsin patients

withatherosclerotic cardiovascular disease orwith

diabetesmellitus andat leastone additionalrisk factor

forcardiovascular disease; nephropathy(consult pro-

ductliterature)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

max.daily dose 2.5mg; see also

notesabove

Renalimpairment

seenotes above; max. dailydose

5mg if eGFR30–60 mL/minute/1.73m

;max. initial

dose1.25 mg oncedaily (do not exceed5 mg once

daily)if eGFR10–30 mL/minute/1.73m

;max. initial

dose1.25 mg oncedaily (do not exceed2.5 mg once

daily)if eGFR less than10 mL/minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; arrhythmias, angina,

chestpain, syncope, cerebrovascular accident,myo-

cardialinfarction, loss of appetite,stomatitis, dry

mouth,skin reactions includinger ythemamultiforme

andpemphigoid exanthema; precipitation orexacer-

bationof Raynaud’s syndrome;conjunctivitis, ony-

cholysis,confusion, nervousness, depression,anxiety,

impotence,decreased libido, alopecia,bronchitis and

musclecramps

Dose

. Hypertension,initially 1.25–2.5 mgonce daily,

increasedat intervals of 2–4 weeksto max. 10mg

oncedaily; if used inaddition to diuretic see notes

above

. Heartfailure (adjunct), initially 1.25mg once daily

underclose medical supervision (see notesabove),

increasedgradually at intervalsof 1–2 weeks tomax.

10mg dailyif tolerated (preferably takenin 2 divided

doses)

. Prophylaxisafter myocardial infarction (startedat

least48 hours after infarction),initially 2.5 mgtwice

daily,increased after 3days to 5mg twice daily

Note

Ifinitial 2.5-mg dosenot tolerated,give 1.25mg twice

dailyfor 2days before increasingto 2.5mg twicedaily, then

5mg twicedaily; withdraw ifdose cannot beincreased to

2.5mg twicedaily

. Prophylaxisof cardiovascular events,initially 2.5 mg

oncedaily, increased after1–2 weeks to 5mg once

daily,then increased aftera further 2–3 weeks to

10mg once daily

120 2.5.5 Drugsaffecting the renin-angiotensin system BNF61

Cardiovascularsystem