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

UKTeratology Information Service

Informationon drug and chemical

exposuresin pregnancy 0844 892 0909

Medicinesfor Children information leaﬂets

Medicinesinformation for parents and carers.

www.medicinesforchildren.org.uk

PatientInformation Lines

NHSDirect 08454647

PoisonsInformation Services

UKNational Poisons Information

Service 08448920111

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 1318

(09.00–17.30hours weekdays)

Departmentof Health and Social Services (Belfast)

(028)9052 2118 (weekdays)

Information on drug therapy relating to dental

treatmentcan be obtained bytele phoning:

Liverpool (0151)794 8206

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

Telephonenumbers and email addresses of manu-

facturerslisted inBNF Publications areshown inthe

Indexof Manufacturers

2011–2012

for children

BNF

Publishedby

BMJGroup

TavistockSquare, London WC1H 9JP, UK

Pharmaceutical Press

Pharmaceutical Press is the publishing division of the

RoyalPharmaceutical Society

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

RCPCHPublications Ltd

5–11Theobalds Road, London WC1X 8SH, UK

Societyof Great Britain, and RCPCH Publications Ltd

2011

ISBN:978 0 85369 959 0

ISSN:1747–5503

Printedby CPI Clausen & Bosse, Leck, Germany

Typesetby Xpage

A catalogue record for this book is available from the

BritishLibrary.

Allrights reserved. No part of this publication may be

reproduced,stored in a retrieval system, or transmitted

inany for m or by any means, without the prior written

permissionof the copyright holder.

Materialpublished in the

BNFfor Children

maynot

beused for anyform of advertising, sales or publicity

withoutprior written permission. Each of the classi-

ﬁcationand the text are protectedby copyright and/

ordatabase right

Papercopies maybe obtained through any bookseller or

directfrom:

PharmaceuticalPress

c/oMacmillan Distribution (MDL)

BrunelRoad

Houndmills

Basingstoke

RG216XS

Tel:+44 (0) 1256 302 692

Fax:+44 (0) 1256 812 521

Email:direct@macmillan.co.uk

www.pharmpress.com

Forall bulk orders of more than 20 copies:

Email:pharmpress@rphar ms.com

Tel:+44 (0) 207 572 2266

PharmaceuticalPress also supplies

BNFfor Children

digital formats suitable for standalonecomputers and

intranets,and for use on mobile devices.

Distributionof BNFCs

The UK health departments distribute BNFCs to NHS

hospitals,doctors, and community pharmacies.

In England, BNFCs are mailed individually to NHS

doctors, pharmacists, and non-medical prescribers

who have prescribing responsibility for children; for

extra copies or changes relating to mailed BNFCs,

contactthe DH Publications Orderline:

Tel:0300 123 1002

InScotland email:

nss.psd-bnf@nhs.net

InWales, telephone the Business Services Centre:

Tel:(01495) 332 000

InNorther nIreland email:

ni.bnf@hscni.net

The

BNFfor Children

is for use by health profes-

sionals engaged in prescribing, dispensing, and

administering medicines to children. It has been

prepared under the guidance of the Paediatric

FormularyCommittee.

BNFfor Children

hasbeen constructed using robust

proceduresfor gathering, assessing and assimilating

informationon paediatric drug treatment. It is, how-

ever, expected that the reader will be relying on

appropriate professional knowledge and expertise

to interpret the contents in the context of the cir-

cumstancesof the individualchild.

BNFfor Children

shouldbe used inconjunction with other appropriate

andup-to-date literature and, where necessary, sup-

plemented by expert advice. Information is also

availablefrom Medicines Information Services (see

insidefront cover).

Special care is required in managing childhood

conditions with unlicensed medicines or with

licensedmedicines for unlicenseduses.

Responsibil-

ity for the appropriate use of medicines lies solely

withthe individual health professional.

Contents

Preface.................................................................................................................................. iv

Acknowledgements................................................................................................................ v

BNFStaff ...............................................................................................................................vi

HowBNF for Children isconstructed ....................................................................................ix

Howto use BNF forChildren ... ..............................................................................................xi

Changesfor this edition............................... .....................................................................xvii

Generalguidance............................... ....................................................................................1

Prescriptionwriting............................ ....................................................................................4

Supplyof medicines ..............................................................................................................6

Emergencysupply of medicines ............................................................................................8

PrescribingControlled Drugs................... ..............................................................................9

Adversereactions to drugs................................................................................................. 12

Prescribingin hepatic impairment...................................................................................... 14

Prescribingin renal impairment .........................................................................................14

Prescribingin pregnancy .................................................................................................... 16

Prescribingin breast-feeding.............................................................................................. 16

Prescribingin palliative care ..............................................................................................17

Prescribingin dental practice........................................................................... ..................22

Drugsand sport............................................ ......................................................................23

Emergencytreatment of poisoning ....................................................................................24

Noteson drugs and Preparations

1: Gastro-intestinal system........................................................................................

2: Cardiovascular system........................................................................................... 73

3: Respiratory system.............................................................................................. 133

4: Central nervoussystem ....................................................................................... 169

5: Infections......................................... ....................................................................242

6: Endocrine system................................................................................................. 348

7: Obstetrics, gynaecology,and urinary-tract disorders......................... ................393

8: Malignant diseaseand immunosuppression .......................................................414

9: Nutrition andblood ..............................................................................................442

10: Musculoskeletal andjoint diseases .................................................................... 499

11: Eye.................. .....................................................................................................517

12: Ear, nose,and oropharynx............... ....................................................................534

13: Skin................................................................................................................. .....550

14: Immunological productsand vaccines............................................................ .....599

15: Anaesthesia .........................................................................................................628

Appendicesand indices

Appendix1: Interactions..................................................................................................

655

Appendix2: Borderlinesubstances...................................... ...........................................743

Appendix3: Cautionaryand advisory labels fordispensed medicines........................... 788

Appendix4: Intravenousinfusions for neonatal intensivecare ......................................791

DentalPractitioners’ Formulary ........................................................................................ 794

NursePrescribers’ Formulary......................................................... ...................................796

Non-medicalprescribing ...................................................................................................799

Indexof manufacturers............................................................... ......................................800

Index................................................................................................................................. 811

Medicalemergencies in the community.................................................... Inside back cover

BNFC 2011–2012 iii

Preface

BNFfor Children

aimsto provide prescribers, phar ma-

cistsand other healthcare professionals with sound up-

to-dateinformation on the use of medicines for treating

children.

A joint publication of the British Medical Association,

theRoyal Pharmaceutical Society of Great Britain, the

RoyalCollege of Paediatrics and Child Health, and the

Neonatal and Paediatric Phar macists Group,

BNF for

Children

(‘BNFC’)is published under the authority of a

PaediatricFormulary Committee.

Many areas of paediatric practicehave suffered from

inadequate information on ef fective medicines. BNFC

addresses this signiﬁcant knowledge gap by providing

practicalinformation on theuse of medicines in children

of all ages from birth to adolescence.

Medicines for

Children

(RCPCH Publications Ltd) and the

British

National Formulary

itself form the basis for BNFC.

Informationin BNFC has been validated against emer-

ging evidence, best-practice guidelines, and crucially,

advicefrom a network of clinical experts.

Drawing information from manufacturers’ literature

whereappropriate, BNFC also includes a great deal of

advicethat goes beyond marketing authorisations (pro-

ductlicences). This is necessary because licensed indi-

cations frequently do not cover the clinical needs of

children; in some cases, products foruse inchildren

needto be specially manufactured or imported. Careful

considerationhas been given to establishing the clinical

need for unlicensed interventions with respect tothe

evidence and experience of their safetyand ef ﬁcacy;

local paediatric formularies, clinical literature and

nationalinformation resources have been invaluable in

thisprocess.

BNFC has been designed forrapid reference and the

informationpresented has been carefully selected to aid

decisionson prescribing, dispensing and administration

of medicines. Less detail is given on areas such as

malignantdisease and the ver y specialist use of medi-

cines generally undertaken intertiar y centres. BNFC

shouldbe interpreted in the light of professional knowl-

edge and it should besupplemented as necessary by

specialised publications. Information isalso available

from Medicines Information Services (see inside front

cover).

It is vital to use the most recent edition of BNFC for

makingclinical decisions. The more important changes

forthis edition are listed on p. xvii.

The website (bnfc.org) includes additional information

of relevance to healthcare professionals.Other digital

formats of BNFC—including intranet and versions for

mobile devices—are produced in parallel with the

printedversion.

BNFC aims to provide information suited to the

needsof the clinician and recognises that, although

thisedition represents a considerable advance inthe

content and presentation of information on the

paediatricuse of medicines, further changes will be

necessary.Comments from healthcare professionals

aretherefore ver y welcome and should be sent to:

BritishNational Formulary Publications, RoyalPhar-

maceuticalSociety of Great Britain, 1 Lambeth High

Street,London SE1 7JN.

bnfc@bnf.org

Thecontact email formanufacturers or pharmaceut-

icalcompanies wishing to contact BNF publications

ismanufacturerinfo@bnf.org

iv BNFC 2011–2012

Acknowledgements

The Paediatric Formulary Committee is grateful to

individualsand organisations that have provided advice

andinformation to the

BNFfor Children

Theprincipal contributors for this edition were:

I.H. Ahmed-Jushuf, M.N. Badminton, S. Bailey, T.G.

Barrett, D.N.Bateman, G.D.L. Bates, H. Bedford, M.W.

Beresford, R.M. Bingham, I.W. Booth, L.Brook, K.G.

Brownlee,R.J. Buckley, M. Burch, I.F. Burgess, A. Cant,

L.J.Carr, R. Carr, E.A. Chalmers, T.D. Cheetham, A.J.

Cotgrove,J.B.S.Coulter, B.G. Craig,S.M. Creighton, J.H.

Cross, A. Dhawan, P.N. Durrington, A. Durward, A.B.

Edgar, J.A. Edge, D.A.C.Elliman, N.D. Embleton, P.J.

Goadsby,P.W.Golightly, J. Gray, J.W. Gregory, P. Grin-

gras, J.P. Harcourt, P.J. Helms, C. Hendriksz, R.F.

Howard, R.G. Hull, H.R. Jenkins, S. Jones, B.A. Judd,

C.J.H.Kelnar, P.T.Khaw, J.M.W.Kirk, P.J.Lee, T.H. Lee,

S. Lewis-Jones, E.G.H. Lyall, A. MacDonald, D.J.

Macrae, P.S. Malone, A.Y. Manzur, S.D. Mar ks, D.F.

Marsh, A.G. Marson, K.A. Matyka, P.J. McKiernan,

L.M.Melvin, E. Miller, R.E. Morton, C. Moss, P.Mulhol-

land, C. Nelson-Piercy, J.M. Neuberger, K.K. Nischal,

C.Y.Ng, L.P. Omerod, J.Y. Paton, G.A. Pearson, M.M.

Ramsay, I.A.G. Roberts, J. Rogers, K.E. Rogstad, P.C.

Rubin, J.W. Sander, N.J. Scolding, M.R. Sharland, N.J.

Shaw,G.J. Shortland, O.F.W.Stumper, M.R.J. Sury, A.G.

Sutcliffe, A. Sutherland, A.M. Szarewski, E.A. Taylor,

A.H.Thomson, M.A. Thomson, J.A. Vale, J.O. Warner,

D.A.Warrell, N.J.A.Webb, A.D.Weeks, R. Welbury, W.P.

Whitehouse,C.E. Willoughby,C. Wren, A. Wright, M.M.

Yaqoob,Z. Zaiwalla, and S.M. Zuberi.

Membersof the British Association of Dermatologists’

Therapy& Guidelines Subcommittee, D.A.Buckley, L.C.

Fuller,J. Hughes, S.E.Hulley, J. Lear, A.J.McDonagh, J.

McLelland,N. Morar, I. Nasr, S. Punjabi, M.J. Tidman,

S.E. Haveron (Secretariat), and M.F. Mohd Mustapa

(Secretariat)have provided valuable advice.

Members of the Advisory Committee on Malaria Pre-

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

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

Pasvol, S. Patel, M. Powell, D.V. Shingadia, C.J.M.

Whitty,M. Blaze (Secretariat), andV. Smith (Secretariat)

haveprovided valuable advice.

Membersof the UK Ophthalmic Pharmacy Group have

alsoprovided valuable advice.

R.Suvarna and colleagues at the MHRA have provided

valuableassistance.

Correspondents in the pharmaceutical industry have

providedinformation on new products and commented

onproducts in the

BNFfor Children

.NHS Prescription

Serviceshas supplied the prices of products in the

BNF

forChildren

Numerousdoctors, pharmacists, nurses andothers have

sentcomments and suggestions.

The

BNFfor Children

hasvaluable access to the

Mar-

tindale

databanks by courtesyof S. Sweetman and staff.

J. E. Macintyre andstaff providedvaluable technical

assistance.

C. Adetola, N. Bansal, J.J. Coleman, S. Foad, E.H.

Glover, T. Hamp, A. Holmes, J. Humphreys, J.M.

James,E. Laughton, H.M.N. Brady, R.M. Patel, J. Rey-

nolds, and E.J. Tong provided considerable assistance

during the production of this edition of

BNFfor Chil-

dren

Xpagehave provided assistance with typesetting devel-

opmentand related production processes.

BNFC 2011–2012 v

BNF Staff

ManagingEditor: Knowledge Creation

JohnMartin

BPharm,PhD, MRPharmS

AssistantEditors

Leigh-AnneClaase

BSc,PhD

BryonyJordan

BSc,DipPharmPract, MRPharmS

ColinR. Macfarlane

BPharm,MSc, MRPharmS

PaulS. Maycock

MPharm,DipPharmPract,

MRPharmS

ClaireL. Preston

BPharm,PGDipMedMan,

MRPharmS

RachelS. M. Ryan

BPharm,MRPharmS

ShamaM. S. Wagle

BPharm,DipPharmPract,

MRPharmS

StaffEditor s

SejalAmin

BPharm,MSc

AngelaK. Bennett

MPharm,DipPharmPract

ShenaS. Chauhan

BPharm,MRPharmS

SusanE. Clarke

BPharm,DipClinPharm, MRPharmS

KristinaFowlie

MPharm,PGCertPharmPract,

MRPharmS

Bele

nGranell Villen

BSc,PGDipClinPharm

ManjulaHalai

BScChem,MPharm

EmmaE. Har ris

MPharm,DipPharmPract,

MRPharmS

AmyE. Har vey

MPharm,PGDipCommPharm

AmberF. Lauder

BPharm,PGCertPharm

AngelaM. G. McFarlane

BSc,DipClinPharm,

MRPharmS

SarahMohamad

MPharm

ElizabethNix

DipPharm(NZ),MRPharmS

SanjayPatel

BPharm

VinayaK. Shar ma

BPharm,MSc, PGDipPIM,

MRPharmS

KatieE. Walters

MPharm,PGCertPharmPract,

MRPharmS

EditorialAssistants

RebeccaS. Bastable

BA,BTEC

CristinaLopez-Bueno

SeniorBNF Administrator

HeidiHomar

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 Production

JohnWilson

SeniorProduction Editor

LindaPaulus

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

vi BNFC 2011–2012

Paediatric Formulary

Committee

2010–2011

Chair

WarrenLenney

MD,FRCP, FRCPCH, DCH

CommitteeMembers

JeffreyK. Aronson

MA,MBChB, DPhil, FRCP, FBPha rmacolS,FFPM

NeilA. Caldwell

BSc,MSc, MRPharmS

IanCostello

BPharm,MSc, MRPharmS

Martin G. Duerden

BMedSci, MB BS, DRCOG,

MRCGP,DipTher, DPH

SimonKeady

BSc,MRPharmS, SP

MartinJ. Kendall

OBE, MB, ChB, MD, FRCP, FFPM

(Chair, Content

StrategyCommittee)

JamesH. Larcombe

MB,ChB, FRCGP, DipAdvGP

E.David G. McIntosh

MB BS, MPH, PhD, FAF PHM, FRACP, FRCPCH,

FFPM,DRCOG, DCH, DipPharmMed

NeenaModi

MB,ChB, MD, FRCP,FRCPC H

MatthewJ. Thatcher

MBBS, FRCS, DRCOG,DM RD

DavidTuthill

MB,BCh, FRCPCH

WilliamG. van’t Hoff

BSc,MB, MD, FRCPCH,FRCP

EdwardR. Wozniak

BSc,MB BS, FRCP,FRCP CH,DCH

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,FFDS (Eng)

DuncanS.T. Enright

MA,PGCE, MInstP, FIDM

AmyE. Har vey

MPharm,PGDipCommPharm

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 RPCS, FDS(Paed

Dent)RSC 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 for dental practice through

itsrepresentatives on the Dental Advisory Group.

BNFC 2011–2012 vii

Nurse Prescribers’

Advisory Group

2010–2011

Chair

NickyA. Cullum (until November 2010)

PhD,RGN

MollyCourtenay (from December 2010)

PhD,MSc, Cert Ed,BSc, RGN

CommitteeMembers

FionaCulley

LLM,RN, BSc, CertEd

DuncanS.T. Enright

MA,PGCE, MInstP, FIDM

PennyM. Franklin

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

Bele

nGranell Villen

BSc,PGDipClinPharm

MargaretF. Helliwell

MB,BS, BSc, MFPHM

BryonyJordan

BSc,DipPharmPract, MRPharmS

MartinJ. Kendall

OBE,MB, ChB, MD,FRCP, FFPM

FionaLynch

BSc,MSc, RGN, RSCN

JohnMartin

BPharm,PhD, MRPharmS

WendyJ. Nicholson

BSc,MA, Cert Ed,RGN ,RSCN

JillM. Shearer

BSc,RGN, RM

RabinaTindale

RN,RSCN, BSc, DipAEN, PGCE

VickyVidler

MA,RGN, RSCN

JohnWright

ExecutiveSecretary

HeidiHomar

viii BNFC 2011–2012

How BNF for Children

is constructed

BNFfor Children

(BNFC)is unique in bringing together

authoritative, independent guidance on best practice

with clinically validated drug information, enabling

healthcare professionals to select safe and effective

medicinesfor individual children.

Informationin BNFC has been validated against emer-

gingevidence, best-practice guidelines, andadvice from

anetwork ofclinical experts. BNFC includes a greatdeal

of advice that goes beyond marketing authorisations

(productlicences or summaries of product characteris-

tics). This is necessary because licensed indications

frequentlydo not cover the clinical needs of children;

insome cases, products for use in children need to be

speciallymanufactured or imported. Careful considera-

tionhas been given to establishing the clinical need for

unlicensed interventions with respect tothe evidence

andexperience of their safety and efﬁcacy.

Hundreds of changes are made between editions, and

themost clinically signiﬁcant changes are listed at the

frontof each edition.

Paediatric Formulary Committee

ThePaediatric Formulary Committee (PFC) is respon-

sible for the content of BNFC. The PFC includes a

neonatologist and paediatricians appointed by the

Royal College of Paediatrics and Child Health,paed-

iatricpharmacists appointed by the Royal Pharmaceut-

ical Society of Great Britain and the Neonatal and

Paediatric Pharmacists Group, doctors appointed by

the BMJ Publishing Group, a GP appointed by the

RoyalCollege of General Practitioners, and representa-

tivesfrom the Medicines and Healthcare products Reg-

ulatory Agency (MHRA) and the UK health depart-

ments. The PFC decides on matters of policy and

reviews amendments to BNFC in the light of new

evidence and expert advice. The Committee meets

every6 months and each member also receives proofs

ofall BNFC chapters for review before publication.

Dental Advisory Group

TheDental Advisory Group oversees the preparation of

advice on the drug management of dental and oral

conditions; the group includes representatives from

theBritish Dental Association.

Editorial team

BNFCstaff editors are pharmacists with a sound under-

standing of how drugs are used in clinical practice,

including paediatrics. Each staf f editor is responsible

forediting, maintaining, and updating speciﬁc chapters

ofBNFC. During the publication cycle the staff editors

reviewinformation in BNFC against a variety ofsources

(seebelow).

Amendments to the text are drafted when the editors

are satisﬁed that anynew information isreliable and

relevant. The draft amendments are passed to expert

advisersfor comment and then presented to the Paed-

iatricFormulary Committee forconsideration. Addition-

ally,for each edition, sections arechosen from every

chapterfor thorough review.These planned reviews aim

toverify all the information in the selected sections and

to draft any amendments to reﬂect current best prac-

tice.

Staffeditors prepare the text for publication and under-

takea number of checks on the knowledge at various

stagesof the production.

Expert advisers

BNFCuses about 80 exper t clinical advisers (including

doctors, pharmacists, nurses, and dentists) throughout

theUK to help with the production of each edition. The

role of these expert advisers is to review existing text

and to comment on amendments drafted by the staf f

editors.These clinical experts help to ensure that BNFC

remainsreliable by:

commenting on the relevance of the text in the

contextof best clinical practice in the UK;

checking draft amendments forappropriate inter-

pretationof any new evidence;

providingexpert opinion in areas of controversy or

whenreliable evidence is lacking;

advisingon areas where BNFC diverges from sum-

mariesof product characteristics;

advising on the use of unlicensed medicines or of

licensed medicines for unlicenseduses (‘of f-label’

use);

providingindependent advice on dr ug interactions,

prescribing in hepatic impairment, renal impair-

ment,pregnancy, breast-feeding,neonatal care, pal-

liativecare, and the emergency treatment of pois-

oning.

In addition to consulting with regular advisers, BNFC

calls on other clinical specialists forspeciﬁc develop-

mentswhen particular expertise is required.

BNFCalso worksclosely with a number ofexpert bodies

that produce clinical guidelines. Drafts or pre-publica-

tion copies of guidelines are routinely received for

commentand for assimilation into BNFC.

Sourcesof BNFC information

BNFCuses a variety of sources for its information; the

mainones are shown below.

Summaries of product characteristics

BNFC

receives summaries of productcharacteristics (SPCs)

ofall new products as well as revised SPCs for existing

products.The SPCs are a key source of product infor-

mation and are carefully processed,despite the ever-

increasing volume of information being issuedby the

pharmaceuticalindustry. Such processing involves:

verifyingthe approved names of all relevant ing re-

dients including ‘non-active’ ingredients (BNFC is

committed to using approved names and descrip-

tionsas laid down by the Medicines Act);

comparingthe indications, cautions, contra-indica-

tions, and side-effects with similarexisting drugs.

Where these are different fromthe expected pat-

tern, justiﬁcation is sought for their inclusion or

exclusion;

seeking independent data on the use ofdrugs in

pregnancyand breast-feeding;

BNFC 2011–2012 ix

incorporating the information into BNFC using

established criteria for the presentation and inclu-

sionof the data;

checking interpretation of the information bytwo

staff editors before submitting toa senior editor;

changesrelating to doses receive an extra check;

identifyingpotential clinical problems or omissions

andseeking further informationfrom manufacturers

orfrom exper t advisers;

careful validation of any areas of divergence of

BNFCfrom the SPC before discussion by the Com-

mittee(in the light of supporting evidence);

constructing, with the help of expert advisers,a

commenton the role of the drug in the context of

similardrugs.

Much of this processing is applicable to the following

sourcesas well.

Expertadvisers

Therole of expert clinical advisers in

providingthe appropriate clinical context for all BNFC

informationis discussed above.

Literature

Staff editors monitor core medical, paed-

iatric, and pharmaceutical journals. Research papers

andreviews relating to drug therapy are carefully pro-

cessed.When a difference between the advice in BNFC

andthe paper is noted, the new infor mation is assessed

for reliability and relevance to UK clinical practice. If

necessary,new text isdrafted and discussed with expert

advisers and the Paediatric Formulary Committee.

BNFCenjoys a close working relationship with a num-

berof national information providers.

Systematic reviews

BNFC has access to various

databases of systematic reviews (including the

Cochrane Library andvarious web-based resources).

These are used for answering speciﬁc queries, for

reviewing existing text and for constructing new text.

Staffeditors receive training in critical appraisal, litera-

ture evaluation, and search strategies. Reviews pub-

lished in Clinical Evidence are used to validate BNFC

advice.

Consensus guidelines

The advice in BNFC is

checked against consensus guidelines produced by

expertbodies. A number of bodies make drafts or pre-

publicationcopies of theguidelines available to BNFC; it

istherefore possible to ensurethat a consistent message

is disseminated. BNFC routinely processes guidelines

from the National Institute for Health and Clinical

Excellence(NICE), the Scottish Medicines Consortium

(SMC),and the Scottish Intercollegiate Guidelines Net-

work(SIGN).

Referencesources

Paediatricformularies and refer-

encesources are used to provide background informa-

tionfor thereview of existing text orfor the construction

of new text. The BNFC team worksclosely withthe

editorialteam that produces

Martindale:The Complete

DrugReference

.BNFC has access to

Martindale

infor-

mation resources and each team keeps the other

informed of signiﬁcant developments and shifts in the

trendsof drug usage.

Statutory information

BNFC routinely processes

relevant information from various Government bodies

includingStatutory Instruments and regulations affect-

ingthe Prescription only Medicines Order.Ofﬁcial com-

pendia such as the British Pharmacopoeia and its

addenda are processed routinely to ensure that BNFC

complies with the relevant sections ofthe Medicines

Act.

BNFC maintains close links with the Home Ofﬁce (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 guidelines on drug use issued by

theUK health departments are processed as a matter of

routine.

Relevant professional statements issuedby the Royal

PharmaceuticalSociety of Great Britain are included in

BNFCas are guidelines from bodies such as the Royal

Collegeof Paediatrics and Child Health.

BNFC reﬂects information from the Drug Tariff, the

Scottish Drug Tariff,and the Northern Ireland Drug

Tariff.

Pricing information

NHS Prescription Services

provide information on prices of medicinal products

andappliances in BNFC. BNFC also receives and pro-

cessesprice lists from product suppliers.

Comments from readers

Readers of BNFC are

invited to send in comments. Numerous letters and

emails are received during the preparation of each

edition. Such feedback helps to ensure that BNFC

provides practical and clinically relevant information.

Manychanges in the presentation and scope of BNFC

haveresulted from comments sent in by users.

Commentsfrom industry

Closescrutiny of BNFC by

the manufacturers provides an additional check and

allowsthem an opportunityto raise issues about BNFC’s

presentation of the role of various drugs; this is yet

another check on the balance of BNFC advice. All

commentsare lookedat with care and, where necessary,

additionalinformation and expert advice are sought.

Virtual user groups

BNFC has set up virtual user

groupsacross various healthcare professions (e.g. doc-

tors,pharmacists, nurses). The aim of these groups will

beto provide feedback to the editors and publishers to

ensure that BNF publications continue to serve the

needsof its users.

Market research

Market research is conducted at

regularintervals to gather feedback on speciﬁc areas of

development, such as drug interactions or changes to

theway information is presented in digital formats.

BNFC is an independent professional publication

that is kept up-to-dateand addresses the day-to-

day prescribing information needs of healthcare

professionalstreating children. Use of this resource

throughout the health service helps to ensure that

medicinesare used safely, effectively, and appropri-

atelyin children.

x BNFC 2011–2012

How to use BNF for Children

BNFfor Children

(BNFC)provides information on

theuse of medicines in children ranging from neo-

nates (including preterm neonates) to adolescents.

Theterms infant, child, and adolescent are not used

consistently in the literature; to avoid ambiguity

actual ages are used in the dose statements in

BNFC.The term neonate is used to describe a new-

born infant aged 0–28 days. The terms child or

childrenare used generically to describe the entire

rangefrom infant to adolescent in BNFC.

Inorder to achieve the safe, effective, and appropriate

use of medicines in children,healthcare professionals

mustbe able to use BNFC effectively, and keep up to

date with signiﬁcant changes ineach new edition of

BNFCthat are relevant to their clinical practice.

Howto

UseBNF for Children

isaimed as a quick refresher for

all healthcare professionals involved with prescribing,

monitoring,supplying, and administering medicines for

children, and as a learning aid for students training to

join these professions. While

How to Use BNF for

Children

is linked to the main elements of rational

prescribing,the generic structure of this section means

that it can be adapted for teaching and learning in

differentclinical settings.

Structure of BNFC

The Contents list (on p. iii) shows that information in

BNFCis divided into:

HowBNF for Childrenis Constructed

(p.ix);

Changesfor this Edition

(p.xvii);

General Guidance

(p.1), which provides practical

information on many aspects of prescribing from

writing a prescription to prescribing in palliative

care;

Emergency Treatmentof Poisoning

(p.24), which

providesan overview on the management of acute

poisoning;

Classiﬁednotes on clinical conditions, drugs, and

preparations

,these notes are divided into 15 chap-

ters,each of which is related to a particular system

ofthe body (e.g. chapter 3, Respiratory System) or

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

Infections). Each chapter is further divided into

classiﬁed sections. Each section usually begins

with

prescribing notes

followed by relevant dr ug

monographs

and

preparations

(see ﬁg. 1). Drugs

are classiﬁed in a section according to their phar-

macologyand therapeutic use;

Appendices and Indices

, includes 4 Appendices

(providinginformation on drug interactions,border-

linesubstances, cautionary and advisory labels for

dispensedmedicines, and intravenous infusions for

neonatal intensive care), theDental Practitioners’

Formulary,the Nurse Prescriber s’ Formulary, Non-

medical Prescribing, Index ofManufacturers, and

themain Index. The information in the Appendices

should be used in conjunction with relevant infor-

mationin the chapters.

Finding information in BNFC

BNFCincludes a number of aids to help access relevant

information:

Index

(p.811), where entries are 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’ brings together topics of relevance to

dental surgeons. The page referenceto thedr ug

monograph is shown inbold type. References to

drugsin Appendices 1 and 3 are not included in the

mainIndex;

Contents

(p.iii), provides a hierarchy of how infor-

mationin BNFC is organised;

Thebeginning of each chapter includes

aclassiﬁed

hierarchy

of how information is organised in that

chapter;

Runningheads

,located next to thepage number on

thetop of each page,show the section of BNFC that

isbeing used;

Thumbnails

,on the outer edge of each page, show

thechapter of BNFC that is being used;

Cross-references

, lead to additional relevant infor-

mationin other parts of BNFC.

Finding dental information in BNFC

Extrasignposts have been added to help access dental

informationin BNFC:

Prescribing in Dental Practice

(p.22), includes a

contentslist dedicated to drugs and topics of rele-

vanceto dentists, together with cross-references to

theprescribing notes in the appropriate sections of

BNFC.For example, a review of this list shows that

informationon the local treatment of oral infections

is located in chapter 12 (Ear, Nose, and Oro-

pharynx) while information on the systemic treat-

mentof these infections isfound in chapter 5 (Infec-

tions).Further guidance for dental practice can be

foundin the BNF.

Side-headings

,in the prescribing notes, side-head-

ings facilitate the identiﬁcation ofadvice onoral

conditions(e.g. Dental and Orofacial Pain, p. 199);

Dentalprescribing on NHS

,in the body of BNFC,

preparationsthat can beprescribed using NHS form

FP10D(GP14 in Scotland, WP10D in Wales)can be

identiﬁedby means of a note headed ‘Dental pre-

scribing on NHS’ (e.g. Aciclovir Oral Suspension,

p.323).

Identifying effective drug treatments

Theprescribing notes in BNFC provide an overview of

thedrug management of common conditions and facil-

itaterapid appraisal of treatment options (e.g. epilepsy,

p.215). For easeof use, information on themanagement

of certain conditions has been tabulated (e.g. acute

asthma,p. 136).

Adviceissued by the National Institute for Health and

Clinical Excellence (NICE) isintegrated within BNFC

BNFC 2011–2012 xi

prescribing notes if appropriate.Summaries of NICE

technology appraisals, and relevant short guidelines,

areincluded in pink panels. BNFC also includes advice

issued by the Scottish Medicines Consortium (SMC)

whena medicine is restricted or not recommended for

usewithin NHS Scotland.

In order to select safe and effective medicines for

individual children, information in the prescribing

notes must be used in conjunction with other pre-

scribing details about the drugs and knowledge of the

child’smedical and dr ug history.

Figure 1 Illustratesthe typical layout of a drug monograph and preparation

records in BNFC

BNFC How to useBNFC xii

DRUG NAME U

Cautions

detailsof precautions required and also

anymonitoring required

Counselling

Verbalexplanation to the patient of spe-

ciﬁcdetails of the drug treatment (e.g. posture when

takinga medicine)

Contra-indications

circumstanceswhen a drug

shouldbe avoided

Hepaticimpairment

adviceon the use of a drug

inhepatic impair ment

Renalimpairment

adviceon the use of a drug in

renalimpairment

Pregnancy

adviceon the use of a drug during

pregnancy

Breast-feeding

adviceon the use of a drug dur-

ingbreast-feeding

Side-effects

verycommon (greater than 1 in 10)

andcommon (1 in 100 to 1 in 10);

lesscommonly

(1in 1000 to 1 in 100);

rarely

(1in 10 000 to 1 in

1000);

veryrarely

(lessthan 1 in 10 000); also

reported,frequency not known

Licenseduse shows if drug unlicensed in the

UK,or ‘off-label’ use of drug licensed in the UK

Indicationand dose

Detailsof uses and indications

Byroute

Child

doseand frequency of administration

(max.dose) for speciﬁc age group

Byalternative route

Child

doseand frequency

Administration

practicaladvice on the adminis-

trationof a drug

ApprovedName (Non-proprietary) A

Pharmaceuticalform

,sugar-free, active ingre-

dientmg/mL, net price, pack size = basic NHS

price.Label: (as in Appendix 3)

Exceptionsto the prescribing status are indicated by a

noteor footnote.

ProprietaryName (Manufacturer) AD

Pharmaceuticalform

,colour, coating, active

ingredientand amount in dosage form, net price,

packsize = basic NHS price. Label: (as in

Appendix3)

Excipients

includeclinically important excipients

Electrolytes

clinicallysigniﬁcant quantities of electrolytes

Note

Speciﬁcnotes about the product e.g. handling

Preparations

Preparationsare included under a non-proprietar y

title,if they are marketed under such a title, if they

arenot otherwise prescribable under the NHS, or if

theymay be prepared extemporaneously.

Inthe case of compound preparations, the indica-

tions,cautions, contra-indications, side-effects, and

interactionsof all constituents should be taken into

accountfor prescribing.

Whenno suitable licensed preparation is available,

details of preparations thatmay beimported or

formulationsavailable as manufactured specials or

extemporaneouspreparations are included.

Drugs

Drugsappear under pharmacopoeial or other non-

proprietary titles. When there is an

appropriate

currentmonograph

(Medicines Act 1968, Section

65)preference is givento a name at the headof that

monograph; otherwise a British ApprovedName

(BAN),if available, is used.

Thesymbol U is used to denote those prepara-

tionsconsidered to be less suitable for prescribing.

Althoughsuch preparations may not be considered

asdrugs of ﬁr st choice, their use may be justiﬁable

incertain circumstances.

Prescription-onlymedicines A

Thissymbol has been placed against preparations

that are available only on a prescription from an

appropriate practitioner. For more detailed infor-

mation see

Medicines

Ethics and Practice

, Lon-

don, Pharmaceutical Press (always consult latest

edition).

The symbols 23KLindicate that the

preparationsare subject tothe prescription require-

ments of the Misuse of Drugs Act. For advice on

prescribingsuch preparations see Prescribing Con-

trolledDrugs, p. 9.

Preparationsnot available for NHS

prescriptionD

Thissymbol has been placed against preparations

that are not prescribable 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

prescribable

by brand name under

theNHS may nevertheless be

dispensed

usingthe

brand name provided that the prescription shows

anappropriate non-proprietar y name.

Prices

Prices have been calculated fromthe basic cost

usedin pricing NHS prescriptions, see also Prices

inBNFC, p. xvi for details.

How to useBNFC

xii BNFC 2011–2012

A brief description ofthe clinical usesof a drugcan

usuallybe foundin the Indication and Dose sectionof its

monograph(e.g. ibuprofen, p. 503); a cross-reference is

providedto any indications for that dr ug that are cov-

eredin other sections of BNFC.

Thesymbol U is used to denote preparations that are

consideredby the JointFormulary Committee to be less

suitable for prescribing. Although such preparations

may not be consideredas drugs ofﬁrst choice,their

usemay be justiﬁable in certain circumstances.

Drug management of medical

emergencies

Guidance on the drug managementof medical emer-

genciescan be foundin the relevant BNFCchapters (e.g.

treatmentof anaphylaxis is included in section 3.4.3). A

summaryof drug doses used for Medical Emergencies

inthe Community can be found in the glossy pages at

theback of BNFC. Algorithms for Newborn, Paediatric

Basic,and PaediatricAdvanced Life Support can also be

foundwithin these pages.

Minimising harm in childrenwith co-

morbidities

Thedrug chosen to treat a particular condition should

have minimal detrimental effectson thechild’s other

diseases and minimise the child’s susceptibility to

adverseef fects. To achieve this, the

Cautions

Contra-

indications

,and

Side-effects

ofthe relevant drug should

be reviewed, and can usually be found in the drug

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

clines, p. 274) share the same cautions, contra-indica-

tions, and side-effects, these are amalgamatedin the

prescribingnotes while thoseunique to a particular drug

in that class are included in its individual dr ug mono-

graph. Occasionally, the cautions, contra-indications,

and side-effects may be included within a preparation

recordif they are speciﬁc to that preparation or if the

preparationis not accompanied by a monograph.

Theinformation under Cautions can be used to assess

therisks of using a drug in a child who has co-morbid-

ities that are also included in the Cautions for that

drug—if a safer alternative cannot be found, the dr ug

may be prescribed while monitoring the child for

adverse-effects or deterioration in the co-morbidity.

Contra-indications are far morerestrictive than Cau-

tions and mean that the drug shouldbe avoided in a

childwith a condition that is contra-indicated.

The impact that potential side-ef fects may have on a

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

instance, in a child who has constipation, it may be

preferable to avoid a drug that frequently causes con-

stipation.The prescribing notes in BNFC may highlight

important safety concerns and differences between

drugsin their ability to cause certain side-effects.

Prescribingfor children with hepatic or

renal impairment

Drugselection should aim to minimise the potential for

drugaccumulation, adverse drug reactions, and exacer-

bation of pre-existing hepatic or renaldisease. If it is

necessaryto prescribe drugs whose effect is altered by

hepaticor renal disease, appropriate dr ug dose adjust-

ments should be made, and the child should be mon-

itoredadequately. Thegeneral principles for prescribing

are outlined under

Prescribingin Hepatic Impairment

(p.14) and

Prescribing in Renal Impairment

(p.14).

Information about drugs that should be avoided or

used with caution inhepatic disease orrenal impair-

mentcan be found in dr ug monographs under

Hepatic

Impairment

and

Renal Impairment

(e.g. ﬂuconazole,

p.301). However, if a class of drugs (e.g. tetracyclines,

p.274) 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 shouldaim to minimise harm to the

fetus,nursing infant, and mother. The infant should be

monitoredfor potential side-effects of drugs used bythe

motherduring pregnancy or breast-feeding.The general

principlesfor prescribing are outlined under

Prescribing

inPregnancy

(p.16) and

Prescribingin Breast-feeding

(p.16). The prescribing notes in BNFC chapters provide

guidanceon the drug treatment of common conditions

thatcan occurduring pregnancy and breast-feeding (e.g.

asthma, p. 133). Information about the use of speciﬁc

drugs during pregnancy and breast-feeding can be

foundin their drug monographs under

Pregnancy

and

Breast-feeding

(e.g.ﬂ uconazole, p. 301). However, if a

classof drugs (e.g. tetracyclines, p. 274) share the same

recommendations for use during pregnancy or breast-

feeding,this advice is amalgamated in the prescribing

notes under

Pregnancy

and

Breast-feeding

while any

advicethat is unique to a particular drug in that class is

includedin its individual drug monograph.

Minimising drug interactions

Drug selection should aim to minimise drug interac-

tions.If it is necessary to prescribe a potentially serious

combination of drugs, children should be monitored

appropriately.The mechanisms underlying drug inter-

actionsare explained in Appendix 1 (p. 655).

Detailsof drug interactions can be found in Appendix 1

ofBNFC (p. 656). Drugs and their interactions are listed

inalphabetical order of the non-proprietar y drug name,

andcross-references to drug classes areprovided where

appropriate.Each drug or dr ug class is listed twice: in

the alphabetical list and also against the drug or class

withwhich it interacts. The symbol . is placed against

interactionsthat are potentially serious and where com-

bined administration of drugs should be avoided (or

onlyundertaken with caution and appropriate monitor-

ing). Interactions that have no symbol do notusually

haveserious consequences.

Ifa drug or drug class hasinteractions, a cross reference

towhere these can be found in Appendix 1 is provided

under the Cautions of the drug monograph or pre-

scribingnotes.

BNFC 2011–2012 xiii

Selecting the dose

Thedr ug dose is usually located in pink panels within

the

Indicationand Dose

sectionof the drug monograph

or within the

Dose

section of the preparationrecord.

Doses are linked to speciﬁc indications androutes of

administration.The dose of a drug may vary according

to different indications, routes of administration,age,

body-weight,and body-surface area.When the dose of a

drug varies according to different indications, each

indication and its accompanying dose is included in a

separatepink panel (e.g. aciclovir, p. 322). The dose is

located within the preparation record whenthe dose

variesaccording to different formulations of that dr ug

(e.g.amphotericin, p. 305) or when a preparation has a

dose different to thatin its monograph. Occasionally,

drugdoses may be included in the prescribing notes for

practical reasons (e.g. doses of drugsin

Helicobacter

pylori

eradication regimens, p.42). The right dose

should be selected for theright age and body-weight

(orbody surface area)of the child, as well asfor the right

indication,route of administration, and preparation.

Dosesin BNFC are usually assigned to speciﬁc age

ranges; neonatal doses are preceded bythe word

Neonate,all other doses are preceded by the word

Child.Age ranges in BNFC are described as shown

inthe following example:

Child1 month–4 years refersto a child from 1

monthold up to their 4

birthday;

Child4–10 years refers to a child from the day of

their4

birthdayup to their 10

birthday.

However,apragmatic approach should be applied to

thesecut-off points depending on the child’s physio-

logical development, condition, and if weight is

appropriatefor the child’s age.

Forsome dr ugs (e.g. gentamicin, p. 278) the neonatal

dose varies according to the

postmenstrual

age of the

neonate. Postmenstrual age is the neonate’s total age

expressed in weeks from the start of the mother’s last

menstrualperiod. For example, a 3 week old baby bor n

at27 weeks gestation is treated as having a postmenstr-

ualage of 30 weeks. A term baby has a postmenstrual

ageof 37–42 weeks when born. For most other drugs,

thedose can be based on the child’s actual date of birth

irrespectiveof postmenstrual age. However, the degree

ofprematurity, the maturity of renal and hepatic func-

tion,and the clinical properties of the drug need to be

consideredon an individual basis.

Many children’s doses in BNFC are standardised by

body-weight

. To calculate thedose for a given child

theweight-standardised dose is multiplied by the child’s

weight (or occasionally by the child’s ideal weight for

height). The calculated dose should not normally

exceedthe maximum recommended dose for an adult.

Forexample, if the dose is 8 mg/kg (max. 300 mg), a

childof 10 kg body-weight should receive 80 mg, but a

child of 40kg body-weight should receive 300mg

(rather than 320mg). Calculation by body-weight in

the overweight child may result in much higher doses

being administered than necessary; in such cases, the

dose should be calculated from an ideal weight for

height.

Occasionally,some doses in BNFC are standardised by

body surface area

because many physiological phe-

nomena correlate better with body surface area. In

thesecases, to calculate the dose for a given child, the

bodysurface area-standardised dose ismultiplied by the

child’sbody surface area. The child’s body surface area

canbe estimated from his or her weight using the tables

forBody Surface Area in Children located in the glossy

pagesat the back of the print version of BNFC.

The doses of some drugs may need to be adjusted if

theiref fects are altered by concomitant use with other

drugs, or in patients with hepatic or renal impair ment

(seeMinimising Drug Interactions, and Prescribing for

Childrenwith Hepatic or Renal Impairment).

Wherever possible, doses are expressed in terms of a

deﬁnite frequency (e.g. if the dose is 1mg/kg twice

daily,a child of body-weight 9 kg would receive 9 mg

twice daily). Occasionally,it is necessary to include

doses in the total daily dose format (e.g. 10mg/kg

dailyin 3 divided doses); in these cases the total daily

dose should be divided intoindividual doses(in this

example a child of body-weight 9kg would receive

30mg 3 times daily).

Most drugs can be administered at slightly irregular

intervalsduring the day.Some drugs, e.g. antimicrobials,

are best given at regular intervals. Some ﬂ exibility

should be allowed in children to avoid wakingthem

duringthe night. For example, the night-time dose may

begiven at the child’s bedtime.

Special care should be takenwhen convertingdoses

fromone metric unit to another, and when calculating

infusionrates or the volume of a preparation to admin-

ister.Conversions for imperial to metric measures can

be found in the glossy pages at the back of BNFC.

Where possible, doses should be rounded to facilitate

administration of suitable volumesof liquid prepara-

tions,or an appropriate strength of tablet or capsule.

Selecting a suitable preparation

Childrenshould be prescribed a preparation that com-

plementstheir daily routine, and that provides the right

dose of drug for the right indication and route of

administration.

InBNFC, preparations usually follow immediately after

themonograph for the drug which is their main ingre-

dient.The preparation record (see ﬁg. 1) provides infor-

mation on the type of formulation (e.g. tablet), the

amountof active drug in a solid dosage form, and the

concentration of active dr ug in a liquid dosageform.

The legal status is shownfor prescription only medi-

cines and controlled dr ugs; any exception to the legal

status is shown by a Note immediatelyafter the pre-

parationrecord or a footnote. If a proprietary prepara-

tion has a distinct colour, coating, scoring, or ﬂ avour,

thisis shown in the preparation record. If a proprietary

preparation includes excipients usually speciﬁed in

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

Excipients

statement,and if it contains clinically signiﬁcant quan-

tities of electrolytes,these are usually shown in the

Electrolytes

statement.

Branded oral liquid preparations that do not contain

fructose, glucose, or sucroseare described as‘sugar-

free’ in BNFC. Preparationscontaining hydrogenated

glucosesyrup, mannitol, maltitol, sorbitol, or xylitol are

alsomarked ‘sugar-free’since there is evidence thatthey

donot cause dentalcaries. Children receiving medicines

containingcariogenic sugars, or their carers, should be

advisedof appropriate dental hygiene measures to pre-

xiv BNFC 2011–2012

vent caries. Sugar-free preparations should be used

wheneverpossible.

Where a drug has several preparations, those of a

similartype may be grouped together under a heading

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

p.143). Where there is good evidence to show that

the preparations for a particular dr ug are not inter-

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

sectionof the monograph or by the group of prepara-

tionsaffected. When the dose ofa drug varies according

to different formulations ofthat drug, the right dose

shouldbe prescribed for the preparation selected.

Inthe case of compound preparations, the prescribing

information of all constituents should be taken into

accountfor prescribing.

Unlicensedpreparations that are available from ‘Special

order’ manufacturers and specialist importing compa-

niesare included (e.g. midazolam buccal liquid, p. 639).

Theavailability of an extemporaneous formulation of a

drugis shown after its other preparations (e.g.captopril,

p.102).

Writing prescriptions

Guidanceis provided on writing prescriptions that will

helpto reduce medication errors, see p. 4. Prescription

requirementsfor controlled drugs are also speciﬁed on

p. 9.

Administering drugs

Basic information on the route of administration is

providedin the Indication and Dose section of a dr ug

monographor the Dose section of a preparation record.

Furtherdetails, such as masking the bitter taste of some

medicines,may be provided in the

Administration

sec-

tionof a dr ug monograph (e.g. proguanil, p. 336). Prac-

ticalinformation is also provided on the preparation of

intravenous drug infusions, including compatibilityof

drugswith standard intravenous infusion ﬂuids, method

of dilution or reconstitution, and administrationrates

(e.g.co-amoxiclav, p. 263). The

Administration

section

islocated within preparation recordswhen this informa-

tion varies according to dif ferent preparations of that

drug(e.g. amphotericin, p. 305). If a class of drugs (e.g.

topicalcorticosteroids, p. 559) share the same adminis-

trationadvice, this may be presented in the prescribing

notes.

Informationon intravenous infusions for neonatalinten-

sivecare can also be found in Appendix 4, p. 791.

Advising children(and carers)

Theprescriber, the child’s carer, and the child (if appro-

priate)should agree on thehealth outcomes desired and

on the strategy for achieving them (see Taking Medi-

cinesto Best Ef fect, p. 1). Taking the time to explain to

the child (and carers) therationale and thepotential

adverse effects of treatment may improve adherence.

Forsome medicines there is a special need for counsel-

ling (e.g. recognising signs of blood, liver, or skin dis-

orderswith carbamazepine); this is shown in

Counsel-

ling

statements, usually in the Cautionsor Indication

andDose section of a monograph, or within a prepara-

tionrecord if it is speciﬁc to that preparation.

Childrenand their carers should be advised if treatment

is likely to affect their abilityto perform skilled tasks

(e.g.driving).

Cautionary and advisory labels that pharmacists are

recommendedto add when dispensing are included in

thepreparation record (see ﬁg.1). Details of these labels

canbe found in Appendix 3 (p. 788).

Monitoring drug treatment

Childrenshould be monitoredto ensure they are achiev-

ingthe expected beneﬁts from drug treatment without

anyunwanted side-effects. The prescribing notes or the

Cautions in the drug monograph specify anyspecial

monitoringrequirements. Further information on mon-

itoringthe plasma concentration of drugs with a narrow

therapeuticindex can be found in the Pharmacokinetics

sectionor as a Note under the Dose section 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. 274) share thesame side-

effects, these are presented in the prescribing notes

while those unique to aparticular drug in that class

are included in itsindividual drug monograph. Occa-

sionally,side-effects may be included within a prepara-

tionrecord if they are speciﬁc to that preparation or if

thepreparation is not accompanied by a monograph.

Side-effects are generally listed in order of frequency

andarranged broadly by body systems. Occasionally a

rareside-effect might be listed ﬁrst if it is considered to

beparticularly important becauseof its seriousness. The

frequencyof side-ef fects is described in ﬁg. 1.

An exhaustive list of side-effects is not included for

drugs that are used by specialists (e.g. cytotoxic drugs

anddrugs used in anaesthesia). Recognising that hyper-

sensitivity reactions can occur with virtually all medi-

cines,this ef fect is generally not listed, unless the drug

carries an increased risk of such reactions. BNFC also

omits effects that are likely to have little clinical con-

sequence(e.g. transient increase in liver enzymes).

Theprescribing notes in BNFC may highlight important

safetyconcerns and differences between drugs in their

ability to cause certain side-ef fects. Safety warnings

issued by the Commission on Human Medicines

(CHM)or Medicines and Healthcare products Regula-

tory Agency (MHRA) can also be found here or in the

drugmonographs.

AdverseReactions to Drugs (p. 12) provides advice on

preventing adverse drug reactions, and guidance on

reporting adverse drug reactions to the MHRA. The

blacktriangle symbol T identiﬁesthose preparations in

BNFCthat are monitored intensively by the MHRA.

BNFC 2011–2012 xv

Finding signiﬁcant changesin a new

edition

BNFCis published in Julyeach year and includes lists of

changes in a new edition thatare relevant to clinical

practice:

The print version includes an

Insert

that sum-

marisesthe background to several key changes. A

copyof the Insert can also be found at bnfc.org in

the section on Updates under ‘What’s new in

BNFC?’;

Changesfor this edition

(p.xvii), provides a list of

signiﬁcant changes, dose changes, classiﬁcation

changes, new names, andnew preparations that

havebeen incor porated into a new edition, as well

asa list of preparations thathave been discontinued

sincethe last edition. For ease of identiﬁcation, the

marginsof these pages are marked in pink;

E-newsletter

,the BNF & BNFC e-newsletter service

isavailable free of charge. It alerts healthcare pro-

fessionals to details of signiﬁcant changes in the

clinicalcontent of these publications andto the way

thatthis information is delivered. Newsletters also

review clinical case studies and provide tips on

usingthese publications effectively. To sign up for

e-newsletters go to bnf.org/newsletter. To visit

the e-newsletter archive, go to bnfc.org/bnfc/

bnfcextra/current/450066.htm.

So many changes are made to eachnew edition of

BNFC, that not all of them canbe accommodated in

the Insert and the Changes section. We encourage

healthcare professionals to review regularly the pre-

scribinginfor mation on dr ugs that they encounter fre-

quently.

Nutrition

Appendix2 (p. 743) includes tables of ACBS-approved

enteralfeeds and nutritional supplementsbased on their

energy and protein content. There are separate tables

forspecialised formulae for speciﬁc clinical conditions.

Classiﬁedsections on foods for special diets and nutri-

tional supplements for metabolic diseases are also

included.

Licensed status of medicines

BNFC includes advice on the use of unlicensed medi-

cines or of licensed medicines for unlicensed applica-

tions(‘of f-label’ use). Such advice reﬂects careful con-

sideration of the options available to manage a given

conditionand the weight of evidence and experience of

theunlicensed intervention. Limitations of the market-

ing authorisation should not precludeunlicensed use

whereclinically appropriate.

The

Licensed Use

statement in a drugmonograph is

usedto indicate that:

adrug is not licensed in the UK (e.g. pyrazinamide,

p.293);

a drug is licensedin theUK, but not for use in

children(e.g. lansoprazole, p. 45);

BNFCadvice for certain indications, age groups of

children, routes of administration, or preparations

falls outside a drug’s mar keting authorisation (e.g.

naproxen,p. 505).

Theabsence of the

LicensedUse

statementfrom a drug

monograph indicates that the dr ug is licensed forall

indications given in the monograph (e.g. zanamivir,

p.327).

Prescribingunlicensed medicines or medicines outside

their marketing authorisation alters (and probably

increases) the prescriber’s professional responsibility

andpotential liability. The prescriber should be able to

justify and feel competent in using such medicines.

Furtherinfor mation can be found in

BNFfor Children

andMarketing Authorisation, p. 2.

Prices in BNFC

Basic net prices are given in BNFC to provide an

indication of relative cost. Where there is a choice of

suitablepreparations for a particular disease or condi-

tionthe relative cost may be used in makinga selection.

Cost-effective prescribing must, however, take into

account other factors (such as dose frequency and

duration of treatment) that affect the total cost. The

useof more expensive drugs is justiﬁed if it will result in

better treatment of the patient, or areduction of the

lengthof an illness, or the time spent in hospital. Prices

havegenerally been calculated fromthe net cost used in

pricingNHS prescriptions in October 2010. Prices gen-

erally reﬂect whole dispensing packs; prices for injec-

tionsare stated per ampoule, vial, or syringe. The price

foran extemporaneously preparedpreparation has been

omitted where the net cost of the ingredients used to

makeit would give a misleadingly lowimpression of the

ﬁnalprice.

BNFC prices are not suitable for quoting topatients

seekingprivate prescriptions orcontemplating over-the-

counter purchases because they do not take into

accountVAT, professional fees, 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; prices in the different tariffs may vary.

Extra resourceson the BNFC website

While the BNFC website (bnfc.org) hosts the digital

content of BNFC proper, it also provides additional

resources such as

Frequently Asked Questions

and

onlinecalculators.

xvi BNFC 2011–2012

Changes for this

edition

Signiﬁcant changes

The

BNFfor Children

isrevised yearly and numerous

changesare made between issues.All copies of

BNFfor

Children2010–2011

shouldtherefore be withdrawnand

replaced by

BNF forChildren 2011–2012

. Signiﬁcant

changes have been made in the following sections for

BNFfor Children 2011–2012

Howto use BNFC, p. xi

Newsymbols introduced throughout

BNFfor Children

toidentify Controlled Drug preparations in Schedules 2,

3,and 4, Prescribing Controlled Drugs

Ibuprofenpoisoning, Emergency treatmentof poisoning

Paracetamolpoisoning [calculating the potentially toxic

doseingested by obese children], Emergency treatment

ofpoisoning

Inﬂiximabfor Crohn’s Disease [NICE guidance], section

1.5

Formoterol[MHRA/CHM advice], section 3.1.1.1

Omalizumab[NICE guidance], section 3.4.2

Fentanyl [counselling for theuse of patches],section

4.7.2

Epilepsyin pregnancy, section 4.8.1

Neonatalseizures, section 4.8.1

Febrileconvulsions, section 4.8.3

Nicotinedependence, section 4.10.2

Summaryof antibacterial therapy [advice refor matted],

section5.1, Table 1

CysticFibrosis, section 5.1, Table 1

Meningitis,section 5.1, Table 1

Erysipelasand cellulitis, section 5.1, Table 1

Preventionof pertussis, section 5.1, Table 2

Preventionof pneumococcal infection in asplenia or in

patientswith sickle-cell disease, section 5.1, Table 2

Prevention of infection in openfractures, section 5.1,

Table2

Urinary-tractinfections [culture and sensitivity testing],

section5.1.13

Treatmentof fungal infections: aspergillosis, section 5.2

HIVinfection [initiation of treatment], section 5.3.1

Antiretroviral drugs [doses included in their mono-

graphs],section 5.3.1

Palivizumab[respiratory syncytial virus], section 5.3.5

Prophylaxisagainst malaria [recommendations for Mor-

occoand Turk menistan removed], section 5.4.1

Dexamethasone [parenteral doses expressed asdexa-

methasonebase], section 6.3.2

Somatropinfor the treatment of growth failure in chil-

dren[NICE guidance], section 6.5.1

Recurrent vulvovaginal candidiasis [updated treatment

regimens],section 7.2.2

Combinedhormonal contraceptive interactions, section

7.3.1

Combinedoral contraceptives [preparations tabulated],

section7.3.1

Progestogen-only contraceptive interactions, section

7.3.2.1and section 7.3.2.2

Nocturnalenuresis, section 7.4.2

Rapamune

tablets[0.5 mg tablet not bioequivalent to

otherstrengths], section 8.2.2

G6PD deﬁciency [rasburicase and risk of haemolysis],

section9.1.5

Calcium gluconate injection [MHRA advice], section

9.5.1.1

Drugsunsafe for use in acute por phyrias, section 9.8.2

Aqueouscream [skin reactions when used as a leave-on

emollient],section 13.2.1

Nappyrash, section 13.2.2

Sunscreens [International Nomenclature for Cosmetic

Ingredients,table added], section 13.8.1

ImmunisationSchedule, section 14.1

Haemophilus type B conjugate vaccine and meningo-

coccal vaccines [in asplenia, splenic dysfunction, or

complementdeﬁciency], section 14.4

Inﬂuenzavaccines, section 14.4

Meningococcalvaccines, section 14.4

Pertussis vaccine [management of contacts], section

14.4

Sedative and analgesic peri-operative drugs, section

15.1.4

Local anaesthesia [section updatedand reorganised],

section15.2

Dose changes

Changes in dose statementsintroduced into

BNF for

Children2011–2012

Aciclovir[herpes simplex suppression], p. 322

Actiq

,p. 206

ACWYVax

,p. 615

AmBisome

,p. 306

Amitriptyline[neuropathic pain], p. 185

Ampicillin,p. 262

Atorvastatin,p. 126

Atropine [premedication by intravenous injection in

neonatesand intra-operative bradycardia in neonates],

p.635

Azathioprine[severe ulcerative colitis and Crohn’s dis-

ease],p. 54

Bendroﬂumethiazide,p. 77

Cervarix

[alternativeschedule], p. 611

Cetirizine[dose and dose in renal impairment], p. 154

Ciproﬂoxacin,p. 254

Co-amoxiclav[intravenous dose], p. 263

Colistimethatesodium (Colistin), p. 288

Dexamethasone,p. 374

Dexamfetamine,p. 189

Diazepam [intravenous dose for status epilepticus],

p.232

BNFC 2011–2012 xvii

EpilimChronosphere

,p. 228

Fersamal

,p. 444

Flucloxacillin [staphylococcal lung infection in cystic

ﬁbrosis],p. 259

Fludrocortisoneacetate [mineralocorticoid replacement

inadrenocortical insufﬁciency in neonates], p. 369

Flumazenil [intravenous injection dose forreversal of

sedativeeffects of benzodiazepines], p. 647

Foradil

[dosefor children under 12 years], p. 138

Freshfrozen plasma, p. 125

Fungizone

[neonataldose], p. 306

Glycopyrronium[premedication at induction in children

12–18 years and controlof muscarinic side-effects of

neostigminein children 12–18 years], p. 636

Hydralazine[intravenous infusion in neonates], p. 93

Hydrocortisone [congenital adrenal hyperplasia and

adrenalhypoplasia, Addison’s disease, chronic mainte-

nanceor replacement therapy], p. 375

Hydrocortisone [paediatric severe or life-threatening

acuteasthma], p. 134 and p. 136

Indometacin[symptomatic ductus arteriosus], p. 130

Ipratropium[dose frequency for severe or life-threaten-

ing acute asthma in children 12–18 years], p. 134 and

p.136

Itraconazole[tinea capitis], p. 303

Isoniazid,p. 255

Lansoprazole[dose in hepatic impairment], p. 45

Levetiracetam [no dose adjustment when switching

betweenintravenous and oral therapy], p. 222

Macrogol Oral Powder, Compound [faecal impaction],

p. 62

Menveo

,p. 615

Mercaptamine,p. 492

Meropenem,p. 273

Metronidazole,p. 296

Midazolam [neonatal dose for sedation in intensive

care],p. 638

Modigraf

,p. 437

Morphine [intravenous injection and oral dose in chil-

dren12–18 years], p. 207

Movicol

[faecalimpaction], p. 62

Movicol

-Half[faecal impaction], p. 62

Naloxone [intravenous infusion dose for overdosage

withopioids], p. 29

Nifedipine [hypertensive crisis, acute angina in Kawa-

sakidisease or progeria], p. 107

Nitrousoxide [maintenance of anaesthesia], p. 635

Paracetamol[severe postoperative pain by mouth and

byrectum], p. 200

Phenytoinsodium, p. 235

Prednisolone [corticosteroid replacement therapy],

p.376

Prograf

,p. 437

Propranolol[migraine prophylaxis], p. 88

Retapamulin,p. 586

Salofalk

tablets,granules, and rectal foam, p. 51

Seleniumsulphide [pityriasis versicolor], p. 584

Sodiumvalproate, p. 227

Sumatriptan[cluster headache], p. 213

Symbicort

100/6

[dosefor children6–12 years], p. 149

Temazepam,p. 639

Tiagabine [adjunctive treatment for focal seizures and

dosein hepatic impairment], p. 226

Topiramate [focal seizures and Lennox-Gastaut

syndrome, migraine prophylaxis, and dose in renal

impairment],p. 226

Tranexamicacid [prevention of excessive bleeding after

dentalprocedures by intravenous injection and menorr-

hagia],p. 123

Trimethoprim,p. 255

Valaciclovir,p. 323

Xylometazolinenasal spray, p. 542

ZydolSR

,p. 211

Classiﬁcation changes

Classiﬁcationchanges have been made in the following

sectionsof

BNFfor Children 2011–2012

Section2.1.2 Phosphodiesterase type-3 inhibitors [title

change]

Section 4.7.1 Non-opioid analgesics and compound

analgesicpreparations [title change]

Section4.10.2 Nicotine dependence [new section]

Section5.2.1 Triazole antifungals [new sub-section]

Section5.2.2 Imidazole antifungals [new sub-section]

Section5.2.3 Polyene antifungals [new sub-section]

Section 5.2.4 Echinocandin antifungals [new sub-sec-

tion]

Section5.2.5 Other antifungals [new sub-section]

Section6.1.2 Antidiabetic drugs [title change]

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]

Section 13.2.1.1Emollient bath additives and shower

preparations[title change]

Section15.1.4.1 Anxiolytics [title change]

New Names

Colistimethatesodium [for merly Colistin], p. 288

Dulcolax

Pico Liquid

and

Pico Perles

[formerly

Dulcolax

Liquidand Perles

],p. 61

Hydrocortisonemucoadhesive buccal tablets [formerly

Corlan

],p. 544

Laxido

Orange

[formerly

Laxido

],p. 62

Oilatum

Junior bath additive

[formerly

Oilatum

Junioremollient bath additive

],p. 555

xviii BNFC 2011–2012

Deleted preparations

Preparationslisted below have been discontinued dur-

ingthe compilation of

BNFfor Children2011–20 12

,or

are still available but arenot considered suitable for

inclusion by the Paediatric Formulary Committee (see

footnote):

Andropatch

Atropineeye ointment

AtroventAerocaps

Baxan

BeclometasoneCyclocaps

Betnesol-N

eyeointment

BudesonideCyclocaps

Chlorohex

Citanest

Crixivan

Dexedrine

Dimercaprol

Ditropan

elixir

Dopram

Dovonex

scalpsolution

Doxapram

Exelderm

Flixotide

Diskhaler

Hewletts

Indinavir

Ledermycin

Linola

Gamma

Loceryl

cream

Metrotop

Mixtard

Neosporin

Norvir

capsules

Octagam

Pharmorubicin

rapiddissolution injection

PolytarAF

Posalﬁlin

Protirelin

Pulmicort

aerosolinhalation

SalbutamolCyclocaps

Salinum

Select-A-Jet

Dopamine

SpectraBan

Sulconazole

Triclofos

Zantac

effervescent tablets

Zefﬁx

oralsolution

New preparations included in this

edition

Preparations included in the relevant sections of

BNF

forChildren 2011–2012

Adoport

[tacrolimus],p. 436

Anthelios

,p. 582

Aquamol

,p. 552

Calcichew-D

500mg/400unit caplets

[calciumcarb-

onatewith colecalciferol], p. 484

Capimune

[ciclosporin],p. 435

Carmize

[carmellosesodium], p. 530

Catacrom

[sodiumcromoglicate], p. 523

Crestor

[rosuvastatin],p. 127

Cyanokit

[hydroxocobalamin],p. 32

DermatonicsHeel Balm

,p. 553

Diovan

[valsartan],p. 104

Dovobet

[betamethasonewith calcipotriol], p. 568

Dovonex

ointment

[calcipotriol],p. 568

Eczmol

,p. 554

Epiduo

[adapalenewith benzoyl peroxide], p. 577

FlebogammaDIF

[normalimmunoglobulin], p. 624

Fulsovin

[griseofulvin],p. 309

Gammanorm

[normalimmunoglobulin], p. 623

Gammaplex

[normalimmunoglobulin], p. 624

Gynoxin

intravaginalcream

[fenticonazole],p. 395

HumulinI KwikPen

[isophaneinsulin], p. 355

Humulin M3 KwikPen

[biphasic isophane insulin],

p.356

Hyabak

[sodiumhyaluronate], p. 531

HydromolHC Intensive

,p. 560

Hylo-Care

[sodiumhyaluronate], p. 531

Insuman

Comb25 Solostar

[biphasic isophane insu-

lin],p. 356

Jext

[adrenaline],p. 161

Kalcipos-D

[calcium carbonate with colecalciferol],

p.484

Lescol

[ﬂuvastatin],p. 127

LopresorSR

[metoprolol],p. 91

Lumecare

LongLasting Tear Gel

[carbomers],p. 530

Lumecare

Preservative Free Tear Drops

[hypro-

mellose],p. 531

Lumecare

SodiumHyaluronate

[sodiumhyaluronate],

p.531

Marol

[tramadol],p. 211

Miphtel

[acetylcholinechloride], p. 532

Moxivig

[moxiﬂoxacin],p. 520

Nebusal

[hypertonicsodium chloride], p. 166

Neokay

[phytomenadione],p. 487

Nexplanon

[etonogestrel],p. 405

NicoretteQuickmist

[nicotine],p. 240

Nivestim

[ﬁlgrastim],p. 456

Norvir

tablets[ritonavir], p. 318

1.Not consideredsuitable for inclusion by the Paediatric

FormularyCommittee

BNFC 2011–2012 xix

TearsNaturale

SingleDose

[hypromellose],p. 531

Tevagrastim

[ﬁlgrastim],p. 456

Tobravisc

[tobramycin],p. 520

Vismed

Gel

[sodiumhyaluronate], p. 531

Vivadex

[tacrolimus],p. 438

VPRIV

[velaglucerasealfa], p. 491

Wellvone

[atovaquone],p. 343

Xenical

[orlistat],p. 191

Zerocream

,p. 553

Zeroguent

,p. 553

Zerolatum

,p. 555

Zerolatum

Plus

,p. 556

Zeroneum

,p. 555

Zerozole

,p. 556

xx BNFC 2011–2012

General guidance

Medicinesshould be given tochildren only when they

arenecessary, and in allcases the potential beneﬁtof

administeringthe medicine should beconsidered in

relationto the risk involved.This is particularly impor-

tantduring pregnancy,when therisk toboth motherand

fetusmust be considered (forfurther details see Pre-

scribingin Pregnancy, p.16).

It is important to discuss treatment options carefully

with the child and the child’scarer (see also Taking

Medicinesto Best Effect,below). In particular,the child

andthe child’scarer should behelped to distinguishthe

adverseef fectsof prescribed drugs from the effects of

themedical disorder. Whenthe beneﬁcial effects ofthe

medicineare likely to be delayed, this should be high-

lighted.

Taking medicines to best effect

Difﬁculties in

adherence to drug treatment occur regardless of age.

Factors that contribute to poor compliance with pre-

scribedmedicines include:

difﬁculty in taking the medicine(e.g. inability to

swallowthe medicine);

unattractiveformulation (e.g. unpleasant taste);

prescriptionnot collected or notdispensed;

purposeof medicine not clear;

perceivedlack of efﬁcacy;

realor perceived adverse effects;

carers’or child’s perceptionof the riskand severity

ofside-effects maydiffer fromthat of theprescriber;

instructionsfor administration not clear.

Theprescriber, the child’scarer, andthe child (ifappro-

priate)should agreeon thehealth outcomes desiredand

onthe strategy forachieving them (‘concordance’).The

prescribershould be sensitive toreligious, cultural, and

personal beliefs of the child’s family that can affect

acceptanceof medicines.

Takingthe time to explainto the child (andcarers) the

rationaleand the potential adverseeffects of treatment

may improve adherence. Reinforcement and elabora-

tion of the physician’s instructions by the pharmacist

and other members of the healthcare team can be

important.Giving adviceon themanagement ofadverse

effectsand the possibilityof alternative treatmentsmay

encourage carers and children to seek advice rather

thanmerely abandon unacceptable treatment.

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.

Drug treatment in children

Children, and particu-

larly neonates, differ from adults in their response to

drugs.Special careis neededin theneonatal period(ﬁrst

28days of life) and doses should alwaysbe calculated

withcare; the risk oftoxicity is increased by areduced

rateof drug clearance and differing targetorgan sensi-

tivity.

Forguidance onselecting dosesof drugs inchildren see

Howto Use

BNFfor Children

,p. xiv.

Administrationof medicines to children

Children

shouldbe involved indecisions about taking medicines

and encouraged to take responsibility for using them

correctly.The degree of such involvementwill depend

onthe child’s age,understanding, and personalcircum-

stances.

Occasionallya medicine orits taste hasto be disguised

or masked with small quantities of food. However,

unless speciﬁcally permitted (e.g. some formulations

of pancreatin), a medicine should not be mixed with

largequantities of food becausethe full dosemight not

be taken and the child might develop an aversion to

foodif the medicine imparts anunpleasant taste. Med-

icinesshould not be mixedor administered in a baby’s

feedingbottle.

Childrenunder 5 years(and some olderchildren) ﬁnd a

liquidformulation more acceptable than tablets or cap-

sules. However, for long-term treatment it may be

possible for a child to be taught to take tablets or

capsules.

Anoral syringe (seebelow) should beused for accurate

measurement andcontrolled administration of an oral

liquidmedicine. The unpleasant taste of an oral liquid

canbe disguisedby ﬂavouring itor bygiving a favourite

foodor drink immediately afterwards,but the potential

forfood-drug interactions should beconsidered.

Advice should be given on dental hygiene to those

receiving medicines containing cariogenic sugars for

long-term treatment; sugar-free medicines should be

providedwhenever possible.

Childrenwith nasalfeeding tubes inplace forprolonged

periods should be encouraged to take medicines by

mouth if possible; enteric feeding should generally be

interrupted beforethe medicine is given(particularly if

enteralfeeds reducethe absorptionof aparticular drug).

Oralliquids canbe given throughthe tubeprovided that

precautions are taken to guard against blockage;the

doseshould be washeddown withwarm water.When a

medicine is given through a nasogastric tube to a

neonate, sterile water must be used to accompany

themedicine or to washit down.

The intravenous route is generally chosen when a

medicine cannot be given by mouth; reliableaccess,

oftena central vein, shouldbe used for childrenwhose

treatment involves irritant or inotropic drugs or who

needto receive the medicine overa long period or for

home therapy. The subcutaneous route is used most

commonly for insulin administration. Intramuscular

injections should preferably be avoided in children,

particularlyneonates, infants,and youngchildren. How-

ever,the intramuscular route maybe advantageous for

administrationof single dosesof medicines when intra-

venous cannulation would be more problematic or

BNFC 2011–2012 1

General guidance

painfulto the child. Certain drugs, e.g. some vaccines,

areonly administered intramuscularly.

Theintrathecal, epiduraland intraosseousroutes should

be used only by staff specially trained to administer

medicines by these routes. Local protocols for the

managementof intrathecal injections must be in place

(section8.1).

Managingmedicines in school

Administrationof a

medicineduring schooltime should beavoided if possi-

ble;medicines should be prescribed for onceor twice-

dailyadministration whenever practicable. If the med-

icine needs to be taken in school, this should be dis-

cussed with parents or carers and the necessary

arrangements made in advance; where appropriate,

involvementof aschool nurse shouldbe sought.

Mana-

ging Medicines in Schools and Early YearsSettings

produced by the Department of Health provides gui-

danceon using medicines inschools (www.dh.gov.uk).

Patientinformation leaﬂets

Manufacturers’patient

informationleaﬂ etsthat accompany a medicine, cover

only the licensed use of the medicine (see

BNF for

Children

and Marketing Authorisation, below). There-

fore,when a medicineis usedoutside its licence,it may

beappropriate to advisethe child andthe child’sparent

orcarer thatsome ofthe information in the leaﬂetmight

not apply to the child’s treatment. Where necessary,

inappropriate advice in the patient information leaﬂet

shouldbe identiﬁedand reassuranceprovided about the

correctuse in the context ofthe child’s condition.

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

the biosimilar and biological reference medicine in

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 trianglestatus (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

andalternative medicine is becoming available.Where

appropriate,the child and the child’s carers should be

askedabout theuse oftheir medicines,including dietary

supplements and topical products.The scope of

BNF

forChildren

is restricted tothe discussion of conven-

tionalmedicines but reference is madeto complemen-

tarytreatments if they affectconventional therapy (e.g.

interactions with St John’s wort—see Appendix 1).

Furtherinformation on herbal medicines isavailable at

www.mhra.gov.uk.

BNF for Children and marketing authorisation

Where appropriate the

doses

indications

cautions

contra-indications

,and

side-effects

BNFfor Children

reﬂect those in themanufacturers’ Summaries of Pro-

ductCharacteristics (SPCs) which,in turn, reﬂect those

inthe correspondingmarketing authorisations(formerly

knownas ProductLicences).

BNFfor Children

doesnot

generally include proprietary medicines that are not

supportedby a valid Summary ofProduct Characteris-

ticsor when themarketing authorisation holderhas not

been able to supply essential information. When a

preparationis available from more than one manufac-

turer,

BNFfor Children

reﬂectsadvice that is themost

clinically relevant regardless of any variation in the

marketing authorisation. Unlicensed products can be

obtainedfrom ‘special-order’ manufacturers or specia-

listimporting companies, see p.809.

Asfar aspossible, medicines shouldbe prescribed with-

in theter ms ofthe marketing authorisation. However,

many children require medicines not speciﬁcally

licensedfor paediatric use. Although medicinescannot

be promoted outside the limits of the licence, the

MedicinesAct does not prohibit the use of unlicensed

medicines.

BNFfor Children

includesadvice involving the use of

unlicensedmedicines or of licensedmedicines for unli-

censeduses (‘off-label’use). Such advicereﬂects careful

considerationof theoptions availableto managea given

conditionand the weightof evidence andexperience of

theunlicensed intervention (see also Unlicensed Med-

icines, p.6). Where the advice falls outside a drug’s

marketing authorisation,

BNF for Children

shows the

licensingstatus in the drug monograph. However,lim-

itationsof the marketing authorisation should not pre-

cludeunlicensed use where clinicallyappropriate.

Prescribing unlicensedmedicines

Prescribingunlicensed medicines or medicinesout-

side the recommendations of their marketing

authorisation alters (and probably increases) the

prescriber’sprofessional responsibilityand potential

liability.The prescribershould be able tojustify and

feelcompetent in using suchmedicines.

Drugs and skilled tasks

Prescribers and other

healthcare professionals should advise children and

their carers if treatment is likely to affect their ability

toperform skilled tasks(e.g. driving).This applies espe-

ciallyto drugs with sedative effects;patients should be

warned that these effects are increased by alcohol.

General information about a patient’s ﬁtness to drive

is available from the Driver and Vehicle Licensing

Agencyat www.dvla.gov.uk.

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).

Excipients

Branded oral liquid preparations that do

notcontain

fructose,glucose

,or

sucrose

aredescribed

as ‘sugar-free’in

BNFfor Children

. Preparationscon-

taininghydrogenated glucose syrup, mannitol, maltitol,

sorbitol, or xylitol are alsomar ked ‘sugar-free’ since

they do not cause dental caries. Children receiving

2 Generalguidance BNFC 2011–2012

General guidance

medicinescontaining cariogenic sugars,or their carers,

should be advisedof dental hygiene measures to pre-

vent caries. Sugar-free preparations should be used

wheneverpossible, particularly if treatment is required

fora long period.

Where informationon the presence of

alcohol

aspar-

tame,gluten

sulphites

tartrazine

arachis(peanut) oil

sesameoil

is available,this is indicated in

BNFfor

Children

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

BNFfor Children

.Benzyl alcohol has been associated

with a fatal toxic syndrome in preterm neonates, and

therefore, parenteral preparations containing the pre-

servative should not be used in neonates. Polyoxyl

castor oils, used as vehicles in intravenous injections,

have beenassociated with severe anaphylactoid reac-

tions.

Thepresence of

propyleneglycol

inoral or parenteral

medicinesis indicatedin

BNFfor Children

;it cancause

adverseeffects ifits elimination isimpaired, e.g.in renal

failure, in neonates and young children, and in slow

metabolisers of the substance. It may interact with

metronidazole.

The

lactose

contentin most medicines is too small to

cause problems in most lactose-intolerant children.

Howeverin severe lactoseintolerance, the lactosecon-

tent should be determined before prescribing. The

amount of lactose varies according to manufacturer,

product,formulation, and strength.

Important

Inthe absence of informationon excipients in

BNF

forChildren

andin the product literature (available

at www.emc.medicines.org.uk), contact the manu-

facturer(see Indexof Manufacturers) ifit isessential

tocheck details.

Health andsafety

When handlingchemical or bio-

logicalmaterials particular attentionshould be given to

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

poisoning. Care is required to avoidsources of heat

(includinghair dryers) when ﬂammable substances are

usedon the skin or hair. Substances, suchas corticos-

teroids,some antimicrobials, phenothiazines,and many

cytotoxics, are irritant or very potentand shouldbe

handledwith caution; contact withthe skin and inhala-

tionof dustshould be avoided.Healthcare professionals

andcarers shouldguard against exposureto sensitising,

toxic or irritant substances if it is necessary to crush

tabletsor open capsules.

EEA and Swiss prescriptions

Pharmacists can

dispense prescriptions issued by doctors and dentists

fromthe EuropeanEconomic Area(EEA) orSwitzerland

(exceptprescriptions for controlled drugs in Schedules

1,2, or 3, or fordrugs without a UKmarketing author-

isation).Prescriptions should bewritten in ink orother-

wiseso as tobe indelible, shouldbe dated, shouldstate

thename of thepatient, 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

individual basis by a prescriber to a speciﬁc child.

However, a Patient Group Direction for supply and

administrationof medicines byother healthcare profes-

sionals can be used where it would beneﬁt the child’s

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) and by the ScottishMedicines Con-

sortium (SMC) is included in

BNF for Children

when

relevant. If advice within aNICE 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.

BNFC 2011–2012 Generalguidance 3

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

thefull name and addressof the patient,and should be

signedin inkby the prescriber

.The ageand the dateof

birthof the childshould preferably bestated, and it isa

legalrequirement in the caseof prescription-only med-

icinesto state the agefor children under 12 years.

Wherever appropriate the prescriber should state the

currentweight ofthe childto enablethe dose prescribed

to be checked. Consideration should also be given to

includingthe doseper unit masse.g. mg/kg orthe dose

perm

body-surfacearea e.g. mg/m

wherethis would

reduceerror.

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.

Careshould be taken toensure the child receives

thecor rectdose of the active drug. Therefore, the

doseshould normallybe statedin terms ofthe mass

ofthe activedrug (e.g.‘125 mg3 timesdaily’); terms

suchas ‘5mL’ or‘1 tablet’should be avoidedexcept

forcompound preparations.

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).

(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. 5to 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).

Fora sample prescription, seebelow.

Abbreviationof titles

Ingeneral, titles of drugsand

preparationsshould be written

infull

.Unofﬁcial abbre-

viations should not beused as they may be misinter-

preted.

Non-proprietarytitles

Wherenon-proprietary (‘gen-

eric’) titles are given, they should be used for pre-

scribing. This will enable any suitable product to be

dispensed, thereby saving delay to the patient and

sometimes expense to the health service. The only

1.These recommendations are acceptablefor prescription-

onlymedicines (A). For itemsmarked 2, 3, K,

andL, see alsoPrescribing Controlled Drugs, p.9.

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

throughout

BNF for Children

; both ‘mL’ and ‘ml’ are

recognisedSI abbreviations.

4 Prescriptionwriting BNFC 2011–2012

Prescription writing

exceptionis wherethere is ademonstrable differencein

clinical effect between each manufacturer’sversion of

the formulation, making it important that the child

should always receivethe same brand;in such cases,

thebrand name or themanufacturer should be stated.

Non-proprietary namesof compound prepara-

tions

Non-proprietarynames of compoundpreparations

which appear in

BNF for Children

are those that

havebeen compiled by the British Pharmacopoeia

Commissionor another recognised body;whenever

possiblethey reﬂect the names of the active ingre-

dients.

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 duration of

action.

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).

BNFC 2011–2012 Prescriptionwriting 5

Prescription writing

Supply of medicines

Whensupplying a medicine fora child, the pharmacist

shouldensure that thechild andthe child’s carerunder-

standthe natureand identity ofthe medicineand how it

should be used. The child and the carer should be

provided with appropriate information (e.g. how long

the medicine should be takenfor and what to do if a

doseis missedor the childvomits soon afterthe dose is

given).

Safetyin the home

Carersand relatives of children

mustbe warned to keep allmedicines out of the reach

and sight of children. Tablets, capsules and oral and

external liquid preparations must be dispensed in a

reclosable

child-resistantcontainer

unless:

themedicine is in an original packor patient pack

suchas to make thisinadvisable;

the child’s carer will have difﬁculty 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 themto a pharmacyfor destruc-

tion.

Strengthand quantities

Ifa pharmacist receivesan

incompleteprescription for asystemically administered

preparation

andconsiders it would notbe appropriate

forthe patient to returnto the prescriber, thefollowing

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.

Unlicensedmedicines

Adrug or formulation thatis

notcovered bya marketing authorisation(see also

BNF

for Children

and Marketing Authorisation) may be

obtained from a pharmaceutical company, imported

bya specialist importer,manufactured bya commercial

or hospital licensed manufacturing unit(see Special-

order Manufacturers, p.809), or prepared extempora-

neously(see below) against aprescription.

The safeguardsthat apply to products with marketing

authorisationshould be extended, asfar as possible, to

the use of unlicensed medicines. The safety, efﬁcacy,

andquality (includinglabelling) ofunlicensed medicines

should be assuredby means of clear policies on their

prescribing,purchase, supply,and administration. Extra

careis required withunlicensed medicinesbecause less

information may be available on the drug and any

formulationof the drug.

Thefollowing should be agreedwith the supplier when

orderingan unlicensed or extemporaneously prepared

medicine:

thespeciﬁcation of the formulation;

documentation conﬁrming the speciﬁcation and

qualityof the product supplied (e.g.a certiﬁcate of

conformityor of analysis);

for imported preparations product and licensing

informationshould be supplied inEnglish.

Extemporaneouspreparations

Aproduct shouldbe

dispensed extemporaneously only when no product

witha marketing authorisationis available. Everyeffort

should be made to ensure that an extemporaneously

prepared product is stable and that it delivers the

requisite dose reliably; the child should be provided

with a consistent formulation regardless of where the

medicine is suppliedto minimise variations in quality.

Where there is doubt about the formulation, advice

shouldbe sought from amedicines information centre,

thepharmacy ata children’shospital, a hospitalproduc-

tionunit, a hospital quality control department, or the

manufacturer.

Inmany casesit is preferableto give alicensed product

byan unlicensed route (e.g.an injection solution given

bymouth) than toprepare a special formulation.When

tabletsor capsules are cut, dispersed, or used for pre-

paring liquids immediately before administration, it is

important to conﬁrm uniform dispersal of the active

ingredient, especially if only a portion of the solid

content (e.g. a tablet segment) isused or if only an

aliquotof the liquid isto be administered.

Insome cases thechild’s clinical conditionmay require

a dose to be administered in the absence of full infor-

mationon the methodof administration. Itis important

toensure that the appropriate supportinginformation is

availableat the earliest opportunity.

Preparationof products thatproduce harmful dust (e.g.

cytotoxic drugs, hormones, or potentially sensitising

1.With theexception of temazepam,an incompleteprescrip-

tionis not acceptable forcontrolled drugs in schedules 2

and3 of theMisuse of Drugs Regulations2001.

6 Supplyof medicines BNFC 2011–2012

Supply ofmedicines

drugs such as neomycin) should be avoidedor under-

takenwith appropriate precautions to protectstaff and

carers(see also Safety inthe Home, above).

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 15–25

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 fora particular preparation.

Seealso Water forInjections, section 9.2.2.

Labelling medicines

The

name

of the medicine

should appear on the label unless the prescriber indi-

catesotherwise; thename shown onthe label shouldbe

that written on the prescription. The

strength

should

also be stated on the label in the case of preparations

thatare available in differentstrengths.

Labelsshould indicate the

totalquantity

ofthe product

dispensedin thecontainer towhich thelabel refers.This

requirementapplies equallyto solid,liquid, internal, and

externalpreparations. If aproduct is dispensedin more

than one container, the reference should be to the

amountin each container.

BNFC 2011–2012 Supplyof medicines 7

Supply ofmedicines

Emergency supply of medicines

Emergency supply requestedby

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,quantity, and, whereappropriate, 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,quantity, and, whereappropriate, 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 requestedby

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 or optometrist

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,quantity, and, whereappropriate, 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 apatient, see

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-

gencysupply ofControlled Drugsin schedules1, 2,or 3,or

drugsthat do not havea UK marketingauthorisation.

8 Emergencysupply of medicines BNFC 2011–2012

Emergencysupply of medicines

Prescribing Controlled Drugs

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 B includes: oral amfetamines, 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 Drug prescription requirements do not

apply (but see Department of Health Guidance,

p.10) 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, 3, and4 of

theMisuse of Drugs Regulations2001 (and subsequent

amendments) are identiﬁed throughout

BNF for Chil-

dren

usingthe following symbols:

2for preparations in Schedule2;

3for preparations in Schedule3;

Kfor preparations in Schedule 4(Part I);

Lfor preparations in Schedule 4(Part II).

The principal legal requirements relating to medical

prescriptions arelisted below (see also Department of

HealthGuidance, p. 10).

Prescriptionrequirements

Prescriptions forControlled Drugs that are subject

toprescription requirements

mustbe indelible

and

must be

signed

by the prescriber,

be dated

, and

specify the prescriber’s

address

. The prescription

mustalways 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;

The words‘for dental treatment only’ if issued

bya dentist.

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 andclear lyattributable tothe pharmacist.

Failureto comply with the regulations concerning the

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

preparationssuch asmethadone mixtureshould be written

inmillilitres.

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

directed’does not.

7.Implementation date for

N.Ireland

notconﬁrmed.

BNFC 2011–2012 Prescribing Controlled Drugs 9

PrescribingControlled Drugs

writing ofprescriptions will result in inconvenience to

patientsand carersand delay insupply ofthe necessary

medicine.A prescription fora Controlled Drugin Sche-

dules2, 3, or4 is valid for28 days fromthe date stated

thereon.

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 in aninstalment prescription to cover

certainsituations; for example, if aphar macyis closed

on theday when an instalment is due. For details 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 in Walesor the NorthernIreland Central

ServicesAgency; in addition,prescriptions mustspecify

the

prescriber’sidentiﬁcation number

.Prescriptions to

besupplied bya pharmacistin hospital areexempt from

therequirement 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 is available atwww.dh.gov.uk.

Fora sample prescription, seeabove.

Dependenceand misuse

Themost serious drugsof

addiction are cocaine, diamorphine (heroin), mor-

phine,and the synthetic opioids.

Despitemarked reduction inthe prescribing ofamfeta-

minesthere is concern that abuseof illicit amfetamine

andrelated compounds is widespread.

Benzodiazepines are commonly misused. However,

themisuse of barbiturates is nowuncommon because

of theirdeclining medicinal use and consequent avail-

ability.

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 which can be

life-threatening.

Thereare concernsover increasesin theavailability and

the misuse of other drugs with variously combined

hallucinogenic, anaesthetic, or sedative properties.

These include ketamine and gamma-hydroxybutyrate

(sodiumoxybate, GHB).

Prescribingdrugs likely tocause dependence or

misuse

Theprescriber has threemain responsibilities:

toavoid creating dependenceby introducing 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 the patient does not graduallyincrease

thedose of adrug, given forgood medical reasons,

to the point where dependence becomes more

likely.The prescriber should keepa close eye on

theamount prescribed to prevent patients or their

carers from accumulating stocks. A minimal

amount should beprescribed in the ﬁrst instance,

orwhen seeing a newpatient for the ﬁrst time;

1.The prescriber mayforward-date theprescription; thestart

datemay also bespeciﬁed in thebody of theprescription.

2.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 prescribed 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.

10 PrescribingControlled Drugs BNFC 2011–2012

PrescribingControlled Drugs

toavoid beingused asan unwittingsource ofsupply

foraddicts andbeing vigilantto methods forobtain-

ingmedicines which includevisiting morethan one

doctor,fabricatingstories, andforging prescriptions.

Patients under temporary care should be given only

smallsupplies of drugs unless they present an unequi-

vocal letter from their own doctor. It is sensible to

reduce dosages steadily or to issue weekly or even

dailyprescriptions for small amounts if dependence is

suspected.

Thestealing and misuse ofprescription forms could be

minimisedby the following precautions:

(a) do not leaveunattended ifcalled awayfrom the

consultingroom or atreception desks; donot leave

ina carwhere they maybe visible; whennot inuse,

keepin a locked drawer within the surgery andat

home;

(b) draw a diagonal line across the blank part of the

formunder the prescription;

when prescribing dr ugs prone to abuse; this is

obligatory for controlled drugs (see Prescriptions,

above);

(d) alterations arebest avoidedbut ifany aremade they

should be clear and unambiguous; add initials

againstaltered items;

(e) if prescriptions areleft forcollection they shouldbe

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

details can be obtained at www.homeofﬁce.gov.uk/

drugs/licensing/personal, orfrom the Home Ofﬁce by

contacting licensing_enquiry.aadu@homeofﬁce.gsi.go-

v.uk(incases of emergency,telephone(020) 70350484).

Applications must be supported by a covering letter

fromthe prescriber and shouldgive details of:

thepatient’s name and currentaddress;

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_enquir-

y.aadu@homeofﬁce.gsi.gov.ukwith a scanned copy of

the covering letter from the prescriber. A minimum of

twoweeks should be allowed for processingthe appli-

cation.

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 wish to take Controlled Drugs abroad

while accompanying patients may similarly be issued

with licences. Licences are not normally issued to

doctors who wish 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

with the Misuse of Dr ugs Act and facilitate passage

throughUK Customs and Excisecontrol. For clearance

in the country to be visited it would be necessary to

approachthat country’s consulate inthe UK.

Notiﬁcation of drug misusers

Doctors should report cases of drug misuse to their

regionalor national drug misuse database or centre—

forfurther advice and contact telephonenumbers con-

sultthe BNF.

BNFC 2011–2012 Prescribing Controlled Drugs 11

PrescribingControlled Drugs

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.

Thereporting of all suspected adverse drug reactions,

no matter how minor, in children under 18 years,

including those relating to unlicensed or off-label use

ofmedicines, is strongly encouraged throughthe Yel-

low Card Scheme even if the intensive monitoring

symbol (T, see below) has been removed. This is

becauseexperience in children maystill be 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;

drugsmay not be extensivelytested in children;

childrenmay bemore susceptibleto developmental

disordersor they may have delayed adverse reac-

tionswhich do not occurin adults;

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.

Spontaneous reporting is particularly valuable for

recognising possible new hazards rapidly. An adverse

reactionshould be reportedeven if it isnot certain that

thedr ughas caused it, or if thereaction is well recog-

nised, or if other drugs have been given at the same

time.Reports ofoverdoses (deliberateor accidental)can

complicate the assessment of adverse drug reactions,

but provide important information on the potential

toxicityof drugs.

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,North

West

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.

MHRADrug Safety Update

DrugSafety Updateis amonthly newsletterfrom the

MHRA andthe Commission on Human Medicines

(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

electronic form at www.yellowcard.gov.uk or by tele-

phoneon 0808 100 3352. Alternatively, patientYellow

Cardsare available from pharmaciesand GP surgeries,

or can be downloaded from www.mhra.gov.uk,where

moredetailed information on patientreporting is avail-

able. Information for patients about theYellow 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 andvaccines

Onlylimited information

is available from clinical trialson the safety of new

medicines. Further understanding about the safety of

12 Adversereactions to drugs BNFC 2011–2012

Adverse reactionsto drugs

medicines depends on the availability ofinformation

fromroutine clinical practice.

Theblack triangle symbol(T) identiﬁesnewly licensed

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

established risks and beneﬁts of that drug, or that

contain a new combination of active substances.

There isno standard time for which products retain a

blacktriangle; safety data are usually reviewed after 2

years.

Adverse reactionsto 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 for Children

The

BNFfor

Children

includes clinically relevant side-effects for

most drugs; an exhaustive list is not included for

drugs thatare used by specialists (e.g. cytotoxicdrugs

anddrugs usedin anaesthesia). Wherecausality hasnot

beenestablished, side-effects in the manufacturers’ lit-

eraturemay be omitted fromthe

BNFfor Children

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

BNFfor Children]

1in 1000 to 1 in 100

Rare 1 in 10 000 to 1 in 1000

Veryrare less than 1 in 10 000

Special problems

Symptoms

Children may be poor at expressing the

symptoms of an adverse drug reaction and parental

opinionmay be required.

Delayed drug effects

Some reactions (e.g.cancers

and effects on development) may become manifest

monthsor years after exposure. Any suspicionof such

anassociation shouldbe reported directlyto theMHRA

throughthe Yellow CardScheme.

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.

Prevention of adversereactions

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

adverse drug reactions. Ask if the child has had

previousreactions to the drug orformulation;

prescribe as few drugs as possible and give very

clearinstructions to the child, parent,or carer;

whenever possibleuse a familiar drug; with anew

drug be particularly alert for adverse reactions or

unexpectedevents;

considerif excipients(e.g. colouringagents) may be

contributingto the adversereaction. If the reaction

isminor, a trial ofan alternative formulation ofthe

same drug may be considered before abandoning

thedrug;

obtain a full drug histor y including asking if the

childis already taking other drugs

includingover-

the-countermedicines

;interactions may occur;

age and hepatic or renal disease may alter the

metabolism or excretion of drugs, particularlyin

neonates,which canaffect the potentialfor adverse

effects.Genetic factors may alsobe responsible for

variations in metabolism, and therefore for the

adverseeffects of the drug;

warn the child, parent, or carer if serious adverse

reactionsare liable to occur.

Defective medicines

Duringthe manufactureor distribution ofa medicine an

erroror accident may occur whereby theﬁnished pro-

ductdoes not conformto itsspeciﬁcation. While sucha

defectmay impair the therapeuticeffect of the product

and could adversely affect the health ofa patient,it

shouldnot be confusedwith an AdverseDrug Reaction

wherethe product conforms toits speciﬁcation.

TheDefective Medicines ReportCentre assists withthe

investigationof problems arising from licensed medic-

inalproducts thought to be defective and co-ordinates

any necessary protective action. Reports on suspect

defectivemedicinal products should include the brand

orthe non-proprietary name,the name ofthe manufac-

turer orsupplier, the strength and dosage form of the

product,the product licencenumber, the batchnumber

ornumbers of theproduct, thenature of thedefect, and

anaccount of anyaction already takenin consequence.

TheCentre can be contactedat:

TheDefective Medicines Report Centre

Medicinesand Healthcare productsRegulatory Agency

151Buckingham Palace Road

London,SW1W 9SZ

Tel:(020) 3080 6588

info@mhra.gsi.gov.uk

BNFC 2011–2012 Adverse reactions to drugs 13

Adverse reactionsto drugs

Prescribing in hepatic impairment

Children have a large reserve of hepatic metabolic

capacityand modiﬁcation of the choice and dosageof

drugsis usually unnecessary evenin apparently severe

liverdisease. However,special considerationis required

inthe following situations:

liverfailure characterisedby severederangement of

liver enzymes and profound jaundice; the useof

sedativedrugs, opioids, anddrugs such asdiuretics

and amphotericin which produce hypokalaemia

mayprecipitate hepatic encephalopathy;

impairedcoagulation, which can affectresponse to

oralanticoagulants;

incholestatic jaundiceelimination may beimpaired

ofdr ugssuch as fusidic acid and rifampicin which

areexcreted in the bile;

in hypoproteinaemia, the effect of highly protein-

bounddrugs suchas phenytoin, prednisolone,warf-

arin,and benzodiazepines may beincreased;

use of hepatotoxic drugs is more likelyto cause

toxicity in children with liver disease; such drugs

shouldbe avoided if possible;

inneonates, particularlypreterm neonates,and also

ininfants metabolicpathways maydif ferfrom older

childrenand adults becauseliver enzyme pathways

maybe immature.

Where care is needed when prescribing in hepatic

impairment, this is indicated under the relevant drug

BNFfor Children

Prescribing in renal impairment

Theuse ofdrugs in childrenwith reducedrenal function

cangive rise to problemsfor several reasons:

reducedrenal excretion ofa drug orits metabolites

mayproduce toxicity;

sensitivityto some drugs is increasedeven if elim-

inationis unimpaired;

manyside-ef fects aretolerated poorly by children

withrenal impairment;

somedrugs are noteffective when renalfunction is

reduced;

neonates,particularly preterm, mayhave immature

renalfunction.

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-

effects,very precise modiﬁcationof thedose regimen is

unnecessaryand a simplescheme for dose reductionis

sufﬁcient

Formore toxic drugs with a small safety margin dose

regimensbased on glomerular ﬁltration rate should be

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.

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-stateplasma concentration. Becausethe plasma

half-lifeof drugs excretedby the kidney isprolonged in

renalimpairment, itcan takemany doses atthe reduced

dosageto achieve a therapeutic plasma concentration.

The loading dose should usually be the same asthe

initialdose for a childwith normal renal function.

Nephrotoxic drugs should, if possible, be avoided in

childrenwith renaldisease becausethe consequencesof

nephrotoxicityare likely to be more serious when the

renalreserve is already reduced.

Glomerular ﬁltration rateis low at birth and increases

rapidlyduring theﬁrst 6 months.Thereafter, glomerular

ﬁltrationrate increasesgradually toreach adultlevels by

1–2years of age, when standardised to a typicaladult

bodysurface area(1.73 m

).In theﬁrst weeksafter birth,

serumcreatinine falls; asingle measure of serumcreat-

inine providesonly a crude estimate of renal function

andobserving the change over days isof more use. In

the neonate,a sustained rise in serum creatinine or a

lackof the expectedpostnatal decline, isindicative of a

reducedglomerular ﬁltration rate.

Dose recommendations are based on the severityof

renalimpair ment.This is expressed in terms of glom-

erular ﬁltrationrate (mL/minute/1.73m

Thefollowing equations provide a guide toglomerular

ﬁltrationrate.

Childover 1 year:

Estimated glomerular ﬁltration rate (mL/minute/

1.73m

)= 40

 height (cm)/serum creatinine (micr-

omol/litre)

Neonate:

Estimated glomerular ﬁltration rate (mL/minute/

1.73m

)= 30

 height (cm)/serum creatinine (micr-

omol/litre)

Theserum-creatinine concentration is sometimes used

asa measureof renal functionbut isonly ar oughguide

evenwhen corrected for age,weight, and sex.

1.The values usedin these formulasmay differ accordingto

localityor laboratory.

14 Prescribingin hepatic impairment BNFC 2011–2012

Prescribingin hepatic impairment

Important

The information on dose adjustment in

BNF for

Children

is expressed in terms of estimated glom-

erularﬁltration rate.

Renal function in adults is increasingly being

reported as estimated glomerular ﬁltration rate

(eGFR) normalised to a body surface area of

1.73m

;however, eGFR is derivedfrom the MDRD

(Modiﬁcation of Diet in Renal Disease) formula

which is not validated for use in children. eGFR

derived from the MDRD formula should not be

used to adjust drug doses in children with renal

impairment.

BNF for Children

, values for measures of renal

functionare included where possible. However, where

such values are not available, the

BNF for Children

reﬂectsthe terms used in thepublished information.

Chronic kidney disease in

adults: UK guidelines for

identiﬁcation, management and referral (March

2006)deﬁnes renal function asfollows:

Degreeof impairment eGFR

mL/minute/1.73m

Normal:Stage 1 Morethan 90 (with other

evidenceof kidney damage)

Mild:Stage 2 60–89(withother evidence

ofkidney damage)

Moderate

:Stage 3 30–59

Severe:Stage 4 15–29

Establishedrenal failure:

Stage5

Lessthan 15

1.Estimated glomerular ﬁltration rate (eGFR) derived from

theModiﬁcation of Diet in Renal Disease (MDRD) formula

foruse in patients over 18 years

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

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

30–44

Dialysis

For prescribing in children on renal replacement

therapyconsult specialist literature.

Drugprescribing should be kept tothe minimum in all

childrenwith 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 relevantdrug in

BNF

forChildren

BNFC 2011–2012 Prescribingin renal impairment 15

Prescribingin renal impairment

Prescribing in pregnancy

Drugscan have harmfuleffects on thefetus at anytime

during pregnancy.It is important to bear this in mind

whenprescribing fora female of

childbearingage

orfor

men

tryingto father

achild.

Duringthe

ﬁrsttrimester

drugsmay 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

drugsmay affect

thegrowth and functional development of the fetusor

have toxic effects on fetal tissues; and drugs given

shortlybefore term or duringlabour may have adverse

effectson labour or onthe neonate after delivery.

BNFfor Children

identiﬁesdrugs which:

may have harmful effects in pregnancy and indi-

catesthe trimester of risk;

arenot known to behar mfulin pregnancy.

Theinfor mationis based on human data but informa-

tion on

animal

studies has been included for some

drugswhen its omissionmight be misleading. Maternal

drug doses may require adjustment during pregnancy

due to changes in maternal physiology but this is

beyondthe scope of

BNFfor Children

Where care isneeded when prescribing in pregnancy,

this is indicated under the relevant drugin

BNF for

Children

Important

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

teratogenic in humans but no drug is safe beyond

alldoubt in early pregnancy. Screening procedures

areavailable where there is aknown risk of certain

defects.

Absenceof information does not implysafety.

Itshould be noted that

BNFfor Children

provides

independentadvice and may notalways agree with

theproduct literature.

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

Outsideof these hours, urgentenquiries 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);

theef ﬁciencyof absorption, distribution and elim-

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).

Most medicines given to a mother cause no harm to

breast-fed infantsand there are few contra-indications

to breast-feeding when maternal medicines are neces-

sary.However, administrationof some drugsto nursing

mothers can harm the infant. Inthe ﬁrst week of life,

some such as preterm or jaundiced infants are at a

slightlyhigher risk of toxicity.

Toxicityto the infant can occur if the drug enters the

milk in pharmacologically signiﬁcant quantities. The

concentration in milk of some drugs (e.g. ﬂuvastatin)

may exceed the concentration in maternal plasma so

thattherapeutic doses in themother can cause toxicity

to the infant. Some drugs inhibit the infant’ssucking

reﬂex(e.g. phenobarbital) whileothers can affect lacta-

tion (e.g.bromocriptine). Drugs in breast milk may, at

least theoretically,cause hypersensitivity inthe infant

even when concentration is too low fora phar macol-

ogicaleffect.

BNFfor Children

identiﬁesdrugs:

which should be used with caution or which are

contra-indicated in breast-feeding for the reasons

givenabove;

which, on present evidence, may be given to the

motherduring breast-feeding, because theyappear

in milk in amounts which are too small to be

harmfulto the infant;

which are not known to be harmful to the infant

although they are present in milk in signiﬁcant

amounts.

Wherecare is needed when prescribingin breast-feed-

ing,this is indicatedunder the relevantdrug in

BNFfor

Children

Important

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 breastmilk informationin

BNFfor Children

shouldbe used onlyas a guide;absence of informa-

tiondoes not imply safety.

16 Prescribingin pregnancy BNFC 2011–2012

Prescribingin pregnancy

Prescribing in palliative care

Palliativecare isthe active total care of children and

young adults who have incurable, life-limitingcondi-

tions and are not expected to survive beyond young

adulthood.

The child may be cared for in a hospice or at home

accordingto theneeds ofthe childand thechild’s family.

In allcases, children should receive total care of their

physical,emotional, social,and spiritualneeds, andtheir

familiesshould be supported throughout. In particular,

specialistpalliative care is essential for end-of-lifecare

ofthe child andfor supporting thefamily through death

andbereavement.

Drug treatment

The numberof dr ugsshould be as

fewas possible. Oral medication is usuallyappropriate

unlessthere is severe nausea andvomiting, dysphagia,

weakness,or coma,when parenteralmedication maybe

necessary.

Pain

Analgesicsare moreef fectivein preventingpain than in

therelief ofestablished pain;it isimportant that theyare

givenregularly.

Paracetamol(p. 200)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

bone secondaries

. Radiotherapy and bisphosphonates

(section6.6.2) may also be usefulfor pain due to bone

metastases.

An opioid analgesic (section 4.7.2) such as codeine

(p.204), 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 notsuf ﬁcient.If these preparations do not control

the pain, morphine (p.207) is the most useful opioid

analgesic.Alternatives to morphine,including transder-

malfentanyl (see below and p.206), are best initiated

bythose with experience inpalliative care. Initiation of

an opioid analgesic should not be delayed by concern

overa theoreticallikelihood ofpsychological orphysical

dependence(addiction).

Equivalentsingle dosesof opioid analgesics

Theseequivalences areintended only asan approximate

guide;patients should be carefully monitored after any

changein medication and dose titration may be required

Analgesic Dose

Morphinesalts (oral) 10mg

Diamorphinehydrochloride (subcutaneous) 3 mg

Hydromorphonehydrochloride 1.3mg

Oxycodone(oral) 5mg

Oralroute

Morphine(p. 207) isgiven

bymouth

asan

oralsolution oras standard (‘immediaterelease’) tablets

regularly every 4 hours, the initial dose depending

largelyon the patient’s previous treatment. If the ﬁrst

doseof morphineis no moreeffective than theprevious

analgesic,the nextdose shouldbe increasedby 30–50%,

theaim being to choose the lowestdose that prevents

pain.The dose should be adjusted withcareful assess-

ment of the pain, and the use of adjuvant analgesics

(suchas NSAIDs) should also be considered.Although

low doses of morphine are usually adequate there

shouldbe no hesitation inincreasing the dose stepwise

accordingto response if necessary.

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

morphinerequirement is established,the dailydose can

be given as a single dose or in 2 divided doses as a

modiﬁed-release preparation

. The ﬁrst dose of the

modiﬁed-releasepreparation is given with, or within 4

hours of, the last dose of the oral solution. The child

shouldbe reviewed regularlyfor treatment efﬁcacyand

side-effects.

MST Continus

tablets or suspension (p. 209) are

designedfor twicedaily administration;

MXL

capsules

(p.209) allowadministration of thetotal dailymor phine

requirementas a single dose.

Alternatively, a

modiﬁed-release preparation

may be

commencedimmediately andthe doseadjusted accord-

ing to pain control. The starting dose of modiﬁed-

release preparationsdesigned for twice daily adminis-

tration is usually 200–800 micrograms/kg every 12

hours if no other analgesic (or only paracetamol) has

been takenpreviously, but to replace a weaker opioid

analgesic(such as codeine) the starting doseis usually

higher.Increments should be made tothe dose, not to

thefrequency ofadministration, which shouldremain at

every12 hours.

If pain occurs between regular doses of morphine

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

dose’)should be given. An additional doseshould also

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 child should be

assessedon an individual basis.

Children often require a higher doseof morphine in

proportion to their body-weight compared to adults.

Childrenare moresusceptible to certainadverse effects

ofopioids suchas urinaryretention (which canbe eased

bycarbachol or bethanechol), and opioid-induced pru-

ritus.

Oxycodone(p. 209) is usedin a child who requiresan

opioid but cannot tolerate morphine. If the child is

already receiving an opioid, oxycodone should be

started at a dose equivalent to the current analgesic

(seeabove).

Parenteralroute

Diamorphine (p.205) is preferred

forinjection because,being moresoluble, itcan begiven

ina smaller volume.The equivalent subcutaneousdose

is approximatelya third of the oral dose of morphine.

Subcutaneousinfusion

ofdiamorphine viaa continuous

infusiondevice can be useful(for details, see p.19).

Ifthe childcan resume takingmedicines bymouth, then

oral morphine may be substituted for subcutaneous

infusion of diamorphine. See table of approximate

equivalentdoses of morphine anddiamor phine,p. 21.

BNFC 2011–2012 Prescribing in palliative care 17

Prescribingin palliative care

Rectal route

Morphine (p.209) is also available for

rectaladministration

assuppositories.

Transdermal route

Transdermal preparations of

fentanyl(p. 206) are available;they are not suitable for

acutepain orin those childrenwhose analgesic require-

ments are changing rapidly because the long time to

steady state prevents rapid titration of the dose. Pre-

scribers should ensure that they are familiar with the

correct use of transdermal preparations (see under

fentanyl,p. 206) 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 by loperamide (p. 47). Hyoscine hydro-

bromide (p.198) may also behelpful in reducingthe

frequencyof spasms;it is givensublingually ata dose of

10micrograms/kg (max.300 micrograms)3 times daily

Kwells

tablets. For the dose by subcutaneous

infusion,see p. 20.

Gastricdistension pain due topressure on thestomach

maybe helped by apreparation incorporating an anta-

cidwith an antiﬂatulent(p. 36) anda prokinetic suchas

domperidone(p. 41) before meals.

Muscle spasm

The pain of muscle spasm can be

helpedby a muscle relaxant suchas diazepam (p. 515)

orbaclofen (p. 514).

Neuropathic pain

Patients with neuropathic pain

(p.212) maybeneﬁt froma trial ofa tricyclicantidepres-

sant,most commonly amitriptyline (p.185), for several

weeks. An anticonvulsant, such as carbamazepine

(p.218), may be added or substituted if pain persists.

Ketamine is sometimes used under specialist supervi-

sionas an adjuvant for neuropathicpain that responds

poorlyto opioid analgesics.

Paindue to ner ve compression may be reduced by a

corticosteroid such as dexamethasone, which reduces

oedemaaround thetumour, thusreducing 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

Anorexiamay be helpedby prednisolone or

dexamethasone.

Anxiety

Anxiety can be treated with a long-acting

benzodiazepine such as diazepam, or by continuous

infusionof the short-acting benzodiazepinemidazolam.

Interventionsfor more acute episodes of anxiety(such

as panicattacks) include short-acting benzodiazepines

such as lorazepam given sublingually or midazolam

given subcutaneously. Temazepam provides useful

night-timesedation in some children.

Capillarybleeding

Capillarybleeding can betreated

with tranexamic acid (p. 123) by mouth; treatment is

usuallycontinued for one week after the bleeding has

stopped but it can be continued at a reduced dose if

bleedingpersists. Alternatively,gauze soaked intranex-

amicacid 100mg/mL or adrenaline(epinephrine) solu-

tion1 mg/mL(1 in 1000)can be appliedto the 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).

Constipation

Constipation is a common cause of

distressand is almost invariableafter administration of

anopioid analgesic.It shouldbe preventedif possibleby

the regular administration of laxatives. Suitable laxa-

tivesinclude osmoticlaxatives (p. 61)(such as lactulose

or macrogols), stimulant laxatives (p.59) (such as co-

danthramerand senna) or thecombination of lactulose

anda sennapreparation. Naloxonegiven by mouthmay

help relieve opioid-induced constipation; it is poorly

absorbed but opioid withdrawal reactions have been

reported.

Convulsions

Intractable seizuresare relatively com-

mon inchildren dying from non-malignant conditions.

Phenobarbital by mouth or as a continuous subcuta-

neousinfusion maybe beneﬁcial;continuous infusion of

midazolamis analternative. Both causedrowsiness, but

this is rarely a concern inthe context of intractable

seizures. For breakthrough convulsions diazepam

(p.232) given rectally(as asolution), buccal midazolam

(p.234), or paraldehyde (p. 234) as an enema may be

appropriate.

For the use of midazolam by subcutaneous infusion

usinga continuous infusion device,see p. 20.

Dry mouth

Dry mouth may be caused by certain

medicationsincluding opioid analgesics,antimuscarinic

drugs (e.g. hyoscine), antidepressants and some anti-

emetics;if possible,an alternativepreparation shouldbe

considered.Dry mouth maybe relieved bygood mouth

care and measures such as chewingsugar-free gum,

suckingice or pineapple chunks, orthe use of artiﬁcial

saliva (p.548); dry mouth associatedwith candidiasis

canbe treated by oral preparationsof nystatin (p. 546)

or miconazole (p. 545); alternatively, ﬂuconazole

(p.301) can be givenby mouth.

Dysphagia

A corticosteroidsuch as dexamethasone

mayhelp, temporarily, ifthere is an obstruction due to

tumour.See also Dry Mouth,above.

Dyspnoea

Breathlessnessat rest may be relieved by

regularoral morphine incarefully titrated doses.Diaze-

pam may be helpful for dyspnoea associated with

18 Prescribingin palliative care BNFC2011–2012

Prescribingin palliative care

anxiety. Sublingual lorazepam or subcutaneous or

buccal midazolam are alternatives. A nebulised short-

actingbeta

agonist(section 3.1.1.1) ora corticosteroid

(section3.2), such as dexamethasone or prednisolone,

may also be helpful for bronchospasm or partial

obstruction.

Excessive respiratory secretion

Excessive respir-

atory secretion (death rattle)may be reduced by hyo-

scine hydrobromide patches (p.198) or by subcuta-

neous or intravenous injection of hyoscine

hydrobromide 10micrograms/kg (max. 600 micr-

ograms) every 4 to 8hours; however,care must be

taken to avoid the discomfort of dry mouth. Alterna-

tively,glycopyrronium (p.636) may be given.

For the administration of hyoscinehydrobromide by

subcutaneous orintravenous infusion using a continu-

ousinfusion device, see p.20.

Fungatingtumours

Fungatingtumours can be trea-

tedby regulardressing andantibacterial drugs;systemic

treatmentwith metronidazole (p. 296)is often required

toreduce malodour, but topical metronidazole(p. 587)

isalso used.

Hiccup

Hiccupdue togastric distensionmay behelped

bya preparation incorporating anantacid with an anti-

ﬂatulent(p. 37).

Hypercalcaemia

Seesection 9.5.1.2.

Insomnia

Children with advanced cancer may not

sleepbecause of discomfort,cramps, nightsweats, joint

stiffness,or fear.There should beappropriate treatment

of these problems before hypnotics (p.169) are used.

Benzodiazepines,such as temazepam, maybe useful.

Intractablecough

Intractablecough may berelieved

bymoist inhalationsor by regularadministration of oral

morphine every4 hours. Methadone linctus should be

avoided because it has a long duration of action and

tendsto accumulate.

Mucosalbleeding

Mucosalbleeding from themouth

and nose occurs commonly in the terminal phase,

particularly in a child suffering from haemopoeitic

malignancy.Bleeding from thenose caused by a single

bleeding point can be arrested by cauterisation or by

dressing it.Tranexamic acid (p. 123) may be effective

appliedtopically or given systemically.

Nausea and vomiting

Nausea and vomiting are

commonin children with advanced cancer.Ideally, the

cause should bedeter mined beforetreatment with an

antiemetic(section 4.6) is started.

Nauseaand vomiting withopioid therapy areless com-

monin children than in adults but may occur particu-

larlyin the initialstages andcan be preventedby giving

anantiemetic. An antiemetic is usually necessary only

for the ﬁrst 4 or 5 days and therefore combined pre-

parations containing an opioid withan antiemetic are

not recommended because they lead to unnecessary

antiemetic therapy (and associated side-effects when

usedlong-term).

Metoclopramidehas a prokinetic actionand is used by

mouthfor nauseaand vomitingassociated withgastritis,

gastricstasis, and functional bowel obstruction. Drugs

withantimuscarinic effects antagonise prokineticdrugs

and, if possible, should not therefore be used concur-

rently.

Haloperidol(p. 174) isused by mouthor by continuous

intravenousor subcutaneous infusion for most metab-

oliccauses of vomiting (e.g.hypercalcaemia, renal fail-

ure).

Cyclizine(p. 193)is usedfor nauseaand vomitingdue to

mechanicalbowel obstruction, raised intracranial pres-

sure,and motion sickness.

Ondansetron(p. 197) is most effectivewhen the vomi-

tingis dueto damagedor irritated gutmucosa (e.g.after

chemotherapyor radiotherapy).

Antiemetictherapy should bereviewed every 24hours;

it maybe necessary to substitute the antiemetic or to

addanother one.

Levomepromazine(p. 175) canbe used ifﬁrst-line anti-

emeticsare inadequate. Dexamethasone bymouth can

beused as an 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 (p.552). Ondansetron may

beeffective in some children. Where opioidanalgesics

causepruritus it maybe appropriate toreview the dose

or to switch to an alternative opioid analgesic. In the

case ofobstr uctivejaundice, further measures include

administrationof colestyramine (p. 70).

Raised intracranial pressure

Headache due to

raised intracranial pressure often responds to a high

doseof a corticosteroid, such as dexamethasone,for 4

to 5 days, subsequently reduced if possible; dexa-

methasoneshould be given before6 p.m.to reduce the

risk of insomnia. Treatmentof headache and of asso-

ciatednausea and vomiting shouldalso be considered.

Restlessnessand confusion

Restlessnessand con-

fusionmay require treatment with haloperidol (p. 174)

10–20micrograms/kg by mouth every 8–12 hours.

Levomepromazine (p. 175) is also used occasionally

forrestlessness. See also p.20.

Continuousinfusion devices

Althoughdr ugscan usually be administered

bymouth

to control symptoms in palliative care, the parenteral

routemay sometimes be necessary.Repeated adminis-

trationof

intramuscularinjections

shouldbe avoided in

children,particularly ifcachectic. Thishas led tothe use

ofportable continuous infusiondevices such as syringe

drivers to give a

continuous subcutaneous infusion

BNFC 2011–2012 Prescribing in palliative care 19

Prescribingin palliative care

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:

inability to take medicines by mouth owing to

nauseaand vomiting, dysphagia, severe weakness,

coma;

malignant bowel obstruction

for which surgery is

inappropriate(avoiding theneed for anintravenous

infusionor for insertion ofa nasogastric tube);

refusal bythe child to take regular medication by

mouth.

Bowelcolic andexcessive respiratory secretions

Hyoscine hydrobromide (p.198) effectively reduces

respiratorysecretions and is sedative (butoccasionally

causes paradoxicalagitation); it is given in a

subcuta-

neous

intravenous infusion dose

of 40–60 micr-

ograms/kg/24hours. Glycopyrronium (p.636) may

alsobe used.

Hyoscine butylbromide (p. 40) is effective in bowel

colic,is less sedative than hyoscine hydrobromide,but

is not always adequate for the control ofrespiratory

secretions;it is givenby

subcutaneousinfusion

(impor-

tant:

hyoscinebutylbromide

mustnot be confusedwith

hyoscinehydrobromide

,above).

Convulsions

Ifa child has previously been 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 (p.234) is thebenzodiazepine anti-

epileptic of choice for

continuous subcutaneous infu-

sion

Nausea and vomiting

Levomepromazine (p. 175)

causes sedationin about 50% of patients. Haloperidol

(p.174) has little sedativeeffect.

Cyclizine (p.193) is particularly likely to precipitate if

mixed with diamorphine or other drugs (see under

Mixingand Compatibility); it is given by

subcutaneous

infusion

Pain control

Diamorphine (p.205) isthe preferred

opioidsince itshigh solubilityper mitsa largedose tobe

givenin asmall volume (seeunder Mixingand Compat-

ibility). Thetable on p. 21 shows approximate equiva-

lentdoses of morphine and diamorphine.

Restlessness and confusion

Haloperidol haslittle

sedativeef fect.Levomepromazine (p. 175) has a seda-

tiveeffect. Midazolam isa sedative andan antiepileptic

thatmay be suitable fora very restless patient.

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

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.

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.

20 Prescribingin palliative care BNFC2011–2012

Prescribingin palliative care

Equivalentdoses of morphine sulphate and

diamorphinehydrochloride given over 24

hours

Theseequivalences areapproximate only andmay

needto be adjustedaccording toresponse

MORPHINE

PARENTERAL

DIAMORPHINE

Oral

morphine

sulphate

Subcutaneous

infusionof

morphinesulphate

Subcutaneous

infusionof

diamorphine

hydrochloride

over24 hours over24 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

injectionequivalent to one-tenth to one-sixth of the

total24-hour subcutaneous infusion dose. With an

intermittentsubcutaneous injection absorption is

smootherso that the risk of adverse effects at peak

absorptionis avoided (an even better method is to use

asubcutaneous butterﬂy needle).

Tominimise the risk of infection no subcutaneous

infusionsolution should be used for longer than 24

hours.

BNFC 2011–2012 Prescribing in palliative care 21

Prescribingin palliative care

Prescribing in dental practice

Adviceon the drug management ofdental and oral

conditionsis covered in the main text. For ease of

access,guidance on suchconditions is usuallyiden-

tiﬁedby meansof arelevant heading(e.g. Dentaland

OrofacialPain) in the appropriatesections.

Thefollowing isa listof topics ofparticular relevanceto

dentalsurgeons.

Generalguidance

Prescribingby dental surgeons, seeBNF

Oralside-effects of drugs, see BNF

Medicalemergencies in dental practice,see BNF

Medicalproblems in dental practice,see BNF

Drug managementof dental and oralconditions

Dentaland orofacial pain, p.199

Neuropathicpain, p. 212

Non-opioidanalgesics and compound analgesic

preparations,p. 199

Opioidanalgesics, p. 204

Non-steroidalanti-inﬂammator ydrugs, p. 500

Oralinfections

Bacterialinfections, p. 244

Phenoxymethylpenicillin,p. 258

Broad-spectrumpenicillins (amoxicillin and

ampicillin),p. 261

Cephalosporins(cefalexin and cefradine),

p.266

Tetracyclines,p. 274

Macrolides(clarithromycin, erythromycin and

azithromycin),p. 280

Clindamycin,p. 283

Metronidazole,p. 296

Fusidicacid p. 587

Fungalinfections, p. 545

Localtreatment, p. 545

Systemictreatment, p. 300

Viralinfections, p. 545

Herpeticgingivostomatitis, local treatment,

p.545

Herpeticgingivostomatitis, systemictreatment,

p.321 and p.545

Herpeslabialis, p. 591

Anaesthetics,anxiolytics and hypnotics

Anaesthesia,sedation, and resuscitationin dental

practice,p. 629

Hypnotics,p. 170

Sedationfor dental procedures, p.637

Localanaesthesia, p. 649

Oralulceration and inﬂammation, p.543

Mouthwashesand gargles, p. 546

Dry mouth,p. 548

Minerals

Fluorides,p. 476

Aromaticinhalations, p. 166

Nasaldecongestants, p. 541

DentalPractitioners’ Formulary, p.794

22 Prescribingin dental practice BNFC 2011–2012

Prescribingin dental practice

Drugs and sport

UKAnti-Doping, the national body responsible for the

UK’santi-doping policy, advises that athletes are per-

sonally responsible should a prohibited substance be

detectedin their body.An advice card listingexamples

of permitted and prohibited substances is available

from:

UKAnti-Doping

OceanicHouse

1aCockspur Street

London SW1Y 5BG

Tel:(020) 7766 7350

information@ukad.org.uk

www.ukad.org.uk

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.

BNFC 2011–2012 Drugs and sport 23

Drugs andsport

Emergency treatment of

poisoning

Thesenotes provide onlyan overview of thetreatment

ofpoisoning and itis strongly recommendedthat either

TOXBASEor the UKNational Poisons Information

Service (see below)be consulted when there is doubt

aboutthe degree of risk or aboutappropriate manage-

ment.

Most childhood poisoning is accidental. Other causes

includeintentional overdose,drug abuse,iatrogenic and

deliberate poisoning. The drugs most commonly

involvedin childhood poisoning are paracetamol, ibu-

profen, orally ingested creams, aspirin, iron prepara-

tions,cough medicines, and thecontraceptive pill.

Hospital admission

Children who havefeatures of

poisoning should generally be admitted to hospital.

Childrenwho have taken poisons with delayedactions

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 Internetto registered 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 childrenrequire activeremoval ofthe poison.

In most children, 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

sought fromthe poisoned child and from their carers.

However,such information should be interpreted with

carebecause itmay notbe complete orentirely reliable.

Sometimes symptoms arise from other illnesses, and

children should be assessed carefully. Accidents may

involvea number of domestic and industrial 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 inunconscious children.

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 children with reduced consciousness to prevent

obstruction,provided ventilationis adequate.Intubation

andventilation should beconsidered in children whose

airway cannot be protected or who have respiratory

acidosis because of inadequate ventilation; such chil-

drenshould 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.

The potentialfor pulmonary aspiration of gastric con-

tentsshould be considered.

Blood pressure

Hypotensionis common in severe poisoningwith cen-

tralnervous system depressants;if severe thismay lead

to ir reversible braindamage or renal tubular necrosis.

Hypotensionshould be correctedinitially by raisingthe

foot of the bed and administration of either sodium

chloride intravenous infusion or a colloidal infusion.

Vasoconstrictor sympathomimetics (section 2.7.2) are

rarelyrequired and theiruse may bediscussed with the

NationalPoisons Information 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-

24 BNFC 2011–2012

Emergencytreatment of poisoning

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 may require treatment (section 2.3.1). If the

QT interval is prolonged, specialist advice should be

soughtbecause the use of some anti-arrhythmic drugs

maybe inappropriate. Supraventriculararrhythmias are

seldomlife-threatening anddr ugtreatment isbest with-

helduntil the child reacheshospital.

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 children taking CNS

stimulants; children are also at risk when taking ther-

apeutic dosesof drugs with antimuscarinic properties.

Hyperthermia is initially managed by removing all

unnecessary clothing and using a fan. Sponging with

tepidwater willpromote evaporation. Adviceshould be

sought fromthe National Poisons Information Service

on the management of severe hyperthermia resulting

fromconditions such as theserotonin syndrome.

Both hypothermia and hyperthermia require urgent

hospitalisation for assessment and supportive treat-

ment.

Convulsions

Singleshort-lived convulsionsdo not requiretreatment.

Ifconvulsions areprotracted or recurfrequently, loraze-

pam100 micrograms/kg(max. 4mg) or diazepam(pre-

ferably as emulsion) 300–400 micrograms/kg (max.

20mg) should be given by slow intravenous injection

intoa large vein. Benzodiazepines should notbe given

bythe intramuscular route forconvulsions. If the intra-

venousroute is not readily available, midazolam [unli-

censeduse] can be given bythe buccal route or diaze-

pam can beadministered as a rectal solution (section

4.8.2).

Removal and elimination

Prevention of absorption

Given by mouth, acti-

vated charcoal can adsorb many poisons in the gas-

tro-intestinalsystem, thereby

reducingtheir absorption

Thesooner itis giventhe moreeffective itis, butit may

still be effective up to 1 hour after ingestion of the

poison—longerin the caseof modiﬁed-releaseprepara-

tions or of drugs with antimuscarinic (anticholinergic)

properties.It is particularly usefulfor the prevention of

absorption of poisons that are toxic in small amounts

suchas antidepressants.

A second dose may occasionally be required when

blood-drug concentration continues to rise suggesting

delayeddrug release or delayedgastric emptying.

Forthe useof charcoal inactive eliminationtechniques,

seebelow.

Active elimination techniques

Repeated doses of

activated charcoal by mouth may

enhance the elim-

ination

of somedrugs after they have been absorbed;

repeateddoses are given afteroverdosage with:

Carbamazepine

Dapsone

Phenobarbital

Quinine

Theophylline

Vomiting should be treated (e.g. with an antiemetic

drug) since it may reduce the efﬁcacy of charcoal

treatment. In cases of intolerance,the dose may be

reduced and the frequency increased but this may

compromiseefﬁcacy.

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.

Removalfrom the gastro-intestinal tract

Gastric

lavageis rarelyrequired asbeneﬁt rarely outweighs risk;

advice should be sought from the National Poisons

Information Service if a signiﬁcant quantityof iron or

lithiumhas been ingested withinthe previous hour.

Wholebowel irrigation

(bymeans of abowel cleansing

preparation) has been used in poisoning with certain

modiﬁed-release or enteric-coated formulations, in

severe poisoning with lithium salts,and if illicit dr ugs

arecarried inthe gastro-intestinaltract (‘body-packing’).

However,it isnot clearthat the procedureimproves

outcome andadvice should be sought from a poisons

informationcentre.

Theadministration of laxativesalone hasno role inthe

managementof the poisoned childand is not arecom-

mended method of gut decontamination. The routine

useof a laxativein combinationwith activated charcoal

has mostly been abandoned. Laxatives should not be

administered to young children because of the likeli-

hoodof ﬂuid and electrolyte imbalance.

CHARCOAL,ACTIVATED

Cautions

drowsyor comatose child (riskof aspira-

tion—ensureairway protected); reduced gastro-

intestinalmotility (risk of obstruction);not for pois-

oningwith petroleumdistillates, corrosivesubstances,

alcohols,malathion, andmetal saltsincluding ironand

lithiumsalts

Side-effects

blackstools

Indicationand dose

Reductionof absorption of poisons

Bymouth

Neonate

1g/kg

Child1 month–12 years

1g/kg (max. 50g)

Child12–18 years

50g

BNFC 2011–2012 Emergency treatmentof poisoning 25

Emergencytreatment of poisoning

Activeelimination of poisons

Bymouth

Neonate

1g/kg every 4hours

Child1 month–12 years

1g/kg (max.50 g)every

4hours

Child12–18 years

50g every 4hours

Administration

suspensionor reconstituted powder

maybe mixed with softdrinks (e.g. caffeine-free diet

cola)or fruit juices to maskthe taste

Actidose-Aqua

Advance(Alliance)

Oralsuspension

,activated charcoal1.04 g/5mL, net

price50-g pack (240mL) = £8.69

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 (particularly potassium) can be

measured; absorption of aspirin may be slow and the

plasma-salicylateconcentration maycontinue torise for

several hours, requiring repeated measurement.

Plasma-salicylate concentration may not correlate

with clinical severity in children, and clinical and bio-

chemicalassessment isnecessary. Generally,theclinical

severityof poisoning is less below a plasma-salicylate

concentration of 500 mg/litre (3.6mmol/litre) unless

thereis evidence of metabolicacidosis. Activated char-

coal should be given within 1 hour of ingesting more

than125 mg/kgaspirin. Fluid lossesshould bereplaced

and intravenous sodium bicarbonate may be given

(ensuring plasma-potassium concentration is main-

tained within the reference range) to enhance urinary

salicylateexcretion (optimumurinary pH7.5–8.5); treat-

mentshould be given ina high dependency unit.

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-

olic acidosis, convulsions, renal failure, pulmonary

oedema or persistently high plasma-salicylate concen-

trationsunresponsive to urinary alkalinisation.

NSAIDs

Mefenamicacid has important consequences

inoverdosage becauseit cancause convulsions,which if

prolonged or recurrent, require treatment with intra-

venouslorazepam or diazepam.

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

100mg/kg hasbeen ingestedwithin thepreceding hour.

Paracetamol

In cases of intravenous paracetamol poisoning

contact the National Poisons Information Service

foradvice on risk assessmentand management.

Singleor repeated dosestotalling as littleas 150mg/kg

of paracetamol ingested within 24hours may cause

severe hepatocellular necrosis and, much less fre-

quently,renal tubular necrosis. Toavoid underestimat-

ingthe potentially toxic paracetamol dose ingested by

obesechildren whoweigh morethan 110kg, usea body-

weightof 110 kg(rather than their actual body-weight)

whencalculating thetotal dose ofparacetamol ingested

(inmg/kg). Childrenat

high-risk

ofliver damage,includ-

ing those taking enzyme-inducing drugs or who are

malnourished (see below), may develop liver toxicity

withas little as 75 mg/kgof paracetamol taken within

24hours. Nausea and vomiting, theonly early features

ofpoisoning, usually settlewithin 24 hours. Persistence

beyondthis time,often associatedwith theonset ofright

subcostalpain and tenderness, usually indicatesdevel-

opmentof hepaticnecrosis. Liverdamage ismaximal 3–

4days after ingestion andmay lead toencephalopathy,

haemorrhage, hypoglycaemia, cerebral oedema, and

death.

Therefore,despite a lackof signiﬁcant early symptoms,

children who have taken an overdose of paracetamol

shouldbe transferred to hospital urgently.

Administrationof activated charcoal should beconsid-

eredif paracetamolin excessof 150mg/kg (orin excess

of75 mg/kgfor those consideredto be at

high-risk

,see

below) is thought to have been ingested within the

previoushour.

Acetylcysteine protectsthe liver if infused up to, and

possiblybeyond, 24hours ofingesting paracetamol.It is

mosteffective if givenwithin 8 hours ofingestion, after

whicheffectiveness declines.In childrenwho present8–

36 hours after a potentiallytoxic ingestion, acetylcys-

teinetreatment should commence immediately even if

plasma-paracetamol concentrations are not yet avail-

able.If more than24 hours have elapsedadvice should

be sought fromthe National Poisons Information Ser-

vice.Giving acetylcysteine bymouth [unlicensed route]

26 Emergencytreatment of poisoning BNFC 2011–2012

Emergencytreatment of poisoning

isan alternative if intravenous accessis not possible—

contact the National Poisons Information Service for

advice. In remote areas, methionine by mouth is an

alternative only if acetylcysteine cannot be given

promptly.Once the child reaches hospital the need to

continue treatment with the antidote will be assessed

fromthe plasma-paracetamol concentration (related to

thetime from ingestion).

Childrenat risk of liverdamage and thereforerequiring

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 plotsof 200 mg/litre (1.32mmol/litre) at

Patientswhose plasma-paracetamolconcentrations areon orabove thenormal treatmentline shouldbe treated

withacetylcysteine by intravenous infusion (or, ifacetylcysteine cannot be used, withmethionine by mouth,

providedthe overdose hasbeen takenwithin 10–12 hoursand the patientis not vomiting).

Childrenat high-risk ofliver damageinclude those:

. taking liverenzyme-inducing drugs (e.g.carbamazepine, phenobarbital, phenytoin,prim idone,rif-

ampicin,rifabutin, efavirenz, nevirapine,alcohol, St John’swort);

. who aremalnourished (e.g. inanorexia or bulimia,cystic ﬁbrosis, hepatitis C,in underweight children

withfailure to thrive,in alcoholism, orthose who areHIV-positive);

. who havea febrile illness;

. who havenot eaten fora few days.

Thesechildren should be treated if their plasma-paracetamolconcentration is on or above the high-risk

treatmentline.

Theprognostic accuracyafter 15hours isuncertain buta plasma-paracetamolconcentration onor above the

relevanttreatment line shouldbe regarded ascarrying a seriousrisk of liverdamage.

Graphreproduced courtesyof Universityof WalesCollege ofMedicine Therapeuticsand ToxicologyCentre

BNFC 2011–2012 Emergency treatmentof poisoning 27

Emergencytreatment of poisoning

4hours and 6.25mg/litre (0.04mmol/litre) at 24 hours

(see p. 27). Those whose plasma-paracetamol concen-

tration is on or above the

normal treatment line

are

treatedwith acetylcysteine by intravenous infusion(or,

if acetylcysteine is not available, with methionineby

mouth, provided the overdose has been taken within

10–12hours

and

thechild is not vomiting).

Childrenat

high-risk

ofliver damage include those:

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

mazepine,phenobarbital, phenytoin, primidone,rif-

ampicin,rifabutin, efavirenz, nevirapine,alcohol, St

John’swort);

whoare malnourished (e.g. in anorexiaor bulimia,

cysticﬁbrosis, hepatitis C, in underweight children

with‘failure to thrive’, in alcoholism,or those who

areHIV-positive);

whohave a febrile illness;

whohave not eaten fora few days.

Thesechildren may develop toxicity at lower plasma-

paracetamolconcentrations andshould be treatedif the

concentrationis onor abovethe

high-risktreatment line

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

cetamol concentrations of the normal treatment line).

The prognostic accuracy of plasma-paracetamol con-

centration taken after 15 hours is uncertain, but a

concentration onor above the relevant treatment line

should be regarded as carrying a serious risk of liver

damage.

Theplasma-paracetamol concentration maybe difﬁcult

tointer pretwhen paracetamol has been ingested over

several hours (staggered overdose). If thereis doubt

about timing or theneed for treatment then the child

shouldbe treated with acetylcysteine.

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

ACETYLCYSTEINE

Cautions

asthma(see Side-effects below, butdo not

delayacetylcysteine treatment); acetylcysteine may

mildlyincrease INR and prothrombintime

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; mildincrease

inINR and prothrombin time

Indicationand dose

Paracetamoloverdosage

seenotes above

Byintravenous infusion

Neonate

initially150 mg/kg in3 mL/kg Glucose

5%and givenover 15minutes, followedby 50mg/

kgin 7mL/kg Glucose5% and givenover 4hour s,

then100 mg/kg in14 mL/kg Glucose5% and

givenover 16 hours

Child1 month–5 years (or body-weight under

20kg)

initially150 mg/kgin 3mL/kg Glucose 5%

andgiven over 15 minutes,followed by 50mg/kg

in7 mL/kg Glucose5% and given over4 hours,

then100 mg/kg in14 mL/kg Glucose5% and

givenover 16 hours

Child5–12 years (or body-weight over 20 kg)

initially150 mg/kg in100 mLGlucose 5% and

givenover 15 minutes, followedby 50mg/kg in

250mL Glucose 5%and given over 4hours, then

100mg/kg in 500mL Glucose5% and given over

16hours

Child12–18 years

initially150 mg/kg (max.

16.5g) in 200mL Glucose5% and given over 15

minutes,followed by 50mg/kg (max. 5.5g) in

500mL Glucose 5%and given over 4hours, then

100mg/kg (max.11g) in 1litre Glucose 5% and

givenover 16 hours

Note

Glucose5%is preferredinfusion ﬂuid;Sodium Chloride

0.9%is an alternativeif Glucose 5%unsuitable

Acetylcysteine(Non-proprietary) A

Concentratefor intravenousinfusion

,acetylcysteine

200mg/mL, net price10-mL amp = £1.96

Parvolex

(UCBPharma) A

Concentratefor intravenousinfusion

,acetylcysteine

200mg/mL, net price10-mL amp = £2.25

Electrolytes

14mmol/10-mL amp

METHIONINE

Hepaticimpairment

mayprecipitate coma

Side-effects

nausea,vomiting, drowsiness, irritability

Indicationand dose

Paracetamoloverdosage

seenotes above

Bymouth

Childunder 6 years

1g every4 hoursfor atotal of

4doses

Child6–18 years

2.5g every4 hours fora totalof

4doses

Methionine(Pharma Nord)

Tablets

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

pack= £9.95

Analgesics (opioid)

Opioids(narcotic analgesics) cause varying degrees of

coma,respiratory depression, and pinpoint pupils.The

speciﬁcantidote naloxone is indicatedif there is coma

orbradypnoea. Sincenaloxone hasa shorter durationof

action than many opioids, close monitoring and

repeatedinjections arenecessary according tothe resp-

iratoryrate and depth ofcoma. When repeated admin-

istration of naloxone is required, it can be given by

continuous intravenous infusion instead and therate

ofinfusion adjustedaccording to vitalsigns. Allchildren

should be observed for at least 6 hours after the last

doseof naloxone. The effects ofsome opioids, such as

buprenorphine,are only partiallyreversed by naloxone.

Dextropropoxyphene and methadone have very long

durationsof action; patientsmay need to bemonitored

forlong periods following largeoverdoses.

Naloxonereverses theopioid effects ofdextropropoxy-

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.

28 Emergencytreatment of poisoning BNFC 2011–2012

Emergencytreatment of poisoning

NALOXONEHYDROCHLORIDE

Cautions

physicaldependence on opioids; cardiac

irritability;naloxone is short-acting, seenotes above

Pregnancy

section15.1.7

Breast-feeding

section15.1.7

Indicationand dose

SafePractice

Doses used in acute opioid overdosage may not be

appropriate for the management of opioid-induced

respiratorydepression andsedation in thosereceiving

palliative care and in chronic opioid use; see also

section15.1.7 for management ofpostoperative resp-

iratorydepression

Overdosagewith opioids

Byintravenous injection

Neonate

10micrograms/kg; if noresponse, give

subsequentdose of 100micrograms/kg (then

reviewdiagnosis); furtherdoses may berequired if

respiratoryfunction deteriorates

Child1 month–12 years

10micrograms/kg; ifno

response,give subsequent dose of100 micr-

ograms/kg(then review diagnosis); furtherdoses

maybe required if respiratory function deterio-

rates

Child12–18 years

0.4–2mg; if noresponse

repeatat intervals of 2–3 minutesto a max. of

10mg (then reviewdiagnosis); further doses may

berequired if respiratory function deteriorates

Bysubcutaneous or intramuscular injection

Asintravenous injection but onlyif intravenous

routenot feasible (onset ofaction slower)

Bycontinuous intravenous infusion usingan

infusionpump

Neonate

rateadjusted according to response

(initially,rate may beset at 60% of the initial

resuscitative

intravenousinjection

doseper hour)

Child1 month–18 years

rateadjusted according

toresponse (initially,rate may beset at60% of the

initialresuscitative

intravenousinjection

doseper

hour)

Note

Theinitial resuscitative

intravenousinjection

dose

isthat which maintainedsatisfactory ventilation forat

least15 minutes

Reversalof postoperative respiratory depres-

sion,reversal of respiratory andCNS depres-

sionin neonate following maternal opioiduse

duringlabour

section15.1.7

Administration

for

continuousintravenous infusion

diluteto aconcentration ofup to200 micrograms/mL

withGlucose 5%

SodiumChloride 0.9%

Naloxone(Non-proprietary) A

Injection

,naloxone hydrochloride 20micrograms/

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

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

preﬁlledsyringe = £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

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-

cinations,are 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.

Intravenouslorazepam ordiazepam (preferablyin emul-

sion form)may be required to treat convulsions. Acti-

vated charcoal given within 1 hour of the overdose

reduces absorption of the drug. Althoughar rhythmias

areworrying, somewill respond tocorrection of hypox-

iaand acidosis.The use ofanti-arrhythmic drugs isbest

avoided,but intravenousinfusion ofsodium bicarbonate

canarrest arrhythmias orprevent themin those withan

extended QRS duration. Diazepam given by mouth is

usuallyadequate to sedate delirious children but large

dosesmay be 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. 25). 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 inchildren withconduction systemdisorders

or impaired myocardial function. Bradycardia is the

most common arrhythmia caused by beta-blockers,

BNFC 2011–2012 Emergency treatmentof poisoning 29

Emergencytreatment of poisoning

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 (40micrograms/kg, max. 3mg). Cardio-

genic shockunresponsive to atropine is probably best

treatedwith an intravenous injection of glucagon (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. 809) 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.

Activated charcoal should be considered if the child

presents within 1 hour of overdosagewith a calcium-

channel blocker; repeated doses of activated charcoal

are considered if a modiﬁed-release preparation is

involved(although activated charcoal may beeffective

beyond1 hour with modiﬁed-release preparations). In

childrenwith signiﬁcant features of poisoning, calcium

chlorideor calcium gluconate (section 9.5.1.1) isgiven

byinjection; atropine is given to correct symptomatic

bradycardia. In severe cases, an insulin and glucose

infusionmay be required in the management of hypo-

tensionand myocardial failure.For the management of

hypotension,the choice of inotropic sympathomimetic

dependson whether hypotensionis secondary to vaso-

dilatation or tomyocardial depression—advice should

be sought fromthe National Poisons Information Ser-

vice.

Hypnotics and anxiolytics

Benzodiazepines

Benzodiazepinestaken alonecause

drowsiness, ataxia, dysarthria, nystagmus,and occa-

sionally respiratory depression, and coma. They

potentiate the effects of other central nervous system

depressants taken concomitantly. Activated charcoal

can be given within 1 hour of ingesting asigniﬁcant

quantityof benzodiazepine, providedthe child isawake

andthe airway is protected.Use of the benzodiazepine

antagonist ﬂumazenil [unlicensed indication] can be

hazardous, particularly in mixed overdoses involving

tricyclic antidepressants or in benzodiazepine-depen-

dent patients. Flumazenil may prevent the need for

ventilation, particularly in children with severe respir-

atorydisorders; it should beused on expertadvice and

notas a diagnostictest in children witha reduced level

ofconsciousness.

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,

shockand metabolicacidosis indicate severepoisoning.

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)

Cautions

section9.1.3

Renalimpairment

section9.1.3

Pregnancy

section9.1.3

Breast-feeding

section9.1.3

Side-effects

section9.1.3

Licenseduse licensed foruse in children (agerange

notspeciﬁed by manufacturer)

Indicationand dose

Ironpoisoning

Bycontinuous intravenous infusion

Neonate

upto 15 mg/kg/hour,reduced after 4–6

hours;max. 80mg/kg in24 hours (insevere cases,

higherdoses on advice fromthe National Poisons

InformationService)

Child1 month–18 years

upto 15 mg/kg/hour,

reducedafter 4–6 hours; max.80 mg/kg in24

hours(in severe cases, higherdoses on advice

fromthe National PoisonsInfor mationService)

Chroniciron overload

section9.1.3

Preparations

Section9.1.3

Lithium

Lithium intoxication can occur as a complication of

long-term therapyand is caused by reduced excretion

of the drug because of a variety offactors including

dehydration,deterioration of renal function, infections,

andco-administration of diuretics or NSAIDs(or other

drugs that interact). Acute deliberate overdoses may

alsooccur withdelayed onsetof symptoms (12hours or

more)due to slow entry oflithium into the tissues and

continuing absorption from modiﬁed-release formula-

tions.

The early clinical features are non-speciﬁc and may

include apathy and restlessness which could be con-

fusedwith mental changesdue to thechild’s depressive

30 Emergencytreatment of poisoning BNFC 2011–2012

Emergencytreatment of poisoning

illness. Vomiting, diarrhoea, ataxia, weakness, dysar-

thria,muscle twitching, and tremor mayfollow. Severe

poisoning is associated with convulsions, coma, renal

failure, electrolyte imbalance, dehydration, and hypo-

tension.

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

arepresent. In acute overdosage, much higher serum-

litiumconcentrations may be present 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.

Whole-bowelirrigation should be consideredfor signif-

icant ingestion, but advice should be sought fromthe

NationalPoisons Information Service, p.24.

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

Phenothiazines and related drugs

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 antipsychotic drugs

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. 24) 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

and cooling measures for hyperthermia (see p. 25);

hypertensionand cardiac effects require speciﬁc treat-

mentand expert advice shouldbe sought.

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-

aemia has also been associated with ecstasy use and

syndromeof inappropriate antidiuretic hormone secre-

tion(SIADH) can occur.

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). Ondansetron (section

4.6)may beeffective forsevere vomitingthat isresistant

to other antiemetics. Hypokalaemia is corrected by

intravenous infusion of potassium chloride (section

9.2.2.1)in 0.9% sodium chloride andmay be so severe

as to requirehigh doses under ECG monitoring. Con-

vulsions shouldbe controlled by intravenous adminis-

tration of lorazepam or diazepam (see Convulsions,

p.25). For the management of agitation associated

withtheophylline overdosage, seek specialistadvice.

Providedthe childdoes not sufferfrom asthma,a short-

acting beta-blocker (section 2.4) can be administered

intravenously to reverse severe tachycardia, hypokal-

aemia,and hyperglycaemia.

Other poisons

Consulteither theNational Poisons InformationService

dayand night or TOXBASE,see p. 24.

BNFC 2011–2012 Emergency treatmentof poisoning 31

Emergencytreatment of poisoning

Cyanides

Oxygen should beadministered to children with cya-

nidepoisoning. The choice of antidotedepends on the

severity of poisoning, certainty of diagnosis, and the

cause.Dicobalt edetate is theantidote 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

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

Indicationand dose

Severepoisoning with cyanides

Byintravenous injection

Consultthe National Poisons InformationService

DicobaltEdetate (Non-proprietary) A

Injection

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

mL(300-mg) amp = £13.75

Arestriction does notapply where administration isfor

savinglife in emergency

HYDROXOCOBALAMIN

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

Indicationand dose

Poisoningwith cyanides

seenotes above

Byintravenous infusion

Childbody-weight 5 kg and over

70mg/kg

(max.5 g) over15 minutes; a seconddose

of70 mg/kg (max.5 g) canbe given over

15minutes–2 hours depending onseverity of

poisoningand patient stability

Administration

for

intravenousinfusion

,reconstitute

2.5-gvial with 100mL Sodium Chloride 0.9%;gently

invertvial forat least 30seconds tomix; do notshake

Cyanokit

(SwedishOrphan) TA

Intravenousinfusion

,powder for reconstitution,

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

Note

Deepred colour ofhydroxocobalamin mayinterfere

withlaboratory tests (seeSide-effects, above)

SODIUM NITRITE

Side-effects

ﬂushingand headache due to vasodila-

tation

Indicationand dose

Poisoningwith cyanides (used in conjunction

withsodium thiosulphate)

Seeunder preparation

SodiumNitrite A

Injection

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

injections

Dose

Byintravenous injection over5–20 minutes

Child1 month–18 years

4–10mg/kg max.300 mg

(0.13–0.33mL/kg, max.10 mL,of 3% solution)followed

bysodium thiosulphateinjection 400mg/kg, max.12.5 g

(0.8mL/kg, max.25 mL,of 50% solution)over 10 min-

utes

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

Arestriction does notapply where administration isfor

savinglife in emergency

SODIUM THIOSULPHATE

Indicationand dose

Poisoningwith cyanides

(usedin conjunctionwith

sodiumnitrite)

Seeabove under Sodium Nitrite

SodiumThiosulphate A

Injection

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

waterfor injections

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

Arestriction does notapply where administration isfor

savinglife in emergency

Ethylene glycol and methanol

Fomepizole (available from ‘special-order’ manufac-

turersor specialist importing companies, see p.809) 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 CALCIUM EDETATE

(SodiumCalciumedetate)

Renalimpairment

usewith caution in mildimpair-

ment;avoid in moderate tosevere impairment—

contactthe National PoisonsInfor mationService for

advice

32 Emergencytreatment of poisoning BNFC 2011–2012

Emergencytreatment of poisoning

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

Licenseduse licensed foruse in children (agerange

notspeciﬁed by manufacturer)

Indicationand dose

Leadpoisoning

Byintravenous infusion

Child1 month–18 years

40mg/kg twicedaily for

upto 5 days; ifnecessary a second coursecan be

givenat least 7 daysafter the ﬁrst course, anda

thirdcourse can be givenat least 7 days afterthe

secondcourse

Administration

for

intravenousinfusion

,dilute to a

concentrationof not more 30mg/mL with Glucose

SodiumChloride 0.9%;give overat least 1hour

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 incomplete combus-

tionof fuel gases in conﬁnedspaces.

Immediatetreatment of carbon monoxide poisoning is

essential. The child should be moved to fresh air,the

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

teredas soon as available. Artiﬁcial respiration should

be given as necessary and continued until adequate

spontaneous breathing starts, or stopped only after

persistentand efﬁcient treatment of cardiac arrest has

failed.The childshould be admittedto hospital because

complicationsmay arise after adelay of hours or days.

Cerebraloedema may occurin severe poisoning andis

treated with an intravenousinfusion of mannitol (sec-

tion 2.2.5). Referral for hyperbaric oxygen treatment

shouldbe discussed withthe National PoisonsInforma-

tion Service if the patient is pregnantor incases of

severe poisoning such as if thechild isor has been

unconscious,or has psychiatricor neurologicalfeatures

otherthan a headache or has myocardialischaemia or

an arrhythmia, or has a blood carboxyhaemoglobin

concentrationof more than 20%.

Sulphur dioxide, chlorine, phosgene, ammoni a

Allof these gasescan cause upperrespiratory tract and

conjunctivalirritation. Pulmonary oedema, with severe

breathlessnessand cyanosis may develop suddenly up

to36 hours after exposure. Death mayoccur. Children

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

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

should be prevented by movingthe child to fresh air,

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 20 micrograms/kg(max. 2 mg)as atropine sul-

phateevery 5to 10minutes (accordingto theseverity of

poisoning)until the skin becomes ﬂushed and dry,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

BNFC 2011–2012 Emergency treatmentof poisoning 33

Emergencytreatment of poisoning

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.24).

The National Poisons Information Ser vice (Tel:

0844892 0111) will provide specialistadvice on all

aspectsof poisoning day andnight

PRALIDOXIME CHLORIDE

Cautions

myastheniagravis

Contra-indications

poisoningwith carbamates or

organophosphoruscompounds without anti-

cholinesteraseactivity

Renalimpairment

usewith caution

Side-effects

drowsiness,dizziness, disturbances of

vision,nausea, tachycardia, headache, hyperventila-

tion,and muscular weakness

Licenseduse licensed foruse in children (agerange

notspeciﬁed by manufacturer)

Indicationand dose

Adjunctto atropine in thetreatment of pois-

oningby organophosphorus insecticide or

nerveagent

Byintravenous infusion over 20minutes

Childunder 18 years

initially30 mg/kg,followed

by8 mg/kg/hour; usualmax. 12g in 24 hours

Note

Theloading dose maybe administered byintra-

venousinjection (diluted toa concentration of50 mg/

mLwith water forinjections) over atleast 5 minutesif

pulmonaryoedema is presentor if itis not practicalto

administeran intravenousinfusion; pralidoxime chloride

dosesmay differ fromthose in productliterature

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 bites and animal stings

Snakebites

Envenomingfrom snake bite is uncom-

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.The contents of one vial (10 mL) of

European viper venom antiserum (available from

Movianto) is given

by intravenous injection

over 10–

15minutes or

byintravenous infusion

over30 minutes

after diluting in sodium chloride intravenous infusion

0.9% (use 5 mL diluent/kg body-weight). The same

dose should be used for adults and children. The

dose can be repeated after 1–2 hours if symptoms of

systemic envenoming

persist. However,for those chil-

drenwho present with clinical features of

severeenve-

noming

(e.g.shock, ECGabnormalities, orlocal swelling

thathas advanced from the foot to above the knee or

fromthe hand toabove the elbowwithin 2 hours ofthe

bite),an initialdose of2 vials(20 mL)of the antiserumis

recommended; if symptoms of

systemic envenoming

persist contact the National Poisons Information Ser-

vice.Adrenaline (epinephrine) injection mustbe imme-

diatelyto hand for treatment of anaphylacticreactions

to theantivenom (for the management of anaphylaxis

seesection 3.4.3).

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. 24).

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-

cular adrenaline (epinephrine); self-administered (or

administeredby a carer) intramuscular adrenaline (e.g.

EpiPen

)is thebest ﬁrst-aid treatmentfor childrenwith

severe hypersensitivity. An inhaled bronchodilator

should be used for asthmatic reactions. For the

managementof anaphylaxis, see section 3.4.3. Ashort

course ofan oral antihistamine or a topical cortico-

steroid may help to reduce inﬂammation and relieve

itching.A vaccine containing extracts ofbee and wasp

venom can be used to reduce the risk of severe

anaphylaxis and systemic reactions in children with

systemichypersensitivity to beeor 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

than458 C). Children stungby 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 can beused to reduce pain.

34 Emergencytreatment of poisoning BNFC 2011–2012

Emergencytreatment of poisoning

1 Gastro-intestinal system

1.1 Dyspepsia and gastro-oeso-

phagealreﬂux disease

1.1.1

Antacidsand simeticone 36

1.1.2 Compound alginatepreparations 38

1.2 Antispasmodics and otherdrugs

alteringgut motility

1.3 Antisecretory drugsand mucosal

protectants

1.3.1

-receptorantagonists 43

1.3.2 Selective antimuscarinics 44

1.3.3 Chelates and complexes 44

1.3.4 Prostaglandin analogues 44

1.3.5 Proton pump inhibitors 45

1.4 Acute diarrhoea 46

1.4.1

Adsorbentsand bulk-forming

drugs

1.4.2 Antimotility drugs 47

1.5 Chronic bowel disorders 48

1.5.1

Aminosalicylates 49

1.5.2 Corticosteroids 53

1.5.3 Drugs affecting the immune

response

1.5.4 Food allergy 56

1.6 Laxatives 57

1.6.1

Bulk-forminglaxatives 57

1.6.2 Stimulant laxatives 59

1.6.3 Faecal softeners 61

1.6.4 Osmotic laxatives 61

1.6.5 Bowel cleansing preparations 64

1.6.6 Peripheral opioid-receptor

antagonists

1.7 Local preparations for analand

rectaldisorders

1.7.1

Soothinganal and rectal pre-

parations

1.7.2 Compound anal and rectalpre-

parationswith corticosteroids

1.7.3 Rectal sclerosants 67

1.7.4 Management of anal ﬁssures 67

1.8 Stoma andenteral feeding tubes 68

1.9 Drugs affecting intestinal secre-

tions

1.9.1

Drugsaffecting biliary composi-

tionand ﬂow

1.9.2 Bile acid sequestrants 70

1.9.3 Aprotinin 70

1.9.4 Pancreatin 70

This chapter includes advice on the drug manage-

mentof the following:

Clostridiumdifﬁcile

infection,p. 49

constipation,p. 57

Crohn’sdisease, p. 48

foodallergy, p. 56

Helicobacterpylori

infection,p. 42

irritablebowel syndrome, p. 49

malabsorptionsyndromes, p. 49

NSAID-associatedulcers, p. 43

ulcerativecolitis, p. 48

1.1

Dyspepsia and gastro-

oesophageal reﬂux

disease

1.1.1 Antacids and simeticone

1.1.2 Compound alginate preparations

Dyspepsia

Dyspepsiacovers upper abdominal pain, fullness, early

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

and duodenal ulceration (section 1.3), gastro-oeso-

phagealreﬂux disease, gastritis, and upper gastro-intes-

tinal motility disorders,but most commonly it is of

uncertainorigin.

Children with dyspepsia should be advised about life-

style changes (see Gastro-oesophagealreﬂux disease,

below).Some medications may cause dyspepsia—these

shouldbe stopped, if possible.

A compound alginate preparation (section1.1.2) may

provide relief from dyspepsia; persistent dyspepsia

requires investigation. Treatment with a H

-receptor

antagonist (section 1.3.1) or a protonpump inhibitor

(section1.3.5) should be initiatedonly on the advice of a

hospitalspecialist.

Helicobacter pylori

may be present in children with

dyspepsia.

H. pylori

eradication therapy (section 1.3)

should be considered for persistent dyspepsia if itis

ulcer-like. However, most children with functional

(investigated,non-ulcer) dyspepsia donot beneﬁt symp-

tomaticallyfrom

H.pylori

eradication.

Gastro-oesophageal reﬂuxdisease

Gastro-oesophagealreﬂux disease includes non-erosive

gastro-oesophageal reﬂux and erosive oesophagitis.

Uncomplicated gastro-oesophageal reﬂux iscommon

in infancy and mostsymptoms, such as intermittent

vomiting or repeated, effortless regurgitation, resolve

BNFC 2011–2012 35

Gastro-intestinalsystem

without treatment between 12 and 18 months of age.

Older children with gastro-oesophageal reﬂux disease

mayhave heartburn, acid regurgitation and dysphagia.

Oesophagealinﬂammation (oesophagitis), ulceration or

stricture formation may develop in early childhood;

gastro-oesophageal reﬂux disease may also be asso-

ciated with chronic respiratory disorders including

asthma.

Parentsand carers of

neonates

and

infants

should be

reassuredthat most symptomsof uncomplicated gastro-

oesophageal reﬂux resolve without treatment. An

increasein the frequency and a decrease in the volume

offeeds may reduce symptoms. Afeed thickener or pre-

thickenedformula feed (Appendix 2) can be used onthe

advice of a dietician. If necessary, a suitable alginate-

containing preparation (section 1.1.2) can be used

insteadof thickened feeds.

Older children

should be advised about life-style

changes such as weight reductionif overweight,and

the avoidance of alcohol and smoking. An alginate-

containingantacid (section 1.1.2) can be used to relieve

symptoms.

Childrenwho do not respond to these measures or who

have problems such as respiratory disorders or sus-

pected oesophagitis need to be referred to hospital.

On the advice of a paediatrician, a histamine H

receptor antagonist (section 1.3.1) can be used to

relievesymptoms of gastro-oesophageal reﬂux disease,

promotemucosal healing and permit reduction in anta-

cid consumption. A proton pump inhibitor (section

1.3.5)can be used for the treatment of moderate, non-

erosive oesophagitis that is unresponsive to an H

receptorantagonist. Endoscopically conﬁrmed

erosive

ulcerative

, or

stricturing

disease in children is usually

treated with a proton pump inhibitor. Reassessment is

necessary if symptomspersist despite 4–6 weeks of

treatment; long-term use of an H

-receptor antagonist

or proton pump inhibitor should not be undertaken

without full assessment of the underlying condition.

For endoscopically conﬁrmed

erosive

ulcerative

, or

stricturing

disease, the proton pump inhibitor usually

needsto be maintained at the minimum effective dose.

Motilitystimulants (section 1.2), such as domperidone

or erythromycin may improve gastro-oesophageal

sphincter contraction and accelerate gastric emptying.

Evidence for the long-term efﬁcacy of motility

stimulants in the management of gastro-oesophageal

reﬂuxin children is unconvincing.

For advice on specialised formula feeds, see section

9.4.2.

1.1.1

Antacids and simeticone

Antacids(usually containing aluminium or magnesium

compounds)can be used for short-term relief of inter-

mittent symptoms of

ulcer dyspepsia

and

non-erosive

gastro-oesophagealreﬂux

(seesection 1.1) in children;

theyare also used in functional (non-ulcer) dyspepsia,

butthe evidence of beneﬁt is uncertain.

Aluminium- and magnesium-containing antacids,

being relatively insoluble in water, are long-acting if

retained in the stomach. Magnesium-containing

antacids tend to be laxative whereasaluminium-con-

tainingantacids may be constipating; antacids contain-

ingboth magnesium and aluminium may reduce these

colonic side-effects. Aluminium-containing antacids

should not be used in children with renal impairment,

or in neonates and infants because accumulation may

leadto increased plasma-aluminium concentrations.

Complexes such as hydrotalcite confer no special

advantage.

Calcium-containingantacids can induce rebound acid

secretion;with modest doses the clinical signiﬁcance of

this is doubtful, but prolonged high dosesalso cause

hypercalcaemiaand alkalosis.

Simeticone (activated dimeticone) is used to treat

infantilecolic, but the evidence of beneﬁt is uncertain.

Simeticone is added to an antacid asan antifoaming

agentto relieve ﬂatulence; such preparations may also

beuseful for the relief of hiccup in palliative care (see

Prescribingin Palliative Care, p. 19).

Alginates act as mucosal protectants ingastro-oeso-

phageal reﬂux disease (section 1.1.2). The amount of

additional ingredient or antacid in individual prepara-

tionsvaries widely,as does their sodium content, so that

preparationsmay not be freely interchangeable.

Hepaticimpairment

Inchildren with ﬂ uid 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 children with ﬂuidretention,

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

Cautions

seenotes above; interactions: Appendix 1

(antacids)

Contra-indications

hypophosphataemia;neonates

andinfants

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Side-effects

seenotes above

36 1.1.1 Antacids and simeticone BNFC 2011–2012

Gastro-intestinalsystem

Indicationand dose

Dyspepsia

fordose see preparations

Hyperphosphataemia

section9.5.2.2

Co-magaldrox

Co-magaldrox is a mixture of aluminium hydroxide and

magnesium hydroxide; the proportions are expressed in the

form

where

and

arethe strengths in milligrams per unit

dose of 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

Bymouth

Child14–18 years

10–20mL20–60 minutes after meals

andat 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

Bymouth

Child12–18 years

10–20mL 3 times daily, 20–60 min-

utesafter meals and at bedtime, or when required

MAGNESIUM TRISILICATE

Cautions

heartfailure, hypertension; metabolic or

respiratoryalkalosis, hyper magnesaemia; interac-

tions:Appendix 1 (antacids)

Contra-indications

severerenal failure; hypopho-

sphataemia

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above; magnesium tri-

silicatemixture has a high sodium content

Side-effects

seenotes above; silica-based renal

stonesreported on long-term treatment

Indicationand dose

Dyspepsia

fordose see under preparation

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

Bymouth

Child5–12 years

5–10mLwith water 3 times daily or as

required

Child12–18 years

10–20mLwith water 3 times daily or

asrequired

Aluminium-magnesium complexes

HYDROTALCITE

Aluminiummagnesium carbonate hydroxide

hydrate

Cautions

seenotes above; interactions: Appendix1

(antacids)

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Side-effects

seenotes above

Indicationand dose

Dyspepsia

fordose see under preparation

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

Bymouth

Child8–12years

5mL4 times daily (betweenmeals and

atbedtime) when required

Child12–18 years

10mL 4 times daily (between meals

andat bedtime) 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

Bymouth

Child12–18 years

5–10mL after meals and at bedtime

orwhen required 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

Bymouth

Child2–5 years

5mL 3 times daily

Child5–12 years

5–10mL 3–4 times daily

Child12–18 years

5–10mL 4 times daily (after meals

andat bedtime) or when required

Simeticone alone

SIMETICONE

Activateddimeticone

Indicationand dose

Colicor wind pain

fordose see under individual

preparations

BNFC 2011–2012 1.1.1 Antacids and simeticone 37

Gastro-intestinalsystem

Dentinox

(DDD)U

Colicdrops

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

dose.Net price 100 mL = £1.73

Dose

Bymouth

Neonate

2.5mLwith or after each feed (max. 6 doses in

24hours); may be added to bottle feed

Child1 month–2 years

2.5mL with or after each feed

(max.6 doses in 24 hours); may be added to bottle feed

Note

Thebrand name

Dentinox

isalso 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

Bymouth

Neonate

0.5–1mL before feeds

Child1 month–2 years

0.5–1mL before feeds

1.1.2

Compound alginate

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

reducing symptoms of reﬂ ux. Alginate-containing pre-

parations are used in the management of mild symp-

toms of dyspepsia andgastro-oesophageal reﬂux dis-

ease (see section 1.1). Antacidsmay damageenteric

coatingsdesigned to prevent dissolutionin the stomach.

For interactions, see Appendix 1 (antacids, calcium

salts).

Preparationscontaining aluminium should not be used

in children with renal impair ment, or in neonates and

infants.

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

Bymouth

Child6–12 years

5–10mL after meals and at bedtime

Child12–18years

10–20mLafter 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

Child6–12 years

5–10mL after meals and at bedtime

Child12–18years

10–20mLafter 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

Bymouth

Child6–18 years

1–2tablets chewed 4times daily (after

mealsand 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

Bymouth

Child6–12years

5–10mL4 times daily (after meals and

atbedtime)

Child12–18 years

5–15mL 4 times daily (after meals

andat 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–tab pack (pepper-

mint-ﬂavour)= £3.07

Excipients

includeaspartame (section 9.4.1)

Dose

Bymouth

Child6–12 years

1tablet to be chewed after meals and

atbedtime (under medical advice only)

Child12–18 years

1–2tablets to be chewed after meals

andat bedtime

Suspension

,sugar-free, aniseed- or peppermint-ﬂ a-

vour,sodium alginate 500 mg, potassium bicarbonate

100mg/5mL. Contains 2.3 mmol Na

,1 mmol K

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

Dose

Bymouth

Child2–12 years

2.5–5mL after meals and at bedtime

(undermedical advice only)

Child12–18 years

5–10mL after meals and at bedtime

Gaviscon

Infant(Reckitt Benckiser)

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

Bymouth

Neonatebody-weight under4.5kg

1‘dose’ mixed with

feeds(or water, for breast-fed infants) when required

(max.6 times in 24 hours)

Neonatebody-weight over4.5 kg

2‘doses’ mixed with

feeds(or water, for breast-fed infants) when required

(max.6 times in 24 hours)

38 1.1.2 Compound alginate preparations BNFC 2011–2012

Gastro-intestinalsystem

Child1 month–2 years

Body-weightunder 4.5kg

doseas for neonate

Body–weightover 4.5kg

2‘doses’ mixed with feeds (or

water,forbreast-fed infants) when required (max. 6 times

in24 hours)

Note

Notto beused in preterm neonates, or whereexcessive

waterloss likely (e.g. fever, diar rhoea, vomiting, high room

temperature),or if intestinal obstruction. Notto be used with

otherpreparations containing thickening agents

SafePractice

Each half of the dual sachet is identiﬁed as‘one

dose’. To avoid er rors prescribe with directions in

termsof ‘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

Bymouth

Child12–18 years

1–3tablets chewed 4 times daily

(aftermeals 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

The dopamine-receptor antagonist domperidone sti-

mulatestransit in the gut.

Antimuscarinics

Antimuscarinics (formerly termed ‘anticholinergics’)

reduce intestinal motility. They are occasionallyused

forthe management of

irritablebowel syndrome

butthe

evidence of their valuehas not beenestablished and

response varies. Other indications for antimuscarinic

drugs include asthma and airways disease (section

3.1.2),motion sickness (section 4.6), urinar y frequency

andenuresis (section 7.4.2), mydriasis and cycloplegia

(section11.5), premedication (section 15.1.3), palliative

care (p. 19), and as anantidote to organophosphorus

poisoning(p. 33).

Antimuscarinics that are used for gastro-intestinal

smoothmuscle spasm include the tertiary amine dicy-

cloverine hydrochloride andthe quaternar y ammon-

iumcompounds propantheline bromide andhyoscine

butylbromide.The quaternary ammonium compounds

areless lipid soluble than atropine and so are less likely

tocross the blood-brain barrier; they are also less well

absorbedfrom the gastro-intestinal tract.

Dicycloverinehydrochloride may also have some direct

action on smooth muscle. Hyoscine butylbromide is

advocated as a gastro-intestinal antispasmodic, but it

ispoorly absorbed; the injection may be useful in endo-

scopyand radiology.

Cautions

Antimuscarinicsshould be used with caution

inchildren (especially children with Down’s syndrome)

dueto increased risk of side-effects; they should also be

used with caution in autonomic neuropathy, hyper-

tension, conditions characterised by tachycardia

(including hyperthyroidism, cardiac insuf ﬁciency, car-

diac surgery), pyrexia, and inchildren susceptible to

angle-closure glaucoma. Antimuscarinics are not used

in children with gastro-oesophageal reﬂux disease,

diarrhoea or ulcerative colitis. 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, and toxic mega-

colon.

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 nausea, vomiting, and

giddiness; very rarely, angle closure glaucoma may

occur.

DICYCLOVERINEHYDROCHLORIDE

(Dicyclominehydrochloride)

Cautions

seenotes above

Contra-indications

seenotes above; child under 6

months

Pregnancy

notknown to be harmful; manufacturer

advisesuse only if essential

Breast-feeding

avoid—presentin milk; apnoea

reportedin infant

Side-effects

seenotes above

Indicationand dose

Symptomaticrelief of gastro-intestinal disor-

derscharacterised by smooth musclespasm

Bymouth

Child6 months–2years

5–10mg 3–4 times daily

15minutes before feeds

Child2–12 years

10mg 3 times daily

Child12–18 years

10–20mg 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 is

60mg

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

Child12–18 years

10–20mL every 4 hours when

required

BNFC 2011–2012 1.2 Antispasmodics and other drugs altering gut motility 39

Gastro-intestinalsystem

HYOSCINE BUTYLBROMIDE

Cautions

seenotes above; also intestinal and urinary

outletobstruction

Contra-indications

seenotes above

Pregnancy

manufactureradvises use only if potential

beneﬁtoutweighs risk

Breast-feeding

amounttoo small to be harmful

Side-effects

seenotes above

Licenseduse

tablets

notlicensed for use in children

under6 years;

injection

notlicensed for use in

children(age range not speciﬁed by manufacturer)

Indicationand dose

Symptomaticrelief of gastro-intestinal orgen-

ito-urinarydisorders characterised by smooth

musclespasm

Bymouth

Child6–12 years

10mg 3 times daily

Child12–18 years

20mg 4 times daily

Excessiverespiratory secretions and bowel

colicin palliative care

(seealso p. 20)

Bymouth

Child1 month–2 years

300–500micrograms/kg

(max.5 mg) 3–4 times daily

Child2–5 years

5mg 3–4 times daily

Child5–12 years

10mg 3–4 times daily

Child12–18 years

10–20mg 3–4 times daily

Byintramuscular or intravenous injection

Child1 month–4 years

300–500micrograms/kg

(max.5 mg) 3–4 times daily

Child5–12 years

5–10mg 3–4 times daily

Child12–18 years

10–20mg 3–4 times daily

Acutespasm, spasm in diagnosticprocedures

Byintramuscular or intravenous injection

Child2–6 years

5mg repeated after 30 minutes if

necessary(may be repeated more frequently in

endoscopy),max. 15 mg daily

Child6–12 years

5–10mg repeated after 30

minutesif necessary (may be repeated more fre-

quentlyin endoscopy), max. 30 mg daily

Child12–18 years

20mg repeated after 30 min-

utesif necessary (may be repeated more fre-

quentlyin endoscopy), max. 80 mg daily

Administration

for

intravenousinjection

,may be

dilutedwith Glucose 5%

SodiumChloride 0.9%;

giveover at least 1 minute.

Foradministration

bymouth

,injection solution may

beused; content of ampoule may be stored in a

refrigeratorfor up to 24 hours after opening

Buscopan

(BoehringerIngelheim) A

Tablets,

coated,hyoscine butylbromide 10 mg, net

price56-tab pack = £2.25

Note

Hyoscinebutylbromidetablets can be sold tothe public

formedically conﬁrmed irritable bowel syndrome, provided

singledose does not exceed 20 mg, daily dose does not

exceed80mg, and pack doesnot contain a total ofmore than

240mg

Injection

,hyoscine butylbromide 20 mg/mL. Net

price1-mL amp = 22p

PROPANTHELINEBROMIDE

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

Licenseduse

tablets

notlicensed for use in children

under12 years

Indicationand dose

Symptomaticrelief of gastro-intestinal disor-

derscharacterised by smooth musclespasm

Bymouth

Child1 month–12 years

300micrograms/kg

(max.15 mg) 3–4 times daily at least one hour

beforefood

Child12–18 years

15mg 3 times daily at least

onehour 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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

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 primary dysmenorrhoea. They have no

serious adverse effects; peppermint oil occasionally

causesheartburn.

ALVERINECITRATE

Contra-indications

paralyticileus

Pregnancy

usewith caution

Breast-feeding

manufactureradvises avoid—limited

informationavailable

Side-effects

nausea;headache, dizziness; pruritus,

rash;hepatitis also reported

Indicationand dose

Adjunctin gastro-intestinal disorders charac-

terisedby smooth muscle spasm,dysmenorr-

hoea

Bymouth

Child12–18 years

60–120mg 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

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

40 1.2 Antispasmodics and other drugs altering gut motility BNFC2011–2012

Gastro-intestinalsystem

Licenseduse

tabletsand liquid

notlicensed for use

inchildren under 10 years;

granules

notlicensed for

usein children under 12 years;

modiﬁed-release

capsules

notlicensed for use in children under 18

years

Indicationand dose

Adjunctin gastro-intestinal disorders charac-

terisedby smooth muscle spasm

Bymouth

Child3–4 years

25mg 3times daily, preferably 20

minutesbefore meals

Child4–8 years

50mg 3times daily, preferably 20

minutesbefore meals

Child8–10 years

100mg 3 times daily,preferably

20minutes before meals

Child10–18 years

135–150mg 3 times daily,

preferably20 minutes before meals

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

Colofac

(AbbottHealthcare) A

Tablets

,s/c, mebeverine hydrochloride 135 mg, net

price100-tab pack = £7.52

Modiﬁedrelease

Colofac

MR(Abbott Healthcare) A

Capsules

,m/r, mebeverine hydrochloride 200 mg,

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

Dose

Irritablebowel syndrome

Bymouth

Child12–18 years

1capsule twice daily

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

Bymouth

Child12–18 years

1sachet in water, morning and

evening30 minutes before food; an additional sachet

mayalso be taken before the midday meal if necessary

Counselling

Preparationsthat swell in contact with liquid

shouldalways be carefully swallowed with water and should

notbe taken immediately before going to bed

10-sachetpack can be sold to the public for use in children

over12 years

PEPPERMINT OIL

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

Indicationand dose

Reliefof abdominal colic anddistension, par-

ticularlyin irritable bowel syndrome

Bymouth

Child15–18 years

1–2capsules, swallowed

wholewith water, 3 times daily for up to 3 months

ifnecessary

Colpermin

(McNeil)

Capsules

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

peppermintoil 0.2 mL. Net price 100-cap pack =

£12.05.Label: 5, 25

Excipients

includearachis (peanut) oil

Motility stimulants

Domperidone and metoclopramide (section 4.6) are

dopaminereceptor antagonists which stimulate gastric

emptyingand small intestinal transit, and enhance the

strengthof oesophageal sphincter contraction.Metoclo-

pramideand occasionally domperidonecan cause acute

dystonicreactions—for further details of this and other

side-effects,see section 4.6.

Alow dose ofer ythromycinstimulates gastro-intestinal

motilityand may be used on the advice of a paediatric

gastroenterologistto promotetolerance of enteral feeds;

erythromycinmay be less effective as a prokinetic drug

inpreterm neonates than in older children.

DOMPERIDONE

Cautions

seeunder Domperidone (section 4.6)

Side-effects

seeunder Domperidone (section 4.6);

alsoQT-interval prolongation reported

Licenseduse notlicensed for use in gastro-intestinal

stasis;not licensed for use in children for gastro-

oesophagealreﬂ ux disease

Indicationand dose

Gastro-oesophagealreﬂux disease(but efﬁcacy

notproven, see section 1.1),gastro -intestinal

stasis

Bymouth

Neonate

100–300micrograms/kg 4–6 times daily

beforefeeds

Child1 month–12 years

200–400micrograms/

kg(max. 20 mg) 3–4 times daily before food

Child12–18 years

10–20mg, 3–4 times daily

beforefood

Nauseaand vomiting

section4.6

Preparations

Section4.6

ERYTHROMYCIN

Cautions

seesection 5.1.5; interactions: Appendix 1

(macrolides)

Side-effects

seesection 5.1.5

BNFC 2011–2012 1.2 Antispasmodics and other drugs altering gut motility 41

Gastro-intestinalsystem

Licenseduse notlicensed for use in gastro-intestinal

stasis

Indicationand dose

Gastro-intestinalstasis

Bymouth

Neonate

3mg/kg 4 times daily

Child1 month–18 years

3mg/kg 4 times daily

Byintravenous infusion

Neonate

3mg/kg 4 times daily

Child1 month–1 year

3mg/kg 4 times daily

Preparations

Section5.1.5

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 the recur-

rence of gastric and duodenal ulcers and therisk of

rebleeding. The presence of

H. pylori

should be con-

ﬁrmedbefore starting eradication treatment. If possible,

the antibacterial sensitivity of the organism should be

establishedat the time of endoscopy and biopsy. Acid

inhibition combined with antibacterial treatment is

highlyeffective in the eradication of

H.pylori

;reinfec-

tion is rare. Antibiotic-associated colitis is anuncom-

monrisk.

Treatment to eradicate

H. pylori

infection in children

should be initiated underspecialist supervision.One-

week triple-therapy regimens that comprise ome-

prazole,amoxicillin, and either clarithromycinor metro-

nidazole are recommended. Resistance to clarithro-

mycin or to metronidazole is much more common

than to amoxicillin and can develop during treatment.

Aregimen containing amoxicillin and clarithromycin is

thereforerecommended for initial therapy and one con-

tainingamoxicillin and metronidazole is recommended

for eradication failure or for a child who has been

treated with a macrolide for other infections. 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-

mentis continued for a further 3 weeks. Lansoprazole

may be considered if omeprazole is unsuitable. Treat-

mentfailure usually indicates antibacterial resistance or

poorcompliance.

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

inhibitorand a single antibacterial produce low rates of

H.pylori

eradicationand are not recommended.

Forthe role of

H.pylori

eradicationtherapy in children

startingor taking NSAIDs,see NSAID-associated ulcers,

below.

Recommendedregimens for Helicobacter pylori eradication

Eradicationtherapy Age range Oraldose

(tobe used in combination with omeprazole, section 1.3.5)

Amoxicillin

1–6years 250mg twice daily (with clarithromycin)

125mg 3 times daily (with metronidazole)

6–12years 500mgtwice daily (with clarithromycin)

250mg 3 times daily (with metronidazole)

12–18years 1 g twice daily (with clarithromycin)

500mg 3 times daily (with metronidazole)

Clarithromycin

1–12years 7.5mg/kg(max. 500 mg) twice daily (with metronidazole or

amoxicillin)

12–18years 500 mg twice daily (with metronidazole or amoxicillin)

Metronidazole

1–6years 100mg twice daily (with clarithromycin)

100mg 3 times daily (with amoxicillin)

6–12years 200mgtwice daily (with clarithromycin)

200mg 3 times daily (with amoxicillin)

12–18years 400 mg twice daily (with clarithromycin)

400mg 3 times daily (with amoxicillin)

42 1.3 Antisecretory drugs and mucosal protectants BNFC 2011–2012

Gastro-intestinalsystem

Testfor Helicobacter pylori

C-Ureabreath test kits are available for conﬁrming the

presenceof gastro-duodenal infectionwith

Helicobacter

pylori

. The test involves collection ofbreath samples

beforeand after ingestion ofan oral solution of

C-urea;

the samples are sent for analysis by an appropriate

laboratory.The test should not be performed within 4

weeks of treatment with an antibacterial or within2

weeksof treatment with an antisecretory drug. A spe-

ciﬁc

C-Urea breath test kit for children is available

(

Helicobacter Test INFAI for children of the age 3–

). However the appropriatenessof testing for

pylori

infection in children has notbeen established.

Breath, saliva, faecal, and urine tests for

H.pylori

are

frequently unreliable in children; the most accurate

methodof diagnosis is endoscopy with biopsy.

HelicobacterTest INFAI forchildren of the age3–

(Infai)A

Oralpowder

C-urea45 mg,net price 1 kit (including

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

trometricanalysis 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)

NSAID-associated ulcers

Gastro-intestinalbleeding and ulceration can occurwith

NSAIDuse (section 10.1.1). In adults, the risk of serious

uppergastro-intestinal side-effects varies between indi-

vidual NSAIDs (see Gastro-intestinal side-effects,

p.501). Whenever possible,NSAIDs shouldbe with-

drawnif an ulcer occurs.

Children at high risk of developing gastro-intestinal

complications with a NSAID include those with a his-

tory of peptic ulcerdisease or serious upper gastro-

intestinal complication, those taking other medicines

that increase the riskof upper gastro-intestinal side-

effects,or those with seriousco-morbidity. In children at

riskof ulceration, aproton pump inhibitor (section 1.3.5)

oran H

-receptorantagonist, such as ranitidine, may be

consideredfor protection against gastric and duodenal

ulcersassociated with non-selective NSAIDs.

NSAIDuse and

H.pylori

infectionare independent risk

factorsfor gastro-intestinal bleeding and ulceration. In

children already taking a NSAID, eradication of

pylori

is unlikely to reduce the risk of NSAID-induced

bleeding or ulceration. However,in children about to

start long-term NSAID treatment who are

H. pylori

positive and have dyspepsia or a history of gastric or

duodenalulcer, eradication of

H.pylori

mayreduce the

overallrisk of ulceration.

If the

NSAIDcan be discontinued

in a child who has

developed an ulcer, aproton pump inhibitor usually

produces the most rapid healing; alternatively the

ulcercan be treated with an H

-receptorantagonist.

NSAID treatment needs to continue

, the ulcer is

treatedwith a proton pump inhibitor (section 1.3.5).

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

used to relieve symptoms of

dyspepsia

and

gastro-

oesophageal reﬂux disease

(section 1.1). H

-receptor

antagonistsshould not normally be used for

Zollinger–

Ellisonsyndrome

becauseproton pump inhibitors (sec-

tion1.3.5) are more effective.

Maintenancetreatment with low doses has largely been

replaced in

Helicobacter pylori

positive children by

eradicationregimens (section 1.3).

-receptorantagonist therapy can promote healing of

NSAID-associatedulcers

(section1.3).

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.

Treatment also reduces the risk of

acid aspiration

obstetricpatients at delivery (Mendelson’s syndrome).

-receptor antagonists are also used to reduce the

degradationof pancreatic enzyme supplements (section

1.9.4)in children with cystic ﬁbrosis.

Side-effects

Side-effects of H

-receptor antagonists

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)

particularly in the very ill,blood disorders (including

leucopenia, thrombocytopenia, and pancytopenia),

arthralgia, and myalgia. There are isolated reportsof

gynaecomastiaand impotence.

RANITIDINE

Cautions

acuteporphyria; interactions: Appendix 1

(histamineH

-antagonists)

Renalimpairment

usehalf normal dose if estimated

glomerularﬁltration rate less than 50 mL/minute/

1.73m

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; also

lesscommonly

blurredvision; also reported pancreatitis, involuntary

movementdisorders, interstitial nephritis, alopecia

Licenseduse

oral

preparationsnot licensed for use

inchildren under 3 years;

injection

notlicensed for

usein children under 6 months

Indicationand dose

Reﬂuxoesophagitis, benign gastric andduo-

denalulceration, prophylaxis of stressulcer-

ation,other conditions where gastricacid

reductionis beneﬁcial

(seenotes above and sec-

tion1.9.4)

Bymouth

Neonate

2mg/kg 3 times daily but absorption

unreliable;max. 3 mg/kg 3 times daily

BNFC 2011–2012 1.3.1 H

-receptor antagonists 43

Gastro-intestinalsystem

Child1–6 months

1mg/kg 3 times daily; max.

3mg/kg 3 times daily

Child6 months–3 years

2–4mg/kg twice daily

Child3–12 years

2–4mg/kg (max. 150mg) twice

daily;increased up to 5 mg/kg (max. 300 mg)

twicedaily in severe gastro-oesophageal reﬂ ux

disease

Child12–18 years

150mg twice daily

300mg

atnight; increased if necessary, to 300 mg twice

daily

150mg 4 times daily for up to 12 weeks in

moderateto severe gastro-oesophageal reﬂux

disease

Note

Infat malabsorption syndrome, give 1–2 hours

beforefood to enhance effects of pancreatic enzyme

replacement

Byslow intravenous injection

Neonate

0.5–1mg/kg every 6–8 hour s

Child1 month–18 years

1mg/kg (max. 50 mg)

every6–8 hours (may be given as an intermittent

infusionat a rate of 25 mg/hour)

Administration

For

slowintravenous injection

dilute

toa concentration of 2.5 mg/mL with Glucose 5%

SodiumChloride 0.9%; give over at least 3 minutes

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, 100 mL = £7.44, 300 mL = £19.61

Excipients

mayinclude alcohol (check with supplier)

Note

Ranitidinecan be sold to the public for children over 16

years (provided packs do not containmore than2 weeks’

supply) for the short-term symptomatic reliefof hear tburn,

dyspepsia, and hyperacidity, and for the prevention of these

symptomswhen associated with consumption of food or drink

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

Injection

,ranitidine (as hydrochloride) 25 mg/mL,

netprice 2-mL amp = 57p

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

Classiﬁcationnot used in

BNFfor Children

1.3.3

Chelates and complexes

Sucralfate is a complex of aluminium hydroxide and

sulphatedsucrose that appears to act by protecting the

mucosafrom acid-pepsin attack; it has minimal antacid

properties. Sucralfate can be used to prevent stress

ulcerationin children receiving intensive care. It should

be used with caution in this situation (impor tant:

reports of bezoar formation, see Bezoar Formation

below).

SUCRALFATE

Cautions

administrationof sucralfate and enteral

feedsshould be separated by 1 hour; interactions:

Appendix1 (sucralfate)

Bezoarformation

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

Licenseduse not licensed for use in children under

15years; tablets not licensed for prophylaxis of

stressulceration

Indicationand dose

Prophylaxisof stress ulceration inchild under

intensivecare

Bymouth

Child1 month–2 years

250mg 4–6 times daily

Child2–12 years

500mg 4–6 times daily

Child12–15 years

1g 4–6 times daily

Child15–18 years

1g 6 times daily; max. 8 g

daily

Benigngastric and duodenal ulceration

Bymouth

Child1 month–2 years

250mg 4–6 times daily

Child2–12 years

500mg 4–6 times daily

Child12–15 years

1g 4–6 times daily

Child15–18 years

2g twicedaily (on rising and at

bedtime)

1g 4 times daily (1 hour before meals

andat bedtime) taken for4–6 weeks, or in resistant

casesup to 12 weeks; max. 8 g daily

Administration

foradministration

bymouth

,sucral-

fateshould be given 1 hour before meals, see also

Cautions,above;

oralsuspension

blocksﬁne-bore

feedingtubes; cr ushed

tablets

maybe dispersed in

water.

Antepsin

(Chugai)A

Tablets

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

£5.77.Label: 5

Suspension

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

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

1.3.4

Prostaglandin analogues

Classiﬁcationnot used in

BNFfor Children

44 1.3.3 Chelates and complexes BNFC2011–2012

Gastro-intestinalsystem

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

parietal cell. Omeprazole is an effective short-term

treatment for

gastric

and

duodenal ulcers

; it is also

usedin combination with antibacterials for the eradica-

tion of

Helicobacterpylo ri

(see p. 42 for speciﬁc regi-

mens). An initial short course of omeprazole is the

treatment of choice in

gastro-oesophageal reﬂux dis-

ease

with severe symptoms; children with endoscopi-

callyconﬁrmed

erosive

ulcerative

,or

stricturingoeso-

phagitis

usuallyneed to be maintained on omeprazole.

Omeprazole is also used for the prevention and treat-

mentof NSAID-associated ulcers (see p. 43).In children

whoneed to continue NSAID treatment after an ulcer

hashealed, the dose of omeprazole should not normally

be reduced because asymptomatic ulcer deterioration

mayoccur.

Omeprazole is effective in the treatment of the

Zollinger-Ellison syndrome

(including cases resistant

toother treatment). It is also used to reduce the deg ra-

dationof pancreatic enzymesupplements (section 1.9.4)

inchildren with cystic ﬁbrosis.

Lansoprazole is not licensed for use in children,but

maybe considered when the available formulations of

omeprazoleare unsuitable.

Esomeprazole can be used for the management of

gastro-oesophageal reﬂux disease whenthe available

formulationsof omeprazole and lansoprazole are unsui-

table.

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 pruritus. Other side-effects reported

rarely

veryrarely

includetaste 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

Cautions

interactions:Appendix 1 (proton pump

inhibitors)

Hepaticimpairment

child1–12 years max. 10 mg

dailyin severe impairment; child 12–18 years max.

20mg daily in severe impairment

Renalimpairment

manufactureradvises caution in

severerenal insufﬁciency

Pregnancy

manufactureradvises caution—no infor-

mationavailable

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

seenotes above

Licenseduse tablets not licensed for use in children

1–12years

Indicationand dose

Gastro-oesophagealreﬂux disease (in the pre-

senceof erosive reﬂux oesophagitis)

Bymouth

Child1–12 years

Body-weight10–20 kg

10mg once daily for 8

weeks

Body-weightover 20kg

10–20mg once daily for

8weeks

Child12–18 years

40mg once daily for 4 weeks,

continuedfor further 4 weeks if not fully healed or

symptomspersist; maintenance 20 mg daily

Symptomatictreatment of gastro-oesophageal

reﬂuxdisease (in the absenceof oesophagitis)

Bymouth

Child1–12 years, body-weight over10 kg

10mg once daily for up to 8 weeks

Child12–18 years

20mg once daily for up to 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

Administration Swallowwhole or disper se in water; do not chew

orcrush tablets

Granules

,yellow, e/c, esomeprazole (as magnesium

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

£25.19.Label: 25, counselling, administration

Administration Disperse the contents of each sachet in approx.

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

beforeadministration and use within 30 minutes; rinse container

with15mL water to obtain full dose; can be administered through

nasogastricor gastric tube

LANSOPRAZOLE

Cautions

interactions:Appendix 1 (proton pump

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

Licenseduse not licensed for use in children

Indicationand dose

Gastro-oesophagealreﬂux disease, acid-

relateddyspepsia, treatment of duodenaland

benigngastric ulcer including thosecompli-

catingNSAID therapy, fat malabsorption

despitepancreatic enzyme replacement ther-

apyin cystic ﬁbrosis

Bymouth

Childbody-weight under 30kg

0.5–1mg/kg

(max.15 mg) once daily in the morning

Childbody-weight over 30kg

15–30mg once

dailyin the morning

BNFC 2011–2012 1.3.5 Proton pump inhibitors 45

Gastro-intestinalsystem

Administration

foradministration by a

nasogastric

tube

oran

oralsyringe

ZotonFasTab

canbe

dispersedin a small amount of water

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,

allowedto disperse and swallowed, or may be swallowed

wholewith a glass of water.

OMEPRAZOLE

Cautions

interactions:Appendix 1 (proton pump

inhibitors)

Hepaticimpairment

nomore than 700 micrograms/

kg(max. 20 mg) once daily

Pregnancy

notknown to be harmful

Breast-feeding

presentin milk but not known to be

harmful

Side-effects

seenotes above; also agitation and

impotence

Licenseduse

capsules

and

tablets

notlicensed for

usein children except for severe ulcerating reﬂux

oesophagitisin children over 1 year;

injection

not

licensedfor use in children under 12 years

Indicationand dose

Gastro-oesophagealreﬂux disease, acid-

relateddyspepsia, treatment of duodenaland

benigngastric ulcers including thosecompli-

catingNSAID therapy, prophylaxis ofacid

aspiration,Zollinger-Ellison syndrome, fat

malabsorptiondespite pancreatic enzyme

replacementtherapy in cystic ﬁbrosis

Bymouth

Neonate

700micrograms/kg oncedaily, increased

ifnecessary after 7–14 days to 1.4 mg/kg; some

neonatesmay require up to 2.8 mg/kg once daily

Child1 month–2 years

700micrograms/kg once

daily,increased if necessary to 3 mg/kg (max.

20mg) once daily

Childbody-weight 10–20 kg

10mg once daily

increasedif necessar y to 20 mg once daily (in

severeulcerating reﬂux oesophagitis, max. 12

weeksat higher dose)

Childbody-weight over 20kg

20mg once daily

increasedif necessar y to 40 mg once daily (in

severeulcerating reﬂux oesophagitis, max. 12

weeksat higher dose)

Byintravenous injection over 5minutes or by

intravenousinfusion

Child1 month–12 years

initially500 micr-

ograms/kg(max. 20 mg) once daily, increased to

2mg/kg (max. 40 mg) once daily if necessary

Child12–18 years

40mg once daily

Helicobacterpylori eradication

(incombination

withantibacterials see p. 42)

Bymouth

Child1–12 years

1–2mg/kg (max. 40 mg) once

daily

Child12–18 years

40mg once daily

Administration

foradministration

bymouth

,swallow

whole,

disperse

LosecMUPS

tabletsin water,

mixcapsule contents or

LosecMUPS

tabletswith

fruitjuice or yoghurt. Preparations consisting of an

e/ctablet within a capsule should not be opened.

Foradministration through an

enteralfeeding tube

use

LosecMUPS

orthe contents of a capsule

containingomeprazole dispersed in a large volume of

water,or in 10 mL Sodium Bicarbonate 8.4% (1mmol

/mL)(allow to stand for 10 minutes before

administration).

For

intermittentintravenous infusion

,dilute reconsti-

tutedsolution to a concentration of 400 micrograms/

mLwith Glucose 5%

SodiumChloride 0.9%; give

over20–30 minutes

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

Note

Somepreparations consist of an e/c tablet within a

capsule

Brandsinclude

Mepradec

Dentalprescribing on NHS

Gastro-resistantomeprazole

capsulesmay be prescribed

Tablets

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

=£5.84; 20mg, 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

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

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—thisis particularly important in infants. Fordetails

of oral rehydration preparations, see section 9.2.1.2.

Severe dehydration requires immediate admission to

hospital and urgent replacementof ﬂ uid and electro-

lytes.

Antimotilitydrugs (section 1.4.2) relieve symptoms of

diarrhoea.They are used in the management of uncom-

plicated acute diarrhoea in adults, but are not recom-

46 1.4 Acute diarrhoea BNFC 2011–2012

Gastro-intestinalsystem

mended for use in children under 12 years. Fluid and

electrolyte replacement (section 9.2.1.2)are ofprime

importancein the treatment of acute diarrhoea.

Antispasmodics(section 1.2) are occasionally of value

intreating abdominal cramp associated with diarrhoea

but they should not be used for primary treatment.

Antispasmodicsand antiemetics should be avoided in

youngchildren withgastro-enteritis since they are rarely

effectiveand have troublesome side-effects.

Antibacterialdrugs are generally unnecessary in simple

gastro-enteritisbecause the complaint usually resolves

quicklywithout such treatment,and infective diarrhoeas

in the UK often have a viral cause. Systemic bacterial

infection does, however, need appropriate systemic

treatment; for drugs usedin campylobacter enteritis,

shigellosis,and salmonellosis, see p. 244

Colestyramine (section 1.9.2) binds unabsorbed bile

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 rarely effective in controlling faecal consistency in

ileostomyand colostomy.

1.4.2

Antimotility drugs

Antimotility drugs have arole in the managementof

uncomplicated

acute diarrhoea

in adults but not in

childrenunder 12 years; see also section 1.4. However,

inthe case of dehydration, ﬂuid and electrolyte replace-

ment(section 9.2.1.2) are of primary importance.

Forcomments on their role in

chronicbowel disorders

see section 1.5. Antimotility drugs are also used in

childrenwith

stoma

(section1.8).

CODEINEPHOSPHATE

Cautions

seesection 4.7.2; tolerance and dependence

mayoccur with prolonged use; interactions: Appen-

dix1 (opioid analgesics)

Contra-indications

seesection 4.7.2; 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

Indicationand dose

Diarrhoea

(butsee notes above)

Bymouth

Child12–18 years

30mg (range 15–60 mg) 3–4

timesdaily

Pain

section4.7.2

Preparations

Section4.7.2

CO-PHENOTROPE

Amixture of diphenoxylate hydrochloride and atro-

pinesulphate in the mass proportions 100 parts to 1

partrespectively

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

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,fever

Licenseduse notlicensed for use in children under4

years

Indicationand dose

Seepreparations

Administration

foradministration

bymouth

tablets

maybe cr ushed

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

Controlof faecal consistencyafter colostomy or

ileostomy,adjunct to rehydrationin acute diarrhoea

(butsee notes above)

Bymouth

Child2–4 years

halftablet 3 times daily

Child4–9 years

1tablet 3 times daily

Child9–12 years

1tablet 4 times daily

Child12–16 years

2tablets 3 times daily

Child16–18 years

initially4 tablets then 2 tablets 4

timesdaily

Note

Co-phenotrope2.5/0.025 can be sold to the public for

childrenover 16 years (provided packs do not contain more

than20 tablets) as an adjunct to rehydration in acute diarr-

hoea(max. daily dose 10 tablets)

LOPERAMIDEHYDROCHLORIDE

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

manufactureradvises avoid—no informa-

tionavailable

Breast-feeding

amountprobably too small to be

harmful

BNFC 2011–2012 1.4.1 Adsorbents and bulk-forming drugs 47

Gastro-intestinalsystem

Side-effects

abdominalcramps, dizziness, drowsi-

ness,and skin reactions including ur ticaria; paralytic

ileusand abdominal bloating also reported

Licenseduse

capsules

notlicensed for use in chil-

drenunder 8 years;

syrup

notlicensed for use in

childrenunder 4 years; not licensed for use in

childrenfor chronic diarrhoea

Indicationand dose

Chronicdiarrhoea

Bymouth

Child1 month–1 year

100–200micrograms/kg

twicedaily,30 minutes before feeds; up to 2mg/kg

dailyin divided doses occasionally required

Child1–12 years

100–200micrograms/kg (max.

2mg) 3–4 times daily; up to 1.25 mg/kg daily in

divideddoses may be required (max. 16 mg daily)

Child12–18 years

2–4mg 2–4 times daily (max.

16mg daily)

Acutediarrhoea

(butsee notes above)

Bymouth

Child4–8 years

1mg 3–4 times daily for

upto 3

daysonly

Child8–12 years

2mg 4 times daily for up to 5

days

Child12–18 years

initially4 mg, then 2 mg after

eachloose stool for up to 5 days (usual dose 6–

8mg daily; max. 16 mg daily)

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, for use in children

over 12 years, provided it is licensed and labelled for the

treatmentof acute diar rhoea

Imodium

(Janssen)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 abdominalcolic

Child12–18 years

initially1 caplet, then 1 caplet after

eachloose stool; max. 4 caplets daily for up to 2 days

1.5

Chronic bowel disorders

Individual symptoms of chronic bowel disorders need

speciﬁc treatment including dietary manipulation as

wellas drug treatment and the maintenance of a liberal

ﬂuidintake.

Inﬂammatory bowel disease

Chronicinﬂammatory bowel diseases include

ulcerative

colitis

and

Crohn’sdisease

.The treatment of inﬂamm-

atorybowel disease in children should be initiated and

supervisedby a paediatric gastroenterologist. Ef fective

management requires drug therapy, attention to nutri-

tion,and in severe or chronic active disease, surger y.

Aminosalicylates (balsalazide, mesalazine, olsalazine,

and sulfasalazine), corticosteroids (hydrocortisone,

budesonide,and prednisolone), and dr ugsthat af fect

the immune response are usedin the treatment of

inﬂammatory bowel disease.

Treatmentof acute ulcerativecolitis and Crohn’s

disease

Acutemild to moderate disease affecting the

rectum(proctitis) or the recto-sigmoid (distal colitis) is

treated initially with local application of an aminosali-

cylate(section 1.5.1); alternatively a local corticosteroid

(section1.5.2) can be used but it is less effective. Foam

preparations and suppositories areuseful for children

whohave dif ﬁculty retaining liquid enemas.

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

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

children with Crohn’s disease affecting theileum and

the ascending colon; it causes fewer systemic side-

effectsthan oral prednisolone, but may be lessef fective.

As an alternative to an oral corticosteroid, enteral

nutrition (Appendix 2) may be used for 6–8 weeks in

childrenwith active Crohn’s disease.

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 (p.375) or

methylprednisolone (p.376); other therapy may

include intravenous ﬂuid and electrolyte replacement,

and possibly parenteral nutrition. Children with ulcer-

ative colitis that fails to respondadequately to these

measuresmay beneﬁt from a short course of ciclospor-

in. Children with unresponsive or chronically active

Crohn’s disease may beneﬁt from azathioprine,

mercaptopurine, or once-weekly methotrexate; these

drugshave a slow onset of action.

Inﬂiximab (section 1.5.3) is used in specialist centres

for children with severe active Crohn’s disease 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.Inﬂiximab has also been used for the treatment of

severe,refractory ulcerative colitis. There are concerns

about the long-ter m safety of inﬂiximab in children;

hepatosplenicT-cell lymphoma has been reported.

Crohn’sdisease ofthe mouth or of the perineum is more

commonin children than in adults and it is difﬁcult to

treat;elimination diets and the use of a topical cortico-

steroid(section 13.4) may be beneﬁcial, but a systemic

corticosteroid(section 6.3.2) and occasionally azathio-

prinemay be required in severe cases.

48 1.5 Chronic bowel disorders BNFC 2011–2012

Gastro-intestinalsystem

NICEguidance

Inﬂiximabfor Crohn’s disease (May 2010)

Inchildren over 6 years of age, inﬂiximab is recom-

mended for the treatment of severe active Crohn’s

disease that has not responded to conventional

therapy (including corticosteroids, other drugs

affecting the immune response, and primary nutri-

tiontherapy) or when conventional therapy cannot

beused because ofintolerance or contra-indications.

Inﬂiximab should be given as a planned course of

treatment for 12 months or until treatment failure,

whicheveris shorter.Treatment should be continued

beyond12 months only if there is evidence of active

disease—in these cases the need for treatment

shouldbe reviewed at least annually. If the disease

relapsesafter stopping treatment, inﬂiximab can be

restarted[but see Hypersensitivity Reactions under

Inﬂiximab,p. 55].

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.

Maintenance of remission of acute ulcerative

colitis and Crohn’s disease

Children should be

advised not to smoke becausesmoking increases the

risk of relapse in Crohn’s disease. Smokingcessation

(section4.10.2) should be encouraged when necessary.

Aminosalicylatesare efﬁcacious in the maintenance of

remissionof ulcerative colitis, but there is no evidence

ofef ﬁcacy in the maintenance of remission of Crohn’s

disease. Corticosteroids are not suitable for mainte-

nancetreatment because of their side-effects. In resis-

tant or frequently relapsing cases either azathioprine

(section1.5.3) or mercaptopur ine(section 1.5.3) may

be helpful. Methotrexate (section 1.5.3) is used in

Crohn’sdisease when azathioprine or mercaptopurine

are ineffective or not tolerated. Inﬂiximab (p. 55) can

beused for maintenance therapy in Crohn’s disease or

ulcerativecolitis in children who respond to the initial

inductioncourse of this drug. There are concerns about

thelong-term safety of inﬂ iximab in children.

FistulatingCrohn’s disease

Treatmentmay not be

necessary for simple,asymptomatic perianal ﬁstulas.

Metronidazole (section 5.1.11) or ciproﬂoxacin (sec-

tion 5.1.12) may be beneﬁcial for the treatment of

ﬁstulating Crohn’s disease [both unlicensed for this

indication].Metronidazole by mouth is used at a dose

of7.5 mg/kg 3times daily, usually for 1month; it should

notbe used for longer than 3 months because of con-

cerns about peripheral neuropathy. Ciproﬂoxacin by

mouthis given at a dose of 5 mg/kg 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. Inﬂiximab is used for ﬁs-

tulating Crohn’s disease refractory to conventional

treatments;maintenance therapy with inﬂiximab should

be considered for patientswho respondto the initial

inductioncourse.

Adjunctivetreatment of inﬂammatorybowel dis-

ease

Dueattention should be paid to diet; high-ﬁbre or

low-residuediets should be used as appropriate.

Antimotilitydrugs such ascodeine phosphate and loper-

amide,and antispasmodic drugs mayprecipitate paraly-

tic ileus and megacolon in active ulcerative colitis;

treatmentof the inﬂammation is more logical. Laxatives

may be required in proctitis. Diar rhoea resulting from

the loss of bile-salt absorption (e.g. inter minal ileal

diseaseor bowel resection) may improve with colestyr-

amine(section 1.9.2), which binds bile salts.

Irritable bowel syndrome

Irritable bowel syndrome can present with pain,con-

stipation, or diarrhoea. Some children have important

psychological aggravating factors which respond to

reassurance.The ﬁbre intake of children with irritable

bowelsyndrome should be reviewed. If an increase in

dietary ﬁbre isrequired, soluble ﬁbre (e.g. oats, isp-

aghula husk, or sterculia)is recommended; insoluble

ﬁbre(e.g. bran) should be avoided. A laxative (section

1.6) can be used to treat constipation. An osmotic

laxative, such as a macrogol, is preferred; lactulose

may cause bloating. Loperamide (section 1.4.2)may

relievediarrhoea and antispasmodic dr ugs (section 1.2)

mayrelieve pain. Opioids with a central action, such as

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

endence.

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 antibacterials are free of this side-

effect. Oral metronidazole (section 5.1.11) or oral

vancomycin(section 5.1.7) are used as speciﬁc treat-

ment; vancomycin may be preferred for very sick

patients. Metronidazole can be given by intravenous

infusionif oral treatment is inappropriate.

Malabsorption syndromes

Individual conditions need speciﬁc management and

also general nutritional consideration. Coeliac disease

(gluten enteropathy) usually needs a gluten-free diet

(Appendix 2) and pancreatic insufﬁciencyneeds pan-

creatinsupplements (section 1.9.4).

For further information on foods for special diets

(ACBS),see Appendix 2.

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-

BNFC 2011–2012 1.5.1 Aminosalicylates 49

Gastro-intestinalsystem

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

cylicacid which cleaves in the lower bowel), the sulfo-

namide-relatedside-effects of sulfasalazine are avoided,

but 5-aminosalicylic acid alone can still cause side-

effectsincluding blood disorders (see recommendation

below)and lupus-like syndrome also seen with sulfasa-

lazine.

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

Childrenreceiving aminosalicylates and their carers

shouldbe advised to report any unexplained bleed-

ing,bruising, purpura, sore throat, fever or malaise

thatoccurs during treatment. A blood count should

beperfor med and the drug 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

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

Licenseduse not licensed for use in children under

18years

Indicationand dose

Treatmentof mildto moderate ulcerativecolitis

andmaintenance of remission

Bymouth

Child12–18 years

acuteattack, 2.25 g 3 times

dailyuntil remission occurs or for up to max. 12

weeks;maintenance, 1.5 g twice daily, adjusted

accordingto response (max. 3 g twice daily)

Colazide

(Almirall)A

Capsules

,beige, balsalazide sodium750 mg, net price

130-cappack = £30.42. Label: 21, 25, counselling,

blooddisorder symptoms (see recommendation

above)

MESALAZINE

Cautions

seenotes above; interactions: Appendix 1

(aminosalicylates)

Blooddisorders

seerecommendation above

Contra-indications

seenotes above; blood clotting

abnormalities

Hepaticimpairment

avoidin severe impairment

Renalimpairment

usewith caution; avoid if esti-

matedglomerular ﬁltration rate less than 20 mL/

minute/1.73m

Pregnancy

negligiblequantity crosses placenta

Breast-feeding

diarrhoeareported but negligible

amountsdetected in breast milk; monitor infant for

diarrhoea

Side-effects

seenotes above

Licenseduse

Asacol

(allpreparations) and

Sal-

ofalk

enemanot licensed for use in children under

18years;

Salofalk

suppositories,

Pentasa

tablets

andsuppositories not licensed for use in children

under15 years;

Pentasa

granulesnot licensed for

usein children under 6 years;

Salofalk

rectalfoam

nodose recommendations for children (age range

notspeciﬁed by manufacturer)

Indicationand dose

Treatmentof mildto moderate ulcerativecolitis

andmaintenance ofremission

fordose see under

preparationsbelow

Note

Thedelivery characteristics of oral mesalazine

preparationsmay vary; these preparations should not be

consideredinterchangeable

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 therectosigmoid region

Byrectum

Child12–18 years

1metered application (mesalazine

1g) into the rectum daily for 4–6 weeks

Acuteattack affecting thedescending colon

Byrectum

Child12–18 years

2metered applications (mesalazine

2g) once daily for 4–6 weeks

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

Treatmentand maintenance ofremission of ulcer-

ativecolitis affecting therectosigmoid region

Byrectum

Child12–18 years

250–500mg 3 times daily, with last

doseat bedtime

50 1.5.1 Aminosalicylates BNFC 2011–2012

Gastro-intestinalsystem

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

Acuteattack

Bymouth

Child12–18 years

800mg 3 times daily

Maintenanceof remission ofulcerative colitis and

Crohn’sileo-colitis

Bymouth

Child12–18 years

400–800mg 2–3 times daily

Note

Preparationsthat 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

Bymouth

Child12–18 years

800mg 3 times daily

Maintenanceof remission

Bymouth

Child12–18 years

400–800mg 3 times daily

MesrenMR

(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

Acuteattack

Bymouth

Child12–18 years

800mg 3 times daily

Maintenanceof remission ofulcerative colitis and

Crohn’sileo-colitis

Bymouth

Child12–18 years

400–800mg 3 times 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

Acuteattack

Bymouth

Child5–15 years

15–20mg/kg (max. 1 g) 3 times daily

Child15–18 years

1–2g twice daily; total daily dose

mayalternatively be given in 3 divided doses

Maintenanceof remission

Bymouth

Child5–15 years

10mg/kg (max. 500 mg) 2–3 times

daily

Child15–18 years

2g once daily

Administration

tabletsmay be halved, quartered, or dis-

persedin water, but should not be chewed

Granules

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

sachet,net price 50-sachet pack = £28.82;

2g/sachet, 60-sachet pack = £72.05. Counselling,

administration(see dose), blood disorder symptoms

(seerecommendation above)

Dose

Acuteattack

Bymouth

Child5–12 years

15–20mg/kg (max. 1 g) 3 times daily

Child12–18 years

1–2g twice daily; total daily dose

mayalternatively be given in 3–4 divided doses

Maintenanceof remission

Bymouth

Child5–12 years

10mg/kg (max. 500 mg) 2–3 times

daily

Child12–18 years

2g once daily

Administration

contentsof one sachet should be weighed

anddivided immediately before use; discard any remaining

granules.Granules should be placed on tongue and washed

downwith water or orange juice without chewing

Retentionenema

,mesalazine 1g in 100-mL pack, net

price7 enemas = £17.73. Counselling, blood disorder

symptoms(see recommendation above)

Dose

Acuteattack affecting therectosigmoid region

Byrectum

Child12–18 years

1g at bedtime

Suppositories

,mesalazine 1 g, net price 28-suppos

pack= £40.01. Counselling, blood disordersymptoms

(seerecommendation above)

Dose

Acuteattack, ulcerative proctitis

Byrectum

Child12–18 years

1g daily for 2–4 weeks

Maintenance,ulcerative proctitis

Byrectum

Child12–18 years

1g daily

Salofalk

(DrFalk) A

Tablets

,e/c, yellow, mesalazine 250 mg, net price

100-tabpack = £16.19; 500 mg, 100-tab pack =

£32.38.Label: 5, 25, counselling, blood disorder

symptoms(see recommendation above)

Dose

Acuteattack

Bymouth

Child6–18 years andbody-weight under40 kg

10–

20mg/kg 3 times daily

Child6–18 yearsand body-weight over40kg

0.5–1g

3times daily

Maintenanceof remission

Bymouth

Child6–18 years andbody-weight under40 kg

5–

10mg/kg3 times daily; total daily dose mayalternatively

begiven in 2 divided doses

Child6–18 yearsand body-weightover 40kg

500mg

3times daily

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. Counselling,

administration(see dose), blood disorder symptoms

(seerecommendation above)

Excipients

includeaspartame (section 9.4.1)

Dose

Acuteattack

Bymouth

Child6–18 years andbody-weight under40 kg

10–

20mg/kg 3 times daily

BNFC 2011–2012 1.5.1 Aminosalicylates 51

Gastro-intestinalsystem

Child6–18 yearsand body-weight over40kg

1.5–3g

oncedaily (preferably in the morning)

0.5–1g 3 times

daily

Maintenanceof remission

Bymouth

Child6–18 years andbody-weight under40 kg

5–

10mg/kg3 times daily; total daily dose mayalternatively

begiven in 2 divided doses

Child6–18 yearsand body-weightover 40kg

500mg

3times daily

Administration

Granulesshould be placed on tongue and

washeddown with water without chewing

Note

Preparationsthat lower stool pH (e.g. lactulose) may

preventrelease of mesalazine

Suppositories

,mesalazine 500 mg. Net price 30-

suppospack = £14.81. Counselling, blood disorder

symptoms(see recommendation above)

Dose

Acuteattack

Byrectum

Child12–18 years

0.5–1g 2–3 times daily adjusted

accordingto response

Enema

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

enemas= £29.92. Counselling, blood disorder symp-

toms(see recommendation above)

Dose

Acuteattack or maintenance

Byrectum

Child12–18 years

2g once daily at bedtime

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 affectingsigmoid colon and

rectum

Byrectum

Child12–18 years

2metered applications (mesalazine

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

OLSALAZINE SODIUM

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

Licenseduse not licensed for use in children under

12years

Indicationand dose

Treatmentof acute attack ofmild ulcerative

colitis

Bymouth

Child2–18 years

500mg twice daily after food

increasedif necessar y over 1 week to max. 1 g 3

timesdaily

Maintenanceof remission of mildulcerative

colitis

Bymouth

Child2–18 years

250–500mg twice daily after

food

Administration

Capsulescan be opened and contents

sprinkledon food

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)

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 with doses over

4g daily; acute porphyria (section 9.8.2); interac-

tions:Appendix 1 (aminosalicylates)

Blooddisorders

seerecommendation above

Contra-indications

seenotes above; also sulfonamide

hypersensitivity;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

smallamount 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

Indicationand dose

Treatmentof acute attack ofmild to moderate

andsevere ulcerative colitis, activeCrohn’s

disease

Bymouth

Child2–12 years

10–15mg/kg (max. 1 g) 4–6

timesdaily until remission occurs; increased to

max.60 mg/kg daily in divided doses, if necessary

Child12–18 years

1–2g 4 times daily until

remissionoccurs

52 1.5.1 Aminosalicylates BNFC 2011–2012

Gastro-intestinalsystem

Maintenanceof remission of mildto moderate

andsevere ulcerative colitis

Bymouth

Child2–12 years

5–7.5mg/kg (max. 500 mg) 4

timesdaily

Child12–18 years

500mg 4 times daily

Treatmentof mild to moderateor severe ulcer-

ativecolitis and maintenance ofremission,

activeCrohn’s disease

Byrectum as suppositories

Child5–8 years

500mg twice daily

Child8–12 years

500mg in the morning and 1 g

atnight

Child12–18 years

0.5–1g twice daily

Juvenileidiopathic arthritis

section10.1.3

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, sulfasalazine 500 mg. Net

price10 = £3.30. Label: 14, counselling, blood dis-

ordersymptoms (see recommendation above), con-

tactlenses may be stained

1.5.2

Corticosteroids

Forthe role of corticosteroids in acute ulcerative colitis

andCrohn’s disease, see Inﬂ ammatory Bowel Disease,

p.48.

BUDESONIDE

Cautions

section6.3.2; interactions: Appendix 1

(corticosteroids)

Contra-indications

section6.3.2

Hepaticimpairment

section6.3.2

Pregnancy

section6.3.2

Breast-feeding

section6.3.2

Side-effects

section6.3.2

Licenseduse not licensed for use in children

Indicationand dose

Seepreparations

Administration

Capsulescan be opened and the

contentsmixed with apple or orange juice

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’sdisease affecting ileumor

ascendingcolon, chronicdiarrhoea due to collage-

nouscolitis

Bymouth

Child12–18 years

3mg 3 timesdaily for up to 8 weeks;

reducedose for the last 2 weeks of treatment. See also

section6.3.2

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, 22, 25

Note

Dispensein original container (contains desiccant)

Dose

Mildto moderateCrohn’s diseaseaffecting theileum

orascending colon

Bymouth

Child12–18 years

9mg once daily in the morning

beforebreakfast for up to 8 weeks; reduce dose for the

last2–4 weeks of treatment. See also section 6.3.2

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 rectaland recto-sigmoid

disease

Byrectum

Child12–18 years

1enema at bedtime for 4 weeks

HYDROCORTISONE

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

Indicationand dose

Inﬂammatorybowel disease

Byintravenous administration

Seep. 375

Byrectum

Seepreparations

Colifoam

(Meda)A

Foam

inaerosol pack, hydrocortisone acetate 10%,

netprice 14-application cannister with applicator =

£9.28

Excipients

include cetyl alcohol, hydroxybenzoates (parabens), propy-

leneglycol

Dose

Ulcerativecolitis, proctitis, proctosigmoiditis

Byrectum

Child2–18 years

initially1 meteredapplication (125 mg

hydrocortisoneacetate) inserted into the rectum once or

twicedaily for 2–3 weeks, then once on alternate days

BNFC 2011–2012 1.5.2 Corticosteroids 53

Gastro-intestinalsystem

PREDNISOLONE

Cautions

section6.3.2; systemic absorption may

occur;prolonged use should be avoided

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

Licenseduse

Predfoam

Predsol

retention

enema

notlicensed for use in children (age range

notspeciﬁed by manufacturer)

Indicationand dose

Ulcerativecolitis, Crohn’sdisease

seealso under

preparations,below

Bymouth

Child2–18 years

2mg/kg (max. 60 mg) once

dailyuntil remission occurs, followed by reducing

doses

Byrectum

Seeunder preparations

Otherindications

section6.3.2

Oralpreparations

Section6.3.2

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

Byrectum

Child12–18 years

initially20 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 cannister with disposable appli-

cators= £6.32

Excipients

includecetostearyl alcohol, disodium edetate, polysorbate

20,sorbic acid

Dose

Proctitisand distal ulcerativecolitis

Byrectum

Child12–18 years

1metered application (20 mg pred-

nisolone)inserted into the rectum once or twice daily for

2weeks, continued for fur ther 2 weeks if good response

Predsol

(UCBPharma) A

Suppositories

,prednisolone 5 mg (as sodium phos-

phate).Net price 10 = £1.35

Dose

Proctitisand rectal complicationsof Crohn’sdisease

Byrectum

Child2–18 years

5mg inserted night and morning after

abowel movement

1.5.3

Drugs affecting the

immune response

Azathioprine, mercaptopurine, or once weekly

methotrexate are used toinduce remissionin unre-

sponsiveor chronically active Crohn’s disease. Azathio-

prineor mercaptopurine may also be helpful for retain-

ing remission in frequently relapsing inﬂ ammatory

bowel disease; once weekly methotrexate is used in

Crohn’sdisease when azathioprine or mercaptopurine

are ineffective or not tolerated. Responseto azathio-

prineor mercaptopurine may not become apparent for

several months. Folicacid (section 9.1.2) should be

givento reduce the possibility of methotrexate toxicity.

Folic acid can be given at a dose of 5 mg weekly;

alternativeregimens may be used in some settings.

Ciclosporin (cyclosporin)is a potent immunosuppres-

sant and is markedly nephrotoxic. In children with

severe ulcerative colitis unresponsive to other treat-

ment,ciclosporin may reduce the need for urgent color-

ectalsurgery.

AZATHIOPRINE

Cautions

section8.2.1; interactions: Appendix 1

(azathioprine)

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

Licenseduse not licensed for use in ulcerative col-

itisor Crohn’s disease

Indicationand dose

Severeulcerative colitis and Crohn’sdisease

Bymouth

Child2–18 years

initially2 mg/kg once daily,

thenincreased if necessary up to 2.5 mg/kg once

daily

Transplantationrejection

section8.2.1

Rheumaticdiseases

section10.1.3

Preparations

Section8.2.1

CICLOSPORIN

Cautions

section8.2.2; interactions: Appendix 1

(ciclosporin)

Hepaticimpairment

section8.2.2

Renalimpairment

section8.2.2

Pregnancy

section8.2.2

Breast-feeding

section8.2.2

Side-effects

section8.2.2

Licenseduse not licensed for use in ulcerative col-

itis

54 1.5.3 Drugs affecting the immune response BNFC2011–2012

Gastro-intestinalsystem

Indicationand dose

Refractoryulcerative colitis

Bymouth

Child2–18 years

initially2 mg/kg twice daily,

doseadjusted according to blood-ciclosporin

concentrationand response; max. 5 mg/kg twice

daily

Important

Foradvice on counselling and conversion

betweenpreparations, see section 8.2.2

Byintravenous infusion

Child3–18 years

initially0.5–1 mg/kg twice

daily,doseadjusted according to blood-ciclosporin

concentrationand response

Nephroticsyndrome

section8.2.2

Transplantationrejection and auto-immune

conditions

section8.2.2

Atopicdermatitis and psoriasis

section13.5.3

Administration

for

intermittentintravenous infusion

diluteto a concentration of 0.5–2.5 mg/mL with

Glucose5%

SodiumChloride 0.9% and give over

2–6hours; not to be used with PVC equipment;

observepatient for signs of anaphylaxis for at least 30

minutesafter starting infusion and at frequent inter-

valsthereafter

Preparations

Section8.2.2

MERCAPTOPURINE

(6-Mercaptopurine)

Cautions

section8.1.3; see also Azathioprine, section

8.2.1

Contra-indications

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

Licenseduse not licensed for use in severe ulcer-

ativecolitis and Crohn’s disease; for other indica-

tions,see section 8.1.3

Indicationand dose

Severeulcerative colitis and Crohn’sdisease

Bymouth

Child2–18 years

1–1.5mg/kg once daily (initial

max.50 mg;may be increased to 75mg once daily)

Acuteleukaemias

section8.1.3

Preparations

Section8.1.3

METHOTREXATE

Cautions

section10.1.3

Contra-indications

section10.1.3

Hepaticimpairment

section10.1.3

Renalimpairment

section8.1.3

Pregnancy

section8.1.3

Breast-feeding

section8.1.3

Side-effects

section10.1.3

Licenseduse not licensed for use in children for

non-malignantconditions

Indicationand dose

Severeacute Crohn’s disease

Bysubcutaneous or intramuscular injection

Child7–18 years

15mg/m

(max.25 mg) once

weekly

Maintenanceof remission of severeCrohn’s

disease

Bymouth or bysubcutaneous orintramuscular

injection

Child7–18 years

15mg/m

(max.25 mg) once

weekly;dose reduced according to response to

lowesteffective dose

SafePractice

Notethat the above dose is a weekly dose. To avoid

errorwith low-dose methotrexate, it is recommended

that:

thechild or their carer is carefully advised of the dose and

frequencyand the reason for taking methotrexate and any

otherprescribed medicine (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;

thechild or their carer is warned to report immediately the

onsetof any feature of blood disorders (e.g. sore throat,

bruising, and mouth ulcers), livertoxicity (e.g. na usea,

vomiting,abdominal discomfort, and dark urine), and resp-

iratoryeffects (e.g. shortness of breath).

Malignantdisease

section8.1.3

Rheumaticdisease

section10.1.3

Psoriasis

section13.5.3

Preparations

Section10.1.3

Cytokinemodulators

Inﬂiximabis a monoclonal antibody which inhibits the

pro-inﬂammatory cytokine, tumour necrosis factor

alpha.It should be administered under specialist super-

visionwhere adequate resuscitation facilities are avail-

ableand is used in the treatment of severe refractory or

ﬁstulatingCrohn’s disease in children.Inﬂ iximab should

beused only when treatment with other immunomodu-

latingdrugs has failedor is not tolerated and forchildren

inwhom surger y is inappropriate.

INFLIXIMAB

Cautions

monitorfor infections before, during, and for

6months after treatment (see also Tuberculosis

below);predisposition to infection; chronic hepatitis

B—monitorfor active infection; heart failure (dis-

continueif symptoms develop or worsen; avoid in

moderateor severe heart failure); demyelinating CNS

disorders(risk of exacerbation); history of malignancy

(considerdiscontinuing treatment if malignancy

BNFC 2011–2012 1.5.3 Drugs affecting the immune response 55

Gastro-intestinalsystem

develops);history of prolonged immunosuppressant

orPUVA treatment in patients with psoriasis; inter-

actions:Appendix 1 (inﬂiximab)

Tuberculosis

Childrenshould be evaluated for tuberculosis

beforetreatment. Active tuberculosis should be treated with

standardtreatment (section 5.1.9) for at least 2 months

beforestarting inﬂiximab. Children who have previously

receivedadequate treatment for tuberculosis can start

inﬂiximabbut should be monitored every 3 months for

possiblerecurrence. In those without active tuberculosis but

whowere previously not treated adequately, chemoprophy-

laxisshould ideally be completed before starting inﬂ iximab.

Inchildren at high risk of tuberculosis who cannot be

assessedby tuberculin skin test, chemoprophylaxis can be

givenconcurrently with inﬂiximab. Children and their carers

shouldbe advised to seek medical attention if symptoms

suggestiveof tuberculosis (e.g. persistent cough, weightloss,

andfever) develop

Hypersensitivityreactions

(includingfever, chest pain, hypotension, hypertension,

dyspnoea,pruritus, urticaria, serum sickness-like reactions,

angioedema,anaphylaxis) reported during or within 1–2

hoursafter infusion (risk greatest during ﬁrst or second

infusionor in children who discontinue other immuno-

suppressants).All children should be observed carefully for

1–2hours after infusion and resuscitation equipment should

beavailable for immediate use. Prophylactic antipyretics,

antihistamines,or hydrocortisone may be administered.

Readministrationnot recommended after inﬂiximab-free

intervalof more than 16 weeks—risk of delayed hyper-

sensitivityreactions. Children and carers should be advised

tokeep Alert card with them at all times and seek medical

adviceif symptoms of delayed hypersensitivity develop

Contra-indications

severeinfections (see also under

cautions)

Pregnancy

useonly if essential; manufacturer advises

adequatecontraception during and for at least 6

monthsafter last dose

Breast-feeding

amountprobably too small to be

harmful

Side-effects

seeunder Cytokine Modulators (section

10.1.3)and Cautions above; also diarrhoea, dys-

pepsia;ﬂushing, chest pain; dyspnoea; dizziness,

fatigue;sinusitis; rash, increased sweating, dr y skin;

lesscommonly

constipation,gastro-oesophageal

reﬂux,cholecystitis, palpitation, arrhythmia, hyper-

tension,hypotension, vasospasm, cyanosis, brady-

cardia,syncope, oedema, thrombophlebitis, epistaxis,

pleurisy,confusion, agitation, nervousness, amnesia,

sleepdisturbances, vaginitis, demyelinating disorders,

antibodyformation, pyelonephritis, myalgia, arthr-

algia,eye disorders, abnormal skin pigmentation,

ecchymosis,cheilitis, and alopecia;

rarely

hepatitis,

intestinalstenosis, intestinal perforation, gastro-

intestinalhaemorrhage, pancreatitis, lymphoma

(includinghepatosplenic T-cell lymphoma), circula-

toryfailure, meningitis, and seizure;

veryrarely

peri-

cardialeffusion, and skin reactions (including Ste-

vens-Johnsonsyndrome and toxic epidermal

necrolysis);also reported interstitial lung disease,

transversemyelitis, neuropathy, paraesthesia, new

onsetor worsening psoriasis

Licenseduse not licensed for ﬁstulating Crohn’s

diseasein children

Indicationand dose

Severeactive Crohn’s disease

Byintravenous infusion

Child6–18 years

initially5 mg/kg, then 5 mg/kg

2weeks and 6 weeks after initial dose, then 5 mg/

kgevery 8 weeks; inter val between maintenance

dosesadjusted according to response; discontinue

ifno response within 10 weeks of initial dose

FistulatingCrohn’s disease

Byintravenous infusion

Child6–18 years

initially5 mg/kg, then 5 mg/kg

2weeks and 6 weeks after initial dose, then if

conditionhas responded, consult literature for

guidanceon fur ther doses

Administration

for

intravenousinfusion

reconstitute

each100-mg vial of powder with 10 mL Water for

Injections;to dissolve, gently swirl vial without shak-

ing;allow to stand for 5 minutes; dilute required dose

withSodium Chloride 0.9% to a ﬁnal volume of

250mL and give through a low protein-binding ﬁlter

(1.2micron or less)over at least 2 hours; start infusion

within3 hour s of reconstitution

Remicade

(Schering-Plough)A

Intravenousinfusion

,powder for reconstitution,

inﬂiximab,net price 100-mg vial = £419.62.Label: 10,

alertcard, counselling, tuberculosis and hypersensi-

tivityreactions

1.5.4

Food allergy

Allergywith classical symptoms of vomiting, colic and

diarrhoea caused by speciﬁc foods such as cow’s milk

shouldbe managed by strict avoidance. The condition

should be distinguished from symptoms of occasional

food intolerance in children with irritable bowel

syndrome. Sodium cromoglicate (sodium cromogly-

cate)may be helpful as an adjunct to dietary avoidance.

SODIUM CROMOGLICATE

(Sodiumcromoglycate)

Pregnancy

notknown to be harmful

Breast-feeding

unlikelyto be present in milk

Side-effects

occasionalnausea, rashes, and joint pain

Indicationand dose

Foodallergy (in conjunction withdietar y

restriction)

Bymouth

Child2–14 years

100mg 4 times daily before

meals,dose may be increased after 2–3 weeks to a

max.40 mg/kg daily and then reduced according

toresponse

Child14–18 years

200mg 4 times daily before

meals,dose may be increased after 2–3 weeks to

max.40 mg/kg daily and then reduced according

toresponse

Asthma

section3.3.1

Allergicconjunctivitis

section11.4.2

Allergicrhinitis

section12.2.1

Administration

capsulesmay be swallowed whole or

thecontents dissolved in hot water and diluted with

coldwater before taking

Nalcrom

(Sanoﬁ-Aventis)A

Capsules

,sodium cromoglicate 100 mg. Net price

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

administration

56 1.5.4 Food allergy BNFC 2011–2012

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

Before prescribing laxatives it is important to be sure

thatthe child

constipatedand that the constipation is

not

secondaryto an underlying undiagnosed complaint.

Laxativesshould be prescribed by a healthcare profes-

sionalexperienced in the management of constipation

inchildren. Delays ofgreater than 3 days between stools

may increase the likelihoodof pain on passing hard

stoolsleading to anal ﬁssure, anal spasm and eventually

toa lear ned response to avoid defaecation.

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 in chil-

dren with chronic constipation ora historyof faecal

impaction; intermittent use may provokerelapses. In

childrenwith chronic constipation, laxatives should be

continued for several weeks after a regular pattern of

bowelmovements or toilet training is established. The

doseof laxatives should then be tapered gradually, over

aperiod of months, according to response. Some chil-

drenmay require laxative therapy for several years.

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.

For the role of laxatives in thetreatment ofirritable

bowelsyndrome,see p. 49. For the preventionof opioid-

inducedconstipation in palliative care, see p. 18.

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.

Laxativesare also ofvalue in

drug-inducedconstipation

(seePrescribing in Palliative Care, p. 18), in

distalintes-

tinalobstruction syndrome

inchildren with cystic ﬁbro-

sis, for the expulsion of

parasites

after anthelmintic

treatment, and to clear the alimentary tract before

surgeryand radiological procedures

(section1.6.5).

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-forminglaxatives are of value ifthe diet is deﬁcient

inﬁbre. They relieve constipation by increasing faecal

mass which stimulates peristalsis; children and their

carers should be advised that the full effect may take

somedays to develop.

Duringtreatment with bulk-forming laxatives, adequate

ﬂuid intake must be maintained to avoid intestinal

obstruction.Proprietary preparations containing a bulk-

ing agent such as ispaghula husk are often difﬁcult to

administerto children.

Bulk-forminglaxatives may be used in the management

ofchildren with

haemorrhoids

analﬁssure

,and

irrita-

blebowel syndrome

ISPAGHULAHUSK

Cautions

adequateﬂuid intake should be maintained

toavoid intestinal obstruction

Contra-indications

difﬁcultyin swallowing, intestinal

obstruction,colonic atony, faecal impaction

Side-effects

ﬂatulenceand abdominal distension

(especiallyduring the ﬁrst few days of treatment),

gastro-intestinalobstruction or impaction; hyper-

sensitivityreported

Licenseduse

Isogel

licensedfor use in children

(agerange not speciﬁed by manufacturer)

BNFC 2011–2012 1.6 Laxatives 57

Gastro-intestinalsystem

Indicationand dose

Seeunder preparations

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

Constipation

Bymouth

Child12–18 years

1–6sachets daily in water in 1–3

divideddoses, 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

Constipation

Bymouth

Child6–12 years

½–1level 5-mL spoonful in water

twicedaily, preferably after meals

Child12–18 years

1sachet (or 2 level 5-mL spoonfuls)

inwater twice daily, preferably after meals

Isogel

(Potters)

Granules

,brown, sugar- and gluten-free, ispaghula

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

selling,see above

Dose

Constipation

Bymouth

Child6–12 years

1level 5-mL spoonfulin water once or

twicedaily, preferably at mealtimes

Child12–18 years

2level 5-mL spoonfuls in wateronce

ortwice daily, preferably at mealtimes

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

Constipation

Bymouth

Child6–12 years

½–1level 5-mL spoonful in water

twicedaily, preferably after meals

Child12–18 years

1sachet (or 2 level 5-mL spoonfuls)

inwater 1–3 times daily, preferably after meals

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

Constipation

Bymouth

Child6–12 years

½–1level 5-mL spoonful in water 1–3

timesdaily, preferably after meals

Child12–18 years

1sachet in 150mL water 1–3 times

daily,preferably after meals

METHYLCELLULOSE

Cautions

seeunder Ispaghula Husk

Contra-indications

seeunder Ispaghula Husk; also

infectivebowel disease

Side-effects

seeunder Ispaghula Husk

Licenseduse noage limit speciﬁed by manufacturer

Indicationand dose

Seeunder preparation 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

Constipation,diarrhoea

(seenotes above)

Bymouth

Child7–12 years

2tablets twice daily

Child12–18 years

3–6tablets twice daily

Administration

Inconstipation the dose should be taken

withat least 300mL liquid. In diarrhoea, ileostomy, and

colostomycontrol, avoid liquid intake for 30 minutes before

andafter dose

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

STERCULIA

Cautions

seeunder Ispaghula Husk

Contra-indications

seeunder Ispaghula Husk

Side-effects

seeunder Ispaghula Husk

Indicationand dose

Constipation

fordose see under preparation

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

Bymouth

Child6–12 years

½–1heaped 5-mL spoonful

the

contentsof ½–1 sachet, washed down without chewing

withplenty of liquid once or twice daily after meals

Child12–18 years

1–2heaped 5-mL spoonfuls

the

contentsof 1–2 sachets, washed down without chewing

withplenty of liquid once or twice daily after meals

Administration

Maybe mixed with soft food (e.g. yoghurt)

beforeswallowing, followed by plenty of liquid.

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

Bymouth

Child6–12 years

½-1heaped 5-mL spoonful

the

contentsof ½-1 sachet, washed down without chewing

withplenty of liquid, once or twice daily after meals

Child12–18 years

1–2heaped 5-mL spoonfuls

the

contentsof 1–2 sachets, washed down without chewing

withplenty of liquid, once or twice daily after meals

58 1.6.1 Bulk-forming laxatives BNFC 2011–2012

Gastro-intestinalsystem

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

intestinal obstruction. Stools should be softened by

increasing dietary ﬁbre and liquid or with an osmotic

laxative (section 1.6.4) before giving a stimulant laxa-

tive.In chronic constipation, especially where withhold-

ing of stool occurs, additional doses of a stimulant

laxative may be required. Long-term use of stimulant

laxativesis sometimes necessar y (see section 1.6), but

excessiveuse can cause diar rhoea and related effects

suchas hypokalaemia.

Glycerolsuppositories act as a lubricant and as a rectal

stimulantby virtue of the mildly irritant action of glyce-

rol.

BISACODYL

Cautions

prolongeduse (risk of electrolyte imbalance)

Contra-indications

intestinalobstruction, acute

abdominalconditions, acute inﬂammatory bowel

disease,severe dehydration

Pregnancy

seePregnancy, p. 57

Side-effects

seenotes above; nausea and vomiting;

colitisalso reported;

suppositories

localirritation

Indicationand dose

Constipation

(tabletsact in 10–12 hours; supposi-

toriesact in 20–60 minutes)

Bymouth

Child4–18 years

5–20mg once daily, adjusted

accordingto response

Byrectum (suppositories)

Child2–18 years

5–10mg once daily, adjusted

accordingto response

Bowelclearance beforeradiological procedures

andsurgery

Bymouth and by rectum

Child4–10 years

bymouth

,5 mg atbedtime for 2

daysbefore procedureand, if necessary,

byrectum

5mg suppository 1 hour before procedure

Child10–18 years

bymouth

,10 mg at bedtime

for2 days before procedure and, if necessary,

rectum

,10 mg suppository 1 hour before proce-

dure

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 5 mg, net price 5

=94p

Note

Thebrand name

Dulcolax

D(Boehringer Ingel-

heim)is used for bisacodyl tablets, net price 10-tab pack =

74p;suppositories (10 mg), 10 = £1.57; paediatric supposi-

tories(5 mg), 5 = 94p

Thebrand names

Dulcolax

PicoLiquid

and

Dulcolax

PicoPerles

areused for sodium picosulfate preparations

DANTRON

(Danthron)

Cautions

avoidprolonged contact with skin (as in

incontinentpatients or infants wearing nappies)—risk

ofirritation and excoriation;

rodent

studiesindicate

potentialcarcinogenic risk

Contra-indications

seeBisacodyl 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; also urine may be

colouredred

Indicationand dose

Constipationin terminally ill children

fordose

seeunder preparations

Withpoloxamer ‘188’ (as co-danthramer)

Note

Co-danthramer suspension 5 mL = one co-danthramer

capsule, but strong co-danthramer suspension 5mL = 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

Bymouth

Child6–12 years

1capsule at night (restricted indica-

tions,see notes above)

Child12–18 years

1–2capsules at night (restricted

indications,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

Bymouth

Child12–18 years

1–2capsules at night (restricted

indications,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)

Brandsinclude

Codalax

Danlax

Dose

Bymouth

Child2–12 years

2.5–5mL at night (restricted indica-

tions,see notes above)

Child12–18 years

5–10mL at night (restricted indica-

tions,see notes above)

Strongsuspension

,co-danthramer 75/1000 in 5 mL

(dantron75 mg, poloxamer ‘188’ 1g/5 mL). Net price

300mL = £30.13. Label: 14, (urine red)

Brandsinclude

CodalaxForte

Dose

Bymouth

Child12–18 years

5mL at night (restricted indications,

seenotes above)

BNFC 2011–2012 1.6.2 Stimulantlaxatives 59

Gastro-intestinalsystem

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)

Brandsinclude

Normax

Dose

Bymouth

Child6–12 years

1capsule at night (restricted indica-

tions,see notes above)

Child12–18 years

1–3capsules at night (restricted

indications,see notes above)

Suspension

,yellow, co-danthrusate 50/60 (dantron

50mg, docusate sodium 60 mg/5 mL). Net price

200mL = £8.75. Label: 14, (urine red)

Brandsinclude

Normax

Dose

Bymouth

Child6–12 years

5mL at night (restricted indications,

seenotes above)

Child12–18 years

5–15mL at night (restricted indica-

tions,see notes above)

DOCUSATESODIUM

(Dioctylsodium sulphosuccinate)

Cautions

seenotes above; do not give with liquid

parafﬁn

Contra-indications

seenotes above; also for

rectal

preparations

,haemorrhoids or anal ﬁssure

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; also rash

Licenseduse

adultoral solution and capsules

not

licensedfor use in children under 12 years

Indicationand dose

Constipation

Bymouth

Child6 months–2 years

12.5mg 3 times daily,

adjustedaccording to response (usepaediatric oral

solution)

Child2–12 years

12.5–25mg 3 times daily,

adjustedaccording to response (usepaediatric oral

solution)

Child12–18 years

upto 500 mg daily in divided

doses,adjusted according to response

Note

Oralpreparations act within 1–2 days; response to

rectaladministration usually occurs within 20 minutes

Adjunctin abdominal radiological procedures

Bymouth

Child12–18 years

400mg with barium meal

Administration

foradministration

bymouth

,solution

maybe mixed with milk or squash

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

Byrectum

Child12–18 years

1enema as a single dose

GLYCEROL

(Glycerin)

Indicationand dose

Constipation

Byrectum

Child1 month–1year

1-gsuppository as required

Child1–12 years

2-gsuppository as required

Child12–18 years

4-gsuppository as required

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)

Administration

Moistenwith water before insertion

SENNA

Cautions

seenotes above

Contra-indications

seenotes above

Pregnancy

seePregnancy, p. 57

Breast-feeding

notknown to be harmful

Side-effects

seenotes above

Licenseduse

tablets

notlicensed for use in children

under6 years;

syrup

notlicensed for use in children

under2 years

Indicationand dose

Constipation

fordose see under preparations

Note

Onsetof action 8–12 hours; initial dose should be

low

Senna(Non-proprietary)

Tablets

,total sennosides (calculated as sennoside B)

7.5mg. Net price 60 = £1.47

Brandsinclude

Senokot

Dose

Bymouth

Child2–4 years

½–2tablets once daily, adjusted

accordingto response

Child4–6 years

½–4tablets once daily, adjusted

accordingto response

Child6–18 years

1–4tablets once daily, adjusted

accordingto response

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

Bymouth

Child12–18 years

1–2level 5-mL spoonfuls at night

withat least150 mL water,fruit juice, milk, or warm drink

Counselling

Preparationsthat swell in contact with liquid

shouldalways be carefully swallowed with water or appro-

priateﬂuid and should not be taken immediately before

goingto bed

60 1.6.2 Stimulant laxatives BNFC 2011–2012

Gastro-intestinalsystem

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

Bymouth

Child1 month–4 years

2.5–10mL once daily, adjusted

accordingto response

Child4–18 years

2.5–20mL once daily, adjusted

accordingto response

SODIUM PICOSULFATE

(Sodiumpicosulphate)

Cautions

seenotes above; active inﬂ ammatory bowel

disease(avoid if fulminant)

Contra-indications

seenotes above; severe dehydra-

tion

Pregnancy

seePregnancy, p. 57

Breast-feeding

notknown to be present in milk but

manufactureradvises avoid unless potential beneﬁt

outweighsrisk

Side-effects

seenotes above

Licenseduse

elixir

,licensed for use in children (age

rangenot speciﬁed by manufacturer);

Perles

not

licensedfor use in children under 4 years

Indicationand dose

Constipation

Bymouth

Child1 month–4 years

2.5–10mg once daily,

adjustedaccording to response

Child4–18 years

2.5–20mg once daily, adjusted

accordingto response

Note

onsetof action 6–12 hours

Bowelevacuation before abdominal radiologi-

caland endoscopic procedures onthe colon,

andsurgery

section1.6.5

SodiumPicosulfate (Non-proprietary)

Elixir

,sodium picosulfate 5 mg/5mL, net price

100mL = £1.85

Note

Thebrand name

Dulcolax

PicoLiquid

(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 used for bisacodyl

tabletsand suppositories

Bowelcleansing preparations

Section1.6.5

1.6.3

Faecal softeners

Enemascontaining arachis oil (ground-nut oil, peanut

oil)lubricate and soften impacted faeces and promote a

bowelmovement.

Bulk laxatives (section 1.6.1) and non-ionic surfactant

‘wetting’ agents e.g. docusate sodium (section 1.6.2)

also have softening properties.Such dr ugs are useful

for oral administration in the management of anal

ﬁssure;glycerol suppositories (section 1.6.2) are useful

forrectal use.

ARACHIS OIL

Cautions

intestinalobstruction; hypersensitivity to

soya

Contra-indications

inﬂammatory bowel disease,

hypersensitivityto arachis oil or peanuts

Licenseduse licensed for use in children (age range

notspeciﬁed by manufacturer

Indicationand dose

Impactedfaeces

Byrectum

Child3–7 years

45–65mL as required

Child7–12 years

65–100mL as required

Child12–18 years

100–130mL as required

Administration

warmenema in warm water before

use

ArachisOil Enema (Non-proprietary)

Enema

,arachis (peanut) oil in 130-mL single-dose

disposablepacks. Net price 130 mL = £7.98

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. Macrogols are an effective non-trau-

matic means of evacuation in children with faecal

impaction and can be used in the long-term manage-

mentof chronic constipation.

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

clearance before radiology, endoscopy, and surgery.

Enemascontaining phosphate or sodium citrate, and

oral bowel cleansing preparations (section 1.6.5)

shouldonly be used on the advice of a specialist practi-

tioner.

LACTULOSE

Cautions

lactoseintolerance; interactions: Appendix

1(lactulose)

Contra-indications

galactosaemia,intestinal obstr uc-

tion

Pregnancy

notknown to be harmful; see also

Pregnancy,p. 57

Side-effects

nausea(can be reduced by administra-

tionwith water, fruit juice or with meals), vomiting,

ﬂatulence,cramps, and abdominal discomfort

BNFC 2011–2012 1.6.3 Faecalsofteners 61

Gastro-intestinalsystem

Licenseduse not licensed for use in children for

hepaticencephalopathy

Indicationand dose

Constipation

(maytake up to 48 hours to act)

Bymouth

Child1 month–1 year

2.5mL twice daily,

adjustedaccording to response

Child1–5 years

2.5–10mL twice daily, adjusted

accordingto response

Child5–18 years

5–20mL twice daily, adjusted

accordingto response

Hepaticencephalopathy

Bymouth

Child12–18 years

30–50mL 3 times daily;adjust

doseto produce 2–3 soft stools per day

Lactulose(Non-proprietary)

Solution

,lactulose 3.1–3.7g/5 mL with otherketoses.

Netprice 300-mL pack = £2.10, 500-mL pack = £2.59

Brandsinclude

Duphalac

Lactugal

Regulose

MACROGOLS

(Polyethyleneglycols)

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

manufacturersadvise use only if essen-

tial—noinformation available

Breast-feeding

manufacturersadvise use only if

essential—noinformation available

Side-effects

abdominaldistension and pain, nausea,

ﬂatulence

Licenseduse

Movicol

PaediatricPlain

not

licensedfor use in faecal impaction in children

under5 years,or for chronic constipation in children

under2 years

Indicationand dose

Seeunder preparations 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

Bymouth

Child12–18 years

1–3sachets daily in divided doses

usuallyfor up to 2 weeks;maintenance, 1–2 sachets daily

Administration

Mixcontents of each sachet in half a

glass(approx. 125 mL) of water

Faecalimpaction

Bymouth

Child12–18 years

4sachets on ﬁrst day,then increased

insteps of 2 sachets daily to max. 8 sachets daily; total

dailydose to be drunk within a 6 hour period

Administration

Mixcontents of 2 sachets in a glass

(approx.250 mL) of water. After reconstitution the solu-

tionshould be kept in a refrigerator and discarded if

unusedafter 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-

ﬂavoured)= £4.45, 30-sachet pack (lime- and lemon-

orchocolate- or plain- ﬂ avoured) = £6.68, 50-sachet

pack(lime- and lemon- or plain- ﬂ avoured) =£11.13.

Label:13

Note

Amountof potassium chloride varies according to

ﬂavourof

Movicol

asfollows: plain-ﬂavour (sugar-free) =

50.2mg/sachet; lime and lemon ﬂavour = 46.6 mg/sachet;

chocolateﬂavour = 31.7mg/sachet. 1 sachet when recon-

stitutedwith 125 mL water provides K

5.4mmol/litre

Cautions patients with cardiovascular impairment should not

takemore than 2 sachets in any 1 hour

Dose

Chronicconstipation

Bymouth

Child12–18 years

1–3sachets daily in divided doses

usuallyfor up to 2 weeks;maintenance, 1–2 sachets daily

Administration

Mixcontents of each sachet in half a

glass(approx. 125 mL) of water

Faecalimpaction

Bymouth

Child12–18 years

4sachets on ﬁrst day,then increased

insteps of 2 sachets daily to max. 8 sachets daily; total

dailydose to be drunk within a 6 hour period

Administration

Mixcontents of 2 sachets in a glass

(approx.250 mL) of water. After reconstitution the solu-

tionshould be kept in a refrigerator and discarded if

unusedafter 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 impaired cardiovascular function should

nottake more than 4 sachets in any 1 hour

Dose

Chronicconstipation

Bymouth

Child12–18 years

2–6sachets daily in divided doses

usuallyfor up to 2 weeks; maintenance,2–4 sachets daily

Administration

Mixcontents ofeach sachet in quarter of

aglass (approx. 60–65 mL) of water

Faecalimpaction

Bymouth

Child12–18 years

8sachets on ﬁrst day,then increased

insteps of 4 sachets daily to max. 16 sachets daily; total

dailydose to be drunk within 6 hours

Administration

Mixcontents of 4 sachets in a glass

(approx.250 mL) of water. After reconstitution the solu-

tionshould be kept in a refrigerator and discarded if

unusedafter 6 hours

Movicol

PaediatricPlain (Norgine) A

Oralpowder

,sugar-free, macrogol ‘3350’ (polyethy-

leneglycol ‘3350’) 6.563 g, sodium bicarbonate

62 1.6.4 Osmotic laxatives BNFC 2011–2012

Gastro-intestinalsystem

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 cardiovascular impairment, renal impair-

ment–—noinformation available

Dose

Chronicconstipation, prevention offaecal impaction

Bymouth

Childunder 1 year

½–1sachet daily

Child1–6 years

1sachet daily; adjust dose to produce

regularsoft stools (max. 4 sachets daily)

Child6–12years

2sachets daily;adjust dose to produce

regularsoft stools (max. 4 sachets daily)

Administration

Mixcontent of each sachet in quarter of

aglass (approx. 60–65 mL) of water

Faecalimpaction

Bymouth

Childunder 1 year

½–1sachet daily

Child1–5 years

(treatuntil impaction resolves) 2

sachetson ﬁrstday, then 4 sachetsdaily for 2 days, then 6

sachetsdaily for 2 days, then 8 sachets daily

Child5–12 years

(treatuntil impaction resolves) 4

sachetson ﬁrst day, then increased in steps of 2 sachets

dailyto max. 12 sachets daily

Administration

Mixeach sachet in quarter of a glass

(approx.60–65 mL) of water; total daily dose to be taken

overa 12-hour period

MAGNESIUM SALTS

Cautions

seealso notes above; interactions: Appen-

dix1 (antacids)

Contra-indications

acutegastro-intestinal conditions

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidor reduce dose; increased

riskof toxicity

Side-effects

colic

Indicationand dose

Constipation

seeunder preparations below

Magnesiumhydroxide

MagnesiumHydroxide Mixture, BP

Aqueoussuspension containing about 8% hydrated

magnesiumoxide. Do not store in cold place

Dose

Bymouth

Child3–12 years

5–10mL with water at bedtime when

required

Child12–18 years

30–45mL with water at bedtime

whenrequired

Bowelcleansing preparations

Section1.6.5

PHOSPHATES(RECTAL)

Cautions

seealso notes above;

withenema

,electro-

lytedisturbances, congestive heart failure, ascites,

uncontrolledhypertension, maintain adequate hydra-

tion

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

Indicationand dose

Constipation,bowel evacuation before abdo-

minalradiological procedures, endoscopy, and

surgery

Fordose see preparations

Carbalax

(Chemidex)

Suppositories

,sodium acid phosphate (anhydrous)

1.3g, sodium bicarbonate 1.08 g, net price 12 = £2.01

Dose

Byrectum

Child12–18 years

1suppository, inserted 30 minutes

beforeevacuation required; moisten with water 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

Byrectum

Child3–7 years

40–60mL once daily

Child7–12 years

60–90mL once daily

Child12–18 years

90–118mL once daily

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

Byrectum

Child3–7 years

45–65mL once daily

Child7–12 years

65–100mL once daily

Child12–18 years

100–128mL once daily

SODIUM CITRATE(RECTAL)

Cautions

seenotes above

Contra-indications

acutegastro-intestinal conditions

Indicationand dose

Constipation

fordose see under preparations

MicoletteMicro-enema

(Pinewood)

Enema

,sodium citrate 450 mg, sodium lauryl sul-

phoacetate45 mg, glycerol 625 mg, together with

citricacid, potassium sorbate, and sorbitol in a vis-

coussolution, in 5-mL single-dose disposable packs

withnozzle. Net price 5 mL = 38p

Dose

Byrectum

Child3–18 years

5–10mL as a single dose

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

Byrectum

Child3–18 years

5mL as a single dose

BNFC 2011–2012 1.6.4 Osmotic laxatives 63

Gastro-intestinalsystem

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

Byrectum

Child1 month–18 years

5mL as a single dose (insert

onlyhalf nozzle length in child 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

Bowelcleansing preparations shouldbe used

withcaution in children, particularly in those with ﬂuid

and electrolyte disturbances. Renal function should be

measuredbefore starting treatment in patients at risk of

ﬂuid and electrolyte disturbances. Hypovolaemia

should be corrected before administration of bowel

cleansing preparations. Adequate hydration should be

maintainedduring treatment. Bowel cleansing prepara-

tions should be used withcaution in colitis (avoid if

acute severe colitis), or in thosewho are debilitated.

Theyshould also be used with caution in patients with

animpaired gag reﬂex or possibility of regurgitation or

aspiration. Other oral drugsshould notbe taken one

hour before or after administration of bowel cleansing

preparationsbecause absor ption may 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

Cautions

seenotes above; also heart failure

Contra-indications

seenotes above; also gastro-

intestinalulceration

Pregnancy

manufacturersadvise use only if essen-

tial—noinformation available

Breast-feeding

manufacturersadvise use only if

essential—noinformation available

Side-effects

seenotes above; also anal discomfort

Licenseduse

Klean-Prep

notlicensed for use in

children

Indicationand 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,counselling

Excipients

includeaspartame (section 9.4.1)

Electrolytes

1sachetwhen reconstituted with 1 litre water providesNa

125mmol,K

10mmol,Cl



35mmol,HCO



20mmol

Dose

Bowelcleansing before radiologicalexamination,

colonoscopy,or surgery

Bymouth

Child12–18 years

aglass (approx. 250 mL) of recon-

stitutedsolution every 10–15 minutes, or by nasogastric

tube20–30 mL/minute, starting on the day before pro-

cedureuntil 4 litres have been consumed; alter natively,

administrationmay be divided into two (2 litres of

reconstitutedsolution taken on the evening before pro-

cedureand 2 litres of reconstituted solution taken on the

morningof procedure). Treatment can be stopped if

bowelmotions become watery and clear. To facilitate

gastricemptying, domperidone (section 1.2) may be

given30 minutes before starting

Distalintestinal obstruction syndrome

Bymouth, nasogastric orgastrostomy tube

Child1–18 years

10mL/kg/hour for 30 minutes, then

20mL/kg/hour for 30 minutes, then increase to 25 mL/

kg/hourif tolerated; max. 100 mL/kg (or 4 litres) over 4

hours;repeat 4-hour treatment if necessary.

Administration

1sachet should be reconstituted with 1 litre

ofwater.Flavouring such as clearfruit cordials may be added

ifrequired. Solid foodshould not be taken for at least 2hours

beforestarting treatment. After reconstitution the solution

shouldbe kept in a refrigerator and discarded if unused after

24hours.

MAGNESIUM CITRATE

Reconstitutionof a sachet containing 11.57g magnesium carb-

onate and 17.79 g anhydrous citric acid produces a solution

containingmagnesium citrate

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidif estimated glomerular ﬁl-

trationrate less than 30 mL/minute/1.73 m

—riskof

hypermagnesaemia

Pregnancy

caution

Breast-feeding

caution

Side-effects

seenotes above

Indicationand dose

Seepreparations

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 on daybefore radiological exam-

ination,colonoscopy, or surgery

Bymouth

Child5–10 years

onday before procedure, one-third of

asachet at 8 a.m. and one-third of a sachet between 2

and4 p.m.

64 1.6.5 Bowel cleansing preparations BNFC2011–2012

Gastro-intestinalsystem

Child10–18 years

onday beforeprocedure, ½–1 sachet

at8 a.m. and ½–1 sachet between 2 and 4 p.m.

Counselling

Onesachet should be reconstituted with

200mL of hot water; the solution should be allowed to cool

forapprox. 30 minutes before drinking. Low residue or ﬂuid

onlydiet(e.g. water, fruit squash,lemonade, clear soup, black

teaor coffee) recommended before procedure (according to

hospitaladvice) and copious intake of clear ﬂ uids recom-

mendeduntil procedure

SODIUM PICOSULFATEWITH

MAGNESIUM CITRATE

Cautions

seenotes above; also recentgastro-intestinal

surgery;cardiac disease (avoid in congestive cardiac

failure)

Contra-indications

seenotes above; also gastroin-

testinalulceration; ascites; congestive cardiac failure

Hepaticimpairment

avoidin hepatic coma if risk of

renalfailure

Renalimpairment

avoidif estimated glomerular ﬁl-

trationrate less than 30 mL/minute/1.73 m

—riskof

hypermagnesaemia

Pregnancy

caution

Breast-feeding

caution

Side-effects

seenotes above; also anal discomfort,

sleepdisturbances, fatigue, and rash

Indicationand dose

Seepreparations

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 daybefore radiological proce-

dure,endoscopy, or surgery

Bymouth

Child1–2 years

¼sachet before8 a.m. then ¼ sachet 6–

8hours later

Child2–4 years

½sachet before8 a.m. then ½ sachet 6–

8hours later

Child4–9 years

1sachet before 8a.m. then ½ sachet 6–

8hours later

Child9–18years

1sachet before8 a.m. then 1 sachet6–

8hours later

Note

Actswithin 3 hours of ﬁrst dose. Low residue diet

recommendedon the day before procedure and copious

intakeof water or other clear ﬂuids recommended during

treatment

Counselling

Onesachet should be reconstituted with

150mL (approx. half a glass) of cold water; children and

carersshould be warned that heat is generated during

reconstitutionandthat the solution should be allowedto cool

beforedrinking

Amidotrizoates

Gastrograﬁn

is an amidotr izoate radiological con-

trast medium with high osmolality; it is used in the

treatment of meconium ileus in neonates and in the

management of distal intestinal obstruction syndrome

inchildren with cystic ﬁbrosis.

AMIDOTRIZOATES

Diatrizoates

Cautions

asthmaor histor y of allergy, latent hyper-

thyroidism,dehydration and electrolyte disturbance

(correctﬁrst); in children with oesophageal ﬁstulae

(aspirationmay lead to pulmonary oedema); benign

nodulargoitre; enteritis; risk of anaphylactoid reac-

tionsincreased by concomitant administration of

beta-blockers

Contra-indications

hypersensitivityto iodine, hyper-

thyroidism

Pregnancy

manufactureradvises caution

Side-effects

diarrhoea,nausea, vomiting; also

reported,abdominal pain, intestinal perforation,

bowelnecrosis, oral mucosal blistering, hypersensi-

tivityreactions, pyrexia, headache, dizziness, distur-

bancesin consciousness, hyperthyroidism, electrolyte

disturbances,and skin reactions (including toxic epi-

dermalnecrolysis)

Licenseduse not licensed for use in distal intestin al

obstructionsyndrome

Indicationand dose

Uncomplicatedmeconium ileus

Byrectum

Neonate

15–30mL as a single dose

Distalintestinal obstruction syndrome

Bymouth or by rectum

Child1 month–2years

15–30mL asa single dose

Childbody-weight 15–25 kg

50mL as a single

dose

Childbody-weight over25 kg

100mL as a single

dose

Administration

Intravenousprehydration is essential

inneonates and infants. Fluid intake should be

encouragedfor 3 hours after administration.

mouth

,for child bodyweight under 25 kg, dilute

Gas-

trograﬁn

with3 times its volume of water or fr uit

juice;for child bodyweight over 25 kg, dilute

Gastro-

graﬁn

withtwice its volume of water or fruit juice.

Byrectum

,administration must be car ried out slowly

underradiological supervision to ensure required site

isreached. For child under 5 years, dilute

Gastro-

graﬁn

with5 times itsvolume of water; forchild over

5years dilute

Gastrograﬁn

with4 times its volume

ofwater.

Radiologicalinvestigations

doseto be recom-

mendedby radiologist

Gastrograﬁn

(BayerSchering)

Solution

,sodium amidotrizoate 100 mg, meglumine

amidotrizoate660 mg/mL, net price 100-mL bottle =

£14.69

Excipients

includedisodium edetate

1.6.6

Peripheral opioid-

receptor antagonists

Classiﬁcationnot used in

BNFfor Children

BNFC 2011–2012 1.6.5 Bowel cleansing preparations 65

Gastro-intestinalsystem

1.7

Local preparations for

anal and rectal disorders

1.7.1 Soothing anal and rectalpreparations

1.7.2 Compound anal and rectal

preparationswith corticosteroids

1.7.3 Rectal sclerosants

1.7.4 Management of anal ﬁssures

Inchildren with perianal soreness or pruritus ani, good

toilethygiene is essential; the use of alcohol-free ‘wet-

wipes’after each bowel motion, regular bathing and the

avoidance of local irritants such as bath additives is

recommended. Excoriated skin isbest treatedwith a

protectivebarrier emollient (section 13.2.2); in children

over1 month, hydrocortisone ointment or cream (sec-

tion 13.4) or a compoundrectal preparation (section

1.7.2) may be used for a shor t period of time, up to a

maximumof 7 days.

Pruritus ani

caused by threadworm infection requires

treatment with an anthelmintic (section 5.5.1). Topical

applicationof white soft parafﬁnor other bland emoll-

ient (section 13.2.1) may reduce anal irritation caused

bythreadworms.

Perianal erythema

caused by streptococcal infection

should be treated initially with an oral antibacterial

such as phenoxymethylpenicillin (section 5.1.1.1) or

erythromycin (section5.1.5), while awaiting results of

cultureand sensitivity testing.

Perianalcandidiasis

(thrush)requires treatment with a

topical antifungal preparation (section 13.10.2). For

treatmentof vulvovaginal candidiasis, see section 7.2.2.

Proctitis

associatedwith inﬂammatory bowel disease in

children is treated with corticosteroids and aminosali-

cylates(section 1.5).

Forthe management of anal ﬁssures, see section 1.7.4.

1.7.1

Soothing anal and rectal

preparations

Haemorrhoids in children are rare, but mayoccur in

infants with portal hypertension. Soothing rectalpre-

parations containing mild astringents such as bismuth

subgallate, zinc oxide, and hammamelis mayprovide

symptomaticrelief, but proprietary preparations which

also contain lubricants, vasoconstrictors, or mild anti-

septicsmay cause further perianal irritation.

Local anaesthetics may be used to relieve pain in

children with anal ﬁssures or pruritus ani, but local

anaesthetics are absorbed through therectal mucosa

andmay cause sensitisation of the anal skin. Excessive

useof local anaesthetics may result in systemic effects,

see section 15.2. Preparations containing local anaes-

theticsshould be used for no longer than 2–3 days.

Lidocaine ointment (section 15.2) may be applied

beforedefaecation to relieve pain associated with anal

ﬁssure,but local anaesthetics cancause stinging initially

andthis may aggravate the child’s fear of pain.

Otherlocal anaesthetics such as tetracaine, cinchocaine

(dibucaine), and pramocaine (pramoxine) may be

included in rectal preparations, but these are more

irritantthan lidocaine.

Corticosteroids are often combined with local anaes-

theticsand soothing agents in topical preparations for

haemorrhoids and proctitis. Topical preparations con-

tainingcorticosteroids (section 1.7.2)should not be used

long-term or if infection (such as herpes simplex) is

present. For further information on the use of topical

corticosteroids,see section 13.4.

1.7.2

Compoundanal and rectal

preparations with

corticosteroids

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

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

applynight and morning and after a

bowelmovement; do not use for longer than 7 days

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

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository night and

morningand after a bowel movement; do not use for

longerthan 7 days

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

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

applynight and morning and after a

bowelmovement; do not use for longer than 7 days

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

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository night and

morningand after a bowel movement; do not use for

longerthan 7 days

Perinal

(Dermal)

Sprayapplication

,hydrocortisone 0.2%, lidocaine

hydrochloride1%. Net price 30-mL pack = £6.11

Dose

Haemorrhoids,pruritus ani

Byrectum

Child2–18 years

sprayonce over the affected area up

to3 timesdaily; do not use for longer than7 days without

medicaladvice (child under 14 years, on medical advice

only)

66 1.7 Local preparations for anal and rectal disorders BNFC 2011–2012

Gastro-intestinalsystem

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

Painand irritationassociated withlocal,non-infected

analor perianal conditions

Byrectum

Child12–18 years

1applicatorful (4–6 mg hydrocorti-

soneacetate, 4–6 mg pramocaine hydrochloride) by

rectum2–3 times daily and after a bowel movement

(max.4 times daily); do not use for longer than 7 days

Proctosedyl

(Sanoﬁ-Aventis)A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,hydrocortisone 0.5%, net price 30 g = £10.34

(withcannula)

Dose

Haemorrhoids,pruritus ani

Byrectum

Child1 month–18 years

applymorning and night and

aftera bowel movement, externally or by rectum; do not

usefor longer than 7 days

Suppositories

,cinchocaine (dibucaine) hydro-

chloride5 mg, hydrocortisone 5 mg, net price 12 =

£4.66

Dose

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository night and

morningand after a bowel movement; do not use for

longerthan 7 days

Scheriproct

(BayerSchering) A

Ointment

,cinchocaine (dibucaine) hydrochloride

0.5%,prednisolone hexanoate 0.19%, net price 30g =

£2.94

Dose

Haemorrhoids,pruritus ani

Byrectum

Child1 month–18years

applytwice daily for 5–7 days

(3–4times daily on 1st day if necessary), then once daily

fora few days after symptoms have cleared

Suppositories

,cinchocaine (dibucaine) hydro-

chloride1 mg, prednisolone hexanoate 1.3 mg, net

price12 = £1.38

Dose

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository daily after a

bowelmovement, for 5–7 days (in severe cases initially

2–3times 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

Haemorrhoids,pruritus ani

Child1 month–18years

applytwice daily for 5–7 days

(3–4times daily on 1st day if necessary), then once daily

fora 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

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository daily after a

bowelmovement, for 5–7 days (in severe cases initially

2–3times daily) then 1 suppository every other 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

Haemorrhoids,pruritus ani

Byrectum

Child1 month–18 years

applytwice daily and after a

bowelmovement, externally or byrectum; do not use for

longerthan 7 days (child under 12 years, on medical

adviceonly)

Suppositories

,cinchocaine (dibucaine) hydro-

chloride5 mg, hydrocortisone 5 mg, net price 12 =

£1.91

Dose

Haemorrhoids,pruritus ani

Byrectum

Child12–18 years

insert1 suppository twice daily and

aftera bowel movement; do not use for longer than 7

days

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

Haemorrhoids,pruritus ani

Byrectum

Child1 month–18 years

applyseveral times daily;

short-termuse only

1.7.3

Rectal sclerosants

Classiﬁcationnot used in

BNFfor Children

1.7.4

Management of anal

ﬁssures

The management of anal ﬁssures includes stoolsoft-

ening(section 1.6) and the short-ter m use of a topical

preparation containing a local anaesthetic (section

1.7.1). If these measures are inadequate, children with

chronic anal ﬁssures shouldbe referredfor specialist

treatmentin hospital. Topicalglycer yltrinitrate, 0.05%

or0.1% ointment, may be used in children to relax the

anal sphincter, relieve pain and aid healing of anal

ﬁssures.Excessive application of topical nitrates causes

side-effects such as headache, ﬂushing, dizziness, and

posturalhypotension.

Beforeconsidering surgery,diltiazem 2% ointmentmay

beused in childrenwith chronic anal ﬁssures resistant to

topicalnitrates.

BNFC 2011–2012 1.7.4 Managementof anal ﬁssures 67

Gastro-intestinalsystem

Ointments containing glyceryl trinitratein a rangeof

strengthsor diltiazem 2% are available as manufactured

specials(see Special-order Manufacturers, p. 809).

1.8

Stoma and enteral

feeding tubes

Stoma

Prescribingfor childrenwith stoma calls for special care.

The following is a brief account of some of the main

pointsto be borne in mind.

When a solid-dose formulation such as a capsule or a

tabletis given the contents of the ostomy bag should be

checkedfor anyremnants; response to treatment should

be carefully monitored because of the possibility of

incomplete absorption.

Enteric-coated

and

modiﬁed-

release

preparationsare unsuitable, particularly in chil-

drenwith an ileostomy, as there may not be suf ﬁcient

releaseof the active ingredient.

Laxatives

Enemas and washouts should be usedin

children with stoma only under specialist super vision;

they should not be prescribed for those with an ileo-

stomyas they may cause rapid and severe loss of water

andelectrolytes.

Childrenwith colostomy may suffer from constipation

andwhenever possible it should be treated by increas-

ingﬂuid intake or dietary ﬁbre. If a laxative (section 1.6)

isrequired, it should generally be used for short periods

only.

Antidiarrhoeals

Loperamide, codeine phosphate,

and co-phenotrope (section 1.4.2) are ef fective for

controlling excessive stool losses. Bulk-for ming drugs

(section 1.6.1) may be tried but itis often difﬁcult to

adjustthe dose appropriately.

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 children with stoma.

Diuretics

Diuretics should be used with caution in

children with an ileostomy because they may become

excessively dehydrated and potassiumdepletion may

easilyoccur. It is usually advisable to use a potassium-

sparingdiuretic (section 2.2.3).

Digoxin

Childrenwith stoma are particularly suscep-

tible to hypokalaemia. This predisposes children on

digoxinto digoxin toxicity;potassium supplements (sec-

tion 9.2.1.1) or a potassium-sparing diuretic (section

2.2.3)may be advisable.

Analgesics

Opioid analgesics (section 4.7.2) may

cause troublesome constipation in children with colo-

stomy.When a non-opioid analgesic is required para-

cetamol is usually suitable; anti-inﬂammatory anal-

gesicsmay cause gastric irritation and bleeding.

Ironpreparations

Ironsupplements may cause loose

stoolsand sore skin at the stoma site. If this is trouble-

someand if iron is deﬁnitely indicated a parenteral iron

preparation(section 9.1.1.2) should be used. Modiﬁed-

releaseiron preparations should be avoided.

Careof stoma

Childrenand carers are usually given

advice about the use of

cleansing agents

protective

creams

lotions

deodorants

,or

sealants

whilstin hos-

pital, either by the surgeon or by a stoma-care nurse.

Voluntary organisations offer help and support to

patientswith stoma.

Enteral feeding tubes

Careis required in choosing an appropriate formulation

of a drug for administration through a nasogastric

narrow-bore feeding tube orthrough apercutaneous

endoscopic gastrostomy (PEG) or jejunostomy tube.

Liquid preparations (or soluble tablets) arepreferred;

injectionsolutions may also be suitable for administra-

tionthrough an enteral tube.

Ifa solid formulation of a medicine needs to be given, it

shouldbe given as a suspension of particles ﬁne enough

to pass through the tube. It is possible to crush many

immediate-release tablets but enteric-coated or modi-

ﬁed-releasepreparations should not be crushed.

Enteralfeeds may affect theabsorption of drugs and it is

therefore important to consider the timing of drug

administration in relation to feeds.If more than one

drugneeds to be given, they should be given separately

and the tube should be ﬂushed with waterafter each

drughas been given.

Clearing blockages

Carbonated (sugar-free) drinks

maybe marginallymore effective than water inunblock-

ing feeding tubes,but mildly acidic liquids (such as

pineapple juice or cola-based drinks) can coagulate

protein in feeds, causing further blockage. If these

measuresfail to clear the enteral feeding tube, an alka-

line solution containing pancreatic enzymes may be

introducedinto the tube (followed after at least 5 min-

utesby water). Speciﬁc products designed to break up

blockagescaused by formula feeds are also available.

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

Bile acids (ursodeoxycholic and chenodeoxycholic

acid) may be used as dietary supplements in children

with inborn errors of bileacid synthesis.Ursodeoxy-

cholicacid is used toimprove the ﬂow of bile in children

withcholestatic conditions such as familial intrahepatic

cholestasis, biliary atresia in infants, cystic-ﬁbrosis-

related liver disease, and cholestasis caused by total

parenteral nutrition or following liver transplantation.

68 1.8 Stoma and enteral feeding tubes BNFC2011–2012

Gastro-intestinalsystem

Ursodeoxycholicacid may also relieve the severe itch-

ingassociated with cholestasis.

In sclerosing cholangitis, ursodeoxycholic acid is used

to lower liver enzyme and ser um-bilirubin concentra-

tions.

Ursodeoxycholic acid is also used in the treatment of

intrahepaticcholestasis in pregnancy.

Smith-Lemli-Opitz syndrome

Chenodeoxycholic

andursodeoxycholic acid have been used with choles-

terol in children with Smith-Lemli-Opitz syndrome.

Chenodeoxycholic acid is also used in combination

withcholic acid to treat bile acid synthesis defects but

cholicacid is difﬁcult to obtain. Chenodeoxycholic acid

andcholesterol are available from ‘special-order’ man-

ufacturersor specialist importing companies,see p. 809.

URSODEOXYCHOLIC ACID

Cautions

interactions:Appendix 1 (bile acids)

Contra-indications

radio-opaquestones; non-func-

tioninggall bladder (in patients with radiolucent

gallstones)

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

rarely

,diarrhoea

Licenseduse not licensed for use in children for

indicationsshown below

Indicationand dose

Cholestasis

Bymouth

Neonate

5mg/kg 3 times daily, adjust dose and

frequencyaccording to response,max. 10 mg/kg 3

timesdaily

Child1 month–2 years

5mg/kg 3 times daily,

adjustdose and frequency according to response,

max.10 mg/kg 3 times daily

Improvementof hepatic metabolism of essen-

tialfatty acids and bileﬂow, in children with

cysticﬁbrosis

Bymouth

Child1 month–18 years

10–15mg/kg twice

daily;total daily dose may alternatively begiven in

3divided doses

Cholestasisassociated with total parenteral

nutrition

Bymouth

Neonate

10mg/kg 3 times daily

Child1 month–18 years

10mg/kg 3 times daily

Sclerosingcholangitis

Bymouth

Child1 month–18 years

5–10mg/kg 2–3 times

daily,adjustedaccording to response, max. 15mg/

kg3 times daily

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

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

Other preparations for bile synthesis

defects

CHENODEOXYCHOLIC ACID

Cautions

seeunder Ur sodeoxycholic Acid; interac-

tions:Appendix 1 (bile acids)

Contra-indications

seeunder Ursodeoxycholic Acid

Pregnancy

avoid—fetotoxicityreported in

animal

studies

Side-effects

seeunder Ursodeoxycholic Acid

Licenseduse not licensed

Indicationand dose

Cerebrotendinousxanthomatosis

Bymouth

Neonate

5mg/kg 3 times daily

Child1 month–18 years

5mg/kg 3 times daily

Defectivesynthesis of bile acid

Bymouth

Neonate

initially5 mg/kg3 times daily, reducedto

2.5mg/kg 3 times daily

Child1 month–18years

initially5 mg/kg 3times

daily,reduced to 2.5 mg/kg 3 times daily

Smith-Lemli-Opitzsyndrome

seenotes above

Bymouth

Neonate

7mg/kg once daily or in divided doses

Child1 month–18years

7mg/kg once dailyor in

divideddoses

Administration

foradministration

bymouth

,add the

contentsof a 250-mg capsule to 25 mL of sodium

bicarbonatesolution 8.4% (1 mmol/mL) to produce a

suspensioncontaining chenodeoxycholic acid 10mg/

mL;use immediately after preparation, discard any

remainingsuspension

BNFC 2011–2012 1.9.1 Drugs affecting biliary composition and ﬂow 69

Gastro-intestinalsystem

Chenofalk(Non-proprietary) A

Capsules

,chenodeoxycholic acid 250 mg

Availablefrom ‘special-order’ manufacturers or specialist

importingcompanies, see p. 809

CHOLESTEROL

Cautions

consultproduct literature

Contra-indications

consultproduct literature

Licenseduse not licensed

Indicationand dose

Smith-Lemli-Opitzsyndrome

Bymouth

Neonate

5–10mg/kg 3–4 times daily

Child1 month–18 years

5–10mg/kg 3–4 times

daily(doses up to 15 mg/kg 4 times daily have

beenused)

Administration

cholesterolpowder can bemixed with

avegetable oil before administration

CholesterolPowder (Non-proprietary)

Availablefrom ‘special-order’ manufacturers or specialist

importingcompanies, see p. 809

1.9.2

Bile acid sequestrants

Colestyramine is an anion-exchange resin that forms

aninsoluble complex with bile acids in the gastro-intes-

tinaltract; it is used to relieve diarrhoea associated with

surgicalprocedures such as ileal resection, or following

radiation therapy. Colestyramine is also used in the

treatmentof familial hypercholesterolaemia (seesection

2.12), and to relievepruritus in children with partial

biliary obstruction, (for treatment of pruritus, see sec-

tion 3.4.1). Colestyramine is not absorbed from the

gastro-intestinaltract, but will interfere with the absorp-

tionof a number of drugs, so timing of administration is

important.

COLESTYRAMINE

(Cholestyramine)

Cautions

section2.12

Contra-indications

section2.12

Pregnancy

section2.12

Breast-feeding

section2.12

Side-effects

section2.12

Licenseduse notlicensed for use in children under6

years

Indicationand dose

Pruritusassociated with partial biliary

obstructionand primary biliary cirrhosis,

diarrhoeaassociated with Crohn’s disease,

ilealresection, vagotomy, diabetic vagal

neuropathy,and radiation

Bymouth

Child1 month–1 year

1g once daily in a suitable

liquid,adjusted according to response; total daily

dosemay alternatively be given in 2–4 divided

doses(max. 9 g daily)

Child1–6 years

2g once daily in asuitable liquid,

adjustedaccording to response; total daily dose

mayalternatively be given in 2–4 divided doses

(max.18 g daily)

Child6–12 years

4g once daily in a suitable

liquid,adjusted according to response; total daily

dosemay alternatively be given in 2–4 divided

doses(max. 24 g daily)

Child12–18 years

4–8g once daily in a suitable

liquid,adjusted according to response; total daily

dosemay alternatively be given in 2–4 divided

doses(max. 36 g daily)

Counselling

Otherdrugs should be taken at least 1 hour

beforeor 4–6 hours after colestyramine to reduce pos-

sibleinterference with absor ption

Note

Fortreatment of diarrhoea induced by bile acid

malabsorption,if no response within 3 days an alterna-

tivetherapy should be initiated

Hypercholesterolaemia

section2.12

Administration

Thecontents of one sachet should be

mixedwith at least 150 mL of water or other suitable

liquidsuch as fruit juice, skimmed milk, thin soups, or

pulpyfruits with a high moisture content

Preparations

Section2.12

1.9.3

Aprotinin

Classiﬁcationnot used in

BNFfor Children

1.9.4

Pancreatin

Pancreatin,containing a mixture of protease, lipase and

amylase in varying proportions, aids thedigestion of

starch,fat, and protein. Supplements of pancreatin are

given by mouth to compensate for reducedor absent

exocrinesecretion in cystic ﬁbrosis, and following pan-

createctomy,total gastrectomy, or chronic pancreatitis.

The dose of pancreatinis adjusted according tosize,

number,and consistency of stools, and the nutritional

status of the child; extra allowancewill be needed if

snacksare taken between meals. Daily dose should not

exceed10 000 lipase units per kg body-weight per day,

(important:see advice on Higher-strength preparations

below).

Pancreatinpreparations

Preparation Protease

units

Amylase

units

Lipase

units

Creon

10000 capsule, e/c

granules

600 8000 10000

Creon

Microe/c granules

(per100 mg)

200 3600 5000

Nutrizym10

capsule,e/c

minitablets

500 9000 10000

Pancrex

granules(per

gram)

300 4000 5000

PancrexV

capsule,powder 430 9000 8000

PancrexV ‘125’

capsule,

powder

160 3300 2950

PancrexV

e/ctablet 110 1700 1900

PancrexV

Fortee/c tablet 330 5000 5600

PancrexV

powder(per

gram)

1400 30000 25000

70 1.9.2 Bile acid sequestrants BNFC 2011–2012

Gastro-intestinalsystem

Higher-strength pancreatin preparations

Pancrease

and

Nutrizym22

havebeen associated with the

developmentof large bowel strictures (ﬁbrosing colono-

pathy) in children with cystic ﬁbrosis aged between 2

and13 years. The following is recommended:

PancreaseHL

Nutrizym22

shouldnot be used

inchildren under 16 years 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.

Possibleriskfactors are gender (boys at greater riskthan

girls),more severe cystic ﬁbrosis, and concomitant use

of laxatives. The peak age for developing ﬁbrosing

colonopathyis between 2 and 8 years.

Higher-strengthpancreatin preparations

Preparation Protease

units

Amylase

units

Lipase

units

Creon

25000 capsule,

e/cpellets

1000 18000 25 000

Creon

40000 capsule,

e/cgranules

1600 25000 40 000

Nutrizym22

capsule,

e/cminitablets

1100 19800 22 000

PancreaseHL

capsule,

e/cminitablets

1250 22500 25 000

Pancreatinis inactivated by gastric acid therefore pan-

creatinpreparations are best taken with food (or imme-

diately before or after food). In children with cystic

ﬁbrosis with persistent fat malabsor ption despite opti-

mal use of enzyme replacement, an H

-receptor

antagonist(section 1.3.1), or a proton pump inhibitor

(section 1.3.5) may improve fat digestion and absor p-

tion.Enteric-coated preparations aredesigned to deliver

ahigher enzyme concentration in the duodenum (pro-

videdthe capsule contentsare swallowed whole without

chewing).If the capsules are opened the enteric-coated

granulesshould be mixed with milk, slightly acidic soft

foodor liquid such as apple juice, and then swallowed

immediately without chewing. Any left-over food or

liquid containing pancreatin should be discarded.

Since pancreatin is also inactivated by heat, excessive

heatshould be avoided if preparations are mixed with

liquidsor food.

Pancreatin can irritate the perioral skin and buccal

mucosa if retained in the mouth, and excessive doses

cancause perianal irritation. Hypersensitivity reactions

mayoccur particular ly if the powder is handled.

PANCREATIN

Cautions

seenotes above; hyperuricaemia and

hyperuricosuriahave been associated with very high

doses;interactions: Appendix 1 (pancreatin)

Pregnancy

notknown to be harmful

Side-effects

nausea,vomiting, abdominal discomfort;

skinand mucosal irritation (see notes above)

Indicationand dose

Pancreaticinsufﬁciency

fordose see individual

preparations,below

Creon

10000 (AbbottHealthcare)

Capsules

,brown/clear, enclosing buf f-coloured e/c

granulesof pancreatin (pork), providing: protease

600units, lipase 10 000units, amylase 8000 units, net

price100-cap pack = £12.93. Counselling, see dose

Dose

Bymouth

Child1 month–18years

initially1–2 capsuleswith each

mealeither taken whole or contents mixed with ﬂuid or

softfood (then swallowedimmediately without chewing),

seenotes above

Creon

Micro(Abbott Healthcare)

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

Bymouth

Neonate

initially100 mg before each feed; granules can

bemixed with a small amount of breast milk or formula

feedand administered immediately (manufacturer

recommendsmixing with a small amount of apple juice

beforeadministration)

Child1 month–18 years

initially100 mg before each

feedor meal; granules can be mixedwith a small amount

ofmilk or soft food and administered immediately

(manufacturerrecommends mixing with acidic liquid or

pureedfruit before administration); see notes above

Note

100mg granules = one measured scoopful (scoop

suppliedwith product). Granules should not be chewed

beforeswallowing.

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

Bymouth

Child1 month–18years

1–2capsules with meals and 1

capsulewith snacks, swallowed whole or contents taken

withwater or mixed with soft food (then swallowed

immediatelywithout chewing, see notes above); higher

dosesmay 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

Excipients

includelactose (7 g per 10 g dose)

Dose

Bymouth

Child2–18 years

5–10gjust before meals washed down

ormixed with 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

Bymouth

Child1 month–1 year

contentsof 1–2 capsules mixed

withfeeds

BNFC 2011–2012 1.9.4 Pancreatin 71

Gastro-intestinalsystem

Child1–18 years

2–6capsules with meals, swallowed

wholeor sprinkled on food

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

Bymouth

Neonate

contentsof 1–2 capsules in each feed (or mix

withfeed and give by spoon)

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

Bymouth

Child2–18 years

5–15tablets before meals

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

Bymouth

Child2–18 years

6–10tablets before meals

Powder

,pancreatin (pork), providing minimum of:

protease1400 units, lipase 25 000 units, amylase

30000units/g, net price 300 g = £24.28. Counselling,

seedose

Dose

Bymouth

Neonate

250–500mg with each feed

Child1 month–18 years

0.5–2g with meals, washed

downor mixed with milk or water

Higher-strengthpreparations

Seewarning above

Counselling

Itis important to ensure adequate hydration at all

timesin children receiving higher-strength pancreatin prepara-

tions.

Creon

25000 (AbbottHealthcare) 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

Bymouth

Child2–18 years

initially1 capsule with meals either

takenwhole or contents mixed with ﬂuid or soft food

(thenswallowed immediately without chewing), see

notesabove

Creon

40000 (AbbottHealthcare) 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

Bymouth

Child2–18 years

initially1–2capsules with meals either

takenwhole or contents mixed with ﬂuid or soft food

(thenswallowed immediately without chewing), see

notesabove

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

Bymouth

Child15–18 years

1–2capsules with meals and 1

capsulewith snacks, swallowed whole or contents taken

withwater or mixed with soft food (then swallowed

immediatelywithout chewing), see notes above

PancreaseHL

(Janssen)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

Bymouth

Child15–18 years

1–2capsules during each mealand 1

capsulewith snacks swallowed whole or contents mixed

withslightly acidic liquid or soft food (then swallowed

immediatelywithout chewing), see notes above

72 1.9.4 Pancreatin BNFC 2011–2012

Gastro-intestinalsystem

2 Cardiovascular system

2.1 Positive inotropic drugs 73

2.1.1

Cardiacglycosides 73

2.1.2 Phosphodiesterase type-3 inhi-

bitors

2.2 Diuretics 76

2.2.1

Thiazidesand related diuretics 76

2.2.2 Loop diuretics 78

2.2.3 Potassium-sparing diuretics and

aldosteroneantagonists

2.2.4 Potassium-sparing diureticswith

otherdiuretics

2.2.5 Osmotic diuretics 81

2.2.6 Mercurial diuretics 82

2.2.7 Carbonic anhydrase inhibitors 82

2.2.8 Diuretics with potassium 82

2.3 Anti-arrhythmic drugs 82

2.3.1

Managementof arrhythmias 82

2.3.2 Drugs for arrhythmias 83

2.4 Beta-adrenoceptor blocking

drugs

2.5 Hypertension 92

2.5.1

Vasodilatorantihypertensive

drugsand pulmonary hyper-

tension

2.5.1.1 Vasodilator antihypertensives 93

2.5.1.2 Pulmonary hypertension 95

2.5.2 Centrally actingantihypertensive

drugs

2.5.3 Adrenergic neurone blocking

drugs

2.5.4 Alpha-adrenoceptor blocking

drugs

2.5.5 Drugs affecting the renin-angio-

tensinsystem

100

2.5.5.1 Angiotensin-converting enzyme

inhibitors

100

2.5.5.2 Angiotensin-II receptor antago-

nists

103

2.6 Nitrates, calcium-channel block-

ers,and other antianginal drugs

104

2.6.1

Nitrates 104

2.6.2 Calcium-channel blockers 105

2.6.3 Other antianginal drugs 110

2.6.4 Peripheral vasodilators and

relateddrugs

110

2.7 Sympathomimetics 110

2.7.1

Inotropicsympathomimetics 110

2.7.2 Vasoconstrictor sympatho-

mimetics

112

2.7.3 Cardiopulmonary resuscitation 114

2.8 Anticoagulants and protamine 114

2.8.1

Parenteralanticoagulants 114

2.8.2 Oral anticoagulants 118

2.8.3 Protamine sulphate 120

2.9 Antiplatelet drugs 120

2.10 Myocardial infarction and ﬁbri-

nolysis

121

2.10.1

Managementof myocardial

infarction

121

2.10.2 Fibrinolytic drugs 121

2.11 Antiﬁbrinolytic drugs and

haemostatics

123

2.12 Lipid-regulating drugs 125

2.13 Local sclerosants 130

2.14 Drugs affecting the ductus

arteriosus

130

Thischapter also includes adviceon the drug man-

agementof the following:

arrhythmias,p. 82

heartfailure, p. 76

hypertension,p. 92

pulmonaryhypertension, p. 95

2.1

Positive inotropic drugs

2.1.1 Cardiac glycosides

2.1.2 Phosphodiesterase type-3 inhibitors

Positiveinotropic drugs increase the force of contrac-

tionof themyocardium. Drugs whichproduce inotropic

effects include cardiac glycosides,phosphodiesterase

inhibitors,and some sympathomimetics (section2.7.1).

2.1.1

Cardiac glycosides

The cardiac glycoside digoxin increases the force of

myocardialcontraction andreduces conductivity within

theatrioventricular (AV) node.

Digoxinis most useful in the treatment ofsupraventri-

culartachycardias, especially forcontrolling ventricular

BNFC 2011–2012 73

Cardiovascularsystem

response in persistent atrial ﬁbrillation (section 2.3.1).

Digoxinhas alimited role inchildren with chronicheart

failure; for reference to the role of digoxin in heart

failure,see section 2.2.

For the management of atrial ﬁbrillation, the mainte-

nancedose of digoxinis determined on thebasis of the

ventricularrate at rest, whichshould not be allowedto

fallbelow an acceptable levelfor the child.

Digoxinis nowrarely usedfor rapidcontrol of heartrate

(see section 2.3.2), even with intravenous administra-

tion, response may take many hours; persistence of

tachycardiais therefore notan indication for exceeding

therecommended dose. Theintramuscular route isnot

recommended.

Inchildren with heartfailure who arein sinus rhythm,a

loadingdose may not berequired.

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 thesymptoms of bothare similar.

The plasma-digoxin concentration alone cannot indi-

cate toxicity reliably, but the likelihood of toxicity

increasesprogressively through therange 1.5 to3 micr-

ograms/litrefor digoxin. Renal function is veryimpor-

tantin determining digoxin dosage.

Hypokalaemiapredisposes the childto digitalis toxicity

andshould be avoided;it is managedby givinga potas-

sium-sparingdiuretic or,if necessary,potassium supple-

ments.

Iftoxicity occurs, digoxinshould be withdrawn;serious

manifestations require urgent specialist management.

Digoxin-speciﬁcantibody fragments are availablefor

reversalof life-threatening overdosage (see below).

DIGOXIN

Cautions

sicksinus syndrome; thyroid disease;

hypoxia;severe respiratory disease; avoidhypokal-

aemia,hypomagnesaemia, hypercalcaemia, and

hypoxia(risk of digitalis toxicity);monitor serum

electrolytesand renal function; avoidrapid intra-

venousadministration (risk of hypertensionand

reducedcoronary ﬂow); interactions: Appendix 1

(cardiacglycosides)

Contra-indications

intermittentcomplete heartblock,

seconddegree AV block; supraventriculararrhyth-

miasassociated with accessory conductingpathways

e.g.Wolff-Parkinson-White syndrome (althoughcan

beused in infancy); ventriculartachycardia or ﬁbril-

lation;hypertrophic cardiomyopathy (unless conco-

mitantatrial ﬁbrillation and heartfailure—but use

withcaution); myocarditis; constrictive pericarditis

(unlessto controlatrial ﬁbrillation orimprove systolic

dysfunction—butuse with caution)

Renalimpairment

usehalf normal dose if estimated

glomerularﬁltration rate is 10–50mL/minute/

1.73m

anduse a quarter normal doseif estimated

glomerularﬁltration rate is less than10 mL/minute/

1.73m

;monitor plasma-digoxin concentration; toxi-

cityincreased by electrolyte disturbances

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

Pharmacokinetics For plasma-digoxin concentra-

tionassay, blood should betaken at least 6 hours

aftera dose; plasma-digoxin concentration should

bemaintained in the range 0.8–2micrograms/litre

(seealso notes above)

Licenseduse heart failure,supraventricular arrhy-

thmias

Indicationand dose

Supraventriculararrhythmias andchronic heart

failure(see also notes above)

consultproduct

literaturefor details

Bymouth

Neonateunder 1.5kg

initially25 micrograms/kg

in3 divided doses for24 hours then 4–6micr-

ograms/kgdaily in 1–2 divideddoses

Neonate1.5–2.5 kg

initially30 micrograms/kgin

3divided dosesfor 24hours then4–6 micrograms/

kgdaily in 1–2 divideddoses

Neonateover 2.5kg

initially45 micrograms/kgin

3divided doses for24 hours then10 micrograms/

kgdaily in 1–2 divideddoses

Child1 month–2 years

initially45 micrograms/

kgin 3 divided dosesfor 24 hours then 10micr-

ograms/kgdaily in 1–2 divideddoses

Child2–5 years

initially35 micrograms/kgin 3

divideddoses for24 hours then10 micrograms/kg

dailyin 1–2 divided doses

Child5–10 years

initially25 micrograms/kg

(max.750 micrograms) in3 divided doses for24

hoursthen 6 micrograms/kgdaily (max.

250micrograms daily) in1–2 divided doses

Child10–18 years

initially0.75–1.5 mg in3

divideddoses for 24 hoursthen 62.5–250 micr-

ogramsdaily in 1–2 divideddoses (higher doses

maybe necessary)

Byintravenous infusion (but rarelynecessary)

Neonateunder 1.5kg

initially20 micrograms/kg

in3 divided doses for24 hours then 4–6micr-

ograms/kgdaily in 1–2 divideddoses

Neonate1.5–2.5 kg

initially30 micrograms/kgin

3divided dosesfor 24hours then4–6 micrograms/

kgdaily in 1–2 divideddoses

Neonateover 2.5kg

initially35 micrograms/kgin

3divided doses for24 hours then10 micrograms/

kgdaily in 1–2 divideddoses

Child1 month–2 years

initially35 micrograms/

kgin 3 divided dosesfor 24 hours then 10micr-

ograms/kgdaily in 1–2 divideddoses

Child2–5 years

initially35 micrograms/kgin 3

divideddoses for24 hours then10 micrograms/kg

dailyin 1–2 divided doses

Child5–10 years

initially25 micrograms/kg

(max.500 micrograms) in3 divided doses for24

hoursthen 6 micrograms/kgdaily (max.

250micrograms daily) in1–2 divided doses

74 2.1.1 Cardiac glycosides BNFC 2011–2012

Cardiovascularsystem

Child10–18 years

initially0.5–1 mg in3 divided

dosesfor 24hours then62.5–250 microgramsdaily

in1–2 divided doses (higherdoses may be neces-

sary)

Note

Theabove dosesmay needto bereduced ifdigoxin (or

anothercardiac glycoside)has beengiven inthe preceding2

weeks.When switching fromintravenous to oralroute may

needto increase doseby 20–30% tomaintain the same

plasma-digoxinconcentration. Plasma monitoringmay be

requiredwhen changing formulationto take accountof

varyingbioavailabilities. Forplasma concentration monitor-

ing,bloodshould ideallybe takenat least6 hoursafter adose

Administration

for

intravenousinfusion

,dilute with

SodiumChloride 0.9%

Glucose5% to a max.

concentrationof 62.5micrograms/mL; loading doses

shouldbe givenover 30–60minutes and maintenance

doseover 10–20 minutes.

For

oral

administration,oral solution must notbe

diluted

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

Excipients

includealcohol, propyleneglycol (seeExcipients, p.2)

Paediatricinjection

,digoxin 100 micrograms/mL

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

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

digitoxinoverdosage when measures beyond thewith-

drawalof the cardiac glycoside and correction of any

electrolyte abnormalities are felt to be necessary (see

alsonotes 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 orPoisons Information Centre

2.1.2

Phosphodiesterase type-

3 inhibitors

Enoximoneand milrinoneare phosphodiesterasetype-

3inhibitors that exert most of theiref fecton the myo-

cardium.They possess positive inotropicand vasodila-

tor activityand are useful in infants and children with

low cardiac output especially after cardiac surgery.

Phosphodiesterase type-3 inhibitors should be limited

toshort-term usebecause long-term oraladministration

hasbeen associated with increased mortality in adults

withcongestive heart failure.

ENOXIMONE

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 children with pre-existingarrhythmias);

hypotension;also headache, insomnia, nauseaand

vomiting,diarrhoea; occasionally, chills,oliguria,

fever,urinary retention; upper andlower limb pain

Licenseduse not licensedfor use in children

Indicationand dose

Congestiveheart failure, low cardiacoutput

followingcardiac surgery

Byintravenous injection and continuousintra-

venousinfusion

Neonate

initialloading dose of 500micrograms/

byslow intravenous injection

,followed by 5–

20micrograms/kg/minute

bycontinuous intra-

venousinfusion

over24 hours adjusted according

toresponse; max 24mg/kg over 24 hours

Child1 month–18 years

initialloading dose of

500micrograms/kg

byslow intravenousinjection

followedby 5–20micrograms/kg/minute

bycon-

tinuousintravenous infusion

over24 hours

adjustedaccording to response; max.24 mg/kg

over24 hours

Administration

for

intravenousadministration

,dilute

toconcentration of 2.5mg/mL withSodium Chloride

0.9%

Waterfor Injections; theinitial loading dose

shouldbe given byslow intravenous injectionover at

least15 minutes. Use plasticapparatus—crystal for-

mationif glass used

Perfan

(INCA-Pharm)A

Injection

,enoximone 5 mg/mL.For dilution before

use.Net price 20-mL amp= £15.02

Excipients

includealcohol, propyleneglycol (seeExcipients, p.2)

MILRINONE

Cautions

seeunder Enoximone; also correct hypo-

kalaemia;monitor renal function; interactions:

Appendix1 (phosphodiesterase type-3 inhibitors)

Renalimpairment

usehalf to three-quarters normal

doseand monitor response if estimatedglomerular

ﬁltrationrate less than 50mL/minute/1.73 m

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risk

BNFC 2011–2012 2.1.2 Phosphodiesterase type-3 inhibitors 75

Cardiovascularsystem

Breast-feeding

manufactureradvises caution—no

informationavailable

Side-effects

ectopicbeats, ventricular tachycardia,

supraventriculararrhythmias (more likely inchildren

withpre-existing arrhythmias), hypotension; head-

ache;

lesscommonly

ventricularﬁbrillation, chest

pain,tremor, hypokalaemia, thrombocytopenia;

very

rarely

bronchospasm,anaphylaxis, and rash

Licenseduse not licensedfor use in children under

18years

Indicationand dose

Congestiveheart failure, low cardiacoutput

followingcardiac surgery, shock

Byintravenous infusion

Neonate

initially50–75 micrograms/kg over30–

60minutes (reduce oromit initial dose ifat risk of

hypotension)then 30–45 micrograms/kg/hourby

continuousintravenous infusion

for2–3 days

(usuallyfor 12 hours aftercardiac surgery)

Child1 month–18 years

initially50–75 micr-

ograms/kgover 30–60 minutes (reduceor omit

initialdose if at riskof hypotension) then 30–

45micrograms/kg/hour by

continuousintra-

venousinfusion

for2–3 days (usuallyfor 12 hours

aftercardiac surgery)

Administration

for

intravenousinfusion

dilutewith

Glucose5%

SodiumChloride 0.9%

Sodium

Chlorideand Glucose intravenous infusionto a con-

centrationof 200 micrograms/mL(higher concentra-

tionsof 400micrograms/mL havebeen used);loading

dosemay be given undilutedif ﬂuid-restricted

Primacor

(Sanoﬁ-Aventis)A

Injection

,milrinone (as lactate) 1mg/mL, net price

10-mLamp = £16.61

2.2

Diuretics

Diureticsare used fora varietyof conditions inchildren

including pulmonary oedema (caused by conditions

suchas respiratory distress syndromeand bronchopul-

monarydysplasia), congestive heart failure, andhyper-

tension. Hypertension in children is often resistant to

therapy and may require the use of several drugs in

combination(see section2.5). Maintenance ofﬂ uidand

electrolytebalance can be difﬁcult in children ondiur-

etics,particularly neonateswhose renalfunction maybe

immature.

Loopdiuretics (section 2.2.2) are used for pulmonary

oedema,congestive heart failure, andin renal disease.

Thiazides(section 2.2.1) are used lesscommonly than

loop diuretics but are often used in combination with

loopdiuretics or spironolactone in the managementof

pulmonary oedema and, in lower doses, for hyper-

tensionassociated with cardiac disease.

Aminophylline infusion has been used with intra-

venousfurosemide to relieveﬂ uidoverload in critically

illchildren.

Heartfailure

Heartfailure is lesscommon in children

thanin adults;it canoccur asa result ofcongenital heart

disease (e.g. septal defects), dilated cardiomyopathy,

myocarditis, or cardiac surgery. Dr ug treatment of

heartfailure due to left ventricularsystolic dysfunction

iscovered below; optimal management ofheart failure

with preserved left ventricular function has not been

established.

Acutehear tfailure can occur after cardiacsurger yor

as a complication in severe acute infections with or

withoutmyocarditis. Therapy consists of volume load-

ing,vasodilator or inotropic drugs.

Chronic heart failure is initially treated with aloop

diuretic(section 2.2.2), usually furosemidesupplemen-

tedwith spironolactone, amiloride, or potassium.

Ifdiuresis withfurosemide is insufﬁcient,the additionof

metolazone ora thiazide diuretic (section 2.2.1) can

beconsidered. With metolazone, the resulting diuresis

canbe profoundand care isneeded to avoidpotentially

dangerouselectrolyte disturbance.

Ifdiuretics are insufﬁcient an ACE inhibitor,titrated to

the maximum tolerateddose, can be used. ACE inhi-

bitors(section 2.5.5.1) are usedfor the treatment ofall

gradesof heart failure in adults and canalso be useful

for children with heart failure. Addition of digoxin

(section2.1.1) canbe consideredin childrenwho remain

symptomatic despitetreatment with a diuretic and an

ACEinhibitor.

Some beta-blockers improve outcome inadults with

heart failure,but data on beta-blockers in children are

limited.Carvedilol (section 2.4) hasvasodilatory prop-

erties and therefore (like ACE inhibitors) alsolowers

afterload.

In children receiving specialist cardiology care, the

phosphodiesterasetype-3 inhibitorenoximone issome-

times used by mouth for its inotropic and vasodilator

effects.Spironolactone (section 2.2.3)is usually usedas

apotassium-sparing drug with aloop diuretic; inadults

low dosesof spironolactone are effective in the treat-

ment of heart failure. Careful monitoring of ser um

potassium is necessar y if spironolactone is used in

combinationwith an ACE inhibitor.

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 particularly dangerous in children

beingtreated with cardiac glycosides.In hepatic failure

hypokalaemia caused by diuretics can precipitate

encephalopathy.

The use of potassium-sparing diuretics (section 2.2.3)

avoidsthe need to takepotassium supplements.

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 are

usuallyadministered earlyin theday so thatthe diuresis

doesnot interfere with sleep.

In the management of

hypertension

a low dose of a

thiazide produces a maximal or near-maximal blood

pressure lowering effect, with ver y little biochemical

disturbance.Higher doses causemore marked changes

in plasma potassium, sodium, uric acid, glucose, and

lipids, with little advantage in blood pressure control.

For reference to the use of thiazides in chronic heart

failuresee section 2.2.

76 2.2 Diuretics BNFC2011–2012

Cardiovascularsystem

Bendroﬂumethiazide is licensed for use in children;

chlorothiazideis also used.

Chlortalidone, a thiazide-related compound, has a

longer duration of action than the thiazides and may

begiven on alternate daysin younger children.

Metolazone is particularly ef fective when combined

witha loop diuretic (even in renal failure) and ismost

effectivewhen given 30–60minutes before furosemide;

profounddiuresis can occurand the childshould there-

forebe monitored carefully.

Cautions

See also section 2.2. Thiazides and related

diuretics can exacerbate diabetes, gout, and systemic

lupuserythematosus. Electrolytes should bemonitored

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-

natraemia, and hypercalcaemia, symptomatic hyper-

uricaemia,and Addison’s disease.

Hepaticimpairment

Thiazidesand related diuretics

shouldbe usedwith caution inmild tomoderate impair-

mentand avoided insevere impairment. Hypokalaemia

may precipitate coma, although hypokalaemia can be

preventedby using a potassium-sparingdiuretic.

Renal impairment

Thiazides and related diuretics

should beused with caution because they can further

reducerenal function. They are ineffectiveif estimated

glomerular ﬁltration rate is less than30 mL/minute/

1.73m

and should be avoided; metolazone remains

effectivebut with a riskof excessive 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,

chlorothiazide,chlortalidone, andmetolazone presentin

milk istoo small to be harmful; large doses may sup-

presslactation.

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, and hyperuricaemia, and gout.

Less common side-effects include blood disorders

including agranulocytosis, leucopenia and thrombocy-

topenia,and impotence.Pancreatitis,intrahepatic chole-

stasis,cardiac arrhythmias,headache, dizziness, paraes-

thesia, visual disturbances, and hypersensitivity

reactions (including pneumonitis, pulmonary oedema,

photosensitivity,and severeskin reactions)have also

beenreported.

BENDROFLUMETHIAZIDE

(Bendroﬂuazide)

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above

Indicationand dose

Oedemain heart failure, renaldisease, and

hepaticdisease; pulmonary oedema; hyper-

tension

Bymouth

Child1 month–2 years

50–100micrograms/kg

dailyadjusted according to response

Child2–12 years

initially50–400 micrograms/kg

(max.10 mg) dailythen 50–100 micrograms/kg

dailyadjusted according to response(max. 10 mg

daily)

Child12–18 years

initially5–10 mg dailyor on

alternatedays (2.5 mgdaily in hypertension) asa

singlemorning dose, adjusted accordingto

response(max. 10 mgdaily)

Bendroﬂumethiazide(Non-proprietary) A

Tablets

,bendroﬂumethiazide 2.5mg, net price28-tab

pack= 79p; 5mg, 28-tab pack =86p

Brandsinclude

Aprinox

Neo-NaClex

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

CHLOROTHIAZIDE

Cautions

seenotes above; also neonate(theoretical

riskof kernicterus if very jaundiced)

Contra-indications

seenotes above

Hepaticimpairment

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above

Licenseduse not licensed

Indicationand dose

Heartfailure, hypertension, ascites

Bymouth

Neonate

10–20mg/kg twice daily

Child1–6 months

10–20mg/kg twice daily

Child6 months–12 years

10mg/kg twice daily

(max.1 g daily)

Child12–18 years

0.25–1g once daily

125–

500mg twice daily

Chronichypoglycaemia

section6.1.4

Diabetesinsipidus

section6.5.2

Preparations

Chlorothiazideoral suspension 250mg/5 mLis avail-

able from ‘special-order’manufacturers or specialist

importingcompanies, see p. 809

BNFC 2011–2012 2.2.1 Thiazides and related diuretics 77

Cardiovascularsystem

CHLORTALIDONE

(Chlorthalidone)

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

jaundice

Indicationand dose

Hypertension

Bymouth

Child5–12 years

0.5–1mg/kg in themorning

every48 hours; max. 1.7mg/kg every 48 hours

Child12–18 years

25mg daily inthe morning,

increasedto 50mg dailyif necessary(but seenotes

above)

Stableheart failure

Bymouth

Child5–12 years

0.5–1mg/kg in themorning

every48 hours; max. 1.7mg/kg every 48 hours

Child12–18 years

25–50mg daily inthe morn-

ing,increased if necessary to100–200 mg daily

(reduceto lowest effective dosefor maintenance)

Ascites,oedema in nephrotic syndrome

Bymouth

Child5–12 years

0.5–1mg/kg in themorning

every48 hours; max. 1.7mg/kg every 48 hours

Child12–18 years

upto 50 mgdaily

Hygroton

(Alliance)A

Tablets

,yellow, scored, chlortalidone 50mg, netprice

28-tabpack = £1.64

METOLAZONE

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

Licenseduse not licensedfor use in children

Indicationand dose

Oedemaresistant to loop diuretics inheart

failure,renal disease, and hepaticdisease;

pulmonaryoedema; adjunctto loopdiure ticsto

inducediuresis

Bymouth

Child1 month–12 years

100–200micrograms/

kgonce or twice daily

Child12–18 years

5–10mg once dailyin the

morning,increased to 5–10mg twice daily in

resistantoedema

Administration

tabletsmay be crushed and mixed

withwater immediately before use

Metenix5

(Sanoﬁ-Aventis)A

Tablets

,blue, metolazone 5mg, net price 100-tab

pack= £18.20

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

2.2.2

Loop diuretics

Loop diuretics inhibit reabsorption of sodium, potas-

sium,and chloride from theascending limb of theloop

ofHenle

inthe renal tubule andare powerful diuretics.

Furosemide and bumetanide are similarin activity;

they produce dose-related diuresis. Furosemide is

used extensivelyin children. It can be used for pulm-

onaryoedema (e.g.in respiratorydistress syndromeand

bronchopulmonarydysplasia), congestive heart failure,

andin renal disease.

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

shouldbe used withcaution in comatoseand precoma-

tosestates associatedwith livercirrhosis. Loopdiuretics

canexacerbate diabetes (buthyperglycaemia less likely

thanwith thiazides) andgout; theycan also causeacute

urinaryretention in childrenwith obstruction ofurinary

outﬂow, therefore adequate urinary output should be

establishedbefore initiating treatment.

Contra-indications

Loopdiuretics should beavoided

insevere hypokalaemia, severe hyponatraemia,anuria,

and inrenal failure due to nephrotoxic or hepatotoxic

drugs.

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), increased calcium excretion (nephrocalcinosis

andnephrolithiasis reported with long-term use of fur-

osemidein preterminfants), hypochloraemia,and hypo-

magnesaemia), metabolic alkalosis, blood disorders

(includingbone marrow depression,thrombocytopenia,

and leucopenia), hyperuricaemia, visual disturbances,

tinnitusand deafness(usually with highdoses and rapid

intravenous administration, and in renal impairment),

rash,and photosensitivity.

78 2.2.2 Loop diuretics BNFC2011–2012

Cardiovascularsystem

BUMETANIDE

Cautions

seenotes above

Contra-indications

seenotes above

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)

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Oedemain heart failure, renaldisease, and

hepaticdisease; pulmonary oedema

Bymouth

Child1 month–12 years

15–50micrograms/kg

1–4times daily (max. singledose 2 mg);do not

exceed5 mg daily

Child12–18 years

1mg inthe morning, repeated

after6–8 hours if necessary; severecases up to

5mg daily

Byintravenous injection

Child12–18 years

1–2mg, repeated after20

minutesif necessary

Byintravenous infusion over 30–60minutes

Child1 month–12 years

25–50micrograms/kg

Child12–18 years

1–5mg

Administration

for

intravenousinfusion

,dilute with

Glucose5%

SodiumChloride 0.9%;concentrations

above25 micrograms/mLmay cause precipitation

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-tab pack= £9.67

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

FUROSEMIDE

(Frusemide)

Cautions

seenotes above;also hypoproteinaemiamay

reduceeffect and increase risk ofside-effects; hepa-

torenalsyndrome; risk ofototoxicity may be reduced

bygiving high oraldoses in 2 ormore divided doses;

effectmay be prolonged inneonates; some liquid

preparationscontain alcohol, caution especiallyin

neonates;interactions: Appendix 1 (diuretics)

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

Indicationand dose

Oedemain heart failure, renaldisease, and

hepaticdisease; pulmonary oedema

Bymouth

Neonate

0.5–2mg/kg every 12–24hours (every

24hours if postmenstrual age under31 weeks)

Child1 month–12 years

0.5–2mg/kg 2–3 times

daily(every 24 hours if postmenstrualage under

31weeks); higher doses maybe required in resis-

tantoedema; max. 12mg/kg daily, notto exceed

80mg daily

Child12–18 years

20–40mg daily,increased in

resistantoedema to 80–120mg daily

Byslow intravenous injection

Neonate

0.5–1mg/kg every 12–24hours (every

24hours if postmenstrual age under31 weeks)

Child1 month–12 years

0.5–1mg/kg repeated

every8 hours as necessary; max.2 mg/kg (max.

40mg) every 8hours

Child12–18 years

20–40mg repeated every8

hoursas necessary; higher dosesmay be required

inresistant cases

Bycontinuous intravenous infusion

Child1 month–18 years

0.1–2mg/kg/hour (fol-

lowingcardiac surgery, initially100 micrograms/

kg/hour,doubled every 2hours until urine output

exceeds1 mL/kg/hour)

Oliguria

Bymouth

Child12–18 years

initially250 mg daily;if

necessary,dose increasedin stepsof 250 mggiven

every4–6 hours; max.single dose2 g(rarely used)

Byintravenous infusion

Child1 month–12years

2–5mg/kg upto 4times

daily(max. 1 gdaily)

Child12–18 years

initially250 mg over1 hour

(ratenot exceeding 4mg/minute), increase to

500mg over2 hoursif satisfactoryurine outputnot

obtained,then give afurther 1g over 4hours if no

satisfactoryresponse withinsubsequent hour, ifno

responseobtained dialysis probably required;

effectivedose (up to1 g)can be repeatedevery 24

hours

Administration

foradministration

bymouth

,tablets

canbe crushed and mixedwith water

injection

solutiondiluted and given bymouth.

For

intravenousinjection

,give over5–10 minutesat a

usualrate of 100micrograms/kg/minute (not

exceeding500 micrograms/kg/minute),max. 4 mg/

minute.

For

intravenousinfusion

,dilute withSodium Chloride

0.9%to a concentration of1–2 mg/mL; glucose

solutionsunsuitable (infusion pH mustbe above 5.5)

BNFC 2011–2012 2.2.2 Loop diuretics 79

Cardiovascularsystem

Furosemide(Non-proprietary) A

Tablets

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

81p;40 mg,28-tab pack= 84p; 500mg, 28-tabpack =

£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 alsoavailable;

brandsinclude

Minijet

2.2.3

Potassium-sparing

diuretics and aldosterone

antagonists

Spironolactoneis themost commonly usedpotassium-

sparingdiuretic in children;it is an aldosteroneantago-

nist and enhances potassium retention and sodium

excretion in the distal tubule. Spironolactone is com-

binedwith other diuretics to reduce urinarypotassium

loss.It isalso usedin nephroticsyndrome, thelong-term

managementof Bartter’ssyndrome, and highdoses can

helpto control ascites in babies with chronic neonatal

hepatitis. The clinical value of spironolactone in the

management of pulmonary oedema in preterm neo-

nateswith chronic lung diseaseis uncertain.

Potassiumcanrenoate, givenintravenously, isan alter-

native aldosterone antagonist that may be useful if a

potassium-sparing diuretic isrequired and the child is

unable to take oral medication. It is metabolised to

canrenone,which isalso ametabolite of spironolactone.

Amiloride on its own is a weak diuretic. It causes

retention of potassium and is therefore given with

thiazide or loop diuretics asan alternative to giving

potassiumsupplements (seesection 2.2.4for compound

preparationswith thiazides or loopdiuretics).

Apotassium-sparing diuretic such asspironolactone or

amiloride may also be used in the management of

amphotericin-inducedhypokalaemia.

Potassiumsupplements must not be given with potas-

sium-sparing diuretics.Administration of a potassium-

sparingdiuretic to achild receiving anACE inhibitor or

anangiotensin-II receptorantagonist (section 2.5.5)can

alsocause severe hyperkalaemia.

AMILORIDEHYDROCHLORIDE

Cautions

monitorelectrolytes; diabetes mellitus;

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

notto be usedfor treating hypertensionin

pregnancy

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

abdominalpain, gastro-intestinal bleed-

ing,dry mouth, thirst, diarrhoea, constipation,ano-

rexia,jaundice, dyspepsia, ﬂatulence, vomiting,

nausea,angina, arrhythmias, palpitation, postural

hypotension,dyspnoea, cough, nasal congestion,

confusion,headache, insomnia, weakness, tremor,

agitation,dizziness, malaise, paraesthesia,

encephalopathy,urinary disturbances, sexualdys-

function,hyperkalaemia, muscle cramp, arthralgia,

visualdisturbances, raised intra-ocular pressure,tin-

nitus,alopecia, pruritus, rash

Licenseduse not licensedfor use in children

Indicationand dose

Adjunctto thiazideor loopdiuretics foroedema

inheart failure, and hepaticdisease (where

potassiumconservation desirable)

Bymouth

Neonate

100–200micrograms/kg twice daily

Child1 month–12 years

100–200micrograms/

kgtwice daily; max. 20mg daily

Child12–18 years

5–10mg twice 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

Seesection 2.2.4

Aldosterone antagonists

SPIRONOLACTONE

Cautions

potentialmetabolic productscarcinogenic in

rodents

;monitor electrolytes (discontinue ifhyper-

kalaemia);acute porphyria (section 9.8.2); interac-

tions: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 butunli-

kelyto be harmful

Side-effects

gastro-intestinaldisturbances, hepato-

toxicity;malaise, headache, confusion, drowsiness,

dizziness;gynaecomastia, benign breast tumour,

breastpain, menstrualdisturbances, changesin libido;

hyperkalaemia(discontinue), hyponatraemia, acute

renalfailure, hyperuricaemia, leucopenia, agranulo-

cytosis,thrombocytopenia; leg cramps; alopecia,

hirsutism,rash, and Stevens-Johnson syndrome

Licenseduse not licensedfor reduction of hypokal-

aemiainduced by diuretics or amphotericin

80 2.2.3 Potassium-sparing diuretics and aldosterone antagonists BNFC 2011–2012

Cardiovascularsystem

Indicationand dose

Oedemain heart failure andin ascites,

nephroticsyndrome, reduction of hypokal-

aemiainduced by diuretics oramphotericin

Bymouth

Neonate

1–2mg/kg dailyin 1–2divided doses; up

to7 mg/kg dailyin resistant ascites

Child1 month–12 years

1–3mg/kg daily in1–2

divideddoses; up to 9mg/kg daily inresistant

ascites

Child12–18 years

50–100mg daily in1–2

divideddoses; up to 9mg/kg daily (max.400 mg

daily)in resistant ascites

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

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

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

POTASSIUMCANRENOATE

Cautions

potentialmetabolic productscarcinogenic in

rodents

;monitor electrolytes (discontinue ifhyper-

kalaemia);hypotension; acute porphyria (section

9.8.2);interactions: Appendix 1 (diuretics)

Contra-indications

hyperkalaemia;hyponatraemia

Renalimpairment

usewith caution and monitor

plasma-potassiumconcentration if estimated glom-

erularﬁltration rate30–60 mL/minute/1.73m

;avoid

ifestimated glomerularﬁltration rateless than30 mL/

minute/1.73m

Pregnancy

crossesplacenta; feminisation and undes-

cendedtestes in male fetusin

animal

studies—man-

ufactureradvises avoid

Breast-feeding

presentin breast milk—manufacturer

advisesavoid

Side-effects

drowsiness,headache, ataxia; menstrual

irregularities;hyperuricaemia; painat injection siteon

rapidadministration;

lesscommonly

thrombocytope-

nia,eosinophilia, and hyperkalaemia;

rarely

hepato-

toxicity,agranulocytosis, osteomalacia, hoarseness

anddeepening of voice, hypersensitivityreactions

(includingurticaria and erythema), andalopecia; also

gastro-intestinaldisturbances, hypotension, transient

confusionwith high doses, hyponatraemia,hypo-

chloraemicacidosis, mastalgia, gynaecomastia, and

hirsutism

Licenseduse not licensedfor use in the UK

Indicationand dose

Short-termdiuresis for oedema inheart failure

andin ascites

Byintravenous injectionover atleast 3minutes

orintravenous infusion

Neonate

1–2mg/kg twice daily

Child1 month–12 years

1–2mg/kg twice daily

Child12–18 years

1–2mg/kg (max. 200mg)

twicedaily

Note

Toconvert toequivalent oral spironolactonedose,

multiplypotassium canrenoate doseby 0.7

Administration

consultproduct literature

Preparations

Potassiumcanrenoate injectionis available from‘spe-

cial-order’manufacturers orspecialist importingcom-

panies,see p. 809

2.2.4

Potassium-sparing

diuretics with other

diuretics

Although it is preferable to prescribe diuretics sepa-

rately in children, the use of ﬁxed combinations may

bejustiﬁed in olderchildren if complianceis a problem.

Themost commonlyused preparations arelisted below

(but they may not be licensed for use in children—

consult product literature), for other preparations see

theBNF. Forinteractions, 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

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

Tablets

,co-amilofruse 5/40 (amiloridehydrochloride

5mg, furosemide40 mg). Netprice 28-tab pack =

£1.17,56-tab pack = £1.42

Brandsinclude

Frumil

Tablets

,co-amilofruse 10/80 (amiloride hydro-

chloride10 mg, furosemide80 mg),net price 28-tab

pack= £11.51

2.2.5

Osmotic diuretics

Mannitolis used totreat cerebraloedema, raised intra-

ocularpressure, peripheral oedema, andascites.

MANNITOL

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

severeheart failure; severe pulm-

onaryoedema; intracranial bleeding (exceptduring

craniotomy);anuria; severe dehydration

Renalimpairment

usewith caution in severeimpair-

ment

Pregnancy

manufactureradvises avoid unless essen-

tial—noinformation available

BNFC 2011–2012 2.2.4 Potassium-sparingdiuretics with other diuretics 81

Cardiovascularsystem

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

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Cerebraloedema, raised intra-ocular pressure

Byintravenous infusion over 30–60minutes

Child1 month–12 years

0.25–1.5g/kg repeated

ifnecessary 1–2 times after 4–8hours

Child12–18 years

0.25–2g/kg repeated if

necessary1–2 times after 4–8 hours

Peripheraloedema and ascites

Byintravenous infusion over 2–6hours

Child1 month–18 years

1–2g/kg

Administration

examineinfusion for crystals; if crys-

talspresent, dissolveby warming infusionﬂuid (allow

tocool to body temperaturebefore administration);

formannitol 20%, an in-line ﬁlteris recommended

(15-micronﬁlters have been used)

Mannitol(Baxter) A

Intravenousinfusion

,mannitol 10%, net price500-

Viaﬂex

bag= £2.26, 500-mL

Viaﬂo

bag=

£2.15;20%, 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

Classiﬁcationnot used in

BNFfor Children

2.2.7

Carbonic anhydrase

inhibitors

The carbonic anhydrase inhibitor acetazolamide is a

weak diuretic although it is little used for its diuretic

effect.Acetazolamide andeye dropsof dorzolamideand

brinzolamideinhibit the formation of aqueous humour

and are used in glaucoma (section 11.6). In children,

acetazolamideis also used inthe treatment of epilepsy

(section4.8.1), and raised intracranialpressure (section

11.6).

2.2.8

Diuretics with potassium

Diuretics and potassium supplements should bepre-

scribedseparately for children.

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-

sis ofthe type of arrhythmia; electrocardiography and

referral to apaediatric cardiologist is essential; under-

lying causes such as heart failure require appropriate

treatment.

Arrhythmiasmay be broadly dividedinto bradycardias,

supraventricular tachycardias,and ventricular arrhyth-

mias.

Bradycardia

Adrenaline(epinephrine) is useful inthe

treatment of symptomatic bradycardia in an infant or

child.

Supraventricular tachycardias

In supraventricular tachycardia adenosine is given by

rapid intravenousinjection. If adenosine is ineffective,

intravenous amiodarone, ﬂecainide, or a beta-blocker

(such asesmolol, see section 2.4) can be tried; verap-

amil can also be considered in children over1 year.

Atenolol, sotalol (section2.4), and ﬂecainide are used

for the prophylaxis of paroxysmal supraventricular

tachycardias.

Theuse of d.c.shock and vagal stimulationalso have a

rolein the treatment ofsupraventricular tachycardia.

Syndromes associatedwith accessory conduct-

ing pathways

Amiodarone, ﬂecainide, or a beta-

blockeris used to preventrecurrence of supraventricu-

lartachycardia in infantsand young childrenwith these

syndromes(e.g. Wolff-Parkinson-White syndrome).

Atrialﬂutter

Inatrial ﬂutter without structural heart

defects, sinus rhythm is restored with d.c. shock or

cardiacpacing; drug treatmentis usually notnecessary.

Amiodarone is used in atrial ﬂutter when structural

heartdefects are present or afterheart surgery. Sotalol

(section2.4) may also beconsidered.

Atrial ﬁbrillation

Atrial ﬁbrillation is very rare in

children. To restore sinus rhythm d.c. shock is used;

beta-blockers, alone or togetherwith digoxin, may be

usefulfor ventricular rate control.

Ectopictachycardia

Intravenousamiodarone isused

in conjunction with body cooling and synchronised

pacingin

postoperative

junctionalectopic tachycardia.

Oral amiodarone or ﬂecainide are used in

congenital

junctionalectopic tachycardia.

Amiodarone, ﬂecainide, or a beta-blocker are used in

atrial ectopic tachycardia; amiodarone is preferred in

thosewith poor ventricular function.

82 2.2.7 Carbonic anhydrase inhibitors BNFC 2011–2012

Cardiovascularsystem

Ventriculartachycardia and ventricular

ﬁbrillation

Pulselessventricular tachycardia or ventricular ﬁbrilla-

tionrequire resuscitation, see PaediatricAdvanced Life

Support algorithm (inside back cover). Amiodarone is

used in resuscitation for pulseless ventricular tachy-

cardia or ventricular ﬁbrillation unresponsive to d.c.

shock; lidocaine can be used as an alternative only if

amiodaroneis not available.

Amiodaroneis also used ina haemodynamically stable

childwhen drug treatmentis required; lidocaine canbe

used asan alternative only if amiodarone is not avail-

able.

Torsadede pointes

Torsadede pointes is afor mof

ventricular tachycardia associated with long QT

syndrome, which maybe congenital or dr ug induced.

Episodesmay be self-limiting, butare frequently recur-

rentand cancause impairmentor loss ofconsciousness.

Ifnot controlled, thearrhythmia can progressto ventri-

cular ﬁbrillation and sometimes death. Intravenous

magnesium sulphate (section 9.5.1.3) can be used to

treattorsade depointes (dose recommendationsvary—

consult local guidelines). Anti-arrhythmics can further

prolongthe QT interval, thusworsening the condition.

2.3.2

Drugs for arrhythmias

Anti-arrhythmic drugs can be classiﬁed clinically as

those acting on supraventricular arrhythmias (aden-

osine, digoxin, and verapamil), those acting on both

supraventricular and ventricular arrhythmias (amio-

darone, beta-blockers, ﬂecainide, and procainamide),

andthose acting onventricular arrhythmias (lidocaine).

Forthe treatment of bradycardia,see section 2.3.1.

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.

Adenosine is the treatment of choice for terminating

supraventricular tachycardias, including those asso-

ciatedwith accessory conducting pathways(e.g. Wolff-

Parkinson-Whitesyndrome). It is alsoused in the diag-

nosis of supraventricular arrhythmias. It is not nega-

tively inotropic and does not cause signiﬁcant hypo-

tension;it can be used safelyin children with impaired

cardiac function or postoperative arrhythmias. The

injection should be administeredby rapid intravenous

injectioninto a central orlarge peripheral vein.

Amiodarone is useful in the management of both

supraventricular and ventricular tachyarrhythmias. It

can be given by intravenous infusion and bymouth,

and causes little or no myocardial depression. Unlike

oral amiodarone, intravenous amiodarone acts rela-

tively rapidly.Intravenous amiodarone is also used in

cardiopulmonary resuscitation for ventricular ﬁbrilla-

tion or pulseless ventricular tachycardia unresponsive

tod.c. shock (see algorithm,inside back cover).

Amiodarone has a very long half-life (extending to

several weeks)and only needs to be given once daily

(buthigh dosesmay causenausea unlessdivided). 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, children and carers should be

advised to shield the child’s skin from light during

treatment and for several months after discontinuing

amiodarone; a wide-spectrum sunscreen (section

13.8.1) should be used to protectagainst both long-

waveultraviolet and visible light.

Amiodaronecontains iodine andcan cause disordersof

thyroid function; both hypothyroidism and hyper-

thyroidismcan occur.Clinical assessmentalone is unre-

liable,and laboratory tests shouldbe performed before

treatmentand every 6 months. Thyroxine(T4) may be

raisedin the absence of hyperthyroidism;therefore tri-

iodothyronine (T3),T4, and thyroid-stimulating horm-

one (thyrotrophin, TSH) should all be measured. 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 isessential; careful supervision isrequired.

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.Amiodarone is also associated with hepatotoxi-

city(see under amiodarone, below).

Beta-blockers actas anti-arrhythmic drugs principally

byattenuating the effectsof the sympatheticsystem on

automaticity and conductivity within the heart, for

detailssee section 2.4. Forspecial reference tothe role

ofsotalol in ventriculararrhythmias, see section 2.4.

Oraladministration of digoxin(section 2.1.1) slowsthe

ventricular ratein atrial ﬁbrillation and in atrial ﬂutter.

However,intravenous infusionof digoxinis rarely effec-

tivefor rapid control ofventricular rate.

Flecainide is useful for the treatment of resistant re-

entry supraventricular tachycardia, ventricular tachy-

cardia,ventricular ectopicbeats, arrhythmiasassociated

withaccessory conducting pathways(e.g. Wolff-Parkin-

son-Whitesyndrome), andparoxysmal atrial ﬁbrillation.

Flecainide crosses the placenta and can be used to

controlfetal supraventricular arrhythmias.

BNFC 2011–2012 2.3.2 Drugsfor arrhythmias 83

Cardiovascularsystem

Lidocaine can be used in cardiopulmonary resusci-

tation inchildren with ventricular ﬁbrillation or pulse-

lessventricular tachycardia unresponsive tod.c. shock,

butonly ifamiodarone is notavailable. Dosesmay need

tobe reduced inchildren with persistentlypoor cardiac

outputand hepatic orrenal failure (seeunder lidocaine,

below).

Verapamil(section 2.6.2) can cause severe haemody-

namiccompromise (refractory hypotensionand cardiac

arrest) when used for the acute treatment of arrhyth-

mias in neonates and infants; it is contra-indicated in

childrenunder 1year. Itis alsocontra-indicated in those

with congestive heart failure, syndromes associated

withaccessory conducting pathways(e.g. Wolff-Parkin-

son-White syndrome)and in most receiving concomi-

tantbeta-blockers. Itcan beuseful inolder children with

supraventriculartachycardia.

ADENOSINE

Cautions

monitorECG and have resuscitationfacil-

itiesavailable; atrial ﬁbrillation orﬂutter with acces-

sorypathway (conduction down anomalouspathway

mayincrease); ﬁrst degree AVblock; 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 (seedose);

interactions:Appendix 1 (adenosine)

Contra-indications

second-or third-degree AV block

andsick sinus syndrome (unlesspacemaker ﬁtted);

longQT syndrome; severehypotension; decompen-

satedheart failure; asthma

Pregnancy

largedoses may produce fetaltoxicity;

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

Licenseduse not licensedfor use in children

Indicationand dose

Arrhythmias(see also section2.3.1), diagnosis

ofarrhythmias

Byrapid intravenous injection

Neonates

150micrograms/kg; ifnecessary repeat

injectionevery 1–2minutes increasingdose by50–

100micrograms/kg until tachycardiaterminated

ormax. single dose of 300micrograms/kg given

Child1 month–1 year

150micrograms/kg; if

necessaryrepeat injection every 1–2 minutes

increasingthe dose by 50–100micrograms/kg

untiltachycardia terminatedor max.single dose of

500micrograms/kg given

Child1–12 years

100micrograms/kg; if

necessaryrepeat injection every 1–2 minutes

increasingdose by 50–100micrograms/kg until

tachycardiaterminated or max. single doseof

500micrograms/kg (max. 12mg) given

Child12–18 years

initially3 mg; ifnecessary

followedby 6mg after 1–2 minutes,and then by

12mg after afurther 1–2 minutes

Note

Insome children over12 years 3-mgdose inef-

fective(e.g. if asmall peripheral veinis used foradmin-

istration)and higher initialdose sometimes used;how-

ever,those with

hearttransplant

arevery sensitive to

theeffects of adenosine,and should notreceive higher

initialdoses. In childrenreceiving dipyridamole reduce

doseto a quarterof usual doseof adenosine

Administration

rapidintravenous injection

over2

secondsinto central orlarge peripheral veinfollowed

byrapid Sodium Chloride 0.9%ﬂ ush;Injection solu-

tionmay be diluted withSodium Chloride 0.9% if

required

Adenocor

(Sanoﬁ-Aventis)A

Injection

,adenosine 3mg/mL inphysiological saline,

netprice 2-mL vial =£4.45 (hosp. only)

Note

Intravenousinfusion of adenosine(

Adenoscan

Sanoﬁ-Aventis)may beused in conjunction withradio-

nuclidemyocardialperfusion imagingin patientswho cannot

exerciseadequately orfor whomexercise is inappropriate—

consultproduct literature

AMIODARONE HYDROCHLORIDE

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); pulmonaryfunction tests andchest

x-rayrequired before treatment; heartfailure; severe

bradycardiaand conductiondisturbances inexcessive

dosage;intravenous use may causemoderate and

transientfall in blood pressure(circulator ycollapse

precipitatedby rapidadministration oroverdosage) or

severehepato-cellular toxicity (monitor transami-

nasesclosely); ECG monitoring andresuscitation

facilitiesmust be available duringintravenous use;

acuteporphyria (section 9.8.2); avoidbenzyl alcohol

containinginjections in neonates (seeExcipients,

p.2); interactions: Appendix1 (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; avoidrapid loading after

cardiacsurgery

Pregnancy

possiblerisk of neonatalgoitre; use only if

noalternative

Breast-feeding

avoid;signiﬁcant amount present in

milk—riskof neonatalhypothyroidism fromrelease of

iodine

Side-effects

nausea,vomiting, taste disturbances,

raisedserum transaminases (may requiredose

reductionor withdrawalif accompaniedby acute liver

disorders),jaundice; bradycardia (see Cautions);

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);

less

commonly

onsetor worsening of arrhythmia,con-

ductiondisturbances (see Cautions), peripheral

84 2.3.2 Drugs for arrhythmias BNFC2011–2012

Cardiovascularsystem

neuropathyand myopathy (usuallyreversible on

withdrawal);

veryrarely

chronicliver disease includ-

ingcirrhosis, sinus arrest, bronchospasm (inpatients

withsevere respiratory failure), ataxia, benignintra-

cranialhypertension, headache, vertigo, epididymo-

orchitis,impotence, haemolytic or aplasticanaemia,

thrombocytopenia,rash (including exfoliative

dermatitis),hypersensitivity including vasculitis, alo-

pecia,impaired vision due tooptic neuritis or optic

neuropathy(including blindness), anaphylaxis on

rapidinjection, also hypotension, respiratorydistress

syndrome,sweating, and hot ﬂushes

Licenseduse notlicensed for usein childrenunder 3

years

Indicationand dose

Supraventricularand ventricular arrhythmias

seenotes above (initiated inhospital or under spe-

cialistsupervision)

Bymouth

Neonate

initially5–10 mg/kgtwice daily for 7–10

days,then reduced to maintenancedose of 5–

10mg/kg once daily

Child1 month–12 years

initially5–10 mg/kg

(max.200 mg) twicedaily for 7–10 days,then

reducedto maintenance doseof 5–10mg/kg once

daily(max. 200 mgdaily)

Child12–18 years

200mg 3 timesdaily for 1

weekthen 200 mgtwice daily for 1week then

usually200 mg dailyadjusted according to

response

Byintravenous infusion

Neonate

initially5 mg/kg over30 minutes then

5mg/kg over 30minutes every 12–24 hours

Child1 month–18 years

initially5–10 mg/kg

over20 minutes–2 hours then

bycontinuous

infusion

300micrograms/kg/hour, increased

accordingto responseto max.1.5 mg/kg/hour;do

notexceed 1.2 gin 24 hours

Ventricularﬁbrillation or pulseless ventricular

tachycardiarefractory to deﬁbrillation

(seealso

section2.3.1)

Byintravenous injection

Neonate

5mg/kg over atleast 3 minutes

Child1 month–18 years

5mg/kg (max.300 mg)

overat least 3 minutes

Administration

intravenousadministration viacentral

venouscatheter recommended if repeated orcontin-

uousinfusion required,as infusionvia peripheralveins

maycause pain and inﬂammation.

For

intravenousinfusion

,dilute to a concentrationof

notless than 600micrograms/mL with Glucose 5%;

incompatiblewith Sodium Chloride infusion;avoid

equipmentcontaining the plasticizer di-2-ethyl-

hexphthalate(DEHP).

Foradministration

bymouth

,tablets may becr ushed

anddispersed in water; injectionsolution should not

begiven orally (irritant)

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)

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

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)

FLECAINIDE ACETATE

Cautions

childrenwith pacemakers (especially those

whomay be pacemaker dependentbecause stimula-

tionthreshold may riseappreciably); atrial ﬁbrillation

followingheart surgery; monitor ECG andhave re-

suscitationfacilities available during intravenoususe;

interactions:Appendix 1 (ﬂecainide)

Contra-indications

heartfailure; abnormal left

ventricularfunction; long-standing atrial ﬁbrillation

whereconversion to sinus rhythmnot attempted;

haemodynamicallysigniﬁcant valvular heart disease;

avoidin sinus node dysfunction,atrial conduction

defects,second-degree or greater AVblock, bundle

branchblock or distal blockunless pacing rescue

available

Hepaticimpairment

avoidor reduce dose insevere

impairment;monitor plasma concentration (see

pharmacokineticsbelow)

Renalimpairment

reducedose by 25–50% ifesti-

matedglomerular ﬁltration rate less than35 mL/

minute/1.73m

andmonitor plasma-ﬂecainide con-

centration(see pharmacokinetics below)

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,

hypoaesthesia,anaemia, leucopenia, thrombocytope-

nia,corneal deposits, tinnitus, increasedantinuclear

antibodies,hypersensitivity reactions (including rash,

urticaria,and photosensitivity), increased sweating

Pharmacokinetics plasma-ﬂecainide concentration

foroptimal response 200–800micrograms/litre;

bloodsample should be taken immediatelybefore

nextdose

BNFC 2011–2012 2.3.2 Drugsfor arrhythmias 85

Cardiovascularsystem

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Resistantre-entry supraventricular tachy-

cardia,ventricular ectopic beats orventricular

tachycardia,arrhythmias associated with

accessoryconduction pathways (e.g. Wolff-

Parkinson-Whitesyndrome), paroxysmal atrial

ﬁbrillation

Bymouth

Neonate

2mg/kg 2–3 timesdaily adjusted

accordingto response and plasma-ﬂecainide con-

centration

Child1 month–12years

2mg/kg 2–3times daily

adjustedaccording to response andplasma-ﬂ e-

cainideconcentration (max. 8mg/kg/day or

300mg daily)

Child12–18 years

initially50–100 mg twice

daily;max. 300 mgdaily (max. 400mg daily for

ventriculararrhythmias in heavily builtchildren)

Byslow intravenous injection orintravenous

infusion

Neonate

1–2mg/kg over 10–30minutes; if

necessaryfollowed bycontinuous infusionat arate

of100–250 micrograms/kg/hour untilarrhythmia

controlled;transfer to

oral

treatmentas above

Child1 month–12 years

2mg/kg over 10–30

minutes;if necessary followed bycontinuous

infusionat arate of 100–250micrograms/kg/hour

untilarrhythmia controlled (max.cumulative dose

600mg in 24hours); transfer to

oral

treatmentas

above

Child12–18 years

2mg/kg (max. 150mg) over

10–30minutes; if necessary followedby continu-

ousinfusion ata rateof 1.5mg/kg/hour for1 hour,

thenreduced to 100–250micrograms/kg/hour

untilarrhythmia controlled (max.cumulative dose

600mg inﬁrst 24hours); transfer to

oral

treatment

asabove

Administration

foradministration

bymouth

,milk,

infantformula, and dairy products mayreduce

absorptionof ﬂecainide—separate doses from feeds.

Liquidhas a local anaestheticef fectand should be

givenat least 30minutes before orafter food. Do not

storeliquid in refrigerator asprecipitation occurs.

For

intravenousadministration

,give initial doseover

30minutes in children withsustained ventricular

tachycardiaor cardiac failure.

Diluteinjection using Glucose 5%;concentrations of

morethan 300 micrograms/mLare unstable in

chloride-containingsolutions

Flecainide(Non-proprietary) A

Tablets

,ﬂecainide acetate 50mg, net price 60-tab

pack= £6.04; 100mg, 60-tab pack= £8.95

Liquid

,available from ‘special-order’ manufacturers

orspecialist importing companies, seep. 809

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

Bymouth

Child12–18 years

200mg oncedaily

Note

Notto be usedto control arrhythmiasin acute

situations;children stabilised on200 mgdaily of

immediate-releaseﬂecainide may betransferred to

Tambocor

LIDOCAINE HYDROCHLORIDE

(Lignocainehydrochloride)

Cautions

lowerdoses in congestive heartfailure and

followingcardiac surgery;monitor ECG; resuscitation

facilitiesshould be available; interactions:Appendix

1(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

Licenseduse notlicensed for usein childrenunder 1

year

Indicationand dose

Ventriculararrhythmias, pulseless ventricular

tachycardiaor ventricular ﬁbrillation

Byintravenous or intraosseous injection,and

intravenousinfusion

Neonate

0.5–1mg/kg by injectionfollowed by

infusionof 0.6–3 mg/kg/hour;if infusion not

immediatelyavailable following initialinjection,

injectionof 0.5–1 mg/kgmay be repeated at

intervalsof not less than 5minutes (to max. total

dose3 mg/kg) untilinfusion can be initiated

Child1 month–12 years

0.5–1mg/kg by injec-

tionfollowed by infusion of0.6–3 mg/kg/hour; if

infusionnot immediately availablefollowing initial

injection,injection of 0.5–1mg/kg may be

repeatedat intervals ofnot less than5 minutes (to

max.total dose 3mg/kg) until infusion canbe

initiated

Child12–18 years

50–100mg by injectionfol-

lowedby infusion of120 mg over30 minutes

then

240mg over 2hours

then

60mg/hour; reduce

dosefurther ifinfusion continuedbeyond 24hours;

ifinfusion not immediately availablefollowing

initialinjection, injection of 50–100mg may be

repeatedat intervals ofnot less than5 minutes (to

max.300 mg in1 hour) until infusioncan be

initiated

86 2.3.2 Drugs for arrhythmias BNFC2011–2012

Cardiovascularsystem

Neonatalseizures

(section4.8.1)

Byintravenous infusion

Neonate

initially2 mg/kg over10 minutes, fol-

lowedby 6mg/kg/hour for 6 hours; reducedose

overthe following 24 hours(4 mg/kg/hour for12

hours,then 2 mg/kg/hourfor 12 hours)

Note

Pretermneonates may requirelower doses

Eye

section11.7

Localanaesthesia

section15.2

Administration

for

intravenousinfusion

,dilute with

Glucose5% or Sodium Chloride0.9%

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

Lidocaine(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, peripheral vascu-

lature,bronchi, pancreas, and liver.

Many beta-blockers are available but experience in

childrenis limited to theuse of only afew.

Differences between beta-blockers may affect choice.

The water-soluble beta-blockers, atenolol and sotalol,

areless likelyto enterthe brainand maytherefore cause

less sleep disturbance and nightmares. Water-soluble

beta-blockers areexcreted by the kidneys and dosage

reductionis often necessary in renalimpairment.

Somebeta-blockers, such as atenolol, have anintrinsi-

callylonger durationof actionand needto be givenonly

once daily. Carvedilol and labetalol are beta-blockers

whichhave, inaddition, anarteriolar vasodilating action

andthus lower peripheralresistance. Although carvedi-

loland labetalol possess both alpha-and beta-blocking

properties, these dr ugs haveno important advantages

over other beta-blockers in the treatment of hyper-

tension.

Beta-blockersslow the heart andcan depress the myo-

cardium; they are contra-indicated in children with

second- or third-degree heart block. Sotalol may pro-

long the QT interval, and it occasionallycauses life-

threatening ventricular arrhythmias (important: parti-

cularcare is requiredto avoidhypokalaemia in children

takingsotalol).

Beta-blockerscan precipitateasthma andshould usually

be avoided in children with a history of asthma or

bronchospasm. If there is no alternative, a child with

well-controlledasthma can be treated fora co-existing

condition(e.g. arrhythmia) with a cardioselectivebeta-

blocker,which should beinitiated with cautionat a low

doseby a specialistand the child monitoredclosely for

adverseeffects. Atenololand metoprololhave lesseffect

on the beta

(bronchial) receptors and are, therefore,

relatively

cardioselective

,but they are not

cardiospeci-

ﬁc

;they have a lesser effect on airways resistance but

arenot free of thisside-ef fect.

Beta-blockersare also associatedwith fatigue, coldness

of the extremities, and sleep disturbances with night-

mares (may be less common with the water-soluble

beta-blockers,see above).

Beta-blockerscan affectcarbohydrate metabolismcaus-

inghypoglycaemia or hyperglycaemia in children with

orwithout diabetes; theycan also interferewith metab-

olicand autonomicresponses tohypoglycaemia thereby

maskingsymptoms suchas tachycardia.However, beta-

blockersare not contra-indicated in diabetes, although

the cardioselective beta-blockers (e.g. atenolol and

metoprolol)may be preferred. Beta-blockers shouldbe

avoided altogether in those with frequent episodes of

hypoglycaemia.

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 affect infants. Atenolol andsotalol are present

inmilk ingreater amountsthan otherbeta-blockers. The

manufacturer of esmolol advises avoidance if breast-

feeding.

Hypertension

Beta-blockersare effectivefor reducing

bloodpressure (section 2.5),but their mode of action is

not understood;they reduce cardiac output, alter bar-

oceptorreﬂ exsensitivity, and block peripheraladreno-

ceptors.Somebeta-blockers depressplasma reninsecre-

tion.It is possible that a central effect mayalso partly

explaintheir modeof action.Blood pressure canusually

becontrolled with relativelyfew side-effects. Ingeneral

thedose of beta-blockerdoes not haveto be high.

Labetalolmay be given intravenously for

hypertensive

emergencies

in children(section 2.5); however, care is

neededto avoid dangerous hypotension orbeta-block-

ade, particularly in neonates. Esmolol is also used

intravenouslyfor thetreatment of hypertensionparticu-

larlyin the peri-operative period.

Beta-blockers canbe used to control the pulse rate in

children 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; phenoxybenzamine should

alwaysbe used together withthe beta-blocker.

BNFC 2011–2012 2.4 Beta-adrenoceptor blocking drugs 87

Cardiovascularsystem

Arrhythmias

Inarrhythmias (section 2.3),beta-block-

ers act principally by attenuating the ef fects of the

sympathetic system on automaticity and conductivity

withinthe heart. Theycan be usedalone or inconjunc-

tionwith digoxinto control theventricular rate in

atrial

ﬁbrillation

.Beta-blockers arealso useful inthe manage-

mentof

supraventriculartachycardias

and

ventricular

tachycardias

particularly to preventrecur rence of the

tachycardia.

Esmololis arelatively cardioselectivebeta-blocker with

aver yshort duration of action, used intravenously for

the short-term treatment of supraventricular arrhyth-

mias and sinus tachycardia, particularly in the peri-

operativeperiod.

Sotalolis a non-cardioselectivebeta-blocker with addi-

tional class III anti-arrhythmic activity.Atenolol and

sotalolsuppress ventricular ectopic beats andnon-sus-

tainedventricular tachycardia (section2.3.1). However,

the pro-arrhythmic effects of sotalol, particularly in

children with sick sinus syndrome, may prolong the

QTinterval and induce torsadede pointes.

Heart failure

Beta-blockers may produce beneﬁt in

heart failure by blocking sympathetic activity and the

addition ofa beta-blocker such as carvedilol to other

treatmentfor heart failuremay bebeneﬁcial. Treatment

shouldbe initiatedby those experiencedin themanage-

mentof heartfailure (see section2.2 for detailson heart

failure).

Thyrotoxicosis

Beta-blockersare usedin themanage-

ment of

thyrotoxicosis

including neonatal thyrotoxic-

osis;propranolol can reverseclinical symptoms within

4days. Beta-blockersare alsoused for thepre-operative

preparation for thyroidectomy; the thyroid gland is

renderedless vascular, thusfacilitating surgery (section

6.2.2).

Otheruses

Intetralogy ofFallot, esmololor proprano-

lol may be given intravenously in the initial manage-

mentof

cyanoticspells

;propranolol is given by mouth

forpreventing cyanotic spells.If a severecyanotic spell

ina child with congenitalheart disease persists despite

optimal use of 100% oxygen, propranolol is given by

intravenousinfusion (fordose, see below).If cyanosis is

stillpresent after 10minutes, sodium bicarbonateintra-

venous infusion is given ina dose of 1mmol/kg to

correctacidosis (ordose calculatedaccording to arterial

blood gas results); sodium bicarbonate 4.2% intra-

venousinfusion is appropriate for a childunder 1 year

and sodium bicarbonate 8.4% intravenous infusion in

children over 1 year. If blood-glucose concentration is

less than 3mmol/litre, glucose 10% intravenous infu-

sionis given ina dose of 2mL/kg (glucose200 mg/kg)

over 10 minutes, followed by morphine in a doseof

100micrograms/kg by intravenous or intramuscular

injection.

Beta-blockers are also used in the

prophylaxis of

migraine

(section 4.7.4.2). Betaxolol, carteolol,

levobunolol,and timololare used topicallyin

glaucoma

(section11.6).

PROPRANOLOLHYDROCHLORIDE

Cautions

seenotes above; also avoidabrupt with-

drawal;ﬁrst-degree AV block;portal hypertension

(riskof deterioration in liverfunction); diabetes (see

alsonotes above); history ofobstr uctiveairways dis-

ease(introduce cautiously and monitorlung func-

tion—seealso notes above); myastheniagravis;

symptomsof thyrotoxicosis maybe masked (seealso

notesabove); psoriasis; history ofhypersensitivity—

mayincrease sensitivity to allergensand result in

moreserious hypersensitivity response, alsomay

reduceresponse to adrenaline (epinephrine);inter-

actions:Appendix 1 (beta-blockers), important:

verapamilinteraction, see also p.109

Contra-indications

asthma(but see notes above),

uncontrolledheart failure, marked bradycardia,

hypotension,sick sinus syndrome, second-or third-

degreeAV block, cardiogenicshock, metabolic aci-

dosis,severe peripheral arterial disease;phaeo-

chromocytoma(apart from speciﬁc usewith alpha-

blockers,see also notes above)

Bronchospasm

Beta-blockers,includingthose consideredto

becardioselective,should usuallybe avoidedin childrenwith

ahistory ofasthma orbronchospasm. However,where there

isno alternativea cardioselective beta-blockercan be given

withcaution under specialistsupervision

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, psychoses; sexual

dysfunction;purpura, thrombocytopenia; visual dis-

turbances;exacerbation of psoriasis, alopecia;

rarely

rashesand dry eyes (reversibleon withdrawal);

overdosage:see Emergency Treatmentof Poisoning,

p. 29

Licenseduse not licensedfor treatment of hyper-

tensionin children under 12 years

Indicationand dose

Arrhythmias

Bymouth

Neonate

250–500micrograms/kg 3 timesdaily,

adjustedaccording to response

Child1 month–18 years

250–500micrograms/

kg3–4 timesdaily, adjustedaccording toresponse;

max.1 mg/kg4 times daily,total dailydose not to

exceed160 mg daily

Byslow intravenous injection, withECG mon-

itoring

Neonate

20–50micrograms/kg repeated if

necessaryevery 6–8 hours

Child1 month–18 years

25–50micrograms/kg

repeatedevery 6–8 hours if necessary

Hypertension

Bymouth

Neonate

initially250 micrograms/kg3 timesdaily,

increasedif necessary to max. 2mg/kg 3 times

daily

Child1 month–12 years

0.25–1mg/kg 3 times

daily,increased at weeklyintervals to max. 5mg/

kgdaily

88 2.4 Beta-adrenoceptor blocking drugs BNFC 2011–2012

Cardiovascularsystem

Child12–18 years

initially80 mg twicedaily;

increasedat weekly intervals asrequired; mainte-

nance160–320 mg daily;slow-release prepara-

tionsmay be used foronce daily administration

Tetralogyof Fallot

Bymouth

Neonate

0.25–1mg/kg 2–3 timesdaily, max.

2mg/kg 3 timesdaily

Child1 month–12years

0.25–1mg/kg 3–4times

daily,max. 5mg/kg daily

Byslow intravenous injection withECG moni-

toring

Neonate

initially15–20 micrograms/kg (max.

100micrograms/kg), repeated every12 hours if

necessary

Child1 month–12 years

initially15–20 micr-

ograms/kg(max. 100 micrograms/kg),repeated

every6–8 hours if necessary; higherdoses rarely

necessary

Migraineprophylaxis

Bymouth

Child2–12 years

initially200–500 micrograms/

kgtwice daily; usual dose10–20 mg twicedaily;

max.2 mg/kg twicedaily

Child12–18 years

initially20–40 mgtwice daily;

usualdose 40–80 mgtwice daily; max. 2mg/kg

(max.120 mg) twicedaily

Administration

for

slowintravenous injection

,give

overat least 3–5 minutes;rate of administration

shouldnot exceed 1mg/minute. Maybe diluted with

SodiumChloride 0.9% or Glucose5%. Incompatible

withbicarbonate.

Note

Excessivebradycardia canbe countered with intra-

venousinjection of atropinesulphate; for overdosagesee

EmergencyTreatment of Poisoning,p. 29

Propranolol(Non-proprietary) A

Tablets

,propranolol hydrochloride 10mg, net price

28-tabpack = 92p; 40mg, 28-tabpack = 93p; 80mg,

56-tabpack = £1.54; 160mg, 56-tabpack = £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 for oncedaily administra-

tion;use in olderchildren only

Half-InderalLA

(AstraZeneca)A

Capsules

,m/r, lavender/pink, propranololhydro-

chloride80 mg. Netprice 28-cap pack =£5.40.

Label:8, 25

Note

Modiﬁed-releasecapsules containing propranolol

hydrochloride80mg alsoavailable; brandsinclude

Bedranol

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-releasecapsules containing propranolol

hydrochloride160 mgalso available; brandsinclude

BedranolSR

Beta-Prograne

Slo-Pro

ATENOLOL

Cautions

seeunder Propranolol Hydrochloride

Contra-indications

seeunder Propranolol Hydro-

chloride

Renalimpairment

initiallyuse 50% of usualdose if

estimatedglomerular ﬁltration rate 10–35mL/min-

ute/1.73m

;initially use 30–50% ofusual dose if

estimatedglomerular ﬁltration rate less than10 mL/

minute/1.73m

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seeunder Propranolol Hydrochloride

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Hypertension

Bymouth

Neonate

0.5–2mg/kg oncedaily; may begiven in

2divided doses

Child1 month–12 years

0.5–2mg/kg oncedaily

(doseshigher than 50mg daily rarely necessary);

maybe given in 2divided doses

Child12–18 years

25–50mg once daily(higher

dosesrarely necessary); maybe given in2 divided

doses

Arrhythmias

Bymouth

Neonate

0.5–2mg/kg oncedaily; may begiven in

2divided doses

Child1 month–12 years

0.5–2mg/kg oncedaily

(max.100 mg daily);may be given in2 divided

doses

Child12–18 years

50–100mg oncedaily; maybe

givenin 2 divided doses

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

CARVEDILOL

Cautions

seeunder Propranolol Hydrochloride;

monitorrenal function during dose titrationin chil-

drenwith heart failure whoalso have low blood

BNFC 2011–2012 2.4 Beta-adrenoceptor blocking drugs 89

Cardiovascularsystem

pressure,renal impairment, ischaemic heartdisease,

ordiffuse 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

Licenseduse not licensedfor use in children under

18years

Indicationand dose

Adjunctin heart failure

(limitedinformation

available)

Bymouth

Child2–18 years

initially50 micrograms/kg

(max.3.125 mg) twicedaily, double doseat inter-

valsof at least 2weeks up to 350micrograms/kg

(max.25 mg) twicedaily

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

ESMOLOLHYDROCHLORIDE

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;

infusioncauses venous irritation and thrombophleb-

itis

Licenseduse not licensedfor use in children

Indicationand dose

Arrhythmias,hypertensive emergencies

(see

alsonotes above and section2.5)

Byintravenous administration

Child1 month–18 years

initiallyby

intravenous

injection

over1 minute 500micrograms/kg then

intravenousinfusion

50micrograms/kg/min-

utefor 4 minutes (ratereduced if low blood pres-

sureor low heart rate);if inadequate response,

repeatloading dose and increasemaintenance

infusionby 50micrograms/kg/minute increments;

repeatuntil effective or max. infusionof

200micrograms/kg/minute reached; dosesover

300micrograms/kg/minute not recommended

Tetralogyof Fallot

Byintravenous administration

Neonate

initiallyby

intravenousinjection

over1–2

minutes600 micrograms/kg thenif necessary by

intravenousinfusion

300–900micrograms/kg/

minute

Administration

givethrough a central venouscathe-

ter;incompatible with bicarbonate

Brevibloc

(Baxter)A

Injection

,esmolol hydrochloride10 mg/mL,net price

10-mLvial = £7.79, 250-mLinfusion bag = £89.69

LABETALOLHYDROCHLORIDE

Cautions

seeunder Propranolol Hydrochloride; inter-

fereswith laboratory tests for catecholamines;liver

damage(see below)

Liverdamage

Severehepatocellular damage reportedafter

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

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

Licenseduse not licensedfor use in children

Indicationand dose

Hypertensiveemergencies

seealso section 2.5

Byintravenous infusion

Neonate

500micrograms/kg/hour adjusted at

intervalsof at least 15 minutesaccording to

response;max. 4 mg/kg/hour

Child1 month–12 years

initially0.5–1 mg/kg/

houradjusted at intervals of atleast 15 minutes

accordingto response; max. 3mg/kg/hour

Child12–18 years

30–120mg/hour adjusted at

intervalsof at least 15 minutesaccording to

response

Note

Consultlocal guidelines. Inhypertensive

encephalopathyreduce blood pressureto normotensive

levelover 24–48hours(more rapidreduction maylead to

cerebralinfarction, blindness, anddeath). If childﬁtting,

reduceblood pressure rapidly,but notto normal levels

Hypertension

Bymouth

Child1 month–12 years

1–2mg/kg 3–4 timesa

day

Child12–18 years

initially50–100 mgtwice daily

increasedif required at intervals of3–14 days to

usualdose of 200–400mg twicedaily (3–4 divided

dosesif higher); max. 2.4g daily

90 2.4 Beta-adrenoceptor blocking drugs BNFC 2011–2012

Cardiovascularsystem

Byintravenous injection

Child1 month–12 years

250–500micrograms/

kgas a single dose;max. 20 mg

Child12–18 years

50mg over atleast 1 minute,

repeatedafter 5 minutes ifnecessar y;max. total

dose200 mg

Note

Excessivebradycardia canbe countered with intra-

venousinjection of atropinesulphate; for overdosagesee

p.2 9

Administration

for

intravenousinfusion

,dilute to a

concentrationof 1 mg/mLin Glucose 5%

Sodium

Chlorideand Glucose 5%; if ﬂuidrestricted may be

givenundiluted, preferably through acentral venous

catheter.

Foradministration

bymouth,

injectionmay be given

orallywith squash or juice

LabetalolHydrochloride (Non-proprietary) A

Tablets

,f/c, labetalolhydrochloride 100mg, netprice

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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

METOPROLOLTARTRATE

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

Licenseduse not licensedfor use in children

Indicationand dose

Hypertension

Bymouth

Child1 month–12 years

initially1 mg/kg twice

daily,increased if necessary tomax. 8mg/kg

(max.400 mg) dailyin 2–4 divided doses

Child12–18 years

initially50–100 mg daily

increasedif necessary to 200mg daily in1–2

divideddoses; max. 400mg daily (but highdoses

rarelynecessary)

Arrhythmias

Bymouth

Child12–18 years

usually50 mg2–3 times daily;

upto 300 mgdaily in divided dosesif necessary

MetoprololTartrate (Non-proprietary) A

Tablets

,metoprolol tartrate 50mg, net price 28-tab

pack= £1.31, 56-tab pack= £1.74; 100mg, 28-tab

pack= £1.59, 56-tab pack= £2.51. Label:8

Lopresor

(Recordati)A

Tablets

,f/c, scored, metoprololtartrate 50mg (pink),

netprice 56-tab pack =£2.57; 100 mg(blue), 56-tab

pack= £6.68. Label: 8

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

Bymouth

Child12–18 years

200mg oncedaily

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

SOTALOLHYDROCHLORIDE

Cautions

seeunder Propranolol Hydrochloride; cor-

recthypokalaemia, hypomagnesaemia, or other

electrolytedisturbances; severe or prolongeddiar r-

hoea;reduce dose or discontinueif corrected QT

intervalexceeds 550 msec

Contra-indications

seeunder Propranolol Hydro-

chloride;congenital or acquired longQT syndrome;

torsadede pointes

Renalimpairment

halvenormal dose if estimated

glomerularﬁltration rate 30–60mL/minute/1.73 m

;

useone-quarter normal dose if estimatedglomerular

ﬁltrationrate 10–30 mL/minute/1.73m

;avoid if

estimatedglomerular ﬁltration rate less than10 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 females)

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Ventriculararrhythmias, life-threatening

ventriculartachyarrhythmia and supraventri-

culararrhythmias

initiatedunder specialist super-

visionand ECG monitoring andmeasurement of

correctedQT interval

Bymouth

Neonate

initially1 mg/kgtwice daily,increased as

necessaryevery 3–4 days to max.4 mg/kg twice

daily

Atrialﬂutter, ventricular arrhythmias, life-

threateningventricular tachyarrhythmia and

supraventriculararrhythmias

initiatedunder

specialistsupervision and ECG monitoring and

measurementof corrected QT interval

Bymouth

Child1 month–12 years

initially1 mg/kg twice

daily,increased as necessaryever y2–3 days to

max.4 mg/kgtwice daily (max.80 mgtwice daily)

Child12–18 years

initially80 mg oncedaily

40mg twice daily,increased gradually atintervals

of2–3 days to usualdose 80–160 mgtwice daily;

higherdoses of 480–640mg daily for life-threa-

teningventricular arrhythmias under specialist

supervision

BNFC 2011–2012 2.4 Beta-adrenoceptor blocking drugs 91

Cardiovascularsystem

Administration

foradministration

bymouth

,tablets

maybe crushed and dispersed inwater

Note

Excessivebradycardia canbe countered with intra-

venousinjection of atropinesulphate; for overdosagesee

EmergencyTreatment of Poisoning,p. 29

Sotalol(Non-proprietary) A

Tablets

,sotalol hydrochloride40 mg,net price 56-tab

pack= £1.29;80 mg,56-tab pack= £1.91; 160mg, 28-

tabpack = £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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

2.5

Hypertension

2.5.1 Vasodilator antihypertensive drugs

andpulmonary hypertension

2.5.2 Centrally acting antihypertensive

drugs

2.5.3 Adrenergic neurone blocking drugs

2.5.4 Alpha-adrenoceptor blocking drugs

2.5.5 Drugs affecting the renin-angiotensin

system

Hypertension in children and adolescents can have a

substantial effect onlong-ter mhealth. Possible causes

of hypertension (e.g. congenital heart disease, renal

disease and endocrine disorders) and the presence of

any complications (e.g. left ventricular hypertrophy)

should beestablished. Treatment should take account

ofcontributory factors andany factorsthat increase the

riskof cardiovascular complications.

Serious hypertension is rare in

neonates

but it can

present with signs of congestive heart failure; the

cause is often renal and can follow embolic arterial

damage.

Children (or their parents or carers) should begiven

adviceon lifestyle changesto reduce blood pressureor

cardiovascular risk;these include weight reduction (in

obese children),reduction of dietary salt, reduction of

total and saturated fat, increasing exercise, increasing

fruitand vegetable intake, andnot smoking.

Indications for antihypertensive therapy in children

include symptomatic hypertension, secondary hyper-

tension, hypertensive target-organ damage, diabetes

mellitus,persistent hypertension despite lifestyle mea-

sures(see above),and pulmonary hypertension(section

2.5.1.2). The effect of antihypertensive treatment on

growth and development is not known; treatment

shouldbe started only ifbeneﬁts are clear.

Antihypertensive therapy should be initiated with a

singledrug at the lowest recommendeddose; the dose

can be increased until the target blood pressure is

achieved. Once the highest recommended dose is

reached, or soonerif the patient begins to experience

side-effects, a second drug may be added if blood

pressure is not controlled. If more than one drug is

required,these should begiven as separate productsto

allow dose adjustment of individual drugs, but ﬁxed-

dose combination products may be useful inadoles-

centsif compliance is aproblem.

Acceptabledrug classes for usein children with hyper-

tensioninclude ACEinhibitors (section 2.5.5.1),alpha-

blockers (section 2.5.4), beta-blockers (section 2.4),

calcium-channelblockers (section2.6.2), and thiazide

diuretics(section 2.2.1).There islimited information on

theuse ofangiotensin-II receptorantagonists (section

2.5.5.2)in children. Diuretics and beta-blockers havea

long history of safety and efﬁcacy in children. The

newer classes of antihypertensive drugs, including

ACE inhibitors and calcium-channel blockers have

been shown to be safe and effective in short-term

studiesin children.Refractory hypertensionmay require

additional treatment with agents such as minoxidil

(section2.5.1.1) or clonidine (section2.5.2).

Other measures to reduce cardiovascular risk

Aspirin (section 2.9) may be used to reduce the risk

of cardiovascular events; however,concerns about an

increasedrisk of bleedingand Reye’ssyndrome need to

beconsidered.

Astatin can be ofbeneﬁt in older childrenwho have a

high risk of cardiovascular disease and have hyper-

cholesterolaemia(see section 2.12).

Hypertension indiabetes

Hypertensioncan occur

intype 2 diabetes and treatmentprevents both macro-

vascular and microvascular complications. ACE inhi-

bitors (section 2.5.5.1) may be considered in children

with diabetes and microalbuminaemia or proteinuric

renal disease (see also section 6.1.5). Beta-blockers

are best avoided in children with, or at a high riskof

developing,diabetes, especially when combinedwith a

thiazidediuretic.

Hypertensionin renal disease

ACEinhibitors may

be considered in children with micro-albuminuria or

proteinuricrenal disease (see also section 6.1.5). High

doses of loopdiuretics may be required. Speciﬁc cau-

tionsapply to theuse of ACEinhibitors in renal impair-

ment, see section 2.5.5.1, but ACE inhibitors may be

effective. Dihydropyridine calcium-channel blockers

maybe added.

Hypertensionin pregnancy

Highblood pressure in

pregnancymay usually be dueto pre-existing essential

hypertension or to pre-eclampsia. Methyldopa (BNF

section 2.5.2) is safe in pregnancy. Beta-blockers are

effectiveand safein thethird trimester.Modiﬁed-release

preparationsof nifedipine[unlicensed] arealso used for

hypertensionin pregnancy. Intravenous administration

oflabetalol (section 2.4) canbe used to controlhyper-

tensive crises; alternatively hydralazine (section

2.5.1.1)can be given bythe intravenous route.

Hypertensiveemergencies

Hypertensiveemergen-

ciesin children maybe accompanied bysigns of hyper-

tensive encephalopathy,including seizures. Controlled

reductionin blood pressure over72–96 hours is essen-

tial; rapid reduction can reduceperfusion leading to

92 2.5 Hypertension BNFC 2011–2012

Cardiovascularsystem

organdamage. Treatmentshould beinitiated with intra-

venous drugs; once blood pressure is controlled, oral

therapycan be started. It may be necessary to infuse

ﬂuids particularly during the ﬁrst 12 hours to expand

plasma volume should the blood pressure drop too

rapidly.

Controlled reductionof blood pressure is achieved by

intravenousadministration of labetalol (section 2.4) or

sodium nitroprusside (section 2.5.1.1).Esmolol (sec-

tion 2.4) is useful for short-term use and has a short

duration of action. Nicardipine (section 2.6.2) can be

administeredas acontinuous intravenous infusionbut it

is not licensed for this use. In less severe cases, nife-

dipinecapsules (section 2.6.2) canbe used.

In resistant cases, diazoxide(section 2.5.1.1) is given

intravenously, but it can cause sudden hypotension.

Otherantihypertensive drugs which canbe given intra-

venouslyinclude hydralazine(section 2.5.1.1)and cloni-

dine(section 2.5.2).

Hypertension in acute nephritis occurs as a result of

sodium and water retention; it should be treated with

sodiumand ﬂuid restriction, and withfurosemide (sec-

tion 2.2.2); antihypertensive drugs may be added if

necessary.

Foradvice on short-term management ofhypertensive

episodes in phaeochromocytoma, see under Phaeo-

chromocytoma,section 2.5.4.

2.5.1

Vasodilator

antihypertensive drugs

and pulmonary

hypertension

2.5.1.1

Vasodilatorantihypertensives

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

Emergencies,p. 92.

Sodiumnitroprusside is given byintravenous infusion

to control severe hypertensive crisis when parenteral

treatmentis necessary.At lowdoses itreduces systemic

vascularresistance andincreases cardiacoutput; athigh

dosesit can produce profoundsystemic hypotension—

continuous blood pressure monitoring is therefore

essential. Sodium nitroprusside may also be used to

control paradoxical hypertension after surgery for

coarctationof the aorta.

Diazoxidehas also been usedby intravenous injection

inhypertensive emergencies; howeverit is notﬁrst-line

therapy.

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-

effectsis lowerif thedose iskept low,but systemiclupus

erythematosus should be suspected ifthere is unex-

plainedweight loss, arthritis, or any otherunexplained

illhealth.

Minoxidil should be reserved for the treatment of

severehypertension resistant to other drugs. Vasodila-

tationis accompanied by increasedcardiac output and

tachycardia and children develop ﬂuid 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 females.

Prazosin and doxazosin (section 2.5.4) have alpha-

blockingand vasodilator properties.

DIAZOXIDE

Cautions

duringprolonged usemonitor white celland

plateletcount, andregular lyassess growth,bone, and

psychologicaldevelopment; interactions:Appendix 1

(diazoxide)

Renalimpairment

dosereduction may be required

Pregnancy

prolongeduse may produce alopecia,

hypertrichosis,and impaired glucose tolerancein

neonate;inhibits uterine activity duringlabour

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

tachycardia,hypotension, hyperglyc-

aemia,sodium and water retention;

rarely

cardiome-

galy,hyperosmolar non-ketotic coma,leucopenia,

thrombocytopenia,and hirsuitism

Licenseduse tablets notlicensed for resistant

hypertension

Indicationand dose

Hypertensiveemergencies

initiatedon specialist

advice

Byintravenous injection

Child1 month–18 years

1–3mg/kg (max.

150mg) as asingle dose, repeat doseafter 5–15

minutesuntil blood pressure controlled;max. 4

dosesin 24 hours

Resistanthypertension

Bymouth

Neonate

initially1.7 mg/kg3 timesdaily, adjusted

accordingto response; usual max.15 mg/kgdaily

Child1 month–18 years

initially1.7 mg/kg 3

timesdaily, adjusted accordingto response; usual

max.15 mg/kg daily

Intractablehypoglycaemia

section6.1.4

Administration

intravenousinjection over 30 sec-

onds.Do not dilute

Eudemine

(Goldshield)AU

Injection

,diazoxide 15mg/mL, net price20-mL amp

=£30.00

Tablets

,see section 6.1.4

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

HYDRALAZINE HYDROCHLORIDE

Cautions

cerebrovasculardisease; occasionally blood

pressurereduction toorapid even withlow parenteral

doses;manufacturer advisestest forantinuclear factor

andfor proteinuria every 6 monthsand check acet-

ylatorstatus before increasing dose,but evidence of

clinicalvalue unsatisfactory; interactions: Appendix

1(hydralazine)

BNFC 2011–2012 2.5.1 Vasodilatorantihypertensive drugs 93

Cardiovascularsystem

Contra-indications

idiopathicsystemic lupus erythe-

matosus,severe tachycardia,high outputheart failure,

myocardialinsufﬁciency due to mechanicalobstruc-

tion,cor pulmonale; acute porphyria (section9.8.2)

Hepaticimpairment

reducedose

Renalimpairment

reducedose if estimated glom-

erularﬁltration rate less than 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 therapy(especially in

slowacetylator individuals); rarely rashes,fever, per-

ipheralneuritis, polyneuritis, paraesthesia, arthralgia,

myalgia,increased lacrimation, nasal congestion,

dyspnoea,agitation, anxiety, anorexia;blood disor-

ders(including leucopenia, thrombocytopenia,

haemolyticanaemia), abnormal liver function,jaun-

dice,raised plasma creatinine, proteinuriaand hae-

maturiareported

Licenseduse not licensedfor use in children

Indicationand dose

Hypertension

Bymouth

Neonate

250–500micrograms/kg every 8–12

hoursincreased as necessary to max.2–3 mg/kg

every8 hours

Child1 month–12 years

250–500micrograms/

kgevery 8–12 hours increased asnecessary to

max.7.5 mg/kgdaily (notexceeding 200mg daily)

Child12–18 years

25mg twicedaily,increased to

usualmax. 50–100 mgtwice daily

Byslow intravenous injection

Neonate

100–500micrograms/kg repeated every

4–6hours as necessary; max. 3mg/kg daily

Child1 month–12 years

100–500micrograms/

kgrepeated every 4–6 hours asnecessary; max.

3mg/kg daily (notexceeding 60mg daily)

Child12–18 years

5–10mg repeated every4–6

hoursas necessary

Bycontinuous intravenous infusion (preferred

routein cardiac patients)

Neonate

12.5–50micrograms/kg/hour; max.

2mg/kg daily

Child1 month–12 years

12.5–50micrograms/

kg/hour;max. 3 mg/kgdaily

Child12–18 years

3–9mg/hour; max. 3mg/kg

daily

Administration

for

intravenousinjection

,initially

reconstitute20 mg with1 mLWater for Injections,

thendilute to a concentrationof 0.5–1 mg/mLwith

SodiumChloride 0.9% and administerover 5–20

minutes.

For

continuousintravenous infusion

,initially recon-

stitute20 mg with1 mLWater for Injections,then

dilutewith Sodium Chloride 0.9%.Incompatible with

Glucoseintravenous infusion.

Foradministration

bymouth

,diluted injectionmay be

givenorally

Hydralazine(Non-proprietary) A

Tablets

,hydralazine hydrochloride 25mg, net price

56-tabpack = £9.32; 50mg, 56-tabpack = £16.84

Apresoline

(Amdipharm)A

Tablets

,yellow,s/c, hydralazinehydrochloride 25mg,

netprice 84-tab pack =£3.38

Excipients

includegluten, propyleneglycol (seeExcipients, p.2)

Injection

,powder for reconstitution, hydralazine

hydrochloride,net price 20-mg amp= £2.22

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

MINOXIDIL

Cautions

seenotes above; acute porphyria(section

9.8.2);interactions: Appendix 1 (vasodilatoranti-

hypertensives)

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

Indicationand dose

Severehypertension

Bymouth

Child1 month–12 years

initially200 micr-

ograms/kgdaily in1–2 divideddoses, increased in

stepsof 100–200micrograms/kg daily at intervals

ofat least 3 days;max. 1 mg/kgdaily

Child12–18 years

initially5 mg dailyin 1–2

divideddoses increased in stepsof 5–10 mgat

intervalsof at least 3 days;max. 100mg daily

(seldomnecessary to exceed 50mg 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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

SODIUM NITROPRUSSIDE

Cautions

hypothyroidism,hyponatraemia, impaired

cerebralcirculation, hypothermia; monitor blood

pressureand blood-cyanide concentration, andif

treatmentexceeds 3 days alsoblood-thiocyanate

concentration;avoid sudden withdrawal—terminate

infusionover 15–30 minutes; interactions:Appendix

1(nitroprusside)

Contra-indications

severevitamin B

deﬁciency;

Leber’soptic atrophy; compensatory hypertension

94 2.5.1 Vasodilator antihypertensive drugs BNFC2011–2012

Cardiovascularsystem

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-effectscaused by excessiveplasma concen-

trationof the cyanidemetabolite include tachycardia,

sweating,hyperventilation, arrhythmias, markedmetabolic

acidosis(discontinue and giveantidote, see p.32)

Licenseduse not licensedfor use in the UK

Indicationand dose

Hypertensiveemergencies

Bycontinuous infusion

Neonate

500nanograms/kg/minute then

increasedin stepsof 200nanograms/kg/minute as

necessaryto max.8 micrograms/kg/minute(max.

4micrograms/kg/minute if usedfor longer than

24hours)

Child1 month–18 years

500nanograms/kg/

minutethen increased insteps of 200nanograms/

kg/minuteas necessary to max. 8micrograms/

kg/minute(max. 4micrograms/kg/minute if used

forlonger than 24 hours)

Administration

for

continuousintravenous infusion

Glucose5%, infuse

via

infusiondevice to allow pre-

cisecontrol; protect infusion fromlight. For further

details,consult product literature

SodiumNitroprusside (Non-proprietary) A

Intravenousinfusion

,powder for reconstitution,

sodiumnitroprusside 10mg/mL. Fordilution and use

asan infusion. Available from‘special-order’ manu-

facturersor specialist importing companies,see

p.809

2.5.1.2

Pulmonaryhypertension

Onlypulmonar y

arterial

hypertensionis currently sui-

table for dr ug treatment. Pulmonar y arterial hyper-

tensionincludes persistent pulmonary hypertension of

the newborn, idiopathic pulmonary arterial hyper-

tensionin children,and pulmonaryhypertension related

tocongenital heart disease andcardiac surgery.

Sometypes ofpulmonar yhypertension aretreated with

vasodilatorantihypertensive therapy and oxygen.Diur-

etics(section 2.2) mayalso have a rolein children with

right-sidedheart failure.

Initial treatmentof

persistentpulmon aryhypertension

of the newborn

involves the administration of nitr ic

oxide; epoprostenol can be used until nitric oxide is

available.Oral sildenaﬁl may be helpful in less severe

cases.Epoprostenol and sildenaﬁl can cause profound

systemic hypotension. In rare circumstances either

tolazoline or magnesium sulphate can be givenby

intravenousinfusion whennitric oxideand epoprostenol

havefailed.

Treatment of

idiopathic pulmonary arterial hyper-

tension

is determined by acute vasodilator testing;

drugs used for treatment include calcium-channel

blockers (usually nifedipine, section 2.6.2), long-term

intravenous epoprostenol, nebulised iloprost, bosen-

tan, or sildenaﬁl. Anticoagulation (usually with warf-

arin) may also be required to prevent secondary

thrombosis.

Inhaled nitric oxide is a potent and selective pulm-

onaryvasodilator. Itacts oncyclic guanosinemonopho-

sphate (cGMP) resulting in smoothmuscle relaxation.

Inhalednitric oxideis usedin thetreatment ofpersistent

pulmonaryhypertension of the newborn,and may also

be useful in other forms of arterial pulmonary hyper-

tension. Dependency can occur with high dosesand

prolonged use; to avoid rebound pulmonary hyper-

tensionthe drug should be withdrawn gradually, often

withthe aid of sildenaﬁl.

Excess nitric oxide can cause methaemoglobinaemia;

therefore, methaemoglobin concentration should be

measuredregularly, particularly inneonates.

Nitricoxide increases the risk of haemorrhageby inhi-

bitingplatelet aggregation, butit doesnot usually cause

bleeding.

Epoprostenol (prostacyclin) is a prostaglandin and a

potentvasodilator. It isused in the treatmentof persis-

tentpulmonary hypertensionof the newborn,idiopathic

pulmonaryarterial hypertension,and in theacute phase

followingcardiac surgery. It isgiven by continuous 24-

hourintravenous infusion.

Epoprostenolis apowerful inhibitor ofplatelet aggrega-

tion and there is a possible risk of haemorrhage. It is

sometimesused asan antiplatelet inrenal dialysiswhen

heparinsare unsuitable or contra-indicated. Itcan also

cause serious systemic hypotensionand, if withdrawn

suddenly,can cause pulmonaryhypertensive crisis.

Childrenon prolonged treatment can become tolerant

to epoprostenol, and therefore require an increase in

dose.

Iloprostis a synthetic analogue ofepoprostenol and is

efﬁcacious when nebulised in adults withpulmonar y

arterialhypertension, but experience inchildren is lim-

ited. It is more stable than epoprostenol and has a

longerhalf-life.

Bosentanis a dualendothelin receptor antagonistused

orallyin the treatment of idiopathicpulmonary arterial

hypertension.The concentrationof endothelin, apotent

vasoconstrictor,is raisedin sustainedpulmonar yhyper-

tension.

Sildenaﬁl,a vasodilator developedfor the treatment of

erectiledysfunction, is also usedfor pulmonary arterial

hypertension.It is usedeither alone or asan adjunct to

otherdrugs and has relativelyfew side-effects.

Sildenaﬁl isa selective phosphodiesterase type-5 inhi-

bitor.Inhibitionof this enzymein thelungs enhancesthe

vasodilatoryeffects ofnitric oxide andpromotes relaxa-

tionof vascular smooth muscle.

Sildenaﬁlhas alsobeen usedin pulmonary hypertension

for weaningchildren of finhaled nitric oxide following

cardiacsurgery,and lesssuccessfully inidiopathic pulm-

onaryarterial hypertension.

Tolazoline is now rarely used to correct pulmonary

artery vasospasm in pulmonary hypertension of the

newborn as better alternatives are available (see

BNFC 2011–2012 2.5.1 Vasodilatorantihypertensive drugs 95

Cardiovascularsystem

above). Tolazoline is an alpha-blocker and produces

bothpulmonary and systemic vasodilation.

BOSENTAN

Cautions

notto be initiated ifsystemic systolic blood

pressureis below 85mmHg; monitor liver function

beforeand atmonthly intervals duringtreatment, and

2weeks after dose increase(reduce dose or suspend

treatmentif liver enzymes raised signiﬁcantly)—dis-

continueif symptoms of liver impairment(see Con-

tra-indicationsbelow); monitor haemoglobin before

andduring treatment(monthly forﬁrst 4months, then

3-monthlythereafter), withdraw treatment gradually;

interactions:Appendix 1 (bosentan)

Contra-indications

acuteporphyria (section 9.8.2)

Hepaticimpairment

avoidin moderate and severe

impairment

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)

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Idiopathicpulmonary arterial hypertension

Bymouth

Child3–18 years and body-weight10–20 kg

initially31.25 mg oncedaily increased after 4

weeksto 31.25 mgtwice daily

Child3–18 years and body-weight20–40 kg

initially31.25 mg twicedaily increased after 4

weeksto 62.5 mgtwice daily

Child12–18 years andbody-weight over 40kg

initially62.5 mgtwice dailyincreased after4 weeks

to125 mg twicedaily; max. 250mg twice daily

Administration

tabletsmay be cut, orsuspended in

wateror non-acidic liquid. Suspensionis stable at

room-temperature(max. 258C) for 24hours

Tracleer

(Actelion)TA

Tablets

,f/c, orange, bosentan (asmonohydrate)

62.5mg, net price56-tab pack =£1510.21; 125 mg,

56-tabpack = £1510.21

EPOPROSTENOL

Cautions

anticoagulantmonitoring required when

givenwith anticoagulants; haemorrhagic diathesis;

avoidabrupt withdrawal (see notesabove); monitor

bloodpressure; concomitant use ofdr ugsthat

increaserisk of bleeding

Contra-indications

severeleft ventricular dysfunc-

tion;pulmonary veno-occlusive disease

Pregnancy

manufactureradvises caution—no infor-

mationavailable

Side-effects

seenotes above; gastro-intestinal distur-

bances,hypotension, bradycardia,tachycardia, pallor,

ﬂushing,sweating with higher doses;headache; las-

situde,anxiety, agitation; drymouth, jaw pain, chest

pain;also reported, hyperglycaemiaand injection-site

reactions

Licenseduse not licensedfor use in children

Indicationand dose

Persistentpulmonary hypertension of the

newborn

Bycontinuous intravenous infusion

Neonate

initially2 nanograms/kg/minute

adjustedaccording to response; usualmax.

20nanograms/kg/minute (rarely upto 40 nan-

ograms/kg/minute)

Idiopathicpulmonary arterial hypertension

Bycontinuous intravenous infusion

Child1 month–18 years

initially2 nanograms/

kg/minuteincreased as necessary up to40 nan-

ograms/kg/minute

Administration

reconstituteusing the glycine buffer

diluentprovided to make aconcentrate (pH 10.5);

ﬁlterthe concentrate using theﬁlter provided. The

concentratecan be administeredvia a centralvenous

catheter,alternatively it maybe diluted further either

withthe glycine buffer diluent

toa minimum

concentrationof 1.43 micrograms/mLwith Sodium

Chloride0.9%. Solution stable for12 hours at room

temperature,although some units usefor 24 hours

andallow for loss ofpotency; solution stable for24

hoursif prepared in glycinebuffer diluent only and

administeredvia an ambulatory coldpouch system

(tomaintain solution at 2–88C).

Neonatalintensive care

,prepare a ﬁltered concen-

trateof 10 micrograms/mLusing the 500-microgram

vial.

Neonatebody-weight under 2kg

,using the

concentrate,dilute 150 micrograms/kgbody-weight

toa ﬁnalvolume of50 mLwith SodiumChloride 0.9%;

anintravenous infusion rateof 0.1 mL/hourprovides

adose of 5nanograms/kg/minute.

Neonatebody-

weightover 2kg

,using the concentrate, dilute

60micrograms/kg body-weight toa ﬁnal volume of

50mL withSodium Chloride 0.9%; an intravenous

infusionrate of 0.1mL/hour provides a doseof

2nanograms/kg/minute

Flolan

(GSK)A

Infusion

,powder for reconstitution, epoprostenol(as

sodiumsalt), net price 500-microgramvial (with

diluent)= £62.05; 1.5-mg vial(T) (with diluent) =

£125.00

ILOPROST

Cautions

unstablepulmonary hypertension with

advancedright heart failure; hypotension(do not

initiateif systolic blood pressurebelow 85 mmHg);

acutepulmonary infection; severe asthma; interac-

tions:Appendix 1 (iloprost)

Contra-indications

decompensatedcardiac failure

(unlessunder medical supervision); severe coronary

heartdisease; severe arrhythmias; congenital or

acquiredvalvular defects of themyocardium; pulm-

onaryveno-occlusive disease; conditions which

increaserisk of haemorrhage

96 2.5.1 Vasodilator antihypertensive drugs BNFC2011–2012

Cardiovascularsystem

Hepaticimpairment

dosemay need to behalved in

livercirrhosis—initially 2.5micrograms at intervalsof

atleast 3 hours (max.6 times daily), adjusted

accordingto response (consult productliterature)

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

Licenseduse not licensedfor use in children under

18years

Indicationand dose

Idiopathicor familial pulmonary arterial

hypertension

Byinhalation of nebulised solution

Child8–18 years

initialdose 2.5 micrograms

increasedto 5 microgramsfor second dose, if

toleratedmaintain at5 micrograms6–9 timesdaily

accordingto response; reduce to2.5 micrograms

6–9times daily if higherdose not tolerated

Raynaud’ssyndrome

section2.6.4.1

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

MAGNESIUM SULPHATE

Cautions

seesection 9.5.1.3

Hepaticimpairment

seesection 9.5.1.3

Renalimpairment

seesection 9.5.1.3

Side-effects

seesection 9.5.1.3

Indicationand dose

Persistentpulmonary hypertension of the

newborn

Byintravenous infusion

Neonate

initially200 mg/kg over20–30 minutes;

ifresponse occurs,then bycontinuous intravenous

infusionof 20–75 mg/kg/hour(to maintain

plasma-magnesiumconcentration between 3.5–

5.5mmol/litre), given forup to 5 days

Severeacute asthma

section3.1

Torsadede pointes

section9.5.1.3

Neonatalhypocalcaemia

section9.5.1.3

Hypomagnesaemia

section9.5.1.3

Administration

for

intravenousinfusion

,dilute to a

max.concentration of 100mg/mL (200 mg/mLif

ﬂuidrestricted) with Glucose 5%

SodiumChloride

0.9%

MagnesiumSulphate (Non-proprietary) A

Injection

,magnesium sulphate 50% (Mg

2þ

approx.

2mmol/mL), net price2-mL (1-g) amp= £2.39,

5-mL(2.5-g) amp = £3.00,10-mL (5-g) amp =69p;

preﬁlled10-mL (5-g) syringe =£4.95

SILDENAFIL

Cautions

hypotension(avoid if severe); intravascular

volumedepletion; leftventricular outﬂowobstruction;

autonomicdysfunction; avoid abrupt withdrawal;

othercardiovascular disease; pulmonary veno-occlu-

sivedisease; predisposition to priapism;anatomical

deformationof the penis;bleeding disorders oractive

pepticulceration; ocular disorders; initiatecautiously

ifchild also on epoprostenol,iloprost, bosentan or

nitricoxide; interactions: Appendix 1(sildenaﬁl)

Contra-indications

recenthistory of stroke;history of

non-arteriticanterior ischaemic optic neuropathy;

hereditarydegenerative retinal disorders; avoidcon-

comitantuse of nitrates

Hepaticimpairment

reducedose if not toleratedin

mildto moderate impairment; manufacturer advises

avoidin severe impairment

Renalimpairment

reducedose if not tolerated

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 vascular occlusion, non-

arteriticanterior ischaemic optic neuropathy(dis-

continueif sudden visual impairmentoccurs), and

suddenhearing loss (advise patientto seek medical

help)

Licenseduse not licensedfor use in children under

18years

Indicationand dose

Pulmonaryhypertension after cardiac surgery,

weaningfrom nitric oxide, idiopathicpulm-

onaryarterial hypertension, persistent pulm-

onaryhypertension of the newborn

Bymouth

Neonate

initially250–500 micrograms/kgever y

4–8hours, adjusted according toresponse; max.

2mg/kg every 6hours; start with lowerdose and

frequencyespecially if used withother vaso-

dilators(see Cautions above); withdrawgradually

Child1 month–18 years

initially250–500 micr-

ograms/kgevery 4–8hours, adjusted accordingto

response;max. 2 mg/kgevery 6 hours; start with

lowerdose and frequency especiallyif used with

othervasodilators (see Cautions above)

Administration

tabletmay be dissolved inwater or

blackcurrantdrink and given bymouth or through a

nasogastrictube

Viagra

(Pﬁzer)AD

Tablets

,all blue, f/c,sildenaﬁl (as citrate), 25mg, net

price4-tab pack= £16.59,8-tab pack= £33.19;50 mg,

4-tabpack = £21.27, 8-tabpack = £45.54;100 mg, 4-

tabpack = £23.50, 8-tabpack = £46.99

BNFC 2011–2012 2.5.1 Vasodilatorantihypertensive drugs 97

Cardiovascularsystem

Revatio

(Pﬁzer)TA

Tablets

,f/c, sildenaﬁl(as citrate),20 mg,net price 90-

tabpack = £373.50

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

TOLAZOLINE

Cautions

mitralstenosis; cardiotoxic accumulation

mayoccur with continuous infusion,particularly in

renalimpairment—monitor blood pressure regularly

forsustained systemic hypotension; interactions:

Appendix1 (alpha-blockers)

Contra-indications

pepticulcer disease

Renalimpairment

accumulatesin renal impairment;

riskof cardiotoxicity; lower dosesmay be necessary

Side-effects

nausea,vomiting, diarrhoea, epigastric

pain;ﬂushing, tachycardia, cardiac arrhythmias;

headache,shivering, sweating; oliguria, metabolic

alkalosis,haematuria, blood dyscrasias (including

thrombocytopenia);blotchy skin;at high doses severe

hypotension,marked hypertension, renal failure,and

haemorrhagereported

Licenseduse not licensedfor use in children

Indicationand dose

Correctionof pulmonary vasospasm inneo-

nates

Byintravenous injection and continuousintra-

venousinfusion (maintenance)

Neonate

initially1 mg/kg

byintravenous injection

over2–5 minutes, followed ifnecessary

bycon-

tinuousintravenous infusion

of200 micrograms/

kg/hourwith careful blood pressuremonitoring;

dosesabove 300 micrograms/kg/hourassociated

withcardiotoxicity and renal failure

Byendotracheal administration

Neonate

200micrograms/kg

Administration

for

continuousintravenous infusion

dilutewith Glucose 5%

SodiumChloride 0.9%.

Preparea fresh solution every 24hours.

For

endotrachealadministration

,dilute with 0.5–

1mL of SodiumChloride 0.9%

Tolazoline(Non-proprietary)

Injection

,tolazoline 25 mg/mL

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

2.5.2

Centrally acting

antihypertensive drugs

Methyldopa, a centrallyacting antihypertensive, is of

little valuein the management of refractory sustained

hypertensionin infants and children.On prolonged use

it is associated with ﬂuid retention (which may be

alleviatedby concomitant use ofdiuretics).

Methyldopais effective for the management of hyper-

tensionin pregnancy (see BNFsection 2.5.2).

Clonidineis alsoa centrally actingantihypertensive but

hasthe disadvantagethat suddenwithdrawal maycause

a hypertensive crisis. Clonidine is also used under

specialist supervision for pain management, sedation,

and opioid withdrawal, attention deﬁcit hyperactivity

disorder,and Tourette syndrome.

CLONIDINEHYDROCHLORIDE U

Cautions

mustbe withdrawn gradually toavoid

hypertensivecrisis; mild to moderatebradyarrhyth-

mia;constipation; polyneuropathy; Raynaud’s

syndromeor other occlusive peripheralvascular dis-

ease;history of depression;interactions: Appendix 1

(clonidine)

Skilledtasks

Drowsinessmay affectperformance of skilled

tasks(e.g. driving); effectsof alcohol maybe enhanced

Contra-indications

severebradyarrhythmia second-

aryto second- or third-degreeAV block orsick sinus

syndrome

Renalimpairment

usewith caution

Pregnancy

maylower fetal heart rate,but risk should

bebalanced against risk ofuncontrolled maternal

hypertension;avoid intravenous injection

Breast-feeding

avoid—presentin milk

Side-effects

constipation,nausea, dry mouth, vomi-

ting,postural hypotension, dizziness, sleepdistur-

bances,headache, malaise, drowsiness,depression,

sexualdysfunction;

lesscommonly

bradycardia,Ray-

naud’ssyndrome, delusion, hallucination,paraes-

thesia,pruritus, rash, urticaria;

rarely

colonicpseudo-

obstruction,AV block, gynaecomastia, decreased

lacrimation,nasal dryness, alopecia;

alsoreported

hepatitis,ﬂuid retention, bradyarrhythmia,confusion,

impairedvisual accommodation

Licenseduse not licensedfor use in children

Indicationand dose

Severehypertension

Bymouth

Child2–18 years

initially0.5–1 microgram/kg3

timesdaily, increased graduallyif necessary; max.

25micrograms/kg daily individed doses (not

exceeding1.2 mg daily)

Byslow intravenous injection

Child2–18 years

2–6micrograms/kg (max.

300micrograms) as asingle dose

Administration

for

intravenousinjection

,give over

10–15minutes; compatible with SodiumChloride

0.9%

Glucose5%.

Foradministration

bymouth

,tablets may becr ushed

anddissolved in water

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

Injection

,clonidine hydrochloride 150micrograms/

mL,net price 1-mL amp= 28p

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

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

98 2.5.2 Centrally acting antihypertensive drugs BNFC 2011–2012

Cardiovascularsystem

theyhave largelyfallen fromuse in adultsand arerarely

usedin children.

2.5.4

Alpha-adrenoceptor

blocking drugs

Doxazosin and prazosin have post-synaptic alpha-

blocking and vasodilator properties andrarely cause

tachycardia.They can, however,reduce blood pressure

rapidlyafter theﬁrst doseand shouldbe introducedwith

caution.

Alpha-blockerscan be usedwith otherantihypertensive

drugsin the treatment of resistanthypertension.

DOXAZOSIN

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 postural hypotension

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 in

animal

stu-

dies—manufactureradvises avoid

Side-effects

gastro-intestinaldisturbances; oedema,

hypotension,postural hypotension, palpitation,

tachycardia;dyspnoea, rhinitis, coughing; asthenia,

fatigue,vertigo, dizziness, headache,paraesthesia,

sleepdisturbance, anxiety, depression;inﬂuenza-like

symptoms;back pain, myalgia;

lesscommonly

weight

changes;angina, myocardial infarction; hypoaesthe-

sia,syncope, tremor, agitation, micturition distur-

bances,impotence, epistaxis,arthralgia, gout,tinnitus,

hypersensitivityreactions (including pruritus,

purpura,rash);

veryrarely

cholestasis,hepatitis,

jaundice,bradycardia, arrhythmias, bronchospasm,

hotﬂushes, gynaecomastia, priapism, abnormal eja-

culation,leucopenia, thrombocytopenia, blurred

vision,and alopecia

Licenseduse not licensedfor use in children

Indicationand dose

Hypertension

(seenotes above)

Bymouth

Child6–12 years

500micrograms once daily,

increasedat 1-week intervals to2–4 mg daily

Child12–18 years

1mg daily,increased after1–2

weeksto 2 mgonce daily, andthereafter to 4mg

oncedaily if necessary; usual max.4 mgdaily

(rarelyup to 16mg daily may berequired)

Dysfunctionalvoiding

section7.4.1

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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

Modiﬁed-release

Note

Childrenstabilised on immediate-release doxazosincan

betransferred to theequivalent dose ofmodiﬁed-release dox-

azosin

Doxazosin(Non-proprietary) A

Tablets

,m/r, doxazosin (as mesilate)4 mg,net price

28-tabpack = £6.33. Label:25, counselling, initial

dose,driving

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, initial dose,driving

PRAZOSIN

Cautions

ﬁrstdose may cause collapsedue to hypo-

tension(therefore should betaken on retiringto bed);

cataractsurgery (risk of intra-operativeﬂ oppyiris

syndrome);interactions: Appendix1 (alpha-blockers)

Driving

Mayaffect performance ofskilled tasks e.g.driving

Contra-indications

notrecommended for congestive

heartfailure dueto mechanicalobstruction (e.g.aortic

stenosis)

Hepaticimpairment

startwith low doses andadjust

accordingto response

Renalimpairment

startwith low doses inmoderate

tosevere impairment; increase with caution

Pregnancy

noevidence of teratogenicity; manufac-

tureradvises use only whenpotential beneﬁt out-

weighsrisk

Breast-feeding

presentin milk; manufacturer advises

usewith caution

Side-effects

gastro-intestinaldisturbances; postural

hypotension,oedema, palpitation; dyspnoea, nasal

congestion;drowsiness, headache, depression, ner-

vousness,vertigo; urinary frequency; weakness;

blurredvision;

lesscommonly

tachycardia,insomnia,

paraesthesia,sweating, impotence, arthralgia, eye

disorders,tinnitus, epistaxis, allergic reactions

includingrash, pruritus, and urticaria;

rarely

pan-

creatitis,ﬂushing, vasculitis, bradycardia, hallucina-

tions,worsening of narcolepsy,gynaecomastia,

priapism,urinary incontinence, and alopecia

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Hypertension

(seenotes above)

Bymouth

Child1 month–12 years

10–15micrograms/kg

2–4times daily (initial doseat bedtime) increased

graduallyto max. 500micrograms/kg daily in

divideddoses (not exceeding 20mg daily)

Child12–18 years

500micrograms 2–3 times

daily(initial dose at bedtime),increased after 3–7

daysto 1mg 2–3times dailyfor a further3–7 days;

furtherincreased gradually if necessary tomax.

20mg daily individed doses

BNFC 2011–2012 2.5.4 Alpha-adrenoceptor blocking drugs 99

Cardiovascularsystem

Congestiveheart failure

(butrarely used, see

section2.2)

Bymouth

Child1 month–12 years

5micrograms/kg twice

daily(initial dose at bedtime),increased gradually

tomax. 100micrograms/kg daily individed doses

Child12–18 years

500micrograms 2–4 times

daily(initial dose at bedtime),increasing to 4mg

dailyin divided doses;maintenance 4–20mg daily

individed doses

Administration

foradministration

bymouth

,tablets

maybe dispersed in water

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

Phaeochromocytoma

Long-term management of phaeochromocytoma

involves surgery. However, surger y should not take

place until there is adequate blockade of both alpha-

andbeta-adrenoceptors. Alpha-blockers areused in the

short-term management of hypertensive episodes in

phaeochromocytoma. Once alpha blockade is estab-

lished, tachycardia can be controlled by the cautious

additionof abeta-blocker (section2.4); acardioselective

beta-blockeris preferred. There is no nationwide con-

sensuson the optimal drug regimen or doses used for

themanagement of phaeochromocytoma.

Phenoxybenzamine,a powerfulalpha-blocker, isef fec-

tivein the management of phaeochromocytoma but it

hasmany side-effects.

PHENOXYBENZAMINE

HYDROCHLORIDE

Cautions

congestiveheart failure; severe ischaemic

heartdisease (see also Contra-indications);cerebro-

vasculardisease (avoid if historyof cerebrovascular

accident);monitor blood pressure regularlyduring

infusion;carcinogenic in

animals

;avoid in acute

porphyria(section 9.8.2); avoidextravasation (irritant

totissues); avoid contact withskin (risk of contact

sensitisation)

Contra-indications

historyof cerebrovascular acci-

dent;avoid infusion in hypovolaemia

Renalimpairment

usewith caution

Pregnancy

hypotensionin newborn may occur

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

Licenseduse not licensedfor use in children

Indicationand dose

Hypertensionin phaeochromocytoma

Bymouth

Child1 month–18years

0.5–1mg/kg twicedaily

adjustedaccording to response

Byintravenous infusion

Child1 month–18 years

0.5–1mg/kg daily

adjustedaccording toresponse; occasionally upto

2mg/kg dailymay berequired; do not repeat dose

within24 hours

Administration

foradministration

bymouth

,capsules

maybe opened.

For

intravenousinfusion

,dilute withSodium Chloride

0.9%and give over atleast 2 hours; max. 4hours

betweendilution and completion ofinfusion

Phenoxybenzamine(Goldshield) A

Injectionconcentrate

,phenoxybenzamine hydro-

chloride50 mg/mL. Tobe diluted beforeuse. Net

price2-mL amp = £57.14(hosp. only)

Dibenyline

(Goldshield)A

Capsules

,red/white, phenoxybenzamine hydro-

chloride10 mg. Netprice 30-cap pack =£10.84

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

2.5.5.1

Angiotensin-convertingenzyme

inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhi-

bitors)inhibit the conversion of angiotensinI to angio-

tensin II. The main indications of ACE inhibitors in

childrenare shownbelow.In infants andyoung children,

captoprilis often considered ﬁrst.

Initiationunder specialist supervision

Treatment

withACE inhibitors should beinitiated under specialist

supervisionand with careful clinicalmonitoring in chil-

dren.

Heartfailure

ACEinhibitors havea valuablerole in all

grades of heart failure, usually combined with a loop

diuretic(section 2.2).Potassium supplementsand potas-

sium-sparing diuretics should be discontinuedbefore

introducing an ACE inhibitor because of the risk of

hyperkalaemia.In adults, a low doseof spironolactone

maybe beneﬁcialin severeheart failureand canbe used

with an ACE inhibitor provided serum potassium is

monitored carefully. Profound ﬁrst-dose hypotension

canoccur when ACE inhibitors are introduced tochil-

dren with heart failure who are already taking a high

doseof aloop diuretic (seeCautions below).Temporary

withdrawalof theloop diuretic reducesthe risk, butcan

causesevere rebound pulmonary oedema.

100 2.5.5 Drugsaffecting the renin-angiotensin system BNFC 2011–2012

Cardiovascularsystem

Hypertension

ACEinhibitors may be considered for

hypertensionwhen thiazidesand beta-blockers arecon-

tra-indicated, not tolerated, or fail to control blood

pressure; they may be considered for hypertension in

childrenwith type1 diabeteswith nephropathy(see also

section6.1.5). ACEinhibitors canreduce blood pressure

very rapidly in some patients particularly in those

receiving diuretic therapy (see Cautions, below); the

ﬁrstdose should preferably begiven at bedtime.

Diabetic nephropathy

Forcomment on the role of

ACEinhibitors in the management of diabetic nephro-

pathy,see section 6.1.5.

Renaleffects

Renalfunction and electrolytes should

bechecked beforestarting ACE inhibitors(or increasing

the dose) and monitored during treatment (more fre-

quently if features mentioned below are present).

Hyperkalaemiaand other side-effects ofACE inhibitors

aremore common inchildren withimpaired renal func-

tionand the dose may need to be reduced (see Renal

Impairment,below).

Concomitanttreatment with NSAIDs increasesthe risk

of renal damage, and potassium-sparing diuretics (or

potassium-containingsalt substitutes) increase the risk

ofhyperkalaemia.

Inchildren 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 contra-indicated in

childrenknown to havethese forms of criticalrenovas-

culardisease.

ACEinhibitor treatment is unlikely to havean adverse

effect onoverall renal function in children 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.

ACEinhibitors are therefore bestavoided in thosewith

known or suspected renovascular disease, unless the

bloodpressure cannot be controlled by other drugs. If

they are used in these circumstances renal function

needsto be monitored.

ACE inhibitors should also be used with particular

caution in children who may have undiagnosed and

clinically silent renovascular disease. ACE inhibitors

are useful for the management of hypertension and

proteinuriain children with nephritis.They are thought

tohave a beneﬁcial effectby reducing intra-glomerular

hypertension andprotecting the glomerular capillaries

andmembrane.

Cautions

ACEinhibitors needto be initiatedwith care

inchildren receiving diuretics (important: see Conco-

mitant Diuretics, below); ﬁrst doses can cause hypo-

tensionespecially in children takinghigh doses of diur-

etics,on a low-sodium diet, ondialysis, dehydrated, or

with heart failure (see above). Discontinue if marked

elevationof hepaticenzymes orjaundice (risk ofhepatic

necrosis). Renal function should be monitored before

andduring treatment. For use in pre-existing renovas-

cular disease, see Renal Effects above. The risk of

agranulocytosisis possibly increasedin collagen vascu-

lar disease (blood counts recommended). ACE inhi-

bitorsshould be used withcare in children with severe

orsymptomatic aorticstenosis (riskof hypotension)and

in hypertrophiccardiomyopathy. They should be used

with care (or avoided)in those with a history of idio-

pathicor hereditaryangioedema. Children withprimary

aldosteronism and Afro-Caribbean children may

respond less well to ACE inhibitors. Interactions:

Appendix1 (ACE inhibitors).

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 children;

treatment should therefore be initiated with very low

doses.In some children the diuretic dosemay need to

bereduced orthe diureticdiscontinued at least24 hours

beforehand(may notbe possiblein heartfailure—risk of

pulmonaryoedema). If high-dose diuretic therapy can-

notbe stopped,close observationis recommended after

administrationof the ﬁrst dose of ACE inhibitor,for at

least2 hours or until theblood pressure has stabilised.

Contra-indications

ACE inhibitors are contra-indi-

catedin childrenwith hypersensitivity toACE inhibitors

(including angioedema) and in bilateral renovascular

disease(see also above).

Renalimpairment

SeeRenal Effectsabove; start with

lowdose and adjust accordingto response.

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.

Side-effects

ACEinhibitors cancause profoundhypo-

tension (see Cautions), renal impairment (see Renal

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,

hypoglycaemiaand blood disordersincluding thrombo-

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.

Neonates

The neonatal response to treatment with

ACE inhibitors is very variable, and some neonates

develop profoundhypotension with even small doses;

atest-dose should be used initially and increased cau-

tiously.Adverse effects such as apnoea,seizures, renal

failure,and severe unpredictable hypotension are very

common in the ﬁrst month of life and itis therefore

BNFC 2011–2012 2.5.5 Drugs affecting the renin-angiotensin system 101

Cardiovascularsystem

recommended that ACE inhibitors are avoided when-

everpossible, particularly in preterm neonates.

CAPTOPRIL

Cautions

seenotes above; acute porphyria(section

9.8.2)

Contra-indications

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

avoidin ﬁrst fewweeks after delivery,

particularlyin preterm infants—risk of profound

neonatalhypotension; can be usedin older infant if

essentialbut monitor infant’s bloodpressure

Side-effects

seenotes above; tachycardia, serum

sickness,weight loss, stomatitis,maculopapular rash,

photosensitivity,ﬂushing and acidosis

Licenseduse not licensedfor use in children under

18years

Indicationand dose

Hypertension,heart failure, proteinuria in

nephritis

(underspecialist supervision)

Bymouth

Neonate

(caution,see neonatal information

above)test dose, 10–50micrograms/kg (10micr-

ograms/kgin neonate less than37 weeks post-

menstrualage), monitor blood pressure carefully

for1–2 hours;if tolerated give10–50 micrograms/

kg2–3 times dailyincreased as necessary tomax.

2mg/kg daily individed doses (max. 300micr-

ograms/kgdaily in divided dosesin neonate less

than37 weeks postmenstrual age)

Child1 month–12 years

testdose, 100 micr-

ograms/kg(max. 6.25 mg),monitor blood pres-

surecarefully for 1–2 hours;if tolerated give 100–

300micrograms/kg 2–3 timesa day, increasedas

necessaryto max. 6mg/kg daily in divideddoses

(max.4 mg/kg dailyin divided doses forchild 1

month–1year)

Child12–18 years

testdose, 100micrograms/kg

6.25mg, monitorblood pressurecarefully for1–

2hours; if tolerated give12.5–25 mg 2–3times a

day,increased as necessary tomax. 150mg daily

individed doses

Diabeticnephropathy

(underspecialist supervi-

sion)

Bymouth

Child12–18 years

testdose, 100micrograms/kg

6.25mg, monitorblood pressurecarefully for1–

2hours; if tolerated, give12.5–25 mg 2–3times a

day,increased as necessary tomax. 150mg daily

individed doses

Administration

Administerunder close supervision,

seenotes above. Give testdose whilst child supine.

Tabletscan be dispersed inwater

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

Liquid

,various strengths available from‘special-

order’manufacturers or specialist importingcompa-

nies,see p. 809

Capoten

(Squibb)A

Tablets

,captopril 25 mg,net price 28-tab pack=

£5.26;50 mg (scored),56-tab pack = £17.96

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

ENALAPRIL MALEATE

Cautions

seenotes above

Contra-indications

seenotes above

Hepaticimpairment

monitorclosely

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

avoidin ﬁrst fewweeks after delivery,

particularlyin preterm infants—risk of profound

neonatalhypotension; can be usedin older infant if

essentialbut monitor infant’s bloodpressure

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

stomatitis,glossitis, Raynaud’s syndrome,pulmonary

inﬁltrates,allergic alveolitis, abnormal dreams,

gynaecomastia,Stevens-Johnson syndrome, toxic

epidermalnecrolysis, exfoliative dermatitis, pemphi-

gus;

veryrarely

gastro-intestinalangioedema

Licenseduse not licensedfor use in children for

congestiveheart failure, proteinuria in nephritisor

diabeticnephropathy; not licensed for usein chil-

drenless than 20kg for hypertension

Indicationand dose

Hypertension,congestive heart failure, protei-

nuriain nephritis

(underspecialist supervision)

Bymouth

Neonate

(limitedinformation) initially 10micr-

ograms/kgonce daily, monitorblood pressure

carefullyfor 1–2 hours,increased as necessary up

to500 micrograms/kg dailyin 1–3 divided doses

Child1 month–12 years

initially100 micr-

ograms/kgonce daily, monitorblood pressure

carefullyfor 1–2 hours,increased as necessary up

tomax. 1 mg/kgdaily in 1–2 divideddoses

Child12–18 years

initially2.5 mg oncedaily,

monitorblood pressure carefully for1–2 hours,

usualmaintenance dose 10–20mg daily in 1–2

divideddoses; max. 40mg daily in 1–2divided

dosesif body-weight over 50kg

Diabeticnephropathy

(underspecialist supervi-

sion)

Bymouth

Child12–18 years

initially2.5 mg oncedaily,

monitorblood pressure carefully for1–2 hours,

usualmaintenance dose 10–20mg daily in 1–2

divideddoses; max. 40mg daily in 1–2divided

dosesif body-weight over 50kg

Administration

tabletsmay be crushed and sus-

pendedin water immediately beforeuse

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

102 2.5.5 Drugsaffecting the renin-angiotensin system BNFC 2011–2012

Cardiovascularsystem

Liquid

,various strengths available from‘special-

order’manufacturers or specialist importingcompa-

nies,see p. 809

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

LISINOPRIL

Cautions

seenotes above

Contra-indications

seenotes above

Renalimpairment

seenotes above

Pregnancy

seenotes above

Breast-feeding

avoid—noinformation available

Side-effects

seenotes above; also

lesscommonly

tachycardia,palpitation, cerebrovascular accident,

Raynaud’ssyndrome, confusion, moodchanges,

vertigo,sleep disturbances, asthenia, impotence;

rarely

drymouth, gynaecomastia, alopecia,psoriasis;

veryrarely

allergicalveolitis, pulmonary inﬁltrates,

profusesweating, pemphigus, Stevens-Johnson

syndrome,and toxic epidermal necrolysis

Licenseduse not licensedfor use in children

Indicationand dose

Hypertension,proteinuria in nephritis

(under

specialistsupervision)

Bymouth

Child6–12 years

initially70 micrograms/kg

(max.5 mg)once daily,increased in intervalsof 1–

2weeks to max. 600micrograms/kg (

40mg)

oncedaily

Child12–18 years

initially5 mgonce daily; usual

maintenancedose 10–20 mgonce daily; max.

80mg once daily

Diabeticnephropathy

(underspecialist supervi-

sion)

Bymouth

Child12–18 years

initially5 mgonce daily; usual

maintenancedose 10–20 mgonce daily; max.

80mg once daily

Heartfailure (adjunct)

(underspecialist supervi-

sion)

Bymouth

Child12–18 years

initially2.5 mg oncedaily;

increasedin steps no greaterthan 10 mgat inter-

valsof at least 2weeks up to max. 35mg once

dailyif tolerated

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

Liquid

,various strengths available from‘special-

order’manufacturers or specialist importingcompa-

nies,see p. 809

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

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

2.5.5.2

Angiotensin-IIreceptor

antagonists

Losartan and valsartan are speciﬁc angiotensin-II

receptor antagonists with many properties similar to

thoseof the ACE inhibitors.However, unlike ACE inhi-

bitors,they do not inhibitthe breakdown of bradykinin

and other kinins,and thus are less likely to cause the

persistentdry cough which cancomplicate ACE inhibi-

tor therapy.They are therefore a useful alternative for

children who have to discontinue an ACE inhibitor

becauseof persistent cough.

Losartanor valsartancan beused asan alternative toan

ACEinhibitor in the managementof hypertension.

Cautions

Angiotensin-II receptor antagonists should

beused with caution in renal artery stenosis (see also

Renal Effects under ACE Inhibitors, section 2.5.5.1).

Monitoring of plasma-potassium concentration is

advised,particularly in children withrenal impairment.

Angiotensin-IIreceptor antagonistsshould be usedwith

cautionin aortic or mitral valve stenosisand in hyper-

trophic cardiomyopathy. They should be used with

cautionin those witha history ofangioedema. Children

with primary aldosteronism, and Afro-Caribbean chil-

dren (particularly those with left ventricular hyper-

trophy),may notbeneﬁt froman angiotensin-II receptor

antagonist. Interactions: Appendix 1 (angiotensin-II

receptorantagonists).

Pregnancy

Angiotensin-IIreceptor antagonistsshould

be avoided in pregnancy, unless essential. They may

adverselyaf fectfetal and neonatal blood pressure and

renal function; oligohydramnios and neonatal skull

defectshave also been reported.

Breast-feeding

Information on the use of angio-

tensin-IIreceptor antagonists inbreast-feeding patients

is limited, so they are not recommended in these

patients. Alternative treatment options, with more

established safety information during breast-feeding,

areavailable.

Side-effects

Side-effects of angiotensin-II receptor

antagonists include symptomatic hypotension (includ-

ing dizziness), particularly in children withhyponatr-

aemia or intravascular volume depletion (e.g. those

takinghigh-dose diuretics).Hyperkalaemia occursocca-

sionally; angioedema has also been reported (some-

timeswith delayed onset).

LOSARTANPOTASSIUM

Cautions

seenotes above; also severeheart failure

Hepaticimpairment

avoid—noinformation available

Renalimpairment

seenotes above; also avoidif

estimatedglomerular ﬁltration rate less than30 mL/

minute/1.73m

—noinformation available

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also malaise,anaemia;

lesscommonly

abdominalpain, constipation, diarr-

BNFC 2011–2012 2.5.5 Drugs affecting the renin-angiotensin system 103

Cardiovascularsystem

hoea,nausea, vomiting, angina, palpitation,oedema,

dyspnoea,cough, headache, sleep disorders,drowsi-

ness,urticaria, pruritus, rash;

rarely

hepatitis,atrial

ﬁbrillation,cerebrovascular accident, and paraes-

thesia;

alsoreported

pancreatitis,depression, erectile

dysfunction,thrombocytopenia, hyponatraemia,

arthralgia,myalgia, rhabdomyolysis, tinnitus,photo-

sensitivity,and vasculitis (includingHenoch-Scho

leinpurpura)

Indicationand dose

Hypertension

(underspecialist supervision)

Bymouth

Child6–18 years

Body-weight20–50 kg

initially700 micrograms/

kg(max. 25 mg)once daily (lower dosein intra-

vascularvolume depletion), adjusted accordingto

response;max. 50 mgonce daily

Body-weight50 kgand over

initially50 mgonce

daily(initially 25 mgonce daily in intravascular

volumedepletion), adjusted according to

response;max. 1.4 mg/kg(max. 100 mg)once

daily

LosartanPotassium (Non-proprietary)

Tablets

,losartan potassium 12.5mg, net price28-tab

pack= £7.70; 25mg, 28-tab pack= £2.64; 50mg, 28-

tabpack = £2.38; 100mg, 28-tabpack = £2.84

Cozaar

(MSD)TA

Tablets

,f/c, losartan potassium 12.5mg (blue), net

price28-tab pack =£8.09; 25mg (white), 28-tabpack

=£16.18; 50mg (white,scored), 28-tabpack =£12.80;

100mg (white), 28-tabpack = £16.18

Oralsuspension

,losartan potassium 12.5mg/5 mL

whenreconstituted with solvent provided,net price

200mL (berry-citrus ﬂavour) =£53.68

VALSARTAN

Cautions

seenotes above

Contra-indications

biliarycirrhosis, cholestasis

Hepaticimpairment

max.80 mg dailyin mild to

moderateimpairment; avoid in severeimpair ment

Renalimpairment

seenotes above; also avoidif

estimatedglomerular ﬁltration rate less than30 mL/

minute/1.73m

—noinformation available

Pregnancy

seenotes above

Breast-feeding

seenotes above

Side-effects

seenotes above; also

lesscommonly

abdominalpain, nausea, diarrhoea, cough, malaise,

headache;

alsoreported

anaemia,renal failure, neu-

tropenia,thrombocytopenia, myalgia, vasculitis,

serumsickness, rash, pruritus

Licenseduse capsules notlicensed for use in chil-

dren

Indicationand dose

Hypertension

(underspecialist supervision)

Bymouth

Child6–18 years

Body-weight18–35 kg

initially40 mgonce daily,

adjustedaccording to response; max.80 mg daily

Body-weight35–80 kg

initially80 mgonce daily,

adjustedaccording toresponse; max. 160mg daily

Body-weight80 kgand over

initially80 mgonce

daily,adjustedaccording to response;max. 320mg

daily

Diovan

(Novartis)TA

Capsules

,valsartan 40 mg(grey), net price 28-cap

pack= £13.97; 80mg (grey/pink), 28-cap pack=

£13.97;160 mg (grey/pink),28-cap pack = £18.41

Tablets

,f/c, scored, valsartan 40mg (yellow), net

price7-tab pack = £3.49;320 mg (darkgrey-violet),

28-tabpack = £20.23

2.6

Nitrates, calcium-channel

blockers, and other

antianginal drugs

2.6.1 Nitrates

2.6.2 Calcium-channel blockers

2.6.3 Other antianginal drugs

2.6.4 Peripheral vasodilators and related

drugs

Nitratesand calcium-channelblockers have avasodilat-

ing and, consequently,blood-pressure lowering effect.

Vasodilatorscan act inheart failure byarteriolar dilata-

tion,which reduces both peripheralvascular resistance

andleft ventricular pressure during systole resultingin

improvedcardiac output. They can also cause venous

dilatation, which results in dilatation of capacitance

vessels,increase of venous pooling, and diminution of

venous return to the heart (decreasingleft ventricular

end-diastolicpressure).

2.6.1

Nitrates

Nitrates are potent coronary vasodilators, but their

principal beneﬁt follows from a reduction in venous

return which reduces left ventricular work. Unwanted

effects suchas ﬂ ushing,headache, and postural hypo-

tension may limit therapy, especially if the child is

unusuallysensitive to the effects ofnitrates or is hypo-

volaemic.

For the use of glyceryl trinitrate in extravasation, see

section10.3.

Childrenreceiving nitrates continuouslythroughout the

day can develop tolerance (with reduced therapeutic

effects). Reduction of blood-nitrate concentrations to

lowlevels for 4 to 8 hours each dayusually maintains

effectivenessin such patients.

GLYCERYLTRINITRATE

Cautions

hypothyroidism;malnutrition; hypothermia;

recenthistory of myocardial infarction;heart failure

dueto obstruction; hypoxaemia orother ventilation

andperfusion abnormalities; susceptibility to angle-

closureglaucoma; metal-containing transdermal sys-

temsshould be removed beforemagnetic resonance

imagingprocedures, cardioversion, or diathermy;

avoidabrupt withdrawal; monitorblood pressure and

heartrate during infusion; tolerance(see notes

above); interactions: Appendix 1(nitrates)

104 2.6 Nitratesand calcium-channel blockers BNFC 2011–2012

Cardiovascularsystem

Contra-indications

hypersensitivityto nitrates; hypo-

tensiveconditions and hypovolaemia; hypertrophic

cardiomyopathy;aortic stenosis; cardiac tamponade;

constrictivepericarditis; mitral stenosis; toxicpulm-

onaryoedema; head trauma; cerebralhaemor rhage;

cerebrovasculardisease; marked anaemia

Hepaticimpairment

cautionin severe impairment

Renalimpairment

manufacturersadvise use with

cautionin severe impairment

Pregnancy

notknown to be harmful

Breast-feeding

noinformation available—manufac-

turersadvise use only ifpotential beneﬁt outweighs

risk

Side-effects

posturalhypotension, tachycardia (but

paradoxicalbradycardia also reported); throbbing

headache,dizziness;

lesscommonly

nausea,vomiting,

heartburn,ﬂushing, syncope, temporaryhypoxaemia,

rash,application-site reactions with transdermal

patches;

veryrarely

angle-closureglaucoma

Injection

Speciﬁcside-effects following injection(particu-

larlyif given toorapidly) include severehypotension, dia-

phoresis,apprehension, restlessness, muscletwitching, ret-

rosternaldiscomfort, palpitation,abdominal pain; prolonged

administrationhas been associatedwith methaemoglobin-

aemia

Licenseduse not licensedfor use in children

Indicationand dose

Hypertensionduring and after cardiacsur gery,

heartfailure after cardiac surgery,coronary

vasoconstrictionin myocardial ischaemia,

vasoconstrictionin shock

Bycontinuous intravenous infusion

Neonate

0.2–0.5micrograms/kg/minute, dose

adjustedaccording to response; usualdose 1–

3micrograms/kg/minute; max. 10micrograms/

kg/minute

Child1 month–18 years

initially0.2–0.5 micr-

ograms/kg/minute,dose adjusted according to

response,usual dose 1–3micrograms/kg/minute;

max.10 micrograms/kg/minute (donot exceed

200micrograms/minute)

Administration

for

continuousintravenous infusion

diluteto max. concentration of400 micrograms/mL

(butconcentration of 1mg/mL has been usedvia a

centralvenous catheter) with Glucose5%

Sodium

Chloride0.9%.

Glassor polyethylene apparatus ispreferable; loss of

potencywill occur if PVCis used.

Neonatalintensive care

,dilute 3 mg/kgbody-weight

toa ﬁnal volume of50 mL withinfusion ﬂuid; an

intravenousinfusion rate of 1mL/hour provides a

doseof 1 microgram/kg/minute

GlycerylTrinitrate (Non-proprietary) A

Injection

,glyceryl trinitrate 1mg/mL. To bediluted

beforeuse or givenundiluted with syringe pump.Net

price50-mL vial = £15.90

Injection

,glyceryl trinitrate 5mg/mL. To bediluted

beforeuse. Netprice 5-mLamp =£6.49; 10-mLamp =

£12.98

Excipients

mayinclude ethanol,propylene glycol

Nitrocine

(UCBPharma) A

Injection

,glyceryl trinitrate 1mg/mL. To bediluted

beforeuse or givenundiluted with syringe pump.Net

price10-mL amp = £5.88;50-mL bottle =£13.77

Excipients

includepropylene glycol

Nitronal

(MerckSerono) A

Injection

,glyceryl trinitrate 1mg/mL. To bediluted

beforeuse or givenundiluted with syringe pump.Net

price5-mL vial = £1.80;50-mL vial =£14.76

2.6.2

Calcium-channel blockers

Calcium-channel blockers (less correctly called ‘cal-

cium-antagonists’) interfere with the inward displace-

ment of calcium ions through the slow channels of

activecell membranes. They inﬂuence the myocardial

cells,the cells withinthe specialised conductingsystem

of theheart, and the cells of vascular smooth muscle.

Thus, myocardial contractility may be reduced, the

formationand propagation ofelectrical impulses within

theheart may be depressed, andcoronar yor systemic

vasculartone may be diminished.

Calcium-channelblockers differ intheir predilection for

thevarious possible sites ofaction and, therefore, their

therapeutic effects are disparate, with much g reater

variationthan those of beta-blockers.There are impor-

tantdif ferencesbetween verapamil, diltiazem, and the

dihydropyridinecalcium-channel blockers (amlodipine,

nicardipine,nifedipine, and nimodipine).Verapamil and

diltiazem should usually be avoided in heart failure

becausethey may further depresscardiac function and

causeclinically signiﬁcant deterioration.

Verapamil is used for the treatment of hypertension

(section2.5) and arrhythmias (section 2.3.2). However,

it is no longer ﬁrst-line treatmentfor arrhythmias in

childrenbecause it has been associated with fatal col-

lapse especially in infants under 1 year; adenosine is

nowrecommended for ﬁrst-line use.

Verapamilis ahighly negativelyinotropic calciumchan-

nel-blocker and it reduces cardiac output, slows the

heartrate, and may impairatrioventricular conduction.

Itmay precipitate heart failure, exacerbate conduction

disorders, and cause hypotension at high doses and

should not be used with beta-blockers (see p.109).

Constipationis the most commonside-ef fect.

Nifedipinerelaxes vascular smooth muscleand dilates

coronaryand peripheral arteries. It hasmore inﬂuence

onvessels andless onthe myocardiumthan doesverap-

amil,and unlikeverapamil has noanti-arrhythmic activ-

ity.It rarelyprecipitates heart failurebecause any nega-

tive inotropic effect is offset by a reduction in left

ventricularwork. Short-actingformulations ofnifedipine

are not recommended for long-ter m management of

hypertension; their use may be associated with large

variations in blood pressure and reﬂex tachycardia.

However,they may be used if a modiﬁed-release pre-

parationdelivering the appropriatedose isnot available

or ifa child is unable to swallow (a liquid preparation

maybe prepared using capsules). Nifedipine may also

beused for themanagement of angina dueto coronary

arterydisease inKawasaki diseaseor progeriaand inthe

managementof Raynaud’s syndrome.

Nicardipine has similar effects to those of nifedipine

andmay produce lessreduction of myocardialcontrac-

tility;it is used totreat hypertensive crisis.

Amlodipine also resembles nifedipineand nicardipine

inits effects and does not reduce myocardial contrac-

tilityor produce clinicaldeterioration in heart failure.It

hasa longer duration of action and canbe given once

daily.Nifedipine and amlodipine areused for the treat-

BNFC 2011–2012 2.6.2 Calcium-channel blockers 105

Cardiovascularsystem

mentof hypertension.Side-effects associatedwith vaso-

dilatationsuch asﬂushing andheadache (whichbecome

less obtrusive after a few days), and ankle swelling

(which may respond only partially to diuretics) are

common.

Nimodipine is related to nifedipine but the smooth

muscle relaxant effect preferentially acts on cerebral

arteries.Its use isconﬁned to preventionand treatment

of vascular spasm followinganeur ysmal subarachnoid

haemorrhage.

Diltiazemis a peripheral vasodilatorand also has mild

depressoref fectson the myocardium. It is used inthe

treatmentof Raynaud’s syndrome.

Withdrawal

There is some evidence that sudden

withdrawal of calcium-channel blockers may be asso-

ciatedwith an exacerbation ofmyocardial ischaemia.

AMLODIPINE

Cautions

acuteporphyria (but see section 9.8.2);

interactions:Appendix 1 (calcium-channel blockers)

Contra-indications

cardiogenicshock, signiﬁcant

aorticstenosis

Hepaticimpairment

mayneed dose reduction—half-

lifeprolonged

Pregnancy

noinformation available—manufacturer

advisesavoid, but risk tofetus should be balanced

againstrisk of uncontrolled maternalhypertension

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

abdominalpain, nausea; palpitation,

ﬂushing,oedema; headache, dizziness, sleepdistur-

bances,fatigue;

lesscommonly

gastro-intestinaldis-

turbances,dry mouth, taste disturbances,hypo-

tension,syncope, chestpain, dyspnoea,rhinitis, mood

changes,asthenia, tremor, paraesthesia,urinar ydis-

turbances,impotence, gynaecomastia, weight

changes,myalgia, muscle cramps,back pain, arthr-

algia,visual disturbances, tinnitus, pruritus,rashes

(includingisolated reports of erythema multiforme),

sweating,alopecia, purpura, and skindiscolouration;

veryrarely

gastritis,pancreatitis, hepatitis, jaundice,

cholestasis,gingival hyperplasia, myocardial infarc-

tion,arrhythmias, tachycardia, vasculitis,coughing,

peripheralneuropathy, hyperglycaemia, thrombocy-

topenia,angioedema, and urticaria

Licenseduse notlicensed for usein childrenunder 6

years

Indicationand dose

Hypertension

Bymouth

Child1 month–12 years

initially100–200 micr-

ograms/kgonce daily; if necessary increaseat

intervalsof 1–2 weeks upto 400 micrograms/kg

oncedaily; max. 10mg once daily

Child12–18 years

initially5 mg oncedaily; if

necessaryincrease at intervals of 1–2weeks to

max.10 mg oncedaily

Administration

tabletsmay be dispersed inwater

Note

Tabletsfrom various suppliers maycontain differentsalts

(e.g.amlodipine besilate, amlodipinemaleate, and amlodipine

mesilate)but the strengthis expressed interms of amlodipine

(base);tablets containing different salts are considered inter-

changeable

Amlodipine(Non-proprietary) A

Tablets

,amlodipine (as maleateor as mesilate) 5mg,

netprice 28-tab pack =£1.05; 10 mg,28-tab pack =

£1.20

Brandsinclude Amlostin

Istin

(Pﬁzer)A

Tablets

,amlodipine (as besilate) 5mg, net price28-

tabpack = £11.08; 10mg, 28-tabpack = £16.55

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

DILTIAZEMHYDROCHLORIDE

Cautions

heartfailure or signiﬁcantly impairedleft

ventricularfunction, bradycardia(avoid ifsevere), ﬁrst

degreeAV block, or prolongedPR interval; interac-

tions:Appendix 1 (calcium-channel blockers)

Contra-indications

severebradycardia, signiﬁcant

aorticstenosis, cardiogenic shock, leftventricular

failurewith pulmonary congestion, second-or third-

degreeAV block (unlesspacemaker ﬁtted), sick sinus

syndrome;acute porphyria (section 9.8.2)

Hepaticimpairment

reducedose

Renalimpairment

startwith smaller dose

Pregnancy

avoid

Breast-feeding

signiﬁcantamount present in milk—

noevidence of harm but avoidunless no safer alter-

native

Side-effects

bradycardia,sino-atrial block, AVblock,

palpitation,dizziness, hypotension, malaise, asthenia,

headache,hot ﬂushes, gastro-intestinal disturbances,

oedema(notably of ankles); rarelyrashes (including

erythemamultiforme and exfoliative dermatitis),

photosensitivity;hepatitis, gynaecomastia, gum

hyperplasia,extrapyramidal symptoms, depression

reported

Licenseduse not licensedfor use in children

Indicationand dose

Raynaud’ssyndrome

Bymouth

Child12–18 years

30–60mg 2–3 timesdaily

Standardformulations

Note

Theseformulations are licensedas generics andthere is

no requirement for brand name dispensing. Although their

means of formulation has calledfor the strict designation

‘modiﬁed-release’their duration ofaction corresponds to that

oftablets requiring administrationmore frequently

Diltiazem(Non-proprietary) A

Tablets

,m/r (but see noteabove), diltiazem hydro-

chloride60 mg, netprice 84-tab pack =£2.93.

Label:25

Brandsinclude

Optil

Tildiem

(Sanoﬁ-Aventis)A

Tablets

,m/r (butsee noteabove), off-white,diltiazem

hydrochloride60 mg,net price 90-tab pack = £7.96.

Label:25

NICARDIPINE HYDROCHLORIDE

Cautions

congestiveheart failure or signiﬁcantly

impairedleft ventricular function; avoidgrapefruit

juice(may affect metabolism); interactions: Appen-

dix1 (calcium-channel blockers)

Contra-indications

cardiogenicshock; signiﬁcant

aorticstenosis; acute porphyria (section 9.8.2)

106 2.6.2 Calcium-channelblockers BNFC 2011–2012

Cardiovascularsystem

Hepaticimpairment

half-lifeprolonged in severe

impairment—mayneed dose reduction

Renalimpairment

startwith smaller dose

Pregnancy

mayinhibit labour; toxicity in

animal

stu-

dies;manufacturer advises avoid, butrisk to fetus

shouldbe balanced against riskof uncontrolled

maternalhypertension

Breast-feeding

manufactureradvises avoid—no

informationavailable

Side-effects

dizziness,headache, peripheral oedema,

ﬂushing,palpitation, nausea; also gastro-intestinal

disturbances,drowsiness, insomnia, tinnitus,hypo-

tension,rashes, dyspnoea, paraesthesia, frequencyof

micturition;thrombocytopenia, depression and

impotencereported

Licenseduse not licensedfor use in children

Indicationand dose

Hypertensivecrisis

Bycontinuous intravenous infusion

Neonate

initially500 nanograms/kg/minute,

adjustedaccording to response; usualmainte-

nanceof 1–4 micrograms/kg/minute

Child1 month–18years

initially500 nanograms/

kg/minute,adjusted according to response;usual

maintenanceof 1–4micrograms/kg/minute (max.

250micrograms/minute)

Administration

for

intravenousinfusion

,dilute to a

concentrationof 100 micrograms/mLwith Glucose

SodiumChloride 0.9%; to minimiseperipheral

venousirritation, change site of infusionevery 12

hours

CardeneIV

Injection

,nicardipine 2.5 mg/mL(10-mL ampoule)

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

NIFEDIPINE

Cautions

seenotes above; also poorcardiac reserve;

heartfailure or signiﬁcantly impairedleft ventricular

function(heart failure deteriorationobserved); severe

hypotension;diabetes mellitus; avoid grapefruitjuice

(mayaffect metabolism); acute porphyria (butsee

section9.8.2); interactions: Appendix 1(calcium-

channelblockers)

Contra-indications

cardiogenicshock; signiﬁcant

aorticstenosis

Hepaticimpairment

dosereduction may be required

insevere liver disease

Pregnancy

mayinhibit labour; manufacturer advises

avoidbefore week 20, butrisk to fetus shouldbe

balancedagainst risk of uncontrolledmaternal

hypertension;use only if othertreatment options are

notindicated or have failed

Breast-feeding

amounttoo small to behar mfulbut

manufactureradvises avoid

Side-effects

gastro-intestinaldisturbance; hypo-

tension,oedema, vasodilatation, palpitation; head-

ache,dizziness, lethargy, asthenia;

lesscommonly

tachycardia,hypotension, syncope, chills,nasal con-

gestion,dyspnoea, anxiety,sleep disturbance,vertigo,

migraine,paraesthesia, tremor, polyuria, dysuria,

nocturia,erectile dysfunction,epistaxis, myalgia, joint

swelling,visual disturbance, sweating,and hyper-

sensitivityreactions (including angioedema,jaundice,

pruritus,urticaria, and rash);

rarely

anorexia,gum

hyperplasia,mood disturbances, hyperglycaemia,

maleinfertility, purpura, and photosensitivityreac-

tions;also reported dysphagia, intestinalobstr uction,

intestinalulcer, bezoar formation, gynaecomastia,

agranulocytosis,and anaphylaxis

Licenseduse not licensedfor use in children

Indicationand dose

Hypertensivecrisis, acute angina in Kawasaki

diseaseor progeria

Bymouth (see Administration, below)

Child1 month–18 years

250–500micrograms/

kg(max. 20 mg)as a single dose

Hypertension,angina in Kawasaki diseaseor

progeria

Bymouth

Child1 month–12 years

200–300micrograms/

kg3 timesdaily; max.3 mg/kgdaily

90mg daily

Child12–18 years

5–20mg 3 timesdaily; max.

90mg daily

Note

Dosefrequency depends onpreparation used

Raynaud’ssyndrome

Bymouth

Child2–18 years

2.5–10mg 2–4times daily;start

withlow doses at nightand increase gradually to

avoidpostural hypotension

Note

Dosefrequency depends onpreparation used

Persistenthyperinsulinaemic hypoglycaemia

seealso section 6.1.4

Bymouth

Neonate

100–200micrograms/kg (max.

600micrograms/kg) 4 timesdaily

Administration

forrapid effect in

hypertensivecrisis

acuteangina

,bite capsules and swallowliquid or

useliquid preparation if 5-mgor 10-mg dose inap-

propriate;if liquid unavailable, extractcontents of

capsulevia a syringe anduse immediately—cover

syringewith foil to protectcontents from light; cap-

sulecontents may be dilutedwith water if necessary.

Modiﬁed-releasetablets may be crushed—this may

alterthe release proﬁle; crushed tabletsshould be

administeredwithin 30–60 seconds toavoid signiﬁ-

cantloss of potency ofdrug

Nifedipine(Non-proprietary) A

Capsules

,nifedipine 5 mg,net price 84-cap pack=

£2.97;10 mg, 84-cappack = £4.00

Dose

Give3 times daily

Oralliquid

,available from ‘special-order’ manufac-

turersor specialist importing companies,see p. 809

Adalat

(BayerSchering) A

Capsules

,orange, nifedipine 5mg, net price 90-cap

pack= £5.73; 10mg, 90-cap pack= £7.30

Note

Adalatliquid gel capsulescontain 5mg nifedipine in

0.17mL and10 mgnifedipine in 0.34mL

Dose

Give3 times daily

BNFC 2011–2012 2.6.2 Calcium-channel blockers 107

Cardiovascularsystem

Modiﬁedrelease

Note

Differentversions of modiﬁed-release preparationsmay

nothave the sameclinical effect. Toavoid confusion between

these different formulations ofnifedipine, prescribers should

specifythe brand to be dispensed. Modiﬁed-releasefor mula-

tionsmay not besuitable for dosetitration in hepaticdisease

Adalat

LA(Bayer Schering) A

LA20 tablets

,m/r, f/c, pink,nifedipine 20 mg,net

price28-tab pack = £4.97.Label: 25

LA30 tablets

,m/r, f/c, pink,nifedipine 30 mg,net

price28-tab pack = £6.85.Label: 25

LA60 tablets

,m/r, f/c, pink,nifedipine 60 mg,net

price28-tab pack = £9.03.Label: 25

Counselling

Tabletmembrane maypass through gastro-

intestinaltract unchanged,but beingporous hasno effecton

efﬁcacy

Cautions

doseform not appropriatefor use inhepatic

impairmentor where thereis a historyof oesophageal or

gastro-intestinalobstruction, decreased lumendiameter of

thegastro-intestinal tract, orinﬂammatory bowel disease

(includingCrohn’s disease)

Dose

Giveonce daily

Adalat

Retard(Bayer Schering) A

Retard10 tablets

,m/r, f/c, grey-pink, nifedipine

10mg, net price56-tab pack =£7.34. Label: 25

Retard20 tablets

,m/r, f/c, grey-pink, nifedipine

20mg, net price56-tab pack =£8.81. Label: 25

Dose

Givetwice daily

Adipine

MR(Chiesi) A

Tablets

,m/r, nifedipine10 mg(pink), net price56-tab

pack= £3.73; 20mg (pink), 56-tab pack= £5.21.

Label:25

Dose

Givetwice daily

Adipine

XL(Chiesi) A

Tablets

,m/r, red, nifedipine 30mg, netprice 28-tab

pack= £4.70; 60mg, 28-tab pack= £7.10. Label: 25

Dose

Giveonce daily

CoractenSR

(UCBPharma) A

Capsules

,m/r, nifedipine 10mg (grey/pink, enclos-

ingyellow pellets), net price60-cap pack = £3.90;

20mg (pink/brown,enclosing yellow pellets), 60-cap

pack= £5.41. Label: 25

Dose

Givetwice daily

CoractenXL

(UCBPharma) A

Capsules

,m/r, nifedipine 30mg (brown), netprice

28-cappack = £4.89; 60mg (orange), 28-cappack =

£7.34.Label: 25

Dose

Giveonce daily

FortipineLA 40

(Goldshield)A

Tablets

,m/r, red, nifedipine 40mg, netprice 30-tab

pack= £9.60. Label: 21,25

Dose

Give1–2 times daily

Hypolar

Retard20 (Sandoz) A

Tablets

,m/r, red, f/c,nifedipine 20mg, net price 56-

tabpack = £5.75. Label:25

Dose

Givetwice daily

Nifedipress

MR(Dexcel) A

Tablets

,m/r, pink, nifedipine10 mg, netprice 56-tab

pack= £9.23; 20mg, 56-tab pack= £10.06. Label:25

Dose

Givetwice daily

Note

Alsoavailable as

Calchan

TensipineMR

(Genus)A

Tablets

,m/r, pink-grey, nifedipine10 mg, netprice

56-tabpack = £4.30; 20mg, 56-tabpack = £5.49.

Label:21, 25

Dose

Givetwice daily

ValniXL

(Winthrop)A

Tablets

,m/r, red, nifedipine 30mg, netprice 28-tab

pack= £7.29; 60mg, 28-tab pack= £9.13. Label: 25

Cautions

doseform not appropriatefor use inhepatic

impairment,or where thereis a historyof oesophageal or

gastro-intestinalobstruction, decreased lumendiameter of

thegastro-intestinal tract, inﬂammatorybowel disease, or

ileostomyafter proctocolectomy

Dose

Giveonce daily

NIMODIPINE

Cautions

cerebraloedema or severely raisedintra-

cranialpressure; hypotension; avoid concomitant

administrationof nimodipine tablets andinfusion,

othercalcium-channel blockers, or beta-blockers;

concomitantnephrotoxic drugs;avoid grapefruit juice

(mayaffect metabolism); interactions: Appendix1

(calcium-channelblockers, alcohol (infusion only))

Contra-indications

acuteporphyria (section 9.8.2)

Hepaticimpairment

eliminationreduced in cirrh-

osis—monitorblood pressure

Renalimpairment

manufactureradvises monitor

renalfunction closelywith intravenousadministration

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risks

Breast-feeding

manufactureradvises avoid—present

inmilk

Side-effects

hypotension,variation in heart-rate,

ﬂushing,headache, gastro-intestinal disorders,

nausea,sweating and feeling ofwarmth; thrombocy-

topeniaand ileus reported

Licenseduse not licensedfor use in children

Indicationand dose

Treatmentof vasospasm following subarach-

noidhaemorrhage

underspecialist advice only

Byintravenous infusion

Child1 month–12years

initially15 micrograms/

kg/hour(max. 500 micrograms/hour)

initially

7.5micrograms/kg/hour if bloodpressure

unstable;increase after2 hours to30 micrograms/

kg/hour(max. 2mg/hour) ifno severe decreasein

bloodpressure; continue for atleast 5 days (max.

14days)

Child12–18 years

initially500 micrograms/hour

(upto 1 mg/hourif body-weight over 70kg and

108 2.6.2 Calcium-channelblockers BNFC 2011–2012

Cardiovascularsystem

bloodpressure stable),increase after 2hours to 1–

2mg/hour if nosevere fall in bloodpressure;

continuefor at least 5days (max. 14 days)

Preventionof vasospasm following subarach-

noidhaemorrhage

Bymouth

Child1 month–18 years

0.9–1.2mg/kg (max.

60mg) 6 timesdaily, starting within4 days of

haemorrhageand continued for 21 days

Administration

for

continuousintravenous infusion

administerundiluted

via

aY-piece on a central

venouscatheter connected to ar unninginfusion of

Glucose5%,

SodiumChloride 0.9%; not tobe

addedto an infusion container;incompatible with

polyvinylchloride giving sets orcontainers; protect

infusionfrom light.

Foradministration

bymouth

,tablets may becr ushed

orhalved but are lightsensitive—administer imme-

diately

Nimotop

(BayerSchering) A

Tablets

,yellow, f/c,nimodipine 30mg, net price100-

tabpack = £33.60

Intravenousinfusion

,nimodipine 200 micrograms/

mL;also contains ethanol 20%and macrogol ‘400’

17%.Net price50-mL vial (withpolyethylene infusion

catheter)= £11.46

Note

Polyethylene,polypropylene,or glassapparatus should

beused; PVC shouldbe avoided

VERAPAMILHYDROCHLORIDE

Cautions

ﬁrst-degreeAV block; patients takingbeta-

blockers(important: see below); avoidg rapefruit

juice(may affect metabolism); interactions:Appen-

dix1 (calcium-channel blockers)

Verapamiland beta-blockers

Verapamilinjection should

notbe given topatients recently treatedwith beta-blockers

becauseof the riskof hypotension andasystole. The sug-

gestionthat whenverapamilinjection hasbeen givenﬁrst, an

intervalof 30 minutesbefore giving abeta-blocker is sufﬁ-

cienthas not beenconﬁrmed.

Itmay also behazardous to giveverapamil and abeta-

blockertogether by mouth(should only becontemplated if

myocardialfunction well preserved).

Contra-indications

hypotension,bradycardia, sec-

ond-and third-degree AVblock, sicksinus syndrome,

cardiogenicshock, sino-atrial block; historyof heart

failureor signiﬁcantly impaired leftventricular func-

tion,even if controlled bytherapy; atrial ﬂutter or

ﬁbrillationcomplicating syndromes associated with

accessoryconducting pathways(e.g. Wolff-Parkinson-

Whitesyndrome); acute porphyria (section9.8.2)

Hepaticimpairment

oraldose may need tobe

reduced

Pregnancy

mayreduce uterine blood ﬂowwith fetal

hypoxia;manufacturer advises avoid duringﬁrst tri-

mesterunless absolutely necessary; may inhibit

labour

Breast-feeding

amounttoo small to behar mful

Side-effects

constipation;

lesscommonly

nausea,

vomiting,ﬂushing, headache, dizziness,fatigue, ankle

oedema;

rarely

allergicreactions (erythema, pruritus,

urticaria,angioedema, Stevens-Johnson syndrome);

myalgia,arthralgia, paraesthesia, erythromelalgia;

increasedprolactin concentration; gynaecomastia

andgingival hyperplasia after long-term treatment;

afterintravenous administration or highdoses, hypo-

tension,heart failure, bradycardia, heartblock, and

asystole;hypersensitivity reactions involving reversi-

blyraised liver function tests

Licenseduse Modiﬁed releasepreparation not

licensedfor use in children

Indicationand dose

Hypertension,prophylaxis of supraventricular

arrhythmias

underspecialist advice only

Bymouth

Child1–2 years

20mg 2–3 timesdaily

Child2–18 years

40–120mg 2–3 timesdaily

Treatmentof supraventricular arrhythmias

Byintravenous injection over 2–3minutes

(withECG and blood-pressure monitoringand

underspecialist advice)

Child1–18 years

100–300micrograms/kg (max.

5mg) asa single dose,repeated after30 minutes if

necessary

Administration

for

intravenousinjection

,may be

dilutedwith Glucose 5%

SodiumChloride 0.9%;

incompatiblewith solutions of pHgreater than 6

Verapamil(Non-proprietary) A

Tablets

,coated, verapamil hydrochloride 40mg, net

price84-tab pack= £1.55;80 mg,84-tab pack= £1.91;

120mg, 28-tab pack= £1.54; 160mg, 56-tab pack=

£28.20

Oralsolution

,verapamil hydrochloride 40mg/5 mL,

netprice 150 mL= £36.90

Brandsinclude

Zolvera

Cordilox

(Dexcel)A

Tablets

,yellow, f/c, verapamilhydrochloride 40mg,

netprice 84-tab pack =£1.50; 80 mg,84-tab pack =

£2.05;120 mg, 28-tabpack = £1.15;160 mg, 56-tab

pack= £2.80

Injection

,verapamil hydrochloride 2.5mg/mL, net

price2-mL amp = £1.11

Securon

(Abbott)A

Injection

,verapamil hydrochloride 2.5mg/mL, net

price2-mL amp = £1.08

Extemporaneousformulations available see

ExtemporaneousPreparations, p. 6

Modiﬁedrelease

HalfSecuron SR

(Abbott)A

Tablets

,m/r, f/c, verapamilhydrochloride 120 mg,

netprice 28-tab pack =£7.71. Label: 25

Dose

Giveonce daily (dosesabove 240mg daily,give 2–3

timesdaily)

SecuronSR

(Abbott)A

Tablets

,m/r, pale green, f/c,scored, verapamil

hydrochloride240 mg,net price 28-tab pack= £5.00.

Label:25

Dose

Giveonce daily (dosesabove 240mg daily,give 2–3

timesdaily)

BNFC 2011–2012 2.6.2 Calcium-channel blockers 109

Cardiovascularsystem

Univer

(Cephalon)A

Capsules

,m/r, verapamil hydrochloride120 mg

(yellow/darkblue), net price 28-cappack = £4.86;

180mg (yellow),56-cap pack = £11.38;240 mg (yel-

low/darkblue), 28-cap pack =£7.67. Label: 25

Excipients

includepropylene glycol(see Excipients,p. 2)

Dose

Giveonce daily

VerapressMR

(Dexcel)A

Tablets

,m/r, palegreen, f/c,verapamil hydrochloride

240mg, net price28-tab pack =£6.04. Label: 25

Dose

Give1–2 times daily

Note

Alsoavailable as

Cordilox

Vertab

SR240 (Chiesi) A

Tablets

,m/r, pale green, f/c,scored, verapamil

hydrochloride240 mg,net price 28-tab pack= £5.45.

Label:25

Dose

Give1–2 times daily

2.6.3

Other antianginal drugs

Classiﬁcationnot used in

BNFfor Children

2.6.4

Peripheral vasodilators

and related drugs

Raynaud’ssyndrome

consistsof recurrent,long-lasting,

and episodic vasospasm of the ﬁngers and toes often

associatedwith exposureto cold.Management includes

avoidanceof exposure tocold and stoppingsmoking (if

appropriate).More severesymptoms may requirevaso-

dilator treatment, which is most often successful in

primary Raynaud’s syndrome. Nifedipine and dilti-

azem (section 2.6.2) are useful for reducing the fre-

quency and severity of vasospastic attacks. In very

severe cases, where digital infarction is likely, intra-

venous infusion of the prostacyclin analogue iloprost

maybe helpful.

Vasodilatortherapy isnot established asbeing effective

for

chilblains

(section13.13).

ILOPROST

Cautions

seesection 2.5.1.2

Contra-indications

seesection 2.5.1.2

Hepaticimpairment

dosemay need to behalved in

livercirrhosis

Side-effects

seesection 2.5.1.2

Licenseduse not licensedfor use in children

Indicationand dose

Raynaud’ssyndrome

seenotes above

Byintravenous infusion

Child12–18 years

initially30 nanograms/kg/

hour,increased gradually to 60–120nanograms/

kg/hourgiven over 6 hoursdaily for 3–5 days

Pulmonaryhypertension

section2.5.1.2

Administration

for

intravenousinfusion

,dilute to a

concentrationof 200 nanograms/mLwith Glucose

5%or Sodium Chloride 0.9%;alternatively, may be

dilutedto a concentration of2 micrograms/mL and

givenvia syringe driver

Iloprost(Non-proprietary)

Concentratefor infusion

,iloprost (as trometamol)

100micrograms/mL

Fordilution anduse as anintravenous infusion

Note

availableon anamedpatient basisfrom BayerSchering

in0.5 mLand 1mL ampoules

2.7

Sympathomimetics

2.7.1 Inotropic sympathomimetics

2.7.2 Vasoconstrictor sympathomimetics

2.7.3 Cardiopulmonary resuscitation

Theproperties of sympathomimetics varyaccording to

whetherthey act onalpha or on betaadrenergic recep-

tors. Response to sympathomimetics can also vary

considerably in children, particularly neonates. It is

important totitrate the dose to the desired effect and

tomonitor the child closely.

2.7.1

Inotropic

sympathomimetics

Thecardiac stimulants dobutamineand dopamine act

onbeta

receptorsin cardiac muscle andincrease con-

tractilitywith little effect on rate.

Dopamine has a variable, unpredictable, and dose

dependentimpact on vascular tone.Low dose infusion

(2micrograms/kg/minute) normallycauses vasodilata-

tion, but there is little evidence that this is clinically

beneﬁcial;moderate dosesincrease myocardialcontrac-

tility andcardiac output in older children, but in neo-

natesmoderate doses maycause a reductionin cardiac

output.High doses causevasoconstriction and increase

vascular resistance,and should therefore be used with

cautionfollowing cardiac surgery,or where there isco-

existingneonatal pulmonary hypertension.

In neonates the response to inotropic sympatho-

mimetics varies considerably, particularly in those

bornprematurely; careful dosetitration and monitoring

arenecessary.

Isoprenaline injectionis available from ‘special-order’

manufacturers or specialist importing companies, see

p.809.

Shock

Shockis amedical emergencyassociated witha

highmortality. The underlying causesof shock such as

haemorrhage,sepsis or myocardialinsufﬁciency should

becorrected. Additional treatment isdependent on the

typeof shock.

Septic shock

is associated with severe hypovolaemia

(dueto vasodilationand capillary leak)which should be

correctedwith crystalloids or colloids(section 9.2.2). If

hypotension persists despite volume replacement,

dopamine should be started. For shock refractory to

treatmentwith dopamine, if cardiac outputis high and

peripheral vascular resistance is low (warm shock),

noradrenaline (norepinephrine) (section 2.7.2) should

be added

if cardiac output is lowand peripheral

110 2.6.4 Peripheralvasodilators and related drugs BNFC 2011–2012

Cardiovascularsystem

vascular resistance is high (cold shock), adrenaline

(epinephrine)(section 2.7.2) shouldbe added.Addition-

ally, in cold shock, a vasodilator such as milrinone

(section 2.1.2), glyceryl trinitrate (section 2.6.1), or

sodiumnitropr usside(on specialist advice only) (sec-

tion2.5.1.1) can be usedto reduce vascular resistance.

Ifthe shock is resistant tovolume expansion and cate-

cholamines, and there issuspected or provenadrenal

insufﬁciency,low dose hydrocortisone (section 6.3.2)

canbe used. ACTH-stimulatedplasma-cortisol concen-

tration should be measured; however, hydrocortisone

canbe started without suchinfor mation.

Alternatively,if the childis resistant to catecholamines,

and vascular resistance is low, vasopressin (section

6.5.2)can be added.

Neonatalseptic shock

canbe complicatedby thetransi-

tion from fetal to neonatalcirculation. Treatment to

reverse right ventricular failure, by decreasing pulm-

onary artery pressures, is commonly neededin neo-

nates with ﬂuid-refractory shock and persistent pulm-

onary hypertension of the newborn(section 2.5.1.2).

Rapid administration of ﬂuid in neonates with patent

ductus arteriosus maycause left-to-right shunting and

congestiveheart failureinduced byventricular overload.

cardiogenic shock

, the aim is to improve cardiac

output and to reduce the afterload on the heart. If

centralvenous pressure islow, cautious volumeexpan-

sion with a colloid or crystalloid can be used. An

inotrope such as adrenaline (epinephrine) (section

2.7.2)or dopamine shouldbe given toincrease cardiac

output. Dobutamineis a peripheral vasodilator and is

analternative if hypotension isnot signiﬁcant.

Milrinone (section2.1.2) has both inotropic and vaso-

dilatory effects and can be used when vascular resis-

tanceis high.Alternatively, glyceryltr initrate(2.6.1) or

sodiumnitropr usside(on specialist advice only) (sec-

tion2.5.1.1) can be usedto reduce vasoconstriction.

Hypovolaemicshock

shouldbe treated with a crystal-

loidor colloid solution(or whole orreconstituted blood

ifsource of hypovolaemia is haemorrhage) andfurther

stepsto improve cardiac output anddecrease vascular

resistancecan be taken, asin cardiogenic shock.

The use of sympathomimetic inotropes and vaso-

constrictorsshould preferably be conﬁnedto the inten-

sivecare setting and undertaken with invasivehaemo-

dynamicmonitoring.

Foradvice on the management of anaphylactic shock,

seesection 3.4.3.

DOBUTAMINE

Cautions

arrhythmias,acute myocardial infarction,

acuteheart failure, severe hypotension,marked

obstructionof cardiac ejection (suchas idiopathic

hypertrophicsubaortic stenosis); correct hypovol-

aemiabefore starting treatment; tolerancemay

developwith continuous infusions longerthan 72

hours;hyperthyroidism; interactions: Appendix 1

(sympathomimetics)

Contra-indications

phaeochromocytoma

Pregnancy

noevidence of harm in

animal

studies—

manufacturersadvise use only ifbeneﬁt outweighs

risk

Breast-feeding

manufacturersadvise avoid—no

informationavailable

Side-effects

nausea;hypotension, hypertension

(markedincrease in systolic bloodpressure indicates

overdose),arrhythmias, palpitation, chest pain;dys-

pnoea,bronchospasm; headache; fever; increased

urinaryurgency; eosinophilia; rash, phlebitis;

very

rarely

myocardialinfarction, hypokalaemia;

also

reported

coronaryartery spasm and thrombocytope-

nia

Licenseduse strong sterilesolution not licensed for

usein children

Indicationand dose

Inotropicsupport in low cardiacoutput states,

aftercardiac surgery, cardiomyopathies, shock

Bycontinuous intravenous infusion

Neonate

initially5 micrograms/kg/minute,

adjustedaccording to response to2–15 micr-

ograms/kg/minute;max. 20 micrograms/kg/

minute

Child1 month–18 years

initially5 micrograms/

kg/minuteadjusted according to responseto 2–

20micrograms/kg/minute

Administration

for

continuousintravenous infusion

usinginfusion pump,dilute to a concentrationof 0.5–

1mg/mL (max. 5mg/mL if ﬂuidrestricted) with

Glucose5% or Sodium Chloride0.9%; infuse higher

concentrationsolutions through central venous

catheteronly. Incompatible withbicarbonate and

otherstrong alkaline solutions.

Neonatalintensive care

,dilute 30mg/kg body-weight

toa ﬁnal volume of50 mL withinfusion ﬂuid; an

intravenousinfusion rate of 0.5mL/hour provides a

doseof 5 micrograms/kg/minute

Dobutamine(Non-proprietary) A

Injection

,dobutamine (as hydrochloride) 5mg/mL.

Tobe diluted beforeuse or given undiluted with

syringepump. Net price50-mL vial = £7.50

Excipients

mayinclude sulphites

Concentratefor intravenou s infusion

,dobutamine

(ashydrochloride) 12.5mg/mL. To be dilutedbefore

use.Net price 20-mL amp= £5.20

Excipients

mayinclude sulphites

DOPAMINEHYDROCHLORIDE

Cautions

correcthypovolaemia; hyperthyroidism;

interactions:Appendix 1 (sympathomimetics)

Contra-indications

tachyarrhythmia,phaeochromo-

cytoma

Pregnancy

manufactureradvises use only ifpotential

beneﬁtoutweighs risk

Side-effects

nausea,vomiting, chestpain, palpitation,

tachycardia,vasoconstriction, hypotension, dys-

pnoea,headache;

lesscommonly

bradycardia,hyper-

tension,gangrene, mydriasis;

rarely

fatalventricular

arrhythmias

Licenseduse not licensedfor use in children under

12years

Indicationand dose

Tocorrect thehaemodynamic imbalance dueto

acutehypotension, shock, cardiac failure,

adjunctfollowing cardiac surgery

Bycontinuous intravenous infusion

Neonate

initially3 micrograms/kg/minute,

adjustedaccording to response (max.20 micr-

ograms/kg/minute)

BNFC 2011–2012 2.7.1 Inotropic sympathomimetics 111

Cardiovascularsystem

Child1 month–18 years

initially5 micrograms/

kg/minuteadjusted according to response(max.

20micrograms/kg/minute)

Administration

for

continuousintravenous infusion

diluteto a max. concentrationof 3.2 mg/mLwith

Glucose5%

SodiumChloride 0.9%. Infuse higher

concentrationsthrough central venouscatheter using

asyringe pump to avoidextravasation and ﬂuid

overload.Incompatible with bicarbonate andother

alkalinesolutions.

Neonatalintensive care

,dilute 30mg/kg body-weight

toa ﬁnal volume of50 mL withinfusion ﬂuid; an

intravenousinfusion rate of 0.3mL/hour provides a

doseof 3 micrograms/kg/minute

Dopamine(Non-proprietary) A

Concentratefor intravenou s infusion

,dopamine

hydrochloride40 mg/mL,net price 5-mLamp = 90p;

160mg/mL, 5-mLamp = £3.40. Tobe diluted before

use

Intravenousinfusion

,dopamine hydrochloride

1.6mg/mL in glucose5% intravenous infusion, net

price250-mL container (400mg) = £11.69. Available

from‘special-order’ manufacturers or specialist

importingcompanies, p. 809

2.7.2

Vasoconstrictor

sympathomimetics

Vasoconstrictor sympathomimetics raise blood pres-

suretransiently byacting on alpha-adrenergicreceptors

to constrict peripheral vessels. They are sometimes

usedas an emergency methodof elevating blood pres-

surewhere other measureshave failed (seealso section

2.7.1).

The danger of vasoconstrictors is that althoughthey

raiseblood pressure they alsoreduce perfusion of vital

organssuch as the kidney.

Ephedrine is used to reverse hypotension caused by

spinaland epidural anaesthesia.

Metaraminol is used as a vasopressor during cardio-

pulmonarybypass.

Phenylephrine causesperipheral vasoconstriction and

increasesarterial pressure.

Ephedrine, metaraminol and phenylephrine are rarely

neededin children and shouldbe used under specialist

supervision.

Noradrenaline(norepinephrine) isreserved forchildren

withlow systemic vascular resistancethat is unrespon-

siveto ﬂuid resuscitation followingseptic shock, spinal

shock,and anaphylaxis.

Adrenaline(epinephrine) ismainly usedfor itsinotropic

action. Low doses (acting on beta receptors) cause

systemic and pulmonary vasodilation, with some

increase in heart rate and stroke volume and also an

increasein contractility; high doses act predominantly

on alpha receptors causingintense systemic vasocon-

striction.

EPHEDRINE HYDROCHLORIDE

Cautions

hyperthyroidism,diabetes mellitus, hyper-

tension,susceptibility to angle-closure glaucoma,

interactions:Appendix 1 (sympathomimetics)

Renalimpairment

usewith caution

Pregnancy

increasedfetal heart rate reportedwith

parenteralephedrine

Breast-feeding

irritabilityand disturbed sleep

reported

Side-effects

nausea,vomiting, anorexia; tachycardia

(sometimesbradycardia), arrhythmias, anginal pain,

vasoconstrictionwith hypertension, vasodilationwith

hypotension,dizziness and ﬂushing; dyspnoea;head-

ache,anxiety, restlessness, confusion,psychoses,

insomnia,tremor; difﬁculty in micturition, urine

retention;sweating, hypersalivation; changes in

blood-glucoseconcentration;

veryrarely

angle-clo-

sureglaucoma

Indicationand dose

Reversalof hypotension from epiduraland

spinalanaesthesia

Byslow intravenous injection ofa solution

containingephedrine hydrochloride 3mg/mL

Child1–12 years

500–750micrograms/kg

17–

25mg/m

every3–4 minutes according to

response;max. 30 mgduring episode

Child12–18 years

3–7.5mg (max. 9mg)

repeatedevery 3–4minutes accordingto response,

max.30 mg duringepisode

Nasalcongestion

section12.2.2

Administration

for

slowintravenous injection

,give

viacentral venous catheter

EphedrineHydrochloride (Non-proprietary) A

Injection

,ephedrine hydrochloride 3mg/mL, net

price10-mL amp =£3.25; 30mg/mL, net price 1-mL

amp= 41p

METARAMINOL

Cautions

seeunder Noradrenaline; longer durationof

actionthan noradrenaline (norepinephrine), see

below;cirrhosis; interactions: Appendix 1

(sympathomimetics)

Hypertensiveresponse

Metaraminolhas a longerduration

ofaction than noradrenaline,and an excessivevasopressor

responsemay cause aprolonged rise inblood pressure

Contra-indications

seeunder Noradrenaline

Pregnancy

mayreduce placental prefusion—manu-

factureradvises useonly ifpotential beneﬁtoutweighs

risk

Breast-feeding

manufactureradvises caution—no

informationavailable

Side-effects

seeunder Noradrenaline; tachycardia;

fatalventricular arrhythmia reported in Laennec’s

cirrhosis

Licenseduse not licensedfor use in children

Indicationand dose

Acutehypotension

Byintravenous infusion

Child12–18 years

15–100mg adjustedaccording

toresponse

Emergencytreatment of acute hypotension

Byintravenous administration

Child12–18 years

initiallyby

intravenousinjec-

tion

0.5–5mg, then by

intravenousinfusion

15–

100mg adjusted accordingto response

112 2.7.2 Vasoconstrictorsympathomimetics BNFC 2011–2012

Cardiovascularsystem

Administration

for

intravenousinfusion

,dilute to a

concentrationof 30–200 micrograms/mLwith Glu-

cose5%

SodiumChloride 0.9% andgive througha

centralvenous catheter

Metaraminol(Non-proprietary) A

Injection

,metaraminol 10 mg(as tartrate)/mL.

Availablefrom ‘special-order’manufacturers or specialist

importingcompanies, see p.809

NORADRENALINE/NOREPINEPHRINE

Cautions

coronary,mesenteric, or peripheralvascular

thrombosis;following myocardial infarction;Prinz-

metal’svariant angina, hyperthyroidism,diabetes

mellitus;hypoxia or hypercapnia; uncorrectedhypo-

volaemia;extravasation at injection sitemay cause

necrosis;susceptibility to angle-closure glaucoma

interactions:Appendix 1 (sympathomimetics)

Contra-indications

hypertension(monitor blood

pressureand rate of ﬂow frequently)

Pregnancy

avoid—mayreduce placental perfusion

Side-effects

anorexia,nausea, vomiting, hypoxia,

arrhythmias,peripheral ischaemia, palpitation,

hypertension,bradycardia, tachycardia, dyspnoea,

headache,insomnia, confusion, anxiety,psychosis,

weakness,tremor, urinary retention, angle-closure

glaucoma

Licenseduse not licensedfor use in children

Indicationand dose

Acutehypotension (septic shock) orshock

secondaryto excessive vasodilation

(as

noradrenaline)

Bycontinuous intravenous infusion

Neonate

20–100nanograms(base)/kg/minute

adjustedaccording to response; max.1 micr-

ogram(base)/kg/minute

Child1 month–18 years

20–100nan-

ograms(base)/kg/minute adjusted accordingto

response;max. 1 microgram(base)/kg/minute

Note

500microgramsof noradrenalinebase isequivalent

to1 mgof acid tartrate.Dose expressed asthe base

Administration

for

continuousintravenous infusion

diluteto amax. concentration ofnoradrenaline (base)

40micrograms/mL (higher concentrationscan be

usedif ﬂuid-restricted) with Glucose 5%

Sodium

Chlorideand Glucose. Infuse throughcentral venous

catheter;discard if discoloured. Incompatiblewith

bicarbonateor alkaline solutions.

Neonatalintensive care

,dilute 600 micr-

ograms(base)/kg body-weight toa ﬁnal volume of

50mL withinfusion ﬂuid;an intravenous infusionrate

of0.1 mL/hour providesa dose of 20nan-

ograms(base)/kg/minute

Noradrenaline/Norepinephrine(Non-proprietary) A

Injection

,noradrenaline base1 mg/mL(equivalent to

noradrenalineacid tartrate 2mg/mL). For dilution

beforeuse. Netprice 2-mL amp= £2.40, 4-mLamp =

£4.40,20-mL amp = £6.35

Note

Fora period oftime preparations onthe UK market

maybe described as

either

noradrenalinebase or

noradrenalineacid tar trate;dosesabove areexpressed asthe

base

PHENYLEPHRINE HYDROCHLORIDE

Cautions

seeunder Noradrenaline; longer durationof

actionthan noradrenaline (norepinephrine), see

below;coronary disease

Hypertensiveresponse

Phenylephrinehas a longerdura-

tionof action thannoradrenaline, and anexcessive vaso-

pressorresponse may causea prolonged risein blood

pressure

Contra-indications

seeunder Noradrenaline; severe

hyperthyroidism

Pregnancy

avoidif possible; malformations reported

followinguse in ﬁrst trimester;fetal hypoxia and

bradycardiareported in late pregnancyand labour

Side-effects

seeunder Noradrenaline; tachycardia or

reﬂexbradycardia

Licenseduse not licensedfor use in children by

intravenousinfusion or injection

Indicationand dose

Acutehypotension

Bysubcutaneous or intramuscular injection

(butintravenous injectionpreferred, seebelow)

Child1–12 years

100micrograms/kg every 1–2

hoursas needed (max. 5mg)

Child12–18 years

2–5mg, followedif necessary

byfurther doses of 1–10mg (max. initialdose

5mg)

Byslow intravenous injection

Child1–12 years

5–20micrograms/kg (max.

500micrograms) repeated asnecessary after at

least15 minutes

Child12–18 years

100–500micrograms repeated

asnecessary after at least 15minutes

Byintravenous infusion

Child1–16 years

100–500nanograms/kg/min-

ute,adjusted according to response

Child16–18 years

initiallyup to 180micr-

ograms/minutereduced to 30–60micrograms/

minuteaccording to response

Administration

for

intravenousinjection

,dilute to a

concentrationof 1 mg/mLwith Water forInjections

andadminister slowly.

For

intravenousinfusion

,dilute to a concentrationof

20micrograms/mL withGlucose 5%

Sodium

Chloride0.9% and administer asa continuous infu-

sionvia a central venouscatheter using a controlled

infusiondevice

Phenylephrine(Sovereign) A

Injection

,phenylephrine hydrochloride 10mg/mL

(1%),net price 1-mL amp= £5.50

ADRENALINE/EPINEPHRINE

Cautions

ischaemicheart disease, severe angina,

obstructivecardiomyopathy, hypertension, arrhyth-

mias,cerebrovascular disease; occlusivevascular

disease,monitor blood pressure andECG; cor pulm-

onale;organic brain damage, psychoneurosis;

phaeochromocytoma;diabetes mellitus, hyper-

thyroidism;hypokalaemia, hypercalcaemia; suscept-

ibilityto angle-closure glaucoma; interactions:

Appendix1 (sympathomimetics)

Renalimpairment

manufacturersadvise use with

cautionin severe impairment

BNFC 2011–2012 2.7.2 Vasoconstrictorsympathomimetics 113

Cardiovascularsystem

Pregnancy

mayreduce placental perfusion andcan

delaysecond stage of labour; manufacturersadvise

useonly if beneﬁt outweighsrisk

Breast-feeding

presentin milk but unlikelyto be

harmfulas poor oral bioavailability

Side-effects

nausea,vomiting, dry mouth, anorexia,

hypersalivation;arrhythmias, palpitation,tachycardia,

syncope,angina, hypertension (risk ofcerebral

haemorrhage),cold extremities, pallor; dyspnoea,

pulmonaryoedema (on excessive dosageor extreme

sensitivity);anxiety, tremor, restlessness,headache,

insomnia,confusion, weakness, dizziness, hallucina-

tions,psychosis; hyperglycaemia; difﬁculty inmic-

turition,urinary retention; metabolic acidosis; hypo-

kalaemia;mydriasis, angle-closure glaucoma; tissue

necrosisat injection site andof extremities, liver and

kidneys,sweating

Indicationand dose

Acutehypotension

Bycontinuous intravenous infusion

Neonate

initially100 nanograms/kg/minute

adjustedaccording toresponse; higher dosesup to

1.5micrograms/kg/minute havebeen used in

acutehypotension

Child1 month–18years

initially100 nanograms/

kg/minuteadjusted according to response;higher

dosesup to 1.5micrograms/kg/minute havebeen

usedin acute hypotension

Anaphylaxis

section3.4.3

Cardiopulmonaryarrest

section2.7.3

Administration

for

continuousintravenous infusion

dilutewith Glucose 5%

SodiumChloride 0.9% and

givethrough a central venouscatheter. Incompatible

withbicarbonate and alkaline solutions.

Neonatalintensive care

,dilute 3 mg/kgbody-weight

toa ﬁnal volume of50 mL withinfusion ﬂuid; an

intravenousinfusion rate of 0.1mL/hour provides a

doseof 100 nanograms/kg/minute

Note

Theseinfusions areusually made upwith adrenaline1

in1000 (1mg/mL) solution;this concentrationof adrenaline

isnot licensed forintravenous administration

Preparations

Section3.4.3

2.7.3

Cardiopulmonary

resuscitation

The algorithmsfor cardiopulmonary resuscitation (see

insideback cover) reﬂect the recommendations of the

ResuscitationCouncil (UK); they coverpaediatric basic

lifesupport, paediatric advanced lifesupport, and new-

born life support. The guidelines are available at

www.resus.org.uk.

Paediatricadvanced lifesupport

Cardiopulmonary

(cardiac)arrest in children israre and frequently repre-

sentsthe terminal event ofprogressive shock orrespir-

atoryfailure.

During cardiopulmonary arrest in children without

intravenous access, the intraosseous routeis chosen

because it provides rapid and effective response; if

circulatory access cannot begained, the endotracheal

tubecan be used. Whenthe endotracheal routeis used

tentimes theintravenous dose shouldbe used;the drug

shouldbe injected quickly downa narrow bore suction

catheterbeyond the tracheal end of the tubeand then

ﬂushedin with 1 or2 mLof sodium chloride 0.9%.The

endotracheal route is useful for lipid-soluble drugs,

includinglidocaine, adrenaline, atropine,and naloxone.

Drugsthat arenot lipid-soluble(e.g. sodiumbicarbonate

and calcium chloride) should not be administered by

thisroute because they willinjure the airways.

Forthe management of acute anaphylaxis see section

3.4.3.

2.8

Anticoagulants and

protamine

2.8.1 Parenteral anticoagulants

2.8.2 Oral anticoagulants

2.8.3 Protamine sulphate

Althoughthrombotic episodes are uncommon inchild-

hood,anticoagulants may be required in children with

congenitalheart disease;in childrenundergoing haemo-

dialysis;for preventing thrombosisin children requiring

chemotherapyand following surgery; and for systemic

venous thromboembolism secondary to inherited

thrombophilias, systemic lupus erythematosus, or

indwellingcentral venous catheters.

2.8.1

Parenteral anticoagulants

Heparin

Heparininitiates anticoagulationrapidly but hasa short

durationof action. It is now often referred toas being

standard or unfractionated heparin to distinguish it

fromthe low molecular weight heparins(see p. 116),

whichhave a longer duration ofaction. For children at

high risk of bleeding, unfractionated heparin ismore

suitablethan low molecular weightheparin because its

effect can be terminated rapidly bystopping the infu-

sion.

Heparinsare usedin boththe treatmentand prophylaxis

of thromboembolic disease, mainly to prevent further

clottingrather than to lyse existingclots—surgery or a

thrombolytic drug may be necessary if a thrombus

obstructsmajor vessels.

Treatment

For the initial treatment of thrombotic

episodes unfractionated heparin is given as anintra-

venous loading dose, followed by continuous intra-

venous infusion (using an infusion pump) or by inter-

mittentsubcutaneous injection; the use of intermittent

intravenousinjection is nolonger recommended. Alter-

natively,a low molecular weightheparin may be given

for initial treatment. If an oral anticoagulant (usually

warfarin,section 2.8.2)is alsorequired, itmay bestarted

atthe sametime as theheparin (theheparin needs tobe

continuedfor at least5 daysand until theINR has been

inthe therapeuticrange for2 consecutivedays). Labora-

114 2.7.3 Cardiopulmonaryresuscitation BNFC2011–2012

Cardiovascularsystem

torymonitoring of coagulation activity,preferably on a

daily basis, involves determination of the activated

partialthromboplastin time (APTT) (for unfractionated

heparinonly) orof the anti-FactorXa concentration(for

low molecular weight heparins). Local guidelines on

recommendedAPTT for neonates and children should

be followed;monitoring of APTT should be discussed

witha specialist prior to treatment for thrombotic epi-

sodesin neonates.

Prophylaxis

Low-doseunfractionated heparinby sub-

cutaneousinjection is used to prevent thrombotic epi-

sodes in ‘high-risk’ patients; laboratory monitoring of

APTToranti-Factor Xaconcentration is alsorequired in

prophylactic regimens in children. Low molecular

weight heparins, aspirin (section 2.9), and warfarin

(section2.8.2) can also beused for prophylaxis.

Pregnancy

Heparinsare used for themanagement of

thromboembolicdisease in pregnancy becausethey do

notcross the placenta. Low molecularweight heparins

areprefer redbecause they have a lower risk ofosteo-

porosisand of heparin-inducedthrombocytopenia. Low

molecularweight heparins are eliminated morerapidly

inpregnancy, requiringalteration ofthe dosage regimen

fordrugs suchas dalteparin,enoxaparin, and tinzaparin.

Treatmentshould bestopped at theonset of labourand

advice sought froma specialist on continuing therapy

afterbirth.

Extracorporeal circuits

Unfractionated heparin is

alsoused in the maintenanceof extracorporeal circuits

incardiopulmonary bypass and haemodialysis.

Haemorrhage

If haemorrhage occurs it is usually

sufﬁcient towithdraw unfractionated or low molecular

weightheparin, but ifrapid reversal ofthe effects ofthe

heparinis required,protamine sulphate(section 2.8.3) is

aspeciﬁc antidote(but onlypartially reversesthe effects

oflow molecular weight heparins).

HEPARIN

Cautions

seenotes above; concomitant useof drugs

thatincrease risk ofbleeding; interactions: Appendix

1(heparin)

Heparin-inducedthrombocytopenia

Clinicallyimportant

heparin-inducedthrombocytopeniais immune-mediatedand

doesnot usually developuntil after 5–10days; it canbe

complicatedby thrombosis. Plateletcounts should bemea-

suredjust before treatmentwith unfractionated orlow

molecularweight heparin,and regularmonitoring of platelet

countsis recommendedif givenfor longerthan 4days. Signs

ofheparin-induced thrombocytopenia includea 50% reduc-

tionof plateletcount, thrombosis, orskin allergy.If heparin-

inducedthrombocytopenia is stronglysuspected or con-

ﬁrmed,the heparin shouldbe stopped andan alternative

anticoagulant,such as danaparoid,should be given.Ensure

plateletcounts return tonormal range inthose who require

warfarin

Hyperkalaemia

Inhibitionof aldosterone secretionby

unfractionatedor lowmolecular weightheparin canresult in

hyperkalaemia;patients withdiabetes mellitus,chronic renal

failure,acidosis, raised plasma-potassiumconcentration, or

thosetaking potassium-sparing drugsseem to bemore

susceptible.The risk appearsto increase withduration of

therapyand plasma-potassium concentrationshould be

measuredin childrenat riskof hyperkalaemiabefore starting

theheparin andmonitored regularlythereafter,particularly if

treatmentis to becontinued for longerthan 7 days

Contra-indications

haemophiliaand other haemor-

rhagicdisorders, thrombocytopenia(including history

ofheparin-induced thrombocytopenia), recent cere-

bralhaemorrhage, severe hypertension; pepticulcer;

aftermajor trauma or recent surgeryto eye or ner-

voussystem; acute bacterial endocarditis;spinal or

epiduralanaesthesia with treatment dosesof unfrac-

tionatedor low molecular weightheparin; hyper-

sensitivityto unfractionated or lowmolecular weight

heparin

Hepaticimpairment

riskof bleeding increased—

reducedose or avoidin severe impairment(including

oesophagealvarices)

Renalimpairment

riskof bleedingincreased insevere

impairment—dosemay need to be reduced

Pregnancy

doesnot cross the placenta;maternal

osteoporosisreported after prolonged use;multidose

vialsmay contain benzyl alcohol—somemanufac-

turersadvise avoid; see alsonotes above

Breast-feeding

notexcreted in milk dueto high

molecularweight

Side-effects

haemorrhage(see notes above), throm-

bocytopenia(see Cautions);

rarely

reboundhyper-

lipidaemiafollowing unfractionated heparin with-

drawal,priapism, hyperkalaemia (see Cautions),

osteoporosis(risk lower with lowmolecular weight

heparins),alopecia on prolonged use,injection-site

reactions,skin necrosis, and hypersensitivityreac-

tions(including urticaria, angioedema, andanaphy-

laxis)

Licenseduse some preparationslicensed for use in

children

Indicationand dose

Maintenanceof neonatal umbilical arterial

catheter

Byintravenous infusion

Neonate

0.5units/hour

Treatmentof thrombotic episodes

Byintravenous administration

Neonate

initially75 units/kg(50 units/kg ifunder

35weeks postmenstrual age)

byintravenous

injection

,then

bycontinuous intravenous infusion

25units/kg/hour, adjustedaccording to APTT

Child1 month–1 year

initially75 units/kg

intravenousinjection

,then

bycontinuous intra-

venousinfusion

25units/kg/hour, adjusted

accordingto APTT

Child1–18 years

initially75 units/kg

byintra-

venousinjection

,then

bycontinuous intravenous

infusion

20units/kg/hour, adjustedaccording to

APTT

Bysubcutaneous injection

Child1 month–18years

250units/kg twicedaily,

adjustedaccording to APTT

Prophylaxisof thrombotic episodes

Bysubcutaneous injection

Child1 month–18 years

100units/kg (max.

5000units) twice daily,adjusted according to

APTT

Preventionof clotting inextracorporeal circuits

consultproduct literature

Maintenanceof cardiac shunts andcritical

stents

consultlocal protocol

BNFC 2011–2012 2.8.1 Parenteral anticoagulants 115

Cardiovascularsystem

Administration

for

continuousintravenous infusion

dilutewith Glucose 5%

SodiumChloride 0.9%.

Maintenanceof neonatal umbilicalarterial catheter

dilute50 unitsto aﬁnal volume of50 mLwith Sodium

Chloride0.45%

useready-made bag containing

500units in 500mL Sodium Chloride0.9%; infuse at

0.5mL/hour.

Neonatalintensive care (treatment ofthrombosis)

dilute1250 units/kgbody-weight to a ﬁnalvolume of

50mL withinfusion ﬂuid;an intravenous infusionrate

of1 mL/hour providesa dose of 25units/kg/hour

HeparinSodium (Non-proprietary) A

Injection

,heparin sodium1000 units/mL,net price1-

mLamp =99p, 5-mL amp= £2.50,5-mL vial =£2.50,

10-mLamp = £4.31,20-mL amp =£7.09; 5000units/

mL,1-mL amp =£1.94, 5-mL amp= £5.06,5-mL vial

=£5.64; 25000 units/mL,0.2-mL amp =£2.49, 1-mL

amp= £5.13, 5-mL vial= £11.11

Excipients

mayinclude benzylalcohol (avoidin neonates, seeExcipi-

ents,p. 2)

HeparinSodium (Baxter)A

IntravenousInfusion

,heparin sodium 1unit/mL, in

sodiumchloride intravenous infusion 0.9%,net price

500–mL(500-unit)

Viaﬂex

bag= £4.87

HeparinCalcium (Non-proprietary) A

Injection

,heparin calcium 25000units/mL, net price

0.2-mLamp = £2.61

Low molecular weight heparins

Dalteparin,enoxaparin, and tinzaparin arelow mole-

cular weight heparins usedfor treatment and prophy-

laxisof thrombotic episodes in children (seealso Hep-

arin,p. 114). Theirduration ofaction is longerthan that

ofunfractionated heparin and in adults and older chil-

dren

once-daily subcutaneous

dosage is sometimes

possible; however, younger children require relatively

higherdoses (possibly dueto larger volume ofdistribu-

tion,altered heparinpharmacokinetics, or lowerplasma

concentrationsof antithrombin) and twicedaily dosage

issometimes necessary.Low molecularweight heparins

areconvenient to use, especially in children withpoor

venous access. Routine monitoring of anti-FactorXa

activity is not usually required except in neonates;

monitoring may also be necessary in severely ill chil-

drenand those with renalor hepatic impairment.

Haemorrhage

Seeunder Heparin.

Hepaticimpairm ent

Reducedose in severe impair-

ment—riskof bleeding may beincreased.

Pregnancy

Notknown to be harmful, low molecular

weight heparins do not cross the placenta; see also

Heparin,p. 115.

Breast-feeding

Dueto the relatively high molecular

weight of these drugs and inactivation in the gastro-

intestinaltract, passage intobreast-milk and absorption

bythe nursinginfant are likelyto benegligible; however

manufacturersadvise avoid.

DALTEPARINSODIUM

Cautions

seeunder Heparin and notesabove

Contra-indications

seeunder Heparin

Hepaticimpairment

seenotes above

Renalimpairment

riskof bleeding may be

increased—dosereduction and monitoring ofanti-

FactorXa may be required;use of unfractionated

heparinmay be preferable

Pregnancy

seenotes above; also multidosevial con-

tainsbenzyl alcohol—manufacturer advises avoid

Breast-feeding

seenotes above

Side-effects

seeunder Heparin

Licenseduse not licensedfor use in children

Indicationand dose

Treatmentof thrombotic episodes

Bysubcutaneous injection

Neonate

100units/kg twice daily

Child1 month–12years

100units/kg twicedaily

Child12–18 years

200units/kg (max.

18000units) once daily, ifincreased risk of bleed-

ingreduced to 100units/kg twice daily

Treatmentof venous thromboembolism in

pregnancy

Bysubcutaneous injection

Child12–18 years

earlypregnancy body-weight

under50 kg, 5000units twice daily; body-weight

50–70kg, 6000units twice daily;body-weight 70–

90kg, 8000units twice daily;body-weight over

90kg, 10000 unitstwice daily

Prophylaxisof thrombotic episodes

Bysubcutaneous injection

Neonate

100units/kg once daily

Child1 month–12 years

100units/kg oncedaily

Child12–18 years

2500–5000units once daily

Fragmin

(Pharmacia)A

Injection

(single-dosesyringe), dalteparin sodium

12500units/mL, net price2500-unit (0.2-mL) syringe

=£1.86; 25000 units/mL, 5000-unit(0.2-mL) syringe

=£2.82, 7500-unit (0.3-mL) syringe= £4.23, 10000-

unit(0.4-mL) syringe = £5.65,12 500-unit (0.5-mL)

syringe= £7.06,15 000-unit (0.6-mL)syringe =£8.47,

18000-unit (0.72-mL) syringe= £10.16

Injection

,dalteparin sodium 2500units/mL (for sub-

cutaneousor intravenous use), netprice 4-mL

(10000-unit) amp =£5.12; 10000-units/mL (for sub-

cutaneousor intravenous use), 1-mL(10 000-unit)

amp= £5.12; 25000 units/mL(for subcutaneous use

only),4-mL (100 000-unit)vial = £48.66

Excipients

includebenzyl alcohol(in 100000-unit/4mL multidosevial)

(avoidin neonates,see, p.2)

Injection

(graduatedsyringe), dalteparin sodium

10000units/mL, net price1-mL (10000-unit) syringe

=£5.65

ENOXAPARINSODIUM

Cautions

seeunder Heparin and notesabove

Contra-indications

seeunder Heparin

Hepaticimpairment

seenotes above

Renalimpairment

riskof bleeding may beincreased;

reducedose ifestimated glomerular ﬁltrationrate less

than30 mL/minute/1.73m

;monitoring of anti-Fac-

torXa maybe required; useof unfractionated heparin

maybe preferable

Pregnancy

seenotes above

116 2.8.1 Parenteralanticoagulants BNFC 2011–2012

Cardiovascularsystem

Breast-feeding

seenotes above

Side-effects

seeunder Heparin

Licenseduse not licensedfor use in children

Indicationand dose

Treatmentof thrombotic episodes

Bysubcutaneous injection

Neonate

1.5–2mg/kg twice daily

Child1–2 months

1.5mg/kg twice daily

Child2 months–18 years

1mg/kg twice daily

Treatmentof venous thromboembolism in

pregnancy

Bysubcutaneous injection

Child12–18 years

earlypregnancy body-weight

under50 kg, 40mg (4000units) twice daily;body-

weight50–70 kg,60 mg (6000units) twice daily;

body-weight70–90 kg,80 mg (8000units) twice

daily;body-weight over 90kg, 100mg

(10000units) twice daily

Prophylaxisof thrombotic episodes

Bysubcutaneous injection

Neonate

750micrograms/kg twice daily

Child1–2 months

750micrograms/kg twicedaily

Child2 months–18 years

500micrograms/kg

twicedaily; max. 40mg daily

Clexane

(Sanoﬁ-Aventis)A

Injection

,enoxaparin sodium 100mg/mL, net price

20-mg(0.2-mL, 2000-units) syringe =£3.03, 40-mg

(0.4-mL,4000-units) syringe =£4.04, 60-mg (0.6-mL,

6000-units)syringe = £4.57, 80-mg(0.8-mL, 8000-

units)syringe = £6.49, 100-mg(1-mL, 10 000-units)

syringe= £8.04, 300-mg (3-mL,30 000-units) vial

(

Clexane

Multi-Dose

)= £21.33; 150mg/mL

(

Clexane

Forte

),120-mg (0.8-mL, 12000-units)

syringe= £9.77, 150-mg (1-mL,15 000-units) syringe

=£11.10

Excipients

includebenzyl alcohol(in 300mg multidosevials) (avoidin

neonates,see, p.2)

TINZAPARINSODIUM

Cautions

seeunder Heparin and notesabove

Contra-indications

seeunder Heparin

Hepaticimpairment

seenotes above

Renalimpairment

riskof bleeding may be

increased—dosereduction and monitoring ofanti-

FactorXa may be required;unfractionated heparin

maybe preferable

Pregnancy

seenotes above; also vialscontain benzyl

alcohol—manufactureradvises avoid

Breast-feeding

seenotes above

Side-effects

seeunder Heparin

Licenseduse not licensedfor use in children

Indicationand dose

Treatmentof thrombotic episodes

Bysubcutaneous injection

Child1–2 months

275units/kg once daily

Child2 months–1 year

250units/kg once daily

Child1–5 years

240units/kg once daily

Child5–10 years

200units/kg once daily

Child10–18 years

175units/kg once daily

Treatmentof venous thromboembolism in

pregnancy

Bysubcutaneous injection

Child12–18 years

175units/kg oncedaily (based

onearly pregnancy body-weight)

Prophylaxisof thrombotic episodes

Bysubcutaneous injection

Child1 month–18 years

50units/kg once daily

Innohep

(LEO)A

Injection

,tinzaparin sodium 10000 units/mL, net

price2500-unit (0.25-mL) syringe =£1.98, 3500-unit

(0.35-mL)syringe = £2.77, 4500-unit(0.45-mL)

syringe= £3.56, 20000-unit (2-mL) vial =£10.56

Injection

,tinzaparin sodium 20000 units/mL, net

price0.5-mL (10 000-unit)syringe = £8.46, 0.7-mL

(14000-unit) syringe =£11.85, 0.9-mL (18000-unit)

syringe= £15.23, 2-mL (40000-unit) vial =£34.20

Excipients

includebenzyl alcohol(in vials)(avoid in neonates,see

Excipients,p. 2),sulphites (in20 000units/mL vialand syringe)

Heparinoids

Danaparoidis a heparinoid that has a rolein children

who develop heparin-induced thrombocytopenia, pro-

vidingthey have no evidenceof cross-reactivity.

DANAPAROIDSODIUM

Cautions

recentbleeding or risk of bleeding; conco-

mitantuse of drugs that increaserisk of bleeding;

antibodiesto heparins (risk ofantibody-induced

thrombocytopenia)

Contra-indications

haemophiliaand other haemor-

rhagicdisorders, thrombocytopenia (unless patient

hasheparin-induced thrombocytopenia), recent

cerebralhaemorrhage, severe hypertension, active

pepticulcer (unless this isthe reason for operation),

diabeticretinopathy, acute bacterialendocarditis,

spinalor epiduralanaesthesia with treatmentdoses of

danaparoid

Hepaticimpairment

cautionin moderate impairment

(increasedrisk of bleeding); avoidin severe impair-

mentunless the child hasheparin-induced thrombo-

cytopeniaand no alternative available

Renalimpairment

usewith caution in moderate

impairment;increased risk of bleeding(monitor anti-

FactorXa activity);avoid insevere impairment unless

childhas heparin-induced thrombocytopenia andno

alternativeavailable

Pregnancy

manufactureradvises avoid—limited

informationavailable but not knownto be harmful

Breast-feeding

amountprobably too small tobe

harmfulbut manufacturer advises avoid

Side-effects

haemorrhage;hypersensitivity reactions

(includingrash)

Licenseduse not licensedfor use in children

Indicationand dose

Thromboembolicdisease in children withhis-

toryof heparin-induced thrombocytopenia

Byintravenous administration

Neonate

initially30 units/kg

byintravenous

injection

then

bycontinuous intravenous infusion

1.2–2units/kg/hour adjusted accordingto coagu-

lationactivity

BNFC 2011–2012 2.8.1 Parenteral anticoagulants 117

Cardiovascularsystem

Child1 month–16 years

initially30 units/kg

(max.1250 units ifbody-weight under 55kg,

2500units if over55 kg)

byintravenous injection

then

bycontinuous intravenous infusion

1.2–

2units/kg/hour adjustedaccording tocoagulation

activity

Child16–18 years

initially2500 units(1250 units

ifbody-weight under 55kg, 3750units if over

90kg)

byintravenous injection

then

bycontinuous

intravenousinfusion

400units/hour for 2hours,

then

300units/hour for 2hours,

then

200units/

hourfor 5 days adjustedaccording to coagulation

activity

Administration

for

intravenousinfusion

,dilute with

Glucose5%

SodiumChloride 0.9%

Orgaran

(Organon)A

Injection

,danaparoid sodium 1250units/mL, net

price0.6-mL amp (750units) = £26.68

Heparin ﬂushes

Theuse ofheparin ﬂushesshould bekept toa minimum.

Formaintaining patencyof peripheral venous catheters,

sodiumchloride 0.9%injection is aseffective asheparin

ﬂushes. The role of heparin ﬂushes in maintaining

patency of arterial and central venous catheters is

unclear.

HeparinSodium (Non-proprietary) A

Solution

,heparin sodium 10units/mL, net price 5-

mLamp = £1.00; 100units/mL, 2-mL amp= £1.05

Excipients

mayinclude benzylalcohol (avoidin neonates, seeExcipi-

ents,p. 2)

Epoprostenol

Epoprostenol (prostacyclin) can be given to inhibit

plateletaggregation duringrenal dialysis whenheparins

areunsuitable or contra-indicated. For itsuse in pulm-

onary hypertension, see section 2.5.1.2. It is a potent

vasodilatorand therefore its side-effects include ﬂush-

ing,headache, and hypotension.

2.8.2

Oral anticoagulants

Oralanticoagulants antagonise the effectsof vitamin K

and takeat least 48 to 72 hours for the anticoagulant

effectto developfully; ifan immediate effectis required,

unfractionatedor lowmolecular weightheparin mustbe

givenconcomitantly.

Uses

Warfarinisthe drug ofchoice forthe treatmentof

systemic thromboembolism in children(not neonates)

after initial heparinisation. It may also be used occa-

sionallyfor thetreatment ofintravascular orintracardiac

thrombi.Warfarin isused prophylactically inthose with

chronic atrial ﬁbrillation, dilated cardiomyopathy,cer-

tainfor msof reconstructive heart surgery, mechanical

prosthetic heart valves,and some forms of hereditary

thrombophilia(e.g. homozygous proteinC deﬁciency).

Unfractionatedor a lowmolecular weight heparin (sec-

tion 2.8.1) is usually preferred for theprophylaxis of

venous thromboembolism in children undergoing sur-

gery;alternatively warfarincan be continuedin selected

childrencurrently taking warfarinand whoare at ahigh

riskof thromboembolism (seek expertadvice).

Dose

Thebase-line prothrombintime should bedeter-

minedbut the initial doseshould not be delayedwhilst

awaitingthe result.

An induction dose is usually given over 4 days (see

under WarfarinSodium below). The subsequent main-

tenance dose depends on the prothrombin time,

reported as INR (international normalised ratio) and

shouldbe taken atthe same time eachday. Thefollow-

ing indications and target INRs

for adults take into

account recommendations of the British Society for

Haematology

;

INR2.5 for treatment ofdeep-vein thrombosis and

pulmonary embolism (including those associated

with antiphospholipidsyndrome or for recurrence

inpatients no longer receiving warfarin), for atrial

ﬁbrillation,cardioversion (highertarget values,such

asan INRof 3, canbe usedfor up to4 weeksbefore

the procedure to avoid cancellations due to low

INR;anticoagulation should continue for at least4

weeksfollowing the procedure),dilated cardiomyo-

pathy, mural thrombus, symptomatic inherited

thrombophilia,coronary artery thrombosis (if anti-

coagulated), andparoxysmal nocturnal haemoglo-

binuria;

INR 3.5 for recurrent deep-vein thrombosis and

pulmonary embolism(in patients currently receiv-

ingwarfarin with INR above2);

Formechanical prosthetic heart valves,the recom-

mendedtarget INR depends on the typeand loca-

tion of the valve. Generally, a target INR of 3 is

recommendedfor mechanicalaortic valves, and3.5

formechanical mitral valves.

Monitoring

Itis essential thatthe INR be determined

daily or on alternate days in early days of treatment,

then

atlonger intervals (depending on response

)

then

upto every 12 weeks.

Haemorrhage

The main adverse effect of all oral

anticoagulants ishaemor rhage.Checking the INR and

omitting doses when appropriate is essential; if the

anticoagulant is stopped but not reversed, the INR

shouldbe measured 2–3 days later to ensure that itis

falling. The following recommendations are based on

the result of the INR and whether there is major or

minor bleeding;the recommendations apply to adults

takingwarfarin:

Major bleeding—stop warfarin; give phytomena-

dione (vitamin K

) 5–10mg byslow intravenous

injection;give dried prothrombin complex (factors

II,VII, IX, and X—section 2.11) 30–50units/kg (if

1.An INR whichis within 0.5units of the target value is

generally satisfactory; larger deviations require dosage

adjustment. Target values (rather than ranges) are now

recommended.

2.Guidelines on Oral Anticoagulation (warfarin): third

edition—2005update.

BrJ Haematol

2005;132: 277–285.

3.Change in child’sclinical condition,particularly associated

withliver disease, intercurrent illness,or drug administra-

tion,necessitates more frequent testing.See also interac-

tions, Appendix 1 (warfarin). Major changes in diet

(especiallyinvolving saladsand vegetables) and inalcohol

consumptionmay also affect warfarin control.

118 2.8.2 Oralanticoagulants BNFC 2011–2012

Cardiovascularsystem