Bnf for children bnfc 2019 2020 1

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Medicines Information Services

Information on drug therapy

Information on any aspect of drug therapy can be obtainedfrom Regional and District Medicines Information Services.Details regarding thelocal services provided within yourregion can be obtained by telephoning the followingnumbers.

. Guy’s Hospital (020)7188 8750,or (020)7188 3849,or (020)7188 3855. Northwick Park Hospital (020)8869 2761,

or (020)8869 3973

Southampton: (023)8120 6908/9Wales

or (029)2074 2251Scotland

Telephone numbers and email addresses of manufacturerslisted in BNF Publications are shown in the Index ofmanufacturers p.1102

UK Teratology Information Service

Information on drug and chemical exposures inpregnancy.

Tel:0344 892 0909www.uktis.org

UK Drugs in Lactation Advisory Service (UKDILAS)Information on the compatibility of drugs withbreastfeeding.

Tel: (0116)258 6491,or (0121)424 7298

Email: /ukdilas

Medicines in Dentistry Specialist Advisory ServiceInformation on drug therapy relating to dental treatment.Liverpool: (0151)794 8206

Driver and Vehicle Licensing Agency (DVLA)

Information on the national medical guidelines offitnessto drive is available from:

Medicines for Children Information LeafletsMedicines information for parents and carers.www.medicinesforchildren.org.uk

Patient Information LinesNHS Urgent Care Services111Poisons Information Services

UK National Poisons Information Service (for healthcareprofessionals only)

Tel:0344 892 0111www.toxbase.org

<small>▶</small>Information regarding the use of medicines in sport isavailable from UK Anti-Doping:

Tel: (020)7842 Anti-DopingFleetbank House2-6Salisbury SquareLondon

<small>▶</small>Information about the prohibited status of specificmedicines based on the current World Anti-DopingAgency Prohibited List is available from Global DrugReference Online:www.globaldro.com/UK/search

Travel Medicine Team, Health Protection Scotland(0141)300 1100(2–4p.m. weekdays)

<small>▶</small>www.travax.nhs.uk(for registered users of the NHSwebsite Travax only)

<small>▶</small>Welsh Government Switchboard English language0300 0603300(9a.m.–5:30p.m. weekdays only)<small>▶</small>Welsh Government Switchboard Yr laith Gymraeg

0300 0604400(9a.m.–5:30p.m. weekdays only)<small>▶</small>Department of Health and Social Services (Belfast)

(028)9052 2118(weekdays)List of Registered Medical Practitioners

Details on whether doctors are registered and hold alicence to practise medicine in the UK can be obtainedfrom the General Medical Council.

Tel: (0161)923 6602www.gmc-uk.org/register

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<b>Since 1949 the British National Formulary (BNF) has been </b>

the UK’s most trusted and authoritative healthcare resource, helping to ensure the safe and effective use of medicines at the point of care.

Now, as part of our anniversary celebrations, we want to showcase the rigorous editorial process that goes into creating the content that you rely on for your everyday practice. We will also go behind the scenes at the BNF in our ‘A day in the life’ articles. To find out more visit<b> bnf.org </b>

We really appreciate the support you have given the BNF for our first 70 years - including the launch of the first edition of the BNF

<i>for Children</i> in 2005, created to meet the needs of healthcare professionals working with children.

If you have a story to tell about how the BNF has been pivotal in your healthcare journey, we would love to hear about it on social

70 years supporting you to make effective decisions

<b>Find out more about the BNF’s first 70 years at bnf.org</b>

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<b>BNF subscription – Take advantage of our print subscription option. We will send you </b>

the new BNF as soon as the book is published. One or two year packages (including or

<i>excluding BNF for Children) are available. Discounted pricing is also available on bulk sales.</i>

<b>BNF app – Stay up to date anywhere with the BNF app available for iOS and Android.BNF eBook – Available as an ePDF. See </b>www.pharmpress.com/bnf.

<b>BNF on MedicinesComplete – Now mobile responsive.</b>

<i>Access the BNF your way</i>

<b>The British National Formulary (BNF) and BNF for Children are updated monthly online via MedicinesComplete, ensuring healthcare professionals always have the latest medicines information.</b>

<b>FormularyComplete </b>

Create, edit and manage your own local formulary content built upon the trusted prescribing advice of

<i>the BNF and BNF for Children.</i>

<b>BNF on MedicinesComplete </b>

<i>Access BNF and BNF for Children </i>

on MedicinesComplete and receive the very latest drug information through monthly online updates.

Eligible healthcare professionals will now receive one print copy a year – the September issue – to supplement online access. If you are entitled to an NHS copy please refer to page ii for full details on distribution, FDOORUHPDLO

<i>For enquiries about the BNF or BNF for </i>

<i>Children in print, contact </i>

<b> </b>

Tel: <b>+44 (0) 1256 302 699</b>

For enquiries concerning

MedicinesComplete, FormularyComplete, or bulk orders of the print edition, contact

Tel: <b>+44 (0) 20 7572 2266</b>

Download mobile apps by visiting your appropriate app store. Available for iOS and Android

For pricing information please visit the website at <b>www.pharmpress.com/bnf</b>

For international sales contact your local sales agent. Contact details at

6WD\XSWRGDWHVLJQXSWRWKH%1)eNewsletter at <b>www.bnf.org/newsletter</b>

<b>PRINT SUBSCRIPTION</b>

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for Children 20192020

September 2019 – 20

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66-68East Smithfield, London E1W1AW, UK

Copyright © BMJ Group, the Royal Pharmaceutical Society ofGreat Britain, and RCPCH Publications Ltd2019.

ISBN:978 0 85711 354 2

ISBN:978 0 85711 353 5(NHS edition)ISBN:978 0 85711 355 9(ePDF)

Printed by GGP Media GmbH, Pưßneck, GermanyTypeset by Data Standards Ltd, UK

Text design by Peter Burgess

A catalogue record for this book is available from the BritishLibrary.

All rights reserved. No part of this publication may bereproduced, stored in a retrieval system, or transmitted inany form or by any means, without the prior writtenpermission of the copyright holder.

Material published in the BNFfor Children (BNFC) may notbe used for any form of advertising, sales or publicity withoutprior written permission. Each of the classification and thetext are protected by copyright and/or database right.Requesting copies of BNF publications

Paper copies may be obtained through any bookseller ordirect from:

Pharmaceutical Press

c/o Macmillan Distribution (MDL)Hampshire International Business ParkLime Tree Way

BasingstokeHampshireRG24 8YJ

Tel: +44(0)1256 302 699Fax: +44(0)1256 812

or via our websitewww.pharmpress.comFor all bulk orders of more than20copies:Tel: +44(0)207 572 2266

BNFC is available as a mobile app, online (bnfc.nice.org.uk/)and also through MedicinesComplete; a PDA version is alsoavailable. In addition, BNFC content can be integrated into alocal formulary by using BNFC on FormularyComplete; seewww.bnf.orgfor details.

Distribution of printed BNFCs

In England, NICE purchases print editions of BNFC fordistribution within the NHS. For details of who iseligible to receive a copy and further contact details, pleaserefer to the NICE website:

national-formulary. If you are entitled to a shared copy of theBNFC, please call (0)1268 495 609or email:

www.nice.org.uk/about/what-we-do/evidence-services/ Scotland, email:

Northern Ireland, email:

BNFC content

TheBNF for Children is for rapid reference by UK healthprofessionals engaged in prescribing, dispensing, andadministering medicines to children.BNF for Children hasbeen constructed using robust procedures for gathering,assessing and assimilating information on paediatric drugtreatment, but may not always include all the informationnecessary for prescribing and dispensing. It is expected thatthe reader will be relying on appropriate professionalknowledge and expertise to interpret the contents in thecontext of the circumstances of the individual child.BNF forChildren should be used in conjunction with otherappropriate and up-to-date literature and, where necessary,supplemented by expert advice. Information is also availablefrom Medicines Information Services.

Special care is required in managing childhood conditionswith unlicensed medicines or with licensed medicines forunlicensed uses. Responsibility for the appropriate use ofmedicines lies solely with the individual health professional.Please refer to digital versions ofBNF for Children for themost up-to-date content.BNF for Children is published inprint but interim updates are issued and published in thedigital versions ofBNF for Children. The publishers work toensure that the information is as accurate and up-to-date aspossible at the date of publication, but knowledge and bestpractice in thisfield change regularly. BNF for Children’saccuracy and currency cannot be guaranteed and neither thepublishers nor the authors accept any responsibility forerrors or omissions. While considerable efforts have beenmade to check the material in this publication, it should betreated as a guide only. Prescribers, pharmacists and otherhealthcare professionals are advised to check

www.bnf.orgfor information about key updates andcorrections.

Numerous requests have been received fromdeveloping countries for BNFCs. The Pharmaid schemeof the Commonwealth Pharmacists Associationwill dispatch old BNFCs to certain Commonwealthcountries. For more information on this scheme seecommonwealthpharmacy.org/what-we-do/pharmaid/.If you would like to donate your copy email:

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BNF for Children aims to provide prescribers, pharmacists,and 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, the Royal College ofPaediatrics and Child Health, and the Neonatal andPaediatric Pharmacists Group, BNF for Children (‘BNFC’) ispublished under the authority of a Paediatric FormularyCommittee which comprises representatives of these bodies,the Department of Health for England, and the Medicinesand Healthcare products Regulatory Agency.

Many areas of paediatric practice have suffered frominadequate information on effective medicines. BNFCaddresses this significant knowledge gap by providingpractical information on the use of medicines in children ofall ages from birth to adolescence. Information in BNFC hasbeen validated against emerging evidence, best-practiceguidelines, and crucially, advice from a network of clinicalexperts.

Drawing information from manufacturers’ literature whereappropriate, BNFC also includes a great deal of advice thatgoes beyond marketing authorisations (product licences).This is necessary because licensed indications frequently donot cover the clinical needs of children; in some cases,products for use in children need to be speciallymanufactured or imported. Careful consideration has beengiven to establishing the clinical need for unlicensedinterventions with respect to the evidence and experience oftheir safety and efficacy; local paediatric formularies, clinicalliterature and national information resources have beeninvaluable in this process.

BNFC has been designed for rapid reference and theinformation presented has been carefully selected to aiddecisions on prescribing, dispensing and administration ofmedicines. Less detail is given on areas such as malignantdisease and the very specialist use of medicines generallyundertaken in tertiary centres. BNFC should be interpretedin the light of professional knowledge and it should besupplemented as necessary by specialised publications.Information is also available from Medicines InformationServices (see inside front cover).

It is important to use the most recent BNFC informationfor making clinical decisions. The print edition ofBNF forChildren is updated in September each year. Monthly updatesare provided online via the BNF Publications websitewww.bnf.org, MedicinesComplete and the NHS Evidence portal.The more important changes listed under Changes p. xvii arecumulative (from one print edition to the next), and can beprinted off each month to show the main changes since thelast print edition as an aide memoire for those using printcopies.

The website (www.bnf.org) includes additional informationof relevance to healthcare professionals. Other digitalformats of BNFC—including versions for mobile devices andintegration into local formularies—are also available.BNF Publications welcomes comments from healthcareprofessionals. Comments and constructive criticism shouldbe sent to:

British National Formulary,Royal Pharmaceutical Society,66–68East SmithfieldLondon

The contact email for manufacturers or pharmaceuticalcompanies wishing to contact BNF Publications

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How BNF publications are constructed viii

How to use BNF Publications in print x

Controlled drugs and drug dependence 10

Guidance on intravenous infusions 17Prescribing in hepatic impairment 18

NOTES ON DRUGS AND PREPARATIONS

8 Immune system and malignant disease 535

16 Emergency treatment of poisoning 859

APPENDICES AND INDICES

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The Paediatric Formulary Committee is grateful toindividuals and organisations that have provided advice andinformation to theBNF for Children (BNFC).

Contributors for this update were:

M.N. Badminton, S. Bailey, G.D.L. Bates, H. Bedford,M.W. Beresford, R.M. Bingham, L. Brook, K.G. Brownlee,I.F. Burgess, A. Cant, R. Carr, T.D. Cheetham, A.G. Cleary,A.J. Cotgrove, J.B.S. Coulter, B.G. Craig, J.H. Cross,A. Dhawan, P.N. Durrington, A.B. Edgar, J.A. Edge,D.A.C. Elliman, N.D. Embleton, A. Freyer, P.J. Goadsby,J. Gray, J.W. Gregory, P. Gringras, J.P. Harcourt, C. Hendriksz,R.F. Howard, R.G. Hull, H.R. Jenkins, S. Jones, B.A. Judd,E. Junaid, P.T. Khaw, J.M.W. Kirk, E.G.H. Lyall, P.S. Malone,S.D. Marks, D.F. Marsh, P. McHenry, P.J. McKiernan,L.M. Melvin, E. Miller, S. Moledina, R.E. Morton,P. Mulholland, C. Nelson-Piercy, J.M. Neuberger,K.K. Nischal, C.Y. Ng, J.Y. Paton, G.A. Pearson, J. Puntis,J. Rogers, K.E. Rogstad, J.W. Sander, N.J. Scolding,M.R. Sharland, N.J. Shaw, O.F.W Stumper, A.G. Sutcliffe,E.A. Taylor, S. Thomas, M.A. Thomson, J.A. Vale, S. Vijay,J.O. Warner, N.J.A. Webb, A.D. Weeks, R. Welbury,W.P. Whitehouse, A. Wright, Z. Zaiwalla, and S.M. Zuberi.Valuable advice has been provided by the following expertgroups: Advisory Committee on Malaria Prevention,Association of British Neurologists, British Association ofDermatologists’ Therapy & Guidelines Sub-committee,British Geriatrics Society, British Society of

Gastroenterology, British Society of PaediatricGastroenterology, Hepatology and Nutrition, Faculty ofSexual and Reproductive Healthcare, Neonatal andPaediatric Pharmacists Group, Royal College ofAnaesthetists, Royal College of Obstetricians andGynaecologists, Royal College of Psychiatrists, VascularSociety.

The MHRA have provided valuable assistance.Correspondents in the pharmaceutical industry haveprovided information on new products and commented onproducts in the BNFC.

Numerous doctors, pharmacists, nurses, and others havesent comments and suggestions.

The BNF team are grateful for the support and access to house expertise at Pharmaceutical Press and acknowledgethe assistance of A. Lourie, J. Macdonald, N. Potter and theirteams.

in-M. D'Souza, D. Isaacson, A. Iqbal, N. Kaur, R.K. Khonsoorkh,I. Lowings, E. Richardson and T.T. Sham providedconsiderable assistance during the production of this updateof BNFC.

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BNF Staff

BNF DIRECTOR

Karen BaxterBSc, MSc, MRPharmS

SENIOR EDITORIAL STAFF

Kiri AikmanBPharm (NZ), PGDipClinPharm (NZ), ARPharmSRebecca BloorBPharm (NZ)

Alison Brayfield BPharm, MRPharmSRobert BuckinghamBSc, SRPharmSCatherine CadartBPharm (AU), BA(Hons),GradDipHospPharm (AU), MRPharmS

Mahinaz HarrisonBPharm, DipPharmPract, IP, MRPharmSRebecca LuckhurstBSc, MSc

Alexander McPhailMPharm, PGDipClinPharmClaire McSherryBPharm (NZ), PGCertClinPharm (NZ)Claire PrestonBPharm, PGDipMedMan, MRPharmSKate TowersBPharm (AU), GCClinPharm (AU)

Elizabeth KingMAPharmT

Marta Leon-AlonsoMPharm (ESP), MRes (ESP), MScClinPharm, MRPharmS

David LipanovicBPharm (NZ), PGCertClinPharm (NZ)Jean MacKershanBSc, PgDip

John MartinBPharm, PhD, MRPharmSAngela McFarlaneBSc, DipClinPharmDeirdre McGuirkBComm, MPharm, MRPharmS

Anna McLachlanBPharm (NZ), PGCertClinPharm (NZ)Liliana Moreira Vilas BoasMPharm(PT), PGDipHPS(PT),PGCertHSM(PT), PGCertGPP, MRPharmS

Merusha NaidooBPharm (NZ), PGCertClinPharm (NZ)Hana NumanBPharm (NZ), PGDipClinPharm (NZ)Kere OdumahMPharm, PGCertClinPharmBarbara OkpalaMPharm, PGDipHospPharmCatherine PittMPharm, PGDipClinPharm, MRPharmSStephanie PowellMBioSci

Rebekah RaymondBSc, DipPharmPrac, MRPharmSHarpreet SandhuMPharm, MRPharmS

Beejal ShahMPharm, PGDipClinPharm, IP, MRPharmSTadeh TahmasiMPharm, MRPharmS

Hannah TanBPharm (AU)Jacob WarnerBPharm (AU)Julia WebbMPharm, PGCertPharmPrac

Hans YuBPharm(Hons) (NZ), PGDipClinPharm (NZ)"

SUPPORT STAFF

Matt BradburyBSc(Hons)Darren ChanBSc, MScLauren CheethamBA(Hons)Filsane HajiBSc, MScHannah KittBSc(Hons)

Philip LeeBSc, PhDVicky PollingtonBSc(Hons)Carina Redig de CamposJannah RyanBSc(Hons)Nikolaos TsimplisBSc, MRes

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Paediatric FormularyCommittee

David TuthillMB, BCh, FRCPCH

BMedSci, MB BS, DRCOG, MRCGP, DipTher, DPHEmily Lam

James H. Larcombe

MB, ChB, PhD, FRCGP, DipAdvGPAlison Lockley

Cert Ed, MA, MA (Econ)John Marriott

BSc, PhD, MRPharmS, FHEAE. David G. McIntosh

MB BS, MPH, LLM, PhD, FAFPHM, FRACP, FRCPCH, FFPM,DRCOG, DCH, DipPharmMed

Angeliki SiapkaraMSc, MD, CCST (Ortho)

Dental Advisory Group

BDS MFDS RCS Ed, M Paed Dent RCPS, FDS (Paed Dent) RCSEd

Barbara Okpala

MPharm, PGDipHospPharmWendy ThompsonBSC(Hons), BDS(Hons), MJDFKate Towers

BPharm (AU), GCClinPharm (AU)

Arianne J. MatlinMA, MSci, PhD

ADVICE ON DENTAL PRACTICE

The British Dental Association has contributed to theadvice on medicines for dental practice through itsrepresentatives on the Dental Advisory Group.

Nurse Prescribers’AdvisoryGroup

Molly CourtenayPhD, MSc, Cert Ed, BSc, RGN

COMMITTEE MEMBERS

Penny M. Franklin

RN, RCN, RSCPHN(HV), MA, PGCEMatt Griffiths

BA(Hons), FAETC, RGN, Cert A&E, NISP, PHECCTracy Hall

BSc, MSc, Cert N, Dip N, RGN, DN, NIP, QNPenny Harrison

BSc(Hons)Julie MacAngusBSc(Hons), RGN, RM, PGCEJoan Myers

MSc, BSc, RGN, RSCN, Dip DNFiona Peniston-BirdBSc(Hons), NIP, RHV, RGNKathy Radley

BSc, RGNKate Towers

BPharm (AU), GCClinPharm (AU)

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How BNF Publications are constructed

The BNFfor Children (BNFC) is an independent professionalpublication that addresses the day-to-day prescribing informationneeds of healthcare professionals involved in the care of children.Use of this resource throughout the health service helps to ensurethat medicines are used safely, effectively, and appropriately.

Hundreds of changes are made between print editions, and arepublished monthly in some digital formats. The most clinicallysignificant updates are listed under Changes p. xvii.

BNFC is unique in bringing together authoritative, independentguidance on best practice with clinically validated druginformation.

Information in BNFC has been validated against emergingevidence, best-practice guidelines, and advice from a network ofclinical experts. BNFC includes a great deal of advice that goesbeyond marketing authorisations (product licences or summariesof product characteristics). This is necessary because licensedindications frequently do not cover the clinical needs of children;in some cases, products for use in children need to be speciallymanufactured or imported. Careful consideration has been givento establishing the clinical need for unlicensed interventions withrespect to the evidence and experience of their safety andefficacy.

Validation of information follows a standardised process.Where the evidence base is weak, further validation is undertakenthrough a process of peer review. The process and its governanceare outlined in greater detail in the sections that follow.

Paediatric Formulary Committee

The Paediatric Formulary Committee (PFC) is responsible for thecontent of BNFC. The PFC comprises pharmacy, medical andnursing representatives with a paediatric background, and layrepresentatives who have worked with children or acted as a carerof a paediatric patient; there are also representatives from theMedicines and Healthcare products Regulatory Agency (MHRA)and the Department of Health for England. The PFC decides onmatters of policy and reviews amendments to BNFC in the light ofnew evidence and expert advice.

Dental Advisory Group

The Dental Advisory Group oversees the preparation of advice onthe drug management of dental and oral conditions; the groupincludes representatives from the British Dental Association anda representative from the UK Health Departments.

Nurse Prescribers’Advisory Group

The Nurse Prescribers’ Advisory Group oversees the list of drugsapproved for inclusion in the Nurse Prescribers’ Formulary; thegroup includes representatives from a range of nursing disciplinesand stakeholder organisations.

Expert advisers

BNFC uses about80expert clinical advisers (including doctors,pharmacists, nurses, and dentists) throughout the UK to help withthe clinical content. The role of these expert advisers is to reviewexisting text and to comment on amendments drafted by theclinical writers. These clinical experts help to ensure that BNFCremains reliable by:

.commenting on the relevance of the text in the context of bestclinical practice in the UK;

.checking draft amendments for appropriate interpretation ofany new evidence;

.providing expert opinion in areas of controversy or whenreliable evidence is lacking;

.advising on the use of unlicensed medicines or of licensedmedicines for unlicensed uses (‘off-label’ use);

.providing independent advice on drug interactions, prescribingin hepatic impairment, renal impairment, pregnancy, breast-feeding, neonatal care, palliative care, and the emergencytreatment of poisoning.

In addition to consulting with regular advisers, BNFC calls onother clinical specialists for specific developments whenparticular expertise is required.

BNFC also works closely with a number of expert bodies that

guidelines are often received for comment and for assimilationinto BNFC.

Editorial team

BNFC clinical writers have all worked as pharmacists or possess apharmacy degree and further, relevant post-graduatequalification, and have a sound understanding of how drugs areused in clinical practice. A number of the clinical writers havespecific experience of paediatric practice. As a team, the clinicalwriters are responsible for editing, maintaining, and updatingBNFC content. They follow a systematic prioritisation process inresponse to updates to the evidence base in order to ensure themost clinically important topics are reviewed as quickly aspossible. In parallel the team of clinical writers undertakes aprocess of rolling revalidation, aiming to review all of the contentin the BNF over a3- to4-year period.

Amendments to the text are drafted when the clinical writersare satisfied that any new information is reliable and relevant. Aset of standard criteria define when content is referred to expertadvisers, the Joint Formulary Committee or other advisorygroups, or submitted for peer review.

Clinical writers prepare the text for publication and undertake anumber of validation checks on the knowledge at various stages ofthe production.

Sources of BNFC information

BNFC uses a variety of sources for its information; the main onesare shown below.

Summaries of product characteristics

BNFC reviews the summaries of product characteristics (SPCs) ofall new products as well as revised SPCs for existing products. TheSPCs are a key source of product information and are carefullyprocessed. Such processing involves:

.verifying the approved names of all relevant ingredientsincluding‘non-active’ ingredients (BNFC is committed to usingapproved names and descriptions as laid down by the HumanMedicines Regulations2012);

.comparing the indications, cautions, contra-indications, andside-effects with similar existing drugs. Where these aredifferent from the expected pattern, justification is sought fortheir inclusion or exclusion;

.seeking independent data on the use of drugs in pregnancy andbreast-feeding;

.incorporating the information into BNFC using establishedcriteria for the presentation and inclusion of the data;

.checking interpretation of the information by a second clinicalwriter before submitting to a content manager; changesrelating to doses receive a further check;

.identifying potential clinical problems or omissions andseeking further information from manufacturers or from expertadvisers;

.constructing, with the help of expert advisers, a comment onthe role of the drug in the context of similar drugs.Much of this processing is applicable to the following sources aswell.

Clinical writers monitor core medical, paediatric, andpharmaceutical journals. Research papers and reviews relating todrug therapy are carefully processed. When a difference betweenthe advice in BNFC and the paper is noted, the new information isassessed for reliability (using tools based on SIGN methodology)and relevance to UK clinical practice. If necessary, new text isdrafted and discussed with expert advisers and the PaediatricFormulary Committee. BNFC enjoys a close working relationshipwith a number of national information providers.

In addition to the routine process, which is used to identify’triggers’ for changing the content, systematic literature searchesare used to identify the best quality evidence available to informan update. Clinical writers receive training in critical appraisal,literature evaluation, and search strategies.

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Consensus guidelines

The advice in BNFC is checked against consensus guidelinesproduced by expert bodies. The quality of the guidelines isassessed using adapted versions of the AGREE II tool. A numberof bodies make drafts or pre-publication copies of the guidelinesavailable to BNFC; it is therefore possible to ensure that aconsistent message is disseminated. BNFC routinely processesguidelines from the National Institute for Health and CareExcellence (NICE), the All Wales Medicines Strategy Group(AWMSG), the Scottish Medicines Consortium (SMC), and theScottish Intercollegiate Guidelines Network (SIGN).

Reference sources

Paediatric formularies and reference sources are used to providebackground information for the review of existing text or for theconstruction of new text. The BNFC team works closely with theeditorial team that producesMartindale: The Complete DrugReference. BNFC has access to Martindale information resourcesand each team keeps the other informed of significantdevelopments and shifts in the trends of drug usage.

Peer review

Although every effort is made to identify the most robust dataavailable, inevitably there are areas where the evidence base isweak or contradictory. While the BNF has the valuable support ofexpert advisers and the Paediatric Formulary Committee, therecommendations made may be subject to a further level ofscrutiny through peer review to ensure they reflect best practice.

Content for peer review is posted on bnf.org and interestedparties are notified via a number of channels, including the BNFe-newsletter.

Statutory information

BNFC routinely processes relevant information from variousGovernment bodies including Statutory Instruments andregulations affecting the Prescription only Medicines Order.Official compendia such as the British Pharmacopoeia and itsaddenda are processed routinely to ensure that BNFC complieswith the relevant sections of the Human Medicines Regulations

BNFC maintains close links with the Home Office (in relation tocontrolled drug regulations) and the Medicines and Healthcareproducts Regulatory Agency (including the BritishPharmacopoeia Commission). Safety warnings issued by theCommission on Human Medicines (CHM) and guidelines on druguse issued by the UK health departments are processed as amatter of routine.

Relevant professional statements issued by the RoyalPharmaceutical Society are included in BNFC as are guidelinesfrom bodies such as the Royal College of Paediatrics and ChildHealth.

Medicines and devices

NHS Prescription Services (from the NHS Business ServicesAuthority) provides non-clinical, categorical information(including prices) on the medicines and devices included in BNFC.

Comments from readers

Readers of BNFC are invited to send in comments. Numerousletters and emails are received by the BNF team. Such feedbackhelps to ensure that BNFC provides practical and clinicallyrelevant information. Many changes in the presentation andscope of BNFC have resulted from comments sent in by users.

Comments from industry

Close scrutiny of BNFC by the manufacturers provides anadditional check and allows them an opportunity to raise issuesabout BNFC’s presentation of the role of various drugs; this is yetanother check on the balance of BNFC advice. All comments arelooked at with care and, where necessary, additional informationand expert advice are sought.

Market research

Market research is conducted at regular intervals to gatherfeedback on specific areas of development.

Assessing the evidence

From January2016, recommendations made in BNFC have beenevidence graded to reflect the strength of the recommendation.The addition of evidence grading is to support clinical decision

The BNFC aims to revalidate all content over a rolling3- to

4-year period and evidence grading will be applied torecommendations as content goes through the revalidationprocess. Therefore, initially, only a small number ofrecommendations will have been graded.

Grading system

The BNFC has adopted afive level grading system from A to E,based on the former SIGN grading system. This grade is displayednext to the recommendation within the text.

Evidence used to make a recommendation is assessed forvalidity using standardised methodology tools based on AGREE IIand assigned a level of evidence. The recommendation is thengiven a grade that is extrapolated from the level of evidence, andan assessment of the body of evidence and its applicability.

Evidence assigned a level1- or2- score has an unacceptablelevel of bias or confounding and is not used to formrecommendations.

Levels of evidence. Level 1++

High quality meta-analyses, systematic reviews of randomisedcontrolled trials (RCTs), or RCTs with a very low risk of bias.

. Level 1+

Well-conducted meta-analyses, systematic reviews, or RCTswith a low risk of bias.

. Level 2+

Well-conducted case control or cohort studies with a low risk ofconfounding or bias and a moderate probability that therelationship is causal.

. Level 2–

Case control or cohort studies with a high risk of confoundingor bias and a significant risk that the relationship is not causal.

. Level 3

Non-analytic studies, e.g. case reports, case series.

. Level 4

Expert advice or clinical experience from respected authorities.

Grades of recommendation

. Grade A: High strength

NICE-accredited guidelines; or guidelines that pass AGREE IIassessment; or at least one meta-analysis, systematic review, orRCT rated as1++, and directly applicable to the targetpopulation; or a body of evidence consisting principally ofstudies rated as1+, directly applicable to the target population,and demonstrating overall consistency of results.

. Grade B: Moderate strength

A body of evidence including studies rated as2++, directlyapplicable to the target population, and demonstrating overallconsistency of results; or extrapolated evidence from studiesrated as1++ or1+.

. Grade C: Low strength

A body of evidence including studies rated as2+, directlyapplicable to the target population and demonstrating overallconsistency of results; or extrapolated evidence from studiesrated as2++.

. Grade D: Very low strength

Evidence level3; or extrapolated evidence from studies rated as

2+; or tertiary reference source created by a transparent,defined methodology, where the basis for recommendation isclear.

. Grade E: Practice point

Evidence level4.

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How to use BNF Publications in print

How to use the BNFfor Children in print

This edition of the BNFfor Children (BNFC) continues todisplay the fundamental change to the structure of thecontent that wasfirst shown in BNFC2015-2016. Thechanges were made to bring consistency and clarity to BNFCcontent, and to the way that the content is arranged withinprint and digital products, increasing the ease with whichinformation can be found.

For reference, the most notable changes to the structure ofthe content include:

— Drug monographs – where possible, all information thatrelates to a single drug is contained within its drugmonograph, moving information previously contained inthe prescribing notes. Drug monographs have alsochanged structurally: additional sections have been added,ensuring greater regularity around where information islocated within the publication.

— Drug class monographs – where substantial amounts ofinformation are common to all drugs within a drug class(e.g. macrolides p.339), a drug class monograph has beencreated to contain the common information.

— Medicinal forms – categorical information about marketedmedicines, such as price and pack size, continues to besourced directly from the Dictionary of Medicines andDevices provided by the NHS Business Services Authority.However, clinical information curated by the BNF team hasbeen clearly separated from the categorical pricing andpack size information and is included in the relevantsection of the drug monograph.

— Section numbering – the BNF and BNFC sectionnumbering has been removed. This section numbering tiedthe content to a rigid structure and enforced the retentionof defunct classifications, such as mercurial diuretics, andhindered the relocation of drugs where therapeutic usehad altered. It also caused constraints between the BNFand BNFC, where drugs had different therapeutic uses inchildren.

— Appendix4– the content has been moved to individualdrug monographs. The introductory notes have beenreplaced with a new guidance section, Guidance onintravenous infusions p.17.

In order to achieve the safe, effective, and appropriate use ofmedicines, healthcare professionals must be able to use theBNFC effectively, and keep up to date with significantchanges in the BNFC that are relevant to their clinicalpractice. ThisHow to Use the BNF for Children is key inreinforcing the details of the new structure of the BNFC to allhealthcare professionals involved with prescribing,monitoring, supplying, and administering medicines, as wellas supporting the learning of students training to join theseprofessions.

As with previous editions, the BNFC provides information onthe use of medicines in children ranging from neonates(including preterm neonates) to adolescents. The termsinfant, child, and adolescent are not used consistently in theliterature; to avoid ambiguity actual ages are used in thedose statements in BNFC. The term neonate is used todescribe a newborn infant aged0–28days. The terms childor children are used generically to describe the entire rangefrom infant to adolescent in BNFC.

Structure of the BNFC

This BNFC edition continues to broadly follow the high levelstructure of earlier editions of the BNFC (i.e. those publishedbefore BNFC2015-2016):

Front matter, comprising information on how to use theBNFC, the significant content changes in each edition, and

guidance on various prescribing matters (e.g. prescriptionwriting, the use of intravenous drugs, particularconsiderations for special patient populations).

Chapters, containing drug monographs describing the uses,doses, safety issues and other considerations involved in theuse of drugs; drug class monographs; and treatmentsummaries, covering guidance on the selection of drugs.Monographs and treatment summaries are divided intochapters based on specific aspects of medical care, such asChapter5, Infections, or Chapter16, Emergency treatmentof poisoning; or drug use related to a particular system of thebody, such as Chapter2, Cardiovascular.

Within each chapter, content is organised alphabetically bytherapeutic use (e.g. Airways disease, obstructive), with thetreatment summariesfirst, (e.g. Asthma, acute p.152),followed by the monographs of the drugs used to manage theconditions discussed in the treatment summary. Within eachtherapeutic use, the drugs are organised alphabetically byclassification (e.g. Antimuscarinics, Beta2-agonistbronchodilators) and then alphabetically within eachclassification (e.g. Formoterol fumarate, Salbutamol,Salmeterol, Terbutaline sulfate).

Appendices, covering interactions, borderline substances,and cautionary and advisory labels.

Back matter, covering the lists of medicines approved by theNHS for Dental and Nurse Practitioner prescribing,proprietary and specials manufacturers’ contact details, andthe index. Yellow cards are also included, to facilitate thereporting of adverse events, as well as quick reference guidesfor life support and key drug doses in medical emergencies,for ease of access.

Navigating theBNF for Children

The contents page provides the high-level layout ofinformation within the BNFC; and in addition, each chapterbegins with a small contents section, describing thetherapeutic uses covered within that chapter. Once in achapter, location is guided by the side of the page showingthe chapter number (thethumbnail), alongside the chaptertitle. The top of the page includes the therapeutic use (therunning head) alongside the page number.

Once on a page, visual cues aid navigation: treatmentsummary information is in black type, with therapeutic usetitles similarly styled in black, whereas the use of colourindicates drug-related information, including drugclassification titles, drug class monographs, and drugmonographs.

Although navigation is possible by browsing, primarilyaccess to the information is via the index, which covers thetitles of drug class monographs, drug monographs andtreatment summaries. The index also includes the names ofbranded medicines and other topics of relevance, such asabbreviations, guidance sections, tables, and images.

Content types

In order to select safe and effective medicines for individual

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used in conjunction with other prescribing details about thedrugs and knowledge of the child’s medical and drug history.

Monographs

In earlier editions (i.e. before BNFC2015-2016), asystemically administered drug with indications for use indifferent body systems was split across the chapters relatingto those body systems. So, for example, codeine phosphatep.283was found in chapter1, for its antimotility effects andchapter4for its analgesic effects. However, the monographin chapter1contained only the dose and some selectedsafety precautions.

Now, all of the information for the systemic use of a drug iscontained within one monograph, so codeine phosphatep.283is now included in chapter4. This carries theadvantage of providing all of the information in one place, sothe user does not need toflick back and forth across severalpages tofind all of the relevant information for that drug.Cross references are included in chapter1, where themanagement of diarrhoea is discussed, to the drugmonograph to assist navigation.

Where drugs have systemic and local uses, for example,chloramphenicol p.368, and the considerations around druguse are markedly different according to the route ofadministration, the monograph is split, as with earliereditions, into the relevant chapters.

This means that the majority of drugs are still placed in thesame chapters and sections as earlier editions, and althoughthere may be some variation in order, all of the relevantinformation will be easier to locate.

One of the most significant changes to the monographstructure is the increased granularity, with a move fromaround9sections to over20sections; sections are onlyincluded when relevant information has been identified. Thefollowing information describes these sections and their usesin more detail.

Monograph titles follow the convention of recommendedinternational non-proprietary names (rINNs), or, in theabsence of a rINN, British Approved Names. Relevantsynonyms are included below the title and, in someinstances a brief description of the drug action is included.Over future editions these drug action statements will berolled out for all drugs.

In some monographs, immediately below the nomenclatureor drug action, there are a number of cross references used tosignpost the user to any additional information they need toconsider about a drug. This is most common for drugsformulated in combinations, where users will be signpostedto the monographs for the individual ingredients (e.g. sennawith ispaghula husk p.49) or for drugs that are related to adrug class monograph (see Drug class monographs, below).

Indication and dose

User feedback has highlighted that one of the main uses ofthe BNFC is identifying indications and doses of drugs.Therefore, indication and dose information has beenpromoted to the top of the monograph and highlighted by acoloured panel to aid quick reference.

The indication and dose section is more highly structuredthan in earlier editions, giving greater clarity around whichdoses should be used for which indications and by whichroute. In addition, if the dose varies with a specificpreparation or formulation that dosing information has beenmoved out of the preparations section and in to theindication and dose panel, under a heading of thepreparation name.

Doses are either expressed in terms of a definite frequency(e.g.1g4times daily) or in the total daily dose format (e.g.

6g daily in3divided doses); the total daily dose should bedivided into individual doses (in the second example, thechild should receive2g3times daily).

Doses for specific patient groups (e.g. neonates) may beincluded if they are different to the standard dose. Doses forchildren can be identified by the relevant age range and mayvary according to their age or body-weight.

Selecting the dose

The dose of a drug may vary according to differentindications, routes of administration, age, body-weight, andbody surface area. The right dose should be selected for theright age and body-weight (or body surface area) of the child,as well as for the right indication, route of administration,and preparation.

In earlier editions of the BNFC, age ranges and weight rangesoverlapped. For clarity and to aid selection of the correctdose, wherever possible these age and weight ranges now donot overlap. When interpreting age ranges it is important tounderstand that a child is considered to be11up until thepoint of their12<small>th</small>birthday, meaning that an age range ofchild12to17years is applicable to a child from the day oftheir12<small>th</small>birthday until the day before their18<small>th</small>birthday.All age ranges should be interpreted in this way. Similarly,when interpreting weight ranges, it should be understoodthat a weight of up to30kg is applicable to a child up to, butnot including, the point that they tip the scales at30kg and aweight range of35to59kg is applicable to a child as soon asthey tip the scales at35kg right up until, but not including,the point that they tip the scales at60kg. All weight rangesshould be interpreted in this way.

A pragmatic approach should be applied to these cut-offpoints depending on the child’s physiological development,condition, and if weight is appropriate for the child’s age.For some drugs (e.g. vancomycin p.335) the neonatal dosevaries according to thecorrected gestational age of theneonate. Corrected gestational age is the neonate’s total ageexpressed in weeks from the start of the mother’s lastmenstrual period. For example, a3week old baby born at27weeks gestation is treated as having a corrected gestationalage of30weeks. A term baby has a corrected gestational ageof37–42weeks when born. For most other drugs, the dosecan be based on the child’s actual date of birth irrespective ofcorrected gestational age. However, the degree ofprematurity, the maturity of renal and hepatic function, andthe clinical properties of the drug need to be considered onan individual basis.

Many children’s doses in BNFC are standardised by weight. To calculate the dose for a given child the weight-standardised dose is multiplied by the child’s weight (oroccasionally by the child’s ideal weight for height). Thecalculated dose should not normally exceed the maximumrecommended dose for an adult. For example, if the dose is8mg/kg (max.300mg), a child of10kg body-weight shouldreceive80mg, but a child of40kg body-weight shouldreceive300mg (rather than320mg). Calculation by body-weight in the overweight child may result in much higherdoses being administered than necessary; in such cases, thedose should be calculated from an ideal weight for height.Occasionally, some doses in BNFC are standardised bybodysurface area because many physiological phenomenacorrelate better with body surface area. In these cases, tocalculate the dose for a given child, the body surface area-standardised dose is multiplied by the child’s body surfacearea. The child’s body surface area can be estimated from hisor her weight using the tables for Body surface area inchildren (image) p.1180.

body-Wherever possible, doses are expressed in terms of a definitefrequency (e.g. if the dose is1mg/kg twice daily, a child ofbody-weight9kg would receive9mg twice daily).

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Typical layout of a monograph and associated medicinal forms*

1Class Monographs and drug monographs

In most cases, all information that relates to an individual drugis contained in its drug monograph and there is no symbol. Classmonographs have been created where substantial amounts ofinformation are common to all drugs within a drug class, theseare indicated by a flag symbol in a circle:<small>f</small>

Drug monographs with a corresponding class

monograph are indicated by a tab with a flag symbol:

!

<small>F</small>1234

The page number of the corresponding class monograph isindicated within the tab. For further information, see How to useBNF Publications

*

2Drug classifications

Used to inform users of the class of a drug and to assist infinding other drugs of the same class. May be based onpharmacological class (e.g. opioids) but can also be associatedwith the use of the drug (e.g. cough suppressants)

*

3Review date

The date of last review of the content

*

4Specific preparation name

If the dose varies with a specific preparation or formulation itappears under a heading of the preparation name

Class monograph*

1

<small>l</small>DRUG ACTIONhow a drug exerts its effect in the body<small>l</small>INDICATIONS AND DOSE

Indications are the clinical reasons a drug is used. Thedose of a drug will often depend on the indicationsIndication

<small>▶</small>Age groups:[Neonate/Child]

Dose and frequency of administration (max. dose)SPECIFIC PREPARATION NAME

*

4

<small>▶</small>Age groups:[Neonate/Child]

Dose and frequency of administration (max. dose)DOSE ADJUSTMENTS DUE TO INTERACTIONSdosinginformation when used concurrently with other drugsDOSES AT EXTREMES OF BODY-WEIGHTdosing informationfor patients who are overweight or underweightDOSE EQUIVALENCE AND CONVERSIONinformation aroundthe bioequivalence between formulations of the samedrug, or equivalent doses of drugs that are members ofthe same class

PHARMACOKINETICShow the body affects a drug(absorption, distribution, metabolism, and excretion)POTENCYa measure of drug activity expressed in terms ofthe concentration required to produce an effect of givenintensity

<small>l</small>UNLICENSED USEdescribes the use of medicines outsidethe terms of their UK licence (off-label use), or use ofmedicines that have no licence for use in the UK

IMPORTANT SAFETY INFORMATION

Information produced and disseminated by drugregulators often highlights serious risks associated withthe use of a drug, and may include advice that ismandatory

<small>l</small>CONTRA-INDICATIONScircumstances when a drug shouldbe avoided

<small>l</small>CAUTIONSdetails of precautions required<small>l</small>INTERACTIONSwhen one drug changes the effects of

another drug; the mechanisms underlying druginteractions are explained in Appendix1

<small>l</small>SIDE-EFFECTSlisted in order of frequency, where known,and arranged alphabetically

<small>l</small>ALLERGY AND CROSS-SENSITIVITYfor drugs that carry anincreased risk of hypersensitivity reactions

<small>l</small>CONCEPTION AND CONTRACEPTIONpotential for a drug tohave harmful effects on an unborn child when prescribingfor a woman of childbearing age or for a man trying tofather a child; information on the effect of drugs on theefficacy of latex condoms or diaphragms

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<small>l</small>PREGNANCYadvice on the use of a drug during pregnancy<small>l</small>BREAST FEEDING<small>g</small>advice on the use of a drug during

monitoring requirements, including information onmonitoring the plasma concentration of drugs with anarrow therapeutic index

<small>l</small>EFFECTS ON LABORATORY TESTSfor drugs that caninterfere with the accuracy of seemingly unrelatedlaboratory tests

<small>l</small>TREATMENT CESSATIONspecifies whether furthermonitoring or precautions are advised when the drug iswithdrawn

<small>l</small>DIRECTIONS FOR ADMINISTRATIONpractical informationon the preparation of intravenous drug infusions; generaladvice relevant to other routes of administration<small>l</small>PRESCRIBING AND DISPENSING INFORMATIONpractical

information around how a drug can be prescribed anddispensed including details of when brand prescribing isnecessary

<small>l</small>HANDLING AND STORAGEincludes information on drugsthat can cause adverse effects to those who handle thembefore they are taken by, or administered to, a patient;advice on storage conditions

<small>l</small>PATIENT AND CARER ADVICEfor drugs with a special needfor counselling

<small>l</small>PROFESSION SPECIFIC INFORMATIONprovides details ofthe restrictions certain professions such as dentalpractitioners or nurse prescribers need to be aware ofwhen prescribing on the NHS

<small>l</small>NATIONAL FUNDING/ACCESS DECISIONS details of NICETechnology Appraisals, SMC advice and AWMSG advice<small>l</small>LESS SUITABLE FOR PRESCRIBINGpreparations that areconsidered by the Paediatric Formulary Committee to beless suitable for prescribing

<small>l</small>EXCEPTION TO LEGAL CATEGORYadvice and informationon drugs which may be sold without a prescription underspecific conditions

<small>l</small>MEDICINAL FORMSForm

CAUTIONARY AND ADVISORY LABELSif applicable

EXCIPIENTSclinically important but not comprehensive[consult manufacturer information for full details]

ELECTROLYTESif clinically significant quantities occur<small>▶</small>Preparation name(Manufacturer/Non-proprietary)

Drug name and strength pack sizes<small>P</small>

*

6Prices

Combinations availablethis indicates a combinationpreparation is available and a cross reference pagenumber is provided to locate this preparation

*

5Evidence grading

Evidence grading to reflect the strengths of recommendationswill be applied as content goes through the revalidation process.A five level evidence grading system based on the former SIGNgrading system has been adopted. The gradesh i j klare displayed next to the recommendations within the text,and are preceded by the symbol:<small>g</small>

For further information, see How BNF Publications areconstructed

*

6Legal categories

<small>P</small>This symbol has been placed against those preparationsthat are available only on a prescription issued by anappropriate practitioner. For more detailed information seeMedicines, Ethics and Practice, London, Pharmaceutical Press(always consult latest edition)

<small>a b c d em</small>These symbols indicate thatthe preparations are subject to the prescription requirements ofthe Misuse of Drugs Act

For regulations governing prescriptions for such preparations,see Controlled Drugs and Drug Dependence

Not all monographs include all possible sections; sectionsare only included when relevant information has beenidentified

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Occasionally, it is necessary to include doses in the totaldaily dose format (e.g.10mg/kg daily in3divided doses); inthese cases the total daily dose should be divided intoindividual doses (in this example a child of body-weight9kgwould receive30mg3times daily).

Most drugs can be administered at slightly irregular intervalsduring the day. Some drugs, e.g. antimicrobials, are bestgiven at regular intervals. Someflexibility should be allowedin children to avoid waking them during the night. Forexample, the night-time dose may be given at the child’sbedtime.

Special care should be taken when converting doses fromone metric unit to another, and when calculating infusionrates or the volume of a preparation to administer. Wherepossible, doses should be rounded to facilitate

administration of suitable volumes of liquid preparations, oran appropriate strength of tablet or capsule.

Other information relevant to Indication and dose

The dose panel also contains, where known, an indication ofpharmacokinetic considerations that may affect thechoice of dose, and dose equivalence information, whichmay aid the selection of dose when switching between drugsor preparations.

The BNFC includes unlicensed use of medicines when theclinical need cannot be met by licensed medicines; such useshould be supported by appropriate evidence andexperience. When the BNFC recommends an unlicensedmedicine or the‘off-label’ use of a licensed medicine, this isshown below the indication and dose panel in the unlicenseduse section.

Minimising harm and drug safety

The drug chosen to treat a particular condition shouldminimise the patient’s susceptibility to adverse effects and,where co-morbidities exist, have minimal detrimental effectson the patient’s other diseases. To achieve this, the Contra-indications, Cautions and Side-effects of the relevant drugshould be reviewed.

The information under Cautions can be used to assess therisks of using a drug in a patient who has co-morbidities thatare also included in the Cautions for that drug—if a saferalternative cannot be found, the drug may be prescribedwhile monitoring the patient for adverse-effects ordeterioration in the co-morbidity. Contra-indications are farmore restrictive than Cautions and mean that the drugshould be avoided in a patient with a condition that iscontra-indicated.

The impact that potential side-effects may have on apatient’s quality of life should also be assessed. For instance,in a child who has constipation, it may be preferable to avoida drug that frequently causes constipation.

TheImportant safety advice section in the BNFC, delineatedby a coloured outline box, highlights important safetyconcerns, often those raised by regulatory authorities orguideline producers. Safety warnings issued by theCommission on Human Medicines (CHM) or Medicines andHealthcare products Regulatory Agency (MHRA) are foundhere.

Drug selection should aim to minimise drug interactions. If itis necessary to prescribe a potentially serious combination ofdrugs, patients should be monitored appropriately. Themechanisms underlying drug interactions are explained inAppendix1, followed by details of drug interactions.

Use of drugs in specific patient populations

Drug selection should aim to minimise the potential for drugaccumulation, adverse drug reactions, and exacerbation ofpre-existing hepatic or renal disease. If it is necessary toprescribe drugs whose effect is altered by hepatic or renaldisease, appropriate drug dose adjustments should be made,

and patients should be monitored adequately. The generalprinciples for prescribing are outlined underPrescribing inhepatic impairment p.18, andPrescribing in renal impairmentp.18. Information about drugs that should be avoided orused with caution in hepatic disease or renal impairment canbe found in drug monographs underHepatic impairment andRenal impairment (e.g. fluconazole p.389).

Similarly, drug selection should aim to minimise harm to thefetus, nursing infant, and mother. The infant should bemonitored for potential side-effects of drugs used by themother during pregnancy or breast-feeding. The generalprinciples for prescribing are outlined under Prescribing inpregnancy p.20and Prescribing in breast-feeding p.20. TheTreatment Summaries provide guidance on the drugtreatment of common conditions that can occur duringpregnancy and breast-feeding (e.g. Asthma, acute p.152).Information about the use of specific drugs during pregnancyand breast-feeding can be found in their drug monographsunderPregnancy, and Breast-feeding (e.g. fluconazole p.389).A new section,Conception and contraception, containinginformation around considerations for females ofchildbearing potential or men who might father a child (e.g.isotretinoin p.780) has been included.

Administration and monitoring

When selecting the most appropriate drug, it may benecessary to screen the patient for certain genetic markers ormetabolic states. This information is included within asection calledPre-treatment screening (e.g. abacavir p.431).This section covers one-off tests required to assess thesuitability of a patient for a particular drug.

Once the drug has been selected, it needs to be given in themost appropriate manner. ADirections for administrationsection contains the information about intravenousadministration previously located in Appendix4. Thisprovides practical information on the preparation ofintravenous drug infusions, including compatibility of drugswith standard intravenous infusionfluids, method ofdilution or reconstitution, and administration rates. Inaddition, general advice relevant to other routes ofadministration is provided within this section (e.g. fentanylp.286) and further details, such as masking the bitter taste ofsome medicines.

Whenever possible, intramuscular injections should beavoided in children because they are painful.

After selecting and administering the most appropriate drugby the most appropriate route, patients should be monitoredto ensure they are achieving the expected benefits from drugtreatment without any unwanted side-effects. TheMonitoring section specifies any special monitoringrequirements, including information on monitoring theplasma concentration of drugs with a narrow therapeuticindex (e.g. theophylline p.171). Monitoring may, in certaincases, be affected by the impact of a drug on laboratory tests(e.g. hydroxocobalamin p.595), and this information isincluded inEffects on laboratory tests.

In some cases, when a drug is withdrawn, further monitoringor precautions may be advised (e.g. clonidine hydrochloridep.103); these are covered underTreatment cessation.

Choice and supply

The prescriber, the child’s carer, and the child (ifappropriate) should agree on the health outcomes desiredand on the strategy for achieving them (seeTaking Medicinesto Best Effect). Taking the time to explain to the child (andthe child’s carer if appropriate) the rationale and thepotential adverse effects of treatment may improveadherence. For some medicines there is a special need forcounselling (e.g. appropriate posture during administrationof doxycycline p.364, or recognising signs of blood, liver, or

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skin disorders with carbamazepine p.200); this is shown inPatient and carer advice.

Other information contained in the latter half of themonograph also helps prescribers and those dispensingmedicines choose medicinal forms (by indicatinginformation such asflavour or when branded products arenot interchangeable e.g. modified-release theophyllinep.171), assess the suitability of a drug for prescribing,understand the NHS funding status for a drug (e.g. sildenafilp.122), or assess when a patient may be able to purchase adrug without prescription (e.g. loperamide hydrochloridep.51).

Medicinal forms

In the BNFC, preparations follow immediately after themonograph for the drug that is their main ingredient.In earlier editions, when a particular preparation had safetyinformation, dose advice or other clinical informationspecific to the product, it was contained within thepreparations section. This information has been moved tothe relevant section in the main body of the monographunder a heading of the name of the specific medicinal form(e.g. peppermint oil p.37).

The medicinal forms (formerly preparations) sectionprovides information on the type of formulation (e.g. tablet),the amount of active drug in a solid dosage form, and theconcentration of active drug in a liquid dosage form. Thelegal status is shown for prescription-only medicines andcontrolled drugs, as well as pharmacy medicines andmedicines on the general sales list. Practitioners arereminded, by a statement under the heading of "MedicinalForm" that not all products containing a specific drugingredient may be similarly licensed. To be clear on theprecise licensing status of specific medicinal forms,practitioners should check the product literature for theparticular product being prescribed or dispensed.Details of all medicinal forms available on the dm+d for eachdrug in BNF Publications appears online on

MedicinesComplete. In print editions, due to spaceconstraints, only certain branded products are included indetail. Where medicinal forms are listed they should not beinferred as equivalent to the other brands listed under thesame form heading. For example, all the products listedunder a heading of“Modified release capsule” will beavailable as modified release capsules, however, the brandslisted under that form heading may have different releaseprofiles, the available strengths may vary and/or theproducts may have different licensing information. As withearlier editions of the BNFC, practitioners must ensure thatthe particular product being prescribed or dispensed isappropriate.

As medicinal forms are derived from dm+d data, some drugsmay appear under names derived from that data; this mayvary slightly from those in earlier BNFC versions, e.g. sodiumacid phosphate, is now sodium dihydrogen phosphateanhydrous.

Children should be prescribed a preparation thatcomplements their daily routine, and that provides the rightdose of drug for the right indication and route ofadministration. When dispensing liquid preparations, asugar-free preparation should always be used in preferenceto one containing sugar. Patients receiving medicinescontaining cariogenic sugars should be advised ofappropriate dental hygiene measures to prevent caries.Earlier editions of the BNFC only included excipients andelectrolyte information for proprietary medicines. Thisinformation is now covered at the level of the dose form (e.g.tablet). It is not possible to keep abreast of all of the genericproducts available on the UK market, and so this informationserves as a reminder to the healthcare professional that, if

the presence of a particular excipient is of concern, theyshould check the product literature for the particular productbeing prescribed or dispensed.

Cautionary and advisory labels that pharmacists arerecommended to add when dispensing are included in themedicinal forms section. Details of these labels can be foundin Appendix3, Guidance for cautionary and advisory labelsp.1094. These labels have now been applied at the level ofthe dose form.

In the case of compound preparations, the prescribinginformation for all constituents should be taken intoaccount.

Prices in the BNFC

Basic NHS net prices are given in the BNFC to provide anindication of relative cost. Where there is a choice of suitablepreparations for a particular disease or condition the relativecost may be used in making a selection. Cost-effectiveprescribing must, however, take into account other factors(such as dose frequency and duration of treatment) thataffect the total cost. The use of more expensive drugs isjustified if it will result in better treatment of the patient, ora reduction of the length of an illness, or the time spent inhospital.

Prices are regularly updated using the Drug Tariff andproprietary price information published by the NHSdictionary of medicines and devices (dm+d,www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance-contractors/dictionary-medicines-and-devices-dmd). The weekly updateddm+d data (including prices) can be accessed using the dm+dbrowser of the NHS Business Services Authority (apps.nhsbsa.nhs.uk/DMDBrowser/DMDBrowser.do). Prices have beencalculated from the net cost used in pricing NHSprescriptions and generally reflect whole dispensing packs.Prices for extemporaneously prepared preparations are notprovided in the BNFC as prices vary between differentmanufacturers.

BNFC prices are not suitable for quoting to patients seekingprivate prescriptions or contemplating over-the-counterpurchases because they do not take into account VAT,professional fees, and other overheads.

A fuller explanation of costs to the NHS may be obtainedfrom the Drug Tariff. Separate drug tariffs are applicable toEngland and Wales (www.ppa.org.uk/ppa/edt_intro.htm),Scotland (www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff/), and Northern Ireland (www.hscbusiness.hscni.net/services/2034.htm); prices in thedifferent tariffs may vary.

Drug class monographs

In earlier editions of the BNFC, information relating to aclass of drug sharing the same properties (e.g. tetracyclinesp.364), was contained within the prescribing notes. In theupdated structure, drug class monographs have been createdto contain the common information; this ensures suchinformation is easier tofind, and has a more regularisedstructure.

For consistency and ease of use, the class monograph followsthe same structure as a drug monograph. Class monographsare indicated by the presence of aflag<small>f</small>(e.g. beta-adrenoceptor blockers (systemic) p.105). If a drugmonograph has a corresponding class monograph, thatneeds to be considered in tandem, in order to understand thefull information about a drug, the monograph is alsoindicated by aflag

eiii

<small>F</small>1234

i

(e.g. metoprolol tartratep.109). Within thisflag, the page number of the drug classmonograph is provided (e.g.1234), to help navigate the userto this information. This is particularly useful whereoccasionally, due to differences in therapeutic use, the drugmonograph may not directly follow the drug classmonograph (e.g. sotalol hydrochloride p.81).

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Evidence grading

The BNF has adopted afive level evidence grading system(see How BNF Publications are constructed p. viii).Recommendations that are evidence graded can be identifiedby a symbol appearing immediately before the

recommendation. The evidence grade is displayed at the endof the recommendation.

Other contentNutrition

Appendix2includes tables of ACBS-approved enteral feedsand nutritional supplements based on their energy andprotein content. There are separate tables for specialisedformulae for specific clinical conditions. Classified sectionson foods for special diets and nutritional supplements formetabolic diseases are also included.

Other useful information

Finding significant changes in the BNFC

. Changes, provides a list of significant changes, dose

changes, classification changes, new names, and newpreparations that have been incorporated into the BNFC,as well as a list of preparations that have been

discontinued and removed from the BNFC. Changes listedonline are cumulative (from one print edition to the next),and can be printed off each month to show the mainchanges since the last print edition as an aide memoire forthose using print copies. So many changes are made foreach update of the BNFC, that not all of them can beaccommodated in theChanges section. We encouragehealthcare professionals to review regularly theprescribing information on drugs that they encounterfrequently;

. Changes to the Dental Practitioners’ Formulary, arelocated at the end of the Dental List;

. E-newsletter, the BNF & BNFC e-newsletter service isavailable free of charge. It alerts healthcare professionalsto details of significant changes in the clinical content ofthese publications and to the way that this information isdelivered. Newsletters also review clinical case studies,provide tips on using these publications effectively, andhighlight forthcoming changes to the publications. To signup for e-newsletters go to

. An e-learning programme developed in collaboration withthe Centre for Pharmacy Postgraduate Education (CPPE),enables pharmacists to identify and assess how significantchanges in the BNF affect their clinical practice. Themodule can be found at

Using other sources for medicines information

The BNFC is designed as a digest for rapid reference. Lessdetail is given on areas such as malignant disease andanaesthesia since it is expected that those undertakingtreatment will have specialist knowledge and access tospecialist literature. The BNFC should be interpreted in thelight of professional knowledge and supplemented asnecessary by specialised publications and by reference to theproduct literature. Information is also available frommedicines information services.

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Monthly updates are provided online via MedicinesComplete and the NHS Evidence portal. The changes listedbelow are cumulative (from one print edition to the next).

Significant changes

Significant changes that appear in the print edition of BNFfor Children2019—2020:

. Side-effects and their further information sections havebeen reviewed against the current product literature andterms used to define these have been standardised acrossall drug monographs.

. Anthrax vaccine p.802: updated guidance in-line withPublic Health England recommendations.

. Attention deficit hyperactivity disorder p.231: updatedguidance on management.

. Carbimazole p.501: increased risk of congenitalmalformations; strengthened advice on contraception[MHRA/CHM advice].

. Carbimazole p.501: risk of acute pancreatitis [MHRA/CHMadvice].

. Cholera vaccine p.803: updated guidance in-line withPublic Health England recommendations.

. Controlled drugs and drug dependence p.10:reclassification of gabapentin p.204and pregabalin asClass C and Schedule3Controlled Drugs.

. Darunavir boosted with cobicistat (darunavir withcobicistat, emtricitabine and tenofovir alafenamidep.440): avoid use in pregnancy due to risk of treatmentfailure and maternal-to-child transmission of HIV-1[MHRA/CHM advice].

. Diabetic complications p.466: updated guidance.. Dinutuximab beta p.547for treating neuroblastoma [NICE

. Direct-acting antivirals for chronic hepatitis C (sofosbuvirp.417): risk of hypoglycaemia in patients with diabetes[MHRA/CHM advice].

. Dolutegravir p.427(Tivicay<small>®</small>,Triumeq<small>®</small>,Juluca<small>®</small>): signalof increased risk of neural tube defects; do not prescribe towomen seeking to become pregnant; exclude pregnancybefore initiation and advise use of effective contraception[MHRA/CHM advice].

. Doxycycline p.364: license extension into children aged8to11years.

. Dyslipidaemias p.130: updated guidance on familialhypercholesterolaemia.

. Ear p.712, Ear infections, antibacterial therapy p.315:updated guidance on management of otitis media.. Eltrombopag p.602(Revolade<small>®</small>): reports of interference

with bilirubin and creatinine test results [MHRA/CHMadvice].

. Elvitegravir boosted with cobicistat: avoid use inpregnancy due to risk of treatment failure and maternal-to-child transmission of HIV-1[MHRA/CHM advice] (seeelvitegravir with cobicistat, emtricitabine and tenofoviralafenamide p.433).

. Emollients (see Emollient and barrier preparations p.737):new information about risk of severe and fatal burns withparaffin-containing and paraffin-free emollients[MHRA/CHM advice].

. Fluoroquinolone antibiotics (ciprofloxacin p.361): newrestrictions and precautions for use due to very rarereports of disabling and potentially long-lasting orirreversible side effects [MHRA/CHM advice].. Gabapentin p.204(Neurontin<small>®</small>) and risk of abuse and

dependence: new scheduling requirements from1April[MHRA/CHM advice].

. Gemtuzumab ozogamicin p.548for untreated acutemyeloid leukaemia [NICE guidance].

. Guidance on prescribing p.1: New Medicines Service andMedicines Use Review service information included, andhighlighted in the relevant treatment summaries.. Heavy menstrual bleeding p.495: updated guidance on

. Hydrocortisone p.456muco-adhesive buccal tablets:should not be used off-label for adrenal insufficiency inchildren due to serious risks [MHRA/CHM advice].. Immunisation schedule p.802: updated guidance for the

routine immunisation schedule in-line with Public HealthEngland recommendations.

. Immunisation schedule p.802: updated Nationalfluimmunisation programme in-line with Public HealthEngland recommendations.

. Influenza vaccine p.806: updated guidance in-line withPublic Health England recommendations.

. Ipilimumab p.549(Yervoy<small>®</small>): reports of cytomegalovirus(CMV) gastrointestinal infection or reactivation[MHRA/CHM advice].

. Japanese encephalitis vaccine p.807: updated guidance line with Public Health England recommendations.. Lyme disease p.374: updated guidance on management.. Malaria, prophylaxis p.401: updated country

in-recommendations in the Recommended regimens forprophylaxis against malaria in-line with Public HealthEngland.

. Malaria, prophylaxis p.401: updated guidance in-line withPublic Health England recommendations.

. Meningococcal vaccine p.808: updated guidance forMeningococcal group B vaccines.

. Methotrexate p.563: updated recommendations forconception and contraception.

. Nusinersen p.671(Spinraza<small>®</small>): reports of communicatinghydrocephalus not related to meningitis or bleeding[MHRA/CHM advice].

. Oropharyngeal infections, antibacterial therapy p.733:updated guidance on sore throat (acute).

. Parenteral amphotericin B p.387: reminder of risk ofpotentially fatal adverse reaction if formulations confused[MHRA/CHM advice].

. Pneumococcal vaccine p.809: updated guidance in-linewith Public Health England recommendations.

. Prescribing in pregnancy p.20: Medicines with teratogenicpotential, what is effective contraception and how often ispregnancy testing needed? [MHRA/CHM advice].. Pressurised metered dose inhalers (pMDI): risk of airway

obstruction from aspiration of loose objects [MHRA/CHMadvice],seeRespiratory system, drug delivery p.147.. Quinolones p.359: new MHRA/CHM advice on restrictions

and precautions for use offluoroquinolone antibiotics.. Renal and ureteric stones p.510: new guidance on

. Respiratory system infections, antibacterial therapyp.318: new guidance for acute exacerbations ofBronchiectasis (non-cysticfibrosis).

. Respiratory system infections, antibacterial therapyp.318: new guidance on management of Cough, acute.. Smoking cessation p.304: updated guidance.. Systemic and inhaled fluoroquinolones (ciprofloxacin

p.361): small increased risk of aortic aneurysm anddissection; advice for prescribing in high-risk patients[MHRA/CHM advice].

. Tapentadol p.295(Palexia<small>®</small>): risk of seizures and reportsof serotonin syndrome when co-administered with othermedicines [MHRA/CHM advice].

. Transdermal fentanyl p.286patches: life-threatening andfatal opioid toxicity from accidental exposure, particularlyin children [MHRA/CHM advice].

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. Typhoid vaccine p.812: updated guidance in-line withPublic Health England recommendations.

. Valproate medicines and serious harms in pregnancy: newAnnual Risk Acknowledgement Form and clinical guidancefrom professional bodies to support compliance with thePregnancy Prevention Programme [MHRA/CHM advice](see sodium valproate p.213and valproic acid p.219).. Valproate medicines (see sodium valproate p.213and

valproic acid p.219): are you in acting in compliance withthe pregnancy prevention measures? [MHRA/CHM advice].. Venous thromboembolism p.90: updated guidance on

. Yellow fever vaccine, live p.829(Stamaril<small>®</small>) and fataladverse reactions: extreme caution needed in people whomay be immunosuppressed [MHRA/CHM advice].. Yellow fever vaccine p.813: updated guidance in-line with

Public Health England recommendations.

Dose changes

Changes in dose statements that appear in the print editionofBNF for Children2019—2020:

. Adalimumab p.665[maintenance dosing updated].. Adenosine p.80[dose clarification for neonate and

children under12years for termination ofsupraventricular tachycardias and diagnosis ofsupraventricular arrhythmias].

. Amoxicillin p.351[update to indications and doses forLyme Disease].

. Anakinra p.662[dosing in severe renal impairment].. Azithromycin p.339[update to indication and doses for

Lyme Disease].

. Budenofalk<small>®</small>[deletion of dosing information forcollagenous colitis and update on advice on reducing dosefollowing treatment in Crohn’s disease].

. Caffeine citrate p.194[maintenance dosing].. Canakinumab p.543.

. Ceftriaxone p.332[update to indications and doses forLyme Disease].

. Clarithromycin p.340[dosing recommendation for LymeDisease deleted in line with updated guidance].. Colistimethate sodium p.358[dosing recommendations

for inhalation of nebulised solution and for intravenoususe].

. Doxycycline p.364[update to indications and doses forLyme Disease].

. Erythromycin p.341[dosing recommendation for LymeDisease deleted in line with updated guidance].. Glycerol phenylbutyrate p.637[dose rounding

recommendation for children under2years].. Haloperidol p.252.

. Hexetidine p.728[update to age-range].

. Hydroxocobalamin p.595[frequency of maintenancedosing for macrocytic anaemia without neurologicalinvolvement].

. Imipenem with cilastatin p.325[dosing recommendationin renal impairment updated].

. Influenza vaccine p.825[update to indication of annualimmunisation against seasonal influenza (for children inclinical risk groups who have not received seasonalinfluenza vaccine previously)].

. Japanese encephalitis vaccine p.826[dosing scheduleupdated].

. Levonorgestrel p.527[update to timings of administrationof intra-uterine devices and advice on additionalcontraceptive precautions].

. Malarone<small>®</small>Paediatric (atovaquone with proguanilhydrochloride p.409) [update to weight ranges forprophylaxis of falciparum malaria].

. Mometasone furoate p.166[prophylaxis and treatment ofseasonal allergic or perennial rhinitis—age rangeextended].

. Raltegravir p.427[directions for administration for

may contain conflicting advice; see individual packs forinstructions for reconstitution].

. Rufinamide p.212[update to age range for use in childrenand dosing information for use with valproate].. Stiripentol p.217[updated dosing information].. Vancomycin p.335[deletion of the statement

recommending the use of ideal body-weight to calculateintravenous doses in obese patients].

. Maviret<small>®</small>[glecaprevir with pibrentasvir p.418].. Nplate<small>®</small>[romiplostim p.603].

. Nucala<small>®</small>[mepolizumab p.167].. Palexia<small>®</small>oral solution [tapentadol p.295].. Qarziba<small>®</small>[dinutuximab beta p.547].. Slenyto<small>®</small>[melatonin p.303].. Sprycel<small>®</small>[dasatinib p.579].

. Symkevi<small>®</small>[tezacaftor with ivacaftor p.190].. Tygacil<small>®</small>[tigecycline p.367].

. Verkazia<small>®</small>eye drops [ciclosporin p.537].. Xgeva<small>®</small>[denosumab p.488].

. Zebinix<small>®</small>[eslicarbazepine acetate p.202].. Zemplar<small>®</small>[paricalcitol p.657].

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Guidance on prescribing

General guidance

Medicines should be given to children only when they arenecessary, and in all cases the potential benefit ofadministering the medicine should be considered in relationto the risk involved. This is particularly important duringpregnancy, when the risk to both mother and fetus must beconsidered.

It is important to discuss treatment options carefully withthe child and the child’s carer. In particular, the child and thechild’s carer should be helped to distinguish the adverseeffects of prescribed drugs from the effects of the medicaldisorder. When the beneficial effects of the medicine arelikely to be delayed, this should be highlighted.Prescribing competency frameworkThe RoyalPharmaceutical Society has published a PrescribingCompetency Framework that includes a common set ofcompetencies that form the basis for prescribing, regardlessof professional background. The competencies have beendeveloped to help healthcare professionals be safe andeffective prescribers with the aim of supporting patients toget the best outcomes from their medicines. It is available atwww.rpharms.com/resources/frameworks/prescribers-competency-framework.

The presence of two or more long-term health conditions ina child (multimorbidity) is generally associated with reducedquality of life, higher mortality, higher rates of adverse drugreactions, greater use of the health service, and a highertreatment burden (due to polypharmacy or multipleappointments).<small>g</small>Treatment decisions should involveconsideration of the child’s needs, preferences fortreatment, health priorities, and lifestyle with the aim ofimproving quality of life by reducing treatment burden,adverse events, and unplanned or uncoordinated care. Allclinicians involved (including primary and secondary care)should work together to minimise the risk of harm. The useof a care plan within a multidisciplinary team with anidentified clinical lead, is recommended.

Prescribers should consider the risks and benefits oftreatments recommended in guidance for single healthconditions, when applied to children with multimorbidity;evidence for these recommendations is commonly drawnfrom children without multimorbidity or who are takingfewer prescribed regular medicines.

Treatments intended to relieve symptoms should bereviewed for clinical response, including reducing orstopping treatment that is no longer effective or necessary.Alternatively, non-pharmacological treatments may beoffered or treatments of limited benefit can be considered fordiscontinuation.l

Transitional services for chronic conditions

The process of moving from paediatric to adult services canlead to a loss of continuity in care and provoke anxiety inchildren and their carers.<small>g</small>Practitioners should startplanning for adult care when the child reaches the age of13or14at the latest and a child-centred approach should betaken. Consider designating a named practitioner amongthose providing care to the child to take a coordinating roleand to act as an advocate for the child, maintaining a linkbetween the various practitioners involved in care (includinga named GP).h

<small>g</small>Discontinuing or reducing the dose of medicines, undersupervision, should be considered regularly to improveoutcomes and reduce burden. Deprescribing should beundertaken as part of routine clinical care involving carefulcounselling alongside shared decision-making with the childand their carers.l

Taking medicines to best effect

Difficulties in adherence to drug treatment occur regardlessof age. Factors that contribute to poor compliance withprescribed medicines include:

. difficulty in taking the medicine (e.g. inability to swallowthe medicine);

. unattractive formulation (e.g. unpleasant taste);. prescription not collected or not dispensed;. purpose of medicine not clear;

. perceived lack of efficacy;. real or perceived adverse effects;

. carers’ or child’s perception of the risk and severity ofside-effects may differ from that of the prescriber;. instructions for administration not clear.The prescriber, the child’s carer, and the child (ifappropriate) should agree on the health outcomes desiredand on the strategy for achieving them (‘concordance’). Theprescriber should be sensitive to religious, cultural, andpersonal beliefs of the child’s family that can affectacceptance of medicines.

Taking the time to explain to the child (and carers) therationale and the potential adverse effects of treatment mayimprove adherence. Reinforcement and elaboration of thephysician’s instructions by the pharmacist and othermembers of the healthcare team can be important. Givingadvice on the management of adverse effects and thepossibility of alternative treatments may encourage carersand children to seek advice rather than merely abandonunacceptable treatment.

Simplifying the drug regimen may help; the need forfrequent administration may reduce adherence, althoughthere appears to be little difference in adherence betweenonce-daily and twice-daily administration. Combinationproducts reduce the number of drugs taken but at theexpense of the ability to titrate individual doses.

Advanced Pharmacy Services

Advanced Services are provided as part of the NHSCommunity Pharmacy Contractual Framework, and includeservices such as the New Medicines Service and MedicinesUse Review service. These services are provided byaccredited community pharmacists, with the aim of targetingspecific children to help manage their medicines moreeffectively, improve adherence, and reduce medicineswastage.

New Medicines ServiceThe New Medicines Service (NMS)provides education and support to children who are newlyprescribed a medicine to manage a long-term condition. Theservice is split into three stages; patient engagement,intervention and follow-up. As of2018, this service isavailable for children living in England who have either beenprescribed a new medicine for one of the followingconditions– asthma, type2diabetes, or hypertension, orhave been prescribed a new antiplatelet or anticoagulant.Children can be offered the service by prescriber referral, oropportunistically by the community pharmacy. For furtherinformation, see:psnc.org.uk/services-commissioning/

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Medicines Use ReviewThe Medicines Use Review (MUR)service consists of structured adherence-centred reviewswith children on multiple medicines, particularly thosereceiving medicines for long-term conditions. The service isundertaken periodically, or when there is a need to make anadherence-focused intervention due to a problem identifiedwhile providing the dispensing service.

The pharmacist providing the service is required to ensurethat at least70% of all MURs undertaken in a year are forchildren who fall into one or more of the national targetgroups. The national target groups for MURs in England are:

. children taking high-risk medicines (NSAIDs,anticoagulants (including low molecular weightheparin), antiplatelets, or diuretics);

. children recently discharged from hospital who have hadchanges made to their medicines;

. children prescribed certain respiratory medicines;. children with, or at risk of cardiovascular disease, and

are regularly prescribed at least four medicines.For further information, see:psnc.org.uk/services-commissioning/advanced-services/murs/.

Wales, Northern Ireland, and Scotland have variations onthis service, including different national target groups.In Wales, seewww.cpwales.org.uk/Contract-support-and-IT/Advanced-Services/Medicines-Use-review-MUR.aspxIn Northern Ireland, seewww.hscbusiness.hscni.net/services/2427.htm.

In Scotland, seecare-services/services/chronic-medication-service/.

www.communitypharmacyscotland.org.uk/nhs-Drug treatment in children

Children, and particularly neonates, differ from adults intheir response to drugs. Special care is needed in theneonatal period (first28days of life) and doses should alwaysbe calculated with care; the risk of toxicity is increased by areduced rate of drug clearance and differing target organsensitivity. The terms infant, child and adolescent are usedinconsistently in the literature. However, for referencepurposes only, the terms generally used to describe thepaediatric stages of development are:

Preterm neonate Born at<37weeks gestationTerm neonate Born at37to42weeks gestationPost-term neonate Born at42weeks gestationNeonate From0up to28days of age (or first

4weeks of life)

Infant From28days up to24months of ageChild From2years up to12years of ageAdolescent From12years up to18years of ageInBNF for Children, the term neonate is used to describe anewborn infant aged0–28days. The terms child or childrenare used generically to describe the entire range from infantto adolescent (1month–17years). An age range is specifiedwhen the dose information applies to a narrower age rangethan a child from1month–17years.

Administration of medicines to children

Children should be involved in decisions about takingmedicines and encouraged to take responsibility for usingthem correctly. The degree of such involvement will dependon the child’s age, understanding, and personal

Occasionally a medicine or its taste has to be disguised ormasked with small quantities of food. However, unlessspecifically permitted (e.g. some formulations of pancreatinp.74), a medicine should not be mixed with large quantitiesof food because the full dose might not be taken and thechild might develop an aversion to food if the medicine

imparts an unpleasant taste. Medicines should not be mixedor administered in a baby’s feeding bottle.

Children under5years (and some older children)find aliquid formulation more acceptable than tablets or capsules.However, for long-term treatment it may be possible for achild to be taught to take tablets or capsules.

An oral syringe should be used for accurate measurementand controlled administration of an oral liquid medicine. Theunpleasant taste of an oral liquid can be disguised byflavouring it or by giving a favourite food or drinkimmediately afterwards, but the potential for food-druginteractions should be considered.

Advice should be given on dental hygiene to those receivingmedicines containing cariogenic sugars for long-termtreatment; sugar-free medicines should be providedwhenever possible.

Children with nasal feeding tubes in place for prolongedperiods should be encouraged to take medicines by mouth ifpossible; enteric feeding should generally be interruptedbefore the medicine is given (particularly if enteral feedsreduce the absorption of a particular drug). Oral liquids canbe given through the tube provided that precautions aretaken to guard against blockage; the dose should be washeddown with warm water. When a medicine is given through anasogastric tube to a neonate, sterile water must be used toaccompany the medicine or to wash it down.

The intravenous route is generally chosen when a medicinecannot be given by mouth; reliable access, often a centralvein, should be used for children whose treatment involvesirritant or inotropic drugs or who need to receive themedicine over a long period or for home therapy. Thesubcutaneous route is used most commonly for insulinadministration. Intramuscular injections should preferablybe avoided in children, particularly neonates, infants, andyoung children. However, the intramuscular route may beadvantageous for administration of single doses ofmedicines when intravenous cannulation would be moreproblematic or painful to the child. Certain drugs, e.g. somevaccines, are only administered intramuscularly.The intrathecal, epidural and intraosseous routes should beused only by staff specially trained to administer medicinesby these routes. Local protocols for the management ofintrathecal injections must be in place.

Managing medicines in school

Administration of a medicine during schooltime should beavoided if possible; medicines should be prescribed for onceor twice-daily administration whenever practicable. If themedicine needs to be taken in school, this should bediscussed with parents or carers and the necessaryarrangements made in advance; where appropriate,involvement of a school nurse should be sought.ManagingMedicines in Schools and Early Years Settings produced by theDepartment of Health provides guidance on using medicinesin schools (www.dh.gov.uk).

Patient information leaflets

Manufacturers’ patient information leaflets that accompanya medicine, cover only the licensed use of the medicine.Therefore, when a medicine is used outside its licence, itmay be appropriate to advise the child and the child’s parentor carer that some of the information in the leaflet might notapply to the child’s treatment. Where necessary,

inappropriate advice in the patient information leafletshould be identified and reassurance provided about thecorrect use in the context of the child’s condition.

Biological medicines

Biological medicines are medicines that are made by orderived from a biological source using biotechnologyprocesses, such as recombinant DNA technology. The sizeand complexity of biological medicines, as well as the way

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they are produced, may result in a degree of naturalvariability in molecules of the same active substance,particularly in different batches of the medicine. Thisvariation is maintained within strict acceptable limits.Examples of biological medicines include insulins andmonoclonal antibodies.<small>g</small>Biological medicines must beprescribed by brand name and the brand name specified onthe prescription should be dispensed in order to avoidinadvertent switching. Automatic substitution of brands atthe point of dispensing is not appropriate for biologicalmedicines.h

Biosimilar medicines

A biosimilar medicine is a biological medicine that is highlysimilar and clinically equivalent (in terms of quality, safety,and efficacy) to an existing biological medicine that hasalready been authorised in the European Union (known asthe reference biological medicine or originator medicine).The active substance of a biosimilar medicine is similar, butnot identical, to the originator biological medicine. Once thepatent for a biological medicine has expired, a biosimilarmedicine may be authorised by the European MedicinesAgency (EMA). A biosimilar medicine is not the same as ageneric medicine, which contains a simpler molecularstructure that is identical to the originator medicine.Therapeutic equivalence<small>g</small>Biosimilar medicines shouldbe considered to be therapeutically equivalent to theoriginator biological medicine within their authorisedindications.hBiosimilar medicines are usually licensed forall the indications of the originator biological medicine, butthis depends on the evidence submitted to the EMA forauthorisation and must be scientifically justified on the basisof demonstrated or extrapolated equivalence.

Prescribing and dispensingThe choice of whether toprescribe a biosimilar medicine or the originator biologicalmedicine rests with the clinician in consultation with thepatient.<small>g</small>Biological medicines (including biosimilarmedicines) must be prescribed by brand name and the brandname specified on the prescription should be dispensed inorder to avoid inadvertent switching. Automatic substitutionof brands at the point of dispensing is not appropriate forbiological medicines.h

Safety monitoringBiosimilar medicines are subject to ablack triangle status (<small>A</small>) at the time of initial authorisation.<small>g</small>It is important to report suspected adverse reactionsusing the Yellow Card Scheme (see Adverse reactions todrugs p.14). For all biological medicines, adverse reactionreports should clearly state the brand name and the batchnumber of the suspected medicine.h

UK Medicines Information centres have developed avalidated tool to determine potential safety issues associatedwith all new medicines. These’in-use product safetyassessment reports’ will be published for new biosimilarmedicines as they become available, seewww.sps.nhs.uk/home/medicines/.

National funding/access decisionsThe Department ofHealth has confirmed that, in England, NICE can decide toapply the same remit, and the resulting technology appraisalguidance, to relevant biosimilar medicines which appear onthe market subsequent to their originator biologicalmedicine. In other circumstances, where a review of theevidence for a particular biosimilar medicine is necessary,NICE will consider producing an evidence summary (seeEvidence summary: new medicines,www.nice.org.uk/about/what-we-do/our-programmes/nice-advice/evidence-summaries-new-medicines).

National informationIn England, seewww.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/biosimilars-statement.pdf.

In Northern Ireland, seeniformulary.hscni.net/ManagedEntry/bios/Pages/default.aspx.

In Scotland, seewww.scottishmedicines.org.uk/About_SMC/Policy_statements/Biosimilar_Medicines.

In Wales, seewww.wales.nhs.uk/sites3/Documents/814/BIOSIMILARS-ABUHBpositionStatement%5BNov2015%5D.pdf.AvailabilityThe following drugs are available as a biosimilarmedicine:

. Adalimumab p.665. Enoxaparin sodium p.96. Epoetin alfa p.586. Epoetin zeta p.588. Etanercept p.667. Filgrastim p.599. Infliximab p.35. Insulin glargine p.476. Insulin lispro p.473. Rituximab p.550. Somatropin p.492

Complementary and alternative medicine

An increasing amount of information on complementary andalternative medicine is becoming available. Whereappropriate, the child and the child’s carers should be askedabout the use of their medicines, including dietarysupplements and topical products. The scope ofBNF forChildren is restricted to the discussion of conventionalmedicines but reference is made to complementarytreatments if they affect conventional therapy (e.g.interactions with St John’s wort). Further information onherbal medicines is available atwww.mhra.gov.uk.

BNF for Children and marketing authorisation

Where appropriate thedoses, indications, cautions, contra-indications, and side-effects in BNF for Children reflect thosein the manufacturers’ Summaries of Product Characteristics(SPCs) which, in turn, reflect those in the correspondingmarketing authorisations (formerly known as ProductLicences).BNF for Children does not generally includeproprietary medicines that are not supported by a validSummary of Product Characteristics or when the marketingauthorisation holder has not been able to supply essentialinformation. When a preparation is available from more thanone manufacturer,BNF for Children reflects advice that is themost clinically relevant regardless of any variation in themarketing authorisation. Unlicensed products can beobtained from‘special-order’ manufacturers or specialistimporting companies.

As far as possible, medicines should be prescribed within theterms of the marketing authorisation. However, manychildren require medicines not specifically licensed forpaediatric use. Although medicines cannot be promotedoutside the limits of the licence, the Human MedicinesRegulations2012do not prohibit the use of unlicensedmedicines.

BNF for Children includes advice involving the use ofunlicensed medicines or of licensed medicines for unlicenseduses (‘off-label’ use). Such advice reflects careful

consideration of the options available to manage a givencondition and the weight of evidence and experience of theunlicensed intervention. Where the advice falls outside adrug’s marketing authorisation, BNF for Children shows thelicensing status in the drug monograph. However,limitations of the marketing authorisation should notpreclude unlicensed use where clinically appropriate.Prescribing unlicensed medicines Prescribing unlicensedmedicines or medicines outside the recommendations oftheir marketing authorisation alters (and probably increases)the prescriber’s professional responsibility and potentialliability. The prescriber should be able to justify and feelcompetent in using such medicines, and also inform the

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patient or the patient’s carer that the prescribed medicine isunlicensed.

Drugs and skilled tasks

Prescribers and other healthcare professionals should advisechildren and their carers if treatment is likely to affect theirability to perform skilled tasks (e.g. driving). This appliesespecially to drugs with sedative effects; patients should bewarned that these effects are increased by alcohol. Generalinformation about a patient’s fitness to drive is availablefrom the Driver and Vehicle Licensing Agency atwww.dvla.gov.uk.

A new offence of driving, attempting to drive, or being incharge of a vehicle, with certain specified controlled drugs inexcess of specified limits, came into force on2nd March2015. This offence is an addition to the existing rules on drugimpaired driving andfitness to drive, and applies to twogroups of drugs—commonly abused drugs, includingamfetamines, cannabis, cocaine, and ketamine p.846, anddrugs used mainly for medical reasons, such as opioids andbenzodiazepines. Anyone found to have any of the drugs(including related drugs, for example, apomorphinehydrochloride) above specified limits in their blood will beguilty of an offence, whether their driving was impaired ornot. This also includes prescribed drugs which metabolise tothose included in the offence, for example, selegilinehydrochloride. However, the legislation provides a statutory“medical defence” for patients taking drugs for medicalreasons in accordance with instructions,if their driving wasnot impaired—it continues to be an offence to drive ifactually impaired. Patients should therefore be advised tocontinue taking their medicines as prescribed, and whendriving, to carry suitable evidence that the drug wasprescribed, or sold, to treat a medical or dental problem, andthat it was taken according to the instructions given by theprescriber, or information provided with the medicine (e.g. arepeat prescription form or the medicine’s patientinformation leaflet). Further information is available fromthe Department for Transport atwww.gov.uk/government/collections/drug-driving.

Oral syringes

An oral syringe is supplied when oral liquid medicines areprescribed in doses other than multiples of5mL. The oralsyringe is marked in0.5-mL divisions from1to5mL tomeasure doses of less than5mL (other sizes of oral syringemay also be available). It is provided with an adaptor and aninstruction leaflet. The5-mL spoon is used for doses of5mL(or multiples thereof).

Branded oral liquid preparations that do not containfructose,glucose, or sucrose are described as ‘sugar-free’ in BNF forChildren. Preparations containing hydrogenated glucosesyrup, mannitol, maltitol, sorbitol, or xylitol are also marked‘sugar-free’ since they do not cause dental caries. Childrenreceiving medicines containing cariogenic sugars, or theircarers, should be advised of dental hygiene measures toprevent caries. Sugar-free preparations should be usedwhenever possible, particularly if treatment is required for along period.

Where information on the presence ofalcohol, aspartame,gluten, sulfites, tartrazine, arachis (peanut) oil or sesame oil isavailable, this is indicated inBNF for Children against therelevant preparation.

Information is provided onselected excipients in skinpreparations, in vaccines, and onselected preservatives andexcipients in eye drops and injections.

The presence ofbenzyl alcohol and polyoxyl castor oil(polyethoxylated castor oil) in injections is indicated inBNFfor Children. Benzyl alcohol has been associated with a fataltoxic syndrome in preterm neonates, and therefore,

parenteral preparations containing the preservative shouldnot be used in neonates. Polyoxyl castor oils, used asvehicles in intravenous injections, have been associated withsevere anaphylactoid reactions.

The presence ofpropylene glycol in oral or parenteralmedicines is indicated inBNF for Children; it can causeadverse effects if its elimination is impaired, e.g. in renalfailure, in neonates and young children, and in slowmetabolisers of the substance. It may interact withmetronidazole p.344.

Thelactose content in most medicines is too small to causeproblems in most lactose-intolerant children. However insevere lactose intolerance, the lactose content should bedetermined before prescribing. The amount of lactose variesaccording to manufacturer, product, formulation, andstrength.

ImportantIn the absence of information on excipients inBNF for Children and in the product literature (available atwww.medicines.org.uk/emc/), contact the manufacturer if it isessential to check details.

Health and safety

When handling chemical or biological materials particularattention should be given to the possibility of allergy,fire,explosion, radiation, or poisoning. Care is required to avoidsources of heat (including hair dryers) whenflammablesubstances are used on the skin or hair. Substances, such ascorticosteroids, some antimicrobials, phenothiazines, andmany cytotoxics, are irritant or very potent and should behandled with caution; contact with the skin and inhalationof dust should be avoided. Healthcare professionals andcarers should guard against exposure to sensitising, toxic orirritant substances if it is necessary to crush tablets or opencapsules.

EEA and Swiss prescriptions

Pharmacists can dispense prescriptions issued by doctorsand dentists from the European Economic Area (EEA) orSwitzerland (except prescriptions for controlled drugs inSchedules1,2, or3, or for drugs without a UK marketingauthorisation). Prescriptions should be written in ink orotherwise so as to be indelible, should be dated, should statethe name of the patient, should state the address of theprescriber, should contain particulars indicating whether theprescriber is a doctor or dentist, and should be signed by theprescriber.

Security and validity of prescriptions

The Councils of the British Medical Association and theRoyal Pharmaceutical Society have issued a joint statementon the security and validity of prescriptions.

In particular, prescription forms should:. not be left unattended at reception desks;. not be left in a car where they may be visible;. when not in use, be kept in a locked drawer within the

surgery and at home.

Where there is any doubt about the authenticity of aprescription, the pharmacist should contact the prescriber. Ifthis is done by telephone, the number should be obtainedfrom the directory rather than relying on the information onthe prescription form, which may be false.

Patient group direction (PGD)

In most cases, the most appropriate clinical care will beprovided on an individual basis by a prescriber to a specificchild. However, a Patient Group Direction for supply andadministration of medicines by other healthcareprofessionals can be used where it would benefit the child’scare without compromising safety.

A Patient Group Direction is a written direction relating tothe supply and administration (or administration only) of a

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Controlled Drugs in specific circumstances) by certainclasses of healthcare professionals; the Direction is signed bya doctor (or dentist) and by a pharmacist. Further

information on Patient Group Directions is available inHealth Service Circular HSC2000/026(England), HDL (2001)7(Scotland), and WHC (2000)116(Wales); see also theHuman Medicines Regulations2012.

NICE, Scottish Medicines Consortium and AllWales Medicines Strategy Group

Advice issued by the National Institute for Health and CareExcellence (NICE), the Scottish Medicines Consortium (SMC)and the All Wales Medicines Strategy Group (AWMSG) isincluded inBNF for Children when relevant. Details of theadvice together with updates can be obtained from:www.nice.org.uk,www.scottishmedicines.org.ukandwww.awmsg.org.

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Prescription writing

Shared care

In its guidelines on responsibility for prescribing (circular EL(91)127) between hospitals and general practitioners, theDepartment of Health has advised that legal responsibilityfor prescribing lies with the doctor who signs theprescription.

Prescriptions should be written legibly in ink or otherwise soas to be indelible (it is permissible to issue carbon copies ofNHS prescriptions as long as they are signed in ink), shouldbe dated, should state the name and address of the patient,the address of the prescriber, an indication of the type ofprescriber, and should be signed in ink by the prescriber(computer-generated facsimile signatures do not meet thelegal requirement). The age and the date of birth of thepatient should preferably be stated, and it is a legalrequirement in the case of prescription-only medicines tostate the age for children under12years. Theserecommendations are acceptable for prescription-onlymedicines. Prescriptions for controlled drugs haveadditional legal requirements.

Wherever appropriate the prescriber should state the currentweight of the child to enable the dose prescribed to bechecked. Consideration should also be given to including thedose per unit mass e.g. mg/kg or the dose per m²body-surface area e.g. mg /m²where this would reduce error.The following should be noted:

. The strength or quantity to be contained in capsules,lozenges, tablets etc. should be stated by the prescriber.In particular, strength of liquid preparations should beclearly stated (e.g.125mg/5mL).

. The unnecessary use of decimal points should beavoided, e.g.3mg, not3.0mg. Quantities of1gram ormore should be written as1g etc. Quantities less than1gram should be written in milligrams, e.g.500mg, not0.5g. Quantities less than1mg should be written inmicrograms, e.g.100micrograms, not0.1mg. Whendecimals are unavoidable a zero should be written infront of the decimal point where there is no otherfigure,e.g.0.5mL, not.5mL. Use of the decimal point isacceptable to express a range, e.g.0.5to1g.. ‘Micrograms’ and ‘nanograms’ should not be

abbreviated. Similarly‘units’ should not be abbreviated.. The term ‘millilitre’ (ml or mL) is used in medicine and

pharmacy, and cubic centimetre, c.c., or cm³should notbe used. (The use of capital‘L’ in mL is a printingconvention throughout the BNF; both‘mL’ and ‘ml’ arerecognised SI abbreviations).

. Dose and dose frequency should be stated; in the case ofpreparations to be taken‘as required’ a minimum doseinterval should be specified. Care should be taken toensure children receive the correct dose of the activedrug. Therefore, the dose should normally be stated interms of the mass of the active drug (e.g.‘125mg3timesdaily’); terms such as ‘5mL’ or ‘1tablet’ should beavoided except for compound preparations. When dosesother than multiples of5mL are prescribed fororal liquidpreparations the dose-volume will be provided by meansof an oral syringe, (except for preparations intended tobe measured with a pipette). Suitable quantities:. Elixirs, Linctuses, and Paediatric Mixtures (5-mL

clearly and not abbreviated, using approved titles only;

avoid creating generic titles for modified-releasepreparations.

. The quantity to be supplied may be stated by indicatingthe number of days of treatment required in the boxprovided on NHS forms. In most cases the exact amountwill be supplied. This does not apply to items directed tobe used as required—if the dose and frequency are notgiven then the quantity to be supplied needs to bestated. When several items are ordered on one form thebox can be marked with the number of days of treatmentprovided the quantity is added for any item for which theamount cannot be calculated.

. Although directions should preferably be in Englishwithout abbreviation, it is recognised that some Latinabbreviations are used.

Sample prescription

Abbreviation of titlesIn general, titles of drugs andpreparations should be writtenin full. Unofficialabbreviations should not be used as they may bemisinterpreted.

Non-proprietary titlesWhere non-proprietary (‘generic’)titles are given, they should be used for prescribing. This willenable any suitable product to be dispensed, thereby savingdelay to the patient and sometimes expense to the healthservice. The only exception is where there is a demonstrabledifference in clinical effect between each manufacturer’sversion of the formulation, making it important that thechild should always receive the same brand; in such cases,the brand name or the manufacturer should be stated.Non-proprietary names of compound preparationsNon-proprietary names of compound preparations whichappear inBNF for Children are those that have been compiled

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by the British Pharmacopoeia Commission or anotherrecognised body; whenever possible they reflect the namesof the active ingredients. Prescribers should avoid creatingtheir own compound names for the purposes of genericprescribing; such names do not have an approved definitionand can be misinterpreted.

Special care should be taken to avoid errors when prescribingcompound preparations; in particular the hyphen in theprefix ‘co-’ should be retained. Special care should also betaken to avoid creating generic names for modified-releasepreparations where the use of these names could lead toconfusion between formulations with different duration ofaction.

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Supply of medicines

When supplying a medicine for a child, the pharmacistshould ensure that the child and the child’s carer understandthe nature and identity of the medicine and how it should beused. The child and the carer should be provided withappropriate information (e.g. how long the medicine shouldbe taken for and what to do if a dose is missed or the childvomits soon after the dose is given).

Safety in the home

Carers and relatives of children must be warned to keep allmedicines out of the reach and sight of children. Tablets,capsules and oral and external liquid preparations must bedispensed in a reclosablechild-resistant container unless:

. the medicine is in an original pack or patient pack suchas to make this inadvisable;

. the child’s carer will have difficulty in opening a resistant container;

child-. a specific request is made that the product shall not bedispensed in a child-resistant container;

. no suitable child-resistant container exists for aparticular liquid preparation.

All patients should be advised to dispose ofunwantedmedicines by returning them to a pharmacy for destruction.

Labelling of prescribed medicines

There is a legal requirement for the following to appear onthe label of any prescribed medicine:

. name of the patient;

. name and address of the supplying pharmacy;. date of dispensing;

. name of the medicine;. directions for use of the medicine;

. precautions relating to the use of the medicine.The Royal Pharmaceutical Society recommends that thefollowing also appears on the label:

. the words ‘Keep out of the sight and reach of children’;. where applicable, the words ‘Use this medicine only on

your skin’.

A pharmacist can exercise professional skill and judgementto amend or include more appropriate wording for the nameof the medicine, the directions for use, or the precautionsrelating to the use of the medicine.

Unlicensed medicines

A drug or formulation that is not covered by a marketingauthorisation may be obtained from a pharmaceuticalcompany, imported by a specialist importer, manufacturedby a commercial or hospital licensed manufacturing unit, orprepared extemporaneously against a prescription.The safeguards that apply to products with marketingauthorisation should be extended, as far as possible, to theuse of unlicensed medicines. The safety, efficacy, and quality(including labelling) of unlicensed medicines should beassured by means of clear policies on their prescribing,purchase, supply, and administration. Extra care is requiredwith unlicensed medicines because less information may beavailable on the drug and any formulation of the drug.The following should be agreed with the supplier whenordering an unlicensed or extemporaneously preparedmedicine:

. the specification 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 licensinginformation should be supplied in English.

Extemporaneous preparations

A product should be dispensed extemporaneously only whenno product with a marketing authorisation is available. Everyeffort should be made to ensure that an extemporaneouslyprepared product is stable and that it delivers the requisitedose reliably; the child should be provided with a consistentformulation regardless of where the medicine is supplied tominimise variations in quality. Where there is doubt aboutthe formulation, advice should be sought from a medicinesinformation centre, the pharmacy at a children’s hospital, ahospital production unit, a hospital quality controldepartment, or the manufacturer.

In many cases it is preferable to give a licensed product by anunlicensed route (e.g. an injection solution given by mouth)than to prepare a special formulation. When tablets orcapsules are cut, dispersed, or used for preparing liquidsimmediately before administration, it is important toconfirm uniform dispersal of the active ingredient, especiallyif only a portion of the solid content (e.g. a tablet segment) isused or if only an aliquot of the liquid is to be administered.In some cases the child’s clinical condition may require adose to be administered in the absence of full information onthe method of administration. It is important to ensure thatthe appropriate supporting information is available at theearliest opportunity.

Preparation of products that produce harmful dust (e.g.cytotoxic drugs, hormones, or potentially sensitising drugssuch as neomycin sulfate p.714) should be avoided orundertaken with appropriate precautions to protect staff andcarers.

The BP direction that a preparation must befreshly preparedindicates that it must be made not more than24hours beforeit is issued for use. The direction that a preparation shouldberecently prepared indicates that deterioration is likely ifthe preparation is stored for longer than about4weeks at15–25°C.

The term water used without qualification means eitherpotable water freshly drawn direct from the public supplyand suitable for drinking or freshly boiled and cooledpurified water. The latter should be used if the public supplyis from a local storage tank or if the potable water isunsuitable for a particular preparation.

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Emergency supply of medicines

Emergency supply requested by member of thepublic

Pharmacists are sometimes called upon by members of thepublic to make an emergency supply of medicines. TheHuman Medicines Regulations2012allows exemptions fromthe Prescription Only requirements for emergency supply tobe made by a person lawfully conducting a retail pharmacybusiness provided:

a) that the pharmacist has interviewed the personrequesting the prescription-only medicine and issatisfied:

i) that there is immediate need for the only medicine and that it is impracticable in thecircumstances to obtain a prescription withoutundue delay;

prescription-ii) that treatment with the prescription-only medicinehas on a previous occasion been prescribed for theperson requesting it;

iii) as to the dose that it would be appropriate for theperson to take;

b) that no greater quantity shall be supplied than willprovide 5 days’ treatment of phenobarbital p. 223,phenobarbital sodium, or Controlled Drugs in Schedules4 or 5 (doctors or dentists from the European EconomicArea and Switzerland, or their patients, cannot requestan emergency supply of Controlled Drugs in Schedules1, 2, or 3, or drugs that do not have a UK marketingauthorisation) or 30 days’ treatment for otherprescription-only medicines, except when theprescription-only medicine is:

i) insulin, an ointment or cream, or a preparation forthe relief of asthma in an aerosol dispenser whenthe smallest pack can be supplied;

ii) an oral contraceptive when a full cycle may besupplied;

iii) an antibiotic in liquid form for oral administrationwhen the smallest quantity that will provide a fullcourse of treatment can be supplied;

c) that an entry shall be made by the pharmacist in theprescription book stating:

i) the date of supply;

ii) the name, quantity and, where appropriate, thepharmaceutical form and strength;

iii) the name and address of the patient;iv) the nature of the emergency;

d) that the container or package must be labelled to show:i) the date of supply;

ii) the name, quantity and, where appropriate, thepharmaceutical form and strength;

iii) the name of the patient;

iv) the name and address of the pharmacy;v) the words‘Emergency supply’;

vi) the words‘Keep out of the reach of children’ (orsimilar warning);

e) that the prescription-only medicine is not a substancespecifically excluded from the emergency supplyprovision, and does not contain a Controlled Drugspecified in Schedules 1, 2, or 3 to the Misuse of DrugsRegulations 2001 except for phenobarbital p. 223 orphenobarbital sodium for the treatment of epilepsy: fordetails seeMedicines, Ethics and Practice, London,Pharmaceutical Press (always consult latest edition).Doctors or dentists from the European Economic Areaand Switzerland, or their patients, cannot request anemergency supply of Controlled Drugs in Schedules 1,2, or 3, or drugs that do not have a UK marketingauthorisation.

Emergency supply requested by prescriber

Emergency supply of a prescription-only medicine may alsobe made at the request of a doctor, a dentist, a

supplementary prescriber, a community practitioner nurseprescriber, a nurse, pharmacist, or optometrist independentprescriber, or a doctor or dentist from the EuropeanEconomic Area or Switzerland, provided:

a) that the pharmacist is satisfied that the prescriber byreason of some emergency is unable to furnish aprescription immediately;

b) that the prescriber has undertaken to furnish aprescription within 72 hours;

c) that the medicine is supplied in accordance with thedirections of the prescriber requesting it;

d) that the medicine is not a Controlled Drug specified inSchedules 1, 2, or 3 to the Misuse of Drugs Regulations2001 except for phenobarbital p. 223 orphenobarbitalsodium for the treatment of epilepsy: for details seeMedicines, Ethics and Practice, London, PharmaceuticalPress (always consult latest edition); (Doctors ordentists from the European Economic Area andSwitzerland, or their patients, cannot request anemergency supply of Controlled Drugs in Schedules 1,2, or 3, or drugs that do not have a UK marketingauthorisation).

e) that an entry shall be made in the prescription bookstating:

i) the date of supply;

ii) the name, quantity and, where appropriate, thepharmaceutical form and strength;

iii) the name and address of the practitioner requestingthe emergency supply;

iv) the name and address of the patient;v) the date on the prescription;

vi) when the prescription is received the entry shouldbe amended to include the date on which it isreceived.

Royal Pharmaceutical Society’s guidelines

1. The pharmacist should consider the medical

consequences of not supplying a medicine in anemergency.

2. If the pharmacist is unable to make an emergencysupply of a medicine the pharmacist should advise thepatient how to obtain essential medical care.For conditions that apply to supplies made at the request of apatient see Medicines, Ethics and Practice, LondonPharmaceutical Press, (always consult latest edition).

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Controlled drugs and drug dependence

Regulations and classification

The Misuse of Drugs Act,1971as amended prohibits certainactivities in relation to‘Controlled Drugs’, in particular theirmanufacture, supply, and possession (except wherepermitted by the2001Regulations or under licence from theSecretary of State). The penalties applicable to offencesinvolving the different drugs are graded broadly according totheharmfulness attributable to a drug when it is misused andfor this purpose the drugs are defined in the following threeclasses:

. Class A includes: alfentanil p.845, cocaine,diamorphine hydrochloride p.284(heroin), dipipanonehydrochloride, fentanyl p.286, lysergide (LSD),methadone hydrochloride p.307,

3,4-methylenedioxymethamfetamine (MDMA,‘ecstasy’), morphine p.290, opium, oxycodonehydrochloride p.292, pethidine hydrochloride p.295,phencyclidine, remifentanil p.845, and class Bsubstances when prepared for injection.. Class B includes: oral amfetamines, barbiturates,

cannabis,Sativex<small>®</small>, codeine phosphate p.283,dihydrocodeine tartrate p.285, ethylmorphine,glutethimide, ketamine p.846, nabilone p.267,pentazocine, phenmetrazine, and pholcodine p.192.. Class C includes: certain drugs related to the

amfetamines such as benzfetamine and

chlorphentermine, buprenorphine p.281, mazindol,meprobamate, pemoline, pipradrol, mostbenzodiazepines, tramadol hydrochloride p.296,zaleplon, zolpidem tartrate, zopiclone, androgenic andanabolic steroids, clenbuterol, chorionic gonadotrophin(HCG), non-human chorionic gonadotrophin,somatotropin, somatrem, somatropin p.492, gabapentinp.204, and pregabalin.

The Misuse of Drugs (Safe Custody) Regulations1973asamended details the storage and safe custody requirementsfor Controlled Drugs.

The Misuse of Drugs Regulations2001(and subsequentamendments) defines the classes of person who areauthorised to supply and possess Controlled Drugs whileacting in their professional capacities and lays down theconditions under which these activities may be carried out.In the2001regulations, drugs are divided intofiveSchedules, each specifying the requirements governing suchactivities as import, export, production, supply, possession,prescribing, and record keeping which apply to them.

. Schedule1includes drugs not used medicinally such ashallucinogenic drugs (e.g. LSD), ecstasy-typesubstances, raw opium, and cannabis. A Home Officelicence is generally required for their production,possession, or supply. A Controlled Drug register mustbe used to record details of any Schedule1ControlledDrugs received or supplied by a pharmacy.. Schedule2includes opiates (e.g. diamorphine

hydrochloride p.284(heroin), morphine p.290,methadone hydrochloride p.307, oxycodonehydrochloride p.292, pethidine hydrochloride p.295),major stimulants (e.g. amfetamines), quinalbarbitone(secobarbital), cocaine, ketamine p.846, and cannabis-based products for medicinal use in humans. Schedule2Controlled Drugs are subject to the full Controlled Drugrequirements relating to prescriptions, safe custody(except for quinalbarbitone (secobarbital) and someliquid preparations), and the need to keep a ControlledDrug register, (unless exempted in Schedule5).Possession, supply and procurement is authorised forpharmacists and other classes of persons named in the2001Regulations.

. Schedule3includes the barbiturates (exceptsecobarbital, now Schedule2), buprenorphine p.281,gabapentin p.204, mazindol, meprobamate, midazolamp.229, pentazocine, phentermine, pregabalin,temazepam p.847, and tramadol hydrochloride p.296.They are subject to the special prescriptionrequirements. Safe custody requirements do apply,except for any5,5disubstituted barbituric acid (e.g.phenobarbital), gabapentin p.204, mazindol,meprobamate, midazolam p.229, pentazocine,phentermine, pregabalin, tramadol hydrochloridep.296, or any stereoisomeric form or salts of the above.Records in registers do not need to be kept (althoughthere are requirements for the retention of invoices for2years).

. Schedule4includes in Part I drugs that are subject tominimal control, such as benzodiazepines (excepttemazepam p.847and midazolam p.229, which are inSchedule3), non-benzodiazepine hypnotics (zaleplon,zolpidem tartrate, and zopiclone) andSativex<small>®</small>. Part IIincludes androgenic and anabolic steroids, clenbuterol,chorionic gonadotrophin (HCG), non-human chorionicgonadotrophin, somatotropin, somatrem, andsomatropin p.492. Controlled drug prescriptionrequirements do not apply and Schedule4ControlledDrugs are not subject to safe custody requirements.Records in registers do not need to be kept (except in thecase ofSativex<small>®</small>).

. Schedule5includes preparations of certain ControlledDrugs (such as codeine, pholcodine p.192or morphinep.290) which due to their low strength, are exempt fromvirtually all Controlled Drug requirements other thanretention of invoices for two years.Since the ResponsiblePharmacist Regulations were published in2008, standingoperation procedures for the management of ControlledDrugs, are required in registered pharmacies.The Health Act2006introduced the concept of the‘accountable officer’ with responsibility for the managementof Controlled Drugs and related governance issues in theirorganisation. Most recently, in2013The Controlled Drugs(Supervision of Management and Use) Regulations werepublished to ensure good governance concerning the safemanagement and use of Controlled Drugs in England andScotland.

Preparations in Schedules1,2,3,4and5of the Misuse ofDrugs Regulations2001(and subsequent amendments) areidentified throughout the BNF and BNF for children using thefollowing symbols:

(Part I)

(Part II)

The principal legal requirements relating to medicalprescriptions are listed below (see also Department of HealthGuidance atwww.gov.uk/dh).

Prescription requirementsPrescriptions for ControlledDrugs that are subject to prescription requirements (allpreparations in Schedules2and3) must be indelible, mustbesigned by the prescriber, include the date on which they

10Controlled drugs and drug dependence

BNFC2019–2020

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were signed, and specify the prescriber’s address (must bewithin the UK). A machine-written prescription isacceptable, but the prescriber’s signature must behandwritten. Advanced electronic signatures can beaccepted for Schedule2and3Controlled Drugs where theElectronic Prescribing Service (EPS) is used. All prescriptionsfor Controlled Drugs that are subject to the prescriptionrequirements must always state:

. the name and address of the patient (use of a PO Box isnot acceptable);

. in the case of a preparation, the form (the dosage forme.g. tablets must be included on a Controlled Drugsprescription irrespective of whether it is implicit in theproprietary name e.g.MST Continus, or whether onlyone form is available), and, where appropriate, thestrength of the preparation (when more than onestrength of a preparation exists the strength requiredmust be specified); to avoid ambiguity, where aprescription requests multiple strengths of a medicine,each strength should be prescribed separately (i.e.separate dose, total quantity, etc);

. for liquids, the total volume in millilitres (in both wordsandfigures) of the preparation to be supplied; for dosageunits (tablets, capsules, ampoules), state the totalnumber (in both words andfigures) of dosage units to besupplied (e.g.10tablets [of10mg] rather than100mgtotal quantity);

. the dose, which must be clearly defined (i.e. theinstruction‘one as directed’ constitutes a dose but ‘asdirected’ does not); it is not necessary that the dose isstated in both words andfigures;

. the words ‘for dental treatment only’ if issued by adentist.

A pharmacist is not allowed to dispense a Controlled Drugunless all the information required by law is given on theprescription. In the case of a prescription for a ControlledDrug in Schedule2or3, a pharmacist can amend theprescriptionif it specifies the total quantity only in words orinfigures or if it contains minor typographical errors,provided that such amendments are indelible and clearlyattributable to the pharmacist (e.g. name, date, signatureand GPhC registration number). The prescription should bemarked with the date of supply at the time the ControlledDrug supply is made.

The Department of Health and the Scottish Governmenthave issued a strong recommendation that the maximumquantity of Schedule2,3or4Controlled Drugs prescribedshould not exceed30days; exceptionally, to cover ajustifiable clinical need and after consideration of any risk, aprescription can be issued for a longer period, but thereasons for the decision should be recorded on the patient’snotes.

A prescription for a Controlled Drug in Schedules2,3, or4isvalid for28days from the date stated thereon (the prescribermay forward-date the prescription; the start date may alsobe specified in the body of the prescription). Schedule5prescriptions are valid for6months from the appropriatedate.

Medicines that are not Controlled Drugs should not beprescribed on the same form as a Schedule2or3ControlledDrug.

See sample prescription:

Instalments and repeatable prescriptionsPrescriptions forSchedule2or3Controlled Drugs can be dispensed byinstalments. An instalment prescription must have aninstalment direction including both the dose and theinstalment amount specified separately on the prescription,and it must also state the interval between each time themedicine can be supplied.

Thefirst instalment must be dispensed within28days of theappropriate day (i.e. date of signing unless the prescriberindicates a date before which the Controlled Drug should notbe dispensed) and the remainder should be dispensed inaccordance with the instructions on the prescription. Theprescription must be marked with the date of each supply.The instalment direction is a legal requirement and needs tobe complied with, however, for certain situations (e.g. if apharmacy is closed on the day an instalment is due) theHome Office has approved specific wording which providespharmacists someflexibility for supply. For details, seeMedicines, Ethics and Practice, London, PharmaceuticalPress (always consult latest edition) or see Home Officeapproved wording for instalment prescribing (Circular027/2015), available atwww.gov.uk/.

Repeatable prescriptions are prescriptions which contain adirection that they can be dispensed more than once (e.g.repeat63). Only Schedule4and5Controlled Drugs arepermitted on repeatable prescriptions.

Private prescriptionsPrivate prescriptions for ControlledDrugs in Schedules2and3must be written on speciallydesignated forms which are provided by local NHS Englandarea teams in England (form FP10PCD), local NHS HealthBoards in Scotland (form PPCD) and Wales (form W10PCD);in addition, prescriptions must specify theprescriber’sidentification number (or a NHS prescriber code in Scotland).

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Prescriptions to be supplied by a pharmacist in hospital areexempt from the requirements for private prescriptions.

Dependence and misuse

The most common drugs of addiction are crack cocaine andopioids, particularly diamorphine hydrochloride p.284(heroin) . For arrangements for prescribing of diamorphinehydrochloride, dipipanone, or cocaine for addicts, seePrescribing of diamorphine (heroin), dipipanone, and cocainefor addicts below.

Along with traditional stimulants, such as amfetamine andcocaine, there has been an emerging use of

methamphetamine and a range of psychoactive substanceswith stimulant, depressant or hallucinogenic properties suchas lysergide (lysergic acid diethylamide, LSD), ketamine orgamma-hydroxybutyrate (sodium oxybate, GHB).Benzodiazepines and z-drugs (i.e. zopiclone, zolpidemtartrate) have their own potential for misuse and

dependence and are often taken in combination with opiatesor stimulants.

Cannabis-based products for medicinal use are Schedule2Controlled Drugs and can be prescribed only by clinicianslisted on the Specialist Register of the General MedicalCouncil. Cannabis with no approved medicinal use is aSchedule1Controlled Drug and cannot be prescribed. Itremains the most frequently used illicit drug by youngpeople and dependence can develop in around10% of users.Cannabis use can exacerbate depression and it may cause anacute short-lived toxic psychosis which resolves withcessation, however paranoid symptoms may persist inchronic users; withdrawal symptoms can occur in some usersand these can contribute to sleep problems, agitation andrisk of self-harm.

Supervised consumption

Supervised consumption is not a legal requirement under the2001Regulations. Nevertheless, when supervisedconsumption is directed on the prescription, the Departmentof Health recommends that any deviation from theprescriber’s intended method of supply should bedocumented and the justification for this recorded.Individuals prescribed opioid substitution therapy can taketheir daily dose under the supervision of a doctor, nurse, orpharmacist during the dose stabilisation phase (usually thefirst3months of treatment), after a relapse or period ofinstability, or if there is a significant increase in the dose ofmethadone. Supervised consumption should continue (inaccordance with local protocols) until the prescriber isconfident that the patient is compliant with their treatment.It is good practice for pharmacists to alert the prescriberwhen a patient has missed consecutive daily doses.

Prescribing drugs likely to cause dependenceor misuse

The prescriber has three main responsibilities:. To avoid creating dependence by introducing drugs to

patients without sufficient reason. In this context, theproper use of the morphine-like drugs is wellunderstood. The dangers of other Controlled Drugs areless clear because recognition of dependence is not easyand its effects, and those of withdrawal, are less obvious.. To see that the patient does not gradually increase the

dose of a drug, given for good medical reasons, to thepoint where dependence becomes more likely. Thistendency is seen especially with hypnotics andanxiolytics. The prescriber should keep a close eye onthe amount prescribed to prevent patients fromaccumulating stocks. A minimal amount should beprescribed in thefirst instance, or when seeing a patientfor thefirst time.

. To avoid being used as an unwitting source of supply foraddicts and being vigilant to methods for obtaining

medicines. Methods include visiting more than onedoctor, fabricating stories, and forging prescriptions.Patients under temporary care should be given only smallsupplies of drugs unless they present an unequivocal letterfrom their own doctor. Doctors should also remember thattheir own patients may be attempting to collect

prescriptions from other prescribers, especially in hospitals.It is sensible to reduce dosages steadily or to issue weekly oreven daily prescriptions for small amounts if it is apparentthat dependence is occurring.

Prescribers are responsible for the security of prescriptionforms once issued to them. The stealing and misuse ofprescription forms could be minimised by the followingprecautions:

. records of serial numbers received and issued should beretained for at least three years;

. blank prescriptions should never be pre-signed;. prescription forms should not be left unattended and

should be locked in a secure drawer, cupboard, orcarrying case when not in use;

. doctors’, dentists’ and surgery stamps should be kept ina secure location separate from the prescription forms;. alterations are best avoided but if any are made and the

prescription is to be used, best practice is for theprescriber to cross out the error, initial and date theerror, then write the correct information;

. if an error made in a prescription cannot be corrected,best practice for the prescriber is to put a line throughthe script and write‘spoiled’ on the form, or destroy theform and start writing a new prescription;

. prescribers and pharmacists dispensing drugs prone toabuse should ensure compliance with all relevant legalrequirements specially when dealing with prescriptionsfor Controlled Drugs (seePrescription requirements andInstalments above);

. at the time of dispensing, prescriptions should bestamped with the pharmacy stamp and endorsed by thepharmacist or pharmacy technician with what has beensupplied; where loss or theft is suspected, the policeshould be informed immediately.

Travelling abroad

Prescribed drugs listed in Schedule4Part II (CD Anab) forself-administration and Schedule5of the Misuse of DrugsRegulations2001(and subsequent amendments) are notsubject to export or import licensing. A personalimport/export licence is required for patients travellingabroad with Schedules2,3, or4Part I (CD Benz) and Part II(CD Anab) Controlled Drugs if, they are carrying more than3months’ supply or are travelling for3calendar months ormore. A Home Office licence is required for any amount of aSchedule1Controlled Drug imported into the UK forpersonal use regardless of the duration of travel. Furtherdetails can be obtained atwww.gov.uk/guidance/controlled-drugs-licences-fees-and-returnsor from the Home Office bycontacting DFLU.ie@homeoffice.gsi.gov.uk. In cases ofemergency, telephone (020)7035 6330.

Applications for obtaining a licence must be supported by acover letter signed by the prescribing doctor or drug worker,which must confirm:

. the patient’s name and address;. the travel itinerary;

. the names of the prescribed Controlled Drug(s), dosesand total amounts to be carried.

Applications for licences should be sent to the Home Office,Drugs & Firearms Licensing Unit, Fry Building,2MarshamStreet, London, SW1P4DF.

Alternatively, completed application forms can be emailed toDFLU.ie@homeoffice.gsi.gov.uk. A minimum of10daysshould be allowed for processing the application.Patients travelling for less than3months or carrying lessthan3months supply of Controlled Drugs do not require a

12Controlled drugs and drug dependence

BNFC2019–2020

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personal export/import licence, but are advised to carry acover letter signed by the prescribing doctor or drug worker.Those travelling for more than3months are advised to makearrangements to have their medication prescribed by apractitioner in the country they are visiting.

Doctors who want to take Controlled Drugs abroad whileaccompanying patients may similarly be issued withlicences. Licences are not normally issued to doctors whowant to take Controlled Drugs abroad solely in case a familyemergency should arise.

Personal export/import licences do not have any legal statusoutside the UK and are issued only to comply with theMisuse of Drugs Act2001and to facilitate passage throughUK Customs and Excise control. For clearance in the countryto be visited it is necessary to approach that country’sconsulate in the UK.

Notification of patients receiving structureddrug treatment for substance dependence

In England, doctors should report cases where they areproviding structured drug treatment for substancedependence to their local National Drug TreatmentMonitoring System (NDTMS) Team. General informationabout NDTMS can be found atwww.gov.uk/government/collections/alcohol-and-drug-misuse-prevention-and-treatment-guidance.

Enquiries about NDTMS, and how to submit data, shouldinitially be directed to:

In Scotland, doctors should report cases to the SubstanceDrug Misuse Database. General information about theScottish Drug Misuse Database can be found inwww.isdscotland.org/Health-Topics/Drugs-and-Alcohol-Misuse/Drugs-Misuse/Scottish-Drug-Misuse-Database/. Enquiries aboutreporting can be directed to:

In Northern Ireland, the Misuse of Drugs (Notification ofand Supply to Addicts) (Northern Ireland) Regulations1973require doctors to send particulars of persons whom theyconsider to be addicted to certain Controlled Drugs to theChief Medical Officer of the Ministry of Health and SocialServices. The Northern Ireland contact is:

Public Health Information & Research BranchDepartment of Health

Annexe2, Castle Buildings, Stormont, Belfast BT4 3SQ028 9052 2340

Public Health Information & Research Branch alsomaintains the Northern Ireland Drug Misuse Database(NIDMD) which collects detailed information on thosepresenting for treatment, on drugs misused and injectingbehaviour; participation is not a statutory requirement.In Wales, doctors should report cases where they areproviding structured drug treatment for substancedependence on the Welsh National Database for SubstanceMisuse; enquiries should be directed to:

Prescribing of diamorphine (heroin),dipipanone, and cocaine for addicts

The Misuse of Drugs (Supply to Addicts) Regulations1997require that only medical practitioners who hold a speciallicence issued by the Home Secretary (or ScottishGovernment’s Chief Medical Officer) may prescribe,administer, or supply diamorphine hydrochloride p.284,dipipanone, or cocaine forthe treatment of drug addiction.Medical prescribers, pharmacists independent prescribers,nurses independent prescribers and supplementaryprescribers do not require a special licence for prescribingdiamorphine hydrochloride p.284, dipipanone, or cocaine

for patients (including addicts) for relieving pain fromorganic disease or injury.

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Adverse reactions to drugs

Yellow card scheme

Any drug may produce unwanted or unexpected adversereactions. Rapid detection and recording of adverse drugreactions is of vital importance so that unrecognised hazardsare identified promptly and appropriate regulatory action istaken to ensure that medicines are used safely. Healthcareprofessionals and coroners are urged to report suspectedadverse drug reactions directly to the Medicines andHealthcare products Regulatory Agency (MHRA) through theYellow Card Scheme using the electronic form atwww.mhra.gov.uk/yellowcard. Alternatively, prepaid Yellow Cards forreporting are available from the address below and are alsobound in the inside back cover of BNF for Children.Send Yellow Cards to:

FREEPOST YELLOW CARD(No other address details required).Tel:0800 731 6789

Suspected adverse drug reactions to any therapeutic agentshould be reported, including drugs (self-medication as wellas thoseprescribed), blood products, vaccines, radiographiccontrast media, complementary and herbal products. Forbiosimilar medicines and vaccines, adverse reaction reportsshould clearly state the brand name and the batch number ofthe suspected medicine or vaccine.

Suspected adverse drug reactions should be reportedthrough the Yellow Card Scheme atwww.mhra.gov.uk/yellowcard. Yellow Cards can be used for reporting suspectedadverse drug reactions to medicines, vaccines, herbal orcomplementary products, whether self-medicated orprescribed. This includes suspected adverse drug reactionsassociated with misuse, overdose, medication errors or fromuse of unlicensed and off-label medicines. Yellow Cards canalso be used to report medical device incidents, defectivemedicines, and suspected fake medicines.

Report all suspected adverse drug reactions that are:. serious, medically significant or result in harm.

Serious events are fatal, life-threatening, a congenitalabnormality, disabling or incapacitating, or resulting inhospitalisation;

. associated with newer drugs and vaccines; the most upto date list of black triangle medicines is available at:www.mhra.gov.uk/blacktriangle

If in doubt whether to report a suspected adverse drugreaction, please complete a Yellow Card.

The identification and reporting of adverse reactions todrugs in children and neonates is particularly importantbecause:

. the action of the drug and its pharmacokinetics inchildren (especially in the very young) may be differentfrom that in adults;

. drugs may not have been extensively tested in children;. many drugs are not specifically licensed for use in

children and are used either‘off-label’ or as unlicensedproducts;

. drugs may affect the way a child grows and develops ormay cause delayed adverse reactions which do not occurin adults;

. suitable formulations may not be available to allowprecise dosing in children or they may containexcipients that should be used with caution in children;. the nature and course of illnesses and adverse drug

reactions may differ between adults and children.Even if reported through the British Paediatric SurveillanceUnit’s Orange Card Scheme, any identified suspected adversedrug reactions should also be submitted to the Yellow CardScheme.

Spontaneous reporting is particularly valuable forrecognising possible new hazards rapidly. An adverse

reaction should be reported even if it is not certain that thedrug has caused it, or if the reaction is well recognised, or ifother drugs have been given at the same time. Reports ofoverdoses (deliberate or accidental) can complicate theassessment of adverse drug reactions, but provide importantinformation on the potential toxicity of drugs.

A freephone service is available to all parts of the UK foradvice and information on suspected adverse drug reactions;contact the National Yellow Card Information Service at theMHRA on0800 731 6789. Outside office hours a telephone-answering machine will take messages.

The following Yellow Card Centres can be contacted forfurther information:

Yellow Card Centre Northwest

2nd Floor,70Pembroke Place, Liverpool, L69 3GFTel: (0151)794 8122

Yellow Card Centre Wales

All Wales Therapeutics and Toxicology Centre, AcademicBuilding, University Hospital Llandough, Penlan Road,Penarth, Vale of Glamorgan, CF64 2XX

Tel: (029)2074 5831

Yellow Card Centre Northern & Yorkshire

Regional Drug and Therapeutics Centre,16/17FramlingtonPlace, Newcastle upon Tyne, NE2 4AB

Tel: (0191)213 7855

Yellow Card Centre West Midlands

City Hospital, Dudley Road, Birmingham, B18 7QHTel: (0121)507 5672

Yellow Card Centre Scotland

CARDS, Royal Infirmary of Edinburgh,51Little FranceCrescent, Old Dalkeith Road, Edinburgh, EH16 4SATel: (0131)242 2919

The MHRA’s database facilitates the monitoring of adversedrug reactions. More detailed information on reporting and alist of products currently under additional monitoring can befound on the MHRA website:www.mhra.gov.uk.

MHRA Drug Safety UpdateDrug Safety Update is a monthlynewsletter from the MHRA and the Commission on HumanMedicines (CHM); it is available atwww.gov.uk/drug-safety-update.

Patients and their carers can also report suspected adversedrug reactions to the MHRA. Reports can be submitteddirectly to the MHRA through the Yellow Card Scheme usingthe electronic form atwww.mhra.gov.uk/yellowcard, bytelephone on0808 100 3352, or by downloading the YellowCard form fromwww.mhra.gov.uk. Alternatively, patientYellow Cards are available from pharmacies and GPsurgeries. Information for patients about the Yellow CardScheme is available in other languages atwww.mhra.gov.uk/yellowcard.

Prescription-event monitoring

In addition to the MHRA’s Yellow Card Scheme, anindependent scheme monitors the safety of new medicinesusing a different approach. The Drug Safety Research Unitidentifies patients who have been prescribed selected newmedicines and collects data on clinical events in thesepatients. The data are submitted on a voluntary basis bygeneral practitioners on green forms. More informationabout the scheme and the Unit’s educational material isavailable fromwww.dsru.org.

Newer drugs and vaccines

Only limited information is available from clinical trials on

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the safety of medicines depends on the availability ofinformation from routine clinical practice.The black triangle symbol identifies newly licensedmedicines that require additional monitoring by theEuropean Medicines Agency. Such medicines include newactive substances, biosimilar medicines, and medicines thatthe European Medicines Agency consider require additionalmonitoring. The black triangle symbol also appears in thePatient Information Leaflets for relevant medicines, with abrief explanation of what it means. Products usually retain ablack triangle for5years, but this can be extended ifrequired.

Medication errors

Adverse drug reactions where harm occurs as a result of amedication error are reportable as a Yellow Card or throughthe local risk management systems into the NationalReporting and Learning System (NRLS). If reported to theNRLS, these will be shared with the MHRA. If the NRLS is notavailable and harm occurs, report using a Yellow Card.

Adverse reactions to medical devices

Suspected adverse reactions to medical devices includingdental or surgical materials, intra-uterine devices, andcontact lensfluids should be reported. Information onreporting these can be found at:www.mhra.gov.uk.

Side-effects in theBNF for Children

TheBNF for Children includes clinically relevant side-effectsfor most drugs; an exhaustive list is not included for drugsthat are used by specialists (e.g. cytotoxic drugs and drugsused in anaesthesia). Where causality has not beenestablished, side-effects in the manufacturers’ literature maybe omitted from theBNF for Children.

Recognising that hypersensitivity reactions (includinganaphylactic and anaphylactoid reactions) can occur withvirtually all drugs, this effect is not generally listed, unlessthe drug carries an increased risk of such reactions or specificmanagement advice is provided by the manufacturer.Administration site reactions have been omitted from theBNF for Children (e.g. pain at injection site). The BNF forChildren also omits effects that are likely to have littleclinical consequence (e.g. transient increase in liverenzymes). Drugs that are applied locally or topically carry atheoretical or low risk of systemic absorption and thereforesystemic side-effects for these drugs are not listed in theBNFfor Children unless they are associated with a high risk topatient safety. Infections are a known complication oftreatment with drugs that affect the immune system (e.g.corticosteroids or immunosuppressants); this side-effect islisted in theBNF for Children as ‘increased risk of infection’.Symptoms of drug withdrawal reactions are not individuallylisted, but are collectively termed‘withdrawal syndrome’.

Description of the frequency of side-effects

Uncommon [formerly’less

commonly’ in BNF publications] 1in1000to1in100

Frequency not known frequency is not defined byproduct literature or theside-effect has beenreported from post-marketing surveillance data

For consistency, the terms used to describe side-effects arestandardised using a defined vocabulary across all of the

drug monographs in theBNF for Children (e.g. posturalhypotension is used for the term orthostatic hypotension).

Special problems

SymptomsChildren may be poor at expressing thesymptoms of an adverse drug reaction and parental opinionmay be required.

Delayed drug effectsSome reactions (e.g. cancers andeffects on development) may become manifest months oryears after exposure. Any suspicion of such an associationshould be reported directly to the MHRA through the YellowCard Scheme.

Congenital abnormalitiesWhen an infant is born with acongenital abnormality or there is a malformed aborted fetusdoctors are asked to consider whether this might be anadverse reaction to a drug and to report all drugs (includingself-medication) taken during pregnancy.

Prevention of adverse reactions

Adverse reactions may be prevented as follows:

. never use any drug unless there is a good indication. Ifthe patient is pregnant do not use a drug unless the needfor it is imperative;

. allergy and idiosyncrasy are important causes of adversedrug reactions. Ask if the child has had previousreactions to the drug or formulation;

. prescribe as few drugs as possible and give very clearinstructions to the child, parent, or carer;

. whenever possible use a familiar drug; with a new drugbe particularly alert for adverse reactions or unexpectedevents;

. consider if excipients (e.g. colouring agents) may becontributing to the adverse reaction. If the reaction isminor, a trial of an alternative formulation of the samedrug may be considered before abandoning the drug;. obtain a full drug history including asking if the child is

already taking other drugsincluding over-the-countermedicines; interactions may occur;

. age and hepatic or renal disease may alter themetabolism or excretion of drugs, particularly inneonates, which can affect the potential for adverseeffects. Genetic factors may also be responsible forvariations in metabolism, and therefore for the adverseeffects of the drug;

. warn the child, parent, or carer if serious adversereactions are liable to occur.

Drug allergy (suspected or confirmed)

Suspected drug allergy is any reaction caused by a drug withclinical features compatible with an immunologicalmechanism. All drugs have the potential to cause adversedrug reactions, but not all of these are allergic in nature. Areaction is more likely to be caused by drug allergy if:

. The reaction occurred while the child was being treatedwith the drug, or

. The drug is known to cause this pattern of reaction, or. The child has had a similar reaction to the same drug or

drug-class previously.

A suspected reaction is less likely to be caused by a drugallergy if there is a possible non-drug cause or if there areonly gastro-intestinal symptoms present.

The following signs, allergic patterns and timing of onset canbe used to help decide whether to suspect drug allergy:Immediate, rapidly-evolving reactions (onset usually less than1hour after drug exposure)

. Anaphylaxis, with erythema, urticaria or angioedema,and hypotension and/or bronchospasm. See alsoAntihistamines, allergen immunotherapy and allergicemergencies p.174

. Urticaria or angioedema without systemic features

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. Exacerbation of asthma e.g. with non-steroidal inflammatory drugs (NSAIDs)

anti-Non-immediate reactions, without systemic involvement (onsetusually6–10days afterfirst drug exposure or3days aftersecond exposure)

. Cutaneous reactions, e.g. widespread red macules and/orpapules, or,fixed drug eruption (localised inflamed skin)Non-immediate reactions, with systemic involvement (onsetmay be variable, usually3days to6weeks afterfirst drugexposure, depending on features, or3days after secondexposure)

. Cutaneous reactions with systemic features, e.g. drugreaction with eosinophilia and systemic signs (DRESS) ordrug hypersensitivity syndrome (DHS), characterised bywidespread red macules, papules or erythroderma, fever,lymphadenopathy, liver dysfunction or eosinophilia. Toxic epidermal necrolysis or Stevens–Johnson

. Acute generalised exanthematous pustulosis (AGEP)<small>g</small>Suspected drug allergy information should be clearlyand accurately documented in clinical notes andprescriptions, and shared among all healthcare

professionals. Children and parents or carers should be giveninformation about which drugs and drug-classes to avoidand encouraged to share the drug allergy status.If a drug allergy is suspected, consider stopping thesuspected drug and advising the child and parent or carer toavoid this drug in future. Symptoms of the acute reactionshould be treated, in hospital if severe. Children presentingwith a suspected anaphylactic reaction, or a severe or non-immediate cutaneous reaction, should be referred to aspecialist drug allergy service. Children presenting with asuspected drug allergic reaction or anaphylaxis to NSAIDs,and local and general anaesthetics may also need to bereferred to a specialist drug allergy service, e.g. in cases ofanaphylactoid reactions or to determine future treatmentoptions. Children presenting with a suspected drug allergicreaction or anaphylaxis associated with beta-lactamantibiotics should be referred to a specialist drug allergyservice if their disease or condition can only be treated by abeta-lactam antibiotic or they are likely to need beta-lactamantibiotics frequently in the future (e.g. immunodeficientchildren).hFor further information see Drug allergy:diagnosis and management. NICE Clinical Guideline183(September2014)www.nice.org.uk/guidance/cg183.

Defective medicines

During the manufacture or distribution of a medicine anerror or accident may occur whereby thefinished productdoes not conform to its specification. While such a defectmay impair the therapeutic effect of the product and couldadversely affect the health of a patient, it should not beconfused with an Adverse Drug Reaction where the productconforms to its specification.

The Defective Medicines Report Centre assists with theinvestigation of problems arising from licensed medicinalproducts thought to be defective and co-ordinates anynecessary protective action. Reports on suspect defectivemedicinal products should include the brand or the non-proprietary name, the name of the manufacturer or supplier,the strength and dosage form of the product, the productlicence number, the batch number or numbers of theproduct, the nature of the defect, and an account of anyaction already taken in consequence. The Centre can becontacted at:

The Defective Medicines Report Centre

Medicines and Healthcare products Regulatory Agency,151Buckingham Palace Road, London, SW1W9SZTel: (020)3080 6574

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Guidance on intravenous infusions

Intravenous infusions for neonatal intensivecare

Intravenous policyA local policy on the dilution of drugswith intravenousfluids should be drawn up by a multi-disciplinary team and issued as a document to the membersof staff concerned.

Centralised additive services are provided in a number ofhospital pharmacy departments and should be used inpreference to making additions on wards.

The information that follows should be read in conjunctionwith local policy documents.

. Drugs should only be diluted with infusion fluid whenconstant plasma concentrations are needed or when theadministration of a more concentrated solution wouldbe harmful.

. In general, only one drug should be mixed with aninfusionfluid in a syringe and the components should becompatible. Ready-prepared solutions should be usedwhenever possible. Drugs should not normally be addedto blood products, mannitol, or sodium bicarbonate.Only specially formulated additives should be used withfat emulsions or amino-acid solutions.

. Solutions should be thoroughly mixed by shaking andchecked for absence of particulate matter before use.. Strict asepsis should be maintained throughout and in

general the giving set should not be used for more than24hours (for drug admixtures).

. The infusion syringe should be labelled with theneonate’s name and hospital number, the name andquantity of drug, the infusionfluid, and the expiry dateand time. If a problem occurs during administration,containers should be retained for a period after use incase they are needed for investigation.

. Administration using a suitable motorised syringe driveris advocated for preparations where strict control overadministration is required.

. It is good practice to examine intravenous infusionsfrom time to time while they are running. If cloudiness,crystallisation, change of colour, or any other sign ofinteraction or contamination is observed the infusionshould be discontinued.

Microbial contamination The accidental entry andsubsequent growth of micro-organisms converts the infusionfluid pathway into a potential vehicle for infection withmicro-organisms, particularly species of Candida,Enterobacter, and Klebsiella. Ready-prepared infusionscontaining the additional drugs, or infusions prepared by anadditive service (when available) should therefore be used inpreference to making extemporaneous additions to infusioncontainers on wards etc. However, when this is necessarystrict aseptic procedure should be followed.

IncompatibilityPhysical and chemical incompatibilitiesmay occur with loss of potency, increase in toxicity, or otheradverse effect. The solutions may become opalescent orprecipitation may occur, but in many instances there is novisual indication of incompatibility. Interaction may takeplace at any point in the infusionfluid pathway, and thepotential for incompatibility is increased when more thanone substance is added to the infusionfluid.

Common incompatibilities Precipitation reactions arenumerous and varied and may occur as a result of pH,concentration changes,‘salting-out’ effects, complexationor other chemical changes. Precipitation or other particle

formation must be avoided since, apart from lack of controlof dosage on administration, it may initiate or exacerbateadverse effects. This is particularly important in the case ofdrugs which have been implicated in either thrombophlebitis(e.g. diazepam) or in skin sloughing or necrosis caused byextravasation (e.g. sodium bicarbonate and parenteralnutrition). It is also especially important to effect solution ofcolloidal drugs and to prevent their subsequent precipitationin order to avoid a pyrogenic reaction (e.g. amphotericin).It is considered undesirable to mix beta-lactam antibiotics,such as semi-synthetic penicillins and cephalosporins, withproteinaceous materials on the grounds that immunogenicand allergenic conjugates could be formed.

A number of preparations undergo significant loss ofpotency when added singly or in combination to largevolume infusions. Examples include ampicillin in infusionsthat contain glucose or lactates.

BloodBecause of the large number of incompatibilities,drugs should not be added to blood and blood products forinfusion purposes. Examples of incompatibility with bloodinclude hypertonic mannitol solutions (irreversiblecrenation of red cells), dextrans (rouleaux formation andinterference with cross-matching), glucose (clumping of redcells), and oxytocin (inactivated).

If the giving set is not changed after the administration ofblood, but used for other infusionfluids, a fibrin clot mayform which, apart from blocking the set, increases thelikelihood of microbial growth.

Intravenous fat emulsionThese may break down withcoalescence of fat globules and separation of phases whenadditions such as antibacterials or electrolytes are made,thus increasing the possibility of embolism. Only speciallyformulated products such asVitlipid N<small>®</small>may be added toappropriate intravenous fat emulsions.

Other infusions Infusions that frequently give rise toincompatibility include amino acids, mannitol, and sodiumbicarbonate.

Ready-prepared infusions should be used wheneveravailable. When dilution of drugs is required to be madeextemporaneously, any product reconstitution instructionssuch as those relating to concentration, vehicle, mixing, andhandling precautions should be strictly followed using anaseptic technique throughout. Once the product has beenreconstituted, further dilution with the infusionfluid shouldbe made immediately in order to minimise microbialcontamination and, with certain products, to preventdegradation or other formulation change which may occur;e.g. reconstituted ampicillin injection degrades rapidly onstanding, and also may form polymers which could causesensitivity reactions.

It is also important in certain instances that an infusionfluidof specific pH be used (e.g. furosemide injection requiresdilution in infusions of pH greater than5.5).

When drug dilutions are made it is important to mixthoroughly; additions should not be made to an infusioncontainer that has been connected to a giving set, as mixingis hampered. If the solutions are not thoroughly mixed, aconcentrated layer of the drug may form owing to differencesin density. Potassium chloride is particularly prone to this‘layering’ effect when added without adequate mixing toinfusions; if such a mixture is administered it may have aserious effect on the heart.

A time limit between dilution and completion ofadministration must be imposed for certain admixtures toguarantee satisfactory drug potency and compatibility. Foradmixtures in which degradation occurs without the

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formation of toxic substances, an acceptable limit is the timetaken for10% decomposition of the drug. When toxicsubstances are produced stricter limits may be imposed.Because of the risk of microbial contamination a maximumtime limit of24hours may be appropriate for additions madeelsewhere than in hospital pharmacies offering centraladditive service.

Certain injections must be protected from light duringcontinuous infusion to minimise oxidation, e.g. sodiumnitroprusside.

Drugs given by continuous intravenousinfusion to neonates

The information provided inBNF for Children covers dilutionwithGlucose intravenous infusion5% and10% andSodiumchloride intravenous infusion0.9%. Compatibility with glucose5% and with sodium chloride0.9% indicates compatibilitywithSodium chloride and glucose intravenous infusion.Infusion of a large volume of hypotonic solution should beavoided, therefore care should be taken if water forinjections is used.

Prescribing in hepatic impairment

Children have a large reserve of hepatic metabolic capacityand modification of the choice and dosage of drugs is usuallyunnecessary even in apparently severe liver disease.However, special consideration is required in the followingsituations:

. liver failure characterised by severe derangement of liverenzymes and profound jaundice; the use of sedativedrugs, opioids, and drugs such as diuretics andamphotericin p.387which produce hypokalaemia mayprecipitate hepatic encephalopathy;

. impaired coagulation, which can affect response to oralanticoagulants;

. in cholestatic jaundice elimination may be impaired ofdrugs such as fusidic acid p.371and rifampicin p.379which are excreted in the bile;

. in hypoproteinaemia, the effect of highly protein-bounddrugs such as phenytoin p.211, prednisolone p.458,warfarin sodium p.99, and benzodiazepines may beincreased;

. use of hepatotoxic drugs is more likely to cause toxicityin children with liver disease; such drugs should beavoided if possible;

. in neonates, particularly preterm neonates, and also ininfants metabolic pathways may differ from olderchildren and adults because liver enzyme pathways maybe immature.

Where care is needed when prescribing in hepaticimpairment, this is indicated under the relevant drug inBNFfor Children.

Prescribing in renal impairment

Issues encountered in renal impairment

The use of drugs in children with reduced renal function cangive rise to problems for several reasons:

. reduced renal excretion of a drug or its metabolites mayproduce toxicity;

. sensitivity to some drugs is increased even if eliminationis unimpaired;

. many side-effects are tolerated poorly by children withrenal impairment;

. some drugs are not effective when renal function isreduced;

. neonates, particularly preterm, may have immaturerenal function.

Many of these problems can be avoided by reducing the doseor by using alternative drugs.

Principles of dose adjustment in renalimpairment

The level of renal function below which the dose of a drugmust be reduced depends on the proportion of the drugeliminated by renal excretion and its toxicity.For many drugs with only minor or no dose-related side-effects, very precise modification of the dose regimen isunnecessary and a simple scheme for dose reduction issufficient.

For more toxic drugs with a small safety margin doseregimens based on glomerularfiltration rate should be used.When both efficacy and toxicity are closely related to

18Prescribing in hepatic impairment

BNFC2019–2020

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