Ebook BNF 74 september 2017 – march 2018: Part 1

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Ebook BNF 74 september 2017 – march 2018: Part 1

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(BQ) Part 1 book “BNF 74 september 2017 – march 2018” has contents: Gastro-intestinal system, cardiovascular system, respiratory system, nervous system, infection, endocrine system. Invite to reference.

Medicines Information Services Information on drug therapy Information on any aspect of drug therapy can be obtained from Regional and District Medicines Information Services Details regarding the local services provided within your Region can be obtained by telephoning the following numbers England Birmingham: (0121) 424 7298 Bristol: (0117) 342 2867 Ipswich: (01473) 704 431 Leeds: (0113) 206 5377 Leicester: (0116) 258 6491 Liverpool: (0151) 794 8113/7, or (0151) 794 8118 London: Guy’s Hospital (020) 7188 8750, or (020) 7188 3849, or (020) 7188 3855 Northwick Park Hospital (020) 8869 2761, or (020) 8869 3973 Newcastle: (0191) 282 4631 Southampton: (023) 8120 6908/9 Wales Cardiff: (029) 2074 2979, or (029) 2074 2251 Scotland Aberdeen: (01224) 552 316 Dundee: (01382) 632 351, or (01382) 660 111 Extn 32351 Edinburgh: (0131) 242 2920 Glasgow: (0141) 211 4407 Northern Ireland Belfast: (028) 9504 0558 Republic of Ireland Dublin: (01) 473 0589, or (01) 453 7941 Extn 2348 United Kingdom Medicines Information Pharmacists Group (UKMIPG) website www.ukmi.nhs.uk Proprietary Manufacturers Telephone numbers and email addresses of proprietary manufacturers listed in BNF Publications are shown in the Index of proprietary manufacturers p 1488 UK Teratology Information Service Information on drug and chemical exposures in pregnancy Tel: 0344 892 0909 www.uktis.org UK Drugs in Lactation Advisory Service (UKDILAS) Information on the compatibility of drugs with breastfeeding Tel: (0116) 258 6491, or (0121) 424 7298 www.ukmi.nhs.uk/ukdilas Medicines in Dentistry Specialist Advisory Service Information on drug therapy relating to dental treatment Liverpool: (0151) 794 8206 Driver and Vehicle Licensing Agency (DVLA) Information on the national medical guidelines of fitness to drive is available from: www.gov.uk/government/publications/at-a-glance Patient Information Lines NHS Urgent Care Services 111 Poisons Information Services UK National Poisons Information Service 0344 892 0111 www.toxbase.org Sport ▶ Information regarding the use of medicines in sport is available from UK Anti-Doping: www.ukad.org.uk Tel: (020) 7842 3450 ukad@ukad.org.uk UK Anti-Doping Fleetbank House 2-6 Salisbury Square London EC4Y 8AE ▶ Information about the prohibited status of specific medicines based on the current World Anti-Doping Agency Prohibited List is available from Global Drug Reference Online: www.globaldro.com/UK/search Travel Immunisation Up-to-date information on travel immunisation requirements may be obtained from: ▶ National Travel Health Network and Centre (for healthcare professionals only) 0845 602 6712 Monday – Friday (closed Wednesday afternoons and Bank Holidays): 09:00–11:45 and 13:00–15:45 ▶ Travel Medicine Team, Health Protection Scotland (0141) 300 1100 (14.00–16.00 hours weekdays) www.travax.nhs.uk (for registered users of the NHS website Travax only) ▶ Welsh Government Switchboard English language 0300 0603300 (09.00–17.30 hours weekdays only) ▶ Welsh Government Switchboard Yr laith Gymraeg 0300 0604400 (09.00–17.30 hours weekdays only) ▶ Department of Health and Social Services (Belfast) (028) 9052 2118 (weekdays) List of Registered Medical Practitioners Details on whether doctors are registered and hold a licence to practise medicine in the UK can be obtained from the General Medical Council Tel: (0161) 923 6602 www.gmc-uk.org/register Access the BNF your way The British National Formulary (BNF) and BNF for Children are updated monthly online via MedicinesComplete, ensuring healthcare professionals always have the latest prescribing advice ONLINE BNF on MedicinesComplete Access BNF and BNF for Children on MedicinesComplete and receive the very latest drug information through monthly online updates FormularyComplete Create, edit and manage your own local formulary content built upon the trusted prescribing advice of the BNF and BNF for Children BNF on Evidence Search Search the BNF and BNF for Children alongside other authoritative clinical and non-clinical evidence and best practice at www.evidence.nhs.uk from NICE PRINT Eligible health 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, call 01268 495 609 or email bnf@binleys.com Turn the page for more details… BNF subscription – Take advantage of our print subscription option We will send you the new BNF as soon as the book is published One or two year packages (including or excluding BNFC) are available Discounted pricing is also available on bulk sales BNF app – Stay up to date anywhere with the BNF app available for iOS, Android and Blackberry BNF eBook – Available as an ePDF See www.pharmpress.com/bnf BNF on MedicinesComplete – Now mobile responsive How to purchase Buy direct from Pharmaceutical Press by visiting www.pharmpress.com/bnf For enquiries about the BNF or BNFC in print, contact direct@macmillan.co.uk Tel: +44 (0) 1256 302 699 For enquiries concerning MedicinesComplete, FormularyComplete, or bulk orders of the print edition, contact pharmpress-support@rpharms.com Tel: +44 (0) 20 7572 2266 Download mobile apps by visiting your appropriate app store Available for iOS, Android and Blackberry For pricing information please visit the website at www.pharmpress.com/bnf For international sales contact your local sales agent Contact details at www.pharmpress.com/agents Stay up to date – sign up to the BNF eNewsletter at www.bnf.org/newsletter BNF 74 September 2017 – March 2018 Published jointly by BMJ Group Tavistock Square, London, WC1H 9JP, UK and Pharmaceutical Press Pharmaceutical Press is the publishing division of the Royal Pharmaceutical Society 66-68 East Smithfield, London E1W 1AW, UK Copyright © BMJ Group and the Royal Pharmaceutical Society of Great Britain 2017 ISBN: 978 85711 298 ISBN: 978 85711 320 (NHS edition) ISBN: 978 85711 319 (ePDF) Printed by GGP Media GmbH, Pưßneck, Germany Typset by Data Standards Ltd, UK Text design by Peter Burgess A catalogue record for this book is available from the British Library All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without the prior written permission of the copyright holder Material published in the British National Formulary may not be used for any form of advertising, sales or publicity without prior written permission Each of the classification and the text are protected by copyright and/or database right Requesting copies of BNF publications Paper copies may be obtained through any bookseller or direct from: Pharmaceutical Press c/o Macmillan Distribution (MDL) Hampshire International Business Park Lime Tree Way Basingstoke Hampshire RG24 8YJ Tel: +44 (0) 1256 302 699 Fax: +44 (0) 1256 812 521 direct@macmillan.co.uk or via our website www.pharmpress.com For all bulk orders of more than 20 copies: Tel: +44 (0) 207 572 2266 pharmpress-support@rpharms.com The BNF is available as a mobile app, online (https://bnf nice.org.uk/) and also through MedicinesComplete; a PDA version is also available In addition, BNF content can be integrated into a local formulary by using BNF on FormularyComplete; see www.bnf.org for details Distribution of printed BNFs In England, NICE purchases print editions of the BNF (September editions only) for distribution within the NHS For details of who is eligible to receive a copy and further contact details, please refer to the NICE website: www.nice.org.uk/about/what-we-do/evidence-services/britishnational-formulary If you are entitled to a shared copy of the BNF, please call (0) 1268 495 609 or email: BNF@wilmingtonhealthcare.com In Scotland, email: nss.psd-bnf@nhs.net In Wales, contact NHS Wales Shared Services Partnership— Contractor Services: Tel: 01792 607420 In Northern Ireland, email: ni.bnf@hscni.net About BNF content The BNF is designed as a digest for rapid reference and it may not always include all the information necessary for prescribing and dispensing Also, less detail is given on areas such as obstetrics, malignant disease, and anaesthesia since it is expected that those undertaking treatment will have specialist knowledge and access to specialist literature BNF for Children should be consulted for detailed information on the use of medicines in children The BNF should be interpreted in the light of professional knowledge and supplemented as necessary by specialised publications and by reference to the product literature Information is also available from Medicines Information Services Please refer to digital versions of BNF for the most up-todate content BNF is published in print but interim updates are issued and published in the digital versions of BNF The publishers work to ensure that the information is as accurate and up-to-date as possible at the date of publication, but knowledge and best practice in this field change regularly BNF’s accuracy and currency cannot be guaranteed and neither the publishers nor the authors accept any responsibility for errors or omissions While considerable efforts have been made to check the material in this publication, it should be treated as a guide only Prescribers, pharmacists and other healthcare professionals are advised to check www.bnf.org for information about key updates and corrections Pharmaid Numerous requests have been received from developing countries for BNFs The Pharmaid scheme of the Commonwealth Pharmacists Association will dispatch old BNFs to certain Commonwealth countries For more information on this scheme see commonwealthpharmacy.org/what-we-do/pharmaid/ If you would like to donate your copy email: admin@commonwealthpharmacy.org iii BNF 74 Preface The BNF is a joint publication of the British Medical Association and the Royal Pharmaceutical Society It is published under the authority of a Joint Formulary Committee which comprises representatives of the two professional bodies, the UK Health Departments, the Medicines and Healthcare products Regulatory Agency, and a national guideline producer The Dental Advisory Group oversees the preparation of advice on the drug management of dental and oral conditions; the Group includes representatives of the British Dental Association and a representative from the UK Health Departments The Nurse Prescribers’ Advisory Group advises on the content relevant to nurses and includes representatives from different parts of the nursing community and from the UK Health Departments The BNF aims to provide prescribers, pharmacists, and other healthcare professionals with sound up-to-date information about the use of medicines The BNF includes key information on the selection, prescribing, dispensing and administration of medicines Medicines generally prescribed in the UK are covered and those considered less suitable for prescribing are clearly identified Little or no information is included on medicines promoted for purchase by the public Information on drugs is drawn from the manufacturers’ product literature, medical and pharmaceutical literature, UK health departments, regulatory authorities, and professional bodies Advice is constructed from clinical literature and reflects, as far as possible, an evaluation of the evidence from diverse sources The BNF also takes account of authoritative national guidelines and emerging safety concerns In addition, the editorial team receives advice on all therapeutic areas from expert clinicians; this ensures that the BNF’s recommendations are relevant to practice The BNF is designed as a digest for rapid reference and it may not always include all the information necessary for prescribing and dispensing Also, less detail is given on areas such as obstetrics, malignant disease, and anaesthesia since it is expected that those undertaking treatment will have specialist knowledge and access to specialist literature BNF for Children should be consulted for detailed information on the use of medicines in children The BNF should be interpreted in the light of professional knowledge and supplemented as necessary by specialised publications and by reference to the product literature Information is also available from medicines information services, see Medicines Information Services (see inside front cover) It is important to use the most recent BNF information for making clinical decisions The print edition of the BNF is updated in March and September each year Monthly updates are provided online via Medicines Complete and the NHS Evidence portal The more important changes are listed under Changes; changes listed online are cumulative (from one print edition to the next), and can be printed off each month to show the main changes since the last print edition as an aide memoire for those using print copies The BNF Publications website (www.bnf.org) includes additional information of relevance to healthcare professionals Other digital formats of the BNF—including versions for mobile devices and integration into local formularies—are also available BNF Publications welcomes comments from healthcare professionals Comments and constructive criticism should be sent to: British National Formulary, Royal Pharmaceutical Society, 66–68 East Smithfield London E1W 1AW editor@bnf.org The contact email for manufacturers or pharmaceutical companies wishing to contact BNF Publications is manufacturerinfo@bnf.org iv BNF 74 Contents Preface Acknowledgements How BNF publications are constructed How to use BNF Publications in print Changes Guidance on Prescribing Prescription writing Emergency supply of medicines Controlled drugs and drug dependence Adverse reactions to drugs Guidance on intravenous infusions Prescribing for children Prescribing in hepatic impairment Prescribing in renal impairment Prescribing in pregnancy Prescribing in breast-feeding Prescribing in palliative care Prescribing for the elderly Drugs and sport Prescribing in dental practice page iii v ix xii xix 12 16 18 19 19 22 22 23 28 29 30 NOTES ON DRUGS AND PREPARATIONS Gastro-intestinal system Cardiovascular system Respiratory system Nervous system Infection Endocrine system Genito-urinary system Immune system and malignant disease Blood and nutrition 10 Musculoskeletal system 11 Eye 12 Ear, nose and oropharynx 13 Skin 14 Vaccines 15 Anaesthesia 16 Emergency treatment of poisoning page 35 96 229 287 479 627 731 785 922 998 1057 1093 1117 1183 1218 1249 APPENDICES AND INDICES Appendix Interactions 1262 Appendix 1420 Borderline substances Appendix 1454 Cautionary and advisory labels for dispensed medicines Appendix 1457 Wound management products and elasticated garments Dental Practitioners’ Formulary 1482 Nurse Prescribers’ Formulary 1484 Non-medical prescribing 1487 Index of proprietary manufacturers 1488 Special-order Manufacturers 1493 Index 1495 Medical emergencies in the community inside back cover BNF 74 Acknowledgements The Joint Formulary Committee is grateful to individuals and organisations that have provided advice and information to the BNF The principal contributors for this update were: K.W Ah-See, M.N Badminton, A.K Bahl, P.R.J Barnes, D Bilton, S.L Bloom, M.F Bultitude, I.F Burgess, D.J Burn, C.E Dearden, D.W Denning, P.N Durrington, D.A.C Elliman, P Emery, M.D Feher, A Freyer, B.G Gazzard, A.M Geretti, N.J.L Gittoes, P.J Goadsby, M Gupta, T.L Hawkins, B.G Higgins, S.P Higgins, S.H.D Jackson, A Jones, D.M Keeling, J.R Kirwan, P.G Kopelman, T.H Lee, A Lekkas, D.N.J Lockwood, A.M Lovering, M.G Lucas, L Luzzatto, P.D Mason, D.A McArthur, K.E.L McColl, L.M Melvin, E Miller, R.M Mirakian, P Morrison, S.M.S Nasser, C Nelson-Piercy, J.M Neuberger, D.J Nutt, L.P Ormerod, R Patel, W.J Penny, A.B Provan, A.S.C Rice, D.J Rowbotham, J.W Sander, J.A.T Sandoe, M Schacter, S.E Slater, J Soar, S.C.E Sporton, M.D Stewart, S Thomas, J.P Thompson, A.D Weeks, A Wilcock, A.P.R Wilson, M.M Yaqoob Expert advice on the management of oral and dental conditions was kindly provided by M Addy, P Coulthard, A Crighton, M.A.O Lewis, J.G Meechan, N.D Robb, C Scully, R.A Seymour, R Welbury, and J.M Zakrzewska S Kaur provided valuable advice on dental prescribing policy Members of the British Association of Dermatologists’ Therapy & Guidelines Subcommittee, D.A Buckley, N Chiang, M Cork, K Gibbon, R.Y.P Hunasehally, G.A Johnston, T.A Leslie, E.C Mallon, P.M McHenry,, J Natkunarajah, C Saunders, S Ungureanu, S Wakelin, F.S Worsnop, A.G Brain (Secretariat), and M.F Mohd Mustapa (Secretariat) have provided valuable advice Members of the Advisory Committee on Malaria Prevention, R.H Behrens, D Bell, P.L Chiodini, V Field, F Genasi, L Goodyer, A Green, J Jones, G Kassianos, D.G Lalloo, D Patel, H Patel, M Powell, D.V Shingadia, N.O Subair, C.J.M Whitty, M Blaze (Secretariat), and V Smith (Secretariat) have provided valuable advice The UK Ophthalmic Pharmacy Group have also provided valuable advice The MHRA have provided valuable assistance Correspondents in the pharmaceutical industry have provided information on new products and commented on products in the BNF Numerous doctors, pharmacists, nurses, and others have sent comments and suggestions BNF interactions are provided by C.L Preston, S.L Jones, H.K Sandhu, and S Sutton The BNF has valuable access to the Martindale data banks by courtesy of A Brayfield and staff Valuable technical assistance provided by J Macdonald, N Judd, J Stott, K Parsons, R Calle, J Marsden-Hockham, H Rowland, M Kingsbury, and O Griffiths C Cadart, S Frau, D Jones, A Kalaparan, M Leon-Alonso, M Lynn, J MacKershan, L Marris, J Martin, J McCall, S Powell, A Raju, M Sills, J Smith, and A Sparshatt provided considerable assistance during the production of this update of the BNF v vi BNF Staff BNF DIRECTOR Karen Baxter BSc, MSc, MRPharmS HEAD OF CONTENT Kate Towers BPharm (AU), GCClinPharm CONTENT MANAGERS Thomas F Corbett BScPharm (IRL), MPharm (IRL) Kristina Fowlie MPharm, CertPharmPract, MRPharmS Claire McSherry BPharm (NZ), PGCertClinPharm (NZ) Heenaben Patel MPharm, DipClinPharm, MRPharmS QUALITY AND PROCESS MANAGER Angela M.G McFarlane BSc, DipClinPharm CLINICAL WRITERS Abby Calder BPharm (NZ), PGCertClinPharm (NZ) Naimah Callachand MPharm Holly Hayne BSc (Pharmacology) (NZ), BPharm (NZ) Angela L Kam BPharm (NZ), PGDipPharmPrac (NZ), PGCertPharmPres (NZ) Philip D Lee BSc, PhD Kirsty Luck BPharm (AU) Nafeesa Mussa BPharm (NZ), PGCertClinPharm (NZ) Kere Odumah MPharm Paridhi K Prashar MPharm, MRPharmS Jacob M Warner BPharm (AU) Sharyn Young BPharm (NZ), PGDipClinPharm (NZ) CLINICAL ASSISTANTS Elizabeth King EDITORIAL ASSISTANTS Hima Bhatt BSc, MA Jaya Venkitachalam BSc, MRes SENIOR BNF ADMINISTRATOR Heidi Homar BA MANAGING DIRECTOR, PHARMACEUTICAL PRESS Alina Lourie B.Ed, MSc SENIOR MEDICAL ADVISER Derek G Waller BSc, MB, BS, DM, FRCP BNF 74 716 Sex hormone responsive conditions Endocrine system ▶ l l l l premenstrual-like syndrome rashes reduced menstrual loss skin reactions sodium retention symptoms of endometriosis may be exacerbated thrombosis (more common when factor V Leiden present or in blood groups A, B, and AB) uterine fibroids may increase in size vaginal candidiasis visual disturbances vomiting weight changes ‘spotting’ in early cycles SIDE-EFFECTS, FURTHER INFORMATION Withdrawal bleeding Cyclical HRT (where a progestogen is taken for 12–14 days of each 28-day oestrogen treatment cycle) usually results in regular withdrawal bleeding towards the end of the progestogen The aim of continuous combined HRT (where a combination of oestrogen and progestogen is taken, usually in a single tablet, throughout each 28-day treatment cycle) is to avoid bleeding, but irregular bleeding may occur during the early treatment stages (if it continues endometrial abnormality should be excluded and consideration given to cyclical HRT instead) PREGNANCY Not known to be harmful BREAST FEEDING Avoid until weaning or for months after birth (adverse effects on lactation) HEPATIC IMPAIRMENT Avoid MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: tablet, capsule, oral suspension Tablet ▶ Ethinylestradiol (Non-proprietary) Ethinylestradiol 10 microgram Ethinylestradiol 10microgram tablets | 21 tablet P £200.00 DT price = £200.00 Ethinylestradiol 50 microgram Ethinylestradiol 50microgram tablets | 21 tablet P £200.00 DT price = £200.00 Ethinylestradiol mg Ethinylestradiol 1mg tablets | 28 tablet P £200.00 DT price = £200.00 Tibolone INDICATIONS AND DOSE Short-term treatment of symptoms of oestrogen deficiency (including women being treated with gonadotrophin releasing hormone analogues) | Osteoporosis prophylaxis in women at high risk of fractures when other prophylaxis contra-indicated or not tolerated l ▶ BY MOUTH ▶ l l Adult: 2.5 mg daily CONTRA-INDICATIONS Active or recent arterial thromboembolic disease (e.g angina or myocardial infarction) active thrombophlebitis acute porphyrias p 969 Dubin-Johnson and Rotor syndrome (or monitor closely) history of breast cancer history of cardiovascular disease history of cerebrovascular disease history of recurrent venous thromboembolism (unless already on anticoagulant treatment) history of thromboembolism history of thrombophlebitis hormone-dependent tumours liver disease (where liver function tests have failed to return to normal) oestrogen-dependent cancer thrombophilic disorder uninvestigated or undiagnosed vaginal bleeding untreated endometrial hyperplasia venous thromboembolism CAUTIONS Acute porphyrias p 969 diabetes (increased risk of heart disease) epilepsy factors predisposing to thromboembolism history of breast nodules—closely monitor breast status (risk of breast cancer) history of endometrial hyperplasia history of fibrocystic disease— closely monitor breast status (risk of breast cancer) history of liver disease hypertriglyceridaemia hypophyseal tumours migraine (or migraine-like headaches) presence of antiphospholipid antibodies BNF 74 (increased risk of thrombotic events) prolonged exposure to unopposed oestrogens may increase risk of developing endometrial cancer risk factors for oestrogen-dependent tumours (e.g breast cancer in first-degree relative) risk of stroke CAUTIONS, FURTHER INFORMATION ▶ Other conditions The product literature advises caution in other conditions including hypertension, renal disease, asthma, epilepsy, sickle-cell disease, melanoma, otosclerosis, multiple sclerosis, and systemic lupus erythematosus (but care required if antiphospholipid antibodies present) Evidence for caution in these conditions is unsatisfactory and many women with these conditions may stand to benefit from HRT l INTERACTIONS → Appendix 1: tibolone l SIDE-EFFECTS ▶ Common or very common Abdominal pain facial hair leucorrhoea vaginal bleeding weight changes ▶ Rare Amnesia ▶ Frequency not known Arthralgia breast cancer depression dizziness gastro-intestinal disturbances headache increased risk of gall-bladder disease migraine myalgia oedema pruritus rash seborrhoeic dermatitis symptoms of endometriosis may be exacerbated uterine fibroids may increase in size visual disturbances SIDE-EFFECTS, FURTHER INFORMATION ▶ Vaginal bleeding Investigate for endometrial cancer if bleeding continues beyond months or after stopping treatment ▶ Reasons to withdraw treatment Withdraw treatment if signs of thromboembolic disease, abnormal liver function tests, or signs of cholestatic jaundice l PREGNANCY Avoid; toxicity in animal studies l BREAST FEEDING Avoid l HEPATIC IMPAIRMENT Avoid in acute liver disease or if history of liver disease and liver function tests not returned to normal l RENAL IMPAIRMENT Patients with renal impairment should be closely monitored (risk of fluid retention) l PRESCRIBING AND DISPENSING INFORMATION Unsuitable for use in the premenopause (unless being treated with gonadotrophin-releasing hormone analogue) and as (or with) an oral contraceptive Also unsuitable for use within 12 months of last menstrual period (may cause irregular bleeding) If transferring from cyclical HRT, start at end of regimen; if transferring from continuous-combined HRT, start at any time l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ▶ ▶ Tibolone (Non-proprietary) Tibolone 2.5 mg Tibolone 2.5mg tablets | 28 tablet P £10.36– £10.43 DT price = £10.36 | 84 tablet P £31.08–£32.63 Livial (Merck Sharp & Dohme Ltd) Tibolone 2.5 mg Livial 2.5mg tablets | 28 tablet P £10.36 DT price = £10.36 | 84 tablet P £31.08 OESTROGENS COMBINED WITH PROGESTOGENS Conjugated oestrogens with medroxyprogesterone Female sex hormone responsive conditions 717 Estradiol with dydrogesterone The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711 l The properties listed below are those particular to the combination only For the properties of the components please consider, conjugated oestrogens (equine) p 710, medroxyprogesterone acetate p 763 l ▶ BY MOUTH Adult: tablet daily for 14 days, white tablet to be taken and started within days of onset of menstruation (or any time if cycles have ceased or are infrequent), then tablet daily for 14 days, grey tablet to be taken, subsequent courses repeated without interval, Femoston ® mg/10 mg given initially and Femoston ® mg/10 mg substituted if symptoms not controlled Osteoporosis prophylaxis in women with a uterus ▶ INDICATIONS AND DOSE PREMIQUE ® LOW DOSE TABLETS Menopausal symptoms in women with a uterus ▶ BY MOUTH ▶ Adult: tablet daily continuously l INTERACTIONS → Appendix 1: hormone replacement therapy l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug ▶ BY MOUTH ▶ Modified-release tablet ▶ Premique (Pfizer Ltd) Conjugated oestrogens 300 microgram, Medroxyprogesterone acetate 1.5 mg Premique Low Dose 0.3mg/1.5mg modified-release tablets | 84 tablet P £6.52 DT price = £6.52 ▶ BY MOUTH Adult: tablet daily for 14 days, red tablet to be taken and started within days of onset of menstruation (or any time if cycles have ceased or are infrequent), then tablet daily for 14 days, yellow tablet to be taken, subsequent courses repeated without interval, Femoston ® mg/10 mg given initially and Femoston ® mg/10 mg substituted if symptoms not controlled Osteoporosis prophylaxis in women with a uterus ▶ The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711 INDICATIONS AND DOSE Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously l ▶ BY MOUTH ▶ ▶ BY MOUTH l l l l Adult: tablet daily continuously, if changing from cyclical HRT begin treatment the day after finishing oestrogen plus progestogen phase Adult: tablet daily for 14 days, red tablet to be taken and started within days of onset of menstruation (or any time if cycles have ceased or are infrequent), then tablet daily for 14 days, yellow tablet to be taken, subsequent courses repeated without interval FEMOSTON ® -CONTI 0.5 MG/2.5MG Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously CAUTIONS Use with care if an increased concentration of potassium might be hazardous INTERACTIONS → Appendix 1: hormone replacement therapy RENAL IMPAIRMENT Avoid if eGFR less than 30 mL/minute/1.73 m2 ▶ BY MOUTH ▶ Adult: tablet daily continuously, if changing from cyclical HRT begin treatment the day after finishing oestrogen plus progestogen phase FEMOSTON ® -CONTI MG/5MG Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ▶ Adult: tablet daily for 14 days, white tablet to be taken and started within days of onset of menstruation (or any time if cycles have ceased or are infrequent), then tablet daily for 14 days, grey tablet to be taken, subsequent courses repeated without interval FEMOSTON ® MG/10 MG Menopausal symptoms in women with a uterus Estradiol with drospirenone ▶ INDICATIONS AND DOSE FEMOSTON ® MG/10 MG Menopausal symptoms in women with a uterus Angeliq (Bayer Plc) Estradiol (as Estradiol hemihydrate) mg, Drospirenone mg Angeliq tablets | 84 tablet P £31.90 DT price = £31.90 ▶ BY MOUTH ▶ l l Adult: tablet daily continuously, if changing from cyclical HRT begin treatment the day after finishing oestrogen plus progestogen phase CONTRA-INDICATIONS Acute porphyrias p 969 genital or breast cancer history during pregnancy of idiopathic jaundice, severe pruritus, or pemphigoid gestationis history of liver tumours severe arterial disease undiagnosed vaginal bleeding CAUTIONS Conditions that may worsen with fluid retention e.g epilepsy, hypertension, migraine, asthma, or cardiac dysfunction diabetes (progestogens can decrease glucose tolerance) history of depression in those Endocrine system BNF 74 718 Sex hormone responsive conditions l l Endocrine system l l l susceptible to thromboembolism (particular caution with high dose) INTERACTIONS → Appendix 1: hormone replacement therapy SIDE-EFFECTS Acne alopecia anaphylactoid reactions bloating breast tenderness change in libido depression dizziness drowsiness fluid retention headache hirsutism insomnia jaundice menstrual disturbances nausea premenstrual-like syndrome pruritus rash skin reactions urticaria weight change HEPATIC IMPAIRMENT Avoid RENAL IMPAIRMENT Use with caution BNF 74 Estradiol with medroxyprogesterone The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711, medroxyprogesterone acetate p 763 l ▶ BY MOUTH MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug ▶ Tablet ▶ ▶ ▶ Estradiol with levonorgestrel l INDICATIONS AND DOSE ® ▶ BY MOUTH ▶ INTERACTIONS → Appendix 1: hormone replacement therapy >l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ▶ ▶ BY TRANSDERMAL APPLICATION Adult: Apply patch once weekly continuously FEMSEVEN SEQUI ® Menopausal symptoms in women with a uterus ▶ BY TRANSDERMAL APPLICATION ▶ l l l Adult: Apply patch once weekly for weeks, phase patches to be applied, then apply patch once weekly for weeks, phase patches to be applied, subsequent courses are repeated without interval INTERACTIONS → Appendix 1: hormone replacement therapy PATIENT AND CARER ADVICE Patient counselling is advised for estradiol with levonorgestrel patches (application) MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Transdermal patch ▶ ▶ FemSeven Conti (Teva UK Ltd) Levonorgestrel microgram per 24 hour, Estradiol 50 microgram per 24 hour FemSeven Conti patches | patch P £15.48 | 12 patch P £44.12 FemSeven Sequi (Teva UK Ltd) FemSeven Sequi patches | patch P £13.18 | 12 patch P £37.54 Adult: tablet daily for 70 days, white tablet to be taken, then tablet daily for 14 days, blue tablet to be taken, then tablet daily for days, yellow tablet to be taken, subsequent courses are repeated without interval l FEMSEVEN CONTI Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously ▶ Adult: Initially 1/2.5 mg daily taken continuously, adjust according to response, to be started at end of scheduled bleed if changing from cyclical HRT TRIDESTRA ® Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus Femoston 1/10 (Mylan Ltd) Femoston 1/10mg tablets | 84 tablet P £16.16 Femoston 2/10 (Mylan Ltd) Femoston 2/10mg tablets | 84 tablet P £16.16 Femoston-conti (Mylan Ltd) Estradiol 500 microgram, Dydrogesterone 2.5 mg Femoston-conti 0.5mg/2.5mg tablets | 84 tablet P £24.43 Estradiol mg, Dydrogesterone mg Femoston-conti 1mg/5mg tablets | 84 tablet P £24.43 DT price = £24.43 The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711, levonorgestrel p 759 INDICATIONS AND DOSE INDIVINA ® TABLETS Menopausal symptoms in women with a uterus whose last menstrual period occurred over years previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over years previously ▶ Indivina (Orion Pharma (UK) Ltd) Estradiol valerate mg, Medroxyprogesterone acetate 2.5 mg Indivina 1mg/2.5mg tablets | 84 tablet P £20.58 DT price = £20.58 Estradiol valerate mg, Medroxyprogesterone acetate mg Indivina 2mg/5mg tablets | 84 tablet P £20.58 DT price = £20.58 Estradiol valerate mg, Medroxyprogesterone acetate mg Indivina 1mg/5mg tablets | 84 tablet P £20.58 DT price = £20.58 Tridestra (Orion Pharma (UK) Ltd) Tridestra tablets | 91 tablet P £20.49 Estradiol with norethisterone The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711, norethisterone p 720 l INDICATIONS AND DOSE CLIMAGEST ® 1-MG Menopausal symptoms ▶ BY MOUTH ▶ Adult: tablet daily for 16 days, grey tablet to be taken and started on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 12 days, white tablet to be taken, subsequent courses are repeated without interval CLIMAGEST ® 2-MG Menopausal symptoms (if symptoms not controlled with lower strength) ▶ BY MOUTH ▶ Adult: tablet daily for 16 days, blue tablet to be taken and started on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 12 days, white tablet to be taken, subsequent courses are repeated without interval Female sex hormone responsive conditions 719 BNF 74 CLIMESSE ® Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously KLIOVANCE ® Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously ▶ BY MOUTH Adult: tablet daily continuously ▶ ® CLINORETTE Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ® NOVOFEM Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ▶ BY MOUTH ▶ Adult: tablet daily for 16 days, white tablets to be taken, starting on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 12 days, pink tablets to be taken, subsequent courses repeated without interval ▶ BY MOUTH ▶ ELLESTE-DUET ® 1-MG Menopausal symptoms Adult: tablet daily for 16 days, white tablet to be taken and started on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 12 days, green tablets to be taken, subsequent courses are repeated without interval ▶ BY MOUTH ELLESTE-DUET ® 2-MG Menopausal symptoms | Osteoporosis prophylaxis ▶ ▶ BY MOUTH ▶ Adult: tablet daily for 16 days, orange tablet to be taken, to be started on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 12 days, grey tablet to be taken, subsequent courses are repeated without interval ELLESTE-DUET ® CONTI Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously Adult: tablet daily continuous basis, if changing from cyclical HRT begin treatment at the end of scheduled bleed EVOREL ® CONTI Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ▶ BY TRANSDERMAL APPLICATION ▶ Adult: Apply patch twice weekly continuously EVOREL ® SEQUI Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ▶ BY TRANSDERMAL APPLICATION ▶ Adult: Apply patch twice weekly for weeks, Evorel ® 50 patch to be applied and started within days of onset of menstruation (or at any time if cycles have ceased or are infrequent), then apply patch twice weekly, Evorel ® Conti patch to be applied, subsequent courses are repeated without interval KLIOFEM ® Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously ▶ BY MOUTH ▶ Adult: tablet daily continuously, to be started at end of scheduled bleed if changing from cyclical HRT Adult: tablet daily continuously, if changing from cyclical HRT, start treatment the day after finishing oestrogen plus progestogen phase TRISEQUENS ® Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ▶ BY MOUTH ▶ l ▶ BY MOUTH ▶ Adult: tablet daily for 16 days, red tablets to be taken, then tablet daily for 12 days, white tablets to be taken, subsequent courses are repeated without interval; start treatment with red tablet at any time or if changing from cyclical HRT, start treatment the day after finishing oestrogen plus progestogen phase NUVELLE ® CONTINUOUS Menopausal symptoms in women with a uterus whose last menstrual period occurred over 12 months previously | Osteoporosis prophylaxis in women with a uterus whose last menstrual period occurred over 12 months previously ▶ BY MOUTH ▶ Adult: tablet daily continuously, to be started at end of scheduled bleed if changing from cyclical HRT l l Adult: tablet daily for 12 days, blue tablets to be taken, followed by tablet daily for 10 days, white tablet to be taken, then tablet daily for days, red tablet to be taken, subsequent courses are repeated without interval INTERACTIONS → Appendix 1: hormone replacement therapy PATIENT AND CARER ADVICE EVOREL ® SEQUI Patients and carers should be advised on the application of Evorel ® Sequi patches MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ▶ ▶ ▶ ▶ ▶ ▶ ▶ ▶ Clinorette (ReSource Medical UK Ltd) Clinorette tablets | 84 tablet P £9.23 Elleste Duet (Meda Pharmaceuticals Ltd) Elleste Duet 1mg tablets | 84 tablet P £9.20 Elleste Duet 2mg tablets | 84 tablet P £9.20 Elleste Duet Conti (Meda Pharmaceuticals Ltd) Norethisterone acetate mg, Estradiol mg Elleste Duet Conti tablets | 84 tablet P £17.02 DT price = £17.02 Kliofem (Novo Nordisk Ltd) Norethisterone acetate mg, Estradiol mg Kliofem tablets | 84 tablet P £11.43 DT price = £17.02 Kliovance (Novo Nordisk Ltd) Norethisterone acetate 500 microgram, Estradiol mg Kliovance tablets | 84 tablet P £13.20 DT price = £13.20 Novofem (Novo Nordisk Ltd) Novofem tablets | 84 tablet P £11.43 Nuvelle Continuous (Bayer Plc) Norethisterone acetate mg, Estradiol mg Nuvelle Continuous tablets | 84 tablet P £19.00 DT price = £17.02 Trisequens (Novo Nordisk Ltd) Trisequens tablets | 84 tablet P £11.10 Endocrine system ▶ BY MOUTH ▶ 720 Sex hormone responsive conditions BNF 74 Transdermal patch ▶ ▶ Breast cancer Evorel Conti (Janssen-Cilag Ltd) Estradiol 50 microgram per 24 hour, Norethisterone acetate 170 microgram per 24 hour Evorel Conti patches | patch P no price available | patch P £13.00 | 24 patch P £37.22 DT price = £37.22 Evorel Sequi (Janssen-Cilag Ltd) Evorel Sequi patches | patch P £11.09 ▶ BY MOUTH Adult: 40 mg daily, increased if necessary to 60 mg daily Short-term contraception ▶ ▶ BY DEEP INTRAMUSCULAR INJECTION Females of childbearing potential: 200 mg, to be administered within first days of cycle or immediately after parturition (duration weeks) To be injected into the gluteal muscle, then 200 mg after weeks if required Contraception ▶ Endocrine system Estradiol with norgestrel The properties listed below are those particular to the combination only For the properties of the components please consider, estradiol p 711 ▶ BY MOUTH ▶ l INDICATIONS AND DOSE CYCLO-PROGYNOVA ® 2MG TABLETS Menopausal symptoms in women with a uterus | Osteoporosis prophylaxis in women with a uterus ▶ BY MOUTH ▶ Adult: tablet daily for 11 days, white tablet to be taken; start on day of menstruation (or at any time if cycles have ceased or are infrequent), then tablet daily for 10 days, brown tablet to be taken, followed by a 7-day tablet free interval l INTERACTIONS → Appendix 1: hormone replacement therapy l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug l Tablets ▶ Cyclo-Progynova (Meda Pharmaceuticals Ltd) Cyclo-Progynova 2mg tablets | 21 tablet P £3.11 PROGESTOGENS Norethisterone ▶ l INDICATIONS AND DOSE Endometriosis l ▶ BY MOUTH Adult: 10–15 mg daily for 4–6 months or longer, to be started on day of cycle; increased to 20–25 mg daily if required, dose only increased if spotting occurs and reduced once bleeding has stopped Dysfunctional uterine bleeding (to arrest bleeding) | Menorrhagia (to arrest bleeding) ▶ ▶ ▶ BY MOUTH Adult: mg times a day for 10 days Dysfunctional uterine bleeding (to prevent bleeding) | Menorrhagia (to prevent bleeding) ▶ ▶ BY MOUTH Adult: mg twice daily, to be taken from day 19 to day 26 of cycle Dysmenorrhoea ▶ ▶ ▶ BY MOUTH Adult: mg times a day for 3–4 cycles, to be taken from day 5–24 of cycle Premenstrual syndrome (but not recommended) ▶ ▶ ▶ BY MOUTH Adult: mg 2–3 times a day for several cycles, to be taken from day 19–26 of cycle Postponement of menstruation ▶ ▶ BY MOUTH ▶ Females of childbearing potential: mg times a day, to be started days before expected onset (menstruation occurs 2–3 days after stopping) ▶ Females of childbearing potential: 350 micrograms daily, dose to be taken at same time each day, starting on day of cycle then continuously, if administration delayed for hours or more it should be regarded as a ‘missed pill’ CONTRA-INDICATIONS GENERAL CONTRA-INDICATIONS Avoid in patients with a history of liver tumours breast cancer (unless progestogens are being used in the management of this condition) genital cancer (unless progestogens are being used in the management of this condition) history during pregnancy of idiopathic jaundice history during pregnancy of pemphigoid gestationis (non-contraceptive indications) history during pregnancy of severe pruritus (non-contraceptive indications) when used as a contraceptive, history of breast cancer (can be used after years if no evidence of disease and non-hormonal contraceptive methods unacceptable) SPECIFIC CONTRA-INDICATIONS With oral use Acute porphyrias p 969 severe arterial disease undiagnosed vaginal bleeding CAUTIONS GENERAL CAUTIONS Asthma cardiac dysfunction conditions that may worsen with fluid retention diabetes (progestogens can decrease glucose tolerance—monitor patient closely) epilepsy history of depression hypertension migraine susceptibility to thromboembolism (particular caution with high dose) SPECIFIC CAUTIONS When used for contraception Active trophoblastic disease (until return to normal of urine- and plasmagonadotrophin concentration)—seek specialist advice arterial disease functional ovarian cysts history of jaundice in pregnancy malabsorption syndromes past ectopic pregnancy sex-steroid dependent cancer systemic lupus erythematosus with positive (or unknown) anti-phospholipid antibodies With intramuscular use Disturbances of lipid metabolism history during pregnancy of deterioration of otosclerosis history during pregnancy of pruritus possible risk of breast cancer CAUTIONS, FURTHER INFORMATION Use as a contraceptive in co-morbidities The product literature advises caution in patients with history of thromboembolism, hypertension, diabetes mellitus and migraine; evidence for caution in these conditions is unsatisfactory Breast cancer risk with contraceptive use There is a small increase in the risk of having breast cancer diagnosed in women using, or who have recently used, a progestogenonly contraceptive pill; this relative risk may be due to an earlier diagnosis The most important risk factor appears to be the age at which the contraceptive is stopped rather than the duration of use; the risk disappears gradually during the 10 years after stopping and there is no excess l l ▶ ▶ l ▶ l ▶ l l l Female sex hormone responsive conditions 721 risk by 10 years A possible small increase in the risk of breast cancer should be weighed against the benefits INTERACTIONS → Appendix 1: norethisterone SIDE-EFFECTS GENERAL SIDE-EFFECTS Acne alopecia anaphylactoid reactions breast tenderness change in libido depression disturbance of appetite dizziness fluid retention headache hirsutism insomnia (non-contraceptive indications) jaundice menstrual disturbances nausea premenstrual-like syndrome pruritus rash skin reactions urticaria vomiting weight change SPECIFIC SIDE-EFFECTS With intramuscular use Injection-site reactions SIDE-EFFECTS, FURTHER INFORMATION Cervical cancer Use of injectable progestogen-only contraceptives may be associated with a small increased risk of cervical cancer, similar to that seen with combined oral contraceptives (use of combined oral contraceptives for years or longer is associated with a small increased risk of cervical cancer; the risk diminishes after stopping and disappears by about 10 years) The risk of cervical cancer with other progestogen-only contraceptives is not yet known PREGNANCY With oral use Masculinisation of female fetuses and other defects reported with non-contraceptive use BREAST FEEDING Progestogen-only contraceptives not affect lactation Higher doses (used in malignant conditions) may suppress lactation and alter milk composition—use lowest effective dose With intramuscular use Withhold breast-feeding for neonates with severe or persistent jaundice requiring medical treatment HEPATIC IMPAIRMENT When used as a contraceptive; caution in severe liver disease and recurrent cholestatic jaundice, avoid in liver tumour Avoid in noncontraceptive indications RENAL IMPAIRMENT Use with caution in noncontraceptive indications PATIENT AND CARER ADVICE Missed oral contraceptive pill The following advice is recommended: ‘If you forget a pill, take it as soon as you remember and carry on with the next pill at the right time If the pill was more than hours overdue you are not protected Continue normal pill-taking but you must also use another method, such as the condom, for the next days.’ The Faculty of Sexual and Reproductive Healthcare recommends emergency contraception if one or more progestogen-only contraceptive tablets are missed or taken more than hours late and unprotected intercourse has occurred before further tablets have been correctly taken Diarrhoea and vomiting with oral contraceptives Vomiting and persistent, severe diarrhoea can interfere with the absorption of oral progestogen-only contraceptives If vomiting occurs within hours of taking an oral progestogen-only contraceptive, another pill should be taken as soon as possible If a replacement pill is not taken within hours of the normal time for taking the progestogen-only pill, or in cases of persistent vomiting or very severe diarrhoea, additional precautions should be used during illness and for days after recovery Starting routine for oral contraceptives One tablet daily, on a continuous basis, starting on day of cycle and taken at the same time each day (if delayed by longer than hours contraceptive protection may be lost) Additional contraceptive precautions are not required if norethisterone is started up to and including day of the menstrual cycle; if started after this time, additional contraceptive precautions are required for days Changing from a combined oral contraceptive Start on the day following completion of the combined oral contraceptive course without a break (or in the case of ED tablets omitting the inactive ones) After childbirth Oral progestogen-only contraceptives can be started up to and including day 21 postpartum without the need for additional contraceptive precautions If started more than 21 days postpartum, additional contraceptive precautions are required for days Contraceptives by injection Full counselling backed by patient information leaflet required before administration— likelihood of menstrual disturbance and the potential for a delay in return to full fertility Delayed return of fertility and irregular cycles may occur after discontinuation of treatment but there is no evidence of permanent infertility l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: oral suspension Solution for injection ▶ Noristerat (Bayer Plc) Norethisterone enantate 200 mg per ml Noristerat 200mg/1ml solution for injection ampoules | ampoule P £4.05 Tablet ▶ ▶ ▶ ▶ Norethisterone (Non-proprietary) Norethisterone mg Norethisterone 5mg tablets | 30 tablet P £2.48 DT price = £2.18 Noriday (Pfizer Ltd) Norethisterone 350 microgram Noriday 350microgram tablets | 84 tablet P £2.10 DT price = £1.80 Primolut N (Bayer Plc) Norethisterone mg Primolut N 5mg tablets | 30 tablet P £2.26 DT price = £2.18 Utovlan (Pfizer Ltd) Norethisterone mg Utovlan 5mg tablets | 30 tablet P £1.40 DT price = £2.18 | 90 tablet P £4.21 Combinations available: Estradiol with norethisterone, p 718 Progesterone l 06-Jun-2017 INDICATIONS AND DOSE CRINONE ® VAGINAL GEL Infertility due to inadequate luteal phase ▶ BY VAGINA ▶ Adult: applicatorful daily, to be started either after documented ovulation or on day 18–21 of cycle, in vitro fertilisation, daily application continued for 30 days after laboratory evidence of pregnancy CYCLOGEST ® PESSARIES Premenstrual syndrome | Post-natal depression ▶ BY VAGINA, OR BY RECTUM ▶ Adult: 200–800 mg daily, doses above 200 mg to be given in divided doses, for premenstrual syndrome start on day 12–14 and continue until onset of menstruation (but not recommended); rectally if barrier methods of contraception are used, in patients who have recently given birth or in those who suffer from vaginal infection or recurrent cystitis GESTONE ® SOLUTION FOR INJECTION Dysfunctional uterine bleeding ▶ BY DEEP INTRAMUSCULAR INJECTION ▶ Adult: 5–10 mg daily for 5–10 days until days before expected onset of menstruation, to be administered into buttocks continued → Endocrine system BNF 74 722 Sex hormone responsive conditions Recurrent miscarriage due to inadequate luteal phase (but not recommended) or following in vitro fertilisation or gamete intra-fallopian transfer BNF 74 l l ▶ BY DEEP INTRAMUSCULAR INJECTION ▶ Adult: 25–100 mg 2–7 times a week from day 15, or day of embryo or gamete transfer, until 8–16 weeks of pregnancy, to be administered into buttocks; maximum 200 mg per day l l ® Endocrine system LUBION Supplementation of luteal phase during assisted reproductive technology (ART) treatment in women for whom vaginal preparations are inappropriate ▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR INJECTION ▶ ▶ l ▶ l Adult: 25 mg once daily from day of oocyte retrieval up to week 12 of pregnancy Scottish Medicines Consortium (SMC) Decisions The Scottish Medicines Consortium has advised (October LUTIGEST ® Luteal support as part of an Assisted Reproductive Technology (ART) treatment programme 2016) that progesterone (Lutigest ®) is accepted for use ▶ BY VAGINA ▶ Adult: 100 mg times a day, to be started the day after oocyte retrieval, and continued for 30 days once pregnancy is confirmed UTROGESTAN ® CAPSULES Progestogenic opposition of oestrogen HRT ▶ BY MOUTH ▶ Adult: 200 mg once daily on days 15–26 of each 28-day oestrogen HRT cycle, alternatively 100 mg once daily on days 1–25 of each 28-day oestrogen HRT cycle UTROGESTAN ® VAGINAL CAPSULES Supplementation of luteal phase during assisted reproductive technology (ART) cycles ▶ BY VAGINA ▶ l l l l ▶ ▶ ▶ l Adult: capsule times a day from day of embryo transfer until at least week of pregnancy up to week 12 of pregnancy CONTRA-INDICATIONS Acute porphyrias p 969 avoid in patients with a history of liver tumours breast cancer (unless progestogens are being used in the management of this condition) genital cancer (unless progestogens are being used in the management of this condition) history during pregnancy of idiopathic jaundice history during pregnancy of pemphigoid gestationis history during pregnancy of severe pruritus history of thromboembolism incomplete miscarriage missed miscarriage severe arterial disease thrombophlebitis undiagnosed vaginal bleeding CAUTIONS Asthma cardiac dysfunction conditions that may worsen with fluid retention diabetes (progestogens can decrease glucose tolerance—monitor patient closely) epilepsy history of depression hypertension migraine susceptibility to thromboembolism (particular caution with high dose) INTERACTIONS → Appendix 1: progesterone SIDE-EFFECTS GENERAL SIDE-EFFECTS Acne alopecia anaphylactoid reactions bloating breast tenderness change in libido depression dizziness drowsiness fluid retention headache hirsutism insomnia jaundice menstrual disturbances nausea premenstrual-like syndrome pruritus rash skin reactions urticaria weight change SPECIFIC SIDE-EFFECTS With intramuscular use or subcutaneous use Injection-site reactions With rectal use Diarrhoea flatulence pain With vaginal use Local irritation PREGNANCY Not known to be harmful BREAST FEEDING Avoid—present in milk HEPATIC IMPAIRMENT Avoid in hepatic impairment Avoid in active liver disease including disorders of hepatic excretion (e.g Dublin-Johnson or Rotor Syndromes), infective hepatitis (until liver function returns to normal) and liver tumours RENAL IMPAIRMENT Use with caution DIRECTIONS FOR ADMINISTRATION With oral use Capsules should be taken at bedtime on an empty stomach PATIENT AND CARER ADVICE With oral use Patient counselling is advised for progesterone capsules (administration) NATIONAL FUNDING/ACCESS DECISIONS LUTIGEST ® l l within NHS Scotland for luteal support as part of an assisted reproductive technology (ART) treatment program for infertile women This advice is contingent upon the continuing availability of the Patient Access Scheme (PAS) in NHS Scotland or a list price that is equivalent or lower UTROGESTAN ® VAGINAL CAPSULES Scottish Medicines Consortium (SMC) Decisions The Scottish Medicines Consortium has advised (May 2017) that micronised progesterone (Utrogestan Vaginal ®) is accepted for use within NHS Scotland for supplementation of the luteal phase during Assisted Reproductive Technology cycles in women This advice is contingent upon the continuing availability of the Patient Access Scheme in Scotland or a list price that is equivalent or lower LESS SUITABLE FOR PRESCRIBING Progesterone pessaries are less suitable for prescribing MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Pessary ▶ ▶ Cyclogest (Actavis UK Ltd) Progesterone 200 mg Cyclogest 200mg pessaries | 15 pessary P £8.95 DT price = £8.95 Progesterone 400 mg Cyclogest 400mg pessaries | 15 pessary P £12.96 DT price = £12.96 Lutigest (Ferring Pharmaceuticals Ltd) Progesterone 100 mg Lutigest 100mg vaginal tablets | 21 pessary P £19.50 DT price = £19.50 Solution for injection ▶ ▶ Gestone (Nordic Pharma Ltd) Progesterone 50 mg per ml Gestone 50mg/1ml solution for injection ampoules | 10 ampoule P £45.00 Gestone 100mg/2ml solution for injection ampoules | 10 ampoule P £45.00 Lubion (Pharmasure Ltd) Progesterone 22.35 mg per ml Lubion 25mg/1.119ml solution for injection vials | vial P £56.00 Vaginal gel ▶ Crinone (Merck Serono Ltd) Progesterone 80 mg per gram Crinone 8% progesterone vaginal gel | 15 unit dose P £30.83 Capsule EXCIPIENTS: May contain Arachis (peanut) oil ▶ Utrogestan (Besins Healthcare (UK) Ltd) Progesterone 100 mg Utrogestan 100mg capsules | 30 capsule P £5.13 Progesterone 200 mg Utrogestan 200mg vaginal capsules with applicators | 21 capsule P £21.00 Male sex hormone responsive conditions 723 BNF 74 ▶ 8.1a Anti-oestrogens Clomid (Sanofi) Clomifene citrate 50 mg Clomid 50mg tablets | 30 tablet £10.15 DT price = £10.15 P OVULATION STIMULANTS 8.2 Male sex hormone responsive conditions (Clomiphene citrate) l DRUG ACTION Anti-oestrogen which induces gonadotrophin release by occupying oestrogen receptors in the hypothalamus, thereby interfering with feedback mechanisms; chorionic gonadotrophin is sometimes used as an adjunct INDICATIONS AND DOSE Treatment of female infertility due to oligomenorrhoea or secondary amenorrhoea (e.g associated with polycystic ovarian disease) l ▶ BY MOUTH ▶ Adult (female): 50 mg daily for days, to be started within about days of onset of menstruation (preferably on 2nd day) or at any time (normally preceded by a progestogen induced withdrawal bleed) if cycles have ceased, followed by 100 mg daily if required for a further days, this second course may be given in absence of ovulation; most patients who are going to respond will so to first course, courses should constitute adequate therapeutic trial; longterm cyclical therapy not recommended IMPORTANT SAFETY INFORMATION The CSM has recommended that clomifene should not normally be used for longer than cycles (possibly increased risk of ovarian cancer) l l l l l l l l l l CONTRA-INDICATIONS Abnormal uterine bleeding of undetermined cause hormone-dependent tumours ovarian cysts CAUTIONS Ectopic pregnancy incidence of multiple births increased (consider ultrasound monitoring) ovarian hyperstimulation syndrome polycystic ovary syndrome (cysts may enlarge during treatment, also risk of exaggerated response to usual doses) uterine fibroids INTERACTIONS → Appendix 1: clomifene SIDE-EFFECTS Abdominal discomfort breast tenderness convulsions depression dizziness endometriosis hair loss headache hot flushes insomnia intermenstrual spotting menorrhagia nausea ovarian hyperstimulation (withdraw) rashes visual disturbances (withdraw and initiate ophthalmological examination) vomiting weight gain CONCEPTION AND CONTRACEPTION Exclude pregnancy before treatment PREGNANCY Possible effects on fetal development BREAST FEEDING May inhibit lactation HEPATIC IMPAIRMENT Avoid in severe liver disease PATIENT AND CARER ADVICE Patient advice required around conception and contraception Patients planning to conceive should be warned that there is a risk of multiple pregnancy (rarely more than twins) MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ▶ Clomifene citrate (Non-proprietary) Clomifene citrate 50 mg Clomifene 50mg tablets | 30 tablet £21.74 DT price = £10.15 P Androgens, anti-androgens and anabolic steroids Androgens Androgens cause masculinisation; they may be used as replacement therapy in castrated adults and in those who are hypogonadal due to either pituitary or testicular disease In the normal male they inhibit pituitary gonadotrophin secretion and depress spermatogenesis Androgens also have an anabolic action which led to the development of anabolic steroids Androgens are useless as a treatment of impotence and impaired spermatogenesis unless there is associated hypogonadism; they should not be given until the hypogonadism has been properly investigated Treatment should be under expert supervision When given to patients with hypopituitarism they can lead to normal sexual development and potency but not to fertility If fertility is desired, the usual treatment is with gonadotrophins or pulsatile gonadotrophin-releasing hormone which will stimulate spermatogenesis as well as androgen production Intramuscular depot preparations of testosterone esters are preferred for replacement therapy Testosterone enantate, propionate or undecanoate, or alternatively Sustanon ®, which consists of a mixture of testosterone esters and has a longer duration of action, may be used Anti-androgens Cyproterone acetate Cyproterone acetate p 725 is an anti-androgen used in the treatment of severe hypersexuality and sexual deviation in the male It inhibits spermatogenesis and produces reversible infertility (but is not a male contraceptive); abnormal sperm forms are produced Fully informed consent is recommended and an initial spermatogram As hepatic tumours have been produced in animal studies, careful consideration should be given to the risk/benefit ratio before treatment Cyproterone acetate is also licensed for use alone in patients with metastatic prostate cancer refractory to gonadorelin analogue therapy and has been used as an adjunct in prostatic cancer and in the treatment of acne and hirsutism in women Dutasteride and finasteride Dutasteride p 741 and finasteride p 742 are alternatives to alpha-blockers particularly in men with a significantly enlarged prostate Finasteride is also licensed for use with doxazosin p 738 in the management of benign prostatic hyperplasia A low strength of finasteride is licensed for treating malepattern baldness in men Anabolic steroids Anabolic steroids have some androgenic activity but they cause less virilisation than androgens in women They are used in the treatment of some aplastic anaemias Anabolic steroids have been given for osteoporosis in women but they are no longer advocated for this purpose The protein-building properties of anabolic steroids have not proved beneficial in the clinical setting Their use as Endocrine system Clomifene citrate 724 Sex hormone responsive conditions BNF 74 body builders or tonics is unjustified; some athletes abuse them l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Tablet ANDROGENS ▶ Androgens Endocrine system l l l ▶ ▶ ▶ ▶ l l l l l ▶ ▶ l f CONTRA-INDICATIONS Breast cancer in males history of liver tumours hypercalcaemia prostate cancer CAUTIONS Cardiac impairment diabetes mellitus elderly epilepsy hypertension ischaemic heart disease migraine pre-pubertal boys (fusion of epiphyses is hastened and may result in short stature)—statural growth and sexual development should be monitored skeletal metastases—risk of hypercalcaemia or hypercalciuria (if this occurs, treat appropriately and restart treatment once normal serum calcium concentration restored) sleep apnoea stop treatment or reduce dose if severe polycythaemia occurs tumours—risk of hypercalcaemia or hypercalciuria (if this occurs, treat appropriately and restart treatment once normal serum calcium concentration restored) SIDE-EFFECTS Common or very common Acne androgenic effects (to be assessed regularly in women) anxiety arthralgia asthenia changes in libido cholestatic jaundice depression electrolyte disturbances excessive duration of penile erection excessive frequency of penile erection gastro-intestinal bleeding gynaecomastia headache hirsutism hypercalcaemia hypertension increased bone growth irritability male-pattern baldness muscle cramps nausea nervousness oedema paraesthesia polycythaemia precocious sexual development in prepubertal males premature closure of epiphyses in prepubertal males prostate abnormalities prostate cancer pruritus seborrhoea sodium retention suppression of virilism in women vomiting weight gain Rare Liver tumours Frequency not known Sleep apnoea SIDE-EFFECTS, FURTHER INFORMATION Polycythaemia Stop treatment or reduce dose if severe polycythaemia occurs PREGNANCY Avoid—causes masculinisation of female fetus BREAST FEEDING Avoid HEPATIC IMPAIRMENT Avoid if possible—fluid retention and dose-related toxicity RENAL IMPAIRMENT Caution—potential for fluid retention MONITORING REQUIREMENTS Monitor haematocrit and haemoglobulin before treatment, every three months for the first year, and yearly thereafter Monitor prostate and PSA in men over 45 years PATIENT AND CARER ADVICE Androgenic effects in women Women should be advised to report any signs of virilisation e.g deepening of the voice or hirsutism eiii i F above l ▶ BY TRANSDERMAL APPLICATION Adult: Apply 50 mg once daily, subsequent application adjusted according to response; maximum 100 mg per day DOSE EQUIVALENCE AND CONVERSION ▶ One tube of g contains 50 mg testosterone ▶ TESTOGEL ® Hypogonadism due to androgen deficiency in men ▶ BY TRANSDERMAL APPLICATION ▶ Adult: Apply 50 mg once daily; increased in steps of 25 mg, adjusted according to response; maximum 100 mg per day DOSE EQUIVALENCE AND CONVERSION ▶ One sachet of g contains 50 mg of testosterone TOSTRAN ® Hypogonadism due to testosterone deficiency in men ▶ BY TRANSDERMAL APPLICATION Adult: Apply 60 mg once daily, subsequent application adjusted according to response; maximum 80 mg per day DOSE EQUIVALENCE AND CONVERSION ▶ g of gel contains 20 mg testosterone ▶ l l INDICATIONS AND DOSE Androgen deficiency | Male infertility associated with hypogonadism l Adult: 25 mg 3–4 times a day for several months, then maintenance 50–75 mg daily in divided doses INDICATIONS AND DOSE TESTIM ® Hypogonadism due to testosterone deficiency in men eiii i F above ▶ BY MOUTH P Testosterone Mesterolone ▶ Pro-Viron (Bayer Plc) Mesterolone 25 mg Pro-Viron 25mg tablets | 30 tablet £4.19 e l SIDE-EFFECTS Allergic reactions local irritation suppression of spermatogenesis DIRECTIONS FOR ADMINISTRATION Avoid skin contact with gel application sites to prevent testosterone transfer to other people, especially pregnant women and children— consult product literature TESTOGEL ® Apply thin layer of gel on clean, dry, healthy skin such as shoulders, arms or abdomen, immediately after sachet is opened Not to be applied on genital area as high alcohol content may cause local irritation Allow to dry for 3–5 minutes before dressing Wash hands with soap and water after applying gel, avoid shower or bath for at least hours TESTIM ® Squeeze entire content of tube on to one palm and apply as a thin layer on clean, dry, healthy skin of shoulder or upper arm, preferably in the morning after washing or bathing (if tubes required use per shoulder or upper arm); rub in and allow to dry before putting on clothing to cover site; wash hands with soap after application; avoid washing application site for at least hours TOSTRAN ® Apply gel on clean, dry, intact skin of abdomen or both inner thighs, preferably in the morning Gently rub in with a finger until dry before dressing Wash hands with soap and water after applying gel; avoid washing application site for at least hours Not to be applied on genital area PATIENT AND CARER ADVICE Patient or carer should be given advice on how to administer testosterone gel Male sex hormone antagonism 725 BNF 74 MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Delayed puberty in males ▶ BY INTRAMUSCULAR INJECTION Adult: 50 mg once weekly Breast cancer in women ▶ Gel EXCIPIENTS: May contain Butylated hydroxytoluene, propylene glycol ▶ ▶ ▶ Testim (Ferring Pharmaceuticals Ltd) Testosterone 50 mg Testim 50mg/5g gel | 30 tube P £32.00 DT price = £32.00 e Testogel (Besins Healthcare (UK) Ltd) Testosterone 50 mg Testogel 50mg/5g gel sachets | 30 sachet P £31.11 DT price = £31.11 e Tostran (Kyowa Kirin Ltd) Testosterone 20 mg per gram Tostran 2% gel | 60 gram P £28.67 DT price = £28.67 e ▶ BY INTRAMUSCULAR INJECTION ▶ SIDE-EFFECTS Suppression of spermatogenesis l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: solution for injection eiii i F 724 Testosterone undecanoate INDICATIONS AND DOSE Androgen deficiency l The properties listed below are those particular to the combination only For the properties of the components please consider, testosterone propionate below ▶ BY MOUTH ▶ Adult: 120–160 mg daily for 2–3 weeks; maintenance 40–120 mg daily Hypogonadism INDICATIONS AND DOSE Androgen deficiency l ▶ BY DEEP INTRAMUSCULAR INJECTION ▶ ▶ BY DEEP INTRAMUSCULAR INJECTION l l Testosterone decanoate, isocaproate, phenylpropionate and propionate ▶ Adult: 100 mg 2–3 times a week Adult: mL every weeks Adult (male): g every 10–14 weeks, to be given over minutes, if necessary, second dose may be given after weeks to achieve rapid steady state plasma testosterone levels and then every 10–14 weeks MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug l SIDE-EFFECTS Suppression of spermatogenesis Solution for injection l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug EXCIPIENTS: May contain Arachis (peanut) oil, benzyl alcohol ▶ Sustanon (Aspen Pharma Trading Ltd) Testosterone propionate 30 mg per ml, Testosterone isocaproate 60 mg per ml, Testosterone phenylpropionate 60 mg per ml, Testosterone decanoate 100 mg per ml Sustanon 250mg/1ml solution for injection ampoules | ampoule P £2.45 e eiii i F 724 Testosterone enantate Solution for injection ▶ Nebido (Bayer Plc) Testosterone undecanoate 250 mg per ml Nebido 1000mg/4ml solution for injection vials | vial P £87.11 DT price = £87.11 e Capsule CAUTIONARY AND ADVISORY LABELS 21, 25 ▶ INDICATIONS AND DOSE Hypogonadism l Restandol (Merck Sharp & Dohme Ltd) Testosterone undecanoate 40 mg Restandol 40mg Testocaps | 30 capsule P £8.55 e | 60 capsule P £17.10 DT price = £17.10 e ▶ BY SLOW INTRAMUSCULAR INJECTION Adult: Initially 250 mg every 2–3 weeks; maintenance 250 mg every 3–6 weeks Breast cancer ▶ 8.2a Male sex hormone antagonism ▶ BY SLOW INTRAMUSCULAR INJECTION ▶ l l l Adult: 250 mg every 2–3 weeks ANTI-ANDROGENS UNLICENSED USE Not licensed for use in breast cancer SIDE-EFFECTS Suppression of spermatogenesis MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Solution for injection ▶ eiii i F 724 INDICATIONS AND DOSE Androgen deficiency l ▶ BY INTRAMUSCULAR INJECTION ▶ Adult: 50 mg 2–3 times a week l INDICATIONS AND DOSE Hyper-sexuality in males | Sexual deviation in males ▶ BY MOUTH Adult: 50 mg twice daily, to be taken after food Prevention of tumour flare with initial gonadorelin analogue therapy ▶ Testosterone enantate (Non-proprietary) Testosterone enantate 250 mg per ml Testosterone enantate 250mg/1ml solution for injection ampoules | ampoule P £79.75 DT price = £79.75 e Testosterone propionate Cyproterone acetate ▶ BY MOUTH Adult (male): 200 mg daily in 2–3 divided doses for 5–7 days before initiation of gonadorelin analogue, followed by 200 mg daily in 2–3 divided doses for 3–4 weeks after initiation of gonadorelin analogue; maximum 300 mg per day Long-term palliative therapy where gonadorelin analogues or orchidectomy contra-indicated, not tolerated, or where oral therapy preferred ▶ ▶ BY MOUTH ▶ Adult (male): 200–300 mg daily in 2–3 divided doses continued → Endocrine system l 726 Thyroid disorders Hot flushes with gonadorelin analogue therapy or after orchidectomy ▶ BY MOUTH ▶ Endocrine system l l l l ▶ ▶ ▶ l l ▶ ▶ ▶ l l Adult (male): Initially 50 mg daily, then adjusted according to response to 50–150 mg daily in 1–3 divided doses CONTRA-INDICATIONS In hypersexuality, Dubin-Johnson syndrome in hypersexuality, history of thromboembolic disorders in hypersexuality, liver-disease in hypersexuality, malignant diseases in hypersexuality, previous or existing liver tumours in hypersexuality, Rotor syndrome in hypersexuality, severe depression in hypersexuality, severe diabetes (with vascular changes) in hypersexuality, sickle-cell anaemia in hypersexuality, wasting diseases meningioma or history of meningioma CAUTIONS Diabetes mellitus in prostate cancer, severe depression in prostate cancer, sickle-cell anaemia ineffective for male hypersexuality in chronic alcoholism (relevance to prostate cancer not known) INTERACTIONS → Appendix 1: cyproterone SIDE-EFFECTS Rare Hypersensitivity reactions osteoporosis rash Frequency not known Breathlessness changes in hair pattern fatigue gynaecomastia (rarely leading to galactorrhoea and benign breast nodules) hepatic failure hepatitis hepatotoxicity inhibition of spermatogenesis jaundice lassitude reduced sebum production (may clear acne) risk of recurrence of thromboembolic disease weight changes SIDE-EFFECTS, FURTHER INFORMATION Hepatotoxicity Direct hepatic toxicity including jaundice, hepatitis and hepatic failure have been reported (fatalities reported, usually after several months, at dosages of 100 mg and above) If hepatotoxicity is confirmed, cyproterone should normally be withdrawn unless the hepatotoxicity can be explained by another cause such as metastatic disease (in which case cyproterone should be continued only if the perceived benefit exceeds the risk) HEPATIC IMPAIRMENT Avoid (unless used for prostate cancer)—dose-related toxicity MONITORING REQUIREMENTS Monitor blood counts initially and throughout treatment Monitor adrenocortical function regularly Monitor hepatic function regularly—liver function tests should be performed before and regularly during treatment and whenever symptoms suggestive of hepatotoxicity occur PATIENT AND CARER ADVICE Driving and skilled tasks Fatigue and lassitude may impair performance of skilled tasks (e.g driving) MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: tablet, capsule, oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 21 ▶ ▶ ▶ Cyproterone acetate (Non-proprietary) Cyproterone acetate 50 mg Cyproterone 50mg tablets | 56 tablet P £48.95 | 168 tablet P £87.00 DT price = £87.00 Cyproterone acetate 100 mg Cyproterone 100mg tablets | 84 tablet P £132.57 DT price = £55.19 Androcur (Bayer Plc) Cyproterone acetate 50 mg Androcur 50mg tablets | 56 tablet P £29.25 Cyprostat (Bayer Plc) Cyproterone acetate 50 mg Cyprostat 50mg tablets | 168 tablet P £87.00 DT price = £87.00 Cyproterone acetate 100 mg Cyprostat 100mg tablets | 84 tablet P £87.00 DT price = £55.19 BNF 74 Thyroid disorders PITUITARY AND HYPOTHALAMIC HORMONES AND ANALOGUES › THYROID STIMULATING HORMONES Thyrotropin alfa (Recombinant human thyroid stimulating hormone; rhTSH) l DRUG ACTION Thyrotropin alfa is a recombinant form of thyrotrophin (thyroid stimulating hormone) INDICATIONS AND DOSE Detection of thyroid remnants and thyroid cancer in postthyroidectomy patients, together with serum thyroglobulin testing (with or without radioiodine imaging) | To increase radio-iodine uptake for the ablation of thyroid remnant tissue in suitable postthyroidectomy patients l ▶ BY INTRAMUSCULAR INJECTION ▶ l l ▶ ▶ ▶ ▶ l l l l Adult: 900 micrograms every 24 hours for doses, dose to be administered into the gluteal muscle, consult product literature for further information on indications and dose CAUTIONS Presence of thyroglobulin autoantibodies may give false negative results SIDE-EFFECTS Common or very common Dizziness fatigue headache nausea vomiting Uncommon Asthenia back pain influenza-like symptoms paraesthesia rash urticaria Rare Diarrhoea Very rare Arthralgia dyspnoea flushing hyperhidrosis injection-site pain injection-site pruritus injection-site rash injection-site reactions myalgia pain at site of metastases palpitation tremor ALLERGY AND CROSS-SENSITIVITY Contra-indicated if previous hypersensitivity to bovine or human thyrotrophin PREGNANCY Avoid BREAST FEEDING Avoid MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Powder for solution for injection ▶ Thyrogen (Genzyme Therapeutics Ltd) Thyrotropin alfa 900 microgram Thyrogen 900microgram powder for solution for injection vials | vial P £583.04 9.1 Hyperthyroidism Antithyroid drugs Overview Antithyroid drugs are used for hyperthyroidism either to prepare patients for thyroidectomy or for long-term management In the UK carbimazole p 727 is the most commonly used drug Propylthiouracil p 728 should be reserved for patients who are intolerant of carbimazole or for those who experience sensitivity reactions to carbimazole (sensitivity is not necessarily displayed to both drugs), and for whom other treatments are inappropriate Both drugs act primarily by interfering with the synthesis of thyroid hormones Hyperthyroidism 727 BNF 74 Pregnancy Radioactive iodine therapy is contra-indicated during pregnancy Propylthiouracil and carbimazole can be given but the blocking-replacement regimen is not suitable Rarely, carbimazole has been associated with congenital defects, including aplasia cutis of the neonate, therefore propylthiouracil remains the drug of choice during the first trimester of pregnancy In the second trimester, consider switching to carbimazole because of the potential risk of hepatotoxicity with propylthiouracil Both propylthiouracil and carbimazole cross the placenta and in high doses may cause fetal goitre and hypothyroidism—the lowest dose that will control the hyperthyroid state should be used (requirements in Graves’ disease tend to fall during pregnancy) Other drugs used for Hyperthyroidism Metoprolol tartrate, p 149 ANTITHYROID DRUGS › SULFUR-CONTAINING IMIDAZOLES Carbimazole INDICATIONS AND DOSE Hyperthyroidism l ▶ BY MOUTH ▶ Adult: 15–40 mg daily continue until the patient becomes euthyroid, usually after to weeks, higher doses should be prescribed under specialist supervision only, then reduced to 5–15 mg daily, reduce dose gradually, therapy usually given for 12 to 18 months Hyperthyroidism (blocking-replacement regimen) in combination with levothyroxine ▶ BY MOUTH Adult: 40–60 mg daily, therapy usually given for 18 months DOSE EQUIVALENCE AND CONVERSION ▶ When substituting, carbimazole mg is considered equivalent to propylthiouracil 10 mg but the dose may need adjusting according to response ▶ IMPORTANT SAFETY INFORMATION NEUTROPENIA AND AGRANULOCYTOSIS Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and the need to stop treatment promptly Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat A white blood cell count should be performed if there is any clinical evidence of infection Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia CONTRA-INDICATIONS Severe blood disorders INTERACTIONS → Appendix 1: carbimazole l SIDE-EFFECTS ▶ Common or very common Arthralgia fever headache jaundice malaise mild gastro-intestinal disturbances nausea pruritus rash taste disturbance ▶ Rare Agranulocytosis alopecia bone marrow suppression jaundice myopathy pancytopenia SIDE-EFFECTS, FURTHER INFORMATION Rashes and pruritus are common with carbimazole but they can be treated with antihistamines without discontinuing therapy; alternatively propylthiouracil can be substituted l PREGNANCY Carbimazole can be given but the blockingreplacement regimen is not suitable Rarely, carbimazole has been associated with congenital defects, including aplasia cutis of the neonate Carbimazole cross the placenta and in high doses may cause fetal goitre and hypothyroidism—the lowest dose that will control the hyperthyroid state should be used (requirements in Graves’ disease tend to fall during pregnancy) l BREAST FEEDING Present in breast milk but this does not preclude breast-feeding as long as neonatal development is closely monitored and the lowest effective dose is used Amount in milk may be sufficient to affect neonatal thyroid function therefore lowest effective dose should be used l HEPATIC IMPAIRMENT Use with caution in mild to moderate impairment Avoid in severe impairment l PATIENT AND CARER ADVICE Warn patient or carers to tell doctor immediately if sore throat, mouth ulcers, bruising, fever, malaise, or non-specific illness develops l l l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: capsule, oral suspension, oral solution Tablet ▶ Carbimazole (Non-proprietary) Carbimazole mg Carbimazole 5mg tablets | 100 tablet P £84.80 DT price = £62.37 Carbimazole 20 mg Carbimazole 20mg tablets | 100 tablet P £216.00 DT price = £166.71 Endocrine system Over-treatment with antithyroid drugs can result in the rapid development of hypothyroidism and should be avoided particularly during pregnancy because it can cause fetal goitre A combination of carbimazole with levothyroxine sodium p 729 daily, may be used in a blocking-replacement regimen; therapy is usually given for 18 months The blockingreplacement regimen is not suitable during pregnancy Iodine has been used as an adjunct to antithyroid drugs for 10 to 14 days before partial thyroidectomy; however, there is little evidence of a beneficial effect Iodine should not be used for long-term treatment because its antithyroid action tends to diminish Radioactive sodium iodide (131 I) solution is used increasingly for the treatment of thyrotoxicosis at all ages, particularly where medical therapy or compliance is a problem, in patients with cardiac disease, and in patients who relapse after thyroidectomy Propranolol hydrochloride p 145 is useful for rapid relief of thyrotoxic symptoms and may be used in conjunction with antithyroid drugs or as an adjunct to radioactive iodine Beta-blockers are also useful in neonatal thyrotoxicosis and in supraventricular arrhythmias due to hyperthyroidism Propranolol hydrochloride has been used in conjunction with iodine to prepare mildly thyrotoxic patients for surgery but it is preferable to make the patient euthyroid with carbimazole Laboratory tests of thyroid function are not altered by beta-blockers Most experience in treating thyrotoxicosis has been gained with propranolol hydrochloride but nadolol p 144 is also used Thyrotoxic crisis (‘thyroid storm’) requires emergency treatment with intravenous administration of fluids, propranolol hydrochloride and hydrocortisone p 637 (as sodium succinate), as well as oral iodine solution and carbimazole or propylthiouracil which may need to be administered by nasogastric tube 728 Thyroid disorders ANTITHYROID DRUGS › THIOURACILS Endocrine system VITAMINS AND TRACE ELEMENTS Propylthiouracil Iodide with iodine l INDICATIONS AND DOSE Hyperthyroidism l INDICATIONS AND DOSE Thyrotoxicosis (pre-operative) ▶ BY MOUTH ▶ BY MOUTH USING ORAL SOLUTION Adult: Initially 200–400 mg daily in divided doses until the patient becomes euthyroid, then reduced to 50–150 mg daily in divided doses, initial dose should be gradually reduced to the maintenance dose DOSE EQUIVALENCE AND CONVERSION ▶ When substituting, carbimazole mg is considered equivalent to propylthiouracil 10 mg but the dose may need adjusting according to response BNF 74 ▶ INTERACTIONS → Appendix 1: propylthiouracil SIDE-EFFECTS ▶ Common or very common Arthralgia fever headache jaundice leucopenia malaise mild gastro-intestinal disturbances nausea pruritus rash taste disturbance ▶ Rare Agranulocytosis alopecia aplastic anaemia bone marrow suppression cutaneous vasculitis encephalopathy hepatic disorders hepatic failure hepatic necrosis hepatitis hypoprothrombinaemia jaundice lupus erythematous-like syndromes myopathy nephritis pancytopenia thrombocytopenia SIDE-EFFECTS, FURTHER INFORMATION ▶ Hepatotoxicity Severe hepatic reactions have been reported, including fatal cases and cases requiring liver transplant— discontinue if significant liver-enzyme abnormalities develop l PREGNANCY Propylthiouracil can be given but the blocking-replacement regimen is not suitable Propylthiouracil crosses the placenta and in high doses may cause fetal goitre and hypothyroidism—the lowest dose that will control the hyperthyroid state should be used (requirements in Graves’ disease tend to fall during pregnancy) l BREAST FEEDING Present in breast milk but this does not preclude breast-feeding as long as neonatal development is closely monitored and the lowest effective dose is used Amount in milk probably too small to affect infant; high doses may affect neonatal thyroid function Monitor infant’s thyroid status l HEPATIC IMPAIRMENT Reduce dose l RENAL IMPAIRMENT Use three-quarters normal dose if eGFR 10–50 mL/minute/1.73 m2 Use half normal dose if eGFR less than 10 mL/minute/1.73 m2 l MONITORING REQUIREMENTS Monitor for hepatotoxicity l PATIENT AND CARER ADVICE Patients should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, or pruritus develop l l l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: oral suspension, oral solution Tablet ▶ Propylthiouracil (Non-proprietary) Propylthiouracil 50 mg Propylthiouracil 50mg tablets | 56 tablet P £71.44 DT price = £59.47 | 100 tablet P £127.57 ▶ l l l l l l Adult: 0.1–0.3 mL times a day CAUTIONS Children not for long-term treatment SIDE-EFFECTS Bronchitis conjunctivitis coryza-like symptoms depression (on prolonged treatment) goitre in infants of mothers taking iodides headache hypersensitivity reactions impotence (on prolonged treatment) insomnia (on prolonged treatment) lacrimation laryngitis pain in salivary glands rashes PREGNANCY Neonatal goitre and hypothyroidism BREAST FEEDING Stop breast-feeding Danger of neonatal hypothyroidism or goitre Appears to be concentrated in milk DIRECTIONS FOR ADMINISTRATION For oral solution, dilute well with milk or water MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Oral solution CAUTIONARY AND ADVISORY LABELS 27 ▶ Iodide with iodine (Non-proprietary) Iodine 50 mg per ml, Potassium iodide 100 mg per ml Iodine aqueous oral solution | 500 ml p £9.58 9.2 Hypothyroidism Thyroid hormones Overview Thyroid hormones are used in hypothyroidism (myxoedema), and also in diffuse non-toxic goitre, Hashimoto’s thyroiditis (lymphadenoid goitre), and thyroid carcinoma Neonatal hypothyroidism requires prompt treatment for normal development Levothyroxine sodium p 729 (thyroxine sodium) is the treatment of choice for maintenance therapy In infants and children with congenital hypothyroidism and juvenile myxoedema, the dose of levothyroxine sodium should be titrated according to clinical response, growth assessment, and measurements of plasma thyroxine and thyroid-stimulating hormone Liothyronine sodium p 729 has a similar action to levothyroxine sodium but is more rapidly metabolised and has a more rapid effect Its effects develop after a few hours and disappear within 24 to 48 hours of discontinuing treatment It may be used in severe hypothyroid states when a rapid response is desired Liothyronine sodium by intravenous injection is the treatment of choice in hypothyroid coma Adjunctive therapy includes intravenous fluids, hydrocortisone p 637, and treatment of infection; assisted ventilation is often required Hypothyroidism 729 THYROID HORMONES Levothyroxine sodium l (Thyroxine sodium) l INDICATIONS AND DOSE Hypothyroidism ▶ BY MOUTH Adult 18–49 years: Initially 50–100 micrograms once daily; adjusted in steps of 25–50 micrograms every 3–4 weeks, adjusted according to response; maintenance 100–200 micrograms once daily, dose to be taken preferably at least 30 minutes before breakfast, caffeine-containing liquids (e.g coffee, tea), or other medication ▶ Adult 50 years and over: Initially 25 micrograms once daily; adjusted in steps of 25 micrograms every weeks, adjusted according to response; maintenance 50–200 micrograms once daily, dose to be taken preferably at least 30 minutes before breakfast, caffeine-containing liquids (e.g coffee, tea), or other medication Hypothyroidism in patients with cardiac disease | Severe hypothyroidism ▶ l l ischaemia), reduce dose or withhold for 1–2 days and start again at a lower dose PREGNANCY Levothyroxine requirement may increase during pregnancy Levothyroxine may cross the placenta Excessive or insufficient maternal thyroid hormones can be detrimental to fetus Assess maternal thyroid function before conception (if possible), at diagnosis of pregnancy, at antenatal booking, during both the second and third trimesters, and after delivery (more frequent monitoring required on initiation or adjustment of levothyroxine) BREAST FEEDING Amount too small to affect tests for neonatal hypothyroidism MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: capsule, oral suspension, oral solution Tablet ▶ ▶ BY MOUTH Adult: Initially 25 micrograms once daily; adjusted in steps of 25 micrograms every weeks, adjusted according to response; maintenance 50–200 micrograms once daily, dose to be taken preferably at least 30 minutes before breakfast, caffeine-containing liquids (e.g coffee, tea), or other medication Hyperthyroidism (blocking-replacement regimen) in combination with carbimazole ▶ ▶ BY MOUTH ▶ Adult: 50–150 micrograms daily therapy usually given for 18 months ▶ l l ▶ l l ▶ CONTRA-INDICATIONS Thyrotoxicosis CAUTIONS Cardiovascular disorders diabetes insipidus diabetes mellitus (dose of antidiabetic drugs including insulin may need to be increased) elderly hypertension long-standing hypothyroidism myocardial infarction myocardial insufficiency panhypopituitarism (initiate corticosteroid therapy before starting levothyroxine) predisposition to adrenal insufficiency (initiate corticosteroid therapy before starting levothyroxine) CAUTIONS, FURTHER INFORMATION Cardiovascular disorders Baseline ECG is valuable because changes induced by hypothyroidism can be confused with ischaemia INTERACTIONS → Appendix 1: levothyroxine SIDE-EFFECTS Anginal pain (usually at excessive dosage) arrhythmias (usually at excessive dosage) diarrhoea (usually at excessive dosage) excitability (usually at excessive dosage) fever flushing headache heat intolerance hypersensitivity reactions insomnia (usually at excessive dosage) muscle cramp muscular weakness oedema palpitation (usually at excessive dosage) pruritus rash restlessness (usually at excessive dosage) sweating tachycardia (usually at excessive dosage) transient hair loss in children tremor (usually at excessive dosage) vomiting (usually at excessive dosage) weightloss SIDE-EFFECTS, FURTHER INFORMATION Initial dosage in patients with cardiovascular disorders If metabolism increases too rapidly (causing diarrhoea, nervousness, rapid pulse, insomnia, tremors and sometimes anginal pain where there is latent myocardial Levothyroxine sodium (Non-proprietary) Levothyroxine sodium anhydrous 12.5 microgram Levothyroxine sodium 12.5microgram tablets | 28 tablet P £12.75–£15.00 DT price = £14.10 Levothyroxine sodium anhydrous 25 microgram Levothyroxine sodium 25microgram tablets | 28 tablet P £4.00 DT price = £2.91 | 500 tablet P £56.25 Levothyroxine sodium 25microgram tablets lactose free | 100 tablet P no price available Levothyroxine sodium anhydrous 50 microgram Levothyroxine sodium 50microgram tablets lactose free | 100 tablet P no price available Levothyroxine sodium 50microgram tablets | 28 tablet P £4.98 DT price = £1.66 | 1000 tablet P £68.21 Levothyroxine sodium anhydrous 75 microgram Levothyroxine sodium 75microgram tablets | 28 tablet P £2.82–£4.00 DT price = £3.34 Levothyroxine sodium anhydrous 100 microgram Levothyroxine sodium 100microgram tablets lactose free | 100 tablet P no price available Levothyroxine sodium 100microgram tablets | 28 tablet P £4.75 DT price = £1.66 | 1000 tablet P £68.57 Eltroxin (AMCo) Levothyroxine sodium anhydrous 25 microgram Eltroxin 25microgram tablets | 28 tablet P £2.33 DT price = £2.91 Levothyroxine sodium anhydrous 50 microgram Eltroxin 50microgram tablets | 28 tablet P £1.33 DT price = £1.66 Levothyroxine sodium anhydrous 100 microgram Eltroxin 100microgram tablets | 28 tablet P £1.33 DT price = £1.66 Oral solution ▶ Levothyroxine sodium (Non-proprietary) Levothyroxine sodium anhydrous microgram per ml Levothyroxine sodium 25micrograms/5ml oral solution sugar free sugar-free | 100 ml P £95.00 DT price = £94.59 Levothyroxine sodium anhydrous 10 microgram per ml Levothyroxine sodium 50micrograms/5ml oral solution sugar free sugar-free | 100 ml P £94.44 DT price = £93.02 Levothyroxine sodium anhydrous 20 microgram per ml Levothyroxine sodium 100micrograms/5ml oral solution sugar free sugar-free | 100 ml P £165.00 DT price = £164.14 Liothyronine sodium (L-Tri-iodothyronine sodium) INDICATIONS AND DOSE Hypothyroidism l ▶ BY MOUTH Adult: Initially 10–20 micrograms daily; increased to 60 micrograms daily in 2–3 divided doses, dose should be increased gradually, smaller initial doses given for the elderly Hypothyroid coma ▶ ▶ BY SLOW INTRAVENOUS INJECTION ▶ Adult: 5–20 micrograms every 12 hours, increased to 5–20 micrograms every hours if required, continued → Endocrine system BNF 74 730 Thyroid disorders alternatively initially 50 micrograms for dose, then 25 micrograms every hours, reduced to 25 micrograms twice daily DOSE EQUIVALENCE AND CONVERSION ▶ 20–25 micrograms of liothyronine sodium is equivalent to approximately 100 micrograms of levothyroxine sodium ▶ Brands without a UK licence may not be bioequivalent and dose adjustment may be necessary Endocrine system l l ▶ l l ▶ l l l CONTRA-INDICATIONS Thyrotoxicosis CAUTIONS Cardiovascular disorders diabetes insipidus diabetes mellitus (dose of antidiabetic drugs including insulin may need to be increased) elderly hypertension long-standing hypothyroidism myocardial infarction myocardial insufficiency panhypopituitarism (initiate corticosteroid therapy before starting liothyronine) predisposition to adrenal insufficiency (initiate corticosteroid therapy before starting liothyronine) CAUTIONS, FURTHER INFORMATION Cardiovascular disorders Baseline ECG is valuable because changes induced by hypothyroidism can be confused with ischaemia INTERACTIONS → Appendix 1: liothyronine SIDE-EFFECTS Anginal pain (usually at excessive dosage) arrhythmias (usually at excessive dosage) diarrhoea (usually at excessive dosage) excitability (usually at excessive dosage) fever flushing headache heat intolerance hypersensitivity reactions insomnia (usually at excessive dosage) muscle cramp muscular weakness oedema palpitation (usually at excessive dosage) pruritus rash restlessness (usually at excessive dosage) sweating tachycardia (usually at excessive dosage) tremor (usually at excessive dosage) vomiting (usually at excessive dosage) weight-loss SIDE-EFFECTS, FURTHER INFORMATION Initial dosage in patients with cardiovascular disorders If metabolism increases too rapidly (causing diarrhoea, nervousness, rapid pulse, insomnia, tremors and sometimes anginal pain where there is latent myocardial ischaemia), reduce dose or withhold for 1–2 days and start again at a lower dose PREGNANCY Liothyronine requirement may increase during pregnancy Does not cross the placenta in significant amounts Excessive or insufficient maternal thyroid hormones can be detrimental to fetus Assess maternal thyroid function before conception (if possible), at diagnosis of pregnancy, at antenatal booking, during both the second and third trimesters, and after delivery (more frequent monitoring required on initiation or adjustment of liothyronine) BREAST FEEDING Amount too small to affect tests for neonatal hypothyroidism PRESCRIBING AND DISPENSING INFORMATION Switching to a different brand Patients switched to a different brand should be monitored (particularly if pregnant or if heart disease present) as brands without a UK licence may not be bioequivalent Pregnant women or those with heart disease should undergo an early review of thyroid status, and other patients should have thyroid function assessed if experiencing a significant change in symptoms If liothyronine is continued long-term, thyroid function tests should be repeated 1–2 months after any change in brand BNF 74 l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug Forms available from special-order manufacturers include: tablet, capsule, oral suspension, oral solution, solution for injection Tablet ▶ Liothyronine sodium (Non-proprietary) Liothyronine sodium 20 microgram Liothyronine 20microgram tablets | 28 tablet P £258.20 DT price = £258.20 Powder for solution for injection ▶ Liothyronine sodium (Non-proprietary) Liothyronine sodium 20 microgram Liothyronine 20microgram powder for solution for injection vials | vial P £1,425.00 ... England Birmingham: ( 012 1) 424 7298 Bristol: ( 011 7) 342 2867 Ipswich: ( 014 73) 704 4 31 Leeds: ( 011 3) 206 5377 Leicester: ( 011 6) 258 64 91 Liverpool: ( 015 1) 794 811 3/7, or ( 015 1) 794 811 8 London: Guy’s... Cardiff: (029) 2 074 2979, or (029) 2 074 22 51 Scotland Aberdeen: ( 012 24) 552 316 Dundee: ( 013 82) 632 3 51, or ( 013 82) 660 11 1 Extn 323 51 Edinburgh: ( 013 1) 242 2920 Glasgow: ( 014 1) 211 4407 Northern... 0845 602 6 712 Monday – Friday (closed Wednesday afternoons and Bank Holidays): 09:0 0 1 1:45 and 13 :0 0 1 5:45 ▶ Travel Medicine Team, Health Protection Scotland ( 014 1) 300 11 00 (14 .0 0 1 6.00 hours

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