Formulary 3rd Edition - Update May 2010 This document includes all drug decisions made by the Medicines & Therapeutics Executive Committee up until April 2010.

Dear Colleague

This Formulary is the result of collaboration between the Bro Taf Localities Drug & Therapeutics Committee and the two Medicines and Therapeutics Executive Committees for North Bro Taf and Cardiff and the Vale. It has been produced at the Welsh Medicines Information Centre. This Update, produced in May 2010, includes drug decisions made since the last hard copy was printed in 2003. Each chapter is currently undergoing review by clinicians and pharmacists across the local area to enable us to produce a fully revised edition. In the meantime, please email us at the address below if you would like to comment or assist with the review process.

Searching the Formulary The quickest way to access information from this pdf document is to use the “edit” option on the toolbar. Drop the menu down to “find on this page” and insert the drug name or other search word. Where possible we have included NICE guidance and CSM warnings. Please refer to the Summary of Product Characteristics for full prescribing information. If you download the formulary from the website, please remember that the formulary on the web will be updated frequently – at least every two months. Hence it will be necessary to download the updated version periodically.

Internet access and updates This formulary is constantly being updated. During transition into the main text of the formulary, drugs will appear on an updates list which will be included as a separate section at the beginning of the document (see next page). Alternatively new additions may be viewed as a separate document by following the D&TC Prescribing Formularies/Additions List link from http://www.wmic.wales.nhs.uk/.

Thank you to all clinicians and pharmacists who have provided advice on various sections, and to our clerical staff for their support.

Any comments? We hope you will find the Bro Taf Localities Formularies useful and that they will help you to improve patient care. Your comments and suggestions for future updates would be welcome and may be made by contacting us at the addresses below:

Contact Information Formulary Issues: Diana Fletcher, Senior Information & Formulary Pharmacist, E-mail: [email protected] Tel: (029) 2074 4298 (secretary) Bro Taf Localities Drug & Therapeutics Committee: Rowena McArtney, Professional Secretary, Senior Information Pharmacist, E-mail: [email protected] Tel: (029) 2074 4298 (secretary) Medicines Information Enquiries – Please contact your local centre Cardiff and Vale North Bro Taf Welsh Medicines Information Centre Medicines Information, Pharmacy Department University Hospital of Wales Royal Glamorgan Hospital Cardiff CF14 4XW Ynysmaerdy, Llantrisant CF72 8R Tel: (029) 2074 3877/2979 Tel: (01443) 443136

Recent Additions to the Bro Taf localities Prescribing Formularies The following changes have been made to the Bro Taf Formulary since the most recent version of the formulary was posted on the WMIC website. Approved products will be incorporated into the main text in due course. For decisions predating Update VIII, please refer to Update VII (attached below) and the main formulary documents. As always, the most recent updates supersede information in earlier updates & the main formularies. Please consult product literature before prescribing.

Update VIII from January 2010

New results, issued following the DTC meeting in February and April 2010 and confirmed locally are shown in bold. Generic Name Drug & Therapeutics Committee Cwm Taf UHB Cardiff And Vale UHB Abbreviated Notes Prescribing Category Prescribing Category alitretinoin For the treatment of severe chronic hand Hospital Only Hospital Only eczema 26.2.10 NICE TA177 August 2009 DTC 24.9.09 Hospital Only in view of the fact that it is an oral retinoid and needs to be started and monitored by a Specialist.

Allevyn First Line First Line First line DTC 11.2.10 Feb 2010 Allevyn Adhesive Specialist Initiated (use Second Line after Specialist Initiated Second Line Biatain). Second Line DTC 11.2.10 Feb 2010 Allevyn Adhesive Remove from the formulary (use Biatain Remove from Formulary Remove Sacral Adhesive.) Feb 2010 DTC 11.2.10 Allevyn cavity Remove. Cavicare is suitable alternative. Remove from Formulary remove DTC 11.2.10 Feb 2010 amiodarone AWMSG has finalised a Shared Care Change to Specialist Noted: Shared care protocol Prescribing template for amiodarone Initiated with Shared Care CV44 now on WMIC Previously posted on Prescribing arrangements. website Website 18.8.08 suppositories For acute treatment of stroke & TIA Second Line First line NICE CG68 July 08. First line. atomoxetine Diagnosis and management of ADHD in children, young people and adults. NICE CG72 September 2008 Note: This guidance includes Hospital Only until the Hospital Only until the adults. Shared Care Protocol is Shared Care Protocol is agreed. agreed. Atomoxetine: Hospital Only until the Shared Feb 2010 Care Protocol is agreed. DTC 11.2.10 brinzolamide/timolol Specialist Initiated Specialist Initiated Specialist Initiated (Azarga®) DTC 11.2.10 Feb 2010 April 2010 Carmellose eye drops Second Line Second Line Second Line (Optive®) DTC 11.2.10 Feb 2010 certolizumab pegol For the treatment of rheumatoid arthritis Decision awaited Hospital Only – the NICE TA186 February 2010. manufacturer provides DTC 22.4.19 Hospital Only – the the first 12 weeks of manufacturer provides the first 12 weeks of treatment free of charge treatment free of charge. cetuximab Cetuximab for the first-line treatment of Hospital Only Hospital Only metastatic colorectal cancer 26.2.10 NICE TA176 August 2009 DTC 24.9.09 Hospital Only Combiderm and Remove from Formulary Remove Remove Combiderm N DTC 24.9.09 dabigatran Venous thrombosis –reducing the risk of Awaiting confirmation Hospital Only venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. NICE CG92 Jan 2010. DTC 11.2.10

Generic Name Drug & Therapeutics Committee Cwm Taf UHB Cardiff And Vale UHB Abbreviated Notes Prescribing Category Prescribing Category darunavir (Prezista®) Co-administered with low dose ritonavir for Hospital Only Hospital Only the treatment of human immunodeficiency Feb 2010 virus (HIV)-1 infection in treatment naive patients. It is not suitable for shared care. AWMSG Advice 2009 December 2009 DTC 11.2.10 Hospital Only dexamfetamine Diagnosis and management of ADHD in Hospital Only Dexamfetamine is not children, young people and adults - See NICE Feb 2010 suitable for shared care CG72 September 2008. NB This guidance also and should remain includes adults DTC 13.11.08 Hospital Only Dexamfetamine is not suitable for shared care and should remain Hospital Only. DTC 11.2.10 diclofenac sodium 3% gel Diclofenac sodium 3% gel (Solaraze®) for the Change from Specialist Noted (Solaraze®) treatment of actinic keratosis Initiated to First Line suitable for initiation in Change from Specialist Initiated to First Line Previously posted on both primary and website DTC 10.7.08 secondary care 18.8.08

diltiazem rectal ointment Unlicensed “special” with widespread usage. To Second Line Noted 2% be added to Unlicensed Product appendix 2 of Previously posted on the formulary. DTC 12.2.09 website donepezil effervescent Added to the Formulary restricted to use in Hospital Only Hospital only patients who cannot tolerate conventional donepezil tablets. Previously posted on DTC 19.11.09 website dosulepin (previously For existing patients only – patients should Decision awaited. Existing patients only dothiepin) be reviewed if they are taking it for depression. NICE CG60 DTC 22.4.10 eslicarbazepine acetate Available for one year assessment Decision awaited Specialist Initiated for a (Zebinix®) period as a Specialist Initiated agent one year assessment DTC 22.4.10 period etravirine (Intelence®) Etravirine (Intelence®▼) is recommended as Hospital Only Hospital Only an option for use within NHS Wales for the 26.2.10 treatment of HIV-1 infected, antiretroviral treatment-experienced adults in combination with a boosted protease inhibitor and other antiretroviral medicinal products. Treatment should be initiated by a specialist in accordance with BHIVA guidelines. Not recommended for use as first line therapy. Not considered suitable for shared care. AWMSG Advice No 0609 August 2009 DTC 24.9.09

Evicel Hospital Only restricted to replacement of Hospital Only Hospital Only restricted to existing use of Quixil. Feb 2010 replacement of existing DTC 11.2.10 use of Quixil April 2010 fesoterodine Second Line agent. Decision awaited Decision deferred DTC 22.4.10 pending review of this class of drugs.

Generic Name Drug & Therapeutics Committee Cwm Taf UHB Cardiff and Vale UHB Abbreviated Notes Prescribing Category Prescribing Category filgrastim (Ratiograstim®) Recommended as an option for use within NHS Hospital only Hospital Only Wales in the treatment of neutropenia. Please 26.2.10 see AWMSG Advice No 1609 August 2009 for full details. Not considered suitable for shared care. Biosimilars should be prescribed by brand name to avoid automatic substitution and ensure consistency in provision. DTC 24.9.09 glucose (Dextrose) liquid First Line First Line First Line (GlucoJuice®) DTC 19.11.09 26.2.10 glucose (Dextrose) First Line First Line First Line tablets (GlucoTabs®) DTC 19.11.09 26.2.10 hylan G-F 201 (Synvisc) Synvisc and Hyalgan should remain in the Hospital Only.16.6.08 Noted (Previously posted on formulary but be annotated to state that NICE website) CG59 February 2008 does not recommend their use in osteoarthritis. DTC 22.5.08 4% LMX4 Topical local anaesthetic cream. Available as For future consideration if Noted Hospital Only item for dermatologists in Cardiff request is received in Cwm (Previously posted on and Vale UHB for 6 month evaluation subject to Taf. website) provision of feedback. Indicators to be established prior to start of evaluation. DTC 19.11.09. liraglutide (Victoza®) Second Line adjunctive treatment for adults with Not to be made available Second Line in patients type 2 diabetes who are intolerant of exenatide. until NICE guidance is intolerant of exenatide, Decision subject to NICE guidance which may published. subject to NICE appraisal supersede this. which may supersede this DTC 19.11.09 decision.26.2.10 loperamide tablets Second line use for patients with a high First Line Second Line (Norimode) output stoma or short bowel syndrome. Feb 2010 April 2010 DTC 11.2.10 mecasermin (Increlex®) Recommended for the long-term treatment of Hospital Only Hospital Only growth failure in children and adolescents with 26.2.10 severe primary insulin-like growth factor-I deficiency. Treatment should be initiated and monitored by physicians who are experienced in the diagnosis and management of patients with growth disorders. Not considered suitable for shared care within NHS Wales. AWMSG Advice No 1709 October 2009 DTC 19.11.09 Hospital Only melatonin (Circadin®) Restricted to Specialist Initiation in patients in Specialist Initiated, Specialist Initiated, whom unlicensed melatonin would otherwise be restricted to patients in restricted to patients in used. DTC 19.11.09 whom unlicensed whom unlicensed melatonin melatonin would otherwise would otherwise be used be used. 26.2.10 methoxy polyethylene Recommended as an option for the treatment of Hospital only until Shared Referred to Shared Care glycol-epoetin beta adults with symptomatic anaemia associated Care issues have been Sub Group – Hospital (Mircera®) with chronic disease. Suitable for shared considered Only in the meantime. care. 26.2.10 AWMSG Advice No 1809 October 2009

DTC 19.11.09 Awaiting discussion by Shared Care Group montelukast Add to Formulary Specialist Initiated Specialist Initiated 4mg granules and DTC 24.9.09 26.2.10 4 mg chewable tablets

Generic Name Drug & Therapeutics Committee Cwm Taf UHB Cardiff and Vale UHB Abbreviated Notes Prescribing Category Prescribing Category Melts Add to Formulary Specialist Initiated Specialist Initiated DTC 24.9.09 26.2.10 pemetrexed For the first-line treatment of non-small-cell lung Hospital Only – already in Hospital Only cancer. NICE TA181 September 2009 Formulary for other 26.2.10 DTC 19.11.09 Hospital Only indications plerixafor (Mozobil®) Recommended as an option for restricted Decision awaited. Hospital Only use within NHS Wales in combination with granulocyte-colony stimulating factor (G- CSF) to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma whose cells mobilise poorly. AWMSG Advice No 0110 March 2010 DTC 22.4.10 Hospital Only prasugrel For the treatment of acute coronary syndromes Specialist Initiated Specialist Initiated with percutaneous coronary intervention 26.2.10 NICE TA182 October 2009 DTC 19.11.09 Specialist Initiated prednisolone 5mg EC To be removed from the formulary Second Line – only for To be removed from the tablets DTC 11.2.10 use where plain cannot formulary be used. Feb 2010 rituximab Rituximab for the first-line treatment of Hospital Only – already Hospital Only chronic lymphocytic leukaemia in Formulary for other 26.2.10 NICE TA174 July 2009. indications Suggested category Hospital Only DTC 24.9.09 rivaroxaban Venous thrombosis –reducing the risk of Decision awaited Hospital Only venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. NICE CG92 Jan 2010 rosuvastatin Formulary status amended from Specialist Third Line Third Line Initiated to Third Line Feb 2010 April 2010 DTC 11.2.10 sugammadex To be made available as a Hospital Only Decision awaited Hospital Only. Audit data (Bridion®) agent in restricted locations – to be used as required for first 10 a rescue only. patients, then status to be DTC 22.4.10 reviewed. sunitinib For the treatment of gastrointestinal stromal Hospital Only – already Hospital Only tumours. NICE TA179 September 2009. included for other 26.2.10 DTC 19.11.09 Hospital Only indications. tenofovir disoproxil For the treatment of chronic hepatitis B. Hospital Only Hospital Only NICE TA173 July 2009. 26.2.10 Suggested category Hospital Only. DTC 24.9.09 For the treatment of recurrent and stage IVB Hospital Only – already in Hospital Only cervical cancer. NICE TA183 October 2009 Formulary for other 26.2.10 DTC 19.11.09 Hospital Only indications topotecan For the treatment of relapsed small-cell lung Hospital Only – already Hospital Only cancer NICE TA184 November 2009 in Formulary for other DTC 11.2.10 Hospital Only indications Feb 2010

Generic Name Drug & Therapeutics Committee Cwm Taf UHB Cardiff and Vale UHB Abbreviated Notes Prescribing Category Prescribing Category trabectedin For the treatment of advanced soft tissue Decision awaited Decision awaited sarcoma NICE TA185 February 2010. DTC 22.4.10 Hospital Only (cost of treatment after 5th cycle is met by the manufacturer) triptorelin (Decapeptyl Specialist Initiated. No Shared Care Protocol Specialist Initiated Specialist Initiated SR®) necessary. DTC 24.9.09 26.2.10 trisodium citrate Hospital Only Hospital Only Hospital Only for (Duralock®) DTC 24.9.09 tunnelled cuff haemodialysis lines 26.2.10 ustekinumab For the treatment of adults with moderate to Hospital Only Hospital Only severe psoriasis 26.2.10 NICE TA180 September 2009 DTC 19.11.09 Hospital Only vildagliptin Type II Diabetes – Newer agents NICE CG87 Second Line Second Line in May 2009 accordance with licenced The Committee advised that both sitagliptin and indications and NICE CG vildagliptin should be included for use within 87 Type 2 Diabetes. their respective licensed indications. Both are to 26.2.10 be listed as Second Line, but within the class, sitagliptin should be used first and vildagliptin second. DTC 24.9.09 [Sitagliptin added Aug 08] Xamiol (betamethasone Second Line Decision awaited. Decision awaited. + calcipotriol scalp gel) DTC 22.4.10

Continued…/

Dermatology Formulary Review November 2009 – Changes approved

Generic Name Drug & Therapeutics Committee Cwm Taf Cardiff And Vale Abbreviated Notes Prescribing Prescribing Category Category acitretin Hospital Only pending review by Shared Care Committee DTC Agreed 19.11.09 Aldara (imiquimod) Second Line as an alternative to Efudix cream for BCC and Agreed actinic keratoses (was Specialist Initiated Cwm Taf only) DTC 19.11.09 benzamycin Remove from Formulary DTC 19.11.09 Agreed Betnovate C Change to First Line (from Second Line) Agreed Good alternative to Fucibet DTC 19.11.09 Betnovate N Change to Specialist Initiated (from Second Line) Agreed Note: neomycin is a strong topical sensitizer Use Betnovate C (clioquinol) in preference DTC 19.11.09 Coal Tar and Remove from Formulary Agreed salicyclic acid DTC 19.11.09 ointment Coal Tar paste BP Remove from Formulary DTC 19.11.09 Agreed Cocois or Sebco First Line DTC 19.11.09 Agreed Dermol cream Second Line DTC 19.11.09 Agreed Dermol 600 Bath First Line DTC 19.11.09 Agreed emollient dithranol with 0.5% Hospital Only (on BAD list) Agreed salicyclic acid in DTC 19.11.09 paraffin base Dovobet Change to Second Line (from Hospital Only) Agreed DTC 19.11.09 Duac First Line Agreed DTC 19.11.09 Ichthamol Ointment Remove from Formulary Agreed BP DTC 19.11.09 Locoid Change to Specialist Initiated (from First Line) DTC 19.11.09 Agreed isotretinoin Remains Hospital Only Agreed DTC 19.11.09 Locoid C Change to Specialist Initiated (from First Line) DTC 19.11.09 Agreed 8 methoxypsoralen Hospital Only (named patient) Agreed gel 0.005% DTC 19.11.09 micanol Remove from Formulary Agreed DTC 19.11.09 phenol 2% in Remove from Formulary Agreed compound zinc paste DTC 19.11.09 pimecrolimus Change to Second Line (was Specialist Initiated). Prescribers Agreed should be experienced in the treatment of atopic eczema. DTC 19.11.09 Polytar emollient Remove from Formulary Agreed (bath) DTC 19.11.09 Synalar gel Change to First Line (was Second Line) Agreed DTC 19.11.09 Synalar N Remove from Formulary Agreed DTC 19.11.09 tacrolimus Change to Second Line (was Specialist Initiated). Prescribers Agreed should be experienced in the treatment of atopic eczema. DTC 19.11.09 zinc and salicyclic Remove from Formulary Agreed paste DTC 19.11.09

Update VII from September – December 2009 The following items have been considered for addition to the Bro Taf Formulary since the most recent version of the formulary was posted on the WMIC website. Results issued at the DTC meeting in November 2009 are shown in bold. Approved products will be incorporated into the main text in due course. For decisions predating this list, please refer to the main formulary documents. Please consult product literature before prescribing.

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category and Recommended as an option for use in Hospital Only Hospital Only fixed dose (Kivexa®) antiretroviral combination therapy for the 8.12.08 treatment of Human Immunodeficiency Virus (HIV-1) infection in adults and adolescents from 12 years of age. Use should be in accordance with the British HIV Association (BHIVA) guidance. Not suitable for Shared Care. AWMSG Advice 2008 Oct 2008 DTC 13.11.08 Abstral SL® sublingual tablets – see fentanyl Acetylcysteine (Fluimucil) Deferred pending receipt of full application Noted 16.6.08 200 mg Sachets 22.5.08 for use in pulmonary fibrosis Actico short stretch® Suggested category Specialist Initiated Specialist Initiated Specialist Initiated DTC 2.4.09 13.5.09 Acticoat® Reserved for use by wound healing specialists Specialist Initiated Specialist Initiated Acticoat Moisture in the treatment of patients whose wounds have 13.5.09 Control® not responded to Aquacel Silver. Suggested category Specialist Initiated DTC 2.4.09

Actiform Cool® Suggested category First Line. First Line First Line (to replace other Hydrosorb and Hydrosorb Comfort to be (decision on hydrosorb hydrogel dressings removed. removal to be confirmed) Hydrosorb and Hydrosorb DTC 2.4.09 Comfort) 3.8.09 Actiq (fentanyl) lozenges To be removed from the Formulary Remove from the Remove from the Formulary (see under fentanyl) Formulary but continue to but continue to be available DTC 4.6.09 be available in short term in short term for existing for existing patients. patients. 3.8.09 Adalimumab, etanercept Adalimumab, etanercept and infliximab for Adalimumab and Hospital Only 4.8.08 and infliximab ankylosing spondylitis NICE TA143 May 2008 etanercept Hospital Only. Hospital Only. 10.7.08 Infliximab not to be included for this indication. 18.8.08 Adalimumab Adalimumab for the treatment of psoriasis Hospital Only 18.8.08 Hospital Only 4.8.08 TA146 June 2008. Hospital Only. 10.7.08 Note recent safety warnings including hepatosplenic T-cell lymphoma.

Agalsidase (Replagal®) Agalsidase for the treatment of Fabry disease. Hospital Only. 18.2.08 Hospital Only AWMSG Advice 1107 Oct. 2007. alemtuzumab Alemtuzumab for restricted use in the treatment Hospital Only Hospital Only (MabCampath®) of patients with B-cell chronic lymphocytic 13.5.09 leukaemia for whom fludarabine combination chemotherapy is not appropriate. AWMSG Advice 2208 December 2008. Hospital Only. DTC 12.2.09.

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category alendronate For the primary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 160 October 2008. alendronate For the secondary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Secondary prevention January 2005). alitretinoin For the treatment of severe chronic hand Hospital Only eczema NICE TA177 August 2009 DTC 24.9.09 Hospital Only in view of the fact that it is an oral retinoid and needs to be started and monitored by Specialist. ambrisentan (Volibris®) For the treatment of patients with pulmonary Hospital Only Hospital Only arterial hypertension (PAH) classified as World Agreed 3.8.09 Health Organisation (WHO) functional class (FC) II and III, to improve exercise capacity. Not suitable for Shared Care. Restricted use see AWMSG Advice 2508 April 2009. Hospital Only. DTC 4.6.09. amiodarone AWMSG has finalised a Shared Care Change to Specialist Prescribing template for amiodarone Initiated with Shared Care Prescribing arrangements. 18.8.08 amlodipine and valsartan NOT APPROVED ( Cardiovascular Group) - - (ExForge®) Noted DTC 15.11.07.

Anastrozole Due to lack of monitoring requirement. Noted Noted 3.8.09 anastrozole will no longer be subject to shared Amend formulary status care requirement to Second Line DTC 4.6.09

Anidulafungin (Ecalta®) Recommended as an option for use within NHS Hospital Only Hospital Only Wales within its licensed indication for the Agreed 3.8.09 treatment of invasive candidiasis in adult non- neutropenic patients. Not suitable for Shared Care. AWMSG Advice 0809 April 2009. Hospital Only. DTC 4.6.09.

Anti-d prophylaxis for Routine antenatal anti-D prophylaxis for women Formulary to be updated rhesus D negative who are rhesus D negative - NICE TA156 (Section 14.5) women August 2008. Replaces NICE TA41 20.10.08 aprepitant (Emend®) Hospital Only, for nausea and vomiting in Hospital Only limited to Hospital Only for patients on patients receiving highly emetogenic Consultant Oncologists for highly emetogenic regimens chemotherapy. patients on highly - restricted to use at emetogenic regimens Velindre Hospital 20.10.08 13.10.08 Aripiprazole For schizophrenia. Change of status to Specialist Initiated without Specialist Initiated without (Abilify®) Specialist Initiated recommended. Usage the need for Shared Care. the need for Shared Care. predictions required for MTECs. 13.3.08. 16.6.08 14.4.08 Aspirin 300mg Diagnosis and initial management of acute Second Line suppositories stroke and transient ischaemic attack NICE CG 68 July 2008. DTC 19.11.09

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Atazanavir (Reyataz®) Atazanavir for the treatment of HIV-1 infected Hospital Only Hospital Only adults in combination with other antiretroviral 13.5.09 medicinal products: for treatment-experienced patients, in accordance with British HIV-1 Association (BHIVA) Guidance. AWMSG Advice 2308 December 2008. Hospital Only. DTC 12.2.09. Atazanavir (Reyataz®) Atazanavir for the treatment of HIV-1 infected Hospital Only Hospital Only adults in combination with other antiretroviral 13.5.09 medicinal products: for treatment-naive patients in accordance with BHIVA Guidance. AWMSG Advice 2408 December 2008. Hospital Only. DTC 12.2.09. atomoxetine Atomoxetine for attention deficit, hyperactivity Noted 20.10.08 disorder. NICE CG72 September 2008 No amendment to Formulary except to Already included as Specialist Initiated. The suggest that a note Shared Care Protocol for atomoxetine will be referring to use in adult updated and consideration given as to whether patients is added to SCP are required for any of the less commonly formulary used drugs. The Guidance also includes adults DTC 13.11.08 Atorvastatin Lipid modification NICE CG67 May 2008 Remains unchanged as Second Line 18.8.08 azelaic acid (Finacea®) Rejected - - DTC 13.11.08 Balsalazide Initial decision - Remove from formulary & Specialist Initiated Specialist Initiated, Second change others in class to Specialist Initiated. 15.12.08 Line for patients who cannot 13.3.08 tolerate mesalazine and Updated information - Balsalazide will be put would otherwise have to be back into the formulary as a Specialist Initiated given more toxic agent. DTC 13.11.08 immunosuppressant drugs 8.12.08 Bevacizumab Bevacizumab for the first-line treatment of No formulary implications Not yet noted metastatic breast cancer NICE TA147 June 18.8.08 2008 (Terminated appraisal) DTC 25.9.08 Bevacizumab Bevacizumab for the treatment of non-small-cell No formulary implications Not yet noted lung cancer NICE TA148 June 2008 18.8.08 (Terminated appraisal) DTC 25.9.08 Bivalirudin (Angiox®) (administered with aspirin and clopidogrel) Hospital Only Hospital Only bivalirudin is recommended as an option for the Agreed 3.8.09 treatment of adult patients with acute coronary syndromes (unstable angina/non-ST segment elevation myocardial infarction [UA/NSTEMI]) planned for urgent or early intervention. Not suitable for Shared Care. AWMSG Advice No 1009 June 2009. DTC 16.7.09 Hospital Only. Breast Cancer – Early & Early and locally advanced breast cancer: Noted Not yet noted Locally advanced diagnosis and treatment. NICE CG80 (Updates and replaces NICE TA 107 (trastuzumab) , TA108 (paclitaxel) & TA 109 (docetaxel) DTC 2.4.09 Breast cancer - Advanced breast cancer: diagnosis Noted Not yet noted Advanced and treatment. NICE CG81 Feb 2009 (Updates and replaces NICE TA62 (capecitabine), TA 54 (vinorelbine) and TA30 (taxanes). DTC 2.4.09 Bretylium Remove from Formulary – no longer available Noted Noted 13.5.09 DTC 2.4.09

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Bupivacaine infusion Not considered by DTC but approved for Hospital Only 18.7.08 Hospital Only 18.7.08 inclusion by Chief Pharmacist. 0.1%, 0.125%, 0.25% strengths added buprenorphine/ Buprenorphine/naloxone (Suboxone®) as Specialist Initiated 18.8.08 Specialist Initiated 4.8.08 naloxone (Suboxone) substitution treatment for opioid dependence AWMSG Advice 1108 DTC 10.7.08 Calfovit D3 sachet First Line Second Line if unable to First Line DTC 4.6.09 take Calcichew D3 forte 3.8.09 captopril Annotate in Formulary ‘for use in paediatrics Noted Noted 13.5.09 and for initial dose titration only’. DTC 2.4.09 Carmustine Carmustine implants for the treatment of No formulary implications Not yet noted recurrent glioblastoma multiforme NICE TA149 18.8.08 June 2008 (Terminated appraisal) DTC 25.9.08 Cetrorelix acetate Hospital Only for specialist use only Hospital Only Hospital Only (Cetrotide®) DTC 16.7.09 3.8.09 Ganirelix to be removed Cetuximab Cetuximab for the treatment of head and neck Hospital Only 18.8.08 Hospital Only 4.8.08 cancer NICE TAG145 June 2008 Hospital Only DTC 10.7.08 Cetuximab Cetuximab for the treatment of metastatic and/or - - recurrent squamous cell carcinoma of the head and neck NICE TAG172 June 2009 – not recommended by NICE DTC 16.7.09 Cetuximab Cetuximab for the treatment of metastatic No formulary implications Not yet noted colorectal cancer following failure of oxaliplatin- 18.8.08 containing chemotherapy NICE TA150 June 2008 (Terminated appraisal) DTC 25.9.08 Cetuximab Cetuximab for the first-line treatment of Hospital Only metastatic colorectal cancer NICE TA176 August 2009 DTC 24.9.09 Hospital Only Chorionic gonadotrophin injection – see Ovitrelle®. Cilostazol HO first line in pts who meet the criteria Remove from formulary as never accepted, not used no longer being prescribed 18.8.08 Clopidogrel 300mg Line extension with no change in dose, Second Line Second Line Tablets indications or cost. Added without need for formulary submission. Coban 2 Multilayer® Suggested category Specialist Initiated Specialist Initiated Specialist Initiated DTC 2.4.09 13.5.09 Combiderm and Remove from Formulary Remove Combiderm N DTC 24.9.09 Dabigatran etexilate Dabigatran etexilate for the prevention of Awaiting confirmation Hospital Only venous thromboembolism after hip or knee 2.11.09 8.12.08 replacement surgery in adults. NICE TA157 September 2008 Hospital Only DTC 13.11.08.

Dasatinib (Sprycel®) AWMSG No 1307 December 2007 Hospital Only (specialist Not yet noted CML Not yet noted use) product for the listed (Recommended for treatment of adults with indications. 21.4.08 chronic phase chronic myeloid leukaemia (CML) and accelerated phase CML where there is resistance or intolerance to prior therapy including imatinib mesilate.)

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category D-alpha-tocopherol (Vita- Oral vitamin E preparation (unlicensed) Specialist Initiated 16.6.08 Specialist Initiated in place E) Gel capsules replacing alpha-tocopherol tablets 50mg and of the previously available 75 iu (50mg), 200mg which are no longer available. tablets. 7.7.08 200 iu (134mg) and Specialist Initiated 22.5.08 400 iu (268mg) deferasirox (Exjade) Deferasirox (Exjade®) for the treatment of Hospital Only for this Hospital Only. chronic iron overload due to blood transfusions specific indication 18..8.08 Recommended in certain AWMSG Advice 0808 July 2008 patients Recommended in certain patients. Not suitable 4.8.08 for shared care. dexamfetamine Dexamphetamine for attention deficit, Noted 20.10.08 hyperactivity disorder - See NICE CG72 No amendment to September 2008 Formulary except to suggest that a note Already included as Specialist Initiated. referring to use in adult Consideration to be given to whether SCP are patients is added to required for any of the less commonly used formulary drugs. The Guidance also includes adults DTC 13.11.08

Diabetes – insulin pump Continuous subcutaneous insulin infusion for No formulary implications Specialist Initiated therapy the treatment of diabetes mellitus NICE TAG151 18.8.08 13.10.08 July 2008. Specialist Initiated 25.9.08 Diabetes : management See NICE CG66 and exenatide notes below. Noted 18.8.08 – see Noted 4.8.08 – see of type 2 exenatide exenatide See NICE CG87 May 2009 and under vildagliptin. DTC 16.7.09 Diclofenac sodium 3% Diclofenac sodium 3% gel (Solaraze®) for the Change from Specialist gel (Solaraze®) treatment of actinic keratosis Initiated to First Line suitable for initiation in both primary and secondary care 18.8.08 Diclofenac sodium Hospital Only. Restricted to Theatre Recovery Hospital Only 16.6.08 Hospital Only where it injection (Dyloject) where it should be Specialist Initiated. 22.5.08 should be Specialist Initiated. Restricted to Theatre Recovery. 7.7.08 Diltiazem rectal ointment Unlicensed “special” with widespread usage. To Second Line 2% be added to Unlicensed Product appendix 2 of the formulary. DTC 12.2.09 dinoprostone NICE CG70 July 2008 Induction of labour. NOT Noted Noted 13.10.08 recommended for oral use. PGE2 (Oral) To be REMOVED from the Formulary. DTC 25.9.08 docetaxel (Taxotere) Docetaxel (Taxotere®) for locally advanced Hospital Only for this Hospital Only squamous cell carcinoma of the head and neck specific indication 18..8.08 Restricted use AWMSG advice 1008 July 2008 4.8.08 Recommended for restricted use – not suitable for shared care. DTC 10.7.08 donepezil effervescent Added to the Formulary restricted to use in Hospital Only patients who cannot tolerate conventional donepezil tablets. DTC 19.11.09 DoubleBase® gel Second line (hospital and GP use) Emollients in Second Line 21.4.08 Second Line. 14.4.08 (Isopropyl myristate 15% the formulary to be reviewed. 13.3.08 Liquid paraffin 15%) Drug-eluting stents Drug eluting stents for the treatment of coronary No formulary implications No formulary implications artery disease NICE TA152 July 2008 18.8.08 (Hospital Only) 13.10.08 DTC 25.9.08 Hospital Only

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Currently second Line Rejected Easy Pod® autoinjector Device for the administration of somatropin Specialist Initiated Specialist Initiated injection, a Specialist Initiated Shared Care 20.10.08 13.10.08 drug. Accepted 25.9.08 Eculizumab (Soliris®) Recommended for restricted use within NHS Hospital Only Hospital Only Wales, according to agreed guidelines, for the 3.8.09 treatment of paroxysmal nocturnal haemoglobinuria. Not suitable for Shared Care. AWMSG Advice No. 0509 April 2009. DTC 4.6.09 Hospital Only Efavirenz / emtricitabine / Recommended for treatment of HIV-1 infection Hospital Only Hospital Only tenofovir disoproxil (as in adults with virological suppression to HIV-1 13.5.09 fumarate) RNA levels of <50 copies/ml on their current (Atripla®) combination antiviral therapy for more than three months and in accordance with current BHIVA guidance. Not suitable for Shared Care. AWMSG Advice No. 0209 February 2009. Effentora® buccal tablets - see Fentanyl Emedastine eye drops Removed 10.7.08 Noted 18.8.08 noted entecavir (Baraclude®) For the treatment of chronic Hepatitis B -NICE Hospital Only, to be Hospital Only TA153 August 2008. Hospital Only DTC prescribed strictly in 13.10.08 25.9.08 accordance with NICE guidance 20.10.08 Epoetin alfa, epoetin beta Anaemia (cancer-treatment induced) - Hospital Only for this Hospital Only for this and darbepoetin alfa erythropoietin (alpha and beta) and darbepoetin: specific indication 18.8.08 specific indication 4.8.08 NICE TA142 May 2008. Hospital Only (restricted to this indication). DTC 10.7.08 Epoetin delta Epoetin delta in the treatment of anaemia in Hospital Only until a Specialist Initiated with (Dynepo ®) patients with chronic renal failure. Shared Care Protocol is Shared care (local shared AWMSG Advice 0408 February 2008 agreed 16.6.08 care protocols will be Noted 13.3.08 updated). 14.4.08 eptifibatide Remove from Formulary. DTC 2.4.09, 4.6.09 Noted - Erlotinib Erlotinib for the treatment of non-small-cell lung Hospital Only Hospital Only cancer. NICE TA162 November 2008. Hospital 13.5.09 Only. DTC 12.2.09. Escitalopram (Cipralex®) Recommended as a Second Line agent Second Line for this Local interest to be for generalised anxiety disorder (GAD) indication for a maximum established before only for maximum 12 months therapy – of 12 months therapy. considering for formulary subject to revision of the costs included in 18.8.08 inclusion 4.8.08 submission. DTC 10.7.08 Not to be added in South Bro Taf as other treatment options for GAD are on the current formulary 13.5.09 Esomeprazole It is proposed that esomeprazole may be Hospital Only Hospital Only made available for limited use in the small 15.12.08 Algorithm agreed to ensure group of patients who have severe GORD appropriate use of (Grade C or D) demonstrated on Esomeprazole; this means endoscopy. In such patients a 4 week that patients with GORD (maximum 8 week) course of grade C or D should be esomeprazole could be supplied by the managed with 40mg Hospital. They would then be swapped to Esomeprazole for 4 – 8 another PPI for maintenance. weeks (from hospital) and DTC 13.11.08 then stepped down to 20mg Omeprazole or 30mg Lansoprazole (from GP) 8.12.08 Prescribing Protocol

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category etidronate For the primary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 160 October 2008. etidronate For the secondary prevention of Noted osteoporotic fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Osteoporosis Secondary prevention January 2005).

Etravirine (Intelence®) Etravirine (Intelence®▼) is recommended as Hospital Only an option for use within NHS Wales for the treatment of HIV-1 infected, antiretroviral treatment-experienced adults in combination with a boosted protease inhibitor and other antiretroviral medicinal products. Treatment should be initiated by a specialist in accordance with BHIVA guidelines. Not recommended for use as first line therapy. Not considered suitable for shared care. AWMSG Advice No 0609 August 2009 DTC 24.9.09

Exemestane Due to lack of monitoring requirements, Noted Noted 3.8.09 exemestane will no longer be subject to shared Amend formulary status care requirement to Second Line DTC 4.6.09 Exenatide Type 2 diabetes: NICE clinical Guidance on the Specialist Initiated to be Specialist Initiated to be Diabetes - type 2 management of type 2 diabetes NICE CG66 used in line with NICE used in line with NICE May 2008 update of clinical guidelines E, F, G Guidance 18.8.08 (update) Guidance 4.8.08 and H). In this guidance exenatide is recommended as an option if certain criteria are met, but not for routine use in type 2 diabetes. Please follow the link above for full information.

Specialist Initiated – with a need to audit against NICE guidance. The diabetologists will be asked to provide a proposal for their use of exenatide and to define the criteria for audit. DTC 10.7.08

Ezetimibe Ezetimibe for the treatment of primary 3rd line. 18.2.08 Second Line. (heterozygous –familial and non-familial) Prescribing guidance will be hypercholesterolaemia circulated to primary and NICE TAG132 November 2007 secondary care prescribers. 14.4.08 Noted 13.3.08 Recommend change from specialist-initiated to second line. 5-Fluorouracil cream 5% Reclassified as Second line 22.5.08 Second Line 16.6.08 Specialist Initiated Second (Efudix) line. 7.7.08 Febuxostat For the management of hyperuricaemia in Specialist Initiated, second Specialist Initiated, second people with gout. NICE TAG164. December line agent line agent 2008. 13.5.09 Specialist Initiated (as a second line agent). DTC 12.2.09 Note: Not yet available because of production problems. 12.2.09

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Fentanyl – Discussed at DTC 4.6.09 and 16.7.09 Abstral SL® (Fentanyl) Abstral SL® (Fentanyl) sublingual tablets will be sublingual tablets will be Abstral SL® sublingual Abstral SL (fentanyl) tablet should be added to added to the formulary as added to the formulary as tablets. the Formulary for Specialist Initiation by Specialist initiated for relief Specialist initiated for relief Oncologists and Palliative Care only. of pain associated with of pain associated with Effentora® buccal It should only be used for pain associated with cancer (Palliative care and cancer (Palliative care and tablets. cancer. Oncology Oncology). Effentora ® Effentora ® (Fentanyl) (Fentanyl) buccal tablets will Effentora (fentanyl) buccal tablet – should not buccal tablets will not be not be added to the be added to the formulary but will be available added to the formulary and formulary and will ONLY be for any patient admitted on it. will ONLY be ordered for ordered for patients patients admitted on it. admitted on it. Both Abstral Abstral and Effentora should be prescribed by Both Abstral and Effentora and Effentora MUST be brand name. MUST be prescribed by prescribed by brand name.

Actiq (fentanyl lozenges) will be removed from brand name. 3.8.09 the formulary.

Fesoterodine Not approved DTC 24.9.09 Not approved Filgrastim Recommended as an option for use within Hospital only (Ratiograstim®) NHS Wales in the treatment of neutropenia. Please see AWMSG Advice No 1609 August 2009 for full details. Not considered suitable for shared care. Biosimilars should be prescribed by brand name to avoid automatic substitution and ensure consistency in provision. DTC 24.9.09

Fondaparinux (Arixtra) AWMSG advice 0608 May 2008 Noted 18.8.08 Hospital Only 4.8.08 Treatment with unstable angina or non- Recommended as an option for use in the and its ST segment elevation treatment of unstable angina or non-ST monitoring/supervision myocardial infarction segment elevation myocardial infarction in should be retained in (UA/NSTEMI) patients for whom urgent (less than 120 Secondary Care. It is not minutes) invasive management (percutaneous suitable for Shared Care. coronary intervention [PCI]) is not indicated. DTC 22.5.08

Fondaparinux (Arixtra) AWMSG advice 0508 May 2008 Noted 18.8.08 Hospital Only 4.8.08 Treatment with ST segment elevation Recommended as an option for use in the fondaparinux and its myocardial infarction treatment of ST segment elevation myocardial monitoring/supervision (STEMI) infarction (STEMI) in patients who are managed should be retained in with thrombolytics or who are initially to receive Secondary Care. It is not no other form of reperfusion therapy. suitable for Shared Care.

Glucose (Dextrose) First Line First Line liquid (GlucoJuice®) DTC 19.11.09 Glucose (Dextrose) First Line First Line tablets (GlucoTabs®) DTC 19.11.09 Glyceryl trinitrate rectal Specialist Initiated. It should be used second Specialist Initiated 16.6.08 Specialist Initiated, to be ointment ( Rectogesic) line after other products such as Anusol. This used Second line after other will replace the unlicensed product. 22.5.08 0.2% preparation to be products such as Anusol. removed This will replace the unlicensed product. 7.7.08 Hylan G-F 201 (Synvisc) Synvisc and Hyalgan should remain in the Hospital Only.16.6.08 formulary but be annotated to state that NICE CG59 February 2008 does not recommend their use in osteoarthritis. DTC 22.5.08

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Gel The care and management of osteoarthritis in Noted 16.6.08 Approved 4.8.08 adults NICE CG59 February 2008 Noted 22.5.08 DTC recommended addition of this topical NSAID to the formulary

Infliximab Infliximab for the treatment of adults with Hospital Only 18.2.08 Hospital Only 14.4.08 psoriasis NICE TAG134 January 2008 Noted 13.3.08. Hospital only. Infliximab Infliximab for acute exacerbations of ulcerative Hospital Only Hospital Only colitis. NICE TAG163. December 2008. 13.5.09 Hospital Only. DTC 12.2.09 Insulin glargine SoloStar delivery system - Specialist Initiated Specialist Initiated 16.6.08 Specialist Initiated 7.7.08 (Lantus SoloStar) 22.5.08 Insulin glulisine SoloStar delivery system - Specialist Initiated Specialist Initiated 16.6.08 Specialist Initiated 7.7.08 (Apidra SoloStar) 22.5.08 Irritable bowel syndrome Irritable bowel syndrome in adults: diagnosis Formulary to be amended, Not yet noted and management of irritable bowel syndrome in if necessary. 21.4.08 primary care NICE CG61 February 2008 Noted 22.5.08 Ketoprofen gel Added for treatment of osteoarthritis in line with Added 18.8.08 Added 4.8.08 NICE CG59. First line. DTC 10.7.08 KwikPen Specialist Initiated for use with Humalog Lispro® Specialist Initiated Specialist Initiated and Humalog Mix® insulins . 3.8.09 The Formulary will be modified to show which insulins should be kept in stock and which may be ordered as required. DTC 12.2.09

Lacosamide (Vimpat®) Suitable for Hospital only use for adjunctive Specialist Initiated for For use by specialists in the treatment of refractory, partial-onset epilepsy. treatment of patients treatment of patients Prescribing status to be reviewed after one year. resistant to standard resistant to standard For initiation by physicians with appropriate antiepileptic treatments antiepileptic treatments experience in the treatment of epilepsy. DTC (Initially Hospital Only. 12.2.09 13.5.09).

Change in status from Hospital only to Specialist Change in status to Initiated agreed at DTC 16.7.09 Specialist Initiated 3.8.09 Lanreotide (Somatuline Treatment of acromegaly or neuroendocrine Already listed in Formulary Specialist Initiated Shared Autogel®) tumours as Specialist Initiated Care 4.8.08 Shared Care Lanthanum carbonate Suitable for specialist initiation without need for Specialist Initiated 18.2.08 Specialist Initiated. (Fosrenol®) a shared care protocol Lenalidomide For the treatment of multiple myeloma in people Hospital Only Hospital Only who have received at least one prior therapy. 3.8.09 NICE TAG 171 June 2009. DTC 16.7.09 Hospital Only.

Letrozole Due to lack of monitoring requirement. letrozole Noted Noted 3.8.09 will no longer be subject to shared care Amend formulary status requirement to Second Line DTC 4.6.09 Lidocaine 4% LMX4 Topical local anaesthetic cream. Available as For future consideration Hospital Only item for dermatologists in if request is received in Cardiff and Vale UHB for 6 month evaluation Cwm Taf. subject to provision of feedback. Indicators to be established prior to start of evaluation. DTC 19.11.09.

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Linezolid To be reclassified as Hospital Only. 25.9.08 Hospital Only 20.10.08 Hospital Only 13.10.08 Liraglutide (Victoza®) Second Line adjunctive treatment for adults Not to be made available with type 2 diabetes who are intolerant of until NICE guidance is exenatide. Decision subject to NICE published. guidance which may superseded this. DTC 19.11.09 Lormetazepam DTC 2.4.09 To be removed from the formulary. Noted Noted 13.5.09 Maraviroc (Celsentri®) Recommended as an option for use within NHS Hospital Only Hospital Only Wales for the treatment of treatment- Agreed 3.8.09 experienced adults infected only with CCR5- tropic HIV-1, in accordance with British HIV Association (BHIVA) guidance. Not suitable for Shared Care. AWMSG Advice No. 0709 April 2009. DTC 4.6.09 Hospital Only. Mecasermin (Increlex®) Recommended for the long-term treatment Hospital Only of growth failure in children and adolescents with severe primary insulin-like growth factor-I deficiency. Treatment should be initiated and monitored by physicians who are experienced in the diagnosis and management of patients with growth disorders. Not considered suitable for shared care within NHS Wales. AWMSG Advice No 1709 October 2009 DTC 19.11.09 Hospital Only Melatonin (Circadin®) Restricted to Specialist Initiation in patients Specialist Initiated in in whom unlicensed melatonin would patients in whom otherwise be used. DTC 19.11.09 unlicensed melatonin would have been used. Mesalazine Prolonged Once daily formulation for ulcerative colitis. Specialist Initiated 21.4.08 Specialist Initiated 14.4.08 Release Tablets. Other members of the class to be changed to (Mezavant XL®) specialist initiated. 13.3.08 powder for oral First Line GP use First Line First Line therapy for solution (Glucophage®) patients with Type 2 DTC 16.7.09 diabetes and swallowing difficulties. 3.8.09 Methoxy polyethylene Recommended as an option for the Hospital only until glycol-epoetin beta treatment of adults with symptomatic Shared Care issues have (Mircera®) anaemia associated with chronic kidney been considered disease. Suitable for shared care. AWMSG Advice No 1809 October 2009

DTC 19.11.09 Awaiting discussion by Shared Care Group methylphenidate Methylphenidate for attention deficit, Noted 20.10.08 Shared care hyperactivity disorder -guidance on use in adult arrangements have been patients NICE CG72 September 2008 agreed for methylphenidate, and the Already included as Specialist Initiated. The protocol added to the Shared Care Protocol for methyphenidate is WMIC website almost finalized and consideration will be given 3.8.09 as to whether SCP are required for any of the less commonly used drugs. The Guidance also includes adults DTC 13.11.08 Midazolam, buccal Specialist Initiated (mentioned in NICE CG20 Specialist Initiated Specialist Initiated Oct 2004). 3.8.09 DTC 4.6.09 Montelukast Add to Formulary Specialist Initiated 4mg granules and DTC 24.9.09 4 mg chewable tablets

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category Morphine sulphate SR Not to be included in light of the recent rapid Not to be included (Zomorph®) response alert from the NPSA regarding the risk 20.10.08 of patients getting the wrong sustained-release opioid product. Not supported 25.9.08 Moviprep Moviprep should be added to the Formulary as First Line First Line for bowel a First Line agent. Dr Green will be asked to let 15.12.08 cleansing prior to the Committee know the outcome of using endoscopy/radiology Moviprep based on the data which is collected, 8.12.08 for information. DTC 13.11.08 Nelarabine (Atriance®) Recommended for restricted use within NHS Hospital Only Hospital Only Wales for the treatment of patients with T-cell Agreed 3.8.09 acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to, or has relapsed, following treatment with at least two chemotherapy regimens. Treatment should be restricted to patients in whom there is an intention to proceed to allogeneic stem cell transplantation, as it is not cost effective when used for palliation. Not suitable for Shared Care. AWMSG Advice No. 0909 April 2009. DTC 4.6.09 Hospital Only nicardipine For addition Second Line Specialist Initiated Second Line 13.5.09 DTC 2.4.09 ( Second line option) norelgestromin & Removed due to low usage Very low usage. Have Never accepted. ethinylestradiol (EVRA advised it could be transdermal) removed. Oftaquix (levofloxacin) Not approved - - eye drops DTC 13.11.08 Omalizumab Omalizumab for severe persistent allergic Hospital Only 18.2.08 Hospital Only 14.4.08 asthma. NICE TAG133 November 2007. Noted 13.3.08 Hospital only. Ondansetron Melts Add to Formulary Specialist Initiated DTC 24.9.09 Oseltamivir, amantadine, Oseltamivir, amantadine, & for the Oseltamivir and zanamivir First Line zanamivir prophylaxis of influenza. NICE TA158 Second Line. 8.12.08 September 2008 (review of TA67) Amantadine NOT to be Oseltamavir and zanamavir First Line for use in included for influenza. line with NICE Guidance. DTC 13.11.08 20.10.08 Oseltamivir, amantadine, Oseltamivir, amantadine, & zanamivir for the Noted zanamivir treatment of influenza TA168 February 2009 (review of NICE TA58). (Note: amantadine not recommended.) Osteoarthritis in adults The care and management of osteoarthritis in - - adults NICE CG59 February 2008 Noted 22.5.08 DTC recommended addition of a topical NSAID to the formulary (see ibuprofen and ketoprofen) Ovitrelle® (chorionic Add Ovitrelle as Hospital Only. Hospital Only Hospital Only gonadotrophin) injection Remove Pregnyl. Pregnyl® will remain in the Pregnyl® will remain in the DTC 16.7.09 Formulary. Formulary. 3.8.09 Pegfilgrastim Recommended for restricted use in neutropenia. Noted Hospital Only AWMSG Advice No 1508 August 2008. 13.10.08 Not suitable for Shared Care. DTC 25.9.08 Pemetrexed Pemetrexed for the treatment of malignant Hospital Only. 18.2.08 Hospital Only 14.4.08 (mesothelioma) pleural mesothelioma. NICE TAG135 January 2008 Noted 13.3.08 Hospital only. Pemetrexed For the first-line treatment of non-small-cell Hospital Only – already

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category lung cancer. NICE TA181 September 2009 in Formulary for other DTC 19.11.09 Hospital Only indications

Perindopril arginine NOT APPROVED 22.5.08 Noted 16.6.08 Endorsed decision 7.7.08 posaconazole (Noxafil®) Oral triazole antifungal for the treatment (NOT Hospital Only 21.4.08 Hospital Only use in line prophylaxis) of fungal infections in adult patients For specialist initiated with Haematology with refractory disease. Hospital only use in line hospital use in neutropenic neutropenic policy 14.4.08 with Haematology neutropenic policy. 13.3.08 patients. Prasugrel For the treatment of acute coronary Specialist Initiated syndromes with percutaneous coronary intervention NICE TA182 October 2009 DTC 19.11.09 Specialist Initiated Pravastatin Lipid modification NICE CG67 May 2008 Remains unchanged as First Line 18.8.08 Pregabalin (Previously approved for 12 month audit period Specialist Initiated Retain as Specialist Initiated for use in Chronic Pain and Palliative Care. after failure of Gabapentin following audit period. (for neuropathic pain) Consultant Initiated after failure of gabapentin) 13.10.08 See Chronic Pain Management Protocol C&V 2007 Progesterone vaginal gel Hospital Only Hospital Only (Crinone®) DTC 16.7.09 3.8.09 quetiapine Prolonged Approved by AWMSG for schizophrenia. May Specialist Initiated – only Noted Release ( Seroquel XL) be suitable for SHARED CARE. for the treatment of AWMSG Advice No 1509 August 2009 schizophrenia raloxifene Not recommended for the primary prevention of Noted osteoporotic fragility fractures in postmenopausal women NICE TAG 160 October 2008 raloxifene For the secondary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Osteoporosis Secondary prevention January 2005)

Raltegravir (Isentress®) Recommended as an option for the treatment of Hospital Only Hospital Only HIV-1 infection in treatment-experienced adults 8.12.08 in accordance with the British HIV Association (BHIVA) guidance. Not suitable for Shared Care. AWMSG Advice No 1808 Oct 2008 DTC 13.11.08

Ranibizumab (Lucentis®) Ranibizumab and pegaptanib for the treatment Ranibizumab Hospital Ranibizumab Hospital Only of age-related macular degeneration. NICE Only. To be prescribed 13.10.08 TA155 August 2008. strictly in accordance with NICE guidance. NHS Pegaptanib NOT recommended by NICE. Trusts must make the Ranibizumab Hospital Only. DTC 25.9.08 necessary arrangements to ensure that the cost beyond 14 injections in the treated eye is met by the manufacturer 20.10.08 Rheumatoid Arthritis Rheumatoid arthritis: The management of rheumatoid arthritis in adults CG79 February 2009 ( replaces TA27 & TA72) DTC 2.4.09 (Rimonabant) Rimonabant for the treatment of overweight and (Second Line 18.8.08) (Second Line 4.8.08)

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category obese patients. NICE TAG144 June 2008 Second Line 10.7.08 Noted Noted DTC 2.4.09 To be removed from the formulary. Removed 2.4.09 Removed 2.4.09 (Marketing authorisation withdrawn.) risedronate For the primary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 160 October 2008 risedronate For the secondary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Osteoporosis Secondary prevention January 2005) Rituximab Rituximab for the treatment of relapsed or Hospital Only use Hospital Only use restricted refractory stage III or IV follicular non-Hodgkin’s restricted to specialists. to specialists. lymphoma. NICE TAG137 February 2008. 21.4.08 Replaces TAG 37 Noted 22.5.08 Rituximab Rituximab for the first-line treatment of Hospital Only – already chronic lymphocytic leukaemia in Formulary for other NICE TA174 July 2009. indications Suggested category Hospital Only DTC 24.9.09 Rivaroxaban For the prevention of venous thromboembolism Decision awaited after total hip or total knee replacement in adults. NICE TAG 170 April 2009. rivastigmine patches For Alzheimer’s patients with swallowing Hospital Only 21.4.08 Hospital Only 14.4.08 (Exelon®) difficulty. Specialist hospital prescribing and monitoring. 13.3.08 SR Specialist Initiated for Parkinson’s disease in Specialist Initiated Specialist Initiated 13.10.08 (Requip XL ®) line with other similar agents 25.9.08 20.10.08 Ropinirole prolonged- Recommended for Parkinson’s disease in Already in Formulary as release (Requip XL ®) patients already stabilised on ropinirole Specialist Initiated immediate-release tablets, in line with AWMSG Advice No 1409 August 2009. Prescribe by brand as Requip XL to reduce risk of error. Suitable for shared care in accordance with appropriate guidance. DTC 24.9.09 Rosuvastatin Lipid modification NICE CG67 May 2008 Remains unchanged as Specialist Initiated 18.8.08 Rufinamide (Inovelon®) Rufinamide (Inovelon®▼) is recommended for Hospital Only use as an adjunctive therapy in patients four years and older with Lennox-Gastaut syndrome in patients where other adjunctive treatments have proved sub-optimal or have not been tolerated. Not suitable for Shared Care. AWMSG Advice No 1708 Oct 2008 Hospital Only DTC 12.2.09 [Note: AWMSG confirmation of this prescribing category is awaited.]

Setopress Prescribing category changed to Specialist Specialist Initiated Specialist Initiated Initiated DTC 2.4.09 13.5.09 Simvastatin Lipid modification NICE CG67 May 2008 Remains unchanged as First Line 18.8.08 Sitagliptin (Januvia®) Recommended for Third Line use. May be Third Line – suitable for Second Line in line with initiated in both primary and secondary care initiation in primary and principles of NICE guidance when Second Line agents have failed or are secondary care 4.8.08 inappropriate. 10.7.08 18.8.08 For the primary prevention of osteoporotic Noted

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category fragility fractures in postmenopausal women NICE TAG 160 October 2008 strontium ranelate For the secondary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Osteoporosis Secondary prevention January 2005)

Sunitinib For the first line treatment of advanced and/or Hospital Only Hospital Only metastatic renal cell carcinoma 3.8.09 NICE TAG 169 March 2009. Hospital Only DTC 4.6.09

Sunitinib For the treatment of gastrointestinal stromal Hospital Only – already tumours. NICE TA179 September 2009. included for other DTC 19.11.09 Hospital Only indications. Surepress To be removed from the formulary Noted Noted DTC 2.4.09 13.5.09 Synvisc 1 (see also Added to the formulary as a Hospital Only Hospital Only Hospital Only treatment for under Hylan) product. DTC 13.11.08 15.12.08 visco-supplementation in osteoarthritis 8.12.08 Telbivudine (Sebivo®) NOT RECOMMENDED for the treatment of Noted 20.10.08 chronic hepatitis B. NICE TA154 August 2008. DTC 25.9.08 Telmisartan (Micardis®) Suggested category Specialist Initiated Specialist Initiated, for Specialist Initiated, for DTC 2.4.09 hypertension only, in ACE hypertension only, in ACE inhibitor – intolerant inhibitor – intolerant patients, with vascular patients, with vascular disease or who are at high disease or who are at high risk of vascular disease, risk of vascular disease, without heart failure without heart failure. 13.5.09 Temocillin Cystic fibrosis patients only. Temocillin should Hospital Only 6.11.06 Awaiting HCW approval for be initiated on the recommendation of a use in Cardiff and the Vale. microbiologist or cystic fibrosis consultant. 21.9.06 Tenofovir disoproxil Recommended for restricted use in adults with Noted Specialist Initiated, may be (as fumarate) chronic hepatitis B (originally noted as suitable suitable for shared care for Shared Care) 13.10.08 AWMSG Advice No 1208 August 2008 DTC 25.9.08 8/12/08 – it has now been agreed that this is NOT 8/12/08 – it has now been agreed that this is suitable for Shared Care – NOT suitable for Shared Care – see AWMSG see AWMSG website website Tenofovir disoproxil For the treatment of chronic hepatitis B. Hospital Only NICE TA173 July 2009. Suggested category Hospital Only. DTC 24.9.09

Tensopress Suggested category Specialist Initiated Specialist Initiated Specialist Initiated DTC 2.4.09 13.5.09 For the secondary prevention of osteoporotic Noted fragility fractures in postmenopausal women NICE TAG 161 October 2008 (Replaces TA 87 Osteoporosis Secondary prevention January 2005). testosterone 2% gel Specialist initiated therapy for male Specialist Initiated Specialist Initiated 14.4.08

Generic Name Drug & Therapeutics Committee North Bro Taf Cardiff And Vale Abbreviated Notes Prescribing Category Prescribing Category (Tostran) hypogonadism. Could replace Testogel. 13.3.08 21.4.08 testosterone sachets Removal suggested – for replacement with Remove Testogel 21.4.08 Remove Testogel 14.4.08 50mg/5g (Testogel) Tostran Thalidomide Recommended in combination with melphalan Hospital Only Hospital Only (Thalidomide Pharmion®) and prednisone as first line treatment of patients 13.5.09 with untreated multiple myeloma, aged ≥65 years, or ineligible for high dose chemotherapy. Should only be prescribed and dispensed according to the Thalidomide Pharmion Pregnancy Prevention Programme. Not suitable for Shared Care. AWMSG Advice No. 0109 February 2009. Tigecycline (Tygacil®) Hospital Only – Consultant Microbiologist Hospital Only – Consultant Hospital Only – Consultant initiated only Microbiologist initiated only Microbiologist initiated only DTC 16.7.09 i.e. Category C antimicrobial. 3.8.09 Tiotropium solution for Second line for use in COPD. 22.5.08 Second Line 16.6.08 Second Line in the inhalation treatment of COPD. 7.7.08 (Spiriva Respimat) Topotecan hydrochloride Topotecan in the treatment of small cell lung Hospital Only 16.6.08 (Hycamtin® ) cancer. AWMSG Advice 0108 March 2008 Noted 13.3.08 Topotecan hydrochloride Topotecan in the treatment of cervical cancer. Hospital Only 21.4.08 Hospital Only 14.4.08 (Hycamtin® ) AWMSG Advice 0208 February 2008 Noted 13.3.08 Topotecan For the treatment of recurrent and stage IVB Hospital Only – already cervical cancer. NICE TA183 October 2009 in Formulary for other DTC 19.11.09 Hospital Only indications Triptorelin (Decapeptyl Specialist Initiated. No Shared Care Protocol Specialist Initiated SR®) necessary. DTC 24.9.09 Trisodium citrate Hospital Only Hospital Only (Duralock®) DTC 24.9.09 urokinase The Committee agreed that it would be Hospital Only Hospital Only (Syner-KINASE®) appropriate to add this new product to the 15.12.08 8.12.08 formulary to replace an unlicensed product ustekinumab For the treatment of adults with moderate to Hospital Only severe psoriasis NICE TA180 September 2009 DTC 19.11.09 Hospital Only Versiva XC Suggested category Specialist Initiated Specialist Initiated Specialist Initiated Hydrocolloid® DTC 2.4.09 13.5.09 Vildagliptin Type II Diabetes – Newer agents NICE CG87 Second Line May 2009 The Committee advised that both sitagliptin and vildagliptin should be included for use within their respective licensed indications. Both are to be listed as Second Line, but within the class, sitagliptin should be used first and vildagliptin second. DTC 24.9.09 infusion Hospital Only for postmenopausal osteoporosis Hospital Only ( for initiation Hospital Only Second line (Aclasta) as a second line agent when generic oral by specialists, second line when generic oral alendronate is contra-indicated, not tolerated or after other agents) 16.6.08 alendronate is contra- where adherence to oral treatments is poor. (For indicated, not tolerated or once yearly intravenous infusion) 22.5.08 where adherence to oral treatments is poor. 7.7.08

End of document

CONTENTS

How to use the Formulary...... 2

Applications for new drugs...... 4

Policy on Prescribing Unlicensed Drugs or Using Drugs for Unlicensed Indications...... 5

CHAPTER 1 GASTRO-INTESTINAL SYSTEM...... 7

CHAPTER 2 CARDIOVASCULAR SYSTEM...... 16

CHAPTER 3 RESPIRATORY SYSTEM ...... 31

CHAPTER 4 CENTRAL NERVOUS SYSTEM...... 41

CHAPTER 5 INFECTIONS ...... 74

CHAPTER 6 ENDOCRINE SYSTEM...... 86

CHAPTER 7 OBSTETRICS, GYNAECOLOGY AND URINARY-TRACT DISORDERS...... 108

CHAPTER 8 MALIGNANT DISEASE AND IMMUNOSUPPRESSION...... 117

CHAPTER 9 NUTRITION AND BLOOD ...... 124

CHAPTER 10 MUSCULOSKELETAL AND JOINT DISEASES...... 135

CHAPTER 11 EYE...... 144

CHAPTER 12 EAR, NOSE AND OROPHARYNX ...... 155

CHAPTER 13 SKIN...... 159

CHAPTER 14 VACCINES...... 176

CHAPTER 15 ANAESTHESIA...... 177

APPENDIX 1 WOUND DRESSINGS...... 182

APPENDIX 2 UNLICENSED MEDICAL PRODUCTS...... 188

APPENDIX 3 PALLIATIVE CARE...... 192

APPENDIX 4 MEDICINES INFORMATION SERVICES AND NHS DIRECT...... 193

APPENDIX 5 PRODUCT DELETIONS...... 194

Please note:

This information contained in this formulary is issued on the understanding that it is the best available from the resources at our disposal at the date of compilation.

Manufacturers may alter the formulation of a product from time to time. Further information on any given product may be obtained from your Medicines Information Centre or the manufacturer. Manufacturers’ Data Sheets or Summary of Product Characteristics should be consulted for full prescribing information.

Extracts from NICE guidance have been added for general information. Please consult the full guidance before making therapeutic decisions.

Although great care has been taken to ensure the information is as up-to-date and accurate as possible, the Bro Taf Localities Drug & Therapeutics Committee and associated Medicines & Therapeutics Executive Committees cannot accept responsibility for any errors or omissions.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 1 HOW TO USE THE FORMULARY

This formulary is divided into sections which correspond to the chapters of the BNF. This should facilitate rapid cross-reference. Each drug has been allocated a prescribing category. These are represented by colour coding and also by use of a symbol to assist readers with impaired colour vision. The categories are as follows:

1st line c A suitable first choice for GPs and non- specialists e.g. SHOs.

2nd line d Also suitable for the above, but possibly reserved until after a first line agent has been tried or rejected on grounds of or allergy. In many cases these will be the more expensive agents.

Specialist Initiated (S) Follow-up prescriptions may be issued by GPs but initiation/stabilisation should be performed by a specialist. This group includes drugs for which shared-care protocols exist.

Hospital Only (H) All prescriptions are issued from hospitals or use only applies to hospitals e.g. anaesthetics, infusions, or “one-off” treatments. Specialists will normally be the sole users of these treatments.

Drugs are usually listed using their 'approved' (generic) name. Exceptions to this are those drugs which have a pharmaceutical and therapeutic basis for prescribing by brand name and those drugs which have several active ingredients. Some drugs may have their brand name in brackets as an aid to avoid confusion between similar sounding and similar looking drug names.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 2 Generic Prescribing and “Generic Substitution”

In order to avoid confusion among patients, their carers and other healthcare workers it is advisable that, whenever appropriate, drugs are prescribed using the generic drug name. The use of the generic drug name also helps promote generic prescribing in primary care. In most cases, hospital pharmacies will dispense “generic equivalents” when the manufacturer’s brand name for a drug is used on the prescription. The formulary identifies drugs which should be prescribed by brand name. In these cases the branded product will be dispensed. rINNs & BANS

The formulary lists drugs by their Recommended International Non- propriety Name (rINN). Again, to avoid confusion, we have included the UK name or the former British Approved Name underneath and in brackets. Please see the BNF section on name changes for further clarification.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 3 APPLICATIONS FOR NEW DRUGS

Consultants wishing to introduce a new drug for inpatient or outpatient use, or to recommend its use by a patient's General Practitioner, should complete an application form which is available from the Welsh Medicines Information Centre. The form is available via e-mail or by post with a floppy disc. The completed application should be emailed back. A hard copy should also be sent with relevant signatures and supporting information (see below). Please see page 1 for contact details. For full information, please see the guidance notes which accompany the application form.

Who may complete the application?

The application should be made by a Consultant or GP. A local Chief Pharmacist may also apply on his/her behalf. Please note: Applications completed by individuals not employed by the College of Medicine or NHS will not be accepted.

Supporting Information

Applications for new drugs should be accompanied with evidence which supports the intended use, such as key clinical trials or systematic reviews which have been fully published in a peer-reviewed journal. Help in locating suitable papers may be sought from your local Medicines Information Centre if necessary.

The new drug application review process

New drug applications are checked for completeness then discussed at the Bro Taf Health Localities Medicines & Therapeutics Advisory Committee. At this stage applications are reviewed for therapeutic safety and efficacy by Hospital Specialists, General Practitioners and Pharmacists. Recommendations are made to both the North Bro Taf Localities and the Cardiff and Vale Medicines and Therapeutics Executive Committees who then consider commissioning issues before making a final decision. The applicant will be informed of the Committee's decision by letter. Occasionally, the use of drugs added to the formulary will be restricted to certain prescribers (e.g., a particular speciality or Consultant only). When a drug is approved temporarily for a period of assessment it may be made available to other Consultants in the speciality if desired.

Clinical Trials and Samples

Materials for clinical trials should be deposited in Pharmacy, from where supply will be made in accordance with the trial protocols.

Free samples of pharmaceuticals should not be left in patient treatment areas. Free drug samples are not normally accepted in Trust Hospital Pharmacies within the Bro Taf locality. For further information, check with the Pharmacy Department of the individual Trust.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 4

POLICY ON PRESCRIBING UNLICENSED DRUGS OR USING DRUGS FOR UNLICENSED INDICATIONS

ƒ The Bro Taf Health Localities Medicines and Therapeutics Advisory Committee recognises that the informed use of unlicensed medicines or of licensed medicines for unlicensed applications is sometimes necessary in medical practice.

ƒ This is accepted by the Welsh Risk Pool which will indemnify participants against incidents arising out of these uses subject to there being an appropriate in-house policy covering the use of drugs in such circumstances approved by a Medicines & Therapeutics Committee. It is also in keeping with the policy statement from the Royal College of Paediatrics and Child Health.

ƒ The Medical Protection Society has stated that the fact that a drug is not licensed does not preclude its use but the prescriber would have to demonstrate that the prescription was in accordance with responsible medical practice by reference to other practitioners, authoritative journals, medical texts or other reliable sources. In addition, the Medicines Act and Regulations provides exemptions which enable doctors to prescribe unlicensed medicines.

ƒ The Committee recommends that because of the medico-legal implications of the use of unlicensed medicines or those being used outside their licensed indications, unless supported by informed consent, specialities within Bro Taf should have a policy for the use of such medicines in their area. These policies should be subject to peer group support and reinforced by reference to standard texts or peer review. Policies should be reviewed regularly e.g. annually, and monitored and audited by local Medicines & Therapeutics Committees and Prescribing Sub-Committees of Local Health Boards.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 5 ƒ The Committee further recommends that:-

- prescribers should choose the medicine which offers the best prospect of benefit for the patient, with due regard to safety and cost.

- Health Professionals should have ready access to sound information on any medicine they prescribe, dispense or administer.

- in general, it is not necessary to take additional steps, beyond those taken when prescribing licensed medicines, to obtain consent to prescribe or administer unlicensed medicines or licensed medicines for unlicensed applications.

- NHS Trusts and Local Health Boards should support therapeutic practices that are in keeping with a respected, responsible body of opinion.

Taken from: Bro Taf Drug & Therapeutics Committee January 2001

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 6 CHAPTER 1 GASTRO-INTESTINAL SYSTEM

1.1 Antacids and Other Drugs for Dyspepsia

1.1.1 Aluminium- and magnesium-containing antacids c magnesium trisilicate mixture c aluminium hydroxide mixture c aluminium & magnesium hydroxide (Maalox)

Other compound antacid preparations H sodium citrate solution 0.3M See Appendix 2

Sodium bicarbonate powder has been removed due to the risk of alkalosis with excessive doses and dangers to patients in heart failure or with liver or renal impairment. carbonate was removed as an antacid due to risk of alkalosis and . Mucaine is no longer commercially available.

Compound alginic acid preparations Alginate containing products have low acid suppressant activity and should be reserved for patients with reflux symptoms.

c Gastrocote tablets liquid c Gaviscon Advance1 liquid (SF)

c Gaviscon tablets (SF) infant sachets (SF)

1 Gaviscon Advance is a new formulation of Gaviscon with reduced sodium (now 2.3mmol Na+ in 5ml) and an increased concentration of alginate. The new dose of Gaviscon Advance Liquid in adults is 5-10ml qds. Suitable for use during labour.

Sodium content of Antacids

Antacid Sodium Content • magnesium trisilicate mixture 10ml = 6mmol Na+ • aluminium and magnesium hydrochloride 10ml < 1mmol Na+ (Maalox) • Gastrocote tablets 2 tabs = 2mmol Na+ • Gastrocote liquid 10ml = 3.6 mmol Na+ • Gaviscon tablets 2 tabs = 4mmol Na+ • Gaviscon Advance liquid 10ml =4.6 mmol Na+ • Gaviscon infant 1 dose=0.92 mmol Na+ (half dual sachet)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 7 1.2 Antispasmodics and other Drugs Altering Gut Motility

Antimuscarinics d hyoscine butylbromide1 tablets 20mg injection 20mg/mL H propantheline see section 7.4.2

Other antispasmodics c peppermint oil capsules 0.2 mL (Colpermin) c mebeverine hydrochloride tablets 135mg liquid 50mg/5mL (SF)

1 Hyoscine butylbromide may be useful in gastro-intestinal disorders characterised by smooth muscle spasm and in palliative care, but anti-cholinergic side effects limit its use. The tablets are poorly absorbed but have been retained on the Formulary as other presentations are available for use following surgery.

Motility stimulants c metoclopramide (see section 4.6) c domperidone (see section 4.6)

Others d peppermint water Liquid See Appendix 2

1.3 Ulcer Healing Drugs

Helicobacter pylori infection • One-week eradication regimens that include a proton pump inhibitor and clarithromycin with either metronidazole or produce H.pylori eradication in 90% or more of patients. • Treatment failure may reflect poor compliance, metronidazole resistance or less commonly clarithromycin resistance. If clarithromycin cannot be used both amoxicillin and metronidazole need to be used instead. • Treatment options are listed in the BNF with a price comparison for a one-week course. • Antisecretory treatment (with a proton pump inhibitor or H2-receptor antagonist) may need to be continued for 4-8 weeks to promote ulcer healing (particularly after ulcer haemorrhage or perforation).

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 8 1.3.1 H2-receptor antagonists c cimetidine1 tablets 200mg, 400mg syrup 200mg/5mL injection 200mg/2mL d ranitidine2 tablets 150mg effervescent tablets 150mg syrup (SF) 75mg/5mL injection 50mg/2mL

1 is the drug of choice when ORAL H2 antagonist therapy is indicated. 2 should be reserved for children and patients: i) receiving drugs whose metabolism is inhibited by cimetidine * warfarin & acenocoumarol (nicoumalone) * theophylline (or aminophylline) * phenytoin & carbamazepine * antiarrhythmics: amiodarone, flecainide, lidocaine (lignocaine), procainamide, propafenone & quinidine ii) intolerant of or unresponsive to cimetidine iii) receiving high dose therapy for hypersecretory states iv) with terminal or advanced cancer Unlike ranitidine, cimetidine is not licensed for prophylaxis of NSAID-induced ulceration.

1.3.3 Chelates and complexes c sucralfate1 dispersible tablets 1g suspension 1g/5mL d bismuth chelate2 tablets 120mg

1 The CSM has issued a warning on bezoar formation associated with sucralfate. Caution in seriously ill patients, especially those receiving concomitant enteral feeds or those with pre-disposing conditions such as delayed gastric emptying. 2 Bismuth chelate has been retained for occasional use in H.pylori eradication and also for treatment of bloating and wind in IBS.

1.3.4 Prostaglandin analogues d misoprostol1 tablets 200micrograms

1 Misoprostol. Avoid in women of childbearing age unless effective contraceptive measures are taken and the patient has been advised of the risks of taking misoprostol if pregnant.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 9 1.3.5 Proton pump inhibitors

General points: • PPIs can mask the symptoms of early gastric cancer and should not be used in patients over 45 years old without regular review. • Significant cost savings may be achieved by ensuring the dose of PPI is reduced to a maintenance level as soon as it becomes appropriate. • INR monitoring is required when patients stabilised on warfarin are prescribed a PPI. Levels of phenytoin and ketoconazole should also be checked.

NICE Clinical Guidelines on Dyspepsia (CG17, August 04). (Quick reference guide) (Please note that this replaces CG7 on proton pump inhibitors.

Key priorities for implementation Referral for endoscopy ● Review medication for possible causes of dyspepsia, e.g. calcium antagonists, nitrates, theophyllines, , corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). In patients requiring referral, suspend NSAID use. ● Urgent specialist referral for endoscopic investigation* is indicated for patients of any age with dyspepsia when presenting with any of the following: chronic gastrointestinal bleeding, progressive unintentional weight loss, progressive difficulty swallowing, persistent vomiting, iron deficiency anaemia, epigastric mass or suspicious barium meal. ● Routine endoscopic investigation of patients of any age, presenting with dyspepsia and without alarm signs, is not necessary. However, for patients over 55, consider endoscopy when symptoms persist despite Helicobacter pylori (H. pylori) testing and acid suppression therapy, and when patients have one or more of the following: previous gastric ulcer or surgery, continuing need for NSAID treatment or raised risk of gastric cancer or anxiety about cancer.

Interventions for un-investigated dyspepsia ● Initial therapeutic strategies for dyspepsia are empirical treatment with a proton pump inhibitor (PPI) or testing for and treating H.pylori. There is currently insufficient evidence to guide which should be offered first. A 2- week washout period following PPI use is necessary before testing for H. pylori with a breath test or a stool antigen test.

Interventions for gastro-oesophageal reflux disease (GORD) ● Offer patients who have GORD a full-dose PPI for 1 or 2 months. ● If symptoms recur following initial treatment, offer a PPI at the lowest dose possible to control symptoms, with a limited number of repeat prescriptions.

Interventions for peptic ulcer disease ● Offer H. pylori eradication therapy to H. pylori-positive patients who have peptic ulcer disease. ● For patients using NSAIDs with diagnosed peptic ulcer, stop the use of NSAIDs where possible. Offer full-dose PPI or H2 receptor antagonist therapy for 2 months to these patients and if H. pylori is present, subsequently offer eradication therapy.

Interventions for non-ulcer dyspepsia ● Management of endoscopically-determined non-ulcer dyspepsia involves initial treatment for H. pylori if present, followed by symptomatic management and periodic monitoring. ● Re-testing after eradication should not be offered routinely, although the information it provides may be valued by individual patients.

Reviewing patient care ● Offer patients requiring long-term management of symptoms for dyspepsia an annual review of their condition, encouraging them to try stepping down or stopping treatment. ● A return to self-treatment with antacid and/or alginate therapy (either prescribed or purchased over-the-counter and taken as required) may be appropriate.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 10

H. pylori testing and eradication ● H. pylori can be initially detected using either a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology where its performance has been locally validated. ● Office-based serological tests for H. pylori cannot be recommended because of their inadequate performance. ● For patients who test positive, provide a 7-day, twice-daily course of treatment consisting of a full-dose PPI with either metronidazole 400 mg and clarithromycin 250 mg or amoxicillin 1 g and clarithromycin 500 mg. * The Guideline Development Group considered that ‘urgent’ meant being seen within 2 weeks.

c lansoprazole capsules 15mg, 30mg suspension 30mg/sachet c omeprazole capsules 10mg, 20mg, 40mg tablets 10mg, 20mg, 40mg infusion 40mg

1.4.2 Antimotility drugs

The cause of diarrhoea should be identified before starting symptomatic treatment. Codeine has addictive properties and should be reserved for short courses only except for patients with inflammatory bowel disease. c codeine phosphate tablets 15mg, 30mg c loperamide tablets 2mg liquid 1mg/5mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 11 1.5 Chronic Bowel Disorders

Aminosalicylates Aminosalicylates should be avoided in salicylate hypersensitivity. The CSM have warned that blood disorders may occur. Patients should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A full blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasia. c sulfasalazine1 tablets 500mg tablets 500mg ec suspension 250mg/5mL suppository 500mg d mesalazine2 (Asacol) tablets 400mg ec foam enema 1g suppositories 250mg, 500mg (Pentasa) tablets 500mg m/r retention enema 1g suppositories 1g S balsalazide3 capsules 750mg

1 Sulfasalazine is useful for patients with concomitant rheumatoid disease. A shared care protocol for use in inflammatory bowel disease is proposed. (No 05(1)) 2 Mesalazine tablets are “modified release” and different brands may have different release characteristics. Therefore brands are not interchangeable and generic prescribing is not recommended. Mesalazine enemas are a useful alternative to steroid enemas in acute and maintenance therapy. Pentasa m/r tablets may be dispersed in water without losing the m/r effect. 3 Balsalazide initiation is restricted to consultant gastroenterologists for 3rd line use.

Anion exchange resins c colestyramine sachet 4g (cholestyramine) Corticosteroids c prednisolone (see section 6.3.2 for oral preparations) suppositories 5mg retention enema 20mg/100mL (Predenema) foam enema 20mg (Predfoam) d budesonide capsules 3mg ec (Entocort CR) retention enema 2mg/100mL Immunosuppressants S azathioprine see section 10.1.3 H ciclosporin (cyclosporin) see section 10.1.3 H infliximab1 injection 100mg

1 See NICE Guidance TA40 (April 2002) for use of infliximab for Crohn’s disease. (Review in progress)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 12 1.6 Laxatives

1.6.1 Bulk-forming laxatives

Preparations that swell in contact with liquid should always be taken carefully and swallowed with plenty of water. They should not be taken immediately before going to bed. c ispaghula sachet 3.5g (Fybogel Orange) c methylcellulose tablets 500mg (Celevac)

1.6.2 Stimulant laxatives c senna1 tablets 7.5mg syrup 7.5mg/5mL c bisacodyl1 tablets 5mg suppositories 5mg, 10mg d co-danthramer2 capsules 25/200 suspension 25/200 in 5mL strong capsules 37.5/500 strong suspension 75/1000 in 5mL d docusate sodium capsules 100mg d glycerin/glycerol suppositories 1g, 2g, 4g d sodium picosulfate liquid 5mg/5mL (Laxoberal) (sodium picosulphate)

Prescribing notes for stimulant laxatives 1 Stimulant laxatives, with prolonged use, can precipitate the onset of an atonic non- functioning colon and hypokalaemia. 2 Co-danthramer. The CSM has advised that use of products containing dantron (danthron) should be restricted to use in prophylaxis and treatment of - induced constipation in terminally ill patients of all ages. The CSM has also advised that the risk/benefit for use in all other indications is no longer favourable due to the weight of pre-clinical evidence, which establishes dantron (danthron) as a potential human carcinogen. Other laxatives are available and are currently being used in similar clinical settings. (Current Problems vol 26, May 2000) The action of co-danthramer takes 6-12 hours. It must be avoided in pregnancy and breast-feeding. Urine may be coloured red and may damage skin on prolonged contact (avoid in incontinent patients).

• Co-danthramer suspension 5mL = one co-danthramer capsule but strong co-danthramer suspension 5mL = two strong co-danthramer capsules. • Co-danthrusate (50/60) has been deleted as capsules are larger and harder to swallow. Caution when converting patients onto co-danthramer as products are not equivalent and dose titration may be necessary.

Most terminally ill patients require both a softening agent and a stimulant laxative such as co-danthramer. A cheaper alternative is magnesium hydroxide and senna.

1.6.3 Faecal softeners d arachis oil1 enema

1 Arachis oil should be avoided in patients allergic to peanuts.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 13 1.6.4 Osmotic laxatives c magnesium hydroxide Mixture c magnesium sulphate powder (Epsom salts) c lactulose1 solution d phosphate enema, suppositories d sodium citrate compound2 micro enema S macrogol powder (Movicol)

1 Lactulose takes up to 48 hours to work and is often inappropriately used “when required”. 2 Micralax, Micolette and Relaxit enemas are bought on hospital contract. Therefore please prescribe them generically.

1.6.5 Bowel cleansing solutions

Bowel cleansing solutions should only be used before colonic surgery, colonoscopy or radiological examination. Adequate counselling is required. They should not be used as laxatives. The radiology department will advise on choice of agent for specific procedures.

S sodium picosulfate/ magnesium oral powder (Picolax) citrate (sodium picosulphate) S magnesium citrate oral powder (Citramag) S macrogol 3350 compound oral powder (Klean-Prep) S sodium dihydrogen phosphate oral solution (SF) sodium phosphate (Fleet Phospho-soda) decahydrate

1.7 Local Preparations for Anal and Rectal Disorders

These preparations should only be used for short periods (not more than a few days) as they cause sensitisation of the skin. Excessive application of preparations containing local anaesthetics should be avoided.

1.7.1 Soothing haemorrhoidal preparations c Anusol rectal ointment rectal cream suppositories

Anal fissure S glyceryl trinitrate ointment 0.2% (available from St Mary’s )

1.7.2 Compound haemorrhoidal preparations with corticosteroids d Anusol HC rectal ointment suppositories d Xyloproct rectal ointment suppositories

1.7.3 Rectal sclerosants

H oily phenol injection 5%

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 14 1.8 Stoma Care

Please contact your local stoma nurse for advice. 1.9 Drugs Affecting Intestinal Secretions

1.9.1 Drugs acting on the gall bladder d ursodeoxycholic acid tablets 150mg, 250mg suspension 250mg/5mL H octreotide (see section 8.3.4) H terlipressin1 vial 1mg + diluent (see also section 6.5.2)

1 Terlipressin is included for patients with bleeding oesophageal varices.

1.9.4 Pancreatin supplements

The CSM has advised of data that associates high-strength pancreatin preparations Nutrizym 22 and Pancreatin HL with the development of large bowel strictures (fibrosing colonopathy) in children with cystic fibrosis aged between 2 and 13 years. No association was found with Creon 25 000. The following was recommended: • Pancrease HL, Nutrizym 22, Panzytrat 25 000 (now discontinued) should not be used in children aged 15 years or less with cystic fibrosis; • the total dose of pancreatic enzyme supplements used in patients with cystic fibrosis should not usually exceed 10 000 units of lipase per kg body-weight daily; • if a patient on any pancreatin preparation develops new abdominal symptoms (or any change in existing abdominal symptoms) the patient should be reviewed to exclude the possibility of colonic damage. Possible risk factors are gender (boys at greater risk than girls), more severe cystic fibrosis, and concomitant use of laxatives. The peak age for developing fibrosing colonopathy is between 2 and 8 years. COUNSELLING. It is important to ensure adequate hydration at all times in patients receiving higher-strength pancreatin preparations.

S pancreatin Creon 10 000, 25 000, 40 000 Creon Micro Pancrex V Powder Pancrease Capsules (Nutrizym 10,000 and 22,000 are retained for existing patients only.)

Miscellaneous Items H sodium tetradecyl sulphate1 injection 3% H adrenaline2 injection 1:10,000 (epinephrine) solution 1:10,0003

1 Sodium tetradecyl sulphate is used in gastroenterology for the injection of oesophageal varices. 2 injection is used in the treatment of bleeding ulcers. 3 Adrenaline 1:10,000 solution used to control bleeding in palliative care. The solution is used to soak gauze which is then applied to ulcerating skin tumours.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 15 CHAPTER 2 CARDIOVASCULAR SYSTEM

Please see NICE Clinical Guidance Hypertension - full guideline (the new recommendations and the evidence they are based on) CG34 June 2006: The management of hypertension in adults in primary care (This is a partial update of CG018 Aug 2004) MI: Secondary prevention in primary and secondary care for patients following a myocardial infarction CG48 May 2007

2.1 Positive Inotropic Drugs

2.1.1 Cardiac glycosides c tablets 62.5, 125, 250micrograms liquid 50micrograms/mL injection 500micrograms/2mL injection 100micrograms/1mL See Appendix 2 (paediatric)

Digoxin specific antibody H digibind injection 38mg

2.1.2 Phosphodiesterase inhibitors

H enoximone injection 100mg/20mL

Sympathomimetics (See section 2.7)

2.2 Diuretics

2.2.1 Thiazides and related diuretics c bendroflumethiazide tablets 2.5mg, 5mg (bendrofluazide) S metolazone1 tablets 5mg S chlorothiazide suspension 250mg/5mL See Appendix 2 and 6.1.4

Indapamide: This diuretic is the cause for major concern in primary care because of its relatively high cost and adverse effects. The cardiologists do however, have a valid case for it in a very small number of patients. It was agreed that indapamide will NOT be added to the Formulary but may be initiated by a cardiologist. In these cases, a clear indication should be stated on the DAL. Cardiff and Vale Only.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 16 2.2.2 Loop diuretics c furosemide2 tablets 20mg, 40mg, 500mg (frusemide) liquid 1mg/mL (SF) liquid 40mg/5mL (SF), See Appendix 2 50mg/5mL (SF) injection 20mg/2mL, 50mg/5mL, 250mg/25mL d bumetanide3 tablets 1mg, 5mg liquid 1mg/5mL (SF) injection 1mg/2mL, 2mg/4mL

Prescribing notes for loop diuretics 1 Metolazone is included as an adjunct to loop diuretics in severe CCF and is usually initiated in hospital. 2 is the first choice loop diuretic on account of relative cost. 3 Bumetanide may be of benefit to some patients who appear resistant to furosemide (frusemide). Bumetanide may be absorbed better than furosemide in patients with severe CCF, oedema or ascites where absorption may be a problem.

2.2.3 Potassium-sparing diuretics

Potassium supplements must not be given with these agents. c amiloride tablets 5mg liquid 5mg/5mL (SF)

Aldosterone antagonists d spironolactone1 tablets 25mg, 50mg, 100mg suspensions 10mg/5mL, 25mg/5mL, See 50mg/5mL (SF) Appendix 2 S eplerenone2 tablets 25mg

1 Spironolactone is only licensed for use in oedema and cirrhosis of the liver, malignant ascites, nephrotic syndrome, congestive heart failure and primary hyperaldosteronism. 2 Eplerenone is licensed for use as an adjunct in left ventricular dysfunction with heart failure following myocardial infarction. For future review by cardiologists.

2.2.4 Potassium-sparing diuretics with other diuretics

There is limited need for the use of combination diuretics. The majority of patients receiving low dose loop diuretics do not require an additional potassium-sparing diuretic. Most products are expensive. Where a combination is essential, generic co-amilofruse is the preferred choice. c co-amilofruse 2.5/20 tablets amiloride 2.5mg plus furosemide (frusemide) 20mg c co-amilofruse 5/40 tablets amiloride 5mg plus furosemide (frusemide) 40mg

2.2.5 Osmotic diuretics

H mannitol1 infusion 10%, 20%

1 Mannitol is generally reserved to treat cerebral oedema and raised intra-ocular pressure.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 17 2.3 Anti-Arrhythmic Drugs Please see The Management of Atrial Fibrillation: NICE CG36 June 2006

2.3.2 Drugs for arrhythmias

Supraventricular arrhythmias c digoxin (see section 2.1.1) S verapamil (see section 2.6.2) S diltiazem (see section 2.6.2) H adenosine injection 6mg/2mL

Supraventricular and ventricular arrhythmias S amiodarone1 tablets 100mg, 200mg injection 150mg/3mL S disopyramide2 capsules 100mg, 150mg injection 50mg/5mL S flecainide3 tablets 50mg, 100mg liquid 25mg/5mL injection 150mg/15mL S propafenone3 tablets 150mg

1 Amiodarone has a very long half-life (extending to several weeks). Following an oral loading dose (e.g. 200mg TDS for 1 week then BD for a further week) maintenance doses are given ONCE DAILY. The BNF recommends 6 monthly thyroid function tests and liver function tests. Amiodarone may cause: • Phototoxic skin reactions which may persist for at least 5 months after stopping. Advise patients to use total sunblock; • Pneumonitis and pulmonary fibrosis; • Corneal microdeposits; • Neurological symptoms such as tremor and tingling. These are often seen in the early stages of peripheral nerve damage. If amiodarone is not stopped at this time, permanent neuropathy may ensue; • Drug interactions with e.g. warfarin (approximately one third of the “normal” warfarin dose is required), and digoxin (approximately half of the “normal” digoxin dose required). Please refer to the current BNF for full information. A shared care protocol is in preparation. 2 Disopyramide is of limited value except in the treatment of vasovagal syncope. 3 Flecainide and propafenone are restricted to cardiologists only.

Ventricular arrhythmias H bretylium injection 500mg/10mL H lidocaine injection 100mg/5mL (lignocaine) infusion 0.4% in 500mL glucose 5% H phenytoin1 (see section 4.8.2)

1 Phenytoin may be of value in arrhythmias secondary to digoxin toxicity.

Other anti-arrhythmic drugs H magnesium sulphate injection 10g/20mL See Appendix 2

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 18 2.4 Beta-adrenoceptor Blocking Drugs

Supplies of non-formulary beta-blockers will be obtained for hospital in-patients previously stabilised on these drugs. c propranolol1 tablets 10mg, 40mg, 80mg, 160mg syrup 40mg/5mL m/r capsules 80mg, 160mg injection 1mg/1mL c atenolol tablets 25mg, 50mg, 100mg syrup 25mg/5mL (SF) injection 5mg/10mL c metoprolol tablets 50mg, 100mg m/r tablets 200mg (Betaloc SA) injection 5mg/5mL d bisoprolol2,3 tablets 1.25mg, 2.5mg, 5mg, 7.5mg, 10mg (Cardicor) d nebivolol4 tablets 5mg S labetalol5 tablets 100mg, 200mg, 400mg injection 100mg/20mL S carvedilol2 tablets 3.125mg, 6.25mg, 12.5mg, 25mg S sotalol6 tablets 40mg, 80mg, 160mg H esmolol injection 100mg/10mL infusion 2.5g/10mL

1 Propranolol may be useful for the management of conditions such as thyrotoxicosis, migraine and anxiety. The modified release capsules should be reserved for patients where a once daily preparation is essential for compliance. 2 and bisoprolol initiation and dose escalation for heart failure is restricted to consultants with special interest in cardiovascular therapeutics. 3 Bisoprolol was previously available as two proprietary preparations. Monocor has now been discontinued, reducing the risk of patient confusion. 4 Nebivolol: Following review in Oct 2006, nebivolol is included for second line use in patients who do not tolerate other beta blockers and as an adjunct in mild to moderate heart failure in patients over 70 years. 5 Labetalol is recommended for the treatment of hypertension in pregnancy 6 Sotalol CSM Advice. The use of sotalol should be limited to the treatment of ventricular arrhythmias or prophylaxis of supraventricular arrhythmias. It should no longer be used for angina, hypertension, thyrotoxicosis or for secondary prevention after myocardial infarction: when stopping sotalol for these indications the dose should be reduced gradually.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 19

2.5 Drugs Affecting the Renin-Angiotensin System and Some Other Antihypertensive Drugs

2.5.1 Vasodilator antihypertensive drugs

S hydralazine tablets 25mg, 50mg injection 20mg S minoxidil1 tablets 2.5mg, 5mg, 10mg H iloprost trometamol2 nebuliser solution 10 micrograms/mL H sodium nitroprusside for infusion 50mg/5mL

2.5.2 Centrally acting antihypertensive drugs d methyldopa3 tablets 125mg, 250mg suspension 250mg/5mL injection 250mg/5mL d moxonidine4 tablets 200micrograms, 400micrograms H clonidine5 injection 150micrograms/1mL

1 Minoxidil is restricted to specialist use in tertiary referral centres for cases of uncontrolled hypertension. 2 Iloprost AWMSG recommendation: Iloprost trometamol (Ventavis®) should be available for use within NHS Wales with the following restrictions: • It is used according to its licensed indications within NHS Wales for the treatment of patients with New York Heart Association Class III primary pulmonary hypertension as a second-line treatment when oral treatments are ineffective or not tolerated. • Iloprost trometamol (Ventavis®) should also be restricted for use only as an alternative in patients receiving other forms of prostacyclin treatment. • Iloprost trometamol (Ventavis®) should be initiated by specialists in centres treating pulmonary hypertension. 3 Methyldopa is used principally for the treatment of hypertension during pregnancy. Drowsiness may affect performance of skilled tasks e.g. driving. 4 Moxonidine may be useful in hypertension refractory to other agents. 5 Clonidine is restricted to specialist use in Intensive Therapy Units to support withdrawal from opioid analgesia.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 20 2.5.3 Adrenergic neurone blocking drugs

S guanethidine monosulphate1 injection 10mg/mL

1 Guanethidine is retained in the formulary solely for use in chronic pain.

2.5.4 Alpha-adrenoceptor blocking drugs

d doxazosin tablets 1mg, 2mg, 4mg m/r tablet 4mg, 8mg (Cardura XL)

Phaeochromocytoma H phenoxybenzamine1 capsules 10mg infusion 100mg/2mL H phentolamine injection 10mg/1mL

1 Phenoxybenzamine may cause contact sensitisation. Health workers should avoid contamination of the hands.

2.5.5 Drugs affecting the renin-angiotensin system

2.5.5.1 Angiotensin-converting enzyme inhibitors

c captopril1 tablets 12.5mg, 25mg, 50mg, 2mg See Appendix 2 c enalapril tablets 2.5mg, 5mg, 10mg, 20mg c lisinopril tablets 2.5mg, 5mg, 10mg, 20mg c perindopril tablets 2mg, 4mg c ramipril capsules 1.25mg, 2.5mg, 5mg c trandolapril capsules 500micrograms, 1mg, 2mg

1 It is recommended that captopril be used for initiation of treatment for heart failure. Close medical supervision is required. Commonly this may be more appropriately initiated in hospital. See BNF for criteria.

2.5.5.2 Angiotensin-II receptor antagonists

d irbesartan1 tablets 75mg, 150mg, 300mg d valsartan 1,2 capsules 40mg, 80mg, 160mg, tablets 40mg d/S candesartan3 Cardiff and Vale : Second line – (seek specialist advice) North Bro Taf: Specialist Initiated. See note 3

tablets 2mg, 4mg, 8mg, 16mg, 32mg

1 Irbesartan and valsartan are licensed for hypertension. They should be reserved for those patients whose hypertension can be controlled by ACE inhibitors, but who suffer from unacceptable side effects e.g. cough. They are much more expensive than ACE inhibitors 2 Valsartan is also licensed for use to improve survival following myocardial infarction in clinically stable patients with signs, symptoms or radiological evidence of left ventricular failure and/or with left ventricular systolic dysfunction. 3. Candesartan is included for treatment of patients with heart failure and impaired left ventricular systolic function as add-on therapy to ACE inhibitors or when ACE- inhibitors are not tolerated.

Losartan is no longer included in the formulary for initiation of therapy; however, it remains available for existing patients.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 21

2.6 Nitrates, Calcium Channel Blockers, and Potassium-Channel Activators

2.6.1 Nitrates c glyceryl trinitrate tablets 500micrograms S/L spray 400micrograms transdermal patches: 5mg/24hr, 10mg/24hr1 m/r buccal tablets 1mg, 2mg, 3mg, 5mg c isosorbide mononitrate tablets 10mg, 20mg2 m/r tablets 60mg3 H isosorbide dinitrate injection for dilution 500micrograms/mL, 1mg/mL H glyceryl trinitrate1 injection for dilution 5mg/mL : 5mL, 10mL amps Injection for dilution or syringe pump 1mg/1mL : 10mL amp, 50mL bottle

1. Glyceryl trinitrate Injection: Glass or polyethylene apparatus is preferable; loss of potency will occur if PVC is used.

Bro Taf Nitrate policy

1 GTN patches are expensive. If used, patients should be instructed to remove them for a minimum 8 hour period in any 24 hours to avoid nitrate tolerance. 2 Isosorbide mononitrate (generic, standard release) administered twice daily (second dose circa 2pm) is the preferred choice for maintenance therapy. 3 Modified release (once daily) preparations are expensive and no more effective than twice daily doses of standard release isosorbide mononitrate.

Suggested dose equivalents:- Imdur 30mg od/ElantanLA 25mg od ÖIsosorbide mononitrate 10mg bd (first dose 8am and second dose 2pm) Imdur 60mg od/Elantan 50mg od Ö Isosorbide mononitrate 20mg bd (first dose 8am and second dose 2pm)

2.6.2 Calcium-channel blockers

Unstable angina: Calcium channel blockers do not reduce the risk of myocardial infarction in unstable angina. The use of diltiazem or verapamil should be restricted to patients resistant to treatment with beta blockers.

Withdrawal: There is some evidence that sudden withdrawal of calcium channel blockers may be associated with an exacerbation of angina.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 22 Calcium Channel blockers c amlodipine tablets 5mg, 10mg c nifedipine1,2 capsules 5mg, 10mg m/r tablets 10mg, 20mg m/r tablets 20mg, 30mg, 60mg c diltiazem1 m/r tablets 60mg (generic) Twice a day preparations: (Tildiem Retard, Adizem SR, Angitil SR, Calcicard CR, Dilcardia SR, Dilzem SR) m/r tabs and caps 90mg, 120mg, 180mg Once a day preparations: (Tildiem LA, Adizem XL, Angitil XL, Dilzem XL, Slozem, Viazem XL, Zemtard XL) m/r capsules 180mg, 200mg, 240mg, 300mg d lercanidipine (Zanidip) tablets 10mg d verapamil tablets 40mg, 80mg, 120mg m/r tablets 120mg, 240mg (Securon SR, Univer, Verapress MR, Vertab SR) liquid 40mg/5mL H nimodipine3 tablets 30mg infusion 10mg/50mL

1 Modified release preparations of nifedipine and diltiazem: Please specify the brand name when prescribing a modified release preparation of nifedipine or diltiazem. This will avoid confusion between the numerous formulations with different doses and dose frequencies now available. If brands other than those routinely stocked in hospital are required, a supply may be obtained specifically for the particular patient. This should be discussed with the ward pharmacist. NB: This does not apply to nifedipine 5mg and 10mg capsules or diltiazem 60mg tablets, usually taken three times a day. Brands of these preparations are interchangeable within any group and so may be prescribed generically. 2 Nifedipine "once daily" preparations are recommended except where dose titration is required e.g. in hepatic disease and where certain GI disorders contraindicate use of once daily preparations. Capsules are included for acute and rapid management e.g. uncontrolled hypertension. 3 Nimodipine is used for the treatment of subarachnoid haemorrhage and the full course will generally be completed before discharge from hospital.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 23 2.6.3 Other antianginal drugs d nicorandil1 tablets 10mg, 20mg S ivabradine2 tablets 5mg, 7.5mg

1 Nicorandil: Patients being started on nicorandil should be warned not to drive or operate machinery until it is established that their performance is unimpaired. 2 Ivabradine: Available as a Specialist Initiated agent for third line use in patients intolerant of beta blockers and rate limiting calcium channel antagonists, or in whom they are otherwise contra-indicated.

2.6.4 Peripheral and cerebral vasodilators

2.6.4.1 Peripheral vasodilators and related drugs

H tolazoline1 injection 25mg/1mL See Appendix 2

1 Tolazoline is restricted to paediatrics only. No further drugs from this category have been included as there is insufficient evidence of clinical benefit to support their use.

2.7 Sympathomimetics

2.7.1 Inotropic sympathomimetics

H dobutamine1 strong sterile solution 250mg/5mL (Posiject) 250mg/20mL (Dobutrex) H dopamine sterile concentrate 200mg/5mL, 800mg/5mL 400mg/5mL See Appendix 2 H dopexamine2 strong sterile solution 10mg/1mL

1 In order to reduce the risk of dobutamine administration errors, only Dobutrex 250mg/20mL should be used on neonatal units. Posiject 250mg/5mL should be used on other wards. 2 Dopexamine is restricted to situations where preservation of splanchnic blood flow is essential in contrast to other inotropes. Specialist initiation required.

2.7.2 Vasoconstrictor sympathomimetics c adrenaline injection 1:1,000 (1mg/mL) (epinephrine) and 1:10,000 (1mg/10mL) S metaraminol injection 10mg/1mL S noradrenaline acid tartrate solution for infusion 8mg/4mL (= base 4mg/4mL) (norepinephrine bitartrate) injection 400micrograms/2mL (= base 200micrograms/4mL) S phenylephrine injection 10mg/1mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 24 2.7.3 Cardiopulmonary resuscitation

The Hospital Pharmacy Departments supply pre-packed Emergency Boxes for use in Cardiac Arrest, General Medical Emergencies and Paediatric Emergencies. Due to variations in local arrangements, we are currently unable to publish information which is valid across the locality. Please contact your local hospital pharmacy department for details of the emergency boxes available. c adrenaline Please refer to the BNF section 3.4.3 for the (epinephrine) use of adrenaline in anaphylaxis

2.8 Anticoagulants and Protamine

Anticoagulation regimens for heparin and/or oral anticoagulants should be prescribed on the ANTICOAGULATION PRESCRIPTION CHART. This also provides guidance on monitoring and dosage adjustment.

2.8.1 Parenteral anticoagulants

Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. See NICE CG46 April 2007.

Note Please refer to local policies

Heparin THROMBOCYTOPENIA. Clinically important thrombocytopenia is immune-mediated, and does not usually develop until after 6 to 10 days; it may be complicated by thrombosis. Platelet counts are recommended for patients receiving heparin (including low molecular weight heparins) for longer than 5 days (heparin should be stopped immediately in those who develop thrombocytopenia). Patients requiring continued anticoagulation should preferably be given lepirudin or a heparinoid such as danaparoid.

HYPERKALAEMIA. Inhibition of aldosterone secretion by heparin (including low molecular weight heparins) may result in hyperkalaemia; patients with diabetes mellitus, chronic renal failure, acidosis, raised plasma potassium or those taking potassium- sparing drugs seen to be more susceptible. The risk appears to increase with duration of therapy and the CSM has recommended that plasma potassium should be measured in patients at risk before starting heparin and monitored regularly thereafter, particularly if heparin is to be continued for more than 7 days.

H heparin sodium prefilled syringes 5000unit/0.2mL ampoules 5000unit/5mL, 25,000unit/5mL, 20,000unit/20mL H heparin calcium prefilled syringes 5000unit/0.2mL, 12,500unit/0.5mL, 20,000unit/0.8mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 25 Low Molecular Weight Heparins

Low molecular weight heparins may now be prescribed on a specialist initiated basis. In Cardiff and the Vale this is strictly for Velindre Hospital cancer patients who have finished their chemotherapy and are being treated with LMW heparins at home.

S tinzaparin injection 5000unit/0.5mL syringe 3500unit/0.35mL S enoxaparin syringe 20mg/0.2mL, 40mg/0.4mL, 60mg/0.6mL, 80mg/0.8mL, 100mg/1mL, 150mg/1mL S dalteparin syringe 2500 unit/0.2mL, 5000unit/0.2mL, 10,000unit/0.4mL, 12,500unit/0.5mL, 15,000unit/0.6mL, 18,000unit/0.72mL injection 10,000 unit/4mL, 10,000unit/1mL, 100,000/4mL

Heparin Flushes Heparin flushes should be reserved for maintaining patency of central and long lines only. For peripheral venous catheters, sodium chloride 0.9% is as effective as a heparin flush.

S heparin sodium 50unit/5mL (Hepsal)

Epoprostenol H epoprostenol for infusion 500micrograms

2.8.2 Oral anticoagulants c warfarin1 tablets 1mg, 3mg, 5mg d phenindione tablets 10mg, 25mg, 50mg

2.8.3 Protamine sulphate

H protamine sulphate injection 50mg/5mL

2.9 Antiplatelet Drugs c aspirin soluble tablets 75mg, 300mg (acetylsalicylic acid) d dipyridamole1,2 tablets 25mg, 100mg m/r capsules 200mg (Persantin Retard) injection 10mg/2mL d aspirin and dipyridamole m/r capsules 25mg/200mg(Asasantin Retard) d clopidogrel2 tablets 75mg H abciximab injection 10mg/5mL H eptifibatide3 injection 2mg/mL infusion 750micrograms/mL H tirofiban3 infusion concentrate 250 micrograms/mL (requires dilution) Please see notes overleaf

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 26 Prescribing notes for antiplatelet drugs 1 Dipyridamole 25mg and 100mg tablets are ONLY licensed as an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. Modified release dipyridamole (Persantin Retard) is licensed for the secondary prevention of ischaemic stroke or transient ischaemic attacks, with or without aspirin. 2 Clopidogrel. Please note the following guidance:

a. NICE Technology Appraisal No 80 July 04 on acute coronary syndromes. Use in combination with low-dose aspirin, is recommended for use in the management of non-ST-segment elevation acute coronary syndrome (ACS) in people who are at moderate to high risk of myocardial infarction (MI) or death. NICE recommends treatment for 12 months, though local practice recommended by the Welsh Cardiac Society is to stop after 9 months for ACS.

After insertion of a bare metal coronary stent use clopidogrel 75 mg for 1 month in combination with aspirin 300mg for 1 month then reduce aspirin dose to 75mg daily. Where the patient has ACS continue as above.

For patients fitted with a drug-eluting stent continue clopidogrel for 9 months. (Some centres use 12 months following anecdotal reports of in-stent thrombosis when clopidogrel is stopped at 9 months. Thrombocytopenia is a rare but serious side effect. When it does occur, it generally appears in the early weeks of treatment. . Clopidogrel use as an anti-platelet agent is restricted to cases of true aspirin intolerance. Use with caution in patients with a history of GI bleeds. b. NICE Technology Appraisal No 90 May 2005: Clopidogrel and modified-release dipyridamole in the prevention of occlusive vascular events. This guidance applies to people who have had an occlusive vascular event (OVE), or who have symptomatic peripheral arterial disease (PAD). This guidance does not apply to people who have had, or are at risk of, a stroke associated with atrial fibrillation, or who require treatment to prevent occlusive events after coronary revascularisation or carotid artery procedures. 1.1 As part of the prevention of occlusive vascular events: 1.1.1 the combination of modified-release (MR) dipyridamole and aspirin is recommended for people who have had an ischaemic stroke or a transient ischaemic attack (TIA) for a period of 2 years from the most recent event. Thereafter, or if MR dipyridamole is not tolerated, preventative therapy should revert to standard care (including long-term treatment with low-dose aspirin) 1.1.2 Clopidogrel alone (within its licensed indications) is recommended for people who are intolerant of low-dose aspirin and either have experienced an occlusive vascular event or have symptomatic peripheral arterial disease. 1.2 For the purposes of this guidance, aspirin intolerance is defined as either of the following: • proven hypersensitivity to aspirin-containing medicines • history of severe dyspepsia induced by lowdose aspirin. Please see full guidance: www.nice.org.uk

3 Glycoprotein IIb/IIIa inhibitors and their role in the treatment of acute coronary syndromes is the subject of revised NICE guidance (No 47) produced September 2002. Please see full guidance: www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 27 2.10 Myocardial Infarction and Fibrinolysis

Please also see NICE Guideline A (April 2001) on prophylaxis for patients who have experienced a myocardial infarction.

2.10.2 Fibrinolytic Drugs

Note Please refer to local policies and NICE TA52 The clinical effectiveness and cost effectiveness of drugs for early thrombolysis in the treatment of acute myocardial infarction. (October 2002)

H streptokinase injection 250,000unit, 1.5million-unit H alteplase1 (rt-PA) injection 20mg, 50mg H urokinase injection 25,000unit, 100,000unit H tenecteplase injection 40mg, 50mg

1. Alteplase: See NICE TA122 Alteplase for the treatment of acute ischaemic stroke June 2007. Alteplase is recommended for the treatment of acute ischaemic stroke when used by physicians trained and experienced in the management of acute stroke. It should only be administered in centres with facilities that enable it to be used in full accordance with its marketing authority.

2.11 Antifibrinolytic Drugs and Haemostatics c tranexamic acid1 tablets 500mg syrup 500mg/5mL injection 500mg/5mL H etamsylate1 tablets 500mg (ethamsylate) injection 250mg/2mL injection (paediatric) See 20mg/1mL Appendix 2

1. Tranexamic acid: Heavy menstrual bleeding. See NICE CG44 Jan 2007. Danazol and etamsylate remain in the formulary for uses other than heavy menstrual bleeding.

Aprotinin has been removed from the formulary in response to the CMO Letter November 2007 reporting that marketing and licences for aprotinin have been suspended. This follows termination of a suggesting that aprotinin may be associated with an increased risk of death compared with tranexamic acid and aminocaproic acid. For further information please visit Aprotinin MHRA Advice Nov 07

Blood Products

H drotrecogin alfa (Xigris)1 powder for solution for infusion 5mg, 20mg

1 Drotrecogin alfa (activated) is recommended for use in adult patients (NICE Technology Appraisal No 84 Sept 02) who have severe sepsis that has resulted in multiple organ failure (that is, two or more major organs have failed) and who are being provided with optimum intensive care support. The use of drotrecogin alfa (activated) should only be initiated and supervised by a specialist consultant with intensive care skills and experience in the care of patients with sepsis.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 28 2.12 Lipid-Regulating Drugs

Anion exchange resins No anion exchange resins have been included in this section because of their unpalatable nature, poor adverse effect profile and their wide potential for drug interactions. For use in diarrhoea please see section 1.5.

Muscle effects The CSM has advised that rhabdomyolysis associated with lipid-regulating drugs such as the fibrates and statins appears to be rare (approx. 1 case in every 100,000 treatment years) but may be increased in those with renal impairment and possibly in those with hypothyroidism. Concomitant treatment with ciclosporin (cyclosporin) may increase plasma-statin concentrations and the risk of muscle toxicity; concomitant treatment with a fibrate and a statin may also be associated with an increased risk of serious muscle toxicity. Advise patients to report promptly unexplained muscle pain, tenderness or weakness.

Statins c simvastatin1 tablets 10mg, 20mg, 40mg, 80mg c pravastatin1 tablets 10mg, 20mg, 40mg d atorvastatin tablets 10mg, 20mg, 40mg S rosuvastatin (Crestor)2 tablets 10mg, 20mg, 40mg

1. The beneficial effect of cholesterol lowering by statins may be a class effect. However, all the available evidence for reduction in mortality relates only to simvastatin and pravastatin. Pravastatin or simvastatin should be used as 1st line drugs in the treatment of hyperlipidaemia. 2. Rosuvastatin is approved for specialist initiation on a temporary basis until further guidance is available. The starting dose should not exceed 10mg for any patient. The 40mg dose is contraindicated in patients with predisposing risk factors for rhabdomyolysis. Increased systemic exposure has been seen in Asian subjects. This should be considered when making dose decisions for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients. Specialist supervision is advised when the 40mg dose is initiated in any patient.

NICE Technology Appraisal No 94 January 2006 - Statins for the prevention of cardiovascular events. This guidance relates only to the initiation of statin therapy in adults with clinical evidence of cardiovascular disease (CVD) and in adults considered to be at risk of CVD. It assumes that other strategies for managing CVD risk are being appropriately considered when initiating statin therapy. The guidance does not include specific advice for genetic dyslipidaemias (for example, familial hypercholesterolaemia). The guidance relates only to the use of statins within their licensed indications. A clinical guideline on cardiovascular risk assessment is currently in development (expected date of publication: September 2007). This guidance should be read in the context of the clinical guideline when it is available. 1.1 Statin therapy is recommended for adults with clinical evidence of CVD. 1.2 Statin therapy is recommended as part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater 10-year risk of developing CVD. This level of CVD risk should be estimated using an appropriate risk calculator, or by clinical assessment for people for whom an appropriate risk calculator is not available (for example, older people, people with diabetes or people in high-risk ethnic groups). 1.3 Within the recommendations outlined in Section 1.1 and Section 1.2, the decision whether to initiate statin therapy should be made after an informed discussion between the responsible clinician and the individual about the risks and benefits of statin treatment, and taking into account additional factors such as comorbidities and life expectancy.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 29 1.4 When the decision has been made to prescribe a statin, it is recommended that therapy should usually be initiated with a drug with a low acquisition cost (taking into account required daily dose and product price per dose). Please see full guidance: www.nice.org.uk

Ezetimibe S ezetimibe (Ezetrol)1 tablets 10mg

1. Ezetimibe is for 3rd line use in accordance with a care pathway.

Fibrates d bezafibrate1 tablets 200mg m/r tablets 400mg (Bezalip Mono) d fenofibrate micronised capsules 67mg, 200mg, 267mg m/r tablets 160mg d ciprofibrate tablets 100mg

1 Bezafibrate may cause myotoxicity: Special care is needed in patients with renal disease as progressive increases in serum creatinine concentration or failure to follow dosage guidelines may result in myotoxicity (rhabdomyolysis).

Nicotinic Acid S nicotinic Acid1 (Niaspan) Prolonged release tablets 500mg, 750mg, 1000mg

1 Nicotinic acid: Doses of standard release and modified release formulations are not equivalent. When switching formulations, initiate treatments with low dose and increase gradually as recommended.

Fish Oils c omega-3-acid ethyl esters Capsules 1g containing 840 mg (Omacor) eicosapentaenoic acid (EPA) ethyl ester 46% and docosahexaenoic acid (DHA) ethyl ester 38%.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 30 CHAPTER 3 RESPIRATORY SYSTEM

Choice of inhaler devices for children with chronic asthma

For children under the age of 5 years with chronic stable asthma, NICE Guidance (No 10 August 2000) recommends • Both corticosteroids and bronchodilator therapy should be routinely delivered by pressurized metered dose inhaler (pMDI) and spacer system, with a facemask where necessary.

• Where this combination is not clinically effective for the child and depending on the child’s condition, nebulised therapy may be considered and in the case of children aged 3-5 years, a dry powder inhaler (DPI) may also be considered.

• Choice of device to be made within the pMDI and spacer range should be primarily governed by specific individual need and the likelihood of good compliance. Once these factors have been taken into account, choice should be made on the basis of cost minimisation.

For older children aged 5-15 years, NICE Guidance (No 38 March 2002) recommends • the choice of device should take into account the ability to maintain an effective technique, suitability for the child and carers lifestyles and willingness to use a particular device.

• A pMDI and suitable spacer device is recommended as the first-line choice for the delivery of inhaled corticosteroids. Where adherence to the pMDI and spacer combination is likely to be poor, other alternative devices should be considered, bearing in mind the need to minimise the risks of systemic absorption of corticosteroids.

• In the case of other inhaled drugs such as bronchodilators, a wider range of devices may be considered to take account of their more frequent spontaneous use and the greater need for portability. Where more than one device satisfies these considerations, it is recommended that the device with the lowest overall cost (taking into account daily required dose and product price per dose) should be chosen.

The following table summarises suitable options for inhalation devices for adults and children.

Drug Type Patient Group Device Corticosteroids Adults and Children Standard MDI via spacer (with mask for very young children) Bronchodilators Child under 5 years as above Child 5 or above Breath-actuated MDI1 Dry powder device2 Child with poor co-ordination MDI via spacer Older children and adults Standard MDI - If unable to use a MDI consider: • standard MDI + spacer • Breath-actuated MDI1 • Dry Powder Device2 1 Breath-actuated MDIs include the Easi-Breathe and Autohaler. 2 Dry powder devices include Turbohalers, Accuhalers & Easyhalers. diskhalers will not be commercially available after September 2006. Choice of inhaler device should be based on patient response and not on quoted required inspiratory flow rates for each device which are largely similar and not of great relevance in well controlled asthma.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 31 3.1 Bronchodilators

3.1.1.1 Adrenoceptor stimulants c salbutamol1,2 oral solution/syrup (SF) 2mg/5mL injection 100micrograms/mL (50mL) injection 500micrograms/mL (1mL) solution for infusion 1mg/mL breath-actuated inhaler 100micrograms/dose CFC free inhaler 100micrograms/dose dry powder for inhalation: Accuhaler 200micrograms/blister Easyhaler Salbutamol 100 micrograms/dose, 200micrograms/dose nebuliser solution 2.5mg/2.5mL nebuliser solution 5mg/2.5mL d terbutaline2 injection 500micrograms/mL (1mL, 5mL) aerosol inhalation 250micrograms/dose Turbohaler 500micrograms/dose nebuliser solution 2.5mg/mL (2mL) d formoterol Turbohaler (eformoterol) 6micrograms,12micrograms/dose c salmeterol Evohaler 25micrograms/dose Accuhaler 50micrograms/dose

1 Salbutamol diskhalers and inhalation capsules will be available for existing patients only. 2 Beta2-adrenoceptor stimulant tablets should be reserved for existing patients.

3.1.2 Antimuscarinic bronchodilators c ipratropium bromide1 aerosol inhalation 20micrograms, 40micrograms/dose breath-actuated inhaler 20micrograms/dose nebuliser solution 250micrograms/mL (1mL, 2mL) d tiotropium2 (Spiriva) Inhalational powder hard capsule 18micrograms (use with HandiHaler device)

1. Ipratropium inhalation capsules will be available for existing patients only. Acute angle-closure glaucoma has been reported in patients given nebulised ipratropium particularly when used in association with nebulised salbutamol. Patients’ eyes may be protected by nebulising ipratropium using a mouthpiece rather than a mask or by ensuring that facemasks fit well and are properly positioned. 2. Tiotropium – patients should be warned not to swallow the capsules but to inhale the contents using the HandiHaler device provided. Use tiotropium in accordance with NICE Clinical Guidance CG 12 March 04. Please see full guidance. www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 32 3.1.3 Theophylline c theophylline1,2,3,4 Slo-Phyllin capsules 60mg, 125mg, 250mg Uniphyllin Continus 200mg, 300mg, 400mg d aminophylline1,2,3 Phyllocontin tablets MR 100mg, 225mg, 350mg injection 25mg/mL (10mL)

1 Patients should remain on the same brand of oral theophylline/aminophylline which should be a prescribed by brand name. 2 Brands other than those listed above will be obtained for individual patients. 3 New patients should be started on the brands listed above. 4 Slo-phyllin capsules may be opened and the contents sprinkled onto soft food prior to administration.

3.1.5 Peak flow meters, inhaler devices and nebulisers

Nebuliser Therapy • For the majority of patients home nebulisers offer no advantage over spacer devices. • Before prescribing nebulisers the patient's existing therapy should be optimised. • Nebuliser therapy should be initiated subject to a formal assessment by a specialist for objective or subjective benefit. • Nebulisers should be serviced at least once on an annual basis with usage and benefit being reviewed by a specialist at the same time. c Peak flow meters standard low range c Inhaler devices Babyhaler1,2 Haleraid1 Nebuhaler3 Volumatic4 Paediatric Volumatic2 Aerochamber4

1 Babyhaler and Haleraid are not available on community NHS prescriptions. 2 Babyhaler for use with Ventolin (salbutamol) 3 Nebuhaler devices are compatible with Bricanyl (terbutaline) and Pulmicort (budesonide) inhalers. 4 Volumatic devices:-

Volumatics were discontinued for a short period and were replaced by Aerochambers. Following concerns raised by the CSM regarding possible changes in drug delivery, GSK has reintroduced the Volumatic device. National product information for the GSK / Allen & Hanburys metered dose inhaler product range now states that only the Volumatic spacer device should be used with GSK products.

Advice for Prescribers The Commission on Human Medicines advises the following, in relation to patients using spacer devices with GSK pressurised metered dose inhalers:

If you are prescribing any spacer device to a patient for the first time, these patients should be monitored frequently in the normal way for the emergence of or worsening of symptoms of disease or adverse effects. Any patients who are switched to a different device should be regarded in the same way as new patients, and the same careful monitoring is required.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 33 • Patients who require a spacer device for the first time with Allen & Hanbury inhalers, from 3 January 2006 should be prescribed a Volumatic spacer device (making best use of the limited interim stocks). New patients should only be dispensed an AeroChamber Plus spacer device if interim stocks of the Volumatic are insufficient or not available.

• Patients who are currently using a Volumatic spacer device should retain the device, and continue to use it in accordance with the manufacturer’s instructions. These devices can be replaced with newly manufactured stock from mid-February 2006, as necessary.

• Patients who have switched to the AeroChamber Plus spacer device have no urgent need to switch back to the Volumatic unless they are experiencing difficulties with the device or their asthma control or the emergence of adverse effects gives cause for concern, therefore: o Patients should continue to use the AeroChamber Plus until the new Volumatic becomes available (mid February 2006). o These patients should be monitored for the emergence of or worsening of symptoms of disease or adverse effects both before and after switching back to the Volumatic. o Priority for switching back to the Volumatic from February 2006 should be given to children and those taking high dose corticosteroids and long- acting ß2 agonists. o Patients taking short-acting bronchodilators only (as required) are a low priority for switching back.

For inhaled ß2 agonist bronchodilators the most frequent signs of toxicity are headache, tremor and palpitations; for inhaled corticosteroids the most serious concern from over exposure is adrenal suppression particularly with high doses administered to children and adolescents.

A questions and answers document will be placed on the website of the Medicines and Healthcare products Regulatory Agency www.mhra.gsi.gov.uk.. For further information please call 020 7084 0000.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 34 3.2 Corticosteroids

CSM Advice on inhaled corticosteroids and adrenal suppression in children was published in October 2002. The CSM advise that adrenal suppression may be under- recognised particularly in children receiving higher than licensed doses of inhaled corticosteroids. Adrenal suppression is a dose-related class effect of all inhaled corticosteroids. Adrenal crisis has been observed more frequently following the use of , possibly because higher than licensed doses of fluticasone are prescribed more widely in children than other inhaled corticosteroids. All inhaled corticosteroids are associated with an increased risk of adrenal crisis when used at higher than licensed doses but prescribers are reminded that fluticasone should normally be used at half the dose of beclomethasone or budesonide because of its greater potency.

These are dose related class effects, and it is strongly advised that the paediatric licensed dosages of all inhaled corticosteroids should not be exceeded.

Prescribers are also reminded that: • it is important to review therapy regularly and titrate down to the lowest dose at which effective control of asthma is maintained. • if a doctor considers that a child’s asthma is not controlled on the maximum licensed dose of their inhaled corticosteroid, despite the addition of other therapies, the child should be referred to a specialist in the management of paediatric asthma.

CFC-FREE INHALERS. Chlorofluorocarbon (CFC) propellants in pressurised aerosol inhalers are being replaced by hydrofluoroalkane (HFA) propellants. Patients receiving CFC-free inhalers should be reassured about the efficacy of the new inhalers and counselled that the aerosol may feel and taste different; any difficulty with the new inhaler should be discussed with the doctor or pharmacist. Healthcare professionals will need to make sure that patients on Becotide or Becloforte inhalers are transferred to an alternative device that suits the patient. This may require adjustment to the dose. Patients who are switched to a different device or medicine should be monitored frequently in the nomal way for the emergence or worsening of symptoms

CSM advice. The CSM has requested doctors to report any adverse reaction to the new HFA-containing inhalers and to include the brand name of the inhaler on the yellow card. The MHRA has advised (August 2006) that CFC-free diproprionate inhalers should be prescribed by brand name as they are not interchangeable.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 35 c beclometasone dipropionate1,2 aerosol inhalation 50, 100, 200, (beclomethasone) 250micrograms/dose (Clenil Modulite or Qvar) breath-actuated 50, 100, 250micrograms/dose (Qvar) dry powder for inhalation: Easyhaler Beclomethasone 100 micrograms/dose, 200 micrograms/dose c budesonide1 aerosol inhalation 50, 200micrograms/dose Turbohaler 100, 200, 400micrograms/dose dry powder for inhalation: Easyhaler Budesonide 100 micrograms/dose, 200 micrograms/dose 400 micrograms/dose S budesonide nebuliser solution 500 micrograms/mL (2mL), 250 micrograms/mL (2mL) d fluticasone propionate1,3 aerosol inhaler 25, 50, 125, 250micrograms/dose Accuhaler 50,100, 250, 500micrograms/dose S fluticasone proprionate4 nebuliser solution 250micrograms/mL(2mL), 1mg/mL(2mL)

Compound preparations d Seretide5 Accuhaler 100, 250, 500 (fluticasone 100, 250, 500 micrograms/blister + salmeterol 50micrograms/blister) Evohaler 50, 125, 250 (fluticasone 50, 125, 250micrograms/dose + salmeterol 25micrograms/dose) d Symbicort5 Turbohaler 100/6, 200/6 (budesonide 80,160 micrograms + formoterol 4.5 micrograms/dose)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 36

1 Beclometasone 250micrograms inhalers should be used in adults only. Higher doses of all inhaled steroids can cause growth retardation in children (e.g.>200micrograms beclometasone, >600micrograms budesonide and >200micrograms fluticasone per day). Growth must be monitored six-monthly. Always use the lowest effective dose and encourage mouth rinsing after administration. Please note the major difference in dose between the available CFC-free BDP inhalers due to the different technology used in each. The Clenil Modulite brand is dose- equivalent to CFC-containing BDP inhalers, whereas the Qvar brand is effectively about twice the potency and thus requires half the inhaled dose. As a result, these products should always be prescribed by brand name and pharmacists will query any prescription for a CFC-free BDP metered-dose inhaler that does not include a brand name.

2 Beclometasone diskhalers and rotacaps will be available for existing patients only. 3 Fluticasone diskhalers will be available for existing patients only. 4 Fluticasone nebules are reserved for initiation by respiratory consultants. 5 Seretide & Symbicort: A long-acting beta 2 agonist such as salmeterol or formoterol may be added, as a separate inhaler, to the regimen of patients poorly controlled on an inhaled corticosteroid. Seretide or Symbicort are options if there is an improvement in asthma control. Please refer to the British Thoracic Society Guidelines for asthma, published February 2003 for the place of these products in therapy of asthma. Note: 1 puff of Symbicort 100/6 = 1 puff of a Pulmicort 100-microgram Turbohaler + 1 puff of an Oxis (formoterol 6-microgram) Turbohaler

1 puff of Symbicort 200/6 = 1 puff of a Pulmicort 200-microgram Turbohaler + 1 puff of an Oxis (formoterol 6-microgram) Turbohaler Seretide Dose equivalents:

I puff of a Seretide 100 Accuhaler = 1 puff of a Flixotide (fluticasone) 100microgram Accuhaler + 1 puff of Serevent (salmeterol) 50 microgram Accuhaler. I puff of a Seretide 250 Accuhaler = 1 puff of a Flixotide (fluticasone) 250 microgram Accuhaler + 1 puff of Serevent (salmeterol) 50 microgram Accuhaler.

I puff of a Seretide 500 Accuhaler = 1 puff of a Flixotide (fluticasone) 500 microgram Accuhaler + 1 puff of Serevent (salmeterol) 50 microgram Accuhaler.

Seretide 250 and 500 Accuhalers are not licensed for children under 12 years. The recommended dose for either preparation is ONE blister twice a day.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 37

3.3 Cromoglicate, Related Therapy and Leukotriene Receptor Antagonists

3.3.1 Cromoglicate and related therapy c sodium cromoglicate aerosol inhalation 5mg/dose breath-actuated inhaler 5mg/dose

3.3.2 Leukotriene receptor antagonists

S montelukast1,2 tablets 10mg chewable tablets 5mg

1 Montelukast is now licensed for children from the age of 2 years and has been incorporated into the new BTS guidelines at steps 3-4. It may be useful in exercise-induced asthma and aspirin-sensitive patients. Please refer to BTS guidelines (Feb. 2003) for full detail. 2 A two-week trial should be carried out. It should be discontinued if there is no objective improvement after this period.

3.4 Antihistamines, Hyposensitisation, and Allergic Emergencies

3.4.1 Antihistamines

Sedating Antihistamines c chlorphenamine maleate tablets 4mg (chlorpheniramine maleate) syrup 2mg/5mL injection 10mg/mL c alimemazine tartrate tablets 10mg (trimeprazine tartrate) syrup 7.5mg/5mL, 30mg/5mL c promethazine hydrochloride tablets 10mg, 25mg elixir 5mg/5mL d brompheniramine maleate1 elixir 2mg/5mL d hydroxyzine hydrochloride2 tablets 10mg, 25mg H promethazine hydrochloride3 injection 25mg/mL

1 Brompheniramine is the only antihistamine licensed for use in children under one year. It should be reserved for use in these patients only. 2 Hydroxyzine is reserved for the treatment of pruritus only. 3 Promethazine injection is reserved for use in Obstetrics and Gynaecology.

Non-sedating antihistamines c cetirizine hydrochloride tablets 10mg oral solution 5mg/5mL (SF) c loratadine tablets 10mg syrup 5mg/5mL c fexofenadine tablets 120mg, 180mg

3.4.3 Allergic emergencies c adrenaline injection 1 in 1000 (0.5mL,1mL) (epinephrine) injection (Min-I-Jet) 1 in 1000 (1mL) auto injector (EpiPen) 0.15mg, 0.3mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 38 3.5 Respiratory Stimulants and Pulmonary Surfactants

3.5.1 Respiratory stimulants

H doxapram hydrochloride1 intravenous infusion 2mg/mL in glucose 5% (500mL) injection 20mg/mL H caffeine citrate2 injection 10mg/mL See Appendix 2 oral solution 10mg/mL See Appendix 2

1 Doxapram injection is for use by Anaesthetists only. 2 Caffeine citrate is for use in Special Care Baby Units only.

3.5.2 Pulmonary surfactants

The choice of surfactant for use in Neonatal Intensive Care should be determined by the Consultant Neonatologist according to local protocol.

H beractant suspension 25mg/mL 8mL vial (Survanta) H colfosceril palmitate suspension for reconstitution 108mg (giving 67.5mg/5mL once reconstituted) (Exosurf Neonatal) H poractant alfa suspension 80mg/mL (1.5mL vial) (Curosurf)

3.5.3 Nitric Oxide

H nitric oxide 1

3.6 OXYGEN

S oxygen cylinders, concentrators refer to Drug Tariff and BNF for full prescribing information

3.7 Mucolytics c carbocisteine1 (Mucodyne) capsules 375mg S acetylcysteine2 sachets 200mg H dornase alfa3 nebuliser solution 1000units(1mg)/mL (2.5mL)

1 Carbocisteine as Mucodyne is included for the adjunctive therapy of respiratory tract disorders. No longer restricted to use in COPD. 2 Acetylcysteine is reserved for cystic fibrosis patients. 3 Dornase alfa should be used only in patients reviewed at UHW/Llandough according to the agreed protocol.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 39 3.8 Aromatic Inhalations d Benzoin Tincture, Compound, BP1

1 Benzoin Tincture Compound BP has no known benefit over steam as an inhalation. It is included as a healing, haemostatic and antiseptic agent for use in chiropody.

3.9 Cough Preparations

3.9.1 Cough suppressants c pholcodine linctus 5mg/5mL d codeine phosphate linctus 15mg/5mL

3.9.2 Expectorant and demulcent cough preparations c Simple linctus, BP linctus c Simple linctus, Paediatric BP linctus

Palliative Care S methadone hydrochloride1 linctus 2mg/5mL

1 Methadone linctus is reserved for prescribing in Palliative Care as it has a long duration of action and tends to accumulate. See Shared Care protocol No 19

3.10 Systemic Nasal Decongestants c pseudoephedrine hydrochloride tablets 60mg elixir 30mg/5mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 40 CHAPTER 4 CENTRAL NERVOUS SYSTEM

4.1 Hypnotics and Anxiolytics

4.1.1 Hypnotics

Before prescribing a hypnotic agent, the causes of the insomnia should be investigated and treated. These include psychiatric conditions such as anxiety or depression, other physical illnesses, dependence on medication or even over-consumption of alcohol. Intermittent use of a short-acting hypnotic may be helpful but the duration of treatment should generally be limited to one week where possible. Hypnotics should be avoided in the elderly, who are at risk of becoming ataxic or confused, and so liable to fall and injure themselves. Drugs initiated for insomnia in hospital should not normally be continued on discharge.

CSM advice on benzodiazepines • Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness. • The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate and unsuitable. • Benzodiazepines should be used to treat insomnia only when it is severe, disabling or subjecting the individual to extreme distress. c temazepam1 tablets 10mg, 20mg liquid 10mg/5mL c lormetazepam1 tablets 500micrograms, 1mg c nitrazepam2 tablets 5mg liquid 2.5mg/5mL S zopiclone3,6 tablets 3.75mg, 7.5mg S chloral hydrate4 liquid 1g/10mL paediatric liquid 200mg/5mL suppositories 25mg, 50mg, 100mg, 250mg, 500mg, 750mg S triclofos sodium5 liquid 500mg/5mL S clomethiazole4 (chlormethiazole) capsules 192mg liquid 250mg/5mL S zopiclone6 tablets 3.75mg, 7.5mg

Please see notes overleaf

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 41

1 Temazepam and lormetazepam are short-acting benzodiazepines. 2 Nitrazepam is included for the treatment of existing patients only. In new patients for whom a benzodiazepine is necessary, a short-acting agent should be selected. 3 Zopiclone is licensed for short-term use in insomnia. Continuation of the drug after discharge from hospital is not recommended. Treatment should be in line with CSM guidelines for insomnia and limited to 28 days. Zopiclone should be specialist initiated and used as a second line agent. 4 Chloral hydrate and clomethiazole (chlormethiazole) should only be used for insomnia after the failure of other agents. 5 Triclofos sodium is included for sedation prior to procedures in children only. 6 Zopiclone (and other “Z” drugs) for the short-term management of insomnia (NICE Technology Appraisal No 77, Apr 04.) When, after due consideration of the use of non-pharmacological measures, hypnotic drug therapy is considered appropriate for the management of severe insomnia interfering with normal daily life, it is recommended that hypnotics should be prescribed for short periods of time only, in strict accordance with their licensed indications. • It is recommended that, because of the lack of compelling evidence to distinguish between zaleplon, zolpidem, zopiclone or the shorter acting benzodiazepine hypnotics, the drug with the lowest purchase cost (taking into account daily required dose and product price per dose) should be prescribed. • It is recommended that switching from one of these hypnotics to another should only occur if a patient experiences adverse effects considered to be directly related to a specific agent. These are the only circumstances in which the drugs with the higher acquisition costs are recommended. • Patients who have not responded to one of these hypnotic drugs should not be prescribed any of the others.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 42 4.1.2 Anxiolytics

Please see NICE Clinical Guideline 22 (December 2004) on management of anxiety in adults in primary, secondary and community care. www.nice.org.uk. This guidance contains the following key messages:

Anxiety disorders are - Common - Chronic - The cause of considerable stress and disablilty - Often unrecognised and untreated If left untreated they are costly to both the individual and to society. A range of effective interventions is available to treat anxiety disorders, including medication, psychological therapies and self-help. Individuals do get better and remain better Involving individuals in an effective partnership with healthcare professionals, with all decision-making being shared, improves outcomes. Access to information, including support groups, is a valuable part of any package of care.

Benzodiazepines Benzodiazepines are licensed for the short-term relief of severe anxiety, but long-term use should be avoided. In general, agents with a sustained action such as diazepam are appropriate. Shorter acting agents such as lorazepam may be preferred in patients with hepatic impairment but they carry a greater risk of withdrawal symptoms. c diazepam tablets 2mg, 5mg, 10mg liquid 2mg/5mL, 5mg/5mL injection 5mg/mL injection (emulsion) 5mg/mL (Diazemuls) rectal tubes 2.5mg, 5mg, 10mg suppositories 10mg S lorazepam tablets 1mg, 2.5mg injection 4mg/1mL S oxazepam1 tablets 10mg, 15mg S chlordiazepoxide2 capsules 5mg, 10mg

1 Oxazepam is restricted to second line use in alcohol withdrawal and in patients with liver disease, see 4.10. 2 Chlordiazepoxide is restricted to use in alcohol withdrawal, see 4.10.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 43 4.2 Drugs Used in Psychoses and Related Disorders

The National Institute for Health and Clinical Excellence has published a Clinical Guideline on core interventions in the management and treatment of schizophrenia in primary and secondary care (CG1, December 2002). The Royal College of Psychiatrists has issued advice on using doses above the BNF upper limit. Please see BNF section 4.2 and 4.2.2.

4.2.1 Antipsychotic drugs

Phenothiazines Phenothiazine derivatives may be divided into three main groups, according to pharmacological profile. Each group is represented among the agents shown below. c chlorpromazine1 tablets 10mg, 25mg, 50mg, 100mg liquid 25mg/5mL, 100mg/5mL injection 25mg/1mL, 50mg/2mL c trifluoperazine2 tablets 1mg, 5mg m/r capsules 2mg, 10mg, 15mg liquid 1mg/5mL, 5mg/5mL S thioridazine3 tablets 10mg, 25mg, 50mg, 100mg liquid 25mg/5mL, 100mg/5mL S levomepromazine tablets 25mg (methotrimeprazine) injection 25mg/1mL S promazine4 tablets 25mg, 50mg liquid 25mg/5mL, 50mg/5mL injection 50mg/1mL

Prescribing notes for phenothiazines 1 Chlorpromazine (group 1) has pronounced sedative effects, and moderate antimuscarinic and extrapyramidal side effects.

2 Trifluoperazine (group 3) has fewer sedative effects, fewer antimuscarinic effects but more pronounced extrapyramidal side effects than the other groups. Antipsychotics from other chemical groups tend to resemble group 3 phenothiazines.

3 Thioridazine (group 2) has moderate sedative effects, marked antimuscarinic effects but fewer extrapyramidal side effects than the other groups.

• The CSM has advised that thioridazine should be restricted to second-line treatment of schizophrenia in adults. The balance of risks and benefits is considered unfavourable for its previous indications. All patients should have baseline ECG monitoring and electrolytes. These should be repeated after each dose escalation and at 6 monthly intervals. Commence with the lowest possible dose and titrate slowly.

• Check patients for potentially interacting drugs or other risk factors for cardiac disease.

• Thioridazine is metabolised by cytochrome P450 2D6; drugs which inhibit this enzyme or are metabolised by it have the potential to increase plasma levels of thioridazine and thus its cardiotoxicity. Examples of such interactions are given in the SPC. Drugs which prolong the QTc interval may cause additive effects if taken with thioridazine.

• Clinically significant cardiac disorders including dysrhythmias, conduction disorders or a history of QTc prolongation are contra-indications to

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 44 thioridazine use.

• Medical conditions or drugs which can lead to electrolyte imbalance also predispose to thioridazine induced ventricular arrhythmias.

• Eyesight should be monitored as acuity may be reduced by brownish colouring the vision.

4 Promazine is not sufficiently active by the oral route to be used in psychosis.

Butyrophenones c capsules 500micrograms tablets 1.5mg, 5mg, 10mg, 20mg liquid 10mg/5mL injection 5mg/1mL S benperidol tablets 250micrograms

Diphenylbutylpiperidines S pimozide1 tablets 2mg, 4mg

Thioxanthenes S zuclopenthixol dihydrochloride tablets 2mg, 10mg, 25mg H zuclopenthixol acetate2 injection 50mg/1mL, 100mg/2mL (Clopixol Acuphase)

Substituted benzamides S sulpiride tablets 200mg, 400mg See liquid (SF 200mg/5mL) Appendix 2

Others S loxapine capsules 10mg, 25mg, 50mg

1 Pimozide CSM WARNING: Following reports of sudden unexplained death, the CSM recommends ECG before treatment. The CSM also recommends that patients on pimozide should have an annual ECG (if the QT interval is prolonged, treatment should be reviewed and either withdrawn or dose reduced under close supervision) and that pimozide should not be given with other antipsychotic drugs (including depot preparations), tricyclic antidepressants or other drugs which prolong the QT interval, such as certain antimalarials, anti-arrhythmic drugs and certain antihistamines and should not be given with drugs which cause electrolyte disturbances (especially diuretics). 2 Clopixol Acuphase is reserved for use in hospital by psychiatrists.

Atypical antipsychotics Atypical antipsychotics may be better tolerated than other antipsychotics: extrapyramidal symptoms and prolactin elevation may be less frequent than with the older agents. While most atypical antipsychotics have not generally been associated with prolongation of the QT interval, caution should be exercised if they are prescribed with other agents known to increase the QT interval.

Atypical antipsychotics should be used with caution in patients with cardiovascular disease, or a history of epilepsy; they should be used with caution in the elderly.

Please see NICE guidance No 43 on the use of atypical antipsychotics in schizophrenia.

S risperidone1 tablets 0.5mg, 1mg, 2mg, 3mg, 4mg, 6mg liquid 1mg/1mL S olanzapine2 tablets 2.5mg, 5mg, 7.5mg, 10mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 45 oral lyophilisates 5mg, 10mg (Velotab) S amisulpride tablets 50mg, 200mg, 400mg S quetiapine tablets 25mg, 100mg, 150mg, 200mg H aripiprazole3 tablets 10mg, 15mg, 30mg H clozapine4 tablets 25mg, 100mg

For long-acting injections see section 4.2.2 below.

1 Risperidone: Take care to avoid confusion with risedronate (a ) 2 Olanzapine. The CSM has issued a warning that Olanzapine can adversely affect blood glucose. Reports of hyperglycaemia, diabetes mellitus or exacerbation of diabetes have been received in the UK. Ketoacidosis and coma have ensued on rare occasions. Clinical monitoring is recommended in diabetic patients and those with risk factors for diabetes. 3 Aripiprazole is reserved for second line use in hospital by specialists. Usage will be reviewed following audit by prescribers and pharmacists at Whitchurch Hospital. 4 Clozapine is reserved for treatment resistant schizophrenic patients i.e. patients who are unresponsive to, or intolerant of conventional neuroleptics. (“Non- responsiveness” is defined as a lack of satisfactory clinical improvement, despite the use of adequate doses of at least two marketed neuroleptics prescribed for adequate duration. “Intolerance” is defined as the impossibility to achieve adequate benefit with conventional neuroleptic drugs because of severe and untreatable neurological adverse reactions such as extrapyramidal symptoms and tardive dyskinesia). The patient must be under the supervision of a specialist and supply of clozapine is restricted to hospital and retail pharmacies registered with the CPMS. Once patients are having their blood sampled every 4 weeks the prescribing can be taken over by the GP and the dispensing by the community chemist as long as they are all registered. Clozapine can cause agranulocytosis. First dose hypotension may cause collapse.

The CSM has warned of rare cases of myocarditis in clozapine users, some of which have been fatal. Clozapine is contra-indicated in patients with severe cardiac disorders. • Patients must have a history and physical examination prior to starting therapy. The treating physician should consider performing a pre-treatment ECG. • Patients who have persistent tachycardia at rest, especially during the first two months of treatment, should be closely observed for other signs or symptoms of myocarditis or cardiomyopathy. These include palpitations, arrhythmias, symptoms mimicking myocardial infarction, chest pain and other unexplained symptoms of heart failure. • Patients in whom myocarditis or cardiomyopathy is suspected should stop clozapine and undergo urgent diagnostic evaluation by a cardiologist. • Patients who develop clozapine-induced myocarditis or cardiomyopathy should not be re-exposed to clozapine.

Clozapine has also been associated with reports of adverse reactions resembling intestinal obstruction. It should be used with caution in patients who are taking other drugs which may cause constipation (e.g. antimuscarinic drugs) or in patients with a history of colonic disease or previous bowel surgery. Patients should be monitored for constipation and laxatives prescribed as appropriate.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 46 4.2.2 Antipsychotic depot injections

Long-acting depot injections are useful for maintenance therapy, especially where compliance with oral medication is unreliable. However, they may give rise to a higher incidence of extrapyramidal side effects than oral preparations. As undesirable side effects will be prolonged, a small test dose should be given at the start of therapy. As individual responses are very variable, the dose and dose interval should be tailored to the needs of each patient. The Royal College of Psychiatrists has issued advice on using doses above the BNF upper limit. Please see BNF section 4.2 and 4.2.2.

S flupentixol decanoate1 injection 20mg/1mL (Depixol) (flupenthixol decanoate) injection 50mg/0.5mL, 100mg/1mL (Depixol Conc) injection 200mg/1mL (Depixol Low Volume) S fluphenazine decanoate1 injection 12.5mg/0.5mL, 25mg/1mL, 50mg/2mL (Modecate) concentrated injection 50mg/0.5mL, 100mg/1mL (Modecate Conc) S haloperidol decanoate1 injection 50mg/1mL, 100mg/1mL (Haldol Decanoate) S zuclopenthixol decanoate1 injection 200mg/1mL (Clopixol) injection 500mg/1mL (Clopixol Conc) S pipotiazine palmitate2 injection 50mg/1mL, 100mg/2mL (Piportil (pipothiazine palmitate) Depot) H olanzapine3 (IM) injection 10mg in 2ml H risperidone4 powder & solvent 25mg, 37.5mg, 50mg (Risperdal Consta)

1 These are agents which specialists are likely to choose as first line agents. 2 Pipotiazine (pipothiazine) is reserved for use where other agents are inappropriate. 3 Olanzapine IM is reserved for rapid tranquilisation by Psychiatrists only. It is unsuitable for use in patients with unstable medical conditions and in patients with drug or alcohol intoxication. Supplies may not be available until June ’03. 4 Risperidone IM should be initiated by a consultant psychiatrist. Follow up injections should be prescribed by hospital staff but may be given by trained members of the Community Mental Health Team. Pre-treatment with oral risperidone is required to assess tolerability.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 47 4.2.3 Antimanic drugs

In an acute attack of mania, treatment with an antipsychotic drug may be necessary as it may take a few days for lithium to attain an antimanic effect. However, high doses of haloperidol, fluphenazine or flupentixol given in conjunction with lithium, have been reported to cause irreversible toxic encephalopathy. Due to its narrow therapeutic range, serum level monitoring of lithium is necessary. The ideal range 12 hours post dose is 0.4-1 mmol/litre. Levels of over 1.5mmol/litre may be fatal. If potentially hazardous signs of toxicity such as tremor, ataxia, dysarthria, nystagmus, renal impairment or convulsions occur, treatment should be stopped, the levels rechecked and steps taken to reverse lithium toxicity. Please see the BNF for patient counselling, important drug interactions and further information.

S lithium carbonate1,5 m/r tablets 200mg, 400mg (Priadel) m/r tablets 450mg (Liskonum) S lithium citrate1,2,5 liquid 520mg/5mL (Priadel) liquid 509mg/5mL (Li-liquid) S carbamazepine5 (see section 4.8.1) S valproic acid3,5 as (semisodium tablets e/c 250mg, 500mg (Depakote) valproate)

1 Lithium preparations vary widely in . Please prescribe by brand name. Priadel is the preferred brand. Liskonium and Camcolit brands should only be prescribed for patients already stabilised on them. An NPA lithium treatment card should be issued to patients. This provides advice for patients on missed doses, adverse effects, interactions and the need for regular monitoring. Lithium is covered by Shared Care Protocol (SC) No 13. 2 Lithium citrate liquid contains approximately 5.4mmol Li+ in 5mL and is approximately equivalent to 200mg lithium carbonate (Priadel) tablet. 3 Semisodium valproate is licensed for treatment of acute mania/hypomania for a maximum of 12 weeks. When mania is controlled the patient should be transferred onto one of the other mood stabilisers for maintenance treatment. Patients should be reviewed on discharge to ensure this has been done. See BNF Section 4.8.1 for information on the cautions, contra-indications and monitoring of patients on valproate and its adverse effect profile. 4 NICE Technology Appraisal No 66 (Sept 03) in line with NICE guidance: • Olanzapine (see section 4.2.1) and valproate semisodium, within their licensed indications, are recommended as options for control of the acute symptoms associated with the manic phase of bipolar I disorder. • Of the drugs available for the treatment of acute mania, the choice of which to prescribe should be made jointly by the individual and the clinician(s) responsible for treatment. The choice should be based on an informed discussion of the relative benefits and side-effect profiles of each drug, and should take into account the needs of the individual and the particular clinical situation. • In all situations where informed discussion is not possible advance directives should be taken fully into account and the individual’s advocate and/or carer should be consulted when appropriate. Please see full guidance: www.nice.org.uk 5 NICE CG 038 July 2006 The Management of bipolar disorder in adults, children and adolescents, in primary and secondary care. Please see full guidance: www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 48 4.3 Antidepressant Drugs The National Institute for Health and Clinical Excellence Clinical Guideline on Depression (No 23 Dec 04) recommends that for mild and moderate depression, psychological treatments specifically focused on depression (such as problem-solving therapy, cognitive behaviour therapy (CBT) and counselling) can be as effective as drug treatments and should be offered as treatment options.

The guideline also recommends that: • Antidepressants should not be used for the initial treatment of mild depression, because the risk-benefit ratio is poor. • Where antidepressants are prescribed for moderate or severe depression it should be a selective serotonin reuptake inhibitor (SSRI), because SSRIs are as effective as tricyclic antidepressants and their use is less likely to be discontinued because of side effects. • All patients prescribed antidepressants should be informed that, although the drugs are not associated with tolerance and craving, discontinuation/withdrawal symptoms may occur on stopping or missing doses or, occasionally, on reducing the dose of the drug. • Screening for all high risk groups - for example, those with a past history of depression, significant physical illnesses causing disability, or other mental health problems such as dementia. • For severe depression, psychological treatment (CBT) should be used in combination with anti-depressant medication.

Anxiety. The guideline recommends that patients should be offered any of the following three types of intervention, taking into account patient preference. In descending order of long term effectiveness, these interventions are: • Psychological therapy, such as CBT. • Medication, such as an SSRI licensed for generalised anxiety disorder. • Self help, such as bibliotherapy (the use of written materials) based on CBT principles.

Self-harm. Please see NICE Clinical Guideline No 16, July 2004, on the short-term physical and psychological management and secondary prevention of self-harm in primary and secondary care.

Please see full guidance. www.nice.org.uk

CSM advice (hyponatraemia). Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.

Please note recent advice of the CSM’s Expert Working Group on the safety of SSRIs

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 49 4.3.1 Tricyclic and related antidepressant drugs

Tricyclic antidepressants c lofepramine tablets 70mg liquid 70mg/5mL d dosulepin tablets 25mg (dothiepin) capsules 75mg S imipramine tablets 10mg, 25mg liquid 25mg/5mL liquid 70mg/5mL S amitriptyline1,2 tablets 10mg, 25mg, 50mg liquid 25mg/5mL, 50mg/5mL injection 10mg/1mL S clomipramine2 capsules 10mg, 20mg, 50mg m/r tablets 75mg liquid 25mg/5mL injection 25mg/2mL See Appendix 2 liquid 25mg/5mL, 75mg/5mL S doxepin3 capsules 10mg, 25mg, 50mg

1 Amitriptyline use in post-herpetic neuralgia is covered in section 4.7.3 of the BNF. 2 Amitriptyline and clomipramine are agents which specialists may initiate as second line options where other treatments are inappropriate or ineffective. 3 Doxepin is included for the treatment of chronic urticaria only. See section 13.3.

Related antidepressants d trazodone capsules 50mg, 100mg tablets 150mg liquid 50mg/5mL

4.3.2 Monoamine-oxidase inhibitors

S phenelzine1 tablets 15mg

Reversible MAOIs S moclobemide1 tablets 150mg, 300mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 50 4.3.3 Selective serotonin re-uptake inhibitors

Key findings of the CSM’s Expert Working Group Report on SSRIs Dec 2004

SSRIs are effective medicines in the treatment of depression and anxiety conditions, and the CSM has concluded that the balance of risks and benefits of all SSRIs in adults remains positive in their licensed indications. Clear advice is to be given in all SSRI product information in 3 areas: dose changes, suicidal behaviour and withdrawal reactions. (See notes below. For more information please visit www.mhra.gov.uk ).

Summary of general prescribing advice

1. Dose changes: For the majority of SSRIs in the treatment of depressive illness, clinical trial data do not show any additional benefit from increasing the dose above the recommended daily dose. In the absence of evidence of a benefit from increasing the dose, good practice would be to maintain patients on the lowest efficacious dose. For patients currently on a dose above the recommended dose, the advice is to complete the course if the patient is well. If a patient is not doing well after starting treatment the possibility of an adverse reaction to the drug should be considered. Patients should be monitored for signs of restlessness or agitation, particularly at the beginning of treatment. Increasing the dose in these circumstances may be detrimental.

2. Suicidal behaviour: Use of SSRIs in adults – suicidal behaviour (from Annex 1 of CEM/CMO/2006/6)

The conclusions of the Group on this issue can be summarised as follows: • There is epidemiological evidence that the risk of self-harm in depressed patients is greatest around the time of presentation to medical services. It is general clinical experience that the risk of suicide may increase in the early stages of treatment for depressive illness. • Careful and frequent patient monitoring by healthcare professionals and, where appropriate, other carers, is important in the early stages of treatment, particularly if a patient experiences worsening of symptoms or new symptoms after starting treatment. • Studies indicate that increases in the prescribing of SSRIs have not been associated with an increase in population suicide rates, although interpretation of these findings is difficult as a range of factors influence population trends in suicide. • From the available clinical trial data, both published and unpublished, a modest increase in the risk of suicidal thoughts and self-harm for SSRIs compared with placebo cannot be ruled out. There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and other antidepressants, with respect to their influence on suicidal behaviour. Evidence from non-experimental studies based on the General Practice Research Database indicates that there is no increased risk of suicidal behaviour with SSRIs compared with tricyclic antidepressants (TCAs). There is no clear evidence that there is an increased risk of self-harm or suicidal thoughts when SSRIs are discontinued.Evidence of a relationship between suicidal behaviour and increasing/decreasing dose is not robust; however, patients should be monitored around the time of dose changes for any new symptoms or worsening of disease. ..continued/

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 51 SSRIs & suicidal behaviour continued/

Young adults • The increased risk of suicidal behaviour seen in children and adolescents with depressive illness treated with SSRIs raised the question as to whether there was a similar increased risk in young adults. The clinical trial data for each product was reviewed in relation to a possible effect in young adults, and the GPRD study looked specifically at this age group. From these analyses, the Group concluded that there is no clear evidence of an increased risk of self- harm and suicidal thoughts in young adults of 18 years or over. However, given that individuals mature at different rates and that young adults are at a higher background risk of suicidal behaviour than older adults, as a precautionary measure young adults treated with SSRIs should be closely monitored. The Group also recommended that in further research on the safety and efficacy of SSRIs, young adults should be assessed separately.

The Chairman of the Commission of Human Medicines has reiterated the above advice in his letter CEM/CMO/2006/6 - 8 May 2006. The CHM and the American Food and Drug Administration are currently evaluating results of an analysis of suicidal behaviour by GSK, the manufacturer of .

3. Withdrawal reactions: To minimise withdrawal reactions on stopping SSRIs, the dose should be tapered gradually over a period of several weeks, according to the patient’s need.

SSRIs c fluoxetine capsules 20mg liquid 20mg/5mL c paroxetine tablets 20mg, 30mg liquid 10mg/5mL c citalopram tablets 10mg, 20mg drops 40mg/mL c sertraline tablets 50mg, 100mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 52

4.3.4 Other antidepressant drugs d flupentixol2 tablets 500micrograms, 1mg (flupenthixol) d mirtazapine3 tablets 30mg d nefazodone tablets 50mg,100mg, 200mg dS venlafaxine4 See CMO Letter tablets 37.5mg, 50mg, 75mg m/r capsules 75mg, 150mg S duloxetine5 capsules 30mg, 60mg (Cymbalta) S reboxetine1 tablets 4mg H l-tryptophan6 tablets 500mg

1 Moclobemide, phenelzine and reboxetine are agents which specialists would use where other treatments were inappropriate or ineffective. 2 Flupentixol may be used in low doses to treat depression. 3 Mirtazapine has been associated with blood disorders. Patients should be asked to report any fever, sore throat, stomatitis or other signs of infection during treatment. If a blood dyscrasia is suspected, the drug should be stopped immediately and a blood count performed. 4. Venlafaxine. Prescribing advice has been updated following the CMO’s letter 31.5.06 : The NICE advice that venlafaxine should be reserved as a second-line treatment (after SSRIs) still stands. The following changes have been authorised in line with the review of the evidence: Specialist supervision (including shared care arrangements) is now only required for initiation of venlafaxine treatment in those severely depressed or hospitalised patients who require doses of 300mg daily, or above.

Contra-indications and warnings: Venlafaxine is contraindicated in patients with an identified high risk of a serious cardiac ventricular arrhythmia. Venlafaxine remains contra-indicated in patients with uncontrolled hypertension.

The contra-indications for patients with an electrolyte imbalance and the requirement for a baseline ECG have been removed from product information.

Venlafaxine should be used with caution in patients with established cardiac disease that may increase the risk of ventricular arrhythmias (e.g. recent myocardial infarction).

Regular measurement of blood pressure is recommended for patients receiving venlafaxine. For patients who experience a sustained increase in blood pressure while receiving venlafaxine, either dose reduction or discontinuation should be considered.

Interactions: Potent CYP3A4 inhibitors (e.g. ketoconazole, erythromycin) or drug combinations that inhibit both CYP3A4 and CYP2D6 should only be co-administered with venlafaxine when strictly indicated, because of the possibility of clinically important interactions in patients with a 'poor metaboliser' phenotype. Specialist supervision is recommended for use of concomitant SSRIs.

5 Duloxetine is included for use after patients have failed to respond to two SSRIs and who also have a contraindication to venlafaxine. Avoid confusion with Yentreve brand for stress urinary incontinence. 6 Tryptophan is available as adjunctive therapy in resistant depression. Due to the association with eosinophilia-myalgia syndrome, patient and prescriber must be registered with the Optimax Information & Clinical Support (OPTICS) Unit.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 53 4.4 Central Nervous System Stimulants

CNS stimulants have very few indications and should not be used to treat depression, obesity, senility debility or for the relief of fatigue. Methylphenidate and dexamfetamine (dexamphetamine) have been found beneficial for hyperactive children but treatment is carried out under close specialist supervision. Please see full guidance: www.nice.org.uk

NICE Technology appraisal No 98 March 2006 - Methylphenidate, atomoxetine and dexamphetamine for attention deficit hyperactive disorder (ADHD) in children and adolescents (replaces NICE Technology appraisal No 13 Oct 2000).

1.1 Where drug treatment is considered appropriate, methylphenidate, atomoxetine and dexamfetamine are recommended, within their licensed indications, as options for the management of ADHD in children and adolescents. 1.2 The decision regarding which product to use should be based on the following: ● the presence of comorbid conditions (for example, tic disorders, Tourette’s syndrome, epilepsy) ● the different adverse effects of the drugs ● specific issues regarding compliance identified for the individual child or adolescent, for example problems created by the need to administer a mid-day treatment dose at school ● the potential for drug diversion (where the medication is forwarded on to others for non-prescription uses) and/or misuse ● the preferences of the child/adolescent and/or his or her parent or guardian. 1.3 If there is a choice of more than one appropriate drug, the product with the lowest cost (taking into account the cost per dose and number of daily doses) should be prescribed. 1.4 Drug treatment should only be initiated by an appropriately qualified healthcare professional with expertise in ADHD and should be based on a comprehensive assessment and diagnosis. Continued prescribing and monitoring of drug therapy may be performed by general practitioners, under shared care arrangements. Please see full guidance: www.nice.org.uk

S atomoxetine1 capsules 10mg, 18mg, 25mg, 40mg, 60mg S methylphenidate2 tablets 5mg, 10mg m/r tablets 18mg, 27mg, 36mg (Concerta XL) m/r capsules 10mg, 20mg, 30mg (Equasym XL) S modafinil3 tablets 100mg, 200mg (narcolepsy) H modafinil4 tablets 100mg, 200mg (Parkinsonism) H dexamfetamine tablets 10mg (dexamphetamine)

1 Atomoxetine - For specialist initiation and use in accordance with the shared care protocol. Following the September 2005 advice on increased risk of suicidal thoughts or behaviour with atomoxetine, the MHRA issued the following warnings in January 2006: Atomoxetine is authorised for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children of 6 years and older, and in adolescents, as part of a comprehensive treatment programme. It must be initiated by, or under the supervision of, a physician with appropriate knowledge and experience in treating ADHD. A Europe wide review of available data on the risks and benefits of atomoxetine has concluded that the overall balance of risks and benefits remains positive in the treatment of ADHD in children of 6 years and older and in adolescents. However, in order to optimise the safe use of atomoxetine it is important that prescribers are aware of the following:

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 54

New Advice to prescribers • Seizures are a potential risk with atomoxetine and therefore it should be introduced with caution in patients with a history of seizure. Discontinuation of atomoxetine should be considered in any patient developing seizure or if there is an increase in seizure frequency. • Reports of QT interval prolongation have been received in association with atomoxetine. Therefore, it should be used with caution in those with congenital or acquired long QT or a family history of QT prolongation. This risk may be increased if atomoxetine is used concomitantly with other drugs that produce QT prolongation, drugs that can cause electrolyte disturbances and those that inhibit cytochrome P450 2D6. Reminder of previous advice • Due to concerns about an increased risk of suicidal thoughts and behaviour, patients should be monitored for signs of depression, suicidal thoughts or suicidal behaviour and referred for appropriate treatment if necessary. • There is a risk of rare, but sometimes severe, hepatic disorders. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. For further information please call the Medicines and Healthcare products Regulatory Agency on 020 7084 2000 or visit the website www.mhra.gov.uk .

2 Methylphenidate should be initiated by a specialist but may be continued by General Practitioners (Shared care protocol pending) The modified release preparation should only be used in patients who have previously been treated with the standard release form. 3 Modafinil is included for the treatment of narcolepsy. For specialist initiation and GP follow-up. 4. Modafinil is also included for hospital only specialist treatment of daytime hypersomnolence in Parkinson patients. See NICE CG35 June 2006 Parkinson's disease: diagnosis and management in primary and secondary care.

4.5 Drugs Used in the Treatment of Obesity

Lifestyle changes, diet and exercise are the first line of therapy in obesity. Drug intervention is a second line of treatment but is only justified where dieting and increased physical activities are also undertaken. must be accompanied by a low fat diet and is particularly suited to those who prepare their own meals. Sibutramine avoids the problems of increased fat , but its potential for adrenergic effects and its central activity mean that it must be used with caution in patients with a history of cardio-vascular problems or who use other . Please refer to NICE Clinical Guidance CG43 December 2006 - Obesity: the prevention, identification, assessment and management of overweight and obesity in adults and children. www.nice.org.uk (This replaces CG46, July 2002 on morbid obesity, TA No 22, March 2001 on orlistat and TA 31, October 2002 on sibutramine.)

4.5.1 Anti-obesity drugs acting on the gastrointestinal tract c orlistat1 Capsules 120mg

1 Orlistat is a pancreatic lipase inhibitor, which reduces the absorption of dietary fat. It is licensed for use in conjunction with a mildly hypocaloric diet in patients with a body mass index (BMI) of 30kg/m2 or greater. It may also be considered in patients with a BMI of 28kg/m2 or greater, who also have other associated risk factors such as type 2 diabetes, hypertension or hypercholesterolaemia. Treatment with orlistat should be discontinued after 12 weeks if patients have been unable to lose at least 5 % of the body weight as measured at the start of drug therapy. Patients may reduce their fat

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 55 intake to avoid severe gastrointestinal side effects including steatorrhoea. A helpline, providing motivation, advice and proactive support for patients and healthcare professionals, is available on 0800 73117138 ( 24 hrs a day). Orlistat is approved for use in accordance with NICE Guidance No 22 (March 2001). Please see full guidance: www.nice.org.uk

4.5.2 Centrally acting appetite suppressants

Sibutramine is a serotonin and noradrenaline reuptake inhibitor. Its central action results in early satiety and increased energy expenditure contributing to weight loss. NICE Guidance No 31, issued October 2001 supports use of sibutramine as part of an overall treatment plan for patients with a BMI over 30kg/m2 (or 27kg/m2 if there are co-morbidities) who have made previous serious attempts to lose weight by diet, exercise and/or other behavioural modifications. A small number of users will have a rise in blood pressure which should be checked every two weeks in the first month. Therapy should be continued only if there is no significant rise in blood pressure, and if there has been a 2kg weight loss after 1 month and at least a 5% weight loss at 3 months. Some experts also recommend a 10% loss at 6 months as an appropriate criterion for continuation of therapy. Arterial disease, uncontrolled hypertension, arrhythmias and concomitant use of anti- depressants are contra-indications. A dose increase from 10mg per day to 15mg per day may be considered if there has been a loss of less than 2kgs after the first month. Treatment is not recommended beyond the licensed indication of 12 months. Please see full guidance: www.nice.org.uk

c sibutramine1 capsules 10mg, 15mg

1 Sibutramine is added to the formulary for use in line with NICE guidance No 31 as part of an overall treatment plan.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 56 4.6 Drugs Used In Nausea and Vertigo

Antihistamines c cinnarizine tablets 15mg c cyclizine tablets 50mg injection 50mg/1mL c promethazine theoclate tablets 25mg (Avomine) c promethazine hydrochloride (see section 3.4.1)

Phenothiazines and related drugs c prochlorperazine tablets 5mg liquid 5mg/5mL injection 12.5mg/1mL buccal tablets 3mg (Buccastem) c trifluoperazine (see section 4.2.1) c haloperidol (see section 4.2.1) d chlorpromazine (see section 4.2.1) d levomepromazine (see section 4.2.1) (methotrimeprazine)

Domperidone and metoclopramide c domperidone tablets 10mg liquid 5mg /5mL suppository 30mg c metoclopramide tablets 10mg liquid 5mg/5mL injection 10mg/2mL, 100mg/20mL

5HT3 antagonists S ondansetron tablets 4mg, 8mg liquid 4mg/5mL suppository 16mg injection 4mg/2mL, 8mg/4mL H palonosetron1 injection 250 micrograms/5mL

Hyoscine d hyoscine hydrobromide tablets 300micrograms injection 400micrograms/mL, 600micrograms/mL patch 1mg/72hours

Other drugs for Meniere's disease S betahistine tablets 8mg, 16mg

1. Palonosetron is included for prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy regimens lasting more than 5 days. It is also available for prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy when control has not been achieved by first line treatments.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 57 4.7

Please see Cardiff & Vale policy for chronic pain management Nov. 2007 (Awaiting confirmation of policy for North Bro Taf)

4.7.1 Non-opioid analgesics

For Non-steroidal anti-inflammatory analgesics see Chapter 10 c aspirin1 tablets 300mg soluble ec tablets 300mg c paracetamol2 tablets 500mg soluble tablets 500mg liquid 120mg/5mL liquid 250mg/5mL suppository 30mg See Appendix 2 suppositories 60mg, 125mg, 240mg, 500mg suppository 1g See Appendix 2 H IV solution for infusion 10mg/ml (Perfalgan) 50ml vial = 500mg 100ml vial = 1000mg

Compound analgesic preparations c co-dydramol tablets c co-codamol 8/500 tablets soluble tablets c co-codamol 30/500 tablets capsules effervescent tablets

1 The CSM has warned that aspirin should not be given to children under 16 unless specifically medically indicated due to the risk of Reye’s syndrome. 2. Feverish illness in children - Assessment and initial management in children younger than 5 years. See NICE CG47 May 2007.

Co-proxamol has been removed from the Formulary due to CSM advice that the balance of risk and benefit for co-proxamol is unfavourable. For more information please see http://www.mhra.gov.uk/NewsCentre/CON2025739

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 58 4.7.2 Opioid analgesics c codeine phosphate tablets 15mg, 30mg, 60mg liquid 25mg/5mL injection 60mg/1mL c tablets 30mg liquid 10mg/5mL m/r tablets 60mg, 90mg, 120mg (DHC Continus) injection 50mg/1mL c morphine sulphate liquid 10mg/5mL (Oramorph) liquid 100mg/5mL (Oramorph Concentrate) tablets 10mg, 20mg, 50mg (Sevredol) m/r tablets 5mg, 10mg, 15mg, 30mg, 60mg, 100mg, 200mg (MST Continus) m/r granules 20mg, 30mg, 100mg, 200mg (MST suspension) 1 suppositories 20mg, 30mg, 60mg, 100mg, 200mg injection 10mg/1mL, 15mg/1mL, 30mg/1mL c diamorphine injection 5mg, 10mg, 30mg, 100mg, 500mg d buprenorphine tablets 200micrograms injection 300micrograms/1mL patch 5micrograms/hr, 10micrograms/hr, 20 micrograms/hr (BuTrans) 2 d pethidine tablets 50mg injection 50mg/1mL, 100mg/2mL d tramadol capsules 50mg m/r capsules 50mg, 100mg, 150mg m/r tablets 100mg, 150mg soluble tablet 50mg injection 100mg/2mL d fentanyl transdermal patches See also Section 25micrograms/hr, 15.1.4.3 50micrograms/hr, 75micrograms/hr, 100micrograms/hr d oxycodone3 Oxynorm: capsules 5mg, 10mg, 20mg liquid 5mg/5mL concentrated oral soln 10mg/mL injection 10mg/mL Oxycontin: m/r tablets 5mg, 10mg, 20mg, 40mg, 80mg S buprenorphine transdermal patch 20mg, 30mg, 40mg (Transtec)4 S meptazinol tablets 200mg injection 100mg/1mL Cont./

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 59 Opioid analgesics cont./

S methadone5,6 tablets 5mg Shared care liquid 1mg/1mL, 10mg/1mL protocol no. 19 injection 10mg/1mL S dextromoramide tablets 5mg, 10mg suppository 10mg See Appendix 2 S fentanyl7 lozenge 200micrograms, 400micrograms, 600micrograms, 800micrograms, 1.2mg, 1.6mg (Actiq)

1. Morphine modified release granules are extremely expensive and rarely used. 2. Buprenorphine patches (BuTrans) are available for moderate to severe pain. Prescribing is subject to adherence to the Pain Management algorithm. See Cardiff & Vale policy for chronic pain management Nov. 2007 3. Oxycodone is included as second line treatment for moderate to severe pain including postoperative pain. 4. Buprenorphine patches (Transtec) are available for treatment of moderate to severe pain unresponsive to non-opioid analgesics. Reserved for initiation by specialists in pain control in line with Chronic Pain Clinic guidelines. 5. Methadone: See Shared Care Protocol CV14 for pain control requiring methadone. 6. Methadone liquids exist in a number of different strengths; prescribers should ensure that dose and formulation are specified clearly ( see also 3.9.2, 4.10) 7. Fentanyl Actiq is retained in the formulary for initiation by clinicians who specialise in managing pain. If a patient is discharged home on this medication, the attention of the patient and carer should be brought to the “instructions for safe disposal” in the patient information leaflet. Please refer to the approved protocol for further details.

With anti-emetic d morphine tartrate with cyclizine tartrate 10mg/50mg (Cyclimorph 10) 15mg/50mg (Cyclimorph 15)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 60 4.7.3 Neuropathic pain Neuropathic pain occurs as a result of dysfunction or damage to neural tissue. Treatment options include: • opioids e.g. morphine, methadone • antidepressants e.g. amitriptyline, lofepramine, fluoxetine • anticonvulsants e.g. sodium valproate, carbamazepine, gabapentin • local anaesthetic congeners e.g. flecainide, mexilitene • corticosteroids e.g. dexamethasone • ketamine • topical agents e.g. capsaicin, EMLA Other options include: • TENS • acupuncture • epidural • nerve blocks • cordotomy Please see the BNF, under the chosen drug’s main indication, for prescribing guidance. However, doses prescribed for neuropathic pain will be lower and will require titration from an initial small dose. The maximum dose is determined by the degree of relief and by adverse effects. For further advice on the initiation and prescribing of these drugs, please contact your local Palliative Care Team.

Trigeminal neuralgia c carbamazepine (see section 4.8.1) d capsaicin 1 cream 0.075% (Axsain) see also 10.3.2 d phenytoin (see section 4.8.1) S pregabalin2 capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 300mg (Lyrica)

1. Capsaicin: For post-herpetic neuralgia and neuropathic pain associated with allodynia. Avoid contact with eyes, and inflamed or broken skin. Hands should be washed immediately after use. Not for use under tight bandages. Avoid taking a hot shower or bath just before or just after applying capsaicin as this enhances the burning sensation.

2. Pregabalin: Available for a 12 month period for use in Chronic Pain and Palliative Care only for the treatment of neuropathic pain. The drug must be Consultant initiated and a Register of patients established. A specific form to audit use and document patient outcomes must be established. A treatment algorithm must also be developed. The consultant issuing the prescription should write to the patient's GP with the following assurances: a)The patient has been tried on gabapentin but has failed to respond b)The patient is now stabilised on Pregabalin c) The patient is part of an evaluative study, the results of which will be reported back to MTEC.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 61 4.7.4 Antimigraine drugs

4.7.4.1 Treatment of acute migraine attack

Two thirds of migraine sufferers can obtain relief by the use of simple analgesics such as paracetamol or aspirin. These are the first line agents (except for children under 16 in whom the CSM has warned that aspirin should not be given unless specifically medically advised due to the risk of Reye’s syndrome). In order to relieve nausea and increase gastric motility they can be combined with certain anti-emetics, for example domperidone or metoclopramide. The use of a dispersible or effervescent form may help to improve absorption, though these are more expensive and contain higher levels of sodium. Non-steroidal anti-inflammatory agents may also be effective. Diclofenac and ibuprofen are two of a number of NSAIDs which are licensed for migraine. 5HT1 receptor agonists (triptans) are usually reserved for patients who do not respond to simple analgesics. For simple analgesics, see sections 4.7.1. If acute medication is required more than twice a week, the most likely diagnosis is chronic daily headache caused by over-use of analgesics, particularly opioids which may have a re-bound effect. For this reason, opioid analgesics are not recommended. They also have addictive potential. c paracetamol with metoclopramide1 tablets 500mg/5mg powder 500mg/5mg (Paramax) c diclofenac sodium for preparations see section 10.1.1 c ibuprofen for preparations see section 10.1.1 d rizatriptan2 tablets 5mg, 10mg wafers 10mg d sumatriptan3 tablets 50mg, 100mg injection 6mg/0.5mL d paracetamol with buclizine and codeine4 tablets (Migraleve)

1 Combinations of aspirin with metoclopramide and of paracetamol with domperidone are good alternatives but these are much more expensive. Metoclopramide can cause severe extra-pyramidal symptoms in children and young adults. See above for CSM warning on aspirin. 2 Rizatriptan dose should be halved in patients taking propranolol; rizatriptan should not be taken within two hours of taking propranolol. This is due to the potentiating effect of sharing a metabolic pathway. 3 has been associated with reports of chest pain and tightness (coronary vasoconstriction). The CSM has therefore emphasised that sumatriptan should not be used in ischaemic heart disease or Prinzmetal’s angina and that use with ergotamine should be avoided. Sumatriptan should not be taken until 24 hours after stopping an ergotamine-containing preparation (ergotamine-containing preparations should not be taken until 6 hours after sumatriptan). A 50mg dose of sumatriptan has a similar efficacy profile to that of a 100mg dose. 4 Migraleve is retained in the formulary for existing patients who find the product useful. It is no longer recommended due to the codeine component.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 62 4.7.4.2 Prophylaxis of migraine

Where migraine attacks are frequent, a search should be made to find provoking factors such as stress, diet (chocolate, cheese, alcohol etc.) or drug therapy such as oral contraceptives. If a patient suffers more than two attacks per month, a prophylactic treatment selected from the following list may be used. Acute treatment for attacks will still be required as preventive therapy only reduces the frequency of attacks. Tricyclic antidepressants and sodium valproate have been found useful in migraine prophylaxis but they are not licensed for this indication. c pizotifen1 tablets 500micrograms, 1.5mg liquid 0.25mg/5mL c propranolol2 (see section 2.4) c nadolol2 c metoprolol2 (see section 2.4) c timolol2

1 Pizotifen may cause drowsiness and weight gain due to its antihistamine and serotonin antagonistic effects. Doses should be given at night and titrated upwards from 500micrograms. 2 Beta blockers are effective but their contra-indications and drug interactions limit use.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 63 4.8 Antiepileptics

4.8.1 Control of epilepsy

• The aim of treatment is to achieve seizure freedom and cause the minimum of side effects to patients. Accurate diagnosis and definition of seizure type and syndrome are of paramount importance. This will influence the choice of drug used. • Monotherapy is preferred as combinations increase the risk of toxicity and interactions. Combination therapy may be necessary after the failure of alternatives given as monotherapy. • Careful dose adjustment is necessary, with titration upwards until seizures are controlled or signs of overdose start to emerge. • The newer antiepileptic drugs gabapentin, , levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin, within their licensed indications, are recommended for the management of epilepsy in people who have not benefited from treatment with the older antiepileptic drugs such as carbamazepine or sodium valproate, or for whom the older antiepileptic drugs are unsuitable. (NICE Technology Appraisal No 76 March 04 Epilepsy (adults) newer drugs) Please see full guidance: www.nice.org.uk • The newer antiepileptic drugs gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin (as an adjunctive therapy for partial seizures), within their licensed indications, are recommended for the management of epilepsy in children who have not benefited from treatment with the older antiepileptic drugs such as carbamazepine or sodium valproate, or for whom the older antiepileptic drugs are unsuitable. Vigabatrin is recommended as a first-line therapy for the management of infantile spasms (West’s Syndrome). (NICE Technology Appraisal No 79 April 04 Epilepsy (Children) newer drugs). Please see full guidance: www.nice.org.uk • Young children metabolise anti-epileptics more rapidly than adults so higher total daily doses per kilogram are required as are more frequent doses. Please refer to APLS Guidelines for treatment of status epilepticus in children. • Complex interactions, usually involving hepatic enzyme inhibition or induction may increase toxicity without enhancing the anti-convulsant effect. The potential for interaction makes plasma monitoring advisable in patients on combination therapy, particularly phenytoin and in most cases, carbamazepine. • Abrupt withdrawal of anti-epileptics should be avoided due to the risk of rebound seizures. In patients receiving a combination of anti-epileptics, only one should be withdrawn at a time. • Patients may drive following a seizure-free period of one year, or three years for attacks occurring solely whilst asleep. Patients should not drive during drug withdrawal or for 6 months afterwards. • The effectiveness of both combined and progestogen-only oral contraceptives may be considerably reduced by carbamazepine, oxcarbazepine, phenytoin, , primidone and topiramate. The Family Planning Association advice relating to women on long term enzyme-inducing drugs is that if they are unable to use an alternative method of contraception, they should be given an oral contraceptive containing ethinylestradiol 50micrograms or more. "Tricycling" with standard monophasic preparations (i.e. taking 3 or 4 packets without a break followed by a short tablet-free interval of 4 days) is another recommended option. • Women with epilepsy should be advised of the teratogenic potential of antiepileptic drugs. This is also important as a medico-legal safeguard. • In order to reduce the risk of neural tube defects, folic acid 5mg daily should be given to women with epilepsy before and during pregnancy. Vitamin K should be given to pregnant mothers before delivery as well as to the neonate if the mother has been taking carbamazepine, phenobarbital (phenobarbitone) or phenytoin. This will counter the risk of neonatal haemorrhagic disease increased by these agents.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 64 Antiepileptic agents c carbamazepine1 tablets 100mg, 200mg, 400mg (Tegretol) liquid 100mg/5mL suppositories 125mg, 250mg m/r tablets 200mg, 400mg (Tegretol Retard) chewtabs 100mg, 200mg c phenytoin2 capsules 25mg, 50mg, 100mg, 300mg (Epanutin) liquid 30mg/5mL, 90mg/5mL chewable tablets 50mg (Infatabs) c sodium valproate3 crushable tablets 100mg ec tablets 200mg, 500mg m/r tablets 200mg, 300mg, 500mg (Epilim Chrono) liquid 200mg/5mL injection 400mg/4mL d lamotrigine4 tablets 25mg, 50mg, 100mg, 200mg dispersible tablets 5mg, 25mg, 100mg d gabapentin capsules 100mg, 300mg, 400mg d topiramate5 tablets 25mg, 50mg, 100mg, 200mg sprinkle capsules 15mg d oxcarbazepine tablets 150mg, 300mg, 600mg S ethosuximide6 capsules 250mg (Emeside) liquid 250mg/5mL (Emeside or Zarontin) S levetiracetam tablets 250mg, 500mg, 1g infusion (as concentrate) 100mg/mL7 (Hospital Only) S phenobarbital8 (phenobarbitone) tablets 15mg, 30mg, 60mg liquid –see note injection 60mg/1mL, 200mg/1mL S primidone tablets 250mg, liquid 250mg in 5 ml (see appendix 2)

Benzodiazepines S clobazam9 tablets 10mg S clonazepam10 tablets 500micrograms, 2mg liquid-various strengths

Other drugs S vigabatrin11 tablets 500mg sugar free powder 500mg S tiagabine tablets 5mg,10mg,15mg S zonisamide12 capsules 25mg, 50mg, 100mg

Please see notes overleaf

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 65 Prescribing notes for antiepileptic agents 1 Carbamazepine is a drug of choice for simple and complex partial seizures and for tonic-clonic seizures secondary to a focal discharge. It is not suitable for absence or myoclonic seizures. Carbamazepine may cause blood, hepatic or skin disorders. Patients or carers should be taught to recognise the signs of these disorders and advised to seek urgent medical attention if they suffer symptoms such as fever, sore throat, rash, mouth ulcers, bruising or bleeding.

2 Phenytoin has a narrow therapeutic range, with "non-linear" kinetics. Hence a small increase in dose may cause a large rise in plasma level. Monitoring of plasma levels greatly assists dosage adjustment. Patients should be taught how to recognise blood or skin disorders. Bioavailability tests between tablets and capsules have not shown clinically relevant differences but there may be a pharmacokinetic basis for maintaining the same brand of phenytoin in some patients.

Please note the availability of two strengths of suspension and take care to avoid confusion. The strength should be specified on all prescriptions.

Care is needed if changing between dosage forms:

• Suspension and Infatabs contain phenytoin base, whereas capsules contain phenytoin sodium.

• Suspension containing phenytoin 90mg (either in 15mL or in 5mL depending on the strength used) is approximately equivalent to one capsule or tablet containing phenytoin sodium 100mg.

3 Sodium valproate has been associated with reports of hyperammonaemia especially in children who have partial defects in the urea cycle. It can also precipitate hyperammonaemia in patients with low carnitine levels. In these cases it is often associated with liver failure. While the SPC states that close monitoring of liver function is required, particularly at the start of therapy, it has been shown on several occasions that this is not helpful, and commonly goes against policy in Paediatric Neurology Units. It is, however, important that if a patient becomes drowsy or experiences nausea, vomiting or abdominal pain soon after starting valproate, medical help should be sought as soon as possible. Blood or hepatic disorders – patients or their carers should be told how to recognise signs of blood or liver disorders, and advised to seek immediate medical attention if symptoms develop (advice is given on PIL). Pancreatitis – patients or their carers should be told how to recognise signs of pancreatitis, and advised to seek immediate medical attention if symptoms such as abdominal pain, nausea and vomiting develop; discontinue sodium valproate if pancreatitis is diagnosed.

4 Lamotrigine may cause serious skin reactions including Stevens-Johnson Syndrome and toxic epidermal necrolysis, especially in children. Dose recommendations should be adhered to closely. The CSM advises that the risks are increased by concomitant use of sodium valproate or when initial lamotrigine doses are higher than recommended or where dose escalation is too rapid. Patients should be warned to contact their doctor immediately if rash or flu-like symptoms associated with hypersensitivity develop.

The CSM has advised prescribers to be alert for symptoms and signs suggestive of bone-marrow failure such as anaemia, bruising or infection. Aplastic anaemia, bone-marrow depression and pancytopenia have been associated rarely with lamotrigine. continued

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 66

5 Topiramate - The CSM has warned that serious eye reactions, including increased intraocular pressure have been reported in both adults and children, typically occurring within one month of the start of treatment. Any change in visual acuity or report of ocular pain should be investigated urgently. If raised intraocular pressure occurs:

• Specialist ophthalmological advice should be sought • Appropriate measures (medical and surgical) to reduce intraocular pressure should be taken • Topiramate should be stopped as rapidly as is clinically feasible

These measures generally result in rapid resolution of the eye symptoms. However, patients may require additional monitoring and alternative treatment to ensure their epilepsy is adequately controlled.

6 Ethosuximide may cause blood disorders. Patients or their carers should be told how to recognise signs of blood disorders, and advised to seek immediate medical attention if symptoms such as fever, sore throat, mouth ulcers, bruising or bleeding develop. New patients requiring capsules should be started on Emeside brand as Zarontin capsules have been discontinued. Syrup formulations are available for both brands. As there are no comparative studies between the brands, take care if if becomes necessary to switch between brands and monitor the patient closely.

7 Levetiracetam injection is included for hospital use only in patients who are nil by mouth or vomiting. For dilution before use.

8 Phenobarbital may be difficult to withdraw due to rebound seizures. Tolerance makes plasma level monitoring less useful than with some other agents. Various strengths of liquid preparation are available. The strength should always be written on the prescription to avoid confusion. The BP formulation is unsuitable for children due to the alcohol content.

9 Clobazam is not prescribable on the NHS except in epilepsy. Prescriptions should be endorsed “SLS”.

10 Clonazepam liquid is extemporaneously prepared and may be available in various strengths (named patient).

11 Vigabatrin is associated with visual field defects which may become apparent from one month to several years after starting therapy. In most cases the defects have persisted despite discontinuation. Visual field testing should be carried out before initiation and at 6 monthly intervals. Patients should be warned to report any new visual symptoms. For this reason vigabatrin is regarded as the absolute last line after all other treatment options.

11 Zonisamide is for adjunctive treatment of partial seizures in adults. Reserved for patients who have failed on a combination of anti-convulsants.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 67 4.8.2 Drugs used in status epilepticus

Major status epilepticus should be treated initially with intravenous lorazepam. Diazepam may also be used intravenously but lorazepam has a longer duration of antiepileptic action. Both lorazepam and diazepam have a risk of respiratory depression. In situations where facilities for resuscitation are not immediately available, small doses can be given intravenously or the drug can be administered as a rectal solution. Absorption from intramuscular injection or from suppositories is too slow for treatment of status epilepticus. The risk of thrombophlebitis from intravenous diazepam is minimised by using Diazemuls emulsion. c diazepam1 rectal tubes 2.5mg, 5mg, 10mg, 20mg injection 10mg/2mL injection 10mg/2mL (Diazemuls) H clonazepam1 injection 1mg/1mL H lorazepam injection 4mg/mL H phenytoin sodium injection 250mg/5mL H paraldehyde2 injection 5mL

1 Lorazepam, diazepam or clonazepam administration by intravenous infusion is potentially hazardous and requires constant observation in specialist centres with intensive care facilities. 2 Paraldehyde is no longer recommended for intravenous use. It may be given by deep intramuscular injection or as a 10% enema in physiological saline. It may also be used rectally, mixed with an equal quantity of olive oil or arachis oil. (Note - arachis oil should not be used in patients with peanut allergy).

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 68 4.9 Drugs Used in Parkinsonism and Related Disorders

4.9.1 Dopaminergic drugs used in Parkinsonism Treatment should be individual and if symptoms are not causing lifestyle problems, drug treatment should be withheld for as long as possible. In the younger patient, treatment should be started with a dopamine agonist whilst in the elderly, levodopa is the first line. Please see NICE Clinical Guidance no 35 June 2006: Parkinson's disease: diagnosis and management in primary and secondary care www.nice.org.uk

SUDDEN ONSET OF SLEEP. Excessive daytime sleepiness can occur with co- careldopa, co-beneldopa, and the dopamine receptor agonists. Sudden onset of sleep has been observed with dopamine agonists such as pramipexole and ropinirole. Patients starting treatment with any dopamine agonist should be warned of the possibility of excessive daytime sleepiness. c co-beneldopa (levodopa capsules 50mg/12.5mg, 100mg/25mg, 200mg/50mg with benserazide) (Madopar) dispersible tablets 50mg/12.5mg, 100mg/25mg (Madopar dispersible) m/r capsules 100mg/25mg (Madopar CR) c co-careldopa (levodopa tablets 50mg/12.5mg (Sinemet 62.5) with carbidopa) tablets 100mg/10mg (Sinemet-110) tablets 100mg/25mg (Sinemet-Plus) tablets 250mg/25mg (Sinemet-275) m/r tablets 100mg/25mg (Half Sinemet CR) m/r tablets 200mg/50mg (Sinemet CR) c/ S levodopa, carbidopa & North Bro Taf 1st Line entacapone (Stalevo) 1 Cardiff and Vale Specialist Initiated tablets 50mg / 12.5mg / 200mg tablets 100mg / 25mg / 200mg tablets 150mg / 37.5mg / 200mg S amantadine capsules 100mg liquid 50mg/5mL S apomorphine2 injection 10mg/mL (2mL, 5mL,3mL pen injection) S entacapone tablets 200mg S pergolide4 For continuation in existing patients only: tablets 50micrograms, 250micrograms, 1mg S pramipexole tablets 88micrograms, 180micrograms, 700micrograms S rasagiline tablets 1mg S ropinirole tablets 250micrograms, 1mg, 2mg, 5mg S rotigotine5 patches 2mg, 4mg, 6mg or 8mg in 24 hours S selegiline3 tablets 5mg, liquid 10mg/5mL

CSM ADVICE. The ergot-derived dopamine-receptor agonists, bromocriptine, cabergoline, lisuride, and pergolide have been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions. The CSM has advised that before starting treatment with these ergot derivatives investigations such as measurement of erythrocyte sedimentation rate, of urea and electrolytes, and a chest X-ray may be appropriate. If long-term treatment is expected, then lung-function tests may also be helpful. Patients should be monitored for progressive fibrotic disorders.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 69

1 Stalevo: Only 1 tablet of Stalevo to be taken for each dose. For patients receiving standard-release co-careldopa or co-beneldopa alone, initiate Stalevo at a dose that provides a similar (or slightly lower) amount of levodopa. For patients with dyskinesia or receiving more than 800 mg levodopa daily, introduce entacapone before transferring to Stalevo (levodopa dose may need to be reduced by 10–30% initially). For patients receiving entacapone and standard-release co-careldopa or co-beneldopa, initiate Stalevo at a dose that provides a similar (or slightly higher) amount of levodopa. 2 Apomorphine – see Shared Care Protocol No 22. 3 Selegiline– restricted to use in existing patients only. 4 Pergolide – see CSM warning above. Restricted to continuation treatment of patients already stabilised on this medication. 5 Rotigotine Patches – For Parkinson’s patients with swallowing difficulty.

Bromocriptine is no longer included in the Formulary (MTAC advice 15/6/06). Cabergoline is retained in the formulary for use in conditions other than Parkinson’s disease.

4.9.2 Antimuscarinic drugs used in Parkinsonism

Avoid antimuscarinics in the elderly due to the high incidence of side effects.

S trihexyphenidyl hydrochloride tablets 2mg, 5mg (benzhexol hydrochloride) liquid 5mg/5mL S (benztropine) tablets 2mg injection 2mg/2mL S procyclidine1 tablets 5mg liquid 5mg/5mL S orphenadrine tablets 50mg liquid 25mg/5mL

1 Procyclidine is also licensed for drug-induced extrapyramidal side effects and dystonic reactions but not for tardive dyskinesias. Suitable for use in general practice for these indications.

4.9.3 Drugs used in essential tremor, chorea, tics & related disorders

S propranolol see section 2.4 S tetrabenazine tablets 25mg S riluzole1 tablets 50mg

Torsion dystonias and other involuntary movements H botulinum A toxin injection 100unit, 500unit H botulinum B toxin2 injection 5000units/ml (0.5mL,1mL,2mL) (NeuroBloc)

1 NICE guidance (riluzole). NICE has recommended riluzole to treat individuals with the amyotrophic lateral sclerosis (ALS) form of motor neurone disease (MND). Treatment should be initiated by a specialist in MND but it can then be supervised under a shared-care arrangement (SCP) involving the general practitioner. (Please see full guidance: www.nice.org.uk (Guidance no. 20, January 2001) and the former Bro Taf Health Authority SCP no. 27.) 2 Botulinum B toxin is reserved for patients who have failed to respond, or who are no longer responding to, type A toxin. Please note: The doses of types A and B are radically different and great care should be taken to avoid errors.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 70 4.10 Drugs Used in Substance Dependence

Information and advice on the treatment of substance dependence may be obtained from:

The Community Drug & Alcohol Team Llwyn-yr-Eos Clinic Main Rd, Church Village Cardiff CF38 1RN Tel.: 01443 217026

The Community Addictions Unit House 56 Cardiff Royal Infirmary Newport Rd Cardiff CF24 0SZ Tel.: 029 2046 1742

Patients who require drug dependency counselling and support may be referred to local agencies. These are registered charities which provide a free and confidential service, offering advice, information and support to drug users, ex-users, their families and friends.

INROADS Cardiff and the Vale Street Drugs Project 43 Lower Cathedral Rd Cardiff CF11 6LW Tel.: 029 2040 7407

INROADS (Barry Office) 10 High St Barry CF62 7DZ Tel.: 01446 450005

Drug Aid MIDAS 2nd Floor, Oldway House Castle St. Merthyr Tydfil CF47 8UX Tel.: 01685 721991

Treatment & Education Drug Service (“Ted’s”) Engine House, Depot Rd. Aberdare CF44 8DL Tel.: 01685 880090

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 71 Substance dependence (cont.)

Drug misuse: psychosocial interventions. Please see NICE CG51 July 2007.

Alcohol dependence

S acamprosate tablets 333mg S disulfiram tablets 200mg

Cigarette smoking See shared care protocol no. 39 c nicotine replacement products1 See BNF/MIMS for products available d amfebutamone2 () tablets 150mg (Zyban) d varenicline3 tablets 500micrograms, 1mg (Champix) (Please see note 3)

Opioid dependence

Drug misuse: opioid detoxification. Please see NICE CG52 July 2007.

S methadone4 liquid 1mg/1mL S buprenorphine4,5 sublingual tablets 400micrograms, 2mg, 8mg (Subutex) S lofexidine tablets 200micrograms S naltrexone6 tablets 50mg

Notes on drugs used in substance dependence 1 Nicotine replacement products have all been made available following NICE guidance TA39 Smoking cessation - bupropion and nicotine replacement therapy March 2002. Please also refer to local policies. A smoking cessation counsellor should be involved whenever possible. Therapy is chosen according to the smoker’s likely compliance, availability of counselling and support, previous experience of smoking-cessation aids, contra-indications and adverse effects of the products, and personal preference of the smoker. A wide range of products therefore needs to be available. 2 Amfebutamone is approved as an adjunct to smoking cessation - use subject to protocol. It is associated with a dose-related risk of seizures. There is also an increased risk of seizures occurring in the presence of factors which lower the seizure threshold. The CSM have issued a safety update reminding prescribers that amfebutamone (bupropion) is contra-indicated in patients with previous or current seizure disorder. A change to the previous dosing schedule has also been published and prescribers are advised to consult the current SPC to ensure that this is followed. Further information on risk factors for seizures, including potential drug interactions can be obtained from the CSM website. 3 Varenicline for smoking cessation - see NICE TA123 July 2007. Varenicline should normally be prescribed only as part of a programme of behavioural support. In Cardiff and the Vale restricted to Primary Care use. In North Bro Taf it may also be used in hospital-based smoking cessation clinics. 4 Methadone and buprenorphine in the management of opioid dependence. NICE TA114 January 07 5 Subutex is restricted to specialist initiation by the Community Drug Clinic in line with local protocols. Use may include GPs with appropriate training covered under Local Development Scheme for GPs. 6 Naltrexone: See NICE TA115 Jan 2007 Management of opioid dependence. Jan 2007

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 72

4.11 Drugs for Dementia

H donepezil tablets 5mg, 10mg (Aricept) H rivastigmine capsules 1.5mg, 3mg, 4.5mg, 6mg liquid 2mg/ml (Exelon) H galantamine tablets 8mg,12mg (4mg discontinued 7/06) capsules m/r 8mg, 16mg, 24mg liquid 4mg/ml (Reminyl)

Please see NICE TA111 November 2006 (Amended September 2007):

Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). (This information replaces Guidance No 19, Treatment of Alzheimer’s Disease, January 2001)

Please also see NICE CG42 December 2006:

Dementia: supporting people with dementia and their carers in health and social care.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 73 CHAPTER 5 INFECTIONS

This chapter indicates the approved by the Bro Taf Drug & Therapeutics Committee. Please refer to your local microbiology department for prescribing policies and advice. This chapter relates to the systemic use of antibiotics. For local/topical preparations, see: Chapter 7, section 7.2 for treatment of vaginal and vulval conditions; Chapter 11 for eye conditions; Chapter 12 for ear, nose, and oropharynx conditions; and Chapter 13 for skin conditions. Requests for new antibiotics to be included in the formulary should be supported by written guidelines describing their place in therapy. As local guidelines vary, most antibiotics have not been allocated a prescribing category.

5.1 Antibacterial Drugs

5.1.1 Penicillins

5.1.1.1 Benzylpenicillin and phenoxymethylpenicillin

benzylpenicillin injection 600mg, 1.2g (Penicillin G) phenoxymethylpenicillin tablets 250mg (Penicillin V) suspension 125mg/5mL, 250mg/5mL procaine penicillin with injection 1.8g/360mg (Bicillin) See Appendix 2 benzylpenicillin

5.1.1.2 Penicillinase-resistant penicillins

flucloxacillin capsules 250mg, 500mg suspension 125mg/5mL, 250mg/5mL injection 250mg, 500mg, 1g H temocillin1 injection 1g (North Bro Taf Only)

1. Temocillin is available in North Bro Taf only for hospital-only use in cystic fibrosis patients. Temocillin should be initiated on the recommendation of a microbiologist or cystic fibrosis consultant. Awaiting HCW approval for use in Cardiff and the Vale.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 74 5.1.1.3 Broad-spectrum penicillins

amoxicillin capsules 250mg, 500mg (amoxycillin) suspension 125mg/5mL, 250mg/5mL sachet 3g (SF) injection 250mg, 500mg, 1g co-amoxiclav1 tablets 375mg, 625mg (Augmentin) tablets 375mg dispersible suspension 125mg/31mg in 5mL suspension 250mg/62mg in 5mL Augmentin Duo 400/57mg in 5mL injection 600mg, 1.2g co-fluampicil capsules 250mg/250mg (Magnapen) suspension 125mg/125mg/5mL injection 250mg/250mg

1 Co-amoxiclav consists of amoxicillin with the beta-lactamase inhibitor . Doses are expressed as the amoxicillin content. Cholestatic Jaundice. The CSM has advised that cholestatic jaundice has been identified as an adverse reaction occurring either during, or shortly after, the use of co-amoxiclav. An epidemiological study has shown that the risk of acute liver toxicity was about 6 times greater with co-amoxiclav than with amoxicillin. Cholestatic jaundice is more common in patients above the age of 65 years and in males; these reactions have only rarely been reported in children. Jaundice is usually self-limiting and very rarely fatal. The duration of treatment should be appropriate to the indication and should not usually exceed 14 days.

Ampicillin has been deleted following microbiologist advice.

5.1.1.4 Antipseudomonal penicillins

H piperacillin with tazobactam injection 250mg/2g (Tazocin) injection 500mg/4g

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 75 5.1.2 Cephalosporins, cephamycins and other beta-lactam antibiotics

Cephalosporins and cephamycins cefradine1 capsules 250mg, 500mg (cephradine) suspension 250mg/5mL injection 500mg, 1g cefalexin1 tablets 250mg, 500mg (cephalexin) suspension 125mg/5mL, 250mg/5mL, 500mg/5mL cefaclor m/r tablets 375mg suspension 125mg/5mL, 250mg/5mL capsules 250mg, 500mg cefixime tablets 200mg suspension 100mg/5mL injection 250mg, 750mg cefotaxime injection 500mg, 1g, 2g ceftazidime injection 250mg, 500mg, 1g, 2g, 3g ceftriaxone injection 250mg,1g, 2g

1 (cephradine) and (cephalexin): These may not both be stocked. Please check local availability.

Other beta-lactam antibiotics H ertapenem1 infusion 1g (powder) H imipenem injection 500mg/500mg H meropenem injection/infusion 250mg, 500mg, 1g

1. Ertapenem: Use based on sensitivity data. Consultant Microbiologist recommendation required.

5.1.3 Tetracyclines

oxytetracycline1 tablets 250mg doxycycline capsules 50mg, 100mg minocycline capsules/tablets 50mg, 100mg m/r capsules 100mg tetracycline1,2 injection 500mg demeclocycline3 capsules 150mg

1 Prescriptions for oral TETRACYCLINE will be substituted with OXYTETRACYCLINE. 2 Tetracycline injection is reserved for intracavital use (named patient only). 3 Demeclocycline is reserved for SIADH (see section 6.5.2).

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H gentamicin injection 20mg/2mL, 80mg/2mL intrathecal injection 5mg/5mL neomycin1 tablets 500mg H tobramycin injection 20mg/2mL, 80mg/2mL H Palacos-R with gentamicin2 bone cement H Collatamp EG2 gentamicin-impregnanted collagen sponge H Copal2 bone cement with clindamycin and gentamicin H Amikacin injection 100mg/2mL, 500mg/2mL

1 Neomycin is reserved for hepatic encephalopathy/bowel sterilisation prior to surgery. 2 Theatres only.

5.1.5 Macrolides

erythromycin ec tablets 250mg suspension (as ethyl succinate) 125mg/5mL, 250mg/5mL infusion (as lactobionate) 1g clarithromycin tablets 250mg, 500mg granules 250mg per sachet suspension 125mg/5mL, 250mg/5mL infusion 500mg azithromycin capsules 250mg suspension 200mg/5mL

5.1.6 Clindamycin

clindamycin capsules 75mg, 150mg suspension 75mg/5mL injection 300mg/2mL, 600mg/4mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 77 5.1.7 Some other antibiotics

chloramphenicol capsules 250mg injection 1g sodium fusidate1 tablets 250mg suspension (as fusidic acid) 250mg/5mL injection 500mg S linezolid2,3 tablets 600mg suspension 100mg/5mL intravenous infusion 600mg in 300mL H quinupristin with dalfopristin4 infusion 150mg/350mg (Synercid)4 H daptomycin5 intravenous infusion (powder for reconstitution) 350mg vial H vancomycin capsules 125mg, 250mg injection 250mg, 500mg, 1g H teicoplanin injection 200mg, 400mg colistin tablets 1.5 million units syrup 250,000units/5mL injection 500,000units, 1 million units

1 Note: Fusidic acid is incompletely absorbed and doses recommended for suspension are proportionately higher than those for sodium fusidate tablets. 2 Linezolid is restricted to specialist initiation on the advice of a microbiologist. It is a reversible, non-selective monoamine oxidase inhibitor, so dietary restrictions and warnings on interactions apply. Please see BNF/Summary of Product Characteristics. 3 Linezolid CSM Advice: Haematopoietic disorders (including thrombocytopenia, anaemia, leucopenia, and pancytopenia) have been reported in patients receiving linezolid. It is recommended that full blood counts are monitored weekly. Close monitoring is recommended in patients who: • receive treatment for more than 10-14 days; • have pre-existing myelosuppression; • are receiving drugs that may have adverse effects on haemoglobin, blood counts, or platelet function; • have severe renal impairment. If significant myelosuppression occurs, treatment should be stopped unless it is considered essential, in which case intensive monitoring of blood counts and appropriate management should be implemented. 4 Synercid is available only on the recommendation of a microbiologist. 5 Daptomycin is reserved for second line hospital use in patients with complicated soft tissue infections caused by susceptible organisms including MRSA. To be used if existing agents (vancomycin, teicoplanin, linezolid, Synercid) are contra- indicated, have caused severe side effects or where the patient has failed to respond. Available only following consultant microbiologist recommendation.

5.1.8 Sulphonamides and trimethoprim

trimethoprim tablets 100mg, 200mg suspension (SF) 50mg/5mL injection 20mg/1mL co-trimoxazole1 dispersible tablets 480mg suspension 240mg/5mL, 480mg/5mL tablets 480mg, 960mg injection 480mg/5mL sulfadiazine tablets 500mg (sulphadiazine) injection 250mg/mL

Please see note overleaf

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1 Co-trimoxazole - CSM recommendations. Co-trimoxazole should be limited to the role of drug of choice in Pneumocystis carinii pneumonia; it is also indicated for toxoplasmosis and nocardiasis. It should now only be considered for use in acute exacerbations of chronic bronchitis and infections of the urinary tract when there is good bacteriological evidence of sensitivity to co-trimoxazole and good reason to prefer this combination to a single antibiotic; similarly it should only be used in acute otitis media in children when there is good reason to prefer it.

5.1.9 Antituberculous drugs Please see NICE Clinical Guidance No 33 March 2006: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. www.nice.org.uk

capsules 150mg, 300mg liquid 100mg/5mL infusions 300mg, 600mg isoniazid tablets 50mg, 100mg liquid 50mg/5mL injection 50mg/2mL See Appendix 2 rifampicin with isoniazid tablets 150mg/100mg, (Rimactazid has (Rifinah), 300mg/150mg been withdrawn) rifampicin with isoniazid and tablets 120mg/50mg/300mg pyrazinamide (Rifater) pyrazinamide tablets 500mg ethambutol tablets 100mg, 400mg streptomycin injection 1g

5.1.10 Antileprotic drugs

dapsone tablets 50mg, 100mg clofazimine capsules 100mg

5.1.11 Metronidazole and tinidazole

metronidazole tablets 200mg, 400mg suspension 200mg/5mL suppositories 500mg, 1g infusion 100mg/20mL, 500mg/100mL

5.1.12 Quinolones1

ciprofloxacin tablets 100mg, 250mg, 500mg, 750mg suspension 250mg/5mL infusions 100mg/50mL, 200mg/100mL, 400mg/200mL ofloxacin2 tablets 200mg, 400mg H levofloxacin3 tablets 250mg, 500mg infusion 500mg/100mL H moxifloxacin4 tablets 400mg

Please see notes overleaf

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1 Quinolones - CSM advice (tendon damage). Tendon damage (including rupture) has been reported rarely in patients receiving quinolones. Tendon rupture may occur within 48 hours of starting treatment. The CSM has reminded that: • quinolones are contra-indicated in patients with a history of tendon disorders related to quinolone use; • elderly patients are more prone to tendinitis; • the risk of tendon rupture is increased by the concomitant use of corticosteroids; • if tendonitis is suspected, the quinolone should be discontinued immediately. 2 Ofloxacin is reserved for genitourinary use. 3 Levofloxacin use is subject to protocol. 4 Moxifloxacin is restricted to hospital only use in line with local guidelines for community acquired pneumonia.

5.1.13 Urinary-tract infections1

nitrofurantoin capsules 50mg, 100mg suspension (SF) 25mg/5mL See Appendix 2

1 Alternative agents for urinary-tract infections are listed in other BNF categories.

5.2 Antifungal Drugs

H amphotericin infusion 50mg (Fungizone) infusion 50mg (Ambisome) 5mg/mL (Abelcet) H caspofungin1 infusion 50mg, 70mg fluconazole capsules 50mg, 150mg, 200mg suspension 50mg/5mL, 200mg/5mL infusions 50mg/25mL, 200mg/100mL H flucytosine injection 2.5g/250mL griseofulvin tablets 125mg, 500mg itraconazole2 capsules 100mg suspension 10mg/mL ketoconazole tablets 200mg nystatin tablets 500,000 units suspension 100,000 units/mL terbinafine tablets 250mg voriconazole tablets 50mg, 200mg powder for oral suspension 200mg/5ml powder for solution for infusion 200mg

1 Caspofungin is reserved for the treatment of aspergillosis in patients who have not responded adequately, or who are intolerant of amphotericin or itraconazole. A prescribing protocol is currently under development. 2 Itraconazole CSM advice (heart failure): Following rare reports of heart failure, the CSM has advised caution when prescribing itraconazole to patients at high risk of heart failure. Those at risk include: • patients receiving high doses and longer treatment courses; • older patients and those with cardiac disease; • patients receiving treatment with negative inotropic drugs e.g. calcium channel blockers.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 80 5.3 Antiviral Drugs

5.3.1 Human immunodeficiency virus

Spontaneous reporting has identified a number of important adverse reactions to anti- HIV drugs. In addition many of the drugs have the potential for significant drug interactions. Prescribers should ensure that they are aware of the current advice and recommendations relating to these issues. Adverse drug reactions to HIV drugs should be reported to the CSM. Patients obtain all supplies of medication through the HIV clinic

Nucleoside reverse transcriptase inhibitors H abacavir tablets 300mg solution 20mg/mL H didanosine tablets 25mg capsules e/c 125mg, 200mg, 250mg, 400mg H emtricitabine1 capsules 200mg oral solution 10ml/mL H lamivudine2 tablets 100mg1,150mg suspension 10mg/mL H stavudine capsules 20mg, 30mg, 40mg solution 1mg/mL H tenofovir tablets 245mg H tenofovir disoproxil with tablets 245mg/200mg emtricitabine (Truvada)3 H (AZT) capsules 100mg, 250mg syrup 50mg/5mL

1 Emtricitabine: See AWMSG appraisal 0407 June 2007. Available as an option for the treatment of HIV-1 infected adults in combination with other antiretroviral agents for use in treatment-naïve patients in line with current BHIVA guidelines. It should only be prescribed by HIV specialists. 2 Lamivudine 100mg tablets are licensed for chronic hepatitis B infection. See 5.3.3. 3 Emtricitabine with tenofovir DF (Truvada): See AWMSG appraisal 0507 June 2007 Recommendation as above.

Protease inhibitors H amprenavir1 capsules 50mg, 150mg oral solution 15mg/mL H darunavir2 tablets 300mg H indinavir capsules 200mg, 400mg H lopinavir with ritonavir3 capsules 133.3mg/33.3mg (Kaletra) oral solution 400mg/100mg in 5mL H tablets 250mg powder 50mg/g H ritonavir solution 400mg/5mL capsules 100mg H saquinavir4 capsules 200mg (Invirase) tablets 500mg H tipranavir5 tablets 250mg

1 Amprenavir oral solution has lower bioavailability than that of amprenavir capsules: the two formulations are not interchangeable on a milligram for milligram basis. 2 Darunavir: See Darunavir : AWMSG approval August 2007 3 Kaletra oral solution 5mL ≡ 3 capsules. Where appropriate, capsules may be used instead of oral solution. 4 Saquinavir: The Fortovase brand of 200mg capsules has been discontinued. 5 Tipranavir: See Tipranavir : AWMSG approval August 2007.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 81

Non-nucleoside reverse transcriptase inhibitors H efavirenz capsules 50mg, 200mg tablets 600mg oral solution 30mg/mL H nevirapine tablets 200mg suspension 50mg/5mL

Other antiretrovirals H enfuvirtide (Fuzeon)1 Injection powder for reconstitution 90mg/mL

1. Enfuvirtide is available for use in line with AWMSG guidance: For use by physicians in secondary care specialising in the management of patients with HIV. For use accordance with criteria defined in the product's SPC and the UK British HIV Association (BHIVA) guidelines.

The AWMSG has requested prescribers also note the following statement: "AWMSG has concerns that instructions in the enfuvirtide Patient Product Information Sheet to “return vials to the pharmacy” may be misinterpreted by patients. This could result in them attempting to return a wider range of clinical waste to the pharmacy. Pharmacists, doctors and nurses may need to instruct patients in the correct disposal of their clinical waste".

Hypersensitivity reactions have been reported. If any signs or symptoms of systemic hypersensitivity develop, withdraw treatment immediately and do not re-challenge. Patients should be told how to recognise signs of hypersensitivity. In such an event they should discontinue enfuvirtide and seek immediate medical advice.

5.3.2 Herpesvirus Infections

5.3.2.1 Herpes simplex and varicella-zoster dispersible tablets and tablets 200mg, 400mg, 800mg suspension (SF) 200mg/5mL infusions 250mg, 500mg famciclovir tablets 125mg, 250mg, 500mg tablets 500mg

5.3.2.2 Cytomegalovirus (CMV) H ganciclovir capsules 250mg infusion 500mg H foscarnet infusion 6g in 250mL H valganciclovir1 tablets 450mg

1 Valganciclovir, a pro-drug of ganciclovir, is only licensed for induction and maintenance treatment of cytomegalovirus retinitis in AIDS patients.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 82

5.3.3 Viral Hepatitis

Chronic Hepatitis B Please see NICE TA96 No 96 - Adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B. February 2006

H adefovir dipivoxil1 tablets 10mg H lamivudine see section 5.3.1 H peginterferon alfa see below

Chronic Hepatitis C Please see NICE TA106 Peginterferon alfa and ribavirin for the treatment of mild hepatitis C (August 2006) and TA75 Interferon alfa and ribavirin for the treatment of chronic hepatitis C ( January 2004) - part review of existing guidance no.14

H adefovir dipivoxil1 tablets 10mg H ribavirin inhalation solution 6g (tribavirin) capsules 200mg H peginterferon alfa peginterferon alfa 2a pre-filled syringe 135micrograms in 0.5ml 180 micrograms in 0.5ml peginterferon alfa 2b injection 50,80,100,120,150micrograms

5.3.4 Influenza d zanamivir1 (Relenza) powder for inhalation (5mg per blister) d oseltamivir1 (Tamiflu) capsules 75mg

1 Use in line with NICE Technology Appraisal No 67(Sept 03) Flu prevention – amantadine and oseltamavir:

NICE has recommended that the drugs described here are not a substitute for vaccination, which remains the most effective way of preventing illness from influenza. When influenza A or influenza B is circulating in the community: • oseltamivir is recommended for post-exposure prophylaxis in at-risk adults and adolescents over 13 years who are not effectively protected by influenza vaccine and who can commence oseltamivir within 48 hours of close contact with someone suffering from influenza-like illness; prophylaxis is also recommended for residents in care establishments (regardless of influenza vaccination) who can commence oseltamivir within 48 hours if influenza-like illness is present in the establishment; • oseltamivir and zanamivir are recommended (in accordance with UK licensing) to treat at-risk adults who can start treatment within 48 hours of the onset of symptoms; oseltamivir is recommended for at-risk children who can start treatment within 48 hours of the onset of symptoms; • amantadine is not recommended for post-exposure prophylaxis, seasonal prophylaxis, or treatment of influenza; • oseltamivir and zanamivir are not recommended for seasonal prophylaxis against influenza; • oseltamivir or zanamivir are not recommended for the post-exposure prophylaxis, or treatment of otherwise healthy individuals with influenza

NICE Techology Appraisal no 58 Feb 2003, Flu treatment – zanamavir (review) amantadine and oseltamavir:

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1. Guidance This guidance has been prepared in the expectation that vaccination against influenza is undertaken in accordance with national guidelines. Vaccination is the most effective way of preventing illness from influenza, and the drugs described in this guidance are not a substitute for vaccination. This guidance does not cover the circumstances of a pandemic, impending pandemic or a widespread epidemic of a new strain of influenza to which there is little or no community resistance.

This guidance pertains only to circumstances where it is known that either influenza A or influenza B is circulating in the community (see 1.6). 1.1 Zanamivir and oseltamivir are not recommended for the treatment of influenza in children or adults unless they are considered to be ‘at risk’. 1.2 At-risk adults and children are defined for the purpose of this guidance as those who are in at least one of the following groups. People who: • have chronic respiratory disease (including asthma and chronic obstructive pulmonary disease) • have significant cardiovascular disease (excluding people with hypertension only) • have chronic renal disease • are immunocompromised • have diabetes mellitus • are aged 65 years or older.

1.3 Amantadine is not recommended for the treatment of influenza. 1.4 Within their licensed indications, zanamivir and oseltamivir are recommended for the treatment of at-risk adults who present with influenza-like illness (ILI) and who can start therapy within 48 hours of the onset of symptoms. 1.5 Within its licensed indications, oseltamivir is recommended for the treatment of at-risk children who present with ILI andwho can start therapy within 48 hours of the onset of symptoms. 1.6 Community-based virological surveillance schemes should be used to indicate when influenza virus is circulating in the community. Community-based virological surveillance schemes, such as those organised by the Royal College of General Practitioners and the Public Health Laboratory Service, should be used to indicate when influenza virus is circulating in the community. Such schemes should ensure that the onset of the circulation of influenza virus (A or B) within a defined area is identified as rapidly as possible.

Please see full guidance. www.nice.org.uk

5.3.5 Respiratory syncytial virus

H ribavirin inhalation solution 6g (tribavirin) capsules 200mg H palivizumab injection 50mg, 100mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 84 5.4 Antiprotozoal Drugs

5.4.1 Antimalarials

chloroquine sulphate tablets 200mg (=150mg base) (Nivaquine) suspension (=50mg base/5mL) injection (=200mg base/5mL) proguanil tablets 100mg primaquine1 tablets 7.5mg pyrimethamine tablets 25mg quinine sulphate tablets 200mg, 300mg quinine dihydrochloride infusion 600mg/2mL mefloquine tablets 250mg

1 Primaquine is named patient only.

5.4.2 Amoebicides

metronidazole See 5.1.11 for preparations

5.4.8 Drugs for pneumocystis pneumonia

atovaquone suspension 750mg/5mL H co-trimoxazole See 5.1.8 for preparations H pentamidine injection 300mg nebuliser solution 300mg

5.5 Anthelmintics

5.5.1 Drugs for threadworms

mebendazole chewable tablets 100mg suspension 100mg/5mL piperazine liquid 750mg/5mL piperazine with sennosides sachet 4g/15.3mg (Pripsen)

5.5.3 Drugs for tapeworm infections

H niclosamide1 tablets 500mg See Appendix 2

Hydatid disease H albendazole1 chewable tablets 400mg See Appendix 2

1 Niclosamide and are available only on a “named patient” basis.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 85 CHAPTER 6 ENDOCRINE SYSTEM

6.1 Drugs Used in Diabetes

6.1.1 Insulins When prescribing insulins, the word ‘unit’ should not be abbreviated. Supplies of hypodermic equipment and injection devices (‘pens’), are available in clinic from the Diabetic Specialist Nurses, who will advise on the most appropriate method of administration for each patient. Pre-loaded pens may be necessary for some patients but these are expensive compared with other options. For the choice of devices available please contact your local Diabetic Specialist Nurse.

The National Institute for Health and Clinical Excellence recommends that structured patient education is made available to all people with diabetes at the time of initial diagnosis and then as required on an ongoing basis, based on a formal, regular assessment of need. Please see NICE Guidance on the use of patient-education models:Technology Appraisal No 60 April 03 (under review) Other NICE Guidance on insulins includes:

Diagnosis and management of type 1 diabetes in children and young people; and in adults: Clinical Guideline No 15, July 04 Clinical and cost-effectiveness of insulin pump therapy: Technology Appraisal No 57 Feb 03 (under review).

6.1.1.1 Short-acting insulins

Insulin Type Brand Vials Cartridges Cartridges Preloaded 10mL 5 x 1.5mL 5 x 3mL pens 5 x 3mL soluble insulin Human sequence S Human 9 x x x Actrapid S Humulin S 9 x x 9 S Insuman x x 9 9 Rapid Highly purified S Pork 9 x x x animal Actrapid S Hypurin 9 9 x x porcine neutral Recombinant S Insulin human insulin Lispro 9 x 9 x analogue (Humalog)1 S Insulin Aspart 9 x 9 9 (NovoRapid) S Insulin Glulisine 9 x 9 9 (Apidra)

1 The CSM has warned of prescribing and dispensing errors due to confusion between Humalog products, particularly Humalog and Humalog Mix 25. The first is a fast acting analogue of human insulin; the second is biphasic insulin. In most of the 7 cases reported since April 1999, hospital admission was necessary. Although the packaging has been redesigned to reduce this risk, awareness of this issue is important.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 86 6.1.1.2 Intermediate- and long-acting insulins

Insulin Type Brand Vials Cartridges Cartridges Preloaded 10mL 5 x 1.5mL 5 x 3mL pens 5 x 3mL Isophane insulin Human S Human 9 x 9 9 sequence Insulatard ge S Humulin I 9 x 9 9 S Insuman 9 x 92 x Basal (5ml)

Highly purified S Pork 9 x x x animal Insulatard S Hypurin 9 x 9 x porcine isophane Insulin detemir1 S Levemir x x 9 9 Insulin S Lantus 9 x 92 9 glargine,2,3

1 Insulin detemir 3ml cartridges are compatible with the Novopen. Also prefilled disposable FlexPen available. 2 Insulin glargine cartridges and Insuman Basal 3mL cartridges are compatible with the Optipen Pro. Patients on insulin glargine may use the Lantus Opticlick device if they have poor eyesight. 3 Insulin glargine, a recombinant human insulin analogue, should be prescribed in line with NICE Guidance No 53, issued December 02: Insulin glargine is recommended as a treatment option for people with type 1 diabetes. It is not recommended for routine use for people with type 2 diabetes who require insulin therapy. Insulin glargine treatment should be considered only for those people with type 2 diabetes who require insulin therapy and who fall into one of the following categories. • Those who require assistance from a carer or healthcare professional to administer their insulin injections. • Those whose lifestyle is significantly restricted by recurrent symptomatic hypoglycaemic episodes. • Those who would otherwise need twice-daily basal insulin injections in combination with oral antidiabetic drugs.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 87 Biphasic Insulins Insulin Brand Vials Cartridges Cartridges Preloaded Type 10mL 5 x 1.5mL 5 x 3mL pens 5 x 3mL Biphasic isophane insulin Human sequence S Human Mixtard 10 x x 9 x S Human Mixtard 20 x x 9 x S Human Mixtard 30 9 x 9 9 S Human Mixtard 40 x x 9 x S Human Mixtard 50 9 x 9 x S Humulin M3 9 x 9 9 S Insuman Comb 25 5ml x 91 9 S Insuman Comb 50 x x 91 9 Highly S Pork Mixtard 30 9 x x x purified animal Biphasic S Novomix 30 x x 9 9 insulin aspart Biphasic S Humalog Mix 25 x x 9 9 insulin S Humalog Mix 50 x x 9 9 lispro

1 Insuman Comb 25 and 50: 3mL cartridges are suitable for use with the Optipen Pro.

6.1.1.3 Hypodermic equipment c lancets Sherwood FTM200 Soft Pro Softclix – 2 lancets c needles for pen devices 8mm/31G – adults, including obese adults 5mm/31G - paediatric size c needle clipping device B-D Safe-clip c syringes U100 - 0.5mL and 1mL disposable - 0.3 and 0.5mL with 8mm needle

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 88 6.1.2 Oral antidiabetic drugs

NICE has produced guidelines on management of the following aspects of type 2 diabetes. Updates are expected January 2008: • Blood pressure and blood lipids (Guideline H, October 2001) • Blood glucose (Guideline G, September 2002) • Renal disease, prevention and early management (Guideline F, February 2002) • Retinopathy (Guideline E, February 2002)

The UKPDS showed a substantial reduction in all diabetes complications in younger type 2 diabetic patients by achieving a mean HbA1c of 7.0% over 10 years. It is appropriate to aim for HbA1c within normal range if this can be achieved without hypoglycaemia. Other risk factors for cardiovascular disease (smoking, hypertension, obesity and hyperlipidaemia) should be addressed. Oral antidiabetic preparations should be considered only if poor control and symptoms persist after appropriate dieting.

6.1.2.1 Sulphonylureas

Sulphonylureas may promote weight gain and should be avoided in pregnancy. Chlorpropamide and tolbutamide have been deleted as newer agents are preferred. Supplies will remain available for existing patients only. c gliclazide1 tablets 80mg c glibenclamide2 tablets 2.5mg, 5mg

1 Gliclazide is the preferred choice in patients with renal deficiency as it is shorter acting and principally metabolised and inactivated in the liver. 2 Glibenclamide may be suitable for younger patients with normal renal function. Its long half-life (often extended in the elderly) may result in hypoglycaemia.

6.1.2.2 Biguanides c metformin1 tablets 500mg, 850mg d metformin modified release1 m/r tablets 500mg (Glucophage SR)

1 Metformin is advantageous in overweight patients. However, it may provoke lactic acidosis which is most likely to occur in patients with renal impairment. It should not be used in patients with even mild renal impairment. It should be avoided or discontinued in other situations which may predispose to lactic acidosis e.g. severe dehydration, infection, shock, heart failure, recent myocardial infarction, severe peripheral vascular disease, hepatic impairment, alcohol dependency, use of x-ray contrast media, pregnancy and breast feeding. 2 Glucophage SR was approved for formulary inclusion as an alternative treatment for patients who cannot tolerate the gastro-intestinal effects of standard release metformin.

Other antidiabetics c acarbose1 tablets 50mg, 100mg d pioglitazone2 tablets 15mg, 30mg d rosiglitazone2 tablets 4mg, 8mg S nateglinide3 tablets 60mg, 120mg,180mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 89

Other antidiabetics with metformin d and metformin2,4 2mg/500mg, 2mg/1g, 4mg/1g (Avandamet)

1 Acarbose should be taken or chewed with the first mouthful of food or swallowed whole with liquid immediately before food. The possibility of GI side effects is reduced by initial small dosage increments.

2 Pioglitazone and rosiglitazone: For second line (including GP) use in line with NICE guidance for type 2 diabetes mellitus. NICE has advised that the use of a thiazolidinedione (pioglitazone or rosiglitazone) as second-line therapy added to either metformin or a sulphonylurea is not recommended, except for: patients who are unable to tolerate metformin and sulphonylurea in combination therapy, or patients in whom either metformin or a sulphonylurea is contra-indicated.

In such cases, the thiazolidinedione should replace whichever drug in the combination is poorly tolerated or contra-indicated. Click to view full Guidance (No 63, August 2003).

The CSM has reminded prescribers that thiazolidinediones should not be prescribed for patients with cardiac failure or a history of cardiac failure, patients with hepatic impairment, or in combination with insulin. Monitoring of liver function is required. See BNF for further information.

3 Nateglinide is available for initiation by specialists, including General Practitioners managing diabetes, for an assessment period. Monitor renal and liver function as recommended. 4 Avandamet – titration of individual components may be desirable before initiation.

6.1.3 Diabetic ketoacidosis - Please consult local guidelines or see BNF

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 90 6.1.4 Treatment of hypoglycaemia c dextrose chewable tablets powder injection 50% c glucose oral gel 10g (Hypostop1) c glucagon injection 1mg (GlucaGen Kit) vials 1mg

1 Hypostop may be safely smeared onto the buccal mucosa of semi-conscious patients providing the swallowing reflex is preserved, which is usually the case in hypoglycaemic individuals. FP10s for Hypostop should be endorsed ACBS.

Chronic hypoglycaemia S diazoxide powder See Appendix 2 S chlorothiazide suspension 250mg/5mL See Appendix 2 S octreotide (See section 8.3.4)

6.1.6 Diagnostic and monitoring agents for diabetes mellitus Please also see NICE guideline G

N.B. Measurement of glycosylated haemoglobin (HbA1c) is the preferred method of monitoring overall diabetic control

Guidelines for Blood Glucose Monitoring Patients should be appropriately advised on the correct place and use of blood glucose monitoring products. If these products are required, patients should be trained to use the system correctly. The frequency of use as well as the costs of prescribing (e.g. diagnostic strips) should also be considered. Meters are not available on prescription and it is recommended that patients seek advice from their GP prior to purchasing a meter.

Type 2 diabetes There is no need for the majority of patients with type 2 diabetes to monitor their blood glucose. Patients who are poorly controlled and being considered for insulin treatment may benefit from doing their own capillary blood glucose monitoring prior to starting insulin.

Insulin-treated patients Blood glucose monitoring should be performed to assist the patient and/or their diabetes carer in diabetes management and insulin dose adjustments. Measurements should be immediately before or after meals, or both, either on a daily basis or one day chosen per week (random days). A high frequency daily rate of monitoring, i.e. qds, should be reserved for: • newly diagnosed type 1 patients; • people who are unwell; • pregnancy; • pre-surgery; • frequent hypoglycaemic episodes; • loss of hypoglycaemia warning signs. For products available please see section 19.1.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 91 6.2 Thyroid and Antithyroid Drugs

6.2.1 Thyroid hormones c levothyroxine sodium tablets 25micrograms, 50micrograms, (thyroxine sodium) 100micrograms S liothyronine sodium tablets 20micrograms injection 20micrograms

6.2.2 Antithyroid drugs

CSM Warning: Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and the need to stop treatment promptly. Patients 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.

Propylthiouracil would be a suitable substitute in patients who suffer sensitivity reactions to carbimazole. d carbimazole tablets 5mg, 20mg S propylthiouracil tablets 50mg S aqueous iodine oral solution 130mg/mL total iodine (Lugol's Solution) S potassium iodide tablets 60mg See Appendix 2 125mg/5mL injection

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 92 6.3 Corticosteroids

6.3.1 Replacement therapy

S fludrocortisone acetate tablets 100micrograms

Glucocorticoid therapy CSM advice: Following concern about severe chickenpox associated with systemic corticosteroids, every patient prescribed a systemic corticosteroid should receive the patient information leaflet supplied by the manufacturer. Steroid treatment cards should also be issued where appropriate.

The guidelines in this section apply to patients receiving immunosuppressive rather than physiological replacement doses of corticosteroids.

Adrenal Suppression. During prolonged therapy, adrenal atrophy may develop and persist for years after stopping. Abrupt withdrawal may lead to adrenal insufficiency, hypotension or death. Withdrawal may also be associated with fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss. Any significant inter-current illness, trauma or surgical procedure requires a temporary increase in dosage or a temporary re- introduction of corticosteroid. Patients should carry a Steroid Treatment Card giving clear guidance on precautions to minimise the risks. It should also provide details of the prescriber, drug, dosage and duration of treatment. Please see BNF notes on increased susceptibility to infections including SEPTICAEMIA, TUBERCULOSIS, AMOEBIASIS, STRONGYLOIDIASIS, CHICKENPOX and MEASLES.

Steroid withdrawal. The CSM has recommended that gradual withdrawal of systemic corticosteroids should be considered in those patients whose disease is unlikely to relapse and have:

• recently received repeated courses, particularly if taken for longer than three weeks; • taken a short term course within one year of stopping long term therapy; • other possible causes of adrenal suppression; • received more than 40mg daily of prednisolone (or equivalent); • have been given repeat doses in the evening; • received more than three weeks’ treatment.

Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and have received treatment for three weeks or less and are not included in the patient groups described above. During corticosteroid withdrawal, the dose may be rapidly reduced down to physiological doses (equivalent to prednisolone 7.5mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.

Prescribing categories have not been allocated to this section due to the wide range of indications. The choice of steroid may be determined by the condition being treated. When corticosteroids are used as replacement therapy, initiation should be restricted to specialists after appropriate investigations have been performed. For other indications please refer to the relevant chapters: gastrointestinal, respiratory, CNS or dermatology.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 93

prednisolone tablets 1mg, 5mg, 25mg tablets ec 2.5mg, 5mg tablets soluble 5mg betamethasone tablets soluble 500micrograms injection 4mg/1mL dexamethasone tablets 500micrograms, 2mg liquid (SF) 2mg/5mL injection 4mg/mL (1mL, 2mL) hydrocortisone injection 24mg/mL (5mL) tablets 10mg, 20mg hydrocortisone sodium succinate injection 100mg (Solu-Cortef) hydrocortisone sodium injection 100mg (Efcortesol) phosphate Methylprednisolone injection 40mg, 125mg, 500mg, 1g, 2g (Solu-Medrone) depot injection 40mg/1mL (Depo-Medrone) Triamcinolone injection (im/ia) 40mg/1mL prefilled syringe 40mg/1mL, 80mg/2mL (im only)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 94

6.4 Sex Hormones

6.4.1 Female sex hormones

6.4.1.1 Oestrogens and HRT

Since April 2002 the CSM has been monitoring emerging evidence on the risks and benefits of long-term combined HRT

Studies have demonstrated that the types of HRT tested • do not prevent coronary heart disease (CHD), • increase risks of breast cancer and venous thromboembolism (VTE) • increase in the risk of stroke and • increase the risk of ovarian cancer (oestrogen-only HRT)

The absolute incidence of any of these conditions is generally small, but most increase with increasing duration of HRT use.

Continuous combined HRT is only indicated for non-hysterectomised women who are at least 12 months post-menopausal. Peri-menopausal women are generally treated with sequential or cyclical combined HRT. Only hysterectomised women should receive oestrogen-only HRT.

More detailed information on the safety of HRT and an information sheet for patients is available on the MHRA website ( www.mhra.gov.uk)

Effectiveness and benefit of HRT depend on compliance. The most common reason for discontinuing HRT is unacceptable bleeding. Several studies suggest that compliance is best with continuous combined or “period free” regimens.

Million Women Study – Updated 19 April 2007 For full information on latest data from the Million Women Study and Women’s Health Initiative Trial please read the MHRA statement 19th April 2007.

This statement includes the following current advice for women and prescribers: For the majority of women who typically use HRT for the short-term treatment of symptoms of the menopause, the benefits of treatment are considered to outweigh the risks. For long-term use women should be made aware of the increased incidence of adverse effects.

HRT should not be considered the first treatment choice for the long-term prevention of osteoporosis in women who are over 50 years of age and at an increased risk of fractures. However, HRT remains an option for those who are intolerant of, or do not respond to, other osteoporosis-prevention therapies. In such cases, the individual balance of risks and benefit should be assessed carefully.

In younger women who have experienced a premature menopause (due to ovarian failure, surgery or other causes) HRT may be used for treatment of menopausal symptoms and for prevention of osteoporosis until the age of 50 years. After this age, therapy for prevention of osteoporosis should be reviewed and HRT considered a second choice.

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Women with uterus The following preparations contain a progestogen as well as an oestrogen and are therefore suitable for women with an intact uterus. They are not suitable for use as (or with) hormonal contraceptives.

1. Sequential Combined (“Cyclical”) HRT

Two prescription charges are payable for these products.

Brand(s) Oestrogen Progestogen Form Bleed Cost / 28 days c Climagest estradiol 1mg, 2mg norethisterone Tabs Monthly £4.25 (oestradiol) 1mg c Prempak-C conj. oestrogens norgestrel Tabs Monthly £4.91 625micrograms, 150micrograms 1.25mg c Nuvelle estradiol 2mg levonorgestrel Tabs Monthly £4.59 (oestradiol) 75micrograms c Femoston estradiol 1mg, 2mg dydrogesterone Tabs Monthly £4.99 (oestradiol) 10mg d Tridestra estradiol 2mg medroxyprogeste- Tabs 3 mthly £7.92 (oestradiol) rone 20mg d Trisequens estradiol 1mg, 2mg norethisterone Tabs Monthly £4.80 (oestradiol) acetate 1mg d Evorel estradiol norethisterone Patch1 Monthly £11.00 Sequi 50micrograms 170micrograms (oestradiol) d FemSeven estradiol levonorgestrel Patch1 Monthly £10.42 Sequi 50micrograms 10micrograms (oestradiol) (during phase 2 only) d Elleste estradiol 1mg, 2mg norethisterone Tabs Monthly £3.24 Duet (oestradiol) 1mg

1 Do not offer patches routinely. Only prescribe for patient preference or if compliance is poor.

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2. Continuous Combined (“Period-Free”) HRT

Continuous combined therapy is unsuitable for use in the perimenopause or within 12 months of the last menstrual period due to the likelihood of irregular bleeding. It may also cause irregular bleeding during the first 6 cycles. If bleeding continues, discontinue or change to cyclical HRT. Tibolone, a gonadomimetic, (see later in this section) is also licensed for period–free prevention of menopausal symptoms and for prophylaxis of osteoporosis. One prescription charge is payable for these products.

Choosing the most suitable period–free regimen Choice of oestrogen dose: 1 mg - reduced incidence of mastalgia - favourable bleeding profile 2 mg - traditional bone protection dose - possible better relief of menopausal symptoms Choice of progestogen: dydrogesterone - more favourable changes in lipid profile and less androgenic than norethisterone if skin problems such as acne and hirsutism occur medroxyprogesterone acetate - similar to dydrogesterone, norethisterone - reduced incidence of bleeding - synergistic effect with oestrogen on bone protection

3. Continuous Combined HRT - preparations available

Brand Oestrogen Progestogen Form Bleed Cost/ 28 days c Femoston-conti1 estradiol 1mg dydrogesterone 5mg Tabs No bleed £7.54 (oestradiol) c Premique conj. oestrogen Medroxyprogesterone Tabs No bleed £7.54 625micrograms 5mg d Kliovance2 estradiol 1mg norethisterone Tabs No bleed £8.65 (oestradiol) 500micrograms d Kliofem estradiol 2mg norethisterone 1mg Tabs No bleed £8.65 (oestradiol) d Livial tibolone 2.5mg - Tabs No bleed £13.05 d Evorel Conti estradiol norethisterone Patch No bleed £12.90 50micrograms 170micrograms (oestradiol) d Elleste-Duet Conti estradiol 2mg norethisterone acetate Tabs No bleed1 £5.99 (oestradiol) 1mg d Nuvelle continuous estradiol 2mg norethisterone acetate Tabs No bleed1 £6.01 (oestradiol) 1mg

1 Femoston-conti is a low dose preparation suitable for patients with a history of cardiovascular disease. 2 Kliovance is a low dose preparation with a good bleeding profile.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 97 Women without uterus c conjugated oestrogens tablets 625micrograms, 1.25mg (Premarin) c estradiol tablets 1mg, 2mg (oestradiol) d estradiol transdermal matrix patches releasing (oestradiol) 25,50, 75 or 100micrograms in 24 hours once/twice weekly, gel 0.06%1, 0.1% 1 H estradiol implants 25mg, 50mg (oestradiol)

1 Estradiol (oestradiol) gels must be applied avoiding the breasts and vulval region. Special counselling on their administration is required. Please see the BNF for further details.

In patients with an intact uterus a progestogen should be added. Estradiol (oestradiol) nasal spray (Aerodiol) has been discontinued

Raloxifene d raloxifene1 tablets 60mg

1 Raloxifene- Protocol for use in Bro Taf Raloxifene should be reserved for the treatment or prevention of: • osteoporosis in postmenopausal women without menopausal symptoms and where HRT and bisphosphonates are either contra-indicated or not tolerated; • there is no upper age limit but treatment is generally limited to 3 years; Osteoporosis should normally be confirmed by DXA scan. Patients who may not require a DXA scan include those over 80 and those with multiple low trauma fractures (especially vertebral) where other causes such as malignancy have been excluded. These guidelines are subject to review.

Tibolone Tibolone combines oestrogenic and progestogenic activity with weak androgenic activity. It is licensed for continuous use without a cyclical progestogen for the relief of menopausal symptoms and for protection against osteoporosis. It may also be used as “add-back” therapy in women being treated with gonadotrophin releasing hormone antagonists. Unsuitable for use within 12 months of last menstrual period (may cause irregular bleeding). d tibolone tablets 2.5mg (Livial)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 98 Ethinylestradiol1 S ethinylestradiol tablets (ethinyloestradiol) 10micrograms, See Appendix 2 50micrograms, 1mg paediatric tablets 2micrograms

1 Ethinylestradiol (ethinyloestradiol) is not recommended for use as oestrogen replacement in postmenopausal women. The 2 micrograms tablets are unlicensed and restricted to paediatric use.

6.4.1.2 Progestogens

Adjuncts to oestrogen for HRT c norethisterone1 tablets 1mg (Micronor HRT), 5mg c dydrogesterone tablets 10mg (Duphaston HRT) c medroxyprogesterone acetate tablets 2.5mg, 5mg, 10mg (Provera) d progesterone pessaries 200mg, 400mg (Cyclogest) injection 25mg, (1mL), 50mg/1mL, (1mL, 2mL) (Gestone)

1. Norethisterone - see NICE CG44 on Heavy menstrual bleeding. January 2007.

6.4.2 Male sex hormones and antagonists c testosterone sachets 50mg/5g (Testogel) S testosterone capsules 40mg (Restandol) patches 2.5mg or 5mg/24h implants 100mg, 200mg injection 100mg (Sustanon 100)1 injection 250mg (Sustanon 250)1 S finasteride tablets 5mg S flutamide tablets 250mg (also see 8.3.4.2) S cyproterone acetate2 tablets 50mg (Androcur) also see 8.3.4.2

1 Sustanon contains arachis (peanut) oil. 2 Cyproterone is available as two different brands with different licensed indications. Care should be taken to ensure the patient does not receive the wrong brand as the information leaflet may cause distress and use would be unlicensed.

6.4.3 Anabolic Steroids

S stanozolol tablets 5mg S oxandrolone1 tablets 2.5mg See Appendix 2

1 Oxandrolone is restricted to paediatric endocrinologists only.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 99 6.5 Hypothalamic & Pituitary Hormones and Anti- Oestrogens

6.5.1 Hypothalamic & anterior pituitary hormones and anti-oestrogens

Anti-oestrogens H clomifene citrate1 tablets 50mg (clomiphene citrate) S tamoxifen (see section 8.3.4.1)

1. Clomifene: The CSM has advised that treatment should not normally be used for longer than six cycles. As patients are reviewed regularly in the out-patient clinic, the status has been changed to Hospital Only.

Anterior pituitary hormones Corticotrophins H tetracosactide injection 250micrograms/1mL (tetracosactrin) (Synacthen) injection 1mg/1mL (Synacthen Depot)

Gonadotrophins H chorionic injection 2000unit (Profasi) gonadotrophin injection 5000unit (Pregnyl) injection 10000unit (Profasi) H follitropin alfa injection 37.5 unit,75 unit, 150 unit, multidose vial 1200 unit (Gonal-F) H follitropin beta injection 50 unit, 100 unit, 150 unit, 200 unit cartridges, 300 unit, 600 unit (Puregon) H human menopausal injection 75unit (Menopur) Shared care gonadotrophins protocol no 7

Continued…

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 100

Growth hormone S somatropin1 injection 5.3mg (16 unit), 12mg (36 unit) (Genotropin)2 Genotropin Miniquick Syringe 0.2mg (0.6 unit), 0.4mg (1.2 unit), 0.6mg (1.8 unit) SimpleXx injections 5mg (15 unit), 10mg (30unit), 15mg (45 unit) (Norditropin SimpleXx)3 injection 6mg (18 unit), 12mg (36 unit), 24mg (72 unit) (Humatrope) injection 1.33mg (4 unit), 3.33mg (10 unit) 8mg (24unit) (Saizen)4 injection 4mg (12 unit) (Zomacton)5

1 Somatropin should be used in children with growth failure in line with NICE guidance No 42 issued May 2002. For adults with growth hormone (GH) deficiency, use only if they fulfil all three of the following: (NICE No 64, Aug 03) • They have severe GH deficiency, defined as a peak GH response of less than 9 mU/litre (3 nanograms/ml) during an insulin tolerance test or a cross- validated GH threshold in an equivalent test. • They have a perceived impairment of quality of life (QoL), as demonstrated by a reported score of at least 11 in the disease-specific ‘Quality of life assessment of growth hormone deficiency in adults’ (QoL-AGHDA) questionnaire. • They are already receiving treatment for any other pituitary hormone deficiencies as required. Please see full guidance: www.nice.org.uk 2 For use with Genotropin Pen 3 For use with Nordipen 4 For use with OneClick device 5 For use with ZomaJet needle free device or with Autojector, or with needles and syringes

Hypothalamic hormones (for diagnostic purposes in hospitals only) H gonadorelin injection 100micrograms/1mL H protirelin injection 200micrograms/2mL H sermorelin injection 50micrograms

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 101 6.5.2 Posterior pituitary hormones and antagonists

Posterior pituitary hormones S terlipressin injection 1mg (Glypressin) S desmopressin1 tablets (Desmotabs) 200micrograms sublingual tablets (DDAVP Melt) 2 60 micrograms, 120 micrograms, 240 micrograms sublingual tablets (DesmoMelt) 3 120 micrograms, 240 micrograms intranasal solution 100 micrograms/mL nasal spray (Desmospray)4 10 micrograms/dose nasal spray (special) See Appendix 2 2.5 micrograms/dose S vasopressin injection 20unit/1mL (Pitressin) H desmopressin injection 4 micrograms/1mL (DDAVP) injection 15 micrograms/mL (Octim) 5

1 Hyponatraemic Convulsions. The CSM has advised that patients being treated for primary nocturnal enuresis should be warned to avoid fluid overload (including during swimming) and to stop taking desmopressin during an episode of vomiting or diarrhoea (until fluid balance normal). The risk of hyponatraemic convulsions can also be minimised by keeping to the recommended starting doses and by avoiding concomitant use of drugs which increase secretion of vasopressin (e.g. tricyclic antidepressants). 2. DDAVP Melt is indicated for the treatment of vasopressin-sensitive cranial diabetes insipidus or in the treatment of post-hypophysectomy polyuria/polydipsia. Prescribe by brand name. 3. DesmoMelt is indicated for the treatment of primary nocturnal enuresis. Prescribe by brand name. See section 7.4.2 4. Desmopressin Nasal Spray: Removal of the Primary Nocturnal Enuresis Indication April 2007. At the request of the MHRA, the indication for the treatment of primary nocturnal enuresis (PNE) has been removed from all desmopressin nasal spray products, including Desmospray. Remaining licensed indications include the treatment of patients with cranial diabetes insipidus or nocturia associated with multiple sclerosis. In comparison with oral formulations of desmopressin, nasal forms were associated with the majority of serious adverse drug reactions (ADRs) reported in patients with PNE. Rare, serious ADRs included hyponatraemia, water intoxication and convulsions. As the risk benefit profile of the oral formulations is more favourable than the nasal spray, the nasal form should no longer be used for the treatment of PNE in adults and children. 5. Octim Injection: For mild to moderate haemophilia and Von Willebrand’s disease. Specialist initiation required. Currently for hospital prescribing only.

Antidiuretic hormone antagonists S demeclocycline 150mg capsules

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 102 6.6 Drugs Affecting Bone Metabolism

Those at risk of osteoporosis should maintain an adequate intake of calcium and and any deficiency should be corrected by increasing the dietary intake or taking supplements. Please also see NICE Technology Appraisal 87 (Jan 05) on bisphosphonates (alendronate, etidronate, risedronate), selective oestrogen receptor modulators (raloxifene) and parathyroid hormone (teriparatide) for the secondary prevention of osteoporotic fragility fractures in postmenopausal women.

6.6.1 and teriparatide

S calcitonin (salcatonin) injection 400unit/2mL H teriparatide (Forsteo)1 prefilled injection 250micrograms/ml H parathyroid hormone2 injection 1.61mg multidose cartridge (Preotact)

1. Teriparatide: NICE Technology appraisal 87 (Jan 05) recommends teriparatide as a treatment option for the secondary prevention of osteoporotic fragility fractures in women aged 65 years and older who have had an unsatisfactory response to bisphosphonates or intolerance to bisphosphonates (as defined in Sections 1.5 and 1.6, respectively), and: • who have an extremely low BMD (with a T-score of approximately –4 SD or below), or • who have a very low BMD (with a T-score of approximately –3 SD or below) plus multiple fractures (that is, more than two) plus one, or more, additional age independent risk factors: - low body mass index (< 19 kg/m2); - family history of maternal hip fracture before the age of 75 years; untreated premature menopause; - conditions associated with prolonged immobility. For full details see NICE Technology Appraisal 87 (Jan 05) on the secondary prevention of osteoporotic fragility fractures in post menopausal women who have sustained a clinically apparent osteoporotic fracture

2. Parathyroid hormone: AWMSG recommendation June 07 for restricted use in the treatment of postmenopausal women with osteoporosis at high risk of fractures. It should be considered as an alternative to teriparatide only in patients who are intolerant of that agent, or where the storage or administration issues are deemed to provide significant added benefit. It should only be initiated by specialists experienced in the treatment of osteoporosis.

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6.6.2 Bisphosphonates and other drugs affecting bone metabolism

(Section updated Jan 2008)

Severe oesophageal reactions have been reported with all oral bisphosphonates: patients should be advised to stop tablets and seek medical attention for symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain, or heartburn. has been reported in patients receiving intravenous bisphosphonates and, rarely, in those taking oral bisphosphonates. Adequate oral hygiene should be maintained during and after treatment with bisphosphonates. Ideally remedial dental work should be carried out before starting bisphosphonate treatment. Following a local review (January 2007) of the use of bisphosphonates for various indications, it is recommended that the agents listed are considered for suitability in the order they appear below. As always, please consult the product literature before prescribing.

Osteoporosis Order of Drug name Forms available Notes selection (and see below) First Choice c alendronic acid1 tablets 10mg (Fosamax) Prevention and tablets 70mg treatment. (Fosamax Once Weekly) Second d risedronate tablets 5mg, Prevention and Choice sodium2 (Actonel) treatment tablets 35mg (Actonel Once A Week) Third Choices S ibandronic acid tablets 150mg Treatment . tablets (Bonviva) (once monthly) Specialist Recommended H ibandronic acid injection 3mg/3ml Treatment. injection (every 3 months) Hospital only (Bonviva) Fourth choice S strontium granules 2g/sachet MHRA/EMEA ranelate3 (Protelos – daily) safety warnings. See note 3

Paget’s Disease Drug name Forms available Notes S risedronate tablets 30mg please see below sodium2 (Actonel) H disodium infusion pamidronate4 15mg, 30mg, 60mg, 90mg vials

H zoledronic acid5 infusion 5mg/100mL . infusion (Aclasta ®)

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Malignancy Drug name Forms available Notes S sodium clodronate capsules 400mg (Bonefos) Hypercalcaemia of malignancy, tablets 520mg (Loron) osteolytic lesions and bone pain in tablets 800mg (Bonefos) bone metastases associated with intravenous solution breast cancer or multiple myeloma. 300mg in 5mL for dilution ( Bonefos)

H disodium infusion Hypercalcaemia of malignancy, pamidronate 15mg, 30mg, 90mg osteolytic lesions and bone pain in (Aredia Dry Powder) bone metastases associated with breast cancer or multiple myeloma. H zoledronic acid5 infusion 4mg (Zometa) Reduction of bone damage in advanced malignancies involving bone, hypercalcaemia of malignancy. H ibandronic acid tabs 50mg (Bondronat) Prevention of skeletal events in injection 2mg in 2mL patients with breast cancer and bone (Bondronat) metastases, hypercalcaemia of malignancy

Etidronate has been removed from the formulary and should only be used for existing patients.

1 . Tablets should be swallowed whole with a full glass of water on an empty stomach at least 30 minutes before breakfast (and any other oral medication). The patient should remain standing or sitting upright for at least 30 minutes and should not lie down until after eating breakfast. The tablets should not be taken at bedtime or before rising. 2 Risedronate is included for ∗ 1st line treatment of Paget’s Disease as an alternative to intravenous pamidronate and as ∗ 2nd line treatment of osteoporosis in patients intolerant of alendronate. Counselling: Swallow standard release (daily) or once weekly tablets whole with a full glass of water on an empty stomach at least 30 minutes before the first food or drink of the day. Alternatively, for daily tablets only, avoid food and drink for at least 2 hours before or after risedronate if taken at any other time of day. Particularly avoid calcium- containing products e.g. milk, also iron and mineral supplements and antacids. Stand or sit upright for at least 30 minute. Do not take tablets at bedtime or before rising. Take care to avoid confusion with risperidone (an antipsychotic). 3 Strontium: For treatment of postmenopausal osteoporosis when the use of oral biphosphonates is not appropriate. Requires DXA scans at initiation and after 2 and 5 years of treatment. Avoid food for 2 hours before and after taking granules, particularly calcium-containing products e.g. milk: also preferably avoid concomitant antacids containing aluminium and magnesium hydroxides for 2 hours after taking granules.

Strontium safety warning: Concerns have arisen about the risk of severe allergic reactions in association with its use. These reactions have included drug rash with eosinophilia systemic symptoms (DRESS). DRESS is a serious and life-threatening type of allergic reaction to some medicines. It starts with a skin rash, accompanied by a fever, swollen glands, increased numbers of white cells in the blood and can effect the liver, kidneys and lung. This can result in kidney or liver failure. Stopping treatment, together with corticosteroid therapy, usually results in the symptoms improving, but recovery can be slow and there is a risk of symptoms returning during the recovery period. The European Medicines Agency has issued a statement advising that the prescribing and patient information for Protelos▼ is being updated as an urgent measure to include warnings about this risk.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 105 Advice to prescribers and patients Women taking Protelos▼ should be alert to the risk of severe allergic reactions and if they develop a rash, they should stop taking the medicine and consult their doctor immediately. Once Protelos▼ treatment has been stopped it should not be re-introduced. For further information please see MHRA response to European Medicines Agency (EMEA) statement on the safety of strontium ranelate

4 Disodium pamidronate: Patients should be warned against driving or operating machinery immediately after treatment, as somnolence or dizziness can occur. 5 Zoledronic acid: Correct any hypocalcaemia before treatment: following infusion, at least 500mg elemental calcium twice daily (with vitamin D) for at least 10 days is recommended.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 106 6.7 Other Endocrine Drugs

6.7.1 Bromocriptine and other dopamine-receptor stimulants

CSM ADVICE. The ergot-derived dopamine-receptor agonists, bromocriptine, cabergoline, lisuride, and pergolide have been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions. The CSM has advised that before starting treatment with these ergot derivatives investigations such as measurement of erythrocyte sedimentation rate, of urea and electrolytes, and a chest X-ray may be appropriate. If long-term treatment is expected, then lung-function tests may be helpful. Patients should be monitored for progressive fibrotic disorders. Progression of fibrosis can be prevented by early diagnosis and cessation of drug treatment.

S cabergoline1 tablets 500micrograms

1. Cabergoline is no longer included in the Formulary for treatment of Parkinson Disease (MTAC advice 15/6/06). Bromocriptine has been removed for all indications.

6.7.2 Drugs affecting gonadotrophins d danazol2 capsules 100mg, 200mg H ganirelix injection 250micrograms

Gonadorelin analogues S goserelin implant 3.6mg (Zoladex) implant 10.8mg (Zoladex LA) S leuprorelin acetate injection 3.75mg (Prostap SR) S nafarelin nasal spray 200micrograms/dose (Synarel) S buserelin nasal spray 150micrograms/spray (Suprecur) injection 1mg in 1mL (Suprecur) S triptorelin acetate2 3.75mg prefilled syringe

1. Heavy menstrual bleeding. See NICE CG44 Jan 2007. Danazol and etamsylate remain in the formulary for uses other than heavy menstrual bleeding. 2. Triptorelin is included for the specialist initiated treatment of precocious puberty and for reduction of endometriosis foci and oestrogen-dependent uterine myomas in women.

6.7.3 Metyrapone

S metyrapone capsules 250mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 107 CHAPTER 7 OBSTETRICS, GYNAECOLOGY AND URINARY- TRACT DISORDERS

7.1 Drugs Used in Obstetrics Antenatal and postnatal mental health: clinical management and service guidance. See NICE CG45 February 2007.

7.1.1 Prostaglandins and oxytocics

For NICE guidance on Induction of labour, please see abbreviated information in BNF or full NICE Clinical Guideline D (June 2001) for details www.nice.org.uk . c ergometrine injection 500micrograms/1mL c ergometrine with injection 500micrograms/5units/1mL oxytocin (Syntometrine) c oxytocin1 injection 5units/1mL, 10units/1mL (Syntocinon) H carboprost injection 250micrograms/1mL (Hemabate) H dinoprostone tablets 500micrograms infusion 0.75mg/0.75mL, 5mg/0.5mL vaginal tablets 3mg extra-amniotic solution 5mg/0.5mL removable pessaries 5mg (Propess) vaginal gels 1mg, 2mg H gemeprost pessary 1mg H misoprostol2 tablets 200micrograms See Appendix 2

1 Oxytocin nasal spray is not included in the formulary. 2 Misoprostol may be used orally or by vagina for the induction of labour but use is unlicensed. Please refer to the protocols held on the maternity unit.

7.1.1.1 Ductus arteriosus

Please see neonatal unit protocols for closure of the ductus arteriosus.

Maintenance of patency H dinoprostone infusion 0.75mg/0.75mL H alprostadil infusion 500micrograms/mL (Prostin VR)

Closure of ductus arteriosus H indometacin (indomethacin) injection 1mg (Indocid PDA)

7.1.2 Mifepristone

S mifepristone1 tablets 200mg

1 Mifepristone can facilitate the process of medical abortion. It makes the uterus more sensitive to subsequent administration of a prostaglandin and therefore abortion occurs in a shorter time and at a lower dose of prostaglandin. Issues are strictly on a recorded name basis.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 108 7.1.3 Myometrial relaxants

S nifedipine1 capsules 10mg SR tablets 10mg, 20mg S ritodrine tablets 10mg injection 50mg/5mL S indomethacin suppositories 100mg capsules 25mg H atosiban2 injection 6.75mg in 0.9ml, concentrate for infusion 37.5mg in 5ml

1 Nifedipine is the recommended first line agent for premature labour in most units in Bro Taf, given according to the protocol (available on Antenatal and Labour wards). Ritodine and indomethacin are reserved for consultant use only. 2 Atosiban is available for use by hospital specialists for an assessment period. It is reserved for second line use after other agents have proved ineffective or inappropriate.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 109 7.2 Treatment of Vaginal and Vulval Conditions

7.2.1 Preparations for vaginal atrophy

Topical HRT c estradiol (oestradiol)1 vaginal tablets 25micrograms (Vagifem)1 c estriol (oestradiol) cream 0.1% (Ovestin) d estradiol (oestradiol) vaginal ring 7.5micrograms in 24h (Estring)

1 Vagifem is suitable for use with barrier-type contraceptives. The effect of Ovestin on latex condoms and diaphragms is not yet known.

7.2.2 Anti-infective drugs

Fungal infections c clotrimazole1,2 cream 1% vaginal cream 10% pessaries 100mg, 200mg, 500mg c fluconazole capsules 150mg d miconazole2 vaginal cream 2% cream 2% pessary 100mg d clotrimazole and hydrocortisone cream 1% clotrimazole/ 1% hydrocortisone (Canesten HC) d miconazole and hydrocortisone cream and ointment 2% miconazole and 1% hydrocortisone (Daktacort) S itraconazole capsules 100mg suspension 10mg/mL

1 Clotrimazole: Consider internal and external use for external itching. 2 Some products damage latex condoms and diaphragms. Check BNF for up-to-date information. All vaginal nystatin preparations have been deleted due to staining of clothes. More acceptable preparations are available.

Other vaginal infections c metronidazole tablets 400mg d metronidazole gel 0.75% d clindamycin cream 2% S povidone iodine pessary 200mg solution 10% (vaginal cleansing kit)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 110 7.3 Contraceptives

7.3.1 Combined oral contraceptives

Low strength c Mercilon c Loestrin 20 c Femodette Standard strength c Ovranette (= Microgynon 30) c Brevinor (= Ovysmen) c Cilest c Marvelon c Femodene c Femodene ED c Norimin1 c Loestrin 30 c Microgynon 30 ED d Yasmin High strength c Norinyl-1

1 Norimin is particularly suitable for breakthrough bleeding. Ovran, Ovran 30 and Eugynon 30 have been removed due to the adverse effect of higher doses of levonorgestrel on high-density lipoproteins.

Phased formulations c Binovum c Synphase c Trinovum c Logynon (= Trinordiol) c Logynon ED

Emergency contraception c levonorgestrel tablets 1.5mg (Levonelle 1500) (Levonelle-2) has been discontinued

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 111 7.3.2 Progestogen-only contraceptives 7.3.2.1 Oral progestogen-only contraceptives c etynodiol diacetate tablets 500 micrograms (Femulen) c norethisterone tablets 350 micrograms (Micronor ) c levonorgestrel tablets 30 micrograms (Norgeston) c/d desogestrel1 tablets 75 micrograms (Cerazette) North Bro Taf 1st line Cardiff & Vale 2nd line

Neogest has been discontinued. 1 Desogestrel (Cerazette) : Available for GP prescribing but in Cardiff and the Vale is restricted to use (a) in young women (below 30), with contra-indications to oestrogen and (b) women of any age with intolerable side effects on other POPs – particularly irregular bleeding.

7.3.2.2 Parenteral progestogen-only contraceptives

The effectiveness of parenteral progestogen-only contraceptives is not affected by broad spectrum antibiotics. Their effectiveness however, but may be reduced by enzyme- inducing drugs. For patients on such drugs the interval between injections of medroxyprogesterone acetate should be reduced from 12 to 10 or even 8 weeks. c medroxyprogesterone acetate1 injection 150mg/1mL (Depo-Provera) c etonogestrel2 implant 68mg (Implanon)

1. Depo-Provera. In November 2004 the CSM advised that: • In adolescents, Depo-Provera may be used as first-line contraception but only after other methods have been discussed with the patient and considered to be unsuitable or unacceptable; • In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out in those who wish to continue use for more than 2 years; • In women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered.

THE EFFECT OF DEPO-PROVERA ON BONE MINERAL DENSITY - Key Points • It is well established that Depo-Provera reduces BMD in many women who use it. • It is not yet known whether the effect on BMD increases the risk of osteoporosis and fractures in later life. • The reduction in BMD is duration-dependent for the first few years of use after which the effect appears to plateau. • There is some evidence that BMD starts to recover when Depo-Provera is stopped but the extent of recovery is currently unknown and may be related to duration of exposure. • The effect of Depo-Provera may be more important in adolescents in whom the usual process of bone mineral accretion may be reversed. In this population, the effect of Depo-Provera on attainment on peak bone mass is not known.

2. Etonogestrel is restricted to doctors who have been trained in the insertion technique.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 112 7.3.2.3 Intra-uterine progestogen-only contraceptives c levonorgestrel intrauterine system (Mirena) 20micrograms/24 hours release rate

See NICE Clinical Guidelines No. 30 (October 2005) - Long–acting Reversible Contraception and NICE Clinical Guidance Heavy menstrual bleeding CG44 Jan 2007. Please see full guidance: www.nice.org.uk

7.3.3 Spermicidal contraceptives

Spermicides CSM advice. Products such as petroleum jelly (vaseline), baby oil and oil-based vaginal and rectal preparations are likely to damage condoms and contraceptive diaphragms made from latex rubber. This may render them less effective as a barrier method of contraception and as a protection from sexually transmitted diseases including HIV.

There is no evidence that the spermicides listed below will harm latex condoms and diaphragms.

c nonoxinol ‘9’ cream 2% (OrthoCreme) pessaries 5% (Orthoforms)

7.3.4 Contraceptive devices

Intra-uterine devices c Multiload Cu375 c Nova-T380 c GyneFix1 intrauterine implant

1 Gynefix usage is restricted to specialists who have been trained in the insertion technique. This may include a limited number of GPs with specialist interest. All specialists should insert a minimum of 10 Gynefix per year to retain accreditation.

Other Contraceptive devices

Contraceptive Caps c Type A Contraceptive pessary Dumas Vault Cap c Type B Contraceptive pessary Cervical Cap c Type C Contraceptive pessary Vimule Cap

Contraceptive Diaphragms c Type A diaphragm with flat spring (Reflexions) c Type B diaphragm with coiled rim (Ortho) c Type C arcing Spring Diaphragm (All Flex)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 113 7.4 Drugs for Genito-Urinary Disorders

7.4.1 Drugs for urinary retention Alpha-blockers Selective alpha-blockers reduce blood pressure. Patients taking antihypertensive treatment may require reduced dosage and specialist supervision. d alfuzosin1 tablets 2.5mg modified release tablets 5mg, 10mg S tamsulosin2 modified release capsules 400micrograms S phenoxybenzamine3 capsules 10mg

1. Alfuzosin should be withdrawn 24 hours before surgery. First dose may cause collapse due to hypotensive effect (therefore should be taken on retiring to bed). Patients should be warned to lie down if symptoms such as dizziness, fatigue or sweating develop, and to remain lying down until they abate completely. 2. Tamsulosin MR. Please prescribe this generically as Flomax MR has been discontinued in the UK due to patent expiry. Kent Pharmaceuticals (01233 638614) are able to supply an imported equivalent (Omnic) until a generic product is available in the UK. Flomaxtra XL is not in the formulary. 3. Phenoxybenzamine is restricted to the Spinal Unit and for phaeochromocytoma.

7.4.2 Drugs for urinary frequency, enuresis, and incontinence Urinary incontinence Please see NICE Clinical Guideline CG40 October 2006: Urinary incontinence: the management of urinary incontinence in women. This replaces TA56 (Stress Incontinence Tape) c oxybutynin tablets 2.5mg, 3mg, 5mg liquid 2.5mg/5mL d tolterodine tablets 1mg, 2mg d trospium tablets 20mg d/S solifenacin North Bro Taf 2nd Line Cardiff and Vale Specialist Initiated tablets 5mg, 10mg H propantheline 15mg tabs H duloxetine (Yentreve brand) North Bro Taf Hospital Only capsules 20mg, 40mg

Propiverine has been removed from the formulary following an assessment period.

Nocturnal enuresis Desmopressin Nasal Spray: Removal of the Primary Nocturnal Enuresis Indication April 2007. At the request of the MHRA, the indication for the treatment of primary nocturnal enuresis (PNE) has been removed from all desmopressin nasal spray products, including Desmospray. In comparison with oral formulations of desmopressin, nasal forms were associated with the majority of serious adverse drug reactions (ADRs) reported in patients with PNE. Rare, serious ADRs included hyponatraemia, water intoxication and convulsions. As the risk benefit profile of the oral formulations is more favourable than the nasal spray, the nasal form should no longer be used for the treatment of PNE in adults and children.

S desmopressin sublingual tablets (DesmoMelt) 1 120 micrograms, 240 micrograms

1 DesmoMelt is indicated for the treatment of primary nocturnal enuresis. Prescribe by brand name to avoid confusion with DDAVP Melt for diabetes insipidus – section 6.5.2

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 114

7.4.3 Drugs used in urological pain

Alkalinisation of urine c potassium citrate mixture BP d sodium bicarbonate capsules 500mg, 1g tablets 600mg

Acidification of urine S ascorbic acid (see section 9.6.3)

7.4.4 Bladder instillations and urological surgery

Urological surgery H sodium chloride solutions 0.9%, 1litre, 2litre, 3litre H glycine solution 1.5%, 2litre

Maintenance of indwelling urinary catheters c sodium chloride solution 0.9% 100mL d solution G solution 100mL

Others These products are only available on a named patient basis.

S dimethyl sulfoxide (dimethyl solution 50% 50mL See Appendix 2 sulphoxide) S dimethyl sulfoxide and See Appendix 2 hydrocortisone cocktail (dimethyl sulphoxide) H BCG Immunotherapeutic vial 81mg (Immucyst) See Appendix 2

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 115

7.4.5 Drugs for erectile dysfunction

Central guidance on prescribing drugs for erectile dysfunction on the NHS is given under the Selected List Scheme in Schedule 11 of the Drug Tariff. GPs may prescribe the drugs below provided the patient is suffering from one of the medical conditions listed. Prescription forms FP10 and FP10 (HP) must be endorsed “SLS”. Patients who do not qualify under these rules but who are suffering from severe distress should be treated in specialist centres. In secondary care, prescribing of drug treatments for erectile dysfunction should be restricted to nominated specialists, normally through Erectile Dysfunction Clinics. Patients will be accepted on the understanding that the referring GP will accept ongoing responsibility for prescribing the recommended agent.

S alprostadil injection 5micrograms, 10micrograms, 20micrograms, 40micrograms (Caverject) urethral applications:- 5micrograms, 10micrograms, 20micrograms (Viridal) 10micrograms, 20micrograms, 40micrograms (Viridal Duo Starter Pack) 10micrograms, 20micrograms, 40micrograms (Viridal Duo Continuation Pack) single use applicators 125micrograms, 250micrograms, 500micrograms, 1mg (MUSE) S papaverine injection 30mg/2mL, 60mg/1mL, 60mg/2mL S sildenafil tablets 25mg, 50mg, 100mg (Viagra) S tadalafil Available in North Bro Taf Only tablets 10mg, 20mg (Cialis) S Available in North Bro Taf Only tablets 5mg, 10mg, 20mg (Levitra)

Apomorphine tablets (Uprima) have been discontinued.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 116 CHAPTER 8 MALIGNANT DISEASE AND IMMUNOSUPPRESSION

The National Institute for Health and Clinical Excellence (NICE) has produced guidance on the use of several agents and techniques relating to the treatment of malignant disease. These are as follows:

Date Published 93 Advanced colorectal carcinoma– irinotecan, oxaliplatin & ralitrexed August 05 23 Breast cancer – temozolomide April 01 30 Breast cancer – taxanes (review) September 01 34 Breast cancer – trastuzumab March 02 41 Breast cancer (familial) - screening October 06 54 Breast cancer – vinorelbine December 02 107 Breast cancer(earlyHER2+ve) - trastuzumab August 06 108 Breast cancer (early node +ve) – paclitaxel September 06 109 Breast cancer (early node +ve) –docetaxel September 06 17 Colorectal carcinoma – laparascopic surgery December 00 61 Colorectal cancer – capecitabine and tegafur uracil May 03 100 Colon cancer (Dukes’ C) - capecitabine & oxaliplatin April 06 70 Leukaemia (chronic myeloid) – imatinib October 03 26 Lung cancer – docetaxel, paclitaxel, gemcitabine and vinorelbine June 01 137 Lymphoma (non-Hodgkin’s) – rituximab Feb 08 110 Lymphoma (follicular) – rituximab September 06 55 Ovarian cancer – paclitaxel January 03 3 Ovarian cancer – taxanes May 00 91 Ovarian cancer – paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan(review) May 05 25 Pancreatic cancer – gemcitabine May 01 101Prostate cancer - docetaxel June 06 ( hormone refractory) Please see full details at www.nice.org.uk All drugs are for specialist initiation only. In many cases they will only be used or supplied from hospitals (H). Drugs which GPs may prescribe, following specialist initiation, are marked (S). Strengths and formulations have been omitted. Please refer to local policies for measurable doses of parenteral cytotoxics.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 117

8.1. Cytotoxic Drugs

Many of these agents are the subject of NICE Guidance. For full detail please see: www.nice.org.uk

8.1.2 Alkylating drugs

H busulfan (busulphan) H carmustine H chlorambucil H cyclophosphamide H ifosfamide H lomustine H melphalan H chlormethine hydrochloride (mustine hydrochloride) H thiotepa H treosulfan

Urothelial toxicity H MESNA

8.1.2 Cytotoxic antibiotics

H aclarubicin H bleomycin H dactinomycin (actinomycin D) H daunorubicin H doxorubicin H doxorubicin (pegylated liposomal)1 H epirubicin hydrochloride H idarubicin hydrochloride H mitomycin H mitoxantrone (mitozantrone)

1 Pegylated liposomal doxorubicin is included in line with reviewed NICE guidance for advanced ovarian carcinoma No 91, May 05. Please see full guidance: www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 118

8.1.3 Antimetabolites

Many of these agents are the subject of NICE Guidance. For full detail please see: www.nice.org.uk

H capecitabine (Xeloda) H cladribine H cytarabine H clofarabine1 H fludarabine phosphate H fluorouracil including cream 5% (Efudix) see 13.8.1 H gemcitabine H mercaptopurine2 H methotrexate3 H tioguanine (thioguanine) H tegafur with uracil

1. Clofarabine: See AWMSG Advice No: 0107 – June 2007 2. Mercaptopurine: See Shared care protocol No 25 on use in inflammatory bowel disease. 3. Methotrexate: Important Note that the dose is a weekly dose. To avoid error with methotrexate, it is recommended that: • the patient is carefully advised of the dose and frequency and the reason for taking methotrexate and any other prescribed medicine (e.g. folic acid); • only one strength of methotrexate tablet (usually 2.5 mg) is prescribed and dispensed; • the prescription and the dispensing label clearly show the dose and frequency of methotrexate administration; • the patient is warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine), and respiratory effects (e.g. shortness of breath).

Folinic acid rescue H calcium folinate (calcium leucovorin)

8.1.4 Vinca alkaloids and etoposide

H etoposide H vinblastine sulphate1 H vincristine sulphate1 H vindesine sulphate1 H vinorelbine1 H vinorelbine (oral2 )

1 Vinblastine, vincristine, vindesine and vinorelbine injections and infusions are for intravenous administration only. They must NOT be given intrathecally due to severe neurotoxicity which is usually fatal. 2 Oral vinorelbine (Navelbine Oral®) is recommended for use within NHS Wales as a single agent (in line with current NICE recommendations for IV vinorelbine), for the treatment of advanced breast cancer stage III and IV relapsing after or refractory to an anthracycline-containing regimen. See AWMSG Guidance 1007. The capsules should be swallowed with water without chewing or sucking.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 119

8.1.5 Other antineoplastic drugs

Many of these agents are the subject of NICE Guidance. For full detail please see: www.nice.org.uk

H asparaginase H amsacrine H bortezomib H carboplatin H cetuximab1 H cisplatin H crisantaspase H dacarbazine H docetaxel H hydroxycarbamide (hydroxyurea) H imatinib (Glivec) H irinotecan hydrochloride H oxaliplatin H paclitaxel H pentostatin H porfimer sodium2 H procarbazine H temozolomide3 H topotecan H trastuzumab4 H tretinoin

1. Cetuximab: AWMSG approval in combination with irinotecan, with specific restrictions applied, for the treatment of EGFR-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy. Treatment must only be initiated and administered under the supervision of a physician experienced in the use of chemotherapeutic agents. June 2006.

2. Porfimer: Photosensitiser for use in Photo Dynamic Therapy as palliative treatment of obstructing endobronchial non-small cell lung cancer. Supported by NICE Intervention Procedure Guidance IPG 87 (2004) and IPG 137 (2005). www.nice.org.uk.

3. Temozolomide : NICE TAG121 June 2007 Glioma (newly diagnosed and high grade) - carmustine implants and temozolomide: Carmustine to remain hospital only, temolozomide to be added as hospital only.

4. Trastuzumab: CARDIOTOXICITY. Monitor cardiac function of all patients before and during treatment - for details of monitoring and managing cardiotoxicity, consult literature. TRASTUZUMAB USE WITH ANTHRACYCLINES. Concomitant use of trastuzumab with anthracyclines (section 8.1.2) is associated with cardiotoxicity. The use of anthracyclines even after stopping trastuzumab can increase the risk of cardiotoxicity and if possible should be avoided for up to 24 weeks. If an anthracycline needs to be used, cardiac function should be monitored closely.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 120

8.2 Drugs Affecting the Immune Response

8.2.1 Antiproliferative immunosuppressants

S azathioprine S mycophenolate mofetil (CellCept) S mycophenolic acid (Myfortic) 1,2

1. Mycophenolic acid as the sodium salt (Myfortic) has been approved by the AWMSG for the prophylaxis (in combination with ciclosporin and corticosteroids) of acute (transplant) rejection in adults receiving allogenic renal transplants, and who are intolerant of mycophenolate mofetil. Its use should be under the supervision of a nephrologist. Please see www.wales.nhs.uk/awmsg 2. Mycophenoilic acid 720mg is approximately equivalent to mycophenolate mofetil 1g but avoid unnecessary switching because of pharmacokinetic differences.

8.2.2 Corticosteroids and other immunosuppressants

Immunosuppressive therapy for renal transplantation in children and adolescents. See NICE TA99 April 06. Renal transplantation - immuno-suppressive regimens (adults) See NICE TA85 Sept 04.

S prednisolone (see section 6.3.2) S ciclosporin Shared care protocol No 01 (cyclosporin) S tacrolimus Shared care protocol No 15 S/H sirolimus1 Cardiff and Vale:Shared Care protocol CV18 North BroTaf: Hospital only H horse lymphoglobulin H rabbit thymoglobulin H basiliximab2 H daclizumab2

1. Sirolimus is reserved for the renal transplant unit. In North Bro Taf restricted to Hospital only use, in Cardiff and the Vale may be Specialist Initiated with GP follow up in line with SCP CV18 2. Basiliximab and daclizumab are both covered by NICE TA 85 and TA99 as above

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 121

8.2.3 Rituximab

H rituximab1

1. Rituximab is included for use within the terms of the following NICE Guidance:

• Rituximab for the treatment of follicular lymphoma, NICE Technology Appraisal Guidance No 110 (Sept 06): Rituximab within its licensed indication (that is, in combination with cyclophosphamide, vincristine and prednisolone) is recommended as an option for the treatment of symptomatic stage III and IV follicular lymphoma in previously untreated patients. • Rituximab for aggressive non-Hodgkin’s Lymphoma NICE guidance No 65, (Sep 03) • Guidance on the use of rituximab for recurrent or refractory stage III or IV follicular Non-Hodgkin’s Lymphoma NICE guidance No 37 ( March 02)

Please see full guidance www.nice.org.uk .

8.2.4 Other immunomodulating drugs

H aldesleukin H interferon alfa1 H peginterferon2 H natalizumab3

1 Interferon alfa: Please refer to NICE guidance No 14 (October 2000) for use in hepatitis C and No 32 November 2001 (under review) for use in multiple sclerosis. Use in hairy cell leukaemia, chronic granulocytic leukaemia, multiple myeloma, and metastatic renal cell carcinoma has been changed to Hospital Only. 2 Peginterferon is included for treatment of hepatitis C. 3 Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. See NICE TA127 August 2007

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 122 8.3 Sex Hormones and Hormone Antagonists in Malignant Disease

8.3.2 Progestogens

S medroxyprogesterone acetate1 S megestrol acetate

1 Medroxyprogesterone acetate: Please prescribe by brand name. Farlutal and Provera may not be bioequivalent.

8.3.4 Hormone antagonists

8.3.4.1 Breast cancer

Please note NICE Guidance: CG14, May 2004. The classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care. www.nice.org.uk TA112 November 2006 Hormonal therapies for the adjuvant treatment of early oestrogen- receptor-positive breast cancer. Please see full guidance www.nice.org.uk

S tamoxifen S anastrozole Shared care protocol No 21 S exemestane Shared care protocol No 23 S letrozole1 See Shared care protocol SC VEL(1)

1. Letrozole: For use under the direction of the shared care protocol in line with the All Wales Professional Guidance on Breast Cancer.

8.3.4.2 Prostate cancer and gonadorelin analogues

S bicalutamide S buserelin S cyproterone acetate1 S flutamide S goserelin S leuprorelin acetate

1 Please state Cyprostat brand to avoid confusion over patient information leaflets.

8.3.4.3 Somatostatin analogues

S lanreotide1 North Bro Taf Only S octreotide Shared Care Protocol 18 and 18(1)

1. Lanreotide, as Somatuline Autogel, is available in North Bro Taf only. For use in acromegaly and neuroendocrine tumours, particularly carcinoid, in accordance with a Shared Care Protocol. Awaiting approval from Cardiff and Vale.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 123 CHAPTER 9 NUTRITION AND BLOOD

9.1 Anaemias and Some Other Blood Disorders

9.1.1 Iron deficiency anaemias

With the exception of patients with severe renal failure receiving haemodialysis, parenteral iron does not produce a faster haemoglobin response than oral iron, provided that the oral iron preparation is taken reliably and is absorbed adequately.

9.1.1.1 Oral iron Preparation Iron salt Form Strength Elemental iron c ferrous sulphate Ferrous sulphate Tablets 200mg 65mg c Fersaday Ferrous fumarate Tablets 322mg 100mg

Liquid preparations Preparation Iron salt Form Strength Elemental iron c Fersamal Ferrous fumarate Syrup 140mg/5mL 45mg/5mL

c Niferex Polysaccharide-iron Liquid 100mg/5mL complex (SF) c Sytron Sodium feredetate Liquid 190mg/5mL 27.5mg/5mL (Sodium (SF) iconedetate)

Iron and folic acid These preparations are used for the prevention of iron and folic acid deficiencies in pregnancy; they should be distinguished from those used for the prevention of neural tube defects in women planning a pregnancy.

Preparation Iron salt Form Elemental iron Folic acid c Pregaday Ferrous fumarate Tablet 100mg 350micrograms

9.1.1.2 Parenteral iron

Please note the danger of confusion between these products and their dose regimens. Refer to local guidance and protocols and to product information to ensure safe prescribing and administration.

S iron sorbitol injection 100mg/2mL for im use (Jectofer) S iron sucrose injection 100mg/5mL for iv use (Venofer) H iron dextran1 injection 100mg/2mL for im or iv use (CosmoFer)

1. Iron dextran is restricted to initiation by specialists and is reserved for in-patient use in line with a local protocol.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 124 9.1.2 Drugs used in megaloblastic anaemias

S folic acid1 tablets 400micrograms, 5mg syrup 2.5mg/5mL S hydroxocobalamin injection 1mg/1mL S folinic acid see section 8.1.3

1 Folic acid, when required for prevention of neural tube defects in pregnancy may be considered a first line agent suitable for GP use.

9.1.3 Drugs used in hypoplastic, haemolytic, and renal anaemias Please see Nice Clinical Guidance 39 September 2006: Anaemia management in chronic kidney disease.

S epoetin1,2,3 pre-filled syringes 1000u/0.5mL, 2000u/0.5mL, (erythropoietin) 3000u/0.3mL, 4000u/0.4mL, 5000u/0.5ml, 6000u/0.6ml, 7000u/0.7ml, 8000u/0.8ml, 9000u/0.9ml, 10,000u/ml (Eprex) pre-filled syringes 4000u/0.4mL, 500u/0.3mL, 1000u/0./3mL, 2000u/0.3mL, 3000u/0.3mL, 4000u/0.3mL, 5000u/0.3mL, 6000u/0.3mL, 10,000u/0.3mL (NeoRecormon) cartridges 10,000u, 20,000u, 60,000u for Reco-Pen (NeoRecormon) S darbepoetin alfa4 pre-filled syringes 10, 15, 20, 30, 40, 50, 60,80, 100micrograms, 150micrograms (Aranesp)

1 CSM Advice – There have been very rare reports of pure red cell aplasia in patients treated with epoetin alfa. The CSM has advised that in patients developing epoetin alfa failure with a diagnosis of pure red cell aplasia, treatment with epoetin alfa must be discontinued and testing for erythropoietin antibodies considered. Corrective treatment should be initiated and patients should not be switched to another erythropoietin. 2 Epoetin: When used to treat renal anaemia, NeoRecormon and Aranesp brands can be given subcutaneously or intravenously whereas the Eprex brand may only be given intravenously. 3 Shared Care Protocol No 3 now applies to epoetin beta only (NeoRecormon). 4 Darbepoetin Shared Care Protocol 03(1) is available on the Bro Taf web site.

Iron overload H desferrioxamine 500mg injection

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 125 9.1.4 Drugs used in platelet disorders

For treatment of ideopathic thrombocytopenic purpura please see BNF section 9.1.4

Primary (essential) thrombycythaemia S anagrelide1 capsule 0.5mg

1. Anagrelide: The Minister for Health and Social Services has endorsed AWMSG's recommendation to support the use of anagrelide within NHS Wales in accordance with its licensed indications (i.e. reduction of elevated platelet counts in at-risk essential thrombocythaemia patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy). Use is subject to the formation of a uniform pathway for the management of patients with essential thrombocythaemia throughout Wales. AWMSG would like haematologists as a professional group to monitor patients and address concerns with regard to long-term safety issues. Please visit www.wales.nhs.uk/awmsg

9.1.6 Drugs used in neutropenia

These drugs should only be used on the advice of a Consultant Haematologist, Oncologist or Paediatric Oncologist.

H filgrastim 30million unit/1mL injection H lenograstim 13.4 million unit, 33.6 million unit vial with 1mL prefilled syringe water for injection

9.2 Fluids and Electrolytes

9.2.1 Oral preparations for fluid and electrolyte imbalance

9.2.1.1 Oral potassium

It is recommended (see BNF) that oral potassium supplements are given as a liquid or effervescent preparation, rather than modified-release tablets, because of the risk of damage to the gastrointestinal tract. c Sando-K tablets effervescent 12mmol K+, 8mmol Cl- S potassium chloride syrup sugar-free 1mmol/1mL (Kay-Cee-L)

Potassium removal H calcium polystyrene powder (Calcium Resonium) sulphonate1 enema 30g/100mL See Appendix 2

1 Calcium resonium may be started after acute treatment. See local guidelines for acute treatment.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 126 9.2.1.2 Oral sodium and water

S sodium chloride capsules 300mg m/r tablets 600mg (Slow Sodium) oral liquid 30mmol/10mL See Appendix 2

Oral rehydration therapy c oral rehydration powder (Dioralyte, Rehydrat Orange)

9.2.1.3 Oral bicarbonate

S sodium bicarbonate capsules 500mg, 1000mg tablets 600mg

9.2.2 Parenteral preparations for fluid and electrolyte imbalance

The range of infusions/injections routinely kept in individual hospitals will depend on local needs.

Sodium chloride infusions/injections H sodium chloride 0.18% polyfusor 500mL H sodium chloride 0.45% infusion 500mL H sodium chloride 0.9% infusions 50mL, 100mL, 250mL, 500mL, 1 litre polyfusor 500mL injection 5mL, 10mL, 50mL H sodium chloride 1.8% polyfusor 500mL H sodium chloride injection 10mL 30mmol/10mL H sodium chloride 5% polyfusor 500mL

Glucose infusions H glucose 5% infusions 50mL, 100mL, 250mL, 500mL, 1 litre polyfusor 500mL H glucose 10% infusion 500mL, 1 litre H glucose 20% infusion 500mL H glucose 25% injection 25mL H glucose 40% infusion 500mL H glucose 50% infusion 500mL injection 50mL pre-filled syringe 50mL

Mixed infusions H glucose and sodium chloride infusion 500mL 2.5%/0.45% H glucose and sodium chloride infusion 500mL 5%/0.45% H glucose and sodium chloride infusion 500mL 10%/0.18% H glucose and sodium chloride infusion 500mL 4%/0.18% H glucose and sodium chloride infusion 500mL, 1 litre 4%/0.18% H glucose 5% with paediatric infusion 500mL electrolytes UHW formula H glucose 10% with paediatric infusion 500mL electrolytes UHW formula H glucose 20% with paediatric infusion 500mL electrolytes UHW formula

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 127 H sodium lactate compound infusion 500mL, 1 litre (Hartmann’s) H sodium lactate compound infusion 500mL, 1 litre (Hartmann’s) half strength infusion H sodium chloride compound polyfusor 500mL (Ringer’s)

Potassium-containing infusions / injections

Safety Warning on Potassium Infusions:

The National Patient Safety Agency (NPSA) issued an alert in July 2002 with guidelines to prevent accidental overdose of intravenous potassium. Concentrated potassium solutions CAN BE FATAL if given inappropriately. The following points apply in all hospitals.

• Potassium infusions should, where possible, be prescribed in concentrations which are available as ready-mixed infusions. • A range of ready-mixed potassium containing fluids is available. Contact your local hospital pharmacy department for details. • Strong Potassium ampoules will be available in Critical Care areas only and MUST be ordered, stored and recorded as controlled drugs. • A second nurse must check the preparation and administration of infusions made using Strong Potassium Injection.

Please refer to your local policy or pharmacy department for full details.

H glucose 5% with potassium infusion 1 litre chloride 20mmol/l H glucose 5% with potassium infusion 1 litre chloride 27mmol/l H glucose 5% with potassium infusions chloride 40mmol/l 500mL, 1 litre H glucose 5% with potassium infusion 1 litre chloride 60mmol/l H glucose and sodium chloride infusions 4%/0.18% with potassium 500mL,1 litre chloride 20mmol/l H glucose and sodium chloride infusions 4%/0.18% with potassium 500mL, 1 litre chloride 27mmol/l H glucose and sodium chloride infusions 4%/0.18% with potassium 500mL, 1 litre chloride 40mmol/l H potassium chloride 15% ampoules (see restrictions above and (20mmol in 10mL)1 10mL note 1) H sodium chloride 0.9% with infusion 1 litre potassium chloride 20mmol/l H sodium chloride 0.9% with infusion 1 litre potassium chloride 27mmol/l H sodium chloride 0.9% with infusions potassium chloride 40mmol/l 500mL, 1 litre H sodium chloride 0.9% with infusion 1 litre potassium chloride 60mmol/l

1 North Glamorgan NHS Trust (only) will continue to use potassium chloride 20% (1g or 13.5mmols in 5 mL).

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 128 Sodium lactate H sodium lactate (1/6 molar) polyfusor 500mL

Sodium bicarbonate infusions/injections H sodium bicarbonate 1.26% polyfusor 500mL H sodium bicarbonate 1.4% polyfusor 500mL H sodium bicarbonate 2.74% polyfusor 500mL H sodium bicarbonate 4.2% polyfusor 500mL H sodium bicarbonate 8.4% polyfusor 200mL pre-filled syringes, 10mL, 50mL injection 10mL, 2mL

Phosphate infusions H sodium phosphate 2.9%/ polyfusor 500mL potassium hydrogen phosphate 0.259%

Water for injections H water for injections injection 2mL, 5mL, 10mL, 20mL, 100mL polyfusor 500mL

Plasma substitutes H dextran 70 in sodium chloride 0.9% infusion 500mL H gelatin (succinylated) 4% and infusion 500mL (Gelofusine) sodium chloride 0.9% H polygeline infusion 500mL (Haemaccel) H pentastarch 10% in sodium infusion 500mL (HAES-steril) chloride 0.9% H pentastarch 6% in sodium chloride infusion 500mL (HAES-steril) 0.9% H albumin 5%1 for resuscitation H albumin 20%2

1 For paediatric use only. 2 For hypoalbuminaemia - supplies from blood bank.

9.2.2.1 Electrolytes and water

Some drugs are incompatible with specific types of plastic used in making infusion fluid containers. The manufacturers listed below have confirmed that their plastic infusion containers are manufactured from the following materials:

Manufacturer Brand Names Materials Used Travenol Viaflex PVC Fresenius Steriflex PVC Fresenius Polyfusor Polyethylene Fresenius Flofusor Polyethylene Macopharma Macoflex PVC

9.2.2.2 Plasma and plasma substitutes

H hydroxyethyl starch 6% in sodium infusion 500ml (Voluven) chloride 0.9%

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 129 9.3 Parenteral Nutrition

Ready to use parenteral nutrition solutions for adults, children and neonates are available in all of the hospitals. Information and advice can be obtained from the ward pharmacist or pharmacy department.

NICE Clinical Guidance No 32. February 2006 - Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. The Guidance focuses on the systematic screening, assessment and treatment of malnourished patients, training for healthcare staff and the provision of specialist nutrition support nurses. Please see full guidance: www.nice.org.uk

9.4 Oral Nutrition

Dietary products, including supplements and feeds prescribed as Borderline Substances, should be prescribed as recommended by the Dietetics Department. For advice and information please contact the dieticians at your local hospital.

9.5 Minerals

9.5.1 Calcium and magnesium

9.5.1.1 Calcium supplements

Preparation Form Calcium Calcium content content in mg in mmol c Sandocal-400 Effervescent tablets 400mg 10mmol c Sandocal-1000 Effervescent tablets 1000mg 25mmol c Calcichew Chewable tablets 500mg 12.6mmol c Calcium-Sandoz Syrup 108.3mg/5mL 2.7mmol/5mL H calcium chloride Injection 10mL 273mg/10mL 6.8mmol/10mL1 10% H calcium gluconate Injection 10mL 89mg/10mL 2.2mmol/10mL 10%

1 See Appendix 2.

9.5.1.2 Hypercalaemia and Hypercalciuria

S cinacalcet1 tablets 30mg, 60mg, 90mg

1. Cinacalcet. See NICE TA117 Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy. Jan 2007.

9.5.1.3 Magnesium

S magnesium tablets 4mmol See Appendix 2 glycerophosphate H magnesium sulphate injection 50% 10g/20mL See Appendix 2

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 130 9.5.2 Phosphorus

9.5.2.1 Phosphate supplements

S Phosphate-Sandoz tablets 16.1mmol H phosphate infusion 50mmol/500mL

9.5.2.2 Phosphate-binding agents

S aluminium hydroxide capsules 475mg (Alu-Cap) S calcium acetate tablets 1g S lanthanum tablets 500mg, 750mg, 1g S sevelamer capsules 403mg

9.5.3 Fluoride

Fluoride products are restricted to initiation in dental clinics.

S sodium fluoride tablets 2.2mg (Fluor-a-day) mouthwash 2% (En-De-Kay Fluorinse)

9.5.4 Zinc

S zinc sulphate capsules 220mg (Zincomed) effervescent tablets 125mg (Solvazinc)

9.6 Vitamins

9.6.1 Vitamin A c vitamins A & D capsules 4000u Vit A/400u Vit D

9.6.2 Vitamin B group c pyridoxine hydrochloride1 tablets 10mg, 20mg, 50mg injection 50mg/2mL c vitamin B Compound tablets c vitamin B Compound Strong tablets c thiamine tablets 25mg, 50mg, 100mg H vitamins B and C2 im injection (Pabrinex IM) iv injection (Pabrinex IV)

1 Pyridoxine at prolonged use of high doses has been linked with reports of possible toxicity. 2 Vitamin B given parenterally may cause potentially serious allergic adverse reactions during or shortly after administration. The CSM has recommended that: • Use be restricted to patients in whom parenteral treatment is essential • Intravenous injections should be administered slowly (over 10 minutes) • Facilities for treating anaphylaxis should be available when it is administered.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 131 9.6.3 Vitamin C c ascorbic acid tablets 100mg, 200mg, 500mg

9.6.4 Vitamin D

Preparation Calcium Calcium Vitamin D Vitamin D content content content in content in in mg in mmol micrograms or units nanograms c calcium and 97mg 2.4mmol 10micrograms 400units ergocalciferol ergocalciferol ergocalciferol tablets c Calcichew D3 500mg 12.6mmol 5micrograms 200units tablets colecalciferol colecalciferol (cholecalciferol) c Calcichew D3 500mg 12.6mmol 10micrograms 400units Forte tablets colecalciferol colecalciferol S alfacalcidol - - 250nanograms 0.25microgram alfacalcidol capsules S alfacalcidol - - 1microgram 1micrograms alfacalcidol capsules S alfacalcidol oral - - 2micrograms/mL drops1 S calciferol tablets - - 250 micrograms 10,000units calciferol calciferol S calciferol tablets - - 1.25mg 50,000units calciferol calciferol S calciferol injection - - 7.5mg/mL 300,000units/ 1mL calciferol mL calciferol S calcitriol injection - - 1micrograms/mL (Calcijex) S calcitriol capsules - - 250 nanograms, (Rocaltrol) 500 nanograms

All patients receiving pharmacological doses of Vitamin D should have the plasma- calcium concentration checked at intervals (initially weekly) and whenever nausea or vomiting are present. Breast milk from women taking pharmacological doses of vitamin D may cause hypercalcaemia if given to an infant.

1 The concentration of alfacalcidol in One-Alpha oral drops is 10 times stronger than that of the former presentation One-Alpha solution.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 132 9.6.5 Vitamin E

S alpha tocopheryl acetate1 suspension 500mg/5mL injection 100mg/2mL inlicensed – See Appendix 2

1. Vitamin E tablets are no longer available. Unlicensed Vita E capsules 75 iu (50mg), 200 iu (134mg) and 400 iu (268mg) are available by special request to pharmacy.

9.6.6 Vitamin K c menadiol sodium phosphate tablets 10mg S phytomenadione injection 10mg/1mL (1mL) (Konakion MM) injection 10mg/1mL (0.2mL)1 (Konakion MM Paediatric) oral drops 1mg (Orakay) See Appendix 2

1 Policies for vitamin K administration in the newborn may vary between trusts. Please refer to local policies.

9.6.7 Multivitamin preparations Please use brand names when prescribing these preparations. c vitamins BPC tablets c Abidec1 oral drops c Dalivit2 oral drops

Vitamin and Mineral Supplements c Forceval capsules junior capsules c Ketovite tablets and liquid

1 Abidec has been reformulated to bring the vitamin A content in line with current recommended daily allowances. 2 Dalivit is reserved for patients with cystic fibrosis due to a higher vitamin A content.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 133 9.8.1 Metabolic disorders Mucopolysaccharidosis I H laronidase (Aldurazyme)1 Concentrate for infusion 500units in 5ml S sodium phenylbutyrate Tablets 500mg (Ammonaps)2 granules 940mg/g H agalsidase beta (Fabrazyme) 3 Intravenous infusion ( powder for reconstitution) 5mg, 35mg vials H alglucosidase alfa (Myozyme) 4 Powder for concentrate for solution for infusion 50mg

1 Laronidase: For hospital use in line with AWMSG guidance: Laronidase is supported for use within NHS Wales in accordance with the drug's SPC, and agreed uniform service standards and clinical guidelines. Any use which falls outside the SPC (such as its short term use before and after Bone Marrow Transplantation) will only be supported if part of an approved clinical trial. Patients from Wales will be treated at either the specialist Lysosomal Storage Clinic in UHW or by one of the six designated Department of Health centres in England. Having received appropriate consent, details of patients receiving treatment will be entered into the Registry for MPS1 held by the Society for Mucopolysaccharide Diseases (the MPS Society). 2 Sodium phenylbutyrate: use in line with AWMSG guidance: Recommended for the treatment of neonates and children suffering from urea cycle disorders with sodium phenylbutyrate within NHS Wales, in accordance with appropriate peer-reviewed guidelines. Please visit www.wales.nhs.uk/awmsg 3 Agalsidase beta (Fabrazyme) is endorsed by AWMSG within NHS Wales for the treatment of Fabry disease in accordance with the licensed indication with the following restrictions: AWMSG recommends that: ® • Patients receiving algalsidase beta (Fabrazyme ) will be entered into the Fabry registry. • Treatment will be administered under the supervision of a physician experienced in the management of Fabry disease or other inherited metabolic diseases. • Treatment will be administered according to agreed guidelines at appropriate centres. Please visit www.wales.nhs.uk/awmsg

4 Alglucosidase alfa (Myozyme) is endorsed by AWMSG within NHS Wales forTreatment of Pompe disease, but with the specific exclusion of Late-onset Pompe disease of the Adult Onset form (Adult Onset disease) because of insufficient evidence of clinical effectiveness. Alglucosidase alfa is available for the treatment of Late Onset Pompe disease of the Juvenile Onset form (Juvenile Onset Disease). AWMSG recommends that: • Patients receiving alglucosidase alfa (MyozymeTM) will be entered into the Pompe registry. • Treatment will be administered under the supervision of a physician experienced in the management of Pompe disease or other neuromuscular disorders. • Treatment will be administered according to agreed guidelines at appropriate centres. Please visit www.wales.nhs.uk/awmsg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 134 CHAPTER 10 MUSCULOSKELETAL AND JOINT DISEASES

10.1 Drugs Used in Rheumatic Diseases and Gout

Osteoarthritis and soft-tissue disorders H Hylan G-F 201 injection (Synvisc) H sodium hyaluronidate1 injection (Hyalgan)

1 Synvisc and Hyalgan will both be available in the short term pending further discussion.

10.1.1 Non-steroidal anti-inflammatory drugs

Interim Update March 2008 From Drug Safety Update Volume 1, Issue 5 December 2007 from MHRA and CHM The ideal anti-inflammatory prescribing choice will vary between patients, depending on individual risk factors, therapeutic response, and patient preference. Patients should use the lowest effective dose, and the shortest duration of treatment necessary to control symptoms

For NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks please see Drug Safety Update: Volume 1, Issue 5, December 2007

To access the NPC’s advice, see NPC - MeReC Bulletin Issue 30 November 2007 This document includes the following practical advice:

• Where NSAIDs are required, prescribing should be based on the safety profiles of individual NSAIDs and on individual patient risk factors. All NSAIDs should generally be used at the lowest effective dose and for the shortest period of time necessary to control symptoms.

• The ideal anti-inflammatory prescribing choice will vary from patient to patient, depending on individual risk factors, therapeutic response, patient preference, and the patient’s attitude to the risk of adverse events.

• Low-dose ibuprofen (≤1200mg per day) is an appropriate first choice NSAID in view of its low risk of GI and CV side effects.

• Low-dose ibuprofen or naproxen 1000mg would appear more appropriate than other NSAIDs for patients in whom CV risk is a significant consideration in decision making.

• Consider prescribing a PPI with any NSAID to reduce the risk of adverse GI effects, particularly in those who are at high GI risk (includes anybody aged 65 years or older) and long-term NSAID users.

• Although coxibs are associated with a lower risk of GI side effects than traditional NSAIDs, there is no good evidence to support the use of coxibs alone ahead of traditional NSAIDs co-prescribed with a PPI. Coxibs also have a higher CV risk than ibuprofen ≤1200mg per day or naproxen 1000mg.

• Medication reviews of NSAIDs should consider:

- Is an NSAID still necessary? - Is the NSAID prescribed appropriate based on the patients CV risk? - Is the NSAID prescribed the one with the lowest GI risk suitable for that patient? - Should a PPI be co-prescribed to reduce the risk of adverse GI effects? - When should treatment/dose next be reviewed?

• When reviewing the treatment of patients already receiving diclofenac, some patients, after discussion, may decide to continue treatment with diclofenac. However, in some cases (especially patients with significant risk factors for CV disease) it may be appropriate to consider alternatives.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 135 Please also note the following CSM warnings:

Asthma - CSM warning: Any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed or (in the case of ibuprofen and others) purchased over the counter. GI side effects - CSM advice: All NSAIDs are associated with serious gastro-intestinal toxicity; the risk is higher in the elderly. Evidence on the relative safety of 7 non-selective NSAIDs indicates differences in the risks of serious upper gastro-intestinal side-effects. Azapropazone [discontinued] is associated with the highest risk and ibuprofen with the lowest; piroxicam, ketoprofen, indometacin, naproxen and diclofenac are associated with intermediate risks (possibly higher in the case of piroxicam). Selective inhibitors of cyclo-oxygenase-2 are associated with a lower risk of serious upper gastro-intestinal side-effects than non-selective NSAIDs.

Recommendations are that NSAIDs associated with low risk e.g. ibuprofen are generally preferred, to start at the lowest recommended dose, not to use more than one oral NSAID at a time, and to remember that all NSAIDs (including selective inhibitors of cyclo- oxygenase-2) are contra-indicated in patients with active peptic ulceration. The CSM also contra-indicates non-selective NSAIDs in patients with a history of peptic ulceration.

The combination of a NSAID and low-dose aspirin may increase the risk of gastro- intestinal side-effects; this combination should only be used if absolutely necessary and the patient monitored closely. Cardiovascular safety – CSM Advice October 2006

Safety of Selective and non-selective NSAIDs New information on non-selective NSAIDs • Non-selective NSAIDs may be associated with a small increased risk of thrombotic events (such as heart attack or stroke) when used at high doses and for long-term treatment.1 • Evidence for diclofenac (particularly at the 150 mg dose) suggests that this drug may have a small thrombotic risk, similar to that of licensed doses of etoricoxib, and possibly other coxibs. These new data are from the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) study. • For ibuprofen, at high doses (e.g. 2400 mg a day) there may be a small thrombotic risk, but overall, at low doses (e.g. 1200 mg or below), epidemiological data do not suggest an increased risk of myocardial infarction. • Naproxen is associated with a lower thrombotic risk than coxibs and, overall, epidemiological data do not suggest an increased risk of myocardial infarction; however, some increase in risk cannot be excluded on the basis of available evidence. For all NSAIDs thrombotic risk is likely to be greater when used at high doses and for long-term treatment.

General advice on prescribing NSAIDs and coxibs • The lowest effective dose of NSAID or coxib should be prescribed for the shortest time necessary for control of symptoms. The need for long-term treatment should be reviewed periodically. • Prescribing should be based on the safety profiles of individual NSAIDs or coxibs and on individual patient risk profiles (eg, gastrointestinal and cardiovascular). • Prescribers should not switch between NSAIDs without careful consideration of the overall safety profile of the products, a patient’s individual risk factors, and patient preference. • Concomitant aspirin (and possibly other antiplatelet drugs) greatly increase the gastrointestinal risks of NSAIDs and severely reduce any gastrointestinal safety advantages of coxibs. Aspirin should only be co-prescribed if absolutely necessary.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 136 Advice relating to selective COX-2 inhibitors remains:

The selective inhibitors of cyclo-oxygenase-2 [celecoxib (Celebrex), etoricoxib (Arcoxia), and parecoxib (Dynastat)] are contra-indicated in: • ischaemic heart disease, • cerebrovascular disease, • peripheral arterial disease, and • moderate or severe heart failure.

The selective inhibitors of cyclo-oxygenase-2 should be used with caution in patients with: • a history of cardiac failure, • left ventricular dysfunction, • hypertension, • in patients with oedema for any other reason, and in patients with • risk factors for heart disease.

March 2008: Prescribing categories have been changed to reflect recent warnings as above. Rheumatologists and other specialists in pain control may use other agents first line as determined by clinical need and risk assessment. c ibuprofen tablets 200mg, 400mg, 600mg low dose ≤1200mg/day oral suspension 100mg/5mL m/r tablets 800mg d ibuprofen preparations as above doses >1200mg/day d diclofenac sodium tablets ec 25mg, 50mg dispersible tablets 50mg m/r tablets 75mg m/r tablets 100mg injection 75mg/3mL suppositories 12.5mg, 25mg, 50mg, 100mg d naproxen tablets ec 250mg, 500mg suspension 125mg/5mL suppositories 500mg d mefenamic acid capsules 250mg tablets 500mg suspension 50mg/5mL d indometacin (indomethacin) capsules 25mg, 50mg m/r capsules 75mg m/r tablets 25mg, 50mg, 75mg liquid 25mg/5mL suppositories 100mg d etodolac m/r tablets 600mg d nabumetone tablets 500mg d meloxicam tablets 7.5mg,15mg suppositories 7.5mg, 15mg d celecoxib1 capsules 100mg, 200mg d etoricoxib2 tablets 60mg, 90mg, 120mg S diclofenac with misoprostol tablets 50mg/200micrograms (Arthrotec 50) tablets 75mg/200micrograms (Arthrotec 75) S phenylbutazone tablets 100mg S sulindac tablets 100mg, 200mg S tenoxicam3 injection 20mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 137

1 Celecoxib is approved for use in line with its licensed indications and where other selective agents have been tried. NICE guidance also states that there is no evidence to justify the simultaneous prescription of gastroprotective agents with COX II selective inhibitors as a means of reducing potential gastro-intestinal adverse events. Hence patients already receiving a gastroprotective agent should be prescribed a standard NSAID. Please refer to NICE guidance No 27 for full information. The CSM has issued a reminder that COX II selective inhibitors do not have antiplatelet activity. 2 Etoricoxib is approved as second line treatment of acute gout in patients fulfilling NICE guidance for use of a COX II agent. Please see full guidance. www.nice.org.uk. 3 Tenoxicam is retained for postoperative use.

10.1.2 Corticosteroids

10.1.2.2 Local corticosteroid injections c methylprednisolone acetate injection 40mg/1mL, 80mg/2ml c methylprednisolone acetate with injection 80mg/20mg/2mL lidocaine c triamcinolone acetonide injection 40mg/1mL (Kenalog Intra-articular/Intramuscular) c dexamethasone phosphate injection 8mg/2mL

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 138 10.1.3 Drugs which suppress the rheumatic disease process

Gold S sodium aurothiomalate injection 10mg/0.5mL, Shared care Protocol No 08 injection 20mg/0.5mL, injection 50mg/0.5mL S auranofin tablets 3mg Shared care Protocol No 09

Penicillamine S penicillamine tablets 125mg, 250mg Shared care Protocol No 04

Antimalarials S chloroquine (see section 5.4.1) S hydroxychloroquine1 tablets 200mg Shared care Protocol No 10 sulphate

Immunosuppressants S azathioprine (see section 8.2.1) Shared care Protocol 24(1)

S ciclosporin (cyclosporin) (see section 8.2.2) Shared care Protocol No 01(2) S methotrexate2 (see section 8.1.3) Shared care Protocol No 11 S cyclophosphamide (see section 8.1.1) S leflunomide tablets 10mg, Shared care Protocol in 20mg,100mg preparation H adalimumab3 pre-filled syringe 40mg see NICE guidance3 H etanercept3,4,5 injection 25mg H infliximab3,4 injection 100mg H rituximab6 concentrate for intravenous infusion 100mg in 10mL 500mg in 50mL

Sulfasalazine S sulfasalazine tablets ec 500mg Shared care Protocol (sulphasalazine) No 05

Please see notes on next page.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 139

1 Hydroxychloroquine: Shared care protocol no. 10 is currently undergoing review. 2 Methotrexate: The CSM has warned of prescription and dispensing errors including fatalities as the dose prescribed is usually a weekly dose. Attention should be paid to the strength of methotrexate tablets prescribed and the frequency of dosing.

CSM advice In view of reports of blood dyscrasias (including fatalities) and liver cirrhosis with low-dose methotrexate, the CSM has advised: • full blood count and renal and liver function tests before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2–3 months • that patients should be advised to report all symptoms and signs suggestive of infection, especially sore throat Treatment with folinic acid (as calcium folinate, section 8.1) may be required in acute toxicity

Important Note that the dose is a weekly dose. To avoid error with low-dose methotrexate, it is recommended that: • the patient is carefully advised of the dose and frequency and the reason for taking methotrexate and any other prescribed medicine (e.g. folic acid); • only one strength of methotrexate tablet (usually 2.5 mg) is prescribed and dispensed; • the prescription and the dispensing label clearly show the dose and frequency of methotrexate administration; • the patient is warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine), and respiratory effects (e.g. shortness of breath). 3 Adalimumab: NICE TAG125 Adalimumab for the treatment of psoriatic arthritis. August 2007. See also NICE TAG130 Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthitis. October 2007 (Replaces TA36 March 02) Prescribers should be encouraged to report all suspected adverse reactions to adalimumab using the yellow card scheme. 4 Etanercept and infliximab: Use in juvenile idiopathic arthritis and rheumatoid arthritis is covered by NICE guidance No 35, March 2002. Use in adults for the treatment of psoriatic arthritis is covered by NICE technology appraisal No 104, July 2006. 5 Etanercept and efalizumab for the treatment of adults with psoriasis: NICE Technology appraisal 103 (July 06). 6 Rituximab for the treatment of rheumatoid arthritis (refractory). See NICE TAG 126 August 2007. For dilution before use.

In all cases please consult product literature for information on administration and warnings. Frequently this is available in the Electronic Medicines Compendium NICE guidance is available at www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 140

10.1.4 Drugs for treatment of gout and cytotoxic-induced hyperuricaemia

Acute attacks of gout c NSAIDs (see 10.1.1 for choice) d colchicine tablets 500micrograms

Long term control of gout c allopurinol tablets 100mg, 300mg d probenecid tablets 500mg See Appendix 2

Hyperuricaemia associated with cytotoxic drugs S allopurinol see previous page H rasburicase1 infusion 1.5mg vial

1 Rasburicase is restricted to use by haematology and cancer centres, and paediatric oncology

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 141 10.2 Drugs Used In Neuromuscular Disorders

10.2.1 Drugs which enhance neuromuscular transmission

S neostigmine tablets 15mg injection 2.5mg/mL S pyridostigmine bromide tablets 60mg S edrophonium chloride injection 10mg/mL

10.2.2 Skeletal muscle relaxants

Treatment of Spasticity

Ideally the treatment of spasticity should be the remit of a Multidisciplinary Team led by an appropriately experienced physiotherapist and physician.

It is vital to identify the goals of treatment. Some patients with lower limb spasticity rely on the hypertonia to maintain a standing position. Treatment of their spasticity may lead to deterioration in their ability to transfer or stand. Therefore, it is vital to establish whether the aim of treatment is a reduction of discomfort, a reduction in spasms or an enhancement of mobility.

Many patients are able to control their spasticity with appropriate exercises. These include standing and stretching regimes as suggested by the physiotherapist. Medical treatment of spasticity can be seen as an adjunct to the essential day to day maintenance of posture and mobility through these exercises.

Problems which may be aggravating spasticity should be identified and addressed. These are wide-ranging and include inappropriate seating, pain of any type and inadequate management of bowel and bladder function. c diazepam1 (see section 4.1.2) d baclofen2 tablets 10mg liquid (SF)5mg/5mL S dantrolene sodium3 capsules 25mg, 100mg S tizanidine4 tablets 2mg, 4mg

Nocturnal leg cramps c quinine sulphate tablets 200mg, 300mg

1 Diazepam is an effective drug in the treatment of spasticity and can be taken by mouth in doses between 2 and 15mg daily. In severe cases a maximum of 60mg daily may be required. It is particularly effective in reducing nocturnal spasms and for the acute treatment of severe spasms. 2 The first line drug is baclofen. Typically the dose is commenced at 5mg tds and increased gradually to a maximum dose of 100mg daily. Abrupt withdrawal may precipitate serious side effects and the CSM advise gradual discontinuation of the drug over one to two weeks. The principal side effect is drowsiness and mild anticholinergic side effects which may affect bladder function. 3 Dantrolene may be used in conjunction with baclofen or as mono therapy. Liver function tests should be monitored before and during therapy at two to three monthly intervals. The therapeutic effect may take a few weeks to develop, but if treatment is ineffective it should be discontinued after four to six weeks. The typical starting dose is 25mg daily, increasing at weekly intervals to a maximum of 100mg four times daily. 4 Tizanidine is restricted to 2nd line use by neurologists and rehabilitation specialists.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 142

10.3 Drugs for the Relief of Soft-Tissue Inflammation

10.3.1 Enzymes

H hyaluronidase injection 1500 unit H chymopapain1

1 Reserved for hospital use by specialists trained in its administration

10.3.2 Rubefacients and other topical anti-rheumatics

Topical NSAIDs and counter-irritants c Algesal cream c Balmosa cream c Transvasin cream d Capsaicin (Axsain) cream 0.075%

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 143 CHAPTER 11 EYE

General Notes on Administration of Drugs To The Eye Eye drops and eye ointments are administered into the pocket formed by gently pulling down the lower eyelid and keeping the eye closed for as long as possible after application, preferably 1-2 minutes. For eye drops, one drop is all that is needed as long as instillation is successful. When two different drops are required at the same time of day, the patient should leave an interval of 5 minutes to avoid dilution and overflow. Many eye preparations contain a preservative e.g. benzalkonium chloride. Those patients sensitive to preservative usually develop the allergy after chronic use. Single use and unpreserved eye drops should be reserved for patients with chronic known allergy to preservatives and/or for diagnostic purposes only. Specials may be supplied when the clinical need for an individual patient demands, given no commercial alternative. Specials do not have a product licence.

11.3 Anti-Infective Eye Preparations

Administration Eye drops (non-viscous) – Prescribe 1 drop at least every 2 hours. The frequency may be reduced as the infection comes under control. Treatment should continue for 48 hours after symptoms have resolved. Eye ointment – Apply either at night (if eye drops used during the day) or 3-4 times daily (if eye ointment used alone). Ideally a swab should be taken before an antibacterial is given. If this is not done and there is no response to treatment, a swab should be taken before changing the antibiotic.

11.3.1 Antibacterials c chloramphenicol1 eye drops 0.5%, eye ointment 1% single use eye drops 0.5% d fusidic acid2 m/r eye drops 1% (Fucithalmic)

1 Chloramphenicol is the drug of choice for superficial eye infections. It has a broad spectrum of activity and is associated with a low level of resistance. Concern has been expressed about a possible link between topical chloramphenicol and bone marrow suppression. The general consensus of opinion is that the link has not been proven but as a precaution, courses should be limited to 5-7 days and topical chloramphenicol be avoided in patients with a personal or family history of blood dyscrasia. 2 Fusidic acid (Fucithalmic) is a second line alternative when chloramphenicol is not indicated or inappropriate.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 144 Ocular antibacterials continued…

H benzylpenicillin eye drops 0.316% preservative free H cefuroxime eye drops 5% See Appendix 2 subconjuctival eye ointment 0.15% H ceftazidime1 eye drops 5% See Appendix 2 H chlorhexidine eye drops 0.02% H ciprofloxacin2 eye drops 0.3% eye drops 0.2% preservative free H gentamicin eye drops 0.3% single use eye drops 0.3% eye drops 1.5% See Appendix 2 H eye drops 1% H propamidine eye drops 0.1% (Brolene) isetionate3 H polymyxin B sulphate eye ointment 10 000u/500u in 1g (Polyfax) H teicoplanin1 eye drops 2% See Appendix 2 H chlortetracycline4 eye ointment 1% (Aureomycin) H vancomycin1 eye drops 5% See Appendix 2

1 Ceftazidime eye drops are manufactured at UHW as a “special”. 2 Ciprofloxacin should be reserved for sight-threatening ocular surface infections and corneal ulcers. Not recommended for simple keratitis in primary care. 3 Propamidine may be bought OTC. It is of little value in bacterial infections but is specific for the rare and potentially devastating acanthamoeba keratitis. Chlorhexidine 0.02% drops are co-administered for this indication. 4 Chlortetracycline may be used for ocular chlamydial infections in conjunction with oral antibiotic therapy. (Consult guidelines).

11.3.2 Antifungals

H amphotericin preservative free eye drops 0.5% See Appendix 2

11.3.3 Antivirals c aciclovir1 eye ointment 3% (acyclovir) S ganciclovir (Virgan)2 eye gel 0.15%

1 Aciclovir may be used for dendritic ulcers caused by herpes simplex. It may also be used in shingles as an adjunct to full dose oral therapy where there is ophthalmic involvement. 2 Ganciclovir is for initiation by consultant ophthalmologists as a second line treatment after failure of aciclovir.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 145 11.4 Corticosteroids and Other Anti-Inflammatory Preparations

11.4.1 Corticosteroids

Topical corticosteroids should normally only be used under expert supervision. They should not be prescribed for undiagnosed “red eye” as they may aggravate herpes simplex infections leading to corneal ulceration with possible loss of vision and even loss of the eye. Bacterial, fungal and amoebic infections pose a similar hazard. Topical corticosteroids may induce glaucoma in predisposed patients. A 'steroid cataract' may follow prolonged use.

Steroid eye drops can raise intra-ocular pressure (IOP) and therefore precipitate glaucoma in patients pre-disposed to chronic simple glaucoma. Evidence suggests that fluorometholone is less likely to raise IOP though this may be a result of poor clinical effect due to reduced penetration of the cornea. Rimexolone is a new topical steroid reported to have the efficacy of prednisolone sodium phosphate 0.5% while having limited effect on IOP.

Steroid-antibiotic ophthalmic combinations are not recommended for routine use. Topical ophthalmic steroids placed in descending order of potency: • prednisolone acetate 1% (most potent) • dexamethasone 0.1% • betamethasone 0.1% • prednisolone sodium phosphate 0.5%, rimexolone1%, hydrocortisone 1% • fluorometholone 0.1% (least potent) The severity of the inflammation determines the choice of steroid. c prednisolone eye drops 0.1%, 0.3%, 0.5% (Predsol) preservative free 0.1%, 0.25%, 1%1 single use eye drops 0.5% S prednisolone with neomycin eye drops 0.5%/0.5% (Predsol N) S hydrocortisone eye ointment 1% S dexamethasone minims 0.1% S betamethasone sodium eye drops 0.1% (Betnesol) phosphate ointment 0.1% S betamethasone with neomycin eye drops 0.1%/0.5% eye ointment 0.1%/0.5% (Betnesol N) S dexamethasone with eye drops 0.1%/0.5% (Maxidex) hypromellose S dexamethasone/ eye/ear drops 0.05%/0.5%/0.005% framycetin/gramicidin (Sofradex) (ointment discontinued) S dexamethasone/neomycin/ ointment 0.1%/0.35%/6000units/g polymixin B (Maxitrol Eye Ointment) H fluorometholone eye drops 0.1% (FML) H prednisolone2 eye drops 1% (Pred Forte) H rimexolone3 eye drops 1%

1 Unbranded multidose preservative-free eye drops require storage in a refrigerator and should be discarded one week after opening 2 Pred Forte is used as part of the ESAP chemotherapy regimen 3 Rimexolone is reserved for second line use in the hospital setting.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 146

11.4.2 Other anti-inflammatory preparations Iatrogenic allergy should be discounted for any allergic conjunctivitis. Common offenders are neomycin, framycetin, atropine, and benzalkonium chloride. c sodium cromoglicate1 eye drops 2% (sodium cromoglycate) eye ointment 4% c lodoxamide eye drops 0.1% d emedastine2 eye drops 0.05% ***removal considered*** d olopatadine (Opatanol) eye drops 1mg/ml

1 Sodium cromoglicate is a mast cell stabiliser which is cheap and effective, particularly as prophylaxis against allergic conjunctivitis. It should be instilled four times a day and may take a couple of weeks to achieve maximal effect. 2 Emedastine is being considered for removal on the advice of the ophthalmology department. Previously included for second line use after sodium cromoglycate. Patients should be monitored for photophobia and lack of response to treatment which may indicate corneal infiltration. The maximum duration of treatment is 6 weeks hence it should not be supplied on “repeat prescriptions”.

Antazoline with xylometazoline (Otrivine-Antistin) has been removed from the Formulary due to the risk of severe follicular conjunctivitis, stinging on application and the four times a day dose regimen. Xylometazoline is a sympathomimetic agent and absorption may result in systemic side effects and the possibility of interactions with other drugs. It should be avoided in angle-closure glaucoma.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 147 11.5 Mydriatics and Cycloplegics

Patients should be warned not to drive or operate machinery for a few hours after mydriasis. Some people will be affected more than others according to age, condition, and current level of vision. The onus is on the person administering drops to warn of POTENTIAL disturbance of vision for “a few hours”.

Antimuscarinics Antimuscarinics dilate the pupil and paralyse the ciliary muscle resulting in mydriasis and cycloplegia. Mydriasis may precipitate acute angle-closure glaucoma in a very few people usually aged over 60 years and long-sighted. c tropicamide1 single use eye drops 0.5%, 1% S cyclopentolate hydrochloride2 eye drops 0.5%, 1% single use eye drops 0.5%, 1% H atropine sulphate3 eye drops 1%, eye ointment 1% single use eye drops 1%

Sympathomimetics H phenylephrine hydrochloride4 single use eye drops 2.5%, 10%

1 Tropicamide is short acting, with an effect lasting approximately 4-6 hours. It is suitable for ophthalmological examination in General Practice. 2 Cyclopentolate activity lasts for up to 24 hours. It may be used to reduce ciliary spasm and pain. 3 Atropine has the longest duration of action, sometimes over a week. It is also used to treat anterior uveitis mainly to prevent posterior synechiae. Atropine has a tendency to cause hypersensitivity. 4 Phenylephrine is used for mydriasis in diagnostic procedures and prevention of posterior synechiae.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 148 11.6 Treatment of Glaucoma

Miotics S pilocarpine1 eye drops 1%, 2%, 4% single use eye drops 1%, 4% ophthalmic gel 4% (Pilogel) Sympathomimetics S brimonidine tartrate2 eye drops 0.2% (Alphagan) S brimonidine tartrate with timolol eye drops 0.2%/0.5% (Combigan) S guanethidine with adrenaline3 eye drops 1%/0.2%, 3%/0.5% (Ganda) 1 Pilocarpine tends to be used as add-on therapy. Darker pupils require higher strength formulations. 2 Brimonidine is a selective alpha-2 adrenoceptor stimulant licensed for use in those patients who are unresponsive to beta-blockers or if beta-blockers are contra- indicated. 3 Guanethidine and adrenaline drops (Ganda) are used at UHW for thyroid eye disease. The use of dipivefrine and adrenaline eye drops has reduced due to associated systemic and ocular side effects. Dipivefrine eye drops should be restricted to existing patients who are well controlled on it.

Beta-blockers Beta-blocker eye drops have traditionally been the drug of choice for treatment of glaucoma. They are however associated with systemic side effects similar to those of oral therapy. The CSM has advised that beta-blockers (even those with apparent cardioselectivity) should not be used in patients with asthma or a history of obstructive airways disease unless no alternative treatment is available. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. Interactions: Since systemic absorption may follow topical application the possibility of interactions in particular with drugs such as verapamil should be borne in mind.

S betaxolol hydrochloride1 eye drops 0.25% suspension minims 0.25% (Betoptic) S timolol maleate2 eye drops 0.25% m/r eye drops 0.25% (Timoptol LA) S metipranolol3 single use eye drops 0.3%, 0.6% S carteolol hydrochloride eye drops 1%, 2%

1 Betaxolol has the best side effect profile in the class and is one of the cheaper agents. 2 Evidence suggests that timolol 0.25% is no less effective than timolol 0.5% and for this reason the 0.5% preparation is not included in this formulary. Metipranolol may be used to control postoperative raised Intra Ocular Pressure.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 149 Carbonic anhydrase inhibitors and systemic drugs Carbonic anhydrase inhibitors act by reducing the production of aqueous humour. They are sulphonamide- related drugs and may give rise to associated side effects e.g. blood disorders, rashes and electrolyte disturbances, especially with systemic treatment. Systemic use also produces a weak diuresis.

S brinzolamide1 eye dops 10mg/mL S dorzolamide2 eye drops 2% (Trusopt) S acetazolamide3 m/r capsules 250mg H acetazolamide tablets 250mg injection 500mg

Carbonic anhydrase inhibitors with timolol S dorzolamide with timolol eye drops 2%/0.5% (Cosopt) S dorzolamide with timolol unit dose eye drops 2%/0.5% (Cosopt preservative-free)

1 Brinzolamide has been added to the formulary in addition to dorzolamide. Both will be subject to review. 2 Dorzolamide is a useful second line agent when beta-blockers are contra-indicated or in addition to a topical beta-blocker as dual therapy is more beneficial than monotherapy. Systemic side effects are less compared to oral/iv acetazolamide. 3 Acetazolamide is generally used as oral or occasionally parenteral therapy for acute glaucoma.

Prostaglandin analogue S bimatoprost1 eye drops 300micrograms/mL S latanoprost1 eye drops 50micrograms/mL S travoprost 1 (Travatan) eye drops 40micrograms/mL

Prostaglandin analogue with timolol These combination products may be initiated by GPs provided the patient is already stabilised on both drugs.

S travoprost 1 with timolol maleate eye drops 40micrograms/5mg/mL (DuoTrav) S bimatoprost1 with timolol maleate eye drops 300micrograms/5mg/mL (Ganfort)

1 Bimatoprost, latanoprost and travoprost are indicated for open-angle glaucoma and ocular hypertension in patients intolerant of, or unresponsive to, other drugs. Lung function tests may assist in the identification of those who are intolerant to beta- blockers. They may darken the colour of the iris (withdraw treatment if possible). This may be particularly important for patients with mixed coloured irides and those receiving treatment in one eye only. Uveitis and macular oedema have been reported.

Others H mannitol infusion 20% (see section 2.2.5)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 150 11.7 Local Anaesthetics

Local anaesthetics should never be used in the management of ocular symptoms. c oxybuprocaine hydrochloride single use eye drops 0.4% H proxymetacaine hydrochloride1 single use eye drops 0.5% H tetracaine hydrochloride2 single use eye drops 0.5%, 1% (amethocaine hydrochloride)2 H proxymetacaine and fluorescein single use eye drops 0.5%/0.25%

1 Proxymetacaine is short acting. It causes less ocular pain on administration than the other local anaesthetics, making it particularly suitable for children. 2 Tetracaine (Amethocaine) has a longer duration of action than the other agents.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 151

11.8 Miscellaneous Ophthalmic Preparations

11.8.1 Tear deficiency, ocular lubricants and astringents

Most ocular lubricants may be purchased over the counter from a Pharmacy at a cost less than the current prescription charge. c sodium chloride single use eye drops 0.9% solution 15mL, c carbomers1 eye drops 0.2% (Viscotears) c hypromellose2 eye drops 0.3%, 2% d carmellose sodium1 single use eye drops 1% (Celluvisc) d liquid paraffin3 eye ointment (Lacri-Lube) d polyvinyl alcohol4 eye drops 1.4% (Liquifilm Tears) single use eye drops 1.4% d povidone5 single use eye drops 5% (Oculotect) S hydroxyethylcellulose6 single use eye drops 0.44% (Artificial Tears) H acetylcysteine with eye drops 5% (Ilube) hypromellose H balanced salt solution7 irrigations 250mL, 500mL (theatre See appendix 2 use only) H BSS plus (theatre use only) See appendix 2

1 Carbomers (Viscotears) may be used for moderate symptoms. It clings to the eye surface which prolongs its effect, allowing administration to be three or four times a day or as required. 2 Hypromellose is included for existing patients but is no longer the preferred ocular lubricant due to the need for frequent reapplications. The standard preparation is 0.3% and may require administration up to every hour. Unpreserved hypromellose is a pharmaceutical special and should only be used where there is a proven allergy to preservative. It has an expiry of 1 week after opening. 3 Liquid paraffin (Lacri-Lube) is included as a lubricating eye ointment for severe symptoms. It may be used in combination with artificial teardrops and applied at night. It contains wool fat derivatives. Equivalent to Simple Eye Ointment. 4 Polyvinyl alcohol (Liquifilm) may be effective where hypromellose-based preparations have failed. 5 Oculotect is similar but is reserved for patients requiring a preservative free preparation. 6 Hydroxyethylcellulose (Artificial Tears) are useful where the condition is severe. Preservatives may be avoided where necessary by use of the minims. 7 Sodium chloride and BSS are included for a variety of irrigation procedures.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 152

11.8.2 Ocular diagnostic and peri-operative preparations and photodynamic treatment

Please note NICE guidance No 68, September 2003 on macular degeneration (age-related) – photodynamic therapy.

Ocular diagnostic preparations c fluorescein sodium1 single use eye drops 2% medicated stick 1% (Fluorets) H rose bengal2 single use eye drops 1%

1 Fluorescein is the standard preparation to detect ocular lesions and foreign bodies. 2 Rose Bengal eye drops are included as a diagnostic aid for dry eye.

Ocular peri-operative drugs H acetylcholine intra-ocular solution 1% (Miochol) S adrenaline1(epinephrine) eye drops 0.1% H apraclonidine single use eye drops 1% H betamethasone injection 4mg in 1mL H diclofenac2 eye drops 0.1% (Voltarol Ophtha) H flurbiprofen single use ophthalmic solution 0.03% (Ocufen) S ketorolac3 eye drops 0.5% (Acular) c sodium chloride irrigation 0.9%, bags 500mL sachets 10mL minims H sodium chondroitin/ prefilled syringe (Viscoat) sodium hyaluronate4 H sodium hyaluronate4,5 syringe 0.5mg/5mL (Provisc) syringe 7.7mg/0.55mL (HealonidGV) H triamcinolone injection (Kenalog) H verteporfin6 injection 15mg

Prescribing notes for ocular peri-operative drugs 1 Adrenaline eye drops are retained for use in squint/glaucoma surgery. 2 Voltarol Ophtha (diclofenac) is a NSAID eye drop indicated for intra-operative and post-operative use. It is only available as single dose eye drops. Very few patients require long term therapy usually under the supervision of an ophthalmologist. 3 Acular (ketorolac) is another NSAID eye drop with similar indications to Voltarol Ophtha. It is available as preserved eye drops and is a fraction of the cost. 4 Provisc, Healonid and Viscoat are restricted to use in theatre. 5 Sodium hyaluronate is widely used during intraocular surgery. Various “basic” and “heavy” forms are available. “Healonid” may also be used to prepare drops for extreme dry eye treatment. 6 Verteporfin is available subject to clarification of funding arrangements.

Other preparations used in ophthalmology These items have occasional use in specialist centres. Prescribing is restricted to consultant ophthalmologists. Please consult departmental protocols for more information.

H 5-fluorouracil injection – strength may vary See Appendix 2 H retinoic acid drops 0.05% H mydricaine injection no1, no2 H mitomycin C topical application H ciclosporin (cyclosporin) drops and oral preparations

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 153 11.9 Contact Lenses

Avoid using preparations containing preservatives with soft contact lenses. Many drugs can affect contact lenses – see BNF for details.

11.10 Unit Dose (Preservative-Free) Eye Drops

These are often used for administering single doses in clinic or theatre. They may also be required as an alternative to standard multidose vials where allergy or intolerance of the preservative is suspected.

The table below lists the drugs which should be available for out-patient prescribing in preservative-free presentations.

S chloramphenicol S prednisolone sodium phosphate S artificial tears H gentamicin H betaxolol or timolol

The following unit dose eye drops should be available for SINGLE use in eye clinics, wards and theatres: c benoxinate c chloramphenicol c fluorescein c sodium chloride c tropicamide 1% H tetracaine amethocaine 1% H atropine H cyclopentolate 0.5%, 1% H lidocaine/fluorescein (lignocaine/fluorescein) H metipranolol H phenylephrine 2.5%, 10% H pilocarpine 1%, 4% H proxymetacaine H proxymetacaine + fluorescein. H rose bengal

The following drugs should also be available for single use in OPDs c Viscotears c chloramphenicol H NSAID (Ocufen or Voltarol) H apraclonidine 1% H fluorets

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 154 CHAPTER 12 EAR, NOSE AND OROPHARYNX 12.1 Drugs Acting on the Ear 12.1.1 Otitis externa

General Note: The use of long term antibiotics is strongly associated with the development of resistance. Therefore, please restrict use to 7 days. Consult with local experts for advice if necessary.

Astringent preparations c aluminium acetate ear drops 8% , 13%

Anti-inflammatory preparations c betamethasone sodium ear drops 0.1% phosphate

With antibacterial c dexamethasone with ear spray 0.1%/3250units/mL neomycin (Otomize) c flumetasone ear drops 0.02%/1% (flumethasone) (Locorten-Vioform) with clioquinol c hydrocortisone with ear drops 1%/0.3% gentamicin (Gentisone-HC) d betamethasone with ear drops 0.1%/0.5% neomycin

Anti-infective preparations c clotrimazole solution 1% c gentamicin ear drops 0.3% c chloramphenicol ear drops 5%, 10% S colistin ear drops 1% (1,000,000unit See Appendix 2 injection)

Other compound anti-infective preparations c hydrocortisone 1%, neomycin ear drops (Otosporin) sulphate 3400 units, polymyxin B sulphate 10,000 units/mL c dexamethasone 0.05%, ear drops, (Sofradex) framycetin sulphate 0.5%, gramicidin 0.005% c triamcinolone acetonide 0.1%, ear ointment gramicidin 0.025%, (Tri-Adcortyl Otic) neomycin 0.25%, nystatin 100,000units/g

12.1.2 Otitis Media Acute otitis media is the commonest cause of severe pain in young children. Viral infections can be treated with a simple analgesic, whereas bacterial infections will require systemic antibacterials, in addition to the analgesic. Topical treatment is considered ineffective and ear drops containing local anaesthetics should be avoided. The CSM has issued a reminder that topical treatment with ototoxic antibotics is contra-indicated in the presence of a perforation. Please see BNF for full details.

12.1.3 Removal of ear wax c olive oil ear drops c sodium bicarbonate ear drops 5% d Cerumol ear drops

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 155

12.2 Drugs Acting on the Nose

12.2.1 Drugs used in nasal allergy c beclometasone dipropionate 50micrograms/spray c azelastine hydrochloride 140micrograms/spray (Rhinolast) c budesonide 100micrograms/puff c 50micrograms/spray (Flixonase) c sodium cromoglicate (sodium nasal spray 4% (Rynacrom) cromoglycate) d mometasone furoate 50micrograms/spray (Nasonex) d betamethasone sodium nasal drops 0.1% phosphate

12.2.2 Topical nasal decongestants

Sympathomimetics c ephedrine hydrochloride nasal drops 0.5%, 1% c xylometazoline hydrochloride nasal drops 0.1%, 0.05% c sodium chloride nasal drops 0.9% c steam inhalations

Antimuscarinic c ipratropium bromide 21micrograms/spray (Rinatec)

12.2.3 Nasal preparations for infection and epistaxis

General Note: the use of long term antibiotics is strongly associated with the development of resistance. Therefore, please restrict use to 7 days. Consult with local experts for advice if necessary.

Nasal staphylococci c chlorhexidine with neomycin cream 0.1%/3250unit/g (Naseptin1) c mupirocin nasal ointment 2% (Bactroban Nasal)

1 Naseptin contains peanut oil.

Epistaxis c bismuth subnitrate & iodoform paste (BIPP) gauze 1.25cm x 100cm gauze 2.5cm x 100cm

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 156

12.3 Drugs Acting on the Oropharynx

12.3.1 Drugs for oral ulceration and inflammation c triamcinolone acetonide oral paste 0.1% (Adcortyl in Orabase) c hydrocortisone pellets 2.5mg (Corlan) c benzydamine hydrochloride oral rinse 0.15% (Difflam) spray 0.15% (Difflam) c chlorhexidine gluconate (see 12.3.4 for preparations) d tetracycline capsules 250mg1 d carmellose sodium oral paste (Orabase) d choline salicylate oral gel (Bonjela)

1 For preparation of a tetracycline mouthwash, the contents of a 250mg tetracycline capsule (see section 5.1.3) can be stirred into a small amount of water, then held in the mouth for 2-3 minutes 3-4 times daily for 3 days; longer courses are sometimes used (but precautions may be required to avoid oral thrush, section 12.3.2): it should preferably not be swallowed [unlicensed indication]. Note. Tetracycline stains teeth; avoid in children under 12 years of age.

12.3.2 Oropharyngeal anti-infective drugs c nystatin oral suspension 100,000units/mL pastilles 100,000units c miconazole oral gel 24mg/mL c amphotericin oral suspension 100mg/mL lozenges 10mg

12.3.3 Lozenges and sprays d Strepsils lozenges d Dequacaine lozenges

12.3.4 Mouthwashes, gargles, and dentifrices c chlorhexidine gluconate mouthwash 0.2% (Corsodyl) dental gel 1% oral spray 0.2% d compound glycerin thymol BP mouthwash d thymol mouthwash solution tablets d hydrogen peroxide mouthwash 6% d povidone – iodine mouthwash 1% (Betadine) S Hammersmith mouthwash1

1 Hammersmith mouthwash is retained by specialist request.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 157 12.3.5 Treatment of dry mouth

Local treatment c Saliva Orthana oral spray, lozenges c Salivix1 pastilles c Biotene Oralbalance1 gel c Raspberry mucilage Oral mixture c saliva stimulating tablets (SST) Tablets H glycerin and lemon mouthwash/sticks

1 Salivix and Biotène Oralbalance1 prescriptions should be endorsed ACBS in the community.

Systemic treatment H pilocarpine hydrochloride tablets 5mg (Salagen)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 158 CHAPTER 13 SKIN

13.2.1 Emollients

Emollient preparations should be chosen according to the needs of each individual patient. In general, greasier preparations such as white soft paraffin are more effective at retaining moisture within the skin, but less acceptable for patients. Patients should be given a choice of several different emollients, with a lighter one for daytime use. Adequate quantities should be prescribed. This is one of the most important aspects in managing patients with many chronic skin conditions. In order to cover the body surface totally, an average size man will require approximately 20 grams of ointment or cream for each application. For application three times a day, a 500g pack could be expected to last one week. There is some concern over the allergenic potential of the topical use of Arachis (peanut) oil. This is particularly the case in children with atopic eczema and this should generally be avoided. For more information on the choice of vehicle, prescribing quantities and common sensitisers, please see BNF chapter 13.1 c aqueous cream c emulsifying ointment c hydrous ointment oily cream c white soft paraffin c Diprobase cream c Diprobase ointment c E45 cream c Kamillosan1 c Oilatum shower emollient c Unguentum M c zinc and castor oil cream c Sudocrem c Cetomacrogol formula A c arachis oil c sun flower oil c white soft paraffin/liquid paraffin 50/50 c olive oil d Aveeno2 d Epaderm d Ultrabase d Dermol 500 Lotion Dermol 200 shower. d Eucerin Intensive 10% Treatment Cream & Lotion

1 Kamillosan is restricted to maternity use. 2 FP10 prescriptions for these products must be in accordance with ACBS advice and endorsed “ACBS”. 3 Dermol contains the antimicrobials benzalkonium chloride and chlorhexidine and is recommended only where infection is present or is a recurrent problem.

Note: Lacticare has been discontinued.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 159 13.2.1.1 Emollient Bath Additives

Patients with eczema, psoriasis or other dry skin conditions need to avoid soap and so should be advised to use an emollient as a soap substitute. Emollient bath additives and shower gels will help prevent the skin becoming too dry after bathing and showering. Patients and carers should be warned of the increased risk of slipping in the bath and use of a non-slip mat is strongly advised. c Oilatum Emollient c Oilatum Plus c Balneum Plus c Alpha Keri Bath c Balneum bath oil d Aveeno bath oil d Hydromol Emollient bath additive

13.2.2 Barrier Preparations

Barrier preparations often contain water-repellent substances such as dimeticone (dimethicone) or other silicones. They help protect the skin from moisture and irritants and are useful around stomas, pressure areas and bedsores. They are no substitute for adequate nursing care. Traditional compound zinc ointments may be as effective as the newer products. c Zinc compound paste c Zinc and castor oil ointment c Lassar’s paste c Conotrane cream c Drapolene cream d Siopel cream d Metanium ointment d Sprilon d Sudocrem d Vasogen S Cavilon

13.3 Topical Local anaesthetics and Antipruritics c Oily calamine lotion c Calamine lotion c Menthol 1% in Aqueous cream c Menthol 2% in Aqueous cream c Crotamiton 10% cream d phenol 2% in compound zinc paste S doxepin cream 5% (Xepin)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 160

13.4 Topical Corticosteroids

Many skin conditions do not respond to weak topical corticosteroids and doctors may consider use of a more potent topical corticosteroid initially, then change to a less potent product as the disease comes under control. If seeking to reduce the risk of side effects such as thinning of the skin and the formation of striae, a mild or moderately potent corticosteroid should be selected. Ointments should be used in preference to creams except where inflamed skin is moist and weeping. Patients can become sensitised to ingredients in topical preparations and even to topical corticosteroids themselves.

NICE Technology No 81 (Aug 04) Atopic dermatitis (eczema) – topical steroids :

This appraisal relates to the frequency of application of topical corticosteroids in the treatment of atopic eczema. It does not include topical agents that combine corticosteroids with other active agents (e.g. antimicrobials or salicylic acid). 1 Topical corticosteroids for atopic eczema should be prescribed for application only once or twice daily. 2 Where more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the drug with the lowest acquisition cost should be prescribed, taking into account pack size and frequency of application. Please see full guidance www.nice.org.uk

MILD c hydrocortisone cream 1%, 2.5% ointment 1%, 2.5% c fluocinolone cream 0.0025% (Synalar 1 in 10)

Compound Preparations d Eurax-Hydrocortisone crotamiton with hydrocortisone cream 10%/0.25%

Mild with antimicrobials c Canesten HC cream hydrocortisone 1% clotrimazole 1% c Daktacort cream hydrocortisone 1%/ miconazole 2% ointment hydrocortisone 1%/ miconazole 2% c Vioform-Hydrocortisone hydrocortisone 1%/clioquinol 3% c Timodine cream hydrocortisone 0.5%, nystatin 100,000units/g benzalkonium chloride 0.2%, dimeticone d Fucidin H cream, ointment, gel hydrocortisone 1%, fusidic acid 2%

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 161

MODERATELY POTENT c Eumovate clobetasone butyrate 0.05% cream ointment c Betnovate RD betamethasone 0.025% (as valerate) cream ointment c Synalar 1 in 4 fluocinolone acetonide 0.00625% cream ointment c Trimovate clobetasone butyrate 0.05%, oxytetracycline 3%, nystatin 100,000units/g cream d Haelan fludroxycortide/ flurandrenolone 0.0125% cream ointment

POTENT c Locoid hydrocortisone butyrate 0.1% cream ointment lipocream scalp application c Betnovate betamethasone 0.1% (as valerate) cream ointment scalp application c Synalar fluocinolone acetonide 0.025% cream ointment gel c Elocon mometasone furoate 0.1% cream ointment lotion d Bettamousse betamethasone valerate 0.12%≡betamethasone 0.1% foam d Cutivate fluticasone propionate 0.005% cream ointment H Haelan fludroxycortide/flurandrenolone 4micrograms/cm2 tape

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 162 Topical corticosteroids cont../

Potent with salicylic acid c Diprosalic betamethasone with salicylic acid ointment 0.05%/3% scalp application 0.05%/2%

Potent with antimicrobials c Locoid C hydrocortisone butyrate with chlorquinaldol cream, ointment 0.1%/3% d Betnovate C betamethasone 0.1%, clioquinol 3% cream ointment d Betnovate N betamethasone 0.1%, neomycin 0.5% cream ointment d Aureocort triamcinolone acetonide 0.1%, chlortetracycline 3% ointment d Fucibet betamethasone 0.1%, fusidic acid 2% cream

Potent with antibacterials d Synalar N fluocinolone acetonide 0.025%, neomycin 0.5% cream ointment d Synalar C fluocinolone acetonide 0.025%, clioquinol 3% cream ointment

VERY POTENT d Dermovate clobetasol propionate 0.05% cream lotion ointment

All Dermovate NN products have been discontinued

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 163 13.5 Preparations for eczema and psoriasis

13.5.1 Preparations for eczema

Please also see related sections: emollients 13.2.1, topical corticosteroids 13.4 topical antibacterials 13.10.1 systemic antibacterials 5.1

d ichthammoll ointment BP

13.5.2 Preparations for Psoriasis

Topical preparations for psoriasis c Dovonex calcipotriol1 cream 50 micrograms/g scalp application 50 micrograms/mL ointment 50 micrograms/g (generic) H Dovobet2 ointment betamethasone 0.05%, calcipotriol 50micrograms/g c Polytar emollient c Cocois coal tar soln 12%’ salicylic acid 2%, precipitated sulphur 4% scalp application c Alphosyl HC coal tar extract 5%, hydrocortisone 0.5%, allantoin 2% cream c Dithrocream3 dithranol cream 0.1%, 0.25%, 0.5%, 1%, 2% c Salicylic acid ointment 2% c Silkis4 calcitriol ointment 3 micrograms/g c Zinc and Salicylic acid paste c Exorex prepared coal tar lotion 1% d Curatoderm tacalcitol ointment 4 micrograms/g d Zorac tazarotene gel 0.05% d Coal Tar and Salicylic acid5 ointments d Coal Tar in Unguentum Merck5 ointments d Dithranol ointment or paste: usual strengths 0.1-2% d Micanol dithranol 1% cream d Coal Tar Paste strong coal tar solution 7.5%

Please see notes overleaf

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 164 Prescribing notes for topical psoriasis preparations 1 Vitamin D analogues do not smell or stain clothing. The use of emollients before treatments should be encouraged to ensure that the cream or ointment reaches the affected area. 2 Dovobet is a combination product containing betamethasone and calcipotriol. It is available for an assessment period, prescribed, in most cases, by Consultant Dermatologists 3 Notes on the use of Dithrocream: • Dithrocream needs to be applied carefully to lesions. Hands should be washed carefully after use. When using a higher concentration of Dithrocream it is advisable to use a wooden spatula or disposable gloves; • Dithrocream will burn any surrounding non-psoriatic skin. Applying Vaseline as a barrier will help prevent this; • Dithrocream should only be applied to psoriatic plaques, avoiding flexural areas. Application in the flexures causes smudging onto clear skin, which results in burning and soreness; • Dithrocream can be left on psoriatic plaques for 30 minutes or longer but preferably not overnight to avoid the risk of it spreading onto healthy skin; • If required for the face it should be applied with caution. On the scalp it may stain fair or grey hair pink which is permanent until the hair grows out. The brown staining of Dithranol on the skin is temporary and will usually disappear approximately 14 days after treatment. It will, however, stain clothing, furniture and bedding permanently. The bath and shower should be cleaned immediately after use to help prevent staining; • Where scalp application is required it should be combed against the direction of growth to help lift the scale. For overnight use, bed clothing should be protected. A tar-based shampoo should be used in the morning to remove the treatment; • Dithrocream is a long-term treatment for psoriasis. It is important to continue with daily applications for several weeks, increasing the strength as necessary. 4 Silkis (calcitriol) ointment: Use in accordance with SPC advice on the duration of treatment. 5 Coal tar with Unguentum Merck or salicylic acid – available in various strengths as extemporaneous products from St Mary’s manufacturing unit.

Oral retinoids for psoriasis H acitretin capsules 10mg, 25mg

Oral preparations for psoriasis H 5 methoxypsoralen1 tablets 20mg H 8 methoxypsoralen1 tablets 10mg bath additive 1.2%

1 Named patient.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 165 13.5.3 Drugs affecting immune response

S ciclosporin (cyclosporin) see section 8.2.2 for preparations Shared Care Protocol 01(1) S methotrexate1 see section 8.1.3 for preparations Shared Care Protocol 11(1) proposed S pimecrolimus 2 cream 1% (Elidel) S tacrolimus2 ointment 0.03%, 0.1% (Protopic) H efalizumab3 injection 125mg

1 Methotrexate: The CSM has warned of prescription and dispensing errors including fatalities as the dose prescribed is usually a weekly dose. Attention should be paid to the strength of methotrexate tablets prescribed and the frequency of dosing.

2 Pimecrolimus and tacrolimus: For use in line with NICE Technology Appraisal No 82 (Aug 04) 2.1 Topical tacrolimus and pimecrolimus are not recommended for the treatment of mild atopic eczema or as first-line treatments for atopic eczema of any severity. 2.2 Topical tacrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate to severe atopic eczema in adults and children aged 2 years and older that has not been controlled by topical corticosteroids (see 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy. 2.3 Pimecrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate atopic eczema on the face and neck in children aged 2 to 16 years that has not been controlled by topical corticosteroids (see 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy. 2.4 For the purposes of this guidance, atopic eczema that has not been controlled by topical corticosteroids refers to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency that is appropriate for the patient’s age and the area being treated. 6.5 It is recommended that only physicians (including general practitioners with a special interest in dermatology) should initiate treatment with tacrolimus or pimecrolimus and then only after careful discussion with the patient about the potential risks and benefits of all appropriate second-line treatment options.

3. Efalizumab: For use after etanercept in line with NICE Technology appraisal 103 (July06): Etanercept and efalizumab for the treatment of adults with psoriasis Please see full guidance www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 166 13.6 Acne and Rosacea

For Rosacea see also 13.10.1.2

13.6.1 Topical Preparations for Acne c PanOxyl benzoyl peroxide gel 2.5%, 5%, 10% c Benzamycin benzoyl peroxide 5% with erythromycin 3% gel c tretinoin cream 0.025% gel 0.025% c Isotrexin isotretinoin 0.05%, erythromycin 2% gel c Differin adapalene 0.1% cream gel c Isotrex isotretinoin 0.05% gel c Dalacin T clindamycin 1% alcoholic solution aqueous lotion c Stiemycin erythromycin 2% alcoholic solution c Zineryt erythromycin 40mg, zinc acetate 12mg/mL topical solution c Skinoren azelaic acid 20% cream c Acnecide benzoyl peroxide 5% gel

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 167 13.6.2 Oral Preparations for Acne

With the exception of patients receiving isotretinoin, all patients with acne should as far as possible be treated with a topical anti-acne preparation whether or not they are also receiving oral antibiotic therapy. Irritant dermatitis is a common side effect of most topical anti-acne preparations with the exception of the pure topical antibiotics. This can be minimised by slowly increasing the area to which the preparations are applied and by initial use on every second or third day. For non-inflammatory (comedonal) acne, topical retinoids (Tretinoin, Isotrex, Isotrexin) are preferred. Generally start with cheaper preparations (benzoyl peroxide – PanOxyl), and progress to other preparations if benzoyl peroxide is not tolerated. If using preparations containing topical erythromycin (Benzamycin, Isotrexin, Erythromycin, Zineryt) try to avoid concomitant administration of oral antibiotics of different classes as there is a theoretical risk of multiple drug resistance developing.

Oral antibacterials for acne Please see section 5.1.3

Hormone treatment for acne c cyproterone1 with ethinylestradiol tabs 2mg/35micrograms (Dianette1) (Co-cyprindiol)

Oral retinoid for acne H isotretinoin capsules 20mg (Roaccutane 5mg)

1 Dianette: The CSM has warned of an increased risk of venous thromboembolism (VTE) in women taking Dianette compared with users of low-dose combined oral contraceptives. Hence, Dianette should NOT be used solely as an oral contraceptive, but should be reserved for severe acne that has not responded to oral antibiotics, or for moderately severe hirsutism. It should be withdrawn 3 to 4 cycles after the treated condition has completely resolved. It is contraindicated in women with a personal or close family history of confirmed, idiopathic VTE and those with a known current venous thrombotic or embolic disorder. Women who have severe acne or hirsutism may have an inherently increased cardiovascular risk.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 168 13.7 Preparations for Warts and Calluses

Children under the age of 11 do not tolerate cryotherapy well and if treatment is required a topical therapy should be used. All of the listed preparations will work if they are used regularly and with enthusiasm. Patients with anogenital warts should be screened for other sexually transmitted diseases. c Salicylic acid 2% ointment c Salicylic acid collodion c Salactol paint c Silver Nitrate sticks 75%, 95% c Posalfilin c Duofilm c Occlusal c Salatac gel c Verrugon d Glutarol d Formaldehyde lotion

Genital warts S Podophyllin 25% in Compound benzoin tincture S Condyline solution 0.5% S Warticon fem solution 0.5% S Warticon fem cream 0.15% d Aldara1 imiquimod 5% cream

1 Imiquimod: Ano-genital warts - use in line with the UK National Guideline available on the following websites: www.agum.org.uk and www.mssud.org.uk .

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 169 13.8 Sunscreens and Camouflagers

13.8.1 Sunscreens

A variety of products are available to allow for photosensitive patients who have differing preferences depending on the physical properties and cosmetic acceptability of the creams. c Sunsense Ultra1,2 lotion (SPF 60 & good UVA protection) d Uvistat Ultrablock1 cream (SPF 30 & UVA protection) d RoC Total Sunblock1 (UVB SPF 25 & good UVA cover) d Uvistat lipscreen

1. ACBS (Borderline substances) – These preparations are prescribable for skin protection against UV radiation in abnormal cutaneous photosensitivity resulting from genetic disorders or photodermatoses, including vitiligo and those resulting from radiotherapy; chronic or recurrent herpes simplex labialis. FP(10) prescriptions should be endorsed “ACBS”. 2. Sunsense Ultra has replaced Sun E45 on the formulary.

Photodamage c diclofenac sodium1 Gel 3% (Solaraze) d fluorouracil2 Cream 5% (Efudix) (Awaiting confirmation of 2nd line status in Cardiff and Vale) S Imiquimod3 Cream 5% (Aldara) North Bro Taf Only H methyl-5-aminolevulinate4 Cream 5% (Metvix)

1. Solaraze: For first line treatment in general practice or hospital. The prescriber MUST ensure accurate diagnosis of actinic keratitis prior to prescribing. The product should be prescribed by brand name in order to avoid confusion with other strengths of topical diclofenac licensed for musculoskeletal conditions. 2. Efudix: The prescriber MUST ensure accurate diagnosis of actinic keratitis prior to prescribing. 3. Imiquimod North Bro Taf Only, for treatment of small superficial basal cell carcinoma. Treatment to be initiated by appropriate specialists in primary and secondary care. See also section 13.7. 4. Metvix: For hospital only use restricted dermatology specialists. Replaces unlicensed 5ALA

13.8.2 Camouflagers

S Veil Cover creams S Veil Finishing powder S Covermark Cover creams S Covermark Finishing powder

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 170 13.9 Shampoos and other preparations for scalp conditions c Capasal shampoo c Alphosyl 2 in 1 shampoo c Nizoral 2% shampoo c Polytar liquid c Cocois scalp ointment d Betadine 4% shampoo d T/gel shampoo d Synalar1 gel (fluocinolone 0.025%) d Tar Pomade ointment d CADE compound d Coal tar with salicylic acid 6%/3% in Cetomacrogol cream

1. See Section 13.4. Note: Polytar AF shampoo and Selsun shampoo application have been discontinued.

Hirsutism

S Eflornithine1 Cream 11.5% (Vaniqa)

1. Eflornithine has been included to treat significant facial hirsutism in women with either idiopathic hirsutism or hirsutism associated with polycystic ovarian syndrome, excluding those with ovarian or adrenal androgen secreting tumours. For Specialist Initiation and GP follow-up in line with local guidelines. Please see Bro Taf Prescribing Protocol for Eflornithine (Vaniqa).

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 171 13.10 Anti-infective skin preparations

13.10.1 Antibacterial Preparations

13.10.1.1 Antibacterial Preparations only used topically

Bactroban ointment is a very effective topical antibiotic useful for both staphylococcal and streptococcal infection. It should not be used in or near the eyes or on mucosal surfaces; a nasal preparation is available. Polyfax ointment is an alternative antibiotic preparation, which can be safely used in and around the eyes. Silver sulfadiazine (sulphadiazine) cream is mainly used in the management of burns and its particular advantage is its low viscosity and ease of application to burnt skin. c Flamazine silver sulfadiazine cream 1% (silver sulphadiazine) c Polyfax1 polymyxin 10,000units, bacitracin zinc 500units/g ointment d Bactroban mupirocin ointment and cream 2%

1 See section 11.3.1 for polyfax eye ointment.

13.10.1.2 Other antibacterial preparations also used systemically d Fucidin fusidic acid cream 2%, ointment 2% oral / i.v. see section 5.1.7 For Rosacea c Metrogel metronidazole gel 0.75% c Rozex metronidazole cream 0.75% For malodorous tumours and skin ulcers d Metrotop metronidazole gel 0.80% d Anabact metronidazole gel 0.75%

13.10.2 Antifungal Preparations

Clotrimazole, miconazole and ketoconazole are effective topical agents for the treatment of both tinea and yeast infections. Terbinafine is a very effective topical antifungal agent for the treatment of tinea infection. c clotrimazole solution, cream, spray 1% c miconazole cream 2% c ketoconazole cream 2% c terbinafine cream 1% d benzoic acid ointment, ointment (Whitfields) compound (BP)

13.10.3 Antiviral Preparations c aciclovir cream 5%

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 172 13.10.4 Parasiticidal Preparations

Head Lice Management Summary

Currently, malathion is recommended as first-line insecticide treatment in Wales because there is evidence of resistance to pyrethroids (permethrin and phenothrin).

The pyrethroids may be used as second-line insecticide treatments, but the only preparation on the market suitable for the treatment of headlice is phenothrin. Lyclear (permethrin 1% Creme Rinse) is no longer recommended as contact time is insufficient.

Carbaryl can be used when there is clinical resistance to malathion and pyrethroids and wet combing cannot be carried out.

Wet combing is the main alternative to insecticide treatment. Dimeticone, a non-insecticide treatment, currently not yet on the formulary but available to buy in retail chemists, has been shown to be as safe and efficacious as phenothrin.

In pregnancy - Wet combing, malathion or dimeticone In breastfeeding mothers - Wet combing, malathion or dimeticone In young children - Infants inder 6 months: use of an insecticide or dimeticone should be under medical supervision only. - Exercise caution in all patients under 1 year. - Wet combing is the main alternative to insecticide treatment.

(For full information please also see WMIC Bulletin July 2006 on head lice)

Head Lice c Prioderm malathion 0.5% alcoholic (lotion) c Suleo M malathion 0.5% alcoholic (lotion) d Full Marks phenothrin 0.5% aqueous (liquid) phenothrin 0.2% alcoholic (lotion) phenothrin 0.5% alcoholic (mousse) d Carylderm carbaryl 1% aqueous (liquid) carbaryl 0.5% alcoholic (lotion)

Scabies For full guidance on the treatment of scabies please see WMIC Scabies Q & A Bulletin Oct 2005

c Derbac M malathion 0.5% aqueous c Lyclear1 permethrin dermal cream 5%

1 Lyclear: Preparations of permethrin differ in licensed indication according to strength. The 5% cream is reserved for scabies and crab lice, the 1% cream rinse is available to buy for head lice but is no longer recommended. (see above)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 173 13.10.5 Preparations for minor cuts and abrasions c Savlon dry powder spray Povidone-iodine 1.14% in a pressurised aerosol unit. S Proflavine cream

Preparations for boils c magnesium sulphate paste

Collodion c Flexible Collodion BP

Surgical tissue adhesive H Indermil H Dermabond

13.11 Skin Cleansers and antiseptics

13.11.1 Alcohols and Saline

Standard skin cleansing prior to surgery should be with 0.5% chlorhexidine in 70% industrial methylated spirit. This preparation is inflammable and care must be taken to ensure that it has completely evaporated prior to the use of cautery or diathermy. c Industrial Methylated Spirit, BP spirit 70%, 95% Surgical spirit, BP. c Normasol (sodium chloride Sterile sachets 0.9%) c Skin prep wipes c Sodium Chloride 0.9% Sterile solution 1ltr c Steripod Sodium Chloride 0.9% Sterile solution

13.11.2 Chlorhexidine Salts c chlorhexidine surgical scrub 4% hand rub 0.5% cream 1% (Hibitane obstetric) solution 4% (Phisomed) spirit 0.5% sachets 0.05% H chlorhexidine chlorhexidine 2% in 70% IPA (Chloraprep) 1

with cetrimide d chlorhexidine with cetrimide sachets 0.015%/0.15%

concentrates c chlorhexidine gluconate concentrate 5% hospital concentrate 20%

1 Chloraprep is reserved for skin preparation prior to central venous catheter insertion. The preparation consists of a single use sterile solution with an application swab.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 174 13.11.4 Chlorine and Iodine c sodium hypochlorite cleansing solution 1% c sodium dichloroisocyanurate solution tab c povidone iodine alcoholic solution 10% antiseptic solution 10% surgical scrub 7.5% antiseptic paint 10% skin cleanser 4% dry powder spray 2.5% ointment 10% (Betadine)

13.11.5 Phenolics d Ster-Zac triclosan bath concentrate 2%

1 Infection control only. Aquasept has been withdrawn

13.11.6 Astringents, Oxidisers and Dyes c potassium permanganate1 solution 0.1% c Permitabs S hydrogen peroxide solution 6% S hydrogen peroxide2 solution 3% S aluminium acetate lotion S Crystal violet paint

1 Potassium permanganate solution requires further dilution. Please see BNF. Stains skin and clothes. Irritant to mucous membranes. 2 Hydrogen peroxide 3% is included for chiropody use.

13.12 Antiperspirants c Anhydrol Forte aluminium chloride hexahydrate 20% c glycopyrronium bromide solution 0.05% c Driclor aluminium chloride hexahydrate 20% c ZeaSORB aldioxa 0.22%, chloroxylenol 0.5%

13.13 Wound Management Products and Elastic Hosiery – See Appendix 1

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 175 CHAPTER 14 VACCINES

THIS SECTION ON VACCINES HAS BEEN REMOVED FOR UPDATING. PLEASE REFER TO THE LATEST BNF FOR CURRENT ADVICE.

14.5 Immunoglobulins

Normal immunoglobulin H for IV Infusion H for IM use

Specific immunoglobulins Note Route of supply for human normal and specific immunoglobulins may vary between hospitals.

Anti-D (Rho) immunoglobulin. Please see NICE guidance No 41, April 2002, Pregnancy - routine antenatal anti-D prophylaxis for rhesus-negative women. www.nice.org.uk

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 176 CHAPTER 15 ANAESTHESIA

15.1 General Anaesthesia

15.1.1 Intravenous anaesthetics

Barbiturates H thiopental injection 500mg/20mL, 2.5g/100mL (thiopentone)

Other intravenous anaesthetics S ketamine1 injection 200mg/10mL, 500mg/10mL, 1000mg/5mL H etomidate injection 20mg/10mL H propofol2 injections 1%: 200mg/20mL, 500mg/50mL, 1g/100mL injections 2%: 1000mg/50mL pre-filled syringes 1% 500mg/50mL, 2% 1g/50mL

1 Ketamine - A shared care agreement for ketamine use in palliative care exists. (Protocol No. 20) 2 Propofol – The CSM has recently clarified its warning on use in children: Propofol is licensed for induction and maintenance of general anaesthesia in children of 1 month and over, but is contraindicated for use as a sedative in children aged 16 and under, who are being ventilated on intensive care units. In addition, the CSM does not recommend use as a sedative during surgical and diagnostic procedures in children due to lack of data on safety and efficacy. Please consult the Summary of Product Characteristics for further information.

15.1.2 Inhalational anaesthetics

Volatile anaesthetics and carboxyhaemoglobinaemia. Carboxyhaemoglobinaemia has been reported during anaesthesia with desflurane, enflurane, or isoflurane used in conjunction with carbon dioxide absorbents in breathing systems in the USA. This phenomenon was very rare and occurred when these absorbents became excessively dried out. The use of barium hydroxide lime produces significantly more carbon monoxide than soda lime particularly at low water content. Barium hydroxide lime is not available in the UK. The CSM has advised that no cases of carboxyhaemoglobinaemia have been reported in the UK and it seems unlikely that this problem will arise with the anaesthetic equipment currently in use in the UK.

Volatile liquid anaesthetics H desflurane H halothane1 H isoflurane H sevoflurane

Please see notes overleaf

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 177

1 Halothane: The CSM advises that severe hepatotoxicity can follow halothane anaesthesia. This occurs more frequently after repeated exposures to halothane and has a high mortality. The risk appears to be increased by repeated exposures within a short time interval but even after a long time interval (sometimes of several years) susceptible patients have been reported to develop jaundice. Since there is no reliable way of identifying susceptible patients the CSM recommends the following precautions prior to use of halothane: • A careful anaesthetic history should be taken to determine previous exposure and previous reactions to halothane • Repeated exposure within a period of at least three months should be avoided unless there are overriding clinical circumstances • A history of unexplained jaundice or pyrexia in a patient following exposure to halothane is an absolute contra-indication to its future use in that patient.

Nitrous oxide H nitrous oxide various sizes available H nitrous oxide 50% and oxygen various sizes available (Entonox) 50%

15.1.3 Antimuscarinic drugs

H atropine injection 600micrograms/1mL prefilled syringes 500micrograms/5mL, 1mg/10mL, 3mg/30mL (Min-I-Jet) prefilled syringes 1mg/5mL, 3mg/10mL (Aurum) H glycopyrronium bromide injection 200micrograms/1mL , 600micrograms/3mL H hyoscine hydrobromide injection 400micrograms/1mL (see also section 4.6)

15.1.4 Sedative and analgesic peri-operative drugs

15.1.4.1 Anxiolytics and neuroleptics

Benzodiazepines (See also section 4.1.1) H midazolam injection 10mg/5mL, 10mg/2mL, 50mg/50mL oral solution 2.5mg/1mL

15.1.4.2 Non-opioid analgesics (See also section 10.1.1)

H ketorolac injection 10mg/1mL, 30mg/1mL H parecoxib1 injection 40mg

1 Parecoxib is available for an assessment period by Consultant Anaesthetists.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 178 15.1.4.3 Opioid analgesics c morphine (see section 4.7.2) d pethidine (see section 4.7.2) d tramadol (see section 4.7.2) S buprenorphine (see section 4.7.2) S meptazinol (see section 4.7.2) H alfentanil injection 1mg/2mL, 5mg/1mL (Rapifen Intensive Care) H fentanyl injection 100micrograms/2mL, 500micrograms/10mL For other preparations see section 4.7.2 H papaveretum injection 15.4mg/1mL (Omnopon) H remifentanil vials for reconstitution 1mg, 2mg, 5mg1

1 Remifentanil use is restricted to use in neuro-anaesthetics only.

15.1.5 Muscle relaxants

Non-depolarising muscle relaxants

This section will be subject to revision in the light of new products becoming available.

H atracurium injection 25mg/2.5mL, 50mg/5mL, 250mg/25mL H cisatracurium injection 5mg/2.5mL, 20mg/10mL H pancuronium injection 4mg/2mL H rocuronium injection 50mg/5mL H vecuronium injection 10mg/5mL

Depolarising muscle relaxants H suxamethonium injection 100mg/2mL

15.1.6 Anticholinesterases used in anaesthesia

H neostigmine injection 2.5mg/1mL H glycopyrronium with injection neostigmine 500micrograms/2.5mg in 1mL (Robinul-Neostigmine) H physostigmine injection 2mg/1mL See Appendix 2

15.1.7 Antagonists for central and respiratory depression c flumazenil injection 500micrograms/5mL c naloxone injection 400micrograms/1mL injection 40micrograms/2mL H doxapram injection 100mg/5mL infusion 1g/500mL

15.1.8 Drugs for malignant hyperthermia

H dantrolene sodium vial 20mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 179 15.2 Local Anaesthesia

Warning: The licensed doses stated in the BNF for lidocaine, bupivacaine and levobupivacaine may not be appropriate in some settings and expert advice should be sought.

Lidocaine/Lignocaine S lidocaine injection 0.5% 50mg/10mL amp (lignocaine) injection 1%: 100mg/10mL syringe 2mL, 5mL, 10mL, 20mL amp injection 2%: 100mg/5mL syringe 2mL, 5mL, 20mL amp epidural injection 1.5% (Xylocaine Epidural), topical sterile solution 4% throat spray 10% ointment 5% gel 2% medicated plasters 5% (Versatis) 1 S lidocaine with adrenaline prefilled syringe: 0.5%/ 1 in 200,000/2.2mL (lignocaine with adrenaline) 0.5%/1 in 200,000/20mL vial 1%/ 1 in 200,000/20mL vial, 10mL amp 2%/ 1 in 200,000/20mL vial, 10mL amp cartridges 2%/ 1 in 80,000 self aspirating cartridge 2%/1 in 80,000 S lidocaine with chlorhexidine gel 2%/0.25% 6mL, 11mL (Instillagel) (lignocaine with chlorhexadine) S lidocaine with prilocaine gel 2.5%/2.5% (Emla) (lignocaine with prilocaine)

1. Lidocaine patches: For initiation by specialists in pain management in accordance with local guidelines.

Bupivacaine S bupivacaine with adrenaline injection 0.25%/ 1 in 200,000/10mL (epinephrine) 0.5%/ 1 in 200,000/10mL H bupivacaine epidural injection 0.25%: 25mg/10mL steripak 0.5%: 50mg/10mL 0.75%: 75mg/10mL H bupivacaine with glucose injection 20mg/ 320mg/4mL (Marcain Heavy)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 180

Levobupivacaine H levobupivacaine1 injection 2.5mg/mL, 5mg/mL (10mL amps)

1 Levobupivacaine is reserved for specialised neural blockade by hospital specialists.

Prilocaine S prilocaine cartridge 4% 80mg/2mL S prilocaine with felypressin cartridge 3% 60mg/0.06unit/2mL H prilocaine injection 0.5%100mg/20mL, 250mg/50mL 1% 200mg/20mL, 500mg/50mL

Tetracaine/amethocaine S tetracaine (amethocaine) gel 4% (Ametop)1

1 Application of Ametop to the skin can result in reactions at the site including slight to severe erythema, oedema and itching. The manufacturers have advised that if blistering occurs the gel should be removed immediately and the affected area treated symptomatically. When using Ametop it is important to be alert to the warning signs and symptoms to minimise the occurrence of local skin reactions.

Ropivacaine H ropivacaine injection 20mg/10mL, 75mg/1mL, 100mg/10mL infusion 200mg/100mL

Other local anaesthetics c alcohol, dehydrated S ethyl chloride aerosol spray BP S cocaine pastes 10%, 25% topical solutions 5%, 10% nasal solution 5% S cocaine with adrenaline topical solution 10%/ 0.1% (epinephrine) S mepivacaine cartridge 3% (Scandonest) H soda lime H aldasorber

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 181 APPENDIX 1 WOUND DRESSINGS

PLEASE NOTE: THIS SECTION HAS NOT BEEN REVIEWED SINCE 2003. RETAINED FOR INFORMATION PURPOSES ONLY

For further information on the characteristics of each dressing please refer to BNF appendix 8. Enquiries and advice relating to this section may be addressed to Ceri Harris, Tissue Viability Specialist Nurse on 029 2074 6506 or via UHW switchboard.

Those dressings which have been categorised as hospital only should be initiated by Specialists in Wound Management.

NICE guidance has been issued on the use of debriding agents (No 24, April 01) and on the risk assessment and prevention of pressure ulcers, (Guideline B April 01) Please see www.nice.org.uk

A1.1.1 Alginate Dressings c Kaltostat1,2 c Sorbsan3 c Sorbsan Plus3

1 Ensure cut to size and shape of wound to avoid maceration of margin. 2 Licensed haemostatic property. 3 Sorbsan is for light to moderately exuding wounds while Sorbsan Plus is reserved for heavy exudates. Usage Moderate/heavy exudating wounds. Not suitable for eschars/dry wounds.

A1.1.2 Foam Dressings c Allevyn (except cavity dressing) c Biatain c Lyofoam1 c Lyofoam Tracheostomy d Tielle S Mepilex

1 White side to wound. Use on light/moderate exudating wounds and for overgranulating tissue.

With Adhesive c Lyofoam Extra c Allevyn Adhesive

Cavity Foam c Allevyn cavity wound c Cavi-care1

1 In the management of open post-operative granulating cavity wounds with no underlying tracts/sinuses.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 182 A1.1.3 Hydrogel dressings

Hydrogels - Used for dry, sloughy, necrotic wounds. c Aquaform c Hydrosorb c Hydrosorb Comfort c Intrasite c Intrasite Conformable d Purilon Gel d Geliperm d Iodoflex d Iodosorb A1.1.4 Hydrocolloid Dressings

Hydrocolloid Sheets - Useful to write date of application on dressing. c Aquacel1 (also Aquacel ribbon) c Granuflex c Comfeel c CombiDERM c DuoDERM (formerly Granuflex) d Combiderm N d Cica-Care2,3

1 Moderate/heavy exudating, sloughy wounds. 2 For hospital use only. 3 Cica Care is a silicone gel sheet.

A1.1.5 Vapour Permeable Films and Membranes

Films - Take care during removal. c Tegaderm c Tegaderm Pad d Opsite

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 183 A1.1.6 Low Adherence Dressing and Wound Contact Materials c Atrauman c Telfa c Silicone NA Ultra1 c Inadine2 c Primapore c Microdon d Melolin d Mepore d Interpose Lite d Surgipad S Mepitel3 H Tegapore

1 Completely NON-adherent. 2 Systemic absorption of iodine may occur. 3 Second line use by specialists.

A1.1.7 Odour Absorbent Dressings c Actisorb Silver 220 (formerly Actisorb Plus) d CarboFLEX 2

1 Use only as secondary dressing. 2 Second line use by specialists.

A1.1.8 Dressing Packs c Sterile dressing pack c Sterile dressing pack with non-woven pads

A1.1.9 Tulle Dressings d Paratulle (10 x 40 cm) d Jelonet

A1.1.10 Capillary dressings

S Vacutex3

A1.1.11 Surgical Absorbents c Listed as All Wales Contract

A1.2 Bandages and Adhesives c Triangular – Frontier + millpledge (different qualities) c White span weave c Orthopaedic wadding “Formflex” c Lestreflex c Elastoplast

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 184 A1.2.1 Non extensible bandages c Open wove bandage type 3 c Triangular calico bandage

A1.2.2 Light weight conforming bandages c Knitted polyamide and cellulose c Contour bandage (≡K Band Perema Ltd) c Cotton conforming bandage (≡ crinx) (Type 1) IW

A1.2.3 Tubular bandages

Tubular Bandages Possible allergic reaction to rubber content in certain bandages. c Surgifix – many sizes c Elasticated tubular bandage (Tubigrip) c Tubinette c Elasticated Viscose stockinette (Tubifast) c Stockinette, foam padded (Tubipad) c Ribbed stockinette – Seton c Elasticated surgical tubular stockinette c Elastic net surgical tubular c stockinette (Netelast) c Ribbed Cotton - viscose surgical tubular stockinette c Cotton stockinette c Tubular gauze bandage (Tubigauze)

A1.2.4 Support bandages c K Plus – light compression Type 3A c K lite – light support Type 2 c Elvic cotton stretch Type 2 c Soffcrepe – sterile double wrapped Type 2 c Cotton stretch bandage – Leukocrepe, K-lite

A1.2.5 High compression bandages

High Compression Bandages and Cohesive Bandages Doppler test essential prior to application. c Sure Press c Seto Press

A1.2.7 Adhesive bandages c Elastic adhesive bandage BP 1993 (Flexoplast, Elastoplast) c Elastic adhesive porous (L-EAB, Steoplase) c Elastic adhesive ventilated (Steroban) c Elastic adhesive thin (Footman Ltd)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 185 A1.2.8 Cohesive bandages c Lestreflex S Coban 3M1

1 For hospital use only.

A1.2.9 Medicated bandages

Medicated Bandages Apply bandage with “pleat” to accommodate lower limb expansion. c Steripaste c Calaband c Icthopaste d Quinaband

A1.2.10 Multilayer compression bandages

Multi-Layer Compression Bandages Doppler test essential prior to application. c Profore range

A1.2.11 Surgical adhesive tapes

Surgical Adhesive Tapes Careful application/removal of product. Avoid use, if possible, on patients with diabetes. Possible allergic reaction. Please see BNF for further details. c Impermeable plastic synthetic (Blenderm) c Non-woven permeable synthetic (Micropore) c Non-woven permeable synthetic apertured (Mefix) c Permeable woven plastic (Transpore) c Permeable woven synthetic (Durapore) c Zinc Oxide plaster Strappal (permeable) Sleek (impermeable) c Steroplast c Elastic adhesive plaster (Elastoplast)

A1.2.12 Adhesive dressings c Microdon c Coverlet eye dressing c Permeable (Fastaid) c Permeable adhesive dressing (Fabric) c Permeable plastic wound dressing c Vapour permeable waterproof plastic wound dressing (Elastoplast Airstrip)

A1.2.13 Skin closure dressings c Steri-strip

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 186 A1.3 Elastic hosiery

Elastic Hosiery Should not be used if arterial disease suspected – risk of ischaemia

H Anti-embolism stockings knee length 1 H Anti-embolism stockings thigh length 1 H Anti-embolism stockings full leg 1

1 For hospital use only.

A1.3.1 Graduated compression hosiery

Provided by orthotic department in hospital. Available on FP(10) in the community.

A1.3.2 Accessories c Felt (Cuxson + Gerrod) c Cellosene wadding c Tubifoam

A1.3.3 Anklets

Provided by orthotic department

A1.3.4 Knee caps

Provided by orthotic department in hospital; Also on FP10 in community.

For use of Cavilon - See Section 13.2.2 – Barrier Preparations

For use of silver sulfadiazine (Flamazine) - See Section 13.10.1.1 – Antibacterial Preparations only used topically

For use of metronidazole gel - See Section 13.10.1.2 - Antibacterial Preparations also used systemically

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 187 APPENDIX 2 UNLICENSED MEDICAL PRODUCTS

PLEASE NOTE: THIS SECTION HAS NOT BEEN UPDATED

The following drugs have been listed separately from the main chapters of the formulary in order to emphasise their unlicensed status. Please consult local policies on prescribing unlicensed drugs or using drugs for unlicensed indications.

1.1.1 Aluminium- and magnesium- containing antacids H Sodium citrate Solution 0.3M

1.2 Antispasmodics and other Drugs Altering Gut Motility d peppermint water oral liquid

2.1.1 Cardiac glycosides c digoxin injection 100micrograms/1ml (paediatric)

2.2.1 Thiazides and related diuretics S chlorothiazide suspension 250mg/5ml

2.2.2 Loop diuretics c furosemide liquids 40mg/5ml (SF), 50mg/5ml (SF)

2.2.3 Potassium-sparing diuretics d spironolactone suspension 10mg/5ml, 25mg/5ml, 50mg/5ml (SF)

2.3.2 Drugs for arrhythmias H magnesium sulphate injection 10g/20ml

2.5.5 Drugs affecting the renin-angiotensin system c captopril tablets 2mg

2.6.4 Peripheral and cerebral vasodilators H tolazoline injection 25mg/1ml

2.7.1 Inotropic sympathomimetics H dopamine 400mg/5ml

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 188 2.11 Antifibrinolytic Drugs and Haemostatics H etamsylate injection (paediatric) 20mg/1ml (ethamsylate)

3.5.1 Respiratory stimulants H caffeine citrate injection 10mg/mL oral solution 10mg/mL

4.2.1 Antipsychotic drugs c sulpiride liquid (SF 200mg/5ml)

4.3.1 Tricyclic and related antidepressant drugs S clomipramine liquids 25mg/5ml, 75mg/5ml

4.7.1 Non-opioid analgesics c paracetamol suppository 30mg, 1g

4.7.2 Opioid analgesics S dextromoramide suppository 10mg

4.8.1 Anti-epileptic agents S primidone liquid 250mg in 5 ml

5.1.1.1 Benzylpenicillin and Phenoxymethylpenicillin procaine penicillin with benzyl 1.8g/360mg penicillin (Bicillin)

5.1.9 Antituberculous drugs isoniazid liquid 50mg/5ml

5.1.13 Urinary-tract infections nitrofurantoin suspension (SF) 25mg/5ml

5.4.1 Antimalarials primaquine tablets 7.5mg

5.5.3 Drugs for Tapeworm infections niclosamide tablets 500mg albendazole tablets 400mg

6.1.4 Treatment of hypoglycaemia S diazoxide powder S chlorothiazide suspension 250mg/5ml

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 189 6.2.2 Antithyroid drugs S potassium iodide tablets 60mg 125mg/5ml injection

6.4.1 Female sex hormones S ethinylestradiol tablet 2micrograms (ethinyloestradiol)

6.4.3 Anabolic steroids S oxandrolone tablets 2.5mg

6.5.2 Posterior pituitary hormones and antagonists S desmopressin nasal spray 2.5micrograms/dose

7.1.1 Prostaglandins and oxytocics H misoprostol tablets 200 micrograms

7.4.4 Bladder instillations and urological surgery S dimethyl sulfoxide (dimethyl solution 50% 50ml sulphoxide) S dimethyl sulfoxide and hydrocortisone cocktail H BCG Immunotherapeutic Vial 8 1mg (Immucyst)

9.2.1 Oral administration H calcium polystyrene sulphonate enema 30g/100ml S sodium chloride oral liquid 30mmol/10ml

9.5.1 Calcium and magnesium S magnesium glycerophosphate tablets 4mmol H magnesium sulphate injection 50% 10g/20ml

9.6.5 Vitamin E S alpha tocopherol acetate injection 100mg/2ml

9.6.6 Vitamin K S phytomenadione oral drops 1mg (Orakay)

10.1.4 Drugs for treatment of gout d probenecid tablets 500mg

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 190 11.3.1 Antibacterials H cefuroxime eye drops 5% H ceftazidime eye drops 5% H gentamicin eye drops 1.5% H teicoplanin eye drops 2% H vancomycin eye drops 5%

11.3.2 Antifungals H amphotericin preservative free eye drops 0.5%, 0.2% H BSS Plus theatre use only

11.4.1 Corticosteroids c prednisolone eye drops 0.1% (extemporaneous)

11.8.2 Ocular diagnostic and peri-operative preparations H 5-fluorouracil injection - strength may vary

12.1.1 Otitis externa S colistin eardrops 1% (1,000,000unit injection) [prepared by Aseptic Unit]

12.3.4 Mouth-washes, gargles, and dentifrices S Hammersmith mouthwash

13.11.5 d Aquasept1 triclosan skin cleanser 2%

14.4 Vaccines c pertussis vaccine c poliomyelitis, inactivated

15.1.6 Anticholinesterases used in anaesthesia H physostigmine injection 2mg in 1ml

15.2 Local Anaesthesia H tetracaine (amethocaine) intrathecal injection 0.5% S morphine 100mg in 50ml syringe, 100mg in 100ml infusion

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 191 APPENDIX 3 PALLIATIVE CARE

PLEASE NOTE: THIS SECTION HAS NOT BEEN UPDATED RECENTLY

PLEASE REFER TO CURRENT BNF FOR PALLIATIVE CARE GUIDANCE

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 192 APPENDIX 4 MEDICINES INFORMATION SERVICES AND NHS DIRECT

For advice relating to the use of medicines, healthcare professionals may contact their nearest Medicines Information Centre:

Welsh Medicines Information Centre Cardiff and Vale NHS Trust Pharmacy Department University Hospital of Wales Heath Park Cardiff CF14 4XW

Tel: 029 2074 3877/2979 Fax: 029 2074 3879

or

Medicines Information Pharmacy Department Royal Glamorgan Hospital Ynysmaerdy Llantrisant CF72 8XR

Tel: 01443 443530 Fax: 01443 443150

Patients, members of the public and relatives should normally be referred to:

NHS Direct on 0845 4647.

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 193 APPENDIX 5 PRODUCT DELETIONS

1.1.1 Mucaine suspension (SF) 2.4 bisoprolol tablets 5mg, 10mg (Monocor) 4.4 disodium etidronate 4.6 Prochlorperazine suppositories 5mg, 25mg 4.7.1 Co-proxamol 4.7.2 morphine sulphate liquid 10mg/5mL withdrawn (Sevredol) 4.11 Galantamine 4mg standard release tabs (withdrawn) 4.9.1 Cabergoline is no longer included in the Formulary for treatment of Parkinson Disease but is retained for other indications (MTAC advice 15/6/06). 4.9.1 Bromocriptine is no longer included in the Formulary (MTAC advice 15/6/06). 4.9.1 Pergolide is restricted to existing patients. 5.1.2 nalidixic acid tablets 500mg liquid 300mg/5mL Removed due to high resitance rates. Susceptibility tests no longer performed. 5.1.1.3 ampicillin all preparations 5.1.1.4 piperacillin injection 1g, 2g withdrawn infusion 4g 5.1.1.4 netilmicin injection 15mg /1.5mL, 50mg/1mL, 150mg/1.5mL no longer available in the UK 5.1.9 Rimactazid 5.3 zalcitabine (DDC) tablets 375micrograms, 750micrograms 5.4.1 pyrimethamine with (Fansidar) Product discontinued sulfadoxine 6.1.1.2 Insulin Zinc Suspension Human Human Monotard sequence 6.1.1.2 Insulin Zinc Suspension(Crystalline) Human Ultratard 6.1.1.2 Biphasic isophane insulin Human Humulin M2, Humulin M5 sequence

6.1.1.2 Deleted presentations Actrapid Novolet, Actrapid Penfill, Insulatard Flexpen, Insulatard Novolet and Mixtard Novolet 6.1.2.2 Avandamet tablets 1mg/500mg 6.4.1.1 Nuvelle TS estradiol levonorgestrel 20micrograms 50micrograms, 80micrograms (oestradiol) 6.4.1.1 Femoston estradiol 2mg dydrogesterone 20mg 2/20 (oestradiol) 6.4.1.1 Trisequens estradiol 1mg, 4mg norethisterone acetate 1mg Forte (oestradiol) 6.4.1.1 Aerodiol estradiol nasal spray 150micrograms per (oestradiol) dose 6.4.1.2 progesterone vaginal gel 4% (Crinone) 6.4.1.2 hydroxyprogesterone caproate injection 250mg/1mL (1mL, 2mL) (hydroxyprogesterone hexanoate (Proluton Depot) 7.1.1 dinoprostone vaginal gels 1mg, 2mg 7.2.1 estradiol (oestradiol) vaginal ring 50micrograms in 24 hours (Menoring) 7.2.2 acetic acid vaginal jelly 0.92% (Aci-Jel) 7.2.2 Sultrin cream 7.3.1 levonorgestrel tablets 750micrograms (Levonelle-2)

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 194 Product Deletions continued

7.3.2.1 Neogest 7.3.3 nonoxinol ‘9’ jelly 2% (Gynol II) 7.3.4 Multiload Cu250 7.3.4 Nova-T 7.4.1 carbachol injection 250micrograms/1mL 7.4.5 apomorphine1 sublingual tablets 2mg, 3mg, 4mg (Uprima) 9.5.2.2 aluminium hydroxide mixture withdrawn (Alu-Cap mixture) capsules still available 9.5.2.2 calcium carbonate with 168mg [4.2mmol] Ca2+/tablets (Titralac) glycine withdrawn 9.6.4 calcitriol injection (Calcijex) 1micrograms/mL, 2micrograms/mL 9.6.6 phytomenadione injection 1mg/0.5mL (Konakion Neonatal) 10.1 rofecoxib withdrawn 10.3.2 Intralgin gel withdrawn 11.4.2 emedastine eye drops 0.05% deletion being considered 11.4 Sofradex Eye Ointment withdrawn 12.1.1 dexamethasone 0.05%, ear ointment (Sofradex) drops remain framycetin sulphate available. 0.5%, gramicidin 0.005% 12.3.1 carbenoxolone sodium gel 2% (Bioral) 12.3.4 sodium perborate 68.6% (Bocasan) withdrawn 13.2.1 LactiCare 13.4 Dermovate NN Ointment & clobetasol propionate 0.025%, cream (June 07) neomycin 0.5%, nystatin 100,000units/g 13.5.1 Efalith ointment lithium succinate with zinc sulphate ointment 8%/0.05% 13.5.2 Alphosyl Cream coal tar extract 5%, allantoin 2% Alphosyl Lotion 13.8 Sun E45 has been replaced by Sunsense Ultra 13.9 Selsun shampoo application 13.9 Polytar AF shampoo 13.10.1.2 Fucidin Gel 2% fusidic acid. Other preparations: cream 2%, ointment 2%, oral / i.v. remain ( see section 5.1.7) 13.11.2 chlorhexidine gluconate with solution 1.5%/15% cetrimide (Hibicet Hosp Concentrate) Hibicet products discontinued 13.11.5 Ster-Zac powder hexachlorophene (hexachlorophane) 0.33% powder A4.1 BM Test 1-44

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 195 INDEX

amfebutamone/ bupropion, 72 A amikacin, 77 amiloride, 17 abacavir, 81 aminophylline, 33 abciximab, 26 amiodarone, 18 acamprosate, 72 amisulpride, 46 acarbose, 89 amitriptyline, 50 acetazolamide, 150 amlodipine, 23 acetic acid, 195 Ammonaps, 134 acetylcholine, 153 amoxicillin, 75 acetylcysteine, 39 amoxycillin, 75 acetylcysteine with hypromellose, 152 amphotericin, 80, 145, 157 aciclovir, 82, 145, 172 amprenavir, 81 acitretin, 165 amsacrine, 120 aclarubicin, 118 Anabact, 172 Aclasta, 104 anastrozole, 123 Acnecide, 167 Anhydrol forte, 175 Actisorb Plus, 184 Anti-embolism stockings Full leg, 187 adalimumab, 139 Anti-embolism stockings Knee length, 187 adefovir dipivoxil, 83 Anti-embolism stockings Thigh length, 187 adenosine, 18 Anusol, 14 adrenaline, 15, 24, 25, 38, 153 Anusol HC, 14 Aerochamber, 33 Apidra, 86 aerodiol, 195 apomorphine, 69, 196 agalsidase beta, 134 apraclonidine, 153 Airstrip, 186 apraclonidine, 154 albendazole, 85 Aquacel sheet and rope, 183 albumin, 129 Aquaform, 183 alcohol, dehydrated, 181 Aquasept, 191 Aldara, 169 aqueous cream, 159 aldasorber, 181 aqueous iodine, 92 aldesleukin, 122 arachis oil, 13, 159 Aldurazyme, 134 Aricept, 73 alendronic acid, 104 aripiprazole, 46 alfacalcidol, 132 artificial tears, 154 alfentanil, 179 ascorbic acid, 115, 132 alfuzosin, 114 asparaginase, 120 Algesal, 143 aspirin, 26, 58 alglucosidase alfa, 134 atenolol, 19 alimemazine tartrate, 38 atorvastatin, 29 Allevyn preparations, 182 atosiban, 109 allopurinol, 141 atovaquone, 85 Alpha Keri Bath, 160 atracurium, 179 alpha tocopheryl acetate, 133 Atrauman, 184 Alphosyl, 197 atropine, 154, 178 Alphosyl 2 in 1, 171 atropine sulphate, 148 Alphosyl HC, 164 Augmentin, 75 alprostadil, 108, 116 auranofin, 139 alteplase, 28 Aureocort, 163 aluminium & magnesium hydroxide, 7 Avandamet, 90 aluminium acetate, 155, 175 Aveeno, 159 aluminium hydroxide, 131, 196 Aveeno bath oil, 160 aluminium hydroxide mixture, 7 Axsain, 61, 143 amantadine, 69 azathioprine, 12, 121, 139 amethocaine, 181, 191 azelastine hydrochloride, 156 amethocaine 1%, 154 azithromycin, 77 amethocaine hydrochloride, 151 Ametop, 181

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 196 B bumetanide, 17 bupivacaine epidural steripak, 180 baclofen, 142 bupivacaine with adrenaline, 180 Bactroban, 172 bupivacaine with glucose, 180 Balanced Salt Solution, 152 buprenorphine, 59, 72, 179 Balmosa, 143 buserelin, 107, 123 Balneum bath oil, 160 busulfan, 118 Balneum Plus, 160 busulphan, 118 balsalazide, 12 BuTrans, 59 basiliximab, 121 BCG Immunotherapeutic, 115 C beclometasone dipropionate, 36, 156 beclomethasone, 36 cabergoline, 107 bendrofluazide, 16 CADE, 171 bendroflumethiazide, 16 caffeine citrate, 39, 189 benoxinate, 154 Calaband, 186 benperidol, 45 Calamine lotion, 160 Benzamycin, 167 Calcichew, 130 benzatropine, 70 Calcichew D3, 132 benzoic acid ointment, compound (BP), 172 Calcichew D3 Forte, 132 Benzoin Tincture, Compound, BP, 40 calciferol, 132 benzydamine hydrochloride, 157 calcitonin, 103 benzylpenicillin, 74, 145 calcitriol, 132, 164, 196 beractant, 39 calcium acetate, 131 Betadine 4%, 171 calcium and ergocalciferol tablets, 132 betahistine, 57 calcium carbonate with glycine, 196 betamethasone, 94, 153 calcium chloride, 130 betamethasone sodium phosphate, 146, 155, 156 calcium folinate, 119 betamethasone with neomycin, 146, 155 calcium gluconate, 130 betaxolol, 154 calcium polystyrene sulphonate, 126 betaxolol hydrochloride, 149 Calcium-Sandoz, 130 Betnovate, 162 candesartan, 21 Betnovate C, 163 Canestan HC, 161 Betnovate N, 163 Capasal, 171 Betnovate RD, 162 capecitabine, 119 Bettamousse, 162 capsaicin, 61, 143 bezafibrate, 30 captopril, 21 Biatain, 182 carbachol, 196 bicalutamide, 123 carbamazepine, 48, 61, 65 bimatoprost, 150 carbenoxolone sodium, 196 bimatoprost with timolol, 150 carbimazole, 92 Binovum, 111 carbocisteine, 39 Biotène Oralbalance, 158 Carboflex, 184 bisacodyl, 13 carbomers, 152 bismuth chelate, 9 carboplatin, 120 bismuth subnitrate & iodoform (BIPP), 156 carboprost, 108 bisoprolol, 19, 194 Cardura XL, 21 bleomycin, 118 carmellose sodium, 157 BM-Test 1-44, 197 carmustine, 118 Bondronat, 105 carteolol hydrochloride, 149 Bonviva, 104 carvedilol, 19 bortezomib, 120 Carylderm, 173 botulinum toxin, 70 caspofungin, 80 bretylium, 18 Cavi-care, 182 Brevinor, 111 Cavilon, 160 brimonidine tartrate, 149 cefaclor, 76 brinzolamide, 150 cefalexin, 76 brompheniramine maleate, 38 cefixime, 76 BSS Plus, 152 cefotaxime, 76 budesonide, 12, 36, 156 cefradine, 76

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 197 ceftazidime, 76, 145 clotrimazole, 110, 155, 172 ceftriaxone, 76 clotrimazole and hydrocortisone, 110 cefuroxime, 76, 145 clozapine, 46 celecoxib, 137 Coal Tar and Salicylic acid, 164 Cellosene wadding, 187 Coal Tar in Unguentum M, 164 cephalexin, 76 Coal Tar Paste, 164 cephradine, 76 Coal tar with salicylic acid, 171 Cerazette, 112 co-amilofruse 2.5/20, 17 Cerumol, 155 co-amilofruse 5/40, 17 cetirizine hydrochloride, 38 co-amoxiclav, 75 Cetomacrogol formula A, 159 Coban 3M, 186 cetuximab, 120 co-beneldopa (levodopa with benserazide), 69 chloral hydrate, 41 cocaine, 181 chlorambucil, 118 cocaine with adrenaline, 181 chloramphenicol, 78, 144, 154, 155 co-careldopa (levodopa with carbidopa), 69 Chloraprep, 174 co-codamol 30/500, 58 chlordiazepoxide, 43 co-codamol 8/500, 58 chlorhexidine, 145, 174 Cocois, 164, 171 chlorhexidine gluconate, 157, 174 co-danthramer, 13 chlorhexidine gluconate with cetrimide, 197 co-danthrusate, 13 chlorhexidine with cetrimide sachets, 174 codeine phosphate, 11, 40, 59 chlorhexidine with neomycin, 156 co-dydramol, 58 chlormethiazole, 41 co-fluampicil, 75 chlormethine hydrochloride, 118 colchicine, 141 chloroquine, 85, 139 colestyramine, 12 chlorothiazide, 16, 91 colfosceril palmitate, 39 chlorphenamine maleate, 38 colistin, 78, 155 chlorpheniramine maleate, 38 Colotamp G, 77 chlorpromazine, 44, 57 CombiDERM, 183 chlortetracycline, 145 Combiderm N, 183 cholestyramine, 12 Combigan, 149 choline salicylate, 157 Comfeel, 183 chorionic gonadotrophin, 100 compound glycerin thymol BP, 157 chymopapain, 143 Condyline, 169 Cica Care, 183 conjugated oestrogens, 98 ciclosporin, 12, 121, 139, 153, 166 Conotrane cream, 160 Cilest, 111 Contour bandage, 185 cimetidine, 9 CosmoFer, 124 cinacalcet, 130 Cosopt, 150 cinnarizine, 57 Cosopt preservative-free, 150 ciprofibrate, 30 co-trimoxazole, 78, 85 ciprofloxacin, 79, 145 Cotton conforming bandage, 185 cisatracurium, 179 Cotton stockinette, 185 cisplatin, 120 Cotton stretch bandage, 185 citalopram, 52 Coverlet eye dressing, 186 cladribine, 119 Covermark Cover, 170 clarithromycin, 77 Covermark Finishing, 170 Clenil Modulite, 36, 37 Crestor, 29 Climagest, 96 crisantaspase, 120 clindamycin, 77, 110 Crotamiton 10%cream, 160 clobazam, 65 Crystal violet, 175 clofarabine, 119 Curatoderm, 164 clofazimine, 79 Cutivate, 162 clomethiazole, 41 cyclizine, 57 clomifene citrate, 100 cyclopentolate 0.5%, 154 clomiphene citrate, 100 cyclopentolate hydrochloride, 148 clomipramine, 50 cyclophosphamide, 118, 139 clonazepam, 65, 68 cyclosporin, 12, 121, 139, 153, 166 clonidine, 20 Cymbalta, 53 clopidogrel, 26 cyproterone acetate, 99, 123

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 198 cyproterone with ethinylestradiol, 168 Diprosalic, 163 cytarabine, 119 dipyridamole, 26 disodium pamidronate, 104, 105 D disopyramide, 18 disulfiram, 72 dacarbazine, 120 Dithranol, 164 daclizumab, 121 Dithrocream, 164 dactinomycin, 118 dobutamine, 24 Daktacort, 161 docetaxel, 117, 120 Dalacin T, 167 docusate sodium, 13 dalteparin, 26 domperidone, 8, 57 danazol, 107 donepezil, 73 dantrolene sodium, 142, 179 dopamine, 24 dapsone, 79 dopexamine, 24 daptomycin, 78 dornase alfa, 39 darbepoetin alfa, 125 dorzolamide, 150 darunavir, 81 dorzolamide with timolol, 150 daunorubicin, 118 dosulepin, 50 DDAVP Melt, 102 dothiepin, 50 demeclocycline, 76, 102 Dovobet, 164 Dequacaine, 157 Dovonex, 164 Derbac M, 173 doxapram, 179 Dermabond, 174 doxapram hydrochloride, 39 Dermol 500 Lotion, 159 doxazosin, 21 Dermovate, 163 doxepin, 50 Dermovate NN, 163, 196 doxorubicin, 118 desferrioxamine, 125 doxorubicin (pegylated liposomal), 118 desflurane, 177 doxycycline, 76 DesmoMelt, 102, 114 Drapolene cream, 160 desmopressin, 102, 114 Driclor, 175 desogestrel, 112 drotrecogin, 28 dexamethasone, 94, 146 duloxetine, 53 dexamethasone phosphate, 138 Duofilm, 169 dexamethasone with hypromellose, 146 DuoTrav, 150 dexamethasone with neomycin, 155 dydrogesterone, 99 dexamethasone/ framycetin/gramicidin, 146 dexamethasone/neomycin/ polymixin B, 146 E dexamfetamine, 54 dexamphetamine, 54 E45 cream, 159 dextran 70 in sodium chloride 0.9%, 129 Easyhaler Beclomethasone, 36 dextromoramide, 60 Easyhaler Budesonide, 36 dextrose, 91 Easyhaler Salbutamol, 32 diamorphine, 59 edrophonium chloride, 142 diazepam, 43, 68, 142 Efalith ointment, 196 diazoxide, 91 efalizumab, 166 diclofenac, 153 efavirenz, 82 Diclofenac gel, 170 eflornithine, 171 diclofenac sodium, 137 eformoterol, 32 diclofenac with misoprostol, 137 Elastic adhesive, 186 didanosine, 81 Elastic adhesive bandage, 185 Differin, 167 Elastic net surgical tubular, 185 digibind, 16 Elasticated surgical tubular stockinette, 185 digoxin, 16, 18 Elasticated tubular bandage, 185 dihydrocodeine, 59 Elasticated Viscose stockinette, 185 diltiazem, 18, 23 Elastoplast, 184 dimethyl sulfoxide, 190 Elleste Duet, 96 dimethyl sulfoxide and hydrocortisone cocktail, 190 Elleste-Duet Conti, 97 dinoprostone, 108, 195 Elocon, 162 Diprobase cream, 159 Elvic cotton stretch, 185 Diprobase ointment, 159 emedastine, 147, 196

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 199 emulsifying ointment, 159 fentanyl, 59, 60, 179 enalapril, 21 ferrous sulphate, 124 enfuvirtide, 82 Fersaday, 124 enoxaparin, 26 Fersamal, 124 enoximone, 16 fexofenadine, 38 entacapone, 69 filgrastim, 126 Epaderm, 159 finasteride, 99 ephedrine hydrochloride, 156 Flamazine, 172 epinephrine, 24, 38, 153 flecainide, 18 epirubicin hydrochloride, 118 Flexible Collodion BP, 174 eplerenone, 17 Flexoplast, 185 epoprostenol, 26 flucloxacillin, 74 eptifibatide, 26 fluconazole, 80, 110 Equasym XL, 54 flucytosine, 80 ergometrine, 108 fludarabine phosphate, 119 ergometrine with oxytocin, 108 fludrocortisone acetate, 93 ertapenem, 76 flumazenil, 179 erythromycin, 77 flumetasone with clioquinol, 155 erythropoietin, 125 flumethasone, 155 esmolol, 19 fluocinolone, 161 estradiol, 98, 110, 195 fluorescein, 154 estriol, 110 fluorescein sodium, 153 etamsylate, 28 fluorets, 154 etanercept, 139 fluorometholone, 146 ethambutol, 79 fluorouracil, 119, 153 ethamsylate, 28 fluoxetine, 52 ethinylestradiol, 99 flupenthixol, 53 ethinyloestradiol, 99 flupenthixol decanoate, 47 ethosuximide, 65 flupentixol, 53 ethyl chloride, 181 flupentixol decanoate, 47 etodolac, 137 fluphenazine decanoate, 47 etomidate, 177 flurbiprofen, 153 etonogestrel, 112 flutamide, 99, 123 etoposide, 119 fluticasone propionate, 36, 156 etoricoxib, 137 folic acid, 125 Eucerin, 159 folinic acid, 125, 126 Eumovate, 162 follitropin alfa, 100 Eurax-Hydrocortisone, 161 follitropin beta, 100 Evorel Conti, 97 Formaldehyde, 169 Evorel Sequi, 96 formoterol, 32 Exelon, 73 Forsteo, 103 exemestane, 123 foscarnet, 82 Exorex, 164 frusemide, 17 ezetimibe, 30 Fucibet, 163 Fucidin, 172, 197 F Fucidin H, 161 Full Marks, 173 Fabrazyme, 134 furosemide, 17 famciclovir, 82 fusidic acid, 144 Fastaid, 186 Felt (Cuxson + Gerrod), 187 G Femodene, 111 Femodene ED, 111 gabapentin, 65 Femodette, 111 galantamine, 73 Femoston, 96 ganciclovir, 82, 145 Femoston 2/20, 195 Ganfort, 150 Femoston-conti, 97 ganirelix, 107 FemSeven Sequi, 96 Gastrocote, 7 Femulen, 112 Gaviscon, 7 fenofibrate, 30 Gaviscon Advance, 7

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 200 gelatin (succinylated) 4% and sodium chloride hydrocortisone sodium phosphate, 94 0.9%, 129 hydrocortisone sodium succinate, 94 Geliperm, 183 hydrocortisone with gentamicin, 155 gemcitabine, 119 hydrogen peroxide, 157, 175 gemeprost, 108 Hydromol Emollient bath additive, 160 gentamicin, 77, 145, 154, 155 Hydrosorb, 183 glibenclamide, 89 Hydrosorb Comfort, 183 gliclazide, 89 hydrous ointment, 159 glucagon, 91 hydroxocobalamin, 125 Glucophage SR, 89 hydroxycarbamide, 120 glucose, 91, 127 hydroxychloroquine sulphate, 139 glucose 5% with paediatric electrolytes UHW hydroxyethyl starch, 129 formula, 127 hydroxyethylcellulose, 152 glucose 5% with potassium chloride, 128 hydroxyprogesterone caproate, 195 glucose and sodium chloride, 127 hydroxyprogesterone hexanoate, 195 glucose and sodium chloride 4%/0.18% with hydroxyurea, 120 potassium chloride, 128 hydroxyzine hydrochloride, 38 Glutarol, 169 Hylan G-F, 135 Glycerin and lemon, 158 hyoscine butylbromide, 8 glycerin/glycerol, 13 hyoscine hydrobromide, 57, 178 glyceryl trinitrate, 14, 22 hypromellose, 152 glycine, 115 Hypurin, 86, 87 glycopyrronium bromide, 175, 178 glycopyrronium with neostigmine, 179 I gonadorelin, 101 goserelin, 107, 123 ibandronic acid, 104, 105 Granuflex, 183 ibuprofen, 137 griseofulvin, 80 ichthammol, 164 guanethidine monosulphate, 21 Icthopaste, 186 guanethidine with adrenaline, 149 idarubicin hydrochloride, 118 GyneFix, 113 ifosfamide, 118 Iloprost trometamol, 20 H imatinib, 120 imipenem, 76 Haelan, 162 imipramine, 50 haloperidol, 45, 57 Imiquimod, 170 haloperidol decanoate, 47 Impermeable plastic synthetic, 186 halothane, 177 Inadine, 184 Hammersmith mouthwash, 157 indapamide, 16 heparin calcium, 25 Indermil, 174 heparin sodium, 25, 26 indinavir, 81 horse lymphoglobulin, 121 indometacin, 108, 137 Humalog, 86 indomethacin, 108, 109 Humalog Mix 25, 88 infliximab, 12, 139 Human Actrapid, 86 Inhaler devices, 33 Human Insulatard, 87 Insulin Aspart, 86 human menopausal gonadotrophins, 100 Insulin glargine, 87 Human Mixtard 10, 88 Insulin glulisine, 86 Human Mixtard 20, 88 Insulin Lispro, 86 Human Mixtard 30, 88 insulin lispro biphasic, 88 Human Mixtard 40, 88 Insulin Zinc Suspension, 195 Human Mixtard 50, 88 insulins, 86, 87, 88 Human Monotard, 195 Insuman Basal, 87 Human Ultratard, 195 Insuman Comb 25, 88 Humulin I, 87 Insuman Comb 50, 88 Humulin M3, 88 Insuman Rapid, 86 Humulin S, 86 Interferon alpha, 122 hyaluronidase, 143 Interpose Lite, 184 hydralazine, 20 intralgin, 196 hydrocortisone, 94, 146, 157, 161 Intrasite, 183

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 201 Intrasite Conformable, 183 levomepromazine, 44, 57 Intra-uterine devices, 113 Levonelle 1500, 111 ipratropium bromide, 32, 156 levonorgestrel, 111, 113, 195 irbesartan, 21 levothyroxine sodium, 92 irinotecan hydrochloride, 120 lidocaine, 18, 180 iron dextran, 124 lidocaine with adrenaline, 180 isoflurane, 177 lidocaine with chlorhexidine, 180 isoniazid, 79 lidocaine with prilocaine, 180 Isophane insulin, 87 lidocaine/fluorescein, 154 isophane insulin biphasic, 88, 195 lignocaine, 18, 180 isosorbide dinitrate, 22 lignocaine with adrenaline, 180 isosorbide mononitrate, 22 lignocaine/fluorescein, 154 isotretinoin, 168 linezolid, 78 Isotrex, 167 liothyronine sodium, 92 Isotrexin, 167 liquid paraffin, 152 ispaghula, 13 lisinopril, 21 itraconazole, 80, 110 lithium carbonate, 48 ivabradine, 24 lithium citrate, 48 Livial, 97 J Locoid, 162 Locoid C, 163 Jelonet, 184 lodoxamide, 147 Loestrin 20, 111 K Loestrin 30, 111 lofepramine, 50 K lite – light support, 185 lofexidine, 72 K Plus – light compression, 185 Logynon, 111 Kaltostat, 182 Logynon ED, 111 Kamillosan, 159 lomustine, 118 ketamine, 177 loperamide, 11 ketoconazole, 80, 172 lopinavir with ritonavir, 81 ketorolac, 153, 178 loratadine, 38 Kliofem, 97 lorazepam, 43, 68 Kliovance, 97 lormetazepam, 41 Knitted polyamide and cellulose, 185 loxapine, 45 l-tryptophan, 53 L Lyclear, 173 Lyofoam, 182 labetalol, 19 Lyofoam Extra, 182 LactiCare, 196 Lyofoam Tracheostomy, 182 lactulose, 14 lamivudine, 81 M lamotrigine, 65 lancets, 88 Maalox, 7 lanreotide, 123 macrogol, 14 lansoprazole, 11 macrogol 3350 compound, 14 Lantus Opticlick, 87 Magnapen, 75 laronidase, 134 magnesium citrate, 14 Lassar’s paste, 160 magnesium glycerophosphate, 130 latanoprost, 150 magnesium hydroxide mixture, 14 L-EAB – elastic adhesive porous, 185 magnesium sulphate, 18, 130 leflunomide, 139 magnesium sulphate paste, 174 lenograstim, 126 magnesium sulphate powder, 14 lercanidipine, 23 magnesium trisilicate mixture, 7 Lestreflex, 184, 186 mannitol, 17, 150 letrozole, 123 Marvelon, 111 leuprorelin acetate, 107, 123 Maxitrol, 146 levetiracetam, 65 mebendazole, 85 Levobupivacaine, 181 mebeverine hydrochloride, 8 levofloxacin, 79 medroxyprogesterone acetate, 99, 112, 123

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 202 mefenamic acid, 137 mometasone furoate, 156 mefloquine, 85 montelukast, 38 megestrol acetate, 123 morphine, 179, 191 Melolin, 184 morphine sulphate, 59, 194 meloxicam, 137 morphine tartrate with cyclizine tartrate, 60 melphalan, 118 moxifloxacin, 79 menadiol sodium phosphate, 133 moxonidine, 20 Menthol 1% in Aqueous cream, 160 Mucaine, 194 Menthol 2% in Aqueous cream, 160 Mucodyne, 39 Mepilex, 182 Multiload Cu375, 113, 196 Mepitel, 184 mupirocin, 156 mepivacaine, 181 mustine hydrochloride, 118 Mepore, 184 mycophenolate mofetil, 121 meptazinol, 59, 179 mycophenolic acid, 121 mercaptopurine, 119 mydricaine, 153 Mercilon, 111 Myozyme, 134 meropenem, 76 mesalazine, 12 N MESNA, 118 Metanium ointment, 160 nabumetone, 137 metaraminol, 24 nadolol, 63 metformin, 89 nafarelin, 107 metformin m/r, 89 nalidixic acid, 194 methadone, 60, 72 naloxone, 179 methadone hydrochloride, 40 naltrexone, 72 methicillin, 145 naproxen, 137 methotrexate, 119, 139, 166 natalizumab, 122 methotrimeprazine, 44, 57 nateglinide, 89 methoxypsoralen, 165 nebivolol, 19 methylcellulose, 13 needle clipping device, 88 methyldopa, 20 needles for pen devices, 88 methylphenidate, 54 nefazodone, 53 methylprednisolone, 94 nelfinavir, 81 methylprednisolone acetate, 138 Neogest, 195 methylprednisolone acetate with lidocaine, 138 neomycin, 77 metipranolol, 149, 154 neostigmine, 142, 179 metoclopramide, 8, 57 Netelast, 185 metolazone, 16 netilmicin, 194 metoprolol, 19, 63 nevirapine, 82 Metrogel, 172 Niaspan, 30 metronidazole, 79, 85, 110 niclosamide, 85 Metrotop, 172 nicorandil, 24 metyrapone, 107 nicotinic Acid, 30 Micanol, 164 nifedipine, 23, 109 miconazole, 110, 157, 172 Niferex, 124 miconazole and hydrocortisone, 110 nimodipine, 23 Microdon, 184, 186 nitrazepam, 41 Microgynon 30 ED, 111 nitrofurantoin, 80 Micronor, 112 nitrous oxide, 178 midazolam, 178 nitrous oxide 50% and oxygen 50%, 178 mifepristone, 108 Nizoral 2%, 171 minocycline, 76 nonoxinol ‘9’, 113, 195 minoxidil, 20 Non-woven permeable Micropore, 186 mirtazapine, 53 noradrenaline, 24 misoprostol, 9 norepinephrine bitartrate, 24 mitomycin, 118 norethisterone, 99 mitomycin C, 153 Norgeston, 112 mitoxantrone, 118 Norimin, 111 moclobemide, 50 Norinyl-1, 111 modafinil, 54 Normal immunoglobulin, 176

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 203 Normasol (sodium chloride 0.9%), 174 paracetamol IV, 58 Nova T380, 113, 196 paracetamol with buclizine and codeine, 62 NovoRapid, 86 paracetamol with metoclopramide, 62 NSAID, 154 paraldehyde, 68 NSAIDs, 141 parathyroid hormone, 103 Nuvelle, 96 Paratulle, 184 Nuvelle TS, 195 parecoxib, 178 Nuvelle continuous, 97 paroxetine, 52 nystatin, 80, 157 Peak flow meters, 33 peginterferon, 122 O penicillamine, 139 penicillin G, 74 Occlusal, 169 penicillin V, 74 Octim, 102 pentamidine, 85 octreotide, 15, 91, 123 pentastarch 10% in sodium chloride 0.9%, 129 oestriol, 110 pentostatin, 120 ofloxacin, 79 peppermint oil, 8 Oilatum Emollient, 160 peppermint water, 8 Oilatum Plus, 160 Perfalgan, 58 Oilatum shower emollient, 159 pergolide, 69 Oily calamine lotion, 160 perindopril, 21 oily phenol, 14 Permeable adhesive dressing (Fabric), 186 olanzapine, 45, 47 Permeable plastic wound dressing, 186 olive oil, 155, 159 Permeable woven plastic, 186 olopatadine, 147 Permeable woven synthetic, 186 omeprazole, 11 Permitabs, 175 ondansetron, 57 pethidine, 59, 179 Opatanol, 147 phenelzine, 50 Open wove bandage type 3, 185 phenindione, 26 Opsite, 183 phenobarbital, 65 Oral balance, 158 phenobarbitone, 65 oral rehydration, 127 phenol 2% in compound zinc paste, 160 orlistat, 55 phenoxybenzamine, 21, 114 orphenadrine, 70 phenoxymethylpenicillin, 74 oseltamivir, 83 phentolamine, 21 Otosporin, 155 phenylbutazone, 137 Ovranette, 111 phenylephrine, 24 oxaliplatin, 120 phenylephrine 2.5%, 154 oxandrolone, 99 phenylephrine hydrochloride, 148 oxazepam, 43 phenytoin, 18, 61, 65 oxcarbazepine, 65 phenytoin sodium, 68 oxybuprocaine hydrochloride, 151 pholcodeine, 40 oxybutynin, 114 phosphate, 14, 131 oxycodone, 59 Phosphate-Sandoz, 131 oxygen, 39 physostigmine, 179 oxytetracycline, 76 phytomenadione, 133, 196 oxytocin, 108 pilocarpine, 149 pilocarpine 1%, 154 P pilocarpine hydrochloride, 158 pimecrolimus, 166 paclitaxel, 117, 120 pimozide, 45 Palacos-r with gentamicin, 77 pioglitazone, 89 palivizumab, 84 piperacillin, 194 palonosetron, 57 piperacillin with tazobactam, 75 pancreatin, 15 piperazine, 85 pancuronium, 179 piperazine with sennosides, 85 PanOxyl, 167 pipothiazine palmitate, 47 papaveretum, 179 pipotiazine palmitate, 47 papaverine, 116 pizotifen, 63 paracetamol, 58

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 204 Podophyllin 25% in Compound benzoin tincture, Protopic, 166 169 proxymet. + fluor, 154 Polyfax, 172 proxymetacaine, 154 polygeline, 129 proxymetacaine and fluorescein, 151 polymyxin B sulphate, 145 proxymetacaine hydrochloride, 151 Polytar, 171 pseudoephedrine hydrochloride, 40 Polytar AF, 197 Purilon Gel, 183 Polytar emollient, 164 pyrazinamide, 79 polyvinyl alcohol, 152 pyridostigmine bromide, 142 poractant alfa, 39 pyridoxine hydrochloride, 131 porfimer, 120 pyrimethamine, 85 Pork Actrapid, 86 pyrimethamine with sulfadoxime, 194 Pork Insulatard, 87 Pork Mixtard 30, 88 Q Posalfilin, 169 potassium chloride, 126, 128 quetiapine, 46 potassium citrate, 115 Quinaband, 186 potassium citrate mixture BP, 115 quinine, 85 potassium iodide, 92 quinine sulphate, 142 potassium permanganate, 175 quinupristin with dalfopristin, 78 povidone, 152 Qvar, 36, 37 povidone – iodine, 157 povidone iodine, 110, 175 R pramipexole, 69 pravastatin, 29 rabbit thymoglobulin, 121 prednisiolone sodium phosphate, 154 raloxifene, 98 prednisolone, 12, 94, 121, 146, 191 ramipril, 21 prednisolone with neomycin, 146 ranitidine, 9 Predsol 0.5%, 154 rasagiline, 69 pregabalin, 61 rasburicase, 141 Pregaday, 124 Raspberry mucilage, 158 Premique, 97 reboxetine, 53 Prempak-C, 96 Recombinant human insulin analogue, 86 prilocaine, 181 remifentanil, 179 prilocaine with felypressin, 181 Reminyl, 73 Primapore, 184 retinoic acid, 153 primaquine, 85 ribavirin, 83, 84 primidone, 65, 189 Ribbed Cotton - viscose surgical tubular stockinette, Prioderm, 173 185 probenecid, 141 Ribbed stockinette, 185 procaine penicillin with benzylpenicillin, 74 rifampicin, 79 procarbazine, 120 rifampicin with isoniazid, 79 prochlorperazine, 57 rifampicin with isoniazid and pyrazinamide, 79 procyclidine, 70 riluzole, 70 Proflavine cream, 174 rimexolone, 146 Profore range, 186 risedronate sodium, 104 progesterone, 99, 195 risperidone, 45, 47 proguanil, 85 ritodrine, 109 promazine, 44 ritonavir, 81 promethazine hydrochloride, 38, 57 rituximab, 122, 139 promethazine theoclate, 57 rivastigmine, 73 propafenone, 18 rizatriptan, 62 propamidine isetionate, 145 RoC Total Sunblock, 170 propantheline, 8, 114 rocuronium, 179 propofol, 177 rofecoxib, 196 propranolol, 19, 63, 70 ropinirole, 69 propylthiouracil, 92 ropivacaine, 181 protamine sulphate, 26 rose bengal, 153, 154 Proteolos, 104 rosiglitazone, 89 protirelin, 101 rosiglitazone and metformin, 90

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 205 rosuvastatin, 29 sodium nitroprusside, 20 rotigotine, 69 sodium perborate, 196 Rozex, 172 sodium phenylbutyrate, 134 sodium phosphate 2.9%/ potassium hydrogen S phosphate 0.259%, 129 sodium picosulfate, 13, 14 Salactol paint, 169 sodium picosulphate, 13 Salatac, 169 sodium tetradecyl sulphate, 15 salbutamol, 32 sodium valproate, 65 Salicylic acid 2%, 164, 169 Soffcrepe – sterile double wrapped, 185 Salicylic acid collodion, 169 Sofradex, 155, 196 Saliva Orthana, 158 Solaraze, 170, 171 Salivix, 158 solifenacin, 114 salmeterol, 32 soluble insulin, 86 Sandocal-1000, 130 solution G, 115 Sandocal-400, 130 somatropin, 101 Sando-K, 126 Somatuline Autogel, 123 saquinavir, 81 Sorbsan, 182 selegiline, 69 Sorbsan Plus, 182 Selsun, 197 sotalol, 19 semisodium valproate, 48 Spiriva, 32 senna, 13 spironolactone, 17 Seretide, 36 Sprilon, 160 sermorelin, 101 SST, 158 sertraline, 52 saliva stimulating tablets, 158 Seto Press, 185 Stalevo, 69 sevelamer, 131 stanozolol, 99 sevoflurane, 177 stavudine, 81 sibutramine, 56 steam inhalations, 156 sildenafil, 116 Sterile dressing pack, 184 Silicone NA Ultra, 184 Steripaste, 186 Silkis, 164 Steripod Sodium Chloride 0.9%, 174 Silver Nitrate, 169 Steri-strip, 186 Simple linctus, BP, 40 Steroplast, 186 Simple linctus, Paediatric BP, 40 Sterzac, 175, 197 simvastatin, 29 Stiemycin, 167 Siopel cream, 160 Stockinette, foam padded, 185 sirolimus, 121 Strepsils, 157 Skin prep, 174 streptokinase, 28 Skinoren, 167 streptomycin, 79 soda lime, 181 strontium, 104 sodium aurothiomalate, 139 Subutex, 72 sodium bicarbonate, 115, 127, 129, 155 sucralfate, 9 sodium chloride, 115, 127, 152, 153, 154, 156 Sudocrem, 159, 160 Sodium Chloride 0.9%, 174 Suleo M, 173 sodium chloride 0.9% with potassium chloride, 128 sulfadiazine, 78 sodium chondroitin/ sodium hyaluronate, 153 sulfasalazine, 12, 139 sodium citrate, 7 sulindac, 137 sodium citrate compound, 14 sulphasalazine, 139 sodium clodronate, 105 sulpiride, 45 sodium cromoglicate, 38, 147, 156 Sultrin, 195 sodium cromoglycate, 147 sumatriptan, 62 sodium dichloroisocyanurate, 175 sun flower oil, 159 sodium dihydrogen phosphate soda, 14 Sunsense, 170 sodium fluoride, 131 Sure Press, 185 sodium fusidate, 78 Surgifix, 185 sodium hyaluronate, 153 Surgipad, 184 sodium hypochlorite, 175 suxamethonium, 179 sodium lactate, 129 Symbicort, 37 sodium lactate compound, 128 Synalar, 162, 171

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 206 Synalar 1 in 4, 162 tirofiban, 26 Synalar C, 163 tizanidine, 142 Synalar N, 163 tobramycin, 77 Synercid, 78 tolazoline, 24 Synphase, 111 tolterodine, 114 syringes, 88 topiramate, 65 Sytron, 124 topotecan, 120 tramadol, 59, 179 T trandolapril, 21 tranexamic acid, 28 T/gel, 171 Transtec, 59 tacrolimus, 121, 166 transvasin, 143 tadalafil, 116 Travatan, 150 Tamiflu, 83 travoprost, 150 tamoxifen, 100, 123 trazodone, 50 tamsulosin, 114 treosulfan, 118 Tar Pomade, 171 tretinoin, 120, 167 Tazocin, 75 Tri-Adcortyl Otic, 155 Tegaderm, 183 triamcinolone, 94, 153 Tegaderm Pad, 183 triamcinolone acetonide, 138, 157 tegafur, 119 Triangular calico bandage, 185 Tegapore, 184 tribavirin, 83, 84 teicoplanin, 78, 145 triclofos sodium, 41 Telfa, 184 Tridestra, 96 temazepam, 41 trifluoperazine, 44, 57 temocillin, 74 trihexyphenidyl hydrochloride/ benzhexol temozolomide, 120 hydrochloride, 70 tenecteplase, 28 trimeprazine tartrate, 38 tenofovir, 81 trimethoprim, 78 tenoxicam, 137 Trimovate, 162 terbinafine, 80, 172 Trinovum, 111 terbutaline, 32 triptorelin, 107 teriparatide, 103 Trisequens, 96 terlipressin, 15, 102 Trisequens Forte, 195 Testogel, 99 tropicamide, 148 testosterone, 99 tropicamide 1%, 154 tetrabenazine, 70 trospium, 114 tetracaine, 154, 181, 191 Truvada, 81 tetracaine hydrochloride, 151 Tubifoam, 187 tetracosactide, 100 Tubinette, 185 tetracosactrin, 100 Tubular gauze bandage, 185 tetracycline, 76, 157 Type A, 113 theophylline, 33 Type A Contraceptive pessary, 113 thiamine, 131 Type B, 113 thiopental, 177 Type B Contraceptive pessary, 113 thiopentone, 177 Type C, 113 thioridazine, 44 Type C Contraceptive pessary, 113 thiotepa, 118 thymol, 157 U thyroxine sodium, 92 tiagabine, 65 Ultrabase, 159 tibolone, 98 Unguentum M, 159 Tielle, 182 urokinase, 28 Timodine, 161 ursodeoxycholic acid, 15 timolol, 63, 154 Uvistat lipscreen, 170 timolol maleate, 149 Uvistat Ultrablock, 170 tinzaparin, 26 tioguanine, 119 V tiotropium, 32 tipranavir, 81 Vacutex, 184

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 207 valaciclovir, 82 water for injections, 129 valganciclovir, 82 white soft paraffin, 159 valproic acid, 48 white soft paraffin/liquid paraffin 50/50, 159 valsartan, 21 vancomycin, 78, 145 X Vapour permeable airstrip, 186 vardenafil, 116 Xepin, 160 varenicline, 72 Xigris, 28 Vasogen, 160 xylometazoline hydrochloride, 156 vasopressin, 102 Xyloproct, 14 vecuronium, 179 Veil Cover, 170 Y Veil Finishing, 170 venlafaxine, 53 Yasmin, 111 Ventavis, 20 verapamil, 18, 23 Z Verrugon, 169 Versatis, 180 zalcitabine (DDC), 194 verteporfin, 153 zanamivir, 83 vigabatrin, 65 Zanidip, 23 vinblastine sulphate, 119 ZeaSORB, 175 vincristine sulphate, 119 zidovudine (AZT), 81 vindesine sulphate, 119 zinc and castor oil cream, 159 vinorelbine, 119 Zinc and castor oil ointment, 160 Vioform hydrocortisone, 161 Zinc and Salicylic acid, 164 Viscotears, 154 Zinc Oxide, 186 vitamin B Compound, 131 zinc sulphate, 131 vitamin B Compound Strong, 131 Zineryt, 167 vitamins A & D, 131 zoledronic acid, 104, 105 vitamins B and C, 131 zonisamide, 65 voriconazole, 80 zopiclone, 41 Zorac, 164 W zuclopenthixol acetate, 45 zuclopenthixol decanoate, 47 warfarin, 26 zuclopenthixol dihydrochloride, 45 Warticon fem, 169

Key to Symbols: 1= First Line, including GP use, 2 = Second line including GP use, S= Specialist Initiated, H = Hospital Only 208