Prescribing Formulary – February 2013
Transcription
Prescribing Formulary – February 2013
Prescribing Formulary th 15 Edition – February 2013 Version 15 Version date: 28 Feb 2013 Somerset CCG - Prescribing Formulary – February 2013 Introduction This formulary has been developed and reviewed by the Somerset CCG Medicines Management team, in liaison with Secondary Care NHS Trusts. It is intended to guide evidence-based and cost-effective prescribing across Somerset. Key points to note with regard to the formulary are: It is intended to only cover first and in some cases second-line drug choices (other than where stated) in uncomplicated patients It is expected that practices will find the options provided are appropriate for the treatment of most new patients It is acknowledged that patients who are intolerant / unresponsive to formulary drugs, may require alternatives which are non-formulary It is anticipated that medication reviews will provide an opportunity to transfer appropriate patients from non-formulary to formulary drugs New products will by default be non-formulary initially and prescribers are thus asked to refrain from prescribing new drugs until they have been assessed and approved for addition to the formulary either by the Prescribing Forum or Drugs and Therapeutics Committee. Drugs which are classified as amber under the Somerset Traffic Light System are not generally included in the formulary. They should be initiated by (or on the advice of) an appropriate specialist. There may be arrangements for Shared Care. The formulary is primarily aimed at prescribing for adults, guidance on prescribing for children can be found in the BNF for children. Full prescribing information about products in the formulary is available in the BNF, available online or as an app for many mobile devices. It is acknowledged that to be effective the formulary needs to be accessible and thus an electronic rather than paper format is preferred by many. To aid decision support at the point of prescribing, this formulary will therefore be made available on general practice clinical systems. It is expected that this formulary will then be set as the default for all users within practices, including partners, retained doctors, locums and non-medical prescribers. The formulary will be reviewed at approximately six-monthly intervals, taking account of emerging evidence, product availability, and pricing. Prices quoted in this edition are taken from the most recent editions of the Drug Tariff and Chemist & Druggist monthly price list. There are often cost-effective alternatives to pharmaceutical specials, including crushing tablets or prescribing licensed liquid preparations of similar medicines. Guidance on the use of pharmaceutical „specials‟ is available on the Medicines Management web page. Prescribers may also contact the Prescribing & Medicines Management Team with any queries. By rationalising the choice of drugs prescribed in Primary Care through adoption of the formulary, and by improving liaison with Secondary Care, it is hoped that prescribing across the Somerset health community can become more rational, cost-effective and seamless. In further support of this objective, the Out of Hours formulary is reproduced as an appendix to this document, and the Palliative Care handbook can be found here. Somerset CCG Medicines Management Team Feb 2013 We believe the information in this document is correct at the time of production. Please notify the Medicines Management Team of any errors. [email protected] Team Administrator Introduction Page 1 ADMISSION AND DISCHARGE PROCESSES Poor communication of information at transition points is responsible for as many as 50% of all medication errors and up to 20% of adverse drug events in hospital. Practices should have a process for medicines reconciliation before admission and after discharge from secondary care and a means of identifying patients at high risk of medicines related adverse events. Please see the following two NHS Somerset guidance documents: From Primary to Secondary Care Provision of patient information on admissions from Primary Care Reconciliation of patient information post-discharge From Secondary to Primary care Complete patient details Complete patient details The presenting condition plus co-morbidities The diagnosis of the presenting condition plus co-morbidities A list of all the medicines currently prescribed for the patient with indications Dose, frequency and route of all the medicines listed Any OTC medicines or supplements the patient takes Medicines stopped and started, with reasons Dose, frequency and route of all the medicines listed Length of courses where appropriate An indication of any medicines that are not intended to be continued (eg.acute prescriptions) Details of increasing or decreasing regimes Known allergies Known allergies Known previous side effects Suggestions for Drug Monitoring in Adults in Primary Care The monitoring parameters cited in the formulary are derived from a range of guidelines, reference sources, and expert opinion and must therefore be considered suggestions only. Adherence to them will not ensure a successful outcome in every case. The ultimate judgement regarding a particular clinical result must be made by the doctor in light of the clinical data presented by the patient and the diagnostic and treatment options available. Please see the Suggestions for Drug Monitoring in Adults in Primary Care document. Admission and discharge processes Page 2 Contents BNF Therapeutic Chapter Page Page Ch. 1 Gastro-intestinal system Helicobacter pylori eradication Ch. 2 6-12 8 Guidance on assessing dehydration in children under 5 years Cardiovascular system 10 13-45 Summary Drug Treatment for Hypertension 20 Summary of drug interactions for Dabigatran & Rivaroxaban 34 NICE Care Pathway for Hypertension 21 Implementation priorities for Dabigatran & Rivaroxaban 35-36 22-26 Lipid-Regulation Guidance Heart Failure Guidance Heart Failure prescribing Guidelines flowchart 27 Primary Prevention in CVD (based on NICE CG 67) 40 Guidelines for the Treatment of Chronic Stable Angina Pectoris 29 Secondary Prevention of CVD (based on NICE CG 67) 41 Management of coumarin induced haemorrhage 32 Ch. 3 Respiratory system COPD Guidance Ch. 4 Summary of drug-statin interations 42 46-62 57 Assessing and managing symptoms in COPD Central nervous system 59 75-84 Hypnotics 63 Migraine 75-80 Antipsychotics 64-65 NICE: CG150 Diagnosis of migraine, cluster & tension type headache 77 Antimanic drugs 65 Epilepsy 80-81 Antidepressants 66-69 Substance Dependence: Smoking & Opioid 81-83 Analgesia 70-73 Drugs in dementia 84 Opioid conversion table 74 Ch. 5 Infections 85-95 Influenza vaccines 88 Urinary tract infections 90-91 Management of infection guidance 89 Gastro-intestinal tract infections 91 Upper respiratory tract infections 90 Genital tract infections 92 Lower respiratory tract infections 90 Skin / soft tissue infections 92-93 Menigitis 90 MRSA decolonistation policy 95 Table of contents Page 3 BNF Therapeutic Chapter Ch. 6 Page Page Endocrine system 96-116 Diabetes Sex hormones Summary chart for the treatment of diabetes 97 Hormone replacement therapy 106 Insulin therapy in diabetes guidance 98 Male sex hormones and antagonists 108 Blood glucose monitoring guidance 104 Drugs affecting bone metabolism 109 Thyroid and anti-thyroid drugs 105 Summary of NICE TAG 160: Primary Prevention of Osteoporosis 111 Corticosteroids 105 Summary of NICE TAG 161: Secondary Prevention of Osteoporosis 112 Ch. 7 Obstetrics, gynaecology, and urinary-tract disorders Contraceptives Emergency hormonal contraception Ch. 8 118-19 Treatment of Urinary Dysfunction 121-23 120 Treatment of erectile dysfunction 123-24 Malignant disease and immunosuppression Prostate cancer & Gonadorelin analogues Ch. 9 117-123 125 125 Somerset Prescribing Forum statement on endometriosis & fibroids Nutrition and blood 125 126-128 Ch. 10 Musculoskeletal and joint diseases 129-134 Non-steroidal anti-inflammatory drugs (NSAIDs) 129 Gout 131 Rubefacients and topical NSAIDs 130 Guidance on the management of osteoarthritis (OA) 132-134 Ch. 11 Eye 134-135 Ch. 12 Ear, nose and oropharynx 136-138 Nasal allergy 137 Decolonisation of nasal MRSA Ch. 13 Skin 137 139-146 Emollients 139-41 Acne 145 Topical corticosteroids 142-43 Anti-infective skin preparations 146 Vitamin D analogues 144 Table of contents Page 4 BNF Therapeutic Chapter Page Page Ch. 15 Anaesthesia Antagonists for central and respiratory depression 147 147 Appendix 1 Borderline substances Food supplements MUST Nutritional Screen 148-146 148 Gluten-free foods 148 149 Pathways for Replacement Milk Formula for Cow‟s Milk allergy/intolerance a) Breast Fed Infants b) Formula Fed Infants Prescribing Quantities Formula Milks 150 151 Appendix 2 Dorset & Somerset Out of Hours Service 152 154-157 Somerset Community Pharmacies holding Palliative Care Drugs 154-55 List of Palliative Care Drugs held by Community Pharmacies 156-57 Useful links Prescribing & Medicines Management intranet pages Traffic Light System Palliative Care Handbook Somerset Prescribing Forum Drug & Therapeutics Committees Prescribing & Medicines Management Group (PAMM) Table of contents Page 5 Therapeutic area Formulary choices Cost for 28 unless stated Rationale for decision / comments BNF Chapter 1: Gastro-intestinal system Top 1.1 Dyspepsia & gastro-oesophageal reflux disease Antacids Asilone Suspension: £2.00 (500ml) A combination of magnesium and aluminium antacids, plus an antiflatulent, also low in sodium. Available OTC Mucogel Suspension: £1.71 (500ml) Low sodium and cost-effective treatment for dyspepsia. At dose of 10-20ml tds & at bedtim provides equivalent magnesium intake required for hypomagnesaemia as an alternative to magnesium glycerophosphate. Alginates Peptac Aniseed and peppermint flavour Gaviscon Advance Aniseed and peppermint flavour Liquid: £1.95 (500ml) Contains 3.1mmol of sodium per 5ml so should be avoided in patients where restriction of sodium intake is desirable. Available OTC Liquid: £4.54 (500ml) Chewable tablets: £2.72 (60) Recommended dose: 10ml Contains 2.3mmol sodium & 1mmol potassium per 5ml dose Acidex Max Strength Aniseed and peppermint flavour Liquid: (500ml) Gastrocote Suspension: £2.67 (500ml) Tablets: £3.51 (100) ® Gastrocote liquid contains 1.8mmol of sodium per 5ml and may therefore be ® more appropriate than Peptac in patients where restriction of sodium intake is ® desirable. Gastrocote tablets contain 1mmol Sodium per tablet. Both suspension and tablets available OTC Severe hypomagnesaemia has been reported infrequently in patients treated with PPIs, although the exact incidence is unknown. Where this is a clinical concern prescribers may also decide to use a magnesium containing product such as magnesium trisilicate or Gastrocote (with alginate). NB Magnesium salts tend to be laxative in effect. Gastro-intestinal System Page 6 Therapeutic area Formulary choices Cost for 28 unless stated Rationale for decision / comments Mebeverine 135mg tablets: £4.81 (100) Avoid prescribing as Colofac IBS as this is the OTC pack and more expensive. 1.2 Antispasmodics Antispasmodics ® 1.3 Antisecretory drugs Related guidance: NICE Clinical Guideline CG17 (2004): Dyspepsia H2 - receptor antagonists Ranitidine 150mg tablets: £2.01 (60) 300mg tablets: £2.06 (30) 75mg/5ml S/F oral solution: £9.09 (300ml) Ranitidine is recommended as first line treatment for mild-moderate GORD in the majority of patients. Ranitidine is available OTC, but only as 75mg tablets 1.3.5 Proton pump inhibitors Based on licensed indications and availability of both as generic capsules, omeprazole and lansoprazole are now considered joint first line PPIs and the need to use other PPIs should therefore be limited. Pantoprazole is the preferred PPI for patients who specifically require a tablet formulation. NB. Refer to NICE guidance on use of PPIs Lansoprazole capsules 15mg capsules: £1.19 30mg capsules: £1.72 Avoid prescribing Lansoprazole orodispersible tablets (Zoton FasTabs) as the cost is greater than generic capsules, except as an alternative to costly special liquid formulations. Omeprazole capsules 10mg capsules: £1.27 20mg capsules: £1.31 As Mepradec 10mg capsules: £1.12 (28) 20mg capsules: £1.14 (28) Avoid prescribing Omeprazole dispersible tablets (Losec MUPS ), as they cost about five times more than generic capsules, except as an alternative to costly special liquid formulations and where lansoprazole orodispersible tablets are not an acceptable alternative. Where Omeprazole 20mg once-daily is not effective, increasing dose to 2x20mg daily (not 1x40mg) or using Lansoprazole 30mg daily is recommended. ® For patients currently taking Nexium tablets who are unable to change to omeprazole, lansoprazole or pantoprazole, product should be prescribed as EMOZUL capsules (esomeprazole capsules 20mg and 40mg) Pantoprazole tablets 20mg tablets: £1.14 40mg tablets: £1.60 Pantoprazole has been included for circumstances where a tablet formulation is necessary. Severe hypomagnesaemia has been reported infrequently in patients treated with PPIs, although the exact incidence is unknown. Where this is a clinical concern prescribers may also decide to use a magnesium containing product such as magnesium trisilicate, magnesium hydroxide (not suitable for patients with short bowel syndrome) or Mucogel. Gastro-intestinal System Page 7 Therapeutic area Formulary choices Cost for 28 unless stated Rationale for decision / comments Helicobacter pylori eradication – Please refer to Infection Management Guidance. First line: PPI (as opposite) + Metronidazole + Clarithromycin all for 7 days or PPI (as opposite) + Amoxicillin + Clarithromycin all for 7 days 400mg BD 250mg BD Helicobacter pylori eradication is indicated in GU, DU and MALT lymphoma, whereas evidence of value in GORD and NUD is inconsistent. Recommended PPI regimes for H. pylori eradication are either Omeprazole capsules 20mg bd or Lansoprazole capsules 30mg bd. 1g BD 500mg BD The combination of a PPI + Clarithromycin and Metronidazole is now a recommended as first line therapy for H. pylori eradication. However the use of Clarithromycin or Metronidazole should be avoided if they have been used in the previous year for the treatment of any other infections as this significantly increases the likelihood of H Pylori being resistant. NB. Different doses of Clarithromycin indicated in the two regimes. Second line: See opposite or seek specialist advice Where patients require a second course of eradication, a regime should be chosen which does not include antibiotics given previously, see BNF for guidance or seek specialist advice. 1.4 Acute diarrhoea Avoid anti-motility agents in children. See page 10 for assessment of dehydration in under 5s in line with NICE CG84 Oral rehydration Electrolade £1.97 (6 sachet) £4.99 (20 sachet) Available as multipack containing mixed flavours, less expensive than Dioralyte . Available OTC. Antimotility agents Loperamide capsules 2mg capsules: £0.94 (30) Available OTC as generic loperamide, various own-brand products and as Imodium. Do not prescribe as branded version owing to high cost. Codeine 15mg tablets: £1.19 30mg tablets: £1.49 (avoid packs of 30 pack as these are twice the cost) Just 3 days of codeine containing medicines can lead to addiction – The PCT strongly recommends that prescribers discuss the risk of addiction when initiating new patients on any opioid containing medication and that this discussion is recorded in the patient notes. Watch for increasing frequency of requests for prescriptions Gastro-intestinal System ® Page 8 Therapeutic area Formulary choices Cost for 28 unless stated Rationale for decision / comments 1.5 Chronic bowel disorders Chronic diarrhoea First line: In line with national guidance it is recommended that Mesalazine is prescribed by brand name. For all mesalazine preparations monitor renal function as recommended in SPC. ® Mesalazine as Octasa MR 400mg tablets: £19.50 (90) Where 400mg tablets are required Octasa tablets are recommended as first line as they are considered to be bioequivalent to the original product Asacol but at a lower cost. 800mg Octasa cost more than 2 x 400mg so for cost-effective dose we recommend using 400mg tabs Mesalazine as c Pentasa SR 500mg tablets £30.74 (100) 1g tablets £36.89 (60) Where 500mg tablets are required Pentasa tablets are recommended. ® Asacol 800mg tablets are not recommended Mesalazine 1g sachets £30.74 (50) ® Salofalk sachets: As Salofalk 1.5g sachets £48.85 (60) 3g sachets £97.70 (60) Mesalazine as 1g suppositories £29.62 (28) 2g/100ml enema £29.92 (7) Salofalk Second line: 1.5g equivalent to 2g pentasa or 2.4g Octasa or Asacol 3g equivalent to 4g Pentasa or 4.8g Octasa or Asacol Mesalazine as ® Mezavant XL 1.2g tablets: £62.44 (60) Consultant initiation only. All patients should have evaluation of renal function prior to initiation and at least twice yearly whilst on treatment. Budesonide 3mg capsules £77.05 (100) 2mg/100ml Rectal Foam £57.11 (14) Capsules enclose enteric coated granules which release budesonide into the ileum and ascending colon. Extraintestinal symptoms, e.g. involving the skin, eyes or joints, are unlikely to respond to Budenofalk 3mg because of its local action. Initial dose is 3mg tds for a maximum of 8 weeks. During week 7, dose should be reduced to two capsules daily and in week 8, reduce to one capsule daily. Budesonide (and conventional glucocorticosteroid) should not be used to maintain remission NICE CG152 1.5.2 Corticosteroids as Budenofalk Gastro-intestinal System Page 9 Assessing dehydration in children under 5 years for use during remote and face-to-face assessments Adapted from ‘Diarrhoea and vomiting in children’ (NICE clinical guideline 84). The quick reference guide and full guidance are available from: www.nice.org.uk/CG84 Increasing severity of dehydration Clinical dehydration Signs (face-to-face assessments) Symptoms (remote and face-toface assessments) No clinically detectable dehydration may indicate children at increased risk of progression to shock Risk Factors for Dehydration: Clinical shock (one or more signs/symptoms present. (-) features do not specifically indicate shock Children younger than 1 year, especially those younger than 6 months infants who were of low birth weight children who have passed six or more diarrhoeal stools in the past 24 hours children who have vomited three times or more in the past 24 hours children who have not been offered or have not been able to tolerate supplementary fluids before presentation Appears well Appears to be unwell or deteriorating – Alert and responsive Altered responsiveness (for example, irritable, lethargic) Decreased level of consciousness Normal urine output Decreased urine output – infants who have stopped breastfeeding during the illness children with signs of malnutrition. Skin colour unchanged Skin colour unchanged Pale or mottled skin Warm extremities Warm extremities Cold extremities Alert and responsive Altered responsiveness (for example, irritable, lethargic) Decreased level of consciousness Skin colour unchanged Skin colour unchanged Pale or mottled skin Warm extremities Warm extremities Cold extremities Eyes not sunken Sunken eyes Moist mucous membranes (except after a drink) Dry mucous membranes (except for „mouth breather') X Box 1 x Suspect hypernatraemic dehydration if there are any of the following: jittery movements increased muscle tone hyperreflexia – convulsions – drowsiness or coma. Laboratory investigations: Normal heart rate Tachycardia Tachycardia Do not routinely perform blood biochemistry. Normal breathing pattern Tachypnoea Tachypnoea Measure plasma sodium, potassium, urea, creatinine and glucose concentrations if: - intravenous fluid therapy is required or Normal peripheral pulses Normal peripheral pulses Weak peripheral pulses Normal capillary refill time Normal capillary refill time Prolonged capillary refill time Normal skin turgor Normal blood pressure Reduced skin turgor Normal blood pressure – Hypotension (decompensated shock) - there are symptoms or signs suggesting hypernatraemia. Measure venous blood acid–base status and chloride concentration if shock is suspected or confirmed. Interpret symptoms and signs taking into account risk factors for dehydration (see box 1). Gastro-intestinal System Page 10 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments 1.6 Laxatives Related guidance: NICE Clinical Guideline CG99 (2010): Constipation in children and young people Bulk-forming laxatives Ispaghula Husk Stimulant laxatives Senna 7.5mg tablets: £2.83 (60) 7.5mg/5ml SF liquid: £2.69 (500ml) Available OTC. Glycerol suppositories 1g: £0.94 (12) 2g: £0.94(12) 4g: £2.15 (12) Glycerin suppository sizes: 3.5g sachets: £2.20 (30) Prescribe generically. Available OTC. 3.4g sachets (e.g. Regulan) are more expensive at £2.44 per 30 1g = infant 2g = child 4g = adult All available OTC Osmotic laxatives 1st Line Macrogol Sachets:£5.34 (30) as Laxido Orange Sugar-free or 2nd Line Lactulose Gastro-intestinal System 3.35g/5ml solution: £3.16 (500ml) NICE Cochrane QP review in June 2010 concluded that polyethylene glycol (macrogol) should be used in preference to lactulose for chronic constipation. Using polyethylene glycol in preference to lactulose is likely to improve the quality of patient care by reducing the use of a less effective treatment. Course of treatment for chronic constipation not normally > 2 weeks. A stimulant laxative should be added if disimpaction is not achieved after 2 weeks. Efficacy requires adequate fluid intake. Contains Na+, care in patients with hypertension / heart failure. Laxido® replaces Movicol® as lower cost brand equivalent. Takes 2 to 3 days to exert effect, “prn” use ineffective; should be taken with additional fluid. Therapeutic dose for adults 15ml twice daily. Available OTC. Page 11 Therapeutic Area Formulary choices Pre-op Bowel Cleansing Solutions N/A Peripheral opioidreceptor antagonist Methylnaltrexone Injection 12mg/0.6ml Cost for 28 unless stated Rationale for decision / comments Bowel cleansing medicine may modify the absorption of regularly prescribed medications. Urea and Electrolytes shou;d be checked in all patients to minimise the risk of electrolyte imbalance particularly patients taking the following medications: Diuretics, corticosteroids, cardiac glycosides, NSAIDs, tricyclics, SSRIa, antipsychotics, carbamazepine. See NPSA Alert and local guidelines for details. £21.05 (single vial) £147.35 (7 vial pack) Injection for opioid-induced constipation in terminally ill patients, when response to other laxatives is inadequate. Used in addition to existing laxative therapy. Not licensed for use in any other circumstance. 1.7 Local preparations for anal and rectal disorders Rectal soothing agents Anusol Cream: £2.15 (23g) Ointment: £2.15 (25g) Suppositories: £2.02 (12) Available as cream, ointment and suppositories. Available OTC. Rectal corticosteroids Scheriproct Ointment: £2.94 (30g) Suppositories: £1.38 (12) Scheriproct is recommended over the traditionally widely used Proctosedyl , as the latter is one of the most costly preparations of its type at £10.34 per tube. Preparations for anal fissures Rectogesic (Glyceryl Trinitrate Ointment 0.4%) Ointment: £34.80 (30g) Glyceryl Trinitrate for the management of anal fissure should be prescribed as ® Rectogesic , which is the only available licensed product for this indication. Prescriptions for other strengths will require the dispensing of “specials” which are unlicensed, often have a short shelf life and usually cost in excess of £100 per pack. Maximum duration of use: 8 weeks All external preparations of diltiazem are unlicensed specials and are nonformulary. Acute trust commissioned to provide full treatment course. Gastro-intestinal System ® ® Page 12 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments BNF Chapter 2: Cardiovascular system Related guidance: NICE Clinical Guideline CG127 (2011): Hypertension: Clinical management of primary hypertension in adults NICE Clinical Guideline CG36 (2006): Atrial fibrillation NICE Clinical Guideline CG48 (2007): MI: secondary prevention NICE Clinical Guideline CG107 (2010): Hypertension in pregnancy NICE Clinical Guideline CG108 (2010): Chronic heart failure NICE Technology Appraisal TAG210 (2010): Clopidogrel and modified-release dipyridamole Top Given the wide overlap between many drug groups and clinical indications and vice-versa, the indications for which each drug is included in the formulary are clearly stated in the comments section. Recommendations and local guidelines for the management of specific cardiovascular conditions are provided as inserts. Hypertension Heart Failure Primary Care Guidelines for the Treatment of Chronic Stable Angina Pectoris Management of anticoagulant-induced haemorrhage Primary Prevention of CVD Secondary Prevention of CVD Drug – statin interactions table 2.1 Positive inotropic drugs Cardiac glycosides Cardiovascular system Digoxin 62.5mcg tablets: £1.60 125mcg tablets: £0.95 250mcg tablets: £0.96 Digoxin is included in the formulary for use: Atrial fibrillation: but not paroxysmal AF Heart failure: where symptoms persist (due to LVSD) despite optimum therapy including ACEIs, B-Blockers and diuretics. U&Es should be checked at least 6-monthly, or when drug treatment is changed. Monitoring serum potassium is particularly important in patients‟ taking digoxin or an aldosterone antagonist. A serum digoxin level should be measured within 8-12 hours of the latest dose only if toxicity or non-adherence is suspected. Page 13 Therapeutic Area Formulary choices Cost for 28 unless stated Indapamide 2.5mg tablets: £1.13 Rationale for decision / comments 2.2 Diuretics Thiazides and related diuretics Hypertension: indapamide 2.5mg daily is considered the optimal dose for hypertension NB People treated with bendroflumethiazide whose blood pressure is stable & well controlled should continue on bendroflumethiazide Heart failure: bendroflumethiazide may have a limited role in mild heart failure or where patients are intolerant of loop diuretics. 1.5mg MR tablets: £3.40 (30) Bendroflumethiazide Loop diuretics Aldosterone Antagonists Furosemide Spironolactone Eplerenone Cardiovascular system 2.5mg tablets £0.74 20mg tablets:£0.71 40mg tablets: £0.71 25mg tablets: £1.32 50mg tablets: £1.98 25mg tablets: £42.72 50mg tablets: £42.72 Furosemide is included in the formulary for use Heart failure: to provide relief of symptoms. Patients‟ who do not respond to 80mg/day will require further specialist advice. Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. Spironolactone is included in the formulary for : Heart failure: for patients with NHYA Grade III-IV who remain symptomatic despite optimisation of therapies such as ACE inhibitors and Beta-blockers. Spironolactone is the aldosterone antagonist of choice in this situation; Eplenerone is considered an alternative only for specialist initiation. Hypertension: For treatment of resistant hypertension at step 4 if blood potassium is ≤ 4.5mmol/l Regular monitoring (maintenance): U&E at 6, 9 & 12 months, thereafter every 6 months. Used, in addition to standard therapy, to reduce the risk of cardiovascular mortality and morbidity after recent myocardial infarction in stable patients with left ventricular dysfunction and clinical evidence of heart failure, as an alternative to spironolactone, where sex hormone mediated adverse effects experienced. Page 14 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments 100mg tablets: £1.50 200mg tablets: £2.01 Treatment should only be initiated by a hospital specialist and only for the treatment of severe rhythm disorders not responding to other therapies. Prescribing at initial loading dose should be limited to 2 weeks. Amiodarone therapy requires monitoring of: 2.3 Anti-arrhythmic drugs Drugs for arrythmias Amiodarone LFTs and TFTs at baseline and then every 6 months. Ophthalmic examination at baseline and then twelve-monthly The long half-life of amiodarone (~50 days) means the therapeutic and adverse effects persist for long periods after discontinuation of therapy. WARNING Do not exceed Simvastatin 20mg in patients taking amiodarone and monitor lipid levels to ensure lowest dose necessary of atorvastatin is used. Dronedarone Cardiovascular system 400mg tablets: £67.50 (60) Although effective in treating atrial fibrillation and flutter, dronedarone is not as effective as amiodarone. However, the different side effect profile has led to its use in patients for whom amiodarone may be contraindicated or otherwise unsuitable. See the Shared Care Agreement or NICE TAG Page 15 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments 2.4 Beta-adrenoreceptor blocking drugs Beta blockers may be considered as initial therapy for hypertension particularly if intolerant or C/I to ACEI/ARB for: younger people (under 55) women of childbearing age people with evidence of increased sympathetic drive at Step 4 if further diuretic therapy is not tolerated, C/I or ineffective Evidence suggests the combination of beta-blocker and thiazide increases risk of Type 2 DM and this is generally considered to be dose related. Cardioselective beta-blockers may be used in well-controlled asthmatic patients, or COPD without significant reversible component for Heart Failure or following an MI. Treatment should be initiated at a low-dose & the patient monitored carefully for adverse effects. Recent evidence-based guidance for angina states that beta-blockers should be the first line therapy for the long-term prevention of angina. Patients with heart failure should only be prescribed with beta-blockers licensed for this indication. Beta-blockers Bisoprolol Atenolol Metoprolol Cardiovascular system 1.25mg tablets: £2.03 2.5mg tablets: £1.52 3.75mg tablets: £2.71 5mg tablets: £1.09 7.5mg tablets: £4.66 10mg tablets: £1.23 25mg tablets: £0.71 50mg tablets: £0.72 100mg tablets: £0.77 50mg tablets: £1.05 100mg tablets: £1.15 Bisoprolol is included in the formulary for: Heart failure: Patients‟ with heart failure should be prescribed a betablocker licensed for heart failure. Bisoprolol is first line drug, initiated at 1.25mg and titrated according to guidelines. Hypertension: in line with NICE guidance. Alternative to Atenolol or Metoprolol Angina: as alternative to Metoprolol Post-MI: as alternative to Metoprolol Atenolol is included in the formulary for: Hypertension: in line with NICE guidance. Atenolol dose for hypertension should not normally exceed 50mg daily. Angina: for prophylaxis of symptoms, some additional benefit may be obtained by increasing the dose to 100mg. Metoprolol is included in the formulary for: Hypertension: in line with NICE guidance. Alternative to Atenolol or Bisoprolol Angina: as alternative to Bisoprolol Post-MI: as alternative to Bisoprolol Page 16 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments 2.5 Drugs affecting the renin-angiotensin system and other antihypertensives ACE-inhibitors (ACEIs) should be used in line with NICE / PCT guidance for hypertension and heart failure. All should be prescribed in a single daily dose where possible. Lisinopril and Ramipril are the recommended first line options. Monitoring requirements U+Es at baseline, repeated 1-2 weeks after each dose increase for heart failure and after final dose increase in hypertension, annually thereafter. Patients exhibiting ACE cough on first choice ACEI should trial a second choice ACEI before an ARB. ACE-inhibitors or Cardiovascular system Lisinopril Ramipril capsules 2.5mg tablets: £0.83 5mg tablets: £0.91 10mg tablets: £0.89 20mg tablets: £1.02 1.25mg capsules:£0.96 2.5mg capsules: £1.01 5mg capsules: £1.10 10mg capsules: £1.20 Lisinopril is included in the formulary for: Hypertension: in line with NICE guidance. Usual dose range 2.5mg 20mg daily. May be commenced at dose of 10mg daily in patients without renal impairment and not on diuretics. Post-MI: titrated to 5-10mg daily if possible Heart failure: as guidelines, titrated to 35mg if possible Diabetic nephropathy: initially 2.5mg once daily, adjusted to achieve sitting diastolic BP of < 75mmHg in normotensive IDDM and < 90mm Hg in hypertensive NIDDM, usual range 10- 20mg once daily Ramipril is included in the formulary for: Hypertension: 1.25mg to 10mg daily, in line with NICE guidance. Post-MI: titrated to 10mg daily if possible Heart failure: as guidelines, titrated to 10mg if possible Page 17 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments ARBs should only be used in patients with persistent troublesome ACEI induced cough. The percentage of patients‟ reporting a cough was between 2-10% in randomised controlled trials. ACEIs have a better evidence base and are more cost-effective. ARBs should be used in line with NICE / PCT guidance for hypertension and heart failure. Patients exhibiting ACE cough on first choice ACEI should trial a second choice ACEI before switching to an ARB. Dual therapy ACEI+ARB is not recommended for any indication, other than under specific conditions for patients with heart failure . (NICE CG108 (2010): Chronic heart failure) Angiotensin-II receptor blockers (ARBs) First line: Losartan Following consideration of available evidence at Somerset Prescribing Forum March 2010 it was agreed that generic versions of losartan may be used for all indications Second line: Third line: Cardiovascular system Candesartan Valsartan capsules 25mg tablets: £1.49 50mg tablets: £1.50 100mg tablets: £1.84 Losartan is included in the formulary for: Hypertension: (where intolerant to ACEI except for people of African or Caribbean origin at step 2where ARB are oreferred to ACE) in line with NICE guidance, dose range 25-100mg once daily Renal protection in Type 2 DM with nephropathy: (where intolerant to ACEI) initially 50mg daily, increased after one month to 100mg daily according to blood pressure Heart failure: (>60 yrs; ACE intolerant; LVEF <40% & clinically stable). Patients with heart failure who have been stabilised with an ACE inhibitor should not be switched to losartan. Initially 12.5mg, titrated at weekly intervals to usual maintenance dose of 50mg, as tolerated by patient. 2mg tablets:£4.53 (7) 4mg tablets:£1.24 (7) 8mg tablets:£3.07 16mg tablets: £3.96 32mg tablets: £4.68 Candesartan is included in the formulary for: 40mg capsules:£2.39 80mg capsules:£2.63 160mg capsules:£3.35 Valsartan is only included in the formulary for: Hypertension: (where intolerant to ACEI) in line with NICE guidance, dose range 2-16mg daily Heart failure: (where intolerant to ACEI) as per guidelines, titrated to 32mg daily if possible. Post-MI: (where symptomatic heart failure and intolerant to ACEI), initially 20mg bd, titrated to 160mg bd where tolerated Not included for hypertension Page 18 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments Centrally acting antihypertensive drugs Methyldopa 125mg tablets: £35.37 (56) 250mg tablets: £6.78 56) 500mg tablets: £9.51 (56) Methyldopa is included in the formulary for: 200mcg tablets: £3.22 300mcg tablets: £3.56 400mcg tablets: £3.98 Moxonidine is included in the formulary for: 1mg tablets: £0.82 2mg tablets: £0.84 4mg tablets: £1.17 Doxazosin is included in the formulary for: Moxonidine Alpha-blockers Doxazosin ® as Doxadura brand Cardiovascular system 1mg tablets: £0.74 2mg tablets: £0.84 4mg tablets: £1.05 Hypertension in pregnancy Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. Benign prostatic hyperplasia: See section 7 ® NB. Doxazosin MR (Cardura XL ) tablets are specifically not recommended for maintenance in hypertension and maximum licensed dose for other indications is 8mg. Stabilised hypertensive patients on Doxazosin MR tablets should be switched to standard 4mg tablets: Doxazosin MR 4mg one daily → Doxazosin 4mg one daily Doxazosin MR 8mg one daily → Doxazosin 4mg two daily Page 19 Summary of Antihypertensive Drug Treatments Step 1 Aged under 55 years Step 3 Step 4 Resistant hypertension Cardiovascular system (NICE CG127) ACE inhibitor or ARB (sartan) Calcium channel blocker (CCB) (Choose a low cost ARB) (a CCB is preferred but consider a thiazide-like diuretic if CCB not tolerated or person has oedema, evidence of HF or high risk of HF) [New 2011] *If choosing an ARB (sartan) choose a low cost Step 2 Aged over 55 years or black person of African or Caribbean origin of any age ACE inhibitor or ARB (sartan) + Calcium channel blocker (CCB) ACE inhibitor or ARB (sartan) + Calcium channel blocker (CCB) + Thiazide-like diuretic ACE inhibitor or ARB (sartan) + Calcium channel blocker (CCB) For black people of African or Caribbean origin, consider an ARB (sartan) in preference to an ACEI, in combination with CCB [new 2011] If diuretic treatment is to be initiated or changed, offer a thiazide-like diuretic such as indapamide 1.5mg MR or 2.5mg daily in preference to conventional thiazide diuretics [new 2011] Consider a low dose of spironolactone (25mg once daily) if blood K is ≤4.5mmol/l or higher doses of a thiazide-like diuretic if >4.5mmol/l. [New 2011] + Thiazide-like diuretic + consider further diuretic or alpha- At the time of publication (August 2011) spironolactone did not have a UK marketing license for this indication. Informed consent should be obtained and documented blocker or beta-blocker Consider seeking expert advice Consider an α-blocker or β-blocker if further diuretic therapy is not tolerated, or contraindicated or ineffective Page 20 Cardiovascular system Page 21 Prescribing Guidelines for HEART FAILURE This guidance is not intended to replace NICE CG108 Chronic heart failure (August 2010), but provides primary care prescribers with a summary of key points relevant in practice. Aims of treatment To relieve symptoms To improve exercise tolerance To reduce incidence of acute exacerbations To reduce hospitalisations To reduce mortality First-line treatment Offer both angiotensin-converting enzyme (ACE) inhibitors and beta-blockers licensed for heart failure, to all patients with heart failure due to left ventricular systolic dysfunction (LVSD). Clinical judgement should guide which drug to start first. ACE Inhibitors (first-line treatment) An ACE inhibitor is recommended for ALL patients with asymptomatic LVSD or symptomatic heart failure (unless contra- indicated). Start with a low dose and titrate upwards at short intervals (e.g. not less than 2 weeks). Where possible, ACE inhibitor treatment should be titrated up to the highest licensed dose which is tolerated. GPs considering initiating ACE inhibitor therapy should consider specialist supervision and/or particularly careful monitoring for those patients: receiving multiple or high dose diuretics (≥ furosemide 80mg) with hypovolaemia with hyponatraemia (<130mmol/l) with pre-existing hypotension (systolic < 90mm Hg) with unstable heart failure with renal impairment (creatinine > 150mmol/l) receiving high-dose vasoldilator therapy aged 70 years or more NB: A small dose of an ACE inhibitor is better than no ACE inhibitor at all. Because of the risk of hypotension, especially in patients with hypovolaemia, consideration should be given to withholding or reducing the dose of diuretics for 24 hours prior to commencement of an ACE inhibitor. Where possible all ACE inhibitors should be used in a single daily dose to aid compliance and costeffectiveness. Formulary recommended ACE inhibitors; LISINOPRIL initially 2.5-5mg ONCE DAILY, titrated up to 30-35mg ONCE DAILY, or RAMIPRIL initially 2.5mg ONCE DAILY (1.25mg if already prescribed a diuretic), titrated up yo 10mg ONCE DAILY Monitoring: serum urea, creatinine, electrolytes and eGFR at initiation and after each dose increment Cardiovascular system Page 22 Beta-blockers (first-line treatment) Offer beta-blockers licensed for heart failure to all patients with heart failure due to left ventricular systolic dysfunction, including: • • older adults and patients with: o peripheral vascular disease o erectile dysfunction o diabetes mellitus o interstitial pulmonary disease and o chronic obstructive pulmonary disease (COPD) without reversibility. Beta-blocker therapy should be initiated by those experienced in the management of heart failure and should commence at a very low dose and titrated up by doubling doses at intervals of not less than two weeks. Heart rate, blood pressure and clinical status should be assessed after each titration. Symptoms may deteriorate initially, calling for adjustment of concomitant therapy, such as temporary increase in dose of diuretics. Stable patients who are already taking a beta-blocker for a comorbidity (for example, angina or hypertension), and who develop heart failure due to left ventricular systolic dysfunction, should be switched to a beta-blocker licensed for heart failure. Formulary recommended beta-blocker for heart failure; BISOPROLOL initially 1.25mg ONCE DAILY, titrated according to response and tolerability to 10mg ONCE DAILY Where an alternative to bisoprolol is required, for example where there is intolerance or concern that unopposed beta-blockade may be undesirable; Carvedilol should be considered as the appropriate alternative beta-blocker for heart-failure patients. There is also a stronger evidence base for carvedilol in those patients with higher grades of heart failure and its use may be preferred in this situation. Prescribers should be aware that carvedilol requires twice-daily dosing and the implications of this for compliance with therapy should be taken into account when selecting a beta-blocker for heart failure. NB. Although doses of beta-blockers should be titrated to the maximum tolerated, a small dose of a beta-blocker is better than no beta-blocker at all. Second-line treatment Seek specialist advice and consider adding one of the following if a patient remains symptomatic despite optimal therapy with an ACE inhibitor and a betablocker: • • • an aldosterone antagonist licensed for heart failure (especially if the patient has moderate to severe heart failure [NYHA class III–IV] or has had an MI within the past month) or an angiotensin II receptor antagonist (ARB) licensed for heart failure (especially if the patient has mild to moderate heart failure [NYHA class II–III]) or hydralazine in combination with nitrate (especially if the patient is of African or Caribbean origin (not including mixed race) and has moderate to severe heart failure [NYHA class III–IV]) Cardiovascular system Page 23 Aldosterone antagonists (second-line treatment) Formulary recommended aldosterone antagonist for heart failure; SPIRONOLACTONE initially 25mg each morning, reducing to 12.5mg daily or 25mg on alternate days if necessary Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter Although the doses of spironolactone recommended for use in heart failure are much lower than those used for ascites, there is still a significant risk of electrolyte disturbance. Patients who have had an acute MI and who have symptoms and/or signs of heart failure and LVSD, should be prescribed an aldosterone antagonist licensed for post-MI treatment. This should be initiated within 3–14 days of the MI, preferably after ACE inhibitor therapy. Formulary recommended aldosterone antagonist for signs or symptoms of heart failure post-MI; EPLERENONE initially 25mg ONCE DAILY, increased within 4 weeks to 50mg ONCE DAILY Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter Angiotensin Receptor Blockers (ARBs) (second-line or alternative first-line treatment) The weight of evidence supporting use of ARBs in heart failure is not as robust as it is for use of ACE inhibitors and therefore an ARB can only be recommended for those patients who are intolerant of ACE inhibitor therapy due to intractable cough. On the basis of the currently available evidence, candesartan and losartan are the only ARBs licensed for use in heart failure. The combination of an ACE-inhibitor, a potassium-sparing diuretic (e.g. spironolactone), and an ARB is not recommended and should be considered only after careful consideration of the potential benefits and risks. Formulary recommended ARB; LOSARTAN initially 12.5mg ONCE DAILY, increased at 1 - 2 weekly intervals, to 50mg ONCE DAILY CANDESARTAN initially 4mg ONCE DAILY, doubling the dose at intervals of no less than 2 weeks, to 32mg ONCE DAILY Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter The triple combination of Valsartan, ACE inhibitor and beta-blocker should be avoided, based on current evidence. As with ACE inhibitors, it is recommended to exert particular care when using ARBs in the patient groups who are at greater risk of complications and consideration given to specialist input where appropriate. Hydralazine in combination with a nitrate (alternative first-line treatment) Hydralazine in combination with nitrate can be considered for patients with heart failure due to LVSD who are intolerant of ACE inhibitors and ARBs. Seek specialist advice. Cardiovascular system Page 24 Third-line treatment Digoxin is appropriate for patients with atrial fibrillation and any degree of heart failure. It is also recommended for those with worsening or severe heartfailure due to LVSD who remain symptomatic despite treatment with an ACE Inhibitor and a beta blocker. Digoxin may improve symptoms, exercise tolerance and reduce hospitalisations. Digoxin has not been shown to reduce mortality. Hypokalaemia predisposes to digoxin toxicity so careful monitoring of U&Es is required, especially where patients are also prescribed loop or thiazide diuretics, particularly if an ACE inhibitor, ARB or spironolactone is not co-prescribed. Formulary recommendation; DIGOXIN 62.5mcg - 125mcg ONCE DAILY (higher doses are rarely appropriate in heart failure not associated with AF) Monitoring: serum urea & electrolytes, particularly potassium, creatinine, & eGFR required Diuretics A diuretic is usually required by most patients with heart failure to reduce symptoms of fluid overload, reduce hospitalisation due to acute exacerbation and increase exercise tolerance. The dose should be titrated (up and down) according to need following the initiation of subsequent heart failure therapies. Formulary recommended loop diuretic; FUROSEMIDE 20mg - 40mg ONCE DAILY (in the morning), titrated according to symptomatic response Monitoring: serum urea & electrolytes, creatinine, & eGFR required A thiazide diuretic may be of benefit in patients with mild heart failure and good renal function; however thiazides are ineffective in patients with poor renal function. Formulary recommended thiazide diuretic; BENDROFLUMETHIAZIDE 2.5mg ONCE DAILY (in the morning) Monitoring: serum urea & electrolytes, creatinine, & eGFR required If diuresis with one diuretic is insufficient, a combination of loop diuretic and thiazide may be tried. Metolazone may still be recommended but has been discontinued in the UK. AMBER in TLS. Indapamide combined with furosemide has been found to be effective in a small trial of patients with massive oedema although this is an unlicensed use. (Tanaka M et al. The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema. Clinical and Experimental Nephrology, June 2005, vol./is. 9/2(122-126) Cardiovascular system Page 25 Calcium channel blockers No Calcium channel blocker is licensed for the treatment of heart failure. The use of calcium channel blockers with a direct effect on cardiac contractility i.e. verapamil or diltiazem should be specifically avoided in heart failure. For those patients who develop heart failure or are at high risk of heart failure NICE 127 recommends they should be changed to a thiazide-like diuretic in place of a CCB. Where continuation of a dihydropyridine calcium channel blocker is considered essential for control of hypertension or angina, this may be justified where use of other therapies such as beta-blocker, ACE-inhibitor and diuretic has been optimised. Ivabradine Initiation only for patients on maximum therapy & with heart rate > 75 beats per minute NICE TA 267 Ivabradine for Treating Chronic heart failure - recommends ivabradine as a possible treatment for people with chronic heart failure provided the following conditions are all met. o New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction o who are in sinus rhythm with a heart rate of 75 beats per minute or more o who are given ivabradine in combination with standard therapy including beta-blocker therapy, angiotensin-converting enzyme (ACE) inhibitors and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated (after 4 week period of stabilisation on these meds) o with a left ventricular ejection fraction of 35% or less Initiation may be by GPwSI or heart failure specialist nurse. Cardiovascular system Page 26 NHS SOMERSET: Heart Failure Prescribing Guidelines Algorithm adapted from NICE CG108 by the Medicines Management team, October 2010 For further details please refer to the full PCT guidance above and to NICE Clinical Guideline 108: Chronic heart failure STANDARD TREATMENT FOR PATIENTS WITH HEART FAILURE DUE TO LVSD OR WITH PRESERVED EJECTION FRACTION New diagnosis of heart failure with preserved ejection fraction New diagnosis of heart failure due to left ventricular systolic dysfunction Manage comorbid conditions such as high blood pressure, ischaemic heart disease and diabetes mellitus in line with relevant NICE guidance FIRST LINE TREATMENT Start ACE-inhibitor OR beta-blocker licensed for heart failure Clinical judgement should guide which to start first e.g. Lisinopril or Bisoprolol, and titrate upwards If ACE-inhibitor not tolerated, trial a second ACE-inhibitor If second ACE-inhibitor not tolerated, considering an ARB (Losartan) If ARB not tolerated, consider hydralazine plus a nitrate Offer rehabilitation and education Diuretics should be prescribed for the relief of congestive symptoms and fluid retention. Start ACE-inhibitor OR beta-blocker licensed for heart failure Which ever is not yet prescribed, and titrate upwards The dose should be titrated up and down according to the patients’ need following initial and subsequent heart failure therapies Ensure both therapies are prescribed at maximum tolerated dose Specialist assessment Ivabradine – option For consultant initiation only for patients on maximum therapy & with heart rate > 75 beats per minute, in sinus rhythm – see p.26 Cardiovascular system SECOND LINE TREATMENT If patient remains symptomatic, seek specialist advice and consider adding spironolactone, an ARB (Losartan), or hydralazine plus a nitrate. THIRD LINE TREATMENT If symptoms persist, consider digoxin Page 27 Therapeutic Area Formulary choices Cost for 28 unless stated Rationale for decision / comments 2.6 Nitrates, calcium channel blockers and potassium channel activators Nitrates Glyceryl trinitrate (GTN) spray 400mcg: £3.29 (200 dose) 400mcg: £2.63 (180 dose) as ® brand Nitromin Glyceryl trinitrate is included in the formulary for: ISMN First line: Isosorbide mononitrate Standard tablets 10mg: £1.74 (56) 20mg: £1.83 (56) 40mg: £2.14 (56) ISMN second line: Sustained-release Isosorbide Mononitrate is included in the formulary for: Angina: for prophylaxis of symptoms as monotherapy where intolerance or C/I to use of a beta-blocker or rate-limiting CCB. As combination therapy with beta-blocker or CCB where monotherapy provides insufficient control. First line is to prescribe standard Isosorbide mononitrate tablets asymmetrically to ensure a nitrate free period is maintained to reduce nitrate tolerance e.g. 20mg bd at 6-8am and 2-4pm. If patients cannot comply with this regime, MR preparations should be prescribed by brand (Tardisc XL for 60mg) and only given once-daily to reduce nitrate tolerance. Where Isosorbide mononitrate has been added to provide symptom control pending angioplasty or CABG, consideration should be given to cautious withdrawal after successful completion of and recovery from the procedure Tardisc XL tablets 60mg: £3.49 (28) Angina: for as required use for relief of symptoms Note that GTN tablets are now significantly more costly than spray ISOSORBIDE DINITRATE is NON-FORMULARY except where initiated by a specialist for left ventricular failure Cardiovascular system Page 28 Cardiovascular system Page 29 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Calcium channel blockers – Dihydropyridines First line: Amlodipine ® as Amlostin brand 5mg tablets: £0.87 10mg tablets: £94 NB. Avoid short-acting dihydropyridines in BP, CHD and CCF. 5mg tablets: £0.78 10mg tablets: £0.85 Amlodipine is first line CCB, with lercanidipine as a second line option for: Hypertension: in line with NICE guidance Second line: Lercanidipine 10mg tablets: £1.64 20mg tablets: £2.11 Angina: as monotherapy where intolerance or C/I to use of a betablocker or rate-limiting CCB. As combination therapy with beta-blocker where monotherapy provides insufficient control. NB: When prescribing Amlodipine generically, this should be as plain ® Amlodipine. Prescriptions for Amlodipine besilate will result in the supply of Istin and incur significantly greater costs. Calcium channel blockers - Rate limiting Prescribe by brand Diltiazem M/R as Slozem 120mg m/r capsules: £7.00 180mg m/r capsules: £7.80 240mg m/r capsules: £8.20 300mg m/r capsules: £8.50 Diltiazem MR (as Slozem) is included in the formulary for: Angina: as monotherapy where intolerance or C/I to use of a betablocker. In combination with a beta-blocker where monotherapy provides insufficient control. - NB. caution required due to risk of bradycardia and heart-block. Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. NB. Prescribing Diltiazem MR as the formulary preferred Slozem brand ensures continuity of supply, as recommended nationally. Verapamil 40mg tablets: £1.69 (84) 80mg tablets: £2.22 (84) and Prescribe by brand Angina: as monotherapy where intolerance or C/I to use of a betablocker. Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. Verapamil M/R as Half-Securon SR or Securon SR Cardiovascular system Verapamil is included in the formulary for: 120mg m/r tablets: £7.71 240mg m/r tablets: £5.55 NB. Verapamil should not be combined with a beta-blocker for any indication due to high risk of bradycardia and heart-block Page 30 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 2.6.3 Other antianginal drugs Potassium Channel Activator Nicorandil 10mg: £5.49 (60) 20mg: £10.53 (60) Where Nicorandil has been added for symptom control pending angioplasty or CABG, strong consideration should be given to cautious withdrawal after successful completion of and recovery from the procedure. Nicorandil is associated with oral, anal, gi & para-stomal ulceration & delayed wound healing. Addition of a PPI is ineffective to promote healing – cessation of the drug is needed. Sinus Node Regulator Ivabradine 5mg: £40.17 7.5mg: £40.17 GREEN for medical management of Stable angina: in line with NICE CG126 See guide p.29 AMBER for management of heart failure (see guidelines page 26) QT prolongation may be exacerbated by heart rate reduction. The ue of ivabradine with other drugs which prolong QT interval eg citalopram, diltiazem, should be avoided. If the combination appears necessary, close cardiac monitoring is needed. Hypokalaemia and hypomagnesaemia can increase the risk of arrhythmia especially in patients with long QT interval, whether congenital or substanceinduced eg with potassium-depleting diuretics (thiazide diuretics and loop diuretics). Caution & careful monitoring is needed. Other Ranolazine 375mg: £48.98 (60) 500mg: £48.98 (60) 750mg: £48.98 (60) Included for medical management of Stable angina: in line with NICE CG126 See guide p. 29 2.6.4 Peripheral vasodilators and related drugs Related guidance: NICE Technology Appraisal TA223 (2011): Treatment of intermittent claudication in people with peripheral vascular disease Vasodilators Cardiovascular system Naftidrofuryl 100mg capsules: £6.16 (84) Naftidrofuryl oxalate is recommended as an option for the treatment of intermittent claudication in people with peripheral arterial disease for whom vasodilator therapy is considered appropriate after taking into account other treatment options (NICE TA223) Cilostazol, pentoxifylline and inositol nicotinate are not recommended for the treatment of intermittent claudication in people with peripheral arterial disease. Page 31 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 2.8 Anticoagulant drugs Parenteral anticoagulants Related guidance: NICE Clinical Guideline CG92 (2010): Venous thromboembolism – reducing the risk A Shared Care agreement is available for the use of Enoxaparin in pregnancy Enoxaparin Pre-filled syringes 20mg/0.2ml: £22.72 (10) 40mg/0.4ml: £30.27 (10) 60mg/0.6ml: £45.65 (10) 80mg/0.8ml: £64.86 (10) 100mg/1ml: £80.33 (10) 120mg/0.8ml: £97.70 (10) 150mg/1ml: £111.01 (10) Enoxaparin is licensed for the prophylaxis and treatment of venous thromboembolism; treatment of unstable angina, non-Q-wave myocardial infarction, acute ST-segment elevation myocardial infarction (STEMI); prevention of thrombus formation in the extracorporeal circulation during haemodialysis. NB. Dalteparin is licensed for treatment of symptomatic VTE and prevention of its recurrence, in patients with solid tumours. Management of haemorrhage: haemorrhage is the main adverse effect of all oral anticoagulants. Checking the INR and omitting doses is essential. If the anticoagulant is stopped but not reversed, the INR should be checked again after 2 to 3 days to ensure that it is falling. The following recommendations apply to patients taking Warfarin and are based on the result of the INR and whether there is major or minor bleeding: Major bleeding: stop Warfarin; give Phytomenadione (Vitamin K1) 5-10mg by slow intra-venous injection; give prothrombin complex concentrate (factirs II, VII, IX and X) 30-50units/kg (or if no concentrate available) fresh frozen plasma 15ml/kg. INR> 8.0, no bleeding or minor bleeding: stop Warfarin, re-start when INR < 5. If there are other risk factors for bleeding, give Phytomenadione (Vitamin K1) 500mcg by slow intra-venous injection or 5mg by mouth, (for partial reversal of anticoagulation give smaller oral doses of Phytomenadione e.g. 0.5mg – 2.5mg, using the intravenous p reparation orally); repeat dose of Phytomenadione if INR still too high after 24 hours. See Chapter 9 for details of Phytomenadione preparations on the formulary. Management of patients on warfarin should be in line with the National Enhanced Service specification. Oral anticoagulants Coumarins (continued on next page) Cardiovascular system Refer to National Patient Safety Agency (NPSA) guidance on safe practices around use of anticoagulants. Warfarin 500mcg tablets: £1.49 1mg tablets: £0.75 3mg tablets: £0.78 5mg tablets: £0.85 Warfarin is included in the formulary for the following indications (with target INRs): Atrial fibrillation: target INR = 2.5 Treatment of DVT or PE: target INR = 2.5 Recurrent DVT or PE: target INR = 3.5 Mechanical prosthetic heart valves: target INR dependent on type and location of valve. Generally a target INR of 3 is recommended for mechanical aortic valves and a target INR of 3.5 for mechanical mitral valves Page 32 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Dabigatran 75mg capsules: £65.90 (60) 75mg only for after elective knee & hip surgery in some patients – RED in TLG 110mg capsules:£65.90 (60) 150mg capsules:£65.90 (60) Dabigatran is included for the prevention of stroke & systemic embolism for people with non-valvular atrial fibrillation where patients fit the criteria in NICE TA249. See Implementation priorities p35 10mg tablets: £63.00 (30) 10mg only for after elective knee & hip surgery – RED in TLG Rivaroxaban is included for the prevention of stroke & systemic embolism for people with non-valvular atrial fibrillation where patients fit the criteria in NICE TA256. See p36 for implementation priorities. and Treatment of DVT and prevention of recurrent DVT and PE as per NICE TA261 Oral anticoagulants (continued) Direct thrombin Inhibitor Direct inhibitor of activated Factor X Rivaroxaban 15mg tablets: £58.80 (28) 20mg tablets: £58.80 (28) Apixaban 2.5mg tablets: £102.90 (60) 5mg tablets: £64.50 (56) See note below for use post elective hip & knee replacement. See note below for use post elective hip & knee replacement. Apixaban is included for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation, with one or more risk factors, as for Dabigatran & Rivaroxaban NICE TA275 RED Indication in TLG: Primary prevention of venous thromboembolic events in adult patients after elective total hip replacement surgery or total knee replacement surgery. The full course should be supplied when the procedure is carried out & there should be no requirement to prescribe for either 10mg rivaroxaban or 75mg dabigatran in primary care. See TA157 Dabigatran, TA170 Rivaroxaban & TA245 Apixaban Cardiovascular system Page 33 Rivaroxaban & dabigatran are “black triangle drugs” ie subject to intensive monitoring by CHM & MHRA. Reports of any adverse drug reactions (however minor) are encouraged. Following is extracted from SPC for the drugs on electronic Medicines Compendium last updated 18/6/2012 (rivaroxaban) & 23/7/12 (dabigatran) Medication Rivaroxaban Dabigatran Any other anticoagulant – (limited experience) ↑bleeding risk ↑bleeding risk. Contra-indicated except when switching treatment Systemic Azoles e.g. ketonconazole, itraconazole AVOID ↑bleeding risk AVOID ↑bleeding risk HIV protease inhibitors eg ritonavir AVOID ↑bleeding risk Not studied – combination not recommended Ciclosporin, tacrolimus AVOID ↑bleeding risk Dronedarone AVOID AVOID Strong CYP34A Inducer eg.Rifampicin, phenytoin, carbamazepine, St Johns Wort CAUTION ↓rivaroxaban plasma levels AVOID ↓dabigatran plasma levels Amiodarone Verapamil, quinidine CYP3A4 inhibitors (e.g Clarithromycin) Caution ↑dabigatran plasma levels (especially in renal impairment) Caution & reduce doseof dabigatran ↑dabigatran plasma levels (especially in renal impairment) ↑rivaroxaban plasma levels, not considered clinically Monitor for signs of bleeding, especially if relevant but Caution if renal impairment renal impairment SSRIs/SNRIs/NSAID/platelet aggregation inhibitors Caution These products typically increase bleeding risks. Care is to be taken. Cardiovascular system Caution ↑bleeding risk Page 34 DABIGATRAN IMPLEMENTATION PRIORITIES: FOR PATIENTS WITH NON VALVULAR AF and 1 or more RISK FACTORS RISK FACTORS Previous stroke, TIA or systemic embolism Left ventricular ejection fraction below 40% Symptomatic heart failure of New York Association (NYHA) class 2 or above Age 75 Years or older Age 65 years or older with one of Diabetes, Coronary artery disease or hypertension EXCLUSIONS DABIGATRAN IS A POWERFUL ANTI-COAGULANT WHICH CAN’T BE REVERSED BY VITAMIN K BEFORE CONSIDERATION PATIENTS MUST HAVE AN UP TO DATE RENAL FUNCTION TEST: Creatinine clearance <30ml/min (eGFR <30) => use of Dabigatran is contra-indicated do not proceed Contra-indicated with ketoconazole, cyclosporine, itraconazole and tacrolimus (see SPC for full list) An online eGFR calculator is available at: http://www.renal.org/eGFRcalc/GFR.pl Mechanical Heart Valve – contra-indicated All new and existing Non Valvular AF patients should discuss with their clinician the risks and benefits of swallow dabigatran compared to–warfarin before initiation or switching Patient unable to whole capsules do not proceed 1st 2nd 3rd 4th Patients with elevated liver enzymes (>2 ULN) were excluded in studies. Use of dabigatran not recommended in this population. Patients newly diagnosed with Non Valvular AF – with good medicine compliance. Dabigatran is NOT suitable for patients using MDS systems because product must remain in original packaging. Age < 80yrs 150mg BD Age >80yrs 110mg BD Patients fitting Criteria currently receiving no preventative treatment Patients fitting Criteria receiving just aspirin – Aspirin offers little protection against stroke in AF compared to warfarin or dabigatran Patients with unstable INR on Warfarin or Phenindione. Starting with those patients most commonly out of treatment range House Bound patients requiring remote monitoring of INR When clinically relevant bleeding occurs, treatment should be interrupted. Bleeding can occur at any site during therapy with dabigatran. An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to a search for a bleeding site Caution - Concomitant administration of strong P-gp inhibitors (such as amiodarone, verapamil, quinidine, ketoconazole and clarithromycin) is expected to result in increased dabigatran plasma concentrations and potential increase in bleeding risk Dabigatran can be given as soon as INR is < 2.0 5th Patients with stable INR on Warfarin or Phenindione - the risks/ benefits of dabigatran compared to warfarin should be discussed as it may be appropriate for stable patients to remain on warfarin Cardiovascular system FURTHER PRESCRIBER GUIDANCE: electronic Medicines Compendium and information on renal function, tests & relationship between creatinine clearance & eGFR here Page 35 RIVAROXABAN IMPLEMENTATION PRIORITIES FOR PATIENTS WITH NON VALVULAR AF and 1 or more RISK FACTORS RISK FACTORS Previous stroke, TIA or systemic embolism Left ventricular ejection fraction below 40% Symptomatic heart failure of New York Association (NYHA) class 2 or above Age 75 Years or older Age 65 years or older with one of Diabetes, Coronary artery disease or hypertension EXCLUSIONS RIVAROXABAN IS A POWERFUL ANTI-COAGULANT WHICH CAN’T EASILY BE REVERSED (prothrombin complex concentrate is an option) BEFORE CONSIDERATION PATIENTS MUST HAVE AN UP TO DATE RENAL FUNCTION TEST: Creatinine clearance <15ml/min (eGFR <20) => use of Ribaroxaban is contra-indicated do not proceed Contra-indicated with ketoconazole, voriconazole, itraconazole and dronedarone (see SPC for full list) An online eGFR calculator is available at: http://www.renal.org/eGFRcalc/GFR.pl Mechanical Heart Valve – contra-indicated Patient unable of to rivaroxaban swallow whole capsulesto–warfarin do not proceed All new and existing Non Valvular AF patients should discuss with their clinician therisks and benefits compared before initiation or switching Patients with elevated liver enzymes (>2 ULN) were excluded in studies. Use of dabigatran not recommended in this population. 1st If a dose is missed the patient should take Patients newly diagnosed with Non Valvular AF – with good medicine rivaroxaban immediately and continue on the compliance. Rivaroxaban is suitable for patients using MDS systems following day with the once daily intake as Dose 20mg ONCE DAILY for all ages recommended. The dose should not be doubled Dose 15mg ONCE DAILY if creatinine clearance 15-49 ml/min within the same day to make up for a missed dose. 2nd House Bound Patients fitting Criteria currently receiving no preventative treatment patients requiring remote Pregnancy monitoring of 3rd Safety and efficacy of rivaroxaban have not Patients fitting Criteria receiving just aspirin – Aspirin offers little INR been established in pregnant women. Studies protection against stroke in AF compared to warfarin or rivaroxaban in animals have shown reproductive toxicity and rivaroxaban passes the placenta. Patients with unstable INR on Warfarin or Phenindione. Start with Contraindicated during pregnancy 4th those patients most commonly out of treatment range. Rivaroxaban can be given as soon as INR is < 3.0 5th Patients with stable INR on Warfarin or Phenindione - the risks/ benefits of rivaroxaban compared to warfarin should be discussed as it may be appropriate for stable patients to remain on warfarin Cardiovascular system FURTHER PRESCRIBER GUIDANCE: electronic Medicines Compendium and information on renal function, tests & relationship between creatinine clearance & eGFR here Page 36 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 2.8 Antiplatelet drugs Related guidance: NICE Technology Appraisal TAG210 (2010): Clopidogrel and modified-release dipyridamole Anti-platelet drugs Aspirin 75mg dispersible tablets: £0.69 ATT meta-analysis : Aspirin for primary prevention of CVD Aspirin is not licensed for the primary prevention of vascular events but there remains the possibility for particular sub-groups of individuals at higher CV risk (including conditions such as diabetes) that the risk:benefit of aspirin is favourable. Until more evidence is available, the use of Aspirin 75mg for primary prevention should be based on an individual risk assessment. Aspirin is included in the formulary for: Secondary prevention of CV events: see notes regarding use in combination with Dipyridamole or Clopidogrel below NB There is evidence that: Aspirin doses >75mg daily increase GI toxicity and general bleed risk Enteric-coated Aspirin does not reduce GI events and may be less effective Dipyridamole m/r 200mg m/r capsules: £10.06 (60) Modified-release dipyridamole alone is recommended by NICE as an option to prevent occlusive vascular events; for people who have had an ischaemic stroke only if aspirin and clopidogrel are contraindicated or not tolerated or for people who have had a transient ischaemic attack only if aspirin is contraindicated or not tolerated. ® Dipyridamole m/r (with Aspirin) as Asasantin Retard Continued on next page Cardiovascular system 200/25mg m/r capsules: £9.84 (60) Modified-release dipyridamole in combination with aspirin (as Asasantin Retard ) is recommended by NICE as an option to prevent occlusive vascular events; for people who have had a transient ischaemic attack or for people who have had an ischaemic stroke only if clopidogrel is contraindicated or not tolerated. Non modified-release dipyridamole products, e.g. dipyridamole liquid, should NOT be prescribed as evidence shows no clinical benefit. Page 37 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Anti-platelet drugs Clopidogrel 75mg tablets: £1.91 (30) Clopidogrel is recommended by NICE as an option to prevent occlusive vascular events; (Continued from previous page) Following consideration of available evidence at Somerset Prescribing Forum Sep 2009 it was agreed that generic versions of clopidogrel may be used for all indications for people who have had an ischaemic stroke or who have peripheral arterial disease or multivascular disease or TIA (by local agreement) for people who have had a myocardial infarction only if aspirin is contraindicated or not tolerated. Clopidogrel is also included in the formulary for: Patients with true aspirin allergy who require secondary prevention of cardiac or vascular disease In combination with Aspirin 75mg daily following acute coronary syndrome (ACS) for a period of 12 months In combination with Aspirin 75mg daily following insertion of drug-eluting stent for a period of 12 months In combination with Aspirin 75mg daily following insertion of non-drugeluting stent for a period of 1 month In combination with Aspirin 75mg daily following a STEMI for a period of 28 days (secondary care provision) In all cases where Clopidogrel is initially used in combination with Aspirin, when the Clopidogrel is stopped, anti-platelet therapy continues with Aspirin 75mg daily alone. Patients requiring treatment with clopidogrel and PPI should avoid omeprazole and esomeprazole which may reduce the effects of clopidogrel on platelet function and lead to poorer long-term patient outcomes (death and readmission). The effect of clopidogrel is also antagonised by calcium-channel blockers and some statins. Prasugrel Prescribers should ensure that all prescriptions for prasugrel have a stop date and that no repeats are issued after that date. Cardiovascular system 5mg tablets: £47.56 10mg tablets:£47.56 Prasugrel in combination with aspirin is recommended as an option for preventing atherothrombotic events in people with acute coronary syndromes having percutaneous coronary intervention, only when: • immediate primary percutaneous coronary intervention for ST-segmentelevation myocardial infarction is necessary or • stent thrombosis has occurred during clopidogrel treatment or • the patient has diabetes mellitus. Treatment should continue for 12 months unless discontinued earlier, e.g. for side effects (NICE TA182: Acute coronary syndrome - prasugrel) Page 38 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Ticagrelor £54.60 (56) Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months as a treatment option in adults with acute coronary syndromes (ACS) as follows: • with ST-segment-elevation myocardial infarction (STEMI) or • with non-ST-segment-elevation myocardial infarction (NSTEMI) or • admitted to hospital with unstable angina – defined as ST or T wave changes on electrocardiogram suggestive of ischaemia plus one of the characteristics defined in guidance. Before ticagrelor is continued beyond the initial treatment, the diagnosis of unstable angina should first be confirmed, ideally by a cardiologist. Prescribers should ensure that all prescriptions for ticagrelor have a stop date and that no repeats are issued after that date. See NICE TA236: Ticagrelor for the treatment of acute coronary syndromes Hyperglycaemia in ACS Hyperglycaemia is common in people admitted to hospital with ACS. Hyperglycaemia at the time of admission with ACS is a powerful predictor of poorer survival and increased risk of complications while in hospital, regardless of whether or not the patient has diabetes. All patients with hyperglycaemia after ACS and without known diabetes tests for should be tested for • HbA1c levels before discharge and • fasting blood glucose levels no earlier than 4 days after the onset of ACS. GPs should offer at least annual monitoring of HbA1c and fasting blood glucose levels to people without known diabetes who have had hyperglycaemia after an episode of ACS Cardiovascular system Page 39 2.12 Lipid-regulation Primary prevention of CVD (based on NICE Clinical Guideline CG67 (2008): Lipid modification) For primary prevention of CVD in primary care, a systematic strategy should be used to identify people aged 40–74 likely to be at high risk. People should be prioritised on the basis of an estimate of their CVD risk before a full formal risk assessment. Their CVD risk should be estimated using CVD risk factors already recorded in primary care electronic medical records. The Framingham 1991 10-year risk equations1 should be used to assess CVD risk. People should be offered information about their absolute risk of CVD and about the absolute benefits and harms of an intervention over a 10-year period. This information should be in a form that: presents individualised risk and benefit scenarios presents the absolute risk of events numerically uses appropriate diagrams and text (See www.npci.org.uk) Before offering lipid modification therapy for primary prevention, all other modifiable CVD risk factors should be considered and their management optimised if possible. Baseline blood tests and clinical assessment should be performed, and comorbidities and secondary causes of dyslipidaemia should be treated. Assessment should include: smoking status alcohol consumption blood pressure (see NICE CG127: Hypertension) body mass index or other measure of obesity (see NICE CG43: Obesity) fasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides (if fasting levels are not already available) fasting blood glucose renal function liver function (transaminases) thyroid-stimulating hormone (TSH) if dyslipidaemia is present 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 risk should be estimated using an appropriate risk calculator, or by clinical assessment for people for whom an appropriate risk calculator is not available or appropriate (for example, older people, people with diabetes or CKD or people in high-risk ethnic groups) (see NICE TA94: Cardiovascular disease – statins) Treatment for the primary prevention of CVD should be initiated with simvastatin 40 mg. If there are potential drug interactions, or simvastatin 40 mg is contraindicated, a lower dose or alternative preparation such as pravastatin may be chosen. 1 Anderson KM, Odell PM, Wilson PW et al. (1991) Cardiovascular disease risk profiles. American Heart Journal 121: 293–8. Cardiovascular system Page 40 Secondary prevention of CVD (based on NICE Clinical Guideline CG67 (2008): Lipid modification) For secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors. Blood tests and clinical assessment should be performed, and co-morbidities and secondary causes of dyslipidaemia should be treated. Assessment should include: smoking status alcohol consumption blood pressure (see NICE CG127: Hypertension) body mass index or other measure of obesity (see NICE CG43: Obesity) fasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides (if fasting levels are not already available) fasting blood glucose (see NICE CG87: Type 2 diabetes – newer agents (a partial update of CG66) renal function (see NICE CG73: Chronic kidney disease) liver function (transaminases) thyroid-stimulating hormone (TSH) if dyslipidaemia is present Statin therapy is recommended for adults with clinical evidence of CVD (see NICE TA94: Cardiovascular disease – statins) Offer statins to people with CKD for secondary prevention of CVD irrespective of baseline lipid values Offer antiplatelet drugs to people with CKD for secondary prevention of CVD Treatment for the secondary prevention of CVD should be initiated with simvastatin 40 mg. If there are potential drug interactions, or simvastatin 40 mg is contraindicated, a lower dose or alternative preparation such as pravastatin may be chosen. Any decision to offer a higher intensity statin should take into account informed preference, comorbidities, multiple drug therapy, and the benefit and risks of treatment. There is an increased risk of myopathy associated with high-dose (80mg) simvastatin. The 80mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks. (see MHRA Drug Safety Update May 2010; 3 (10)) People with acute coronary syndrome should be treated with a higher intensity statin. Any decision to offer a higher intensity statin should take into account the patient's informed preference, comorbidities, multiple drug therapy, and the benefits and risks of treatment. ‘Higher intensity statins’ are statins used in doses that produce greater cholesterol lowering than simvastatin 40 mg. For people with diabetes and existing or newly diagnosed CVD (or an increased albumin excretion rate) intensifying cholesterol lowering therapy with a more effective statin (first line) or ezetimibe (second line) to achieve TC < 4 or LDL <2. Cardiovascular system Page 41 Drug – statin interactions No restriction Monitor Atorvastatin (ATV) Amiodarone Monitor lipid levels to ensure lowest dose ATV used No interaction No interaction Recommended max dose 20mg SMV Amlodipine No interaction No interaction No interaction Recommended max dose 20mg SMV Ciclosporin Recommended maximum dose 10mg ATV Recommended start dose 20mg PRV, titrate to max 40mg with caution Contraindicated Recommended max dose 10mg SMV Clarithromycin If on 40mg or 80mg ATV: reduce dose or temporarily suspend ATV Monitor No interaction Contraindicated Diltiazem Monitor lipid levels to ensure lowest dose ATV used No interaction No interaction Recommended max dose 20mg SMV No interaction May increase risk of myopathy No interaction May increase risk of myopathy Rosuvastatin (RSV) Dosing restrictions Drug Ezetimibe Pravastatin (PRV) Contraindicated / not recommended No interaction May increase risk of myopathy Simvastatin (SMV) No interaction May increase risk of myopathy Gemfibrozil Recommended start dose 10mg ATV and clinical monitoring Not recommended Recommended start dose 5mg RSV, max dose 20mg Recommended max dose 10mg SMV Grapefruit juice Large quantities of grapefruit juice not recommended No interaction No interaction Not recommended Itraconazole If on 80mg ATV: reduce dose or temprorarily suspend ATV No interaction No dose restrictions recommended Contraindicated Protease inhibitors Monitor lipid levels to ensure lowest dose ATV used No interaction Not recommended Contraindicated Verapamil Monitor lipid levels to ensure lowest dose ATV used No interaction No interaction Recommended max dose 20mg SMV Warfarin More frequent INR monitoring No interaction (usual INR monitoring) More frequent INR monitoring More frequent INR monitoring Fusidic acid Contraindicated – suspend ATV Eslicarbazepine No interaction No interaction No interaction Contraindicated – suspend SMV No interaction Eslicarbazepine reduces systemic exposure to RSV when coadministered Eslicarbazepine reduces systemic exposure to SMV when coadministered All data sourced from SmPCs for ATV, PRV, RSV, and SMV. Ezetimibe information taken from Stockley‟s Drug Interactions, accessed online on 28.10.2010. Cardiovascular system Page 42 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 2.12 Lipid-regulating drugs Monitoring of statin treatment for primary and secondary prevention: People on a statin should be advised to seek medical advice if they develop muscle symptoms (pain, tenderness or weakness). If this occurs, creatine kinase should be measured. Creatine kinase should not be routinely monitored in asymptomatic people who are being treated with a statin. Baseline liver enzymes should be measured before starting a statin. Liver function (transaminases) should be measured within 3 months of starting treatment and at 12 months, but not again unless clinically indicated. People who have liver enzymes (transaminases) that are raised but are less than 3 times the upper limit of normal should not be routinely excluded from statin therapy. If a person develops an unexplained peripheral neuropathy, statins should be discontinued and specialist advice sought. It is recommended that attempts should always be made to get patients to national cholesterol levels with statin monotherapy, using all formulary statins, before consideration is given to adding in or changing to another agent. A summary of drug –statins interactions is given on p.42 Statins First line: Simvastatin 10mg tablets: £0.74 20mg tablets: £0.82 40mg tablets: £1.05 80mg tablets: £1.82 ® as Simvador 10mg tablets: £0.67 20mg tablets: £0.74 40mg tablets: £0.95 80mg tablets: £1.64 Simvastatin is first line statin for all new patients unless contra-indicated. It is included in the formulary for: Hypercholesterolaemia Primary prevention of cardiovascular events (where 10year CVD risk ≥ 20%) Secondary prevention of CV events Please note: Simvastatin should be prescribed at night to optimise effect. Simvastatin 10mg should only be prescribed for patients who cannot tolerate a higher evidence-based dose of statin therapy Simvastatin doses should not exceed 20mg for patients on Amiodarone, Verapamil, Amlodipine or Diltiazem See BNF or SPC for further information on interactions There is an increased risk of myopathy associated with high-dose (80mg) simvastatin. The 80mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks. (see MHRA Drug Safety Update May 2010; 3 (10)) Continued on next page Cardiovascular system Page 43 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Atorvastatin 10mg tablets: £1.30 20mg tablets: £1.76 40mg tablets: £1.99 80mg tablets: £3.73 Atorvastatin is included as a second line choice, for use where there are potential drug interactions with Simvastatin 40 mg or where it is contraindicated, and as high intensity statin first line for: Statins Continued from previous page 2nd line: Pravastatin 10mg tablets: £1.65 20mg tablets: £2.08 40mg tablets: £2.75 patients with Familial Hypercholesterolaemia patients with Acute Coronary Syndrome (ACS) It should be noted that the maximum reduction in total cholesterol which can be expected from Pravastatin is 24%. Higher intensity statins should not routinely be offered to people for the primary prevention of CVD. A target for total or LDL cholesterol is not recommended for people who are treated with a statin for primary prevention of CVD. 3rd line: Other lipid lowering drugs Cardiovascular system Rosuvastatin 5mg tablets: £18.03 10mg tablets: £18.03 20mg tablets: £26.02 40mg tablets: £29.69 Pravastatin and Rosuvastatin have a different metabolic pathway so may be tolerated when Simvastatin or Atorvastatin are not. In general, the evidence for an effect on outcomes is less robust than for statin therapy. Additional monitoring may be required, particularly when Fibrates or Nicotinic Acid are used in combination with statins, due to increased risk of myopathy. Page 44 Therapeutic Area 4th line Formulary Choices Cost for 28 unless stated Rationale for decision / comments Ezetimibe 10mg tablets: £26.31 Ezetimibe is included in the formulary only for: Use as monotherapy for patients intolerant to a minimum of two formulary statins Use in addition to a statin for patients not at target on statin monotherapy, where higher doses of that statin and an alternative statin have been tried and are not tolerated The ENHANCE study showed the addition of Ezetimibe had no effect on primary or secondary endpoints and emerging evidence contributes to lack of positive cardiovascular outcomes with ezetimibe alone. Note: Ezetimibe & Simvastatin combination (Inegy) is non-formulary due to its greater cost compared to separate Ezetimibe and Simvastatin. Other lipid lowering drugs Fenofibrate micronized as Supralip brand Nicotinic acid Anionic exchange resins Questran Colestipol Colesevelam 200mg capsules: £2.56 160mg capsules: £6.69 Specialist recommendation ONLY Primary prevention of CVD: Fibrates should not be routinely offered but may be considered if Statins are not tolerated. Fibrates may be considered for the secondary prevention of CVD for patients unable to tolerate statins. Prescribe a fibrate (fenofibrate) if triglyceride levels remain above 4.5mmol/litre despite attention to other causes. If cardiovascular risk is high eg. Type 2 diabetes; consider adding a fibrate (fenofibrate) to statin therapy if TG levels remain in the range 2.3-4.5mmol/litre despite statin therapy. These lipid lowering drugs are usually initiated in secondary care by clinical biochemists for patients with complex dyslipidaemias. Nicotinic acid should not be offered for the primary prevention of CVD. Nicotinic acid may be considered for the secondary prevention of CVD for patients unable to tolerate statins. Tredaptive (Nicotinic acid + laropiprant) is not recommended. Product withdrawn Jan 2013 as results of HPS2-THRIVE trial failed to show reduced risk of CV events & incidence of serious adverse events in the treatment group was higher. Anion exchange resins may be considered for the secondary prevention of CVD for patients unable to tolerate statins. Note: A meta-analysis of 14 RCTs of omega-3 fatty acid supplementation in the secondary prevention of cardiovascular disease found it did not reduce the risk of cardiovascular events or all-cause mortality. Therefore, omega-3-acid ethyl esters (Omacor) is now non-formulary and should no longer be prescribed for secondary prevention after ischaemic events. Cardiovascular system Page 45 Top BNF Chapter 3: Respiratory System Related guidance: NICE Technology Appraisal TAG138 (2008): Asthma (in adults) - corticosteroids BTS / SIGN Guideline 101 (May 2011): British Guideline on the Management of Asthma Written personalised action plans as part of self-management education have been shown to improve health outcomes for people with asthma and should be offered to all patients. Asthma Self Care Plan on NHS Somerset website Note on inhaler devices Patients ability to use different devices varies; assessment of response to a prescribed treatment should include evaluation of inhaler technique as demonstrated by the patient First line recommendation is an MDI plus spacer on grounds of cost Aerochamber Plus® spacer (medium-volume) has a flexible gasket & should fit all MDIs however SPC should be checked to ensure device is compatible Correct inhaler technique is vital to ensure maximum benefit is obtained from inhaled therapies. Because the force of inhalation is different for MDI and dry powder inhalers, where possible patients should have just one type of device i.e. all MDI or all DPI (see Types of Inhaler patient information leaflet) Safer use of inhaled corticosteroids (ICS) ALL patients on high dose ICS (ie > 1000mcg beclomethasone or equivalent daily) should be issued with a Steroid Card. ICS can have serious side effects: one study has shown an increased risk of diabetes onset and progression. The risk increased with higher doses – patients on ICS doses of 1000mcg fluticasone/day or more (2000mcg beclometasone) had a 64% increased risk of developing diabetes compared to no ICS use. Stepping-down asthma therapy helps reduce the ICS dose and can be considered in patients with complete asthma control (for at least 12 weeks). For patients on combination therapy the preferred approach is to reduce the ICS by approximately 50% while continuing LABA at the same dose initially. See the asthma step-down guide for combination ICS/LABA inhalers p.54/55 Different ICS have different potencies and the equivalent dose can also vary between devices. Standard practice is to express the dose equivalent to beclometasone dipropionate in the old CFC-containing inhalers (and now in Clenil Modulite®) as shown below. Weight for weight, the inhaled steroid in Qvar®, Fostair® and all fluticasone inhalers deliver a much higher steroid dose. REDUCE DOSE ACCORDINGLY IN THESE PREPARATIONS. 400mcg Clenil Modulite® = 400mcg BDP 200mcg Qvar® = 400-500mcg BDP 200mcg Fostair® = 500mcg BDP 400mcg budesonide (Pulmicort®/Symbicort®/Easyhaler®) = 400mcg BDP 200mcg fluticasone (Flixotide®/Seretide®/Flutiform®) = 400mcg BDP Respiratory System – Bronchodilators Page 46 Therapeutic Area Formulary Choices Cost per inhaler unless stated Rationale for decision / comments 3.1 Bronchodilators Short acting beta-2 agonist bronchodilators (SABAs) First line: Using TWO or more canisters of beta-2 agonist per month is a marker of poorly controlled asthma that puts patients at risk of fatal or near-fatal asthma (BTS/SIGN 2008 revised 2011). Salbutamol Cfc-free MDI 100mcg/dose: £1.50 (200 dose inhaler) First line: MDI (plus spacer if necessary) on grounds of cost If patient cannot manage an MDI plus spacer, consider a breath-activated MDI or a dry powder device. Second line: Breath actuated cfc-free MDI as Airomir Autohaler 100mcg/dose: £6.02 (200 dose) as Salamol Easi-breathe 100mcg/dose: £6.30 (200 dose) or Dry powder inhaler as Salbutamol Easyhaler 100mcg/dose: £3.31 (200 dose) 200mcg/dose: £6.63 (200 dose) Respiratory System – Bronchodilators Page 47 Therapeutic Area Formulary Choices Long acting Beta-2 agonist bronchodilators (LABAs) In asthma LABAs should only be added if regular use of a standard dose ICS has failed to control asthma adequately and should be discontinued if there is no response to treatment. LABA should only be started in patients who are already on inhaled corticosteroids, and the inhaled corticosteroid should be continued. Consider stopping LABAs in well-controlled patients once inhaled corticosteroid dose has been reduced (see step-down guidance p54) In COPD, LABAs should be used in line with the local COPD guidance (page 57) If no benefit after trial period, stop treatment First line: Cost per inhaler unless stated Rationale for decision / comments Formoterol Dry powder inhaler as Easyhaler as OxisTurbohaler 12mcg: £23.75 (120 dose) Formoterol is the first line LABA as Easyhaler. Maintenance dose is 12mcg once or twice daily. 6mcg: £24.80 (60 dose) Turbohaler formulation is second line Formoterol option. It costs 2-4 times per dose more than an Easyhaler. 12mg and 6mg strengths cost the same so use 1x 12mcg bd rather than 2x6mcg bd. Licensed over age of 6 years. 12mcg: £30.06 (100 dose) MDI version licensed for over age of 12 years 25mcg: £29.26 (120 dose inhaler) Salmeterol is the second line LABA Usual maintenance dose of Salmeterol is 50mcg bd so the cost of the MDI and Accuhaler is the same at this dose. Licensed over the age of 4 years MDI as Atimos Second line: Salmeterol as cfc-free MDI as Accuhaler Indacaterol as Breezhaler Short acting anticholinergic bronchodilators Ipratropium as cfc-free MDI Respiratory System – Bronchodilators 50mcg: £29.26 (60 dose inhaler) 150mcg: £29.26 (30 dose inhaler) ® 300mcg: £29.26 (30 dose inhaler) 20mcg: £5.05 (200 dose inhaler) Indacaterol is indicated for maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD. This is a cost neutral alternative to established treatments and may be appropriate for patients for whom once-daily administration is appropriate, especially those not requiring inhaled corticosteroids. It has been approved by the SMC. Ipratropium should not be co-prescribed with Tiotropium due to risk of increased anticholingeric adverse effects Page 48 Therapeutic Area Formulary Choices Long acting anticholinergic bronchodilators Aclidinium bromide as Eklira Genuair ▼ Dry powder inhaler Glycopyrronium bromide as Seebri Breezhaler® ▼ Cost per inhaler unless stated 400mcg: £28.60 (60 dose pack) as Handihaler Dry powder inhaler Aclidinium is licensed for the maintenance treatment of COPD. The dose is 400mcg bd. The device may be suitable for some patients who are unable to use a Handihaler®. NB. Each 400 mcg metered inhalation of aclidinium bromide delivers 322 mcg of aclidinium 50mcg: £27.50 (30 capsules plus device) 50mcg: £27.50 (30 dose refill pack) Tiotropium Rationale for decision / comments 18mcg: £34.87 (30 dose starter pack) 18mcg: £33.50 (30 dose refill pack) Glycopyrronium is licensed for the maintenance treatment of COPD. The dose is 50mcg od. Each 50 microgram capsule delivers a dose of 44 micrograms of glycopyrronium Tiotropium is only licensed for use in COPD and should be prescribed in line with the local COPD guidance, which is consistent with the NICE guidance, see page57 for more information. If no benefit after trial period, stop treatment. Repeat prescriptions should only be for refill packs owing to cost. Tiotropium should not be combined with Ipratropium due to increased risk of anticholinergic side-effects as Respimat ▼ 2.5mcg: £35.50 (60 dose pack) Tiotropium Respimat (mist inhaler) was included in the formulary for patient choice, however MHRA advise Tiotropium delivered by a mist inhaler was associated with a non-significant increase in all-cause mortality (vs placebo) while Tiotropium Handihaler was associated with a decrease in all-cause mortality (vs placebo). The reasons are unclear. A more recent meta-analysis has provided further evidence of a possible increased risk of all-cause and death from cardiovascular causes (compared to placebo and other inhaled treatments) associated with tiotropium delivered by the Respimat device. Use the mist inhaler with caution in patients with known cardiac rhythm disorder and do not exceed recommended once daily dose for either preparation Respiratory System – Bronchodilators Page 49 Therapeutic Area Formulary Choices Cost per inhaler unless stated Theophylline Theophylline MR Reduce the dose of theophyline if macrolide or quinolones antibiotics (or other drugs known to interact) are prescribed to treat an exacerbation. ® as Nuelin SA 175mg tablets: £6.38 (60) 250mg tablets: £8.92 (60) Offer theophylline only after trials of short- and long-acting bronchodilators, or to people who cannot use inhaled therapy. as Slo-Phyllin 60mg capsules: £2.76 (56) 125mg capsules: £3.48 (56) 250mg capsules: £4.34 (56) Theophylline can be used in combination with beta2 agonists and muscurinic antagonists. Please note, the risk of hypokalaemia is increased when theophylline is given in combination with a beta2 agonist. as Uniphyllin ® Continus 200mg tablets: £2.95 (56) 300mg tablets: £4.77 (56) 400mg tablets: £5.65 (56) Take care when prescribing theophylline to older people. Consider altered pharmacokinetics, comorbidities, and interactions with other medicines; Prescribe by brand. The rate of absorption from modified-release preparations can vary between brands. If a brand name is not specified on the prescription, pharmacists should contact the prescriber to establish which brand is to be dispensed. Rationale for decision / comments ® Plasma theophylline level is increased in heart failure, hepatic impairment, viral infections, in the elderly, and by drugs that inhibit its metabolism. Plasma theophylline level is decreased in smokers, by alcohol consumption, and by drugs that induce its metabolism. Aminophylline Aminophylline m/r as Phyllocontin ® Continus Respiratory System – Bronchodilators 225mg tablets: £2.39 (56) 350mg tablets: £4.22 (56) Page 50 Therapeutic Area 3.2 Corticosteroids Inhaled corticosteroids (ICS) Formulary Choices Cost per inhaler Rationale for decision / comments (See advice on safer use of inhaled corticosteroids p ) BTS / SIGN Guideline (101) on the management of asthma states: many children with recurrent episodes of viral-induced wheezing in infancy do not develop chronic atopic asthma and do not require regular inhaled steroids. NICE TAG138 states: for patients with chronic asthma in whom an ICS is appropriate, the least costly product that is suitable for the individual, within its license, is recommended Beclometasone NB. Prescribe beclometasone MDIs by brand name to avoid confusion over the product intended. Clenil Modulite and Qvar are not equipotent – see p46 ® Children up to age 15 should use these products with a Volumatic . CFC-free MDIs as Clenil Modulite 50mcg: £3.70 (200 dose) 100mcg: £7.42 (200 dose) 200mcg: £16.17 (200 dose) 250mcg: £16.29 (200 dose) as Qvar 50mcg: £7.87 (200 dose) 100mcg: £17.21 (200 dose) Dry powder ® as Easyhaler 200mcg: £14.93 (200 dose) Breath-actuated CFC-free MDI as Qvar Easi-breathe 50mcg: £7.74 (200 dose) 100mcg: £16.95 (200 dose) Budesonide as Easyhaler 100mcg:£8.86 (200 dose) 200mcg £17.71 (200 dose) 400mcg: £17.71 (100 dose) Licensed from age 6 years. Therapeutic Area Formulary Choices Cost per inhaler unless stated Rationale for decision / comments Respiratory System – Inhaled Corticosteroids Qvar is not licensed in patients under 12yrs. Page 51 Combination long-acting beta-agonist steroid inhalers NICE TAG 138 states that for patients with chronic asthma in whom an ICS and LABA is appropriate, the following apply: - Use of a combination device within license is recommended as an option to ensure that long-acting β2 agonists are not taken without an inhaled steroid. The decision to use combinations or separates should be made on an individual basis. If a combination is chosen the least costly device that is suitable for the individual, within its license, is recommended Flutiform ▼ (Fluticasone / Formoterol) CFC-free MDI 50mg/5mcg £18 125mg/5mcg £29.26 250mg/10mcg £45.56 (120 dose inhaler) Licensed for asthma only at Step 3 or above of the BTS / SIGN guidelines. Flutiform 50mcg and 125mcg are licensed for adults and children over 12 yrs.. The 250mcg strength is licensed for over 18 years only and is nonformulary owing to limited indication for high dose fluticasone in asthma (estimated only 1% asthma patients should need such high dose combination) Fostair ▼ (Beclomethasone / Formeterol) CFC-free MDI 100/6mcg: £29.32 (120 dose inhaler) OVER 18 YEARS ONLY WARNING: beclomethasone 100mcg in Fostair is equivalent to 250mcg of standard beclomethasone because of extra fine particle size – see p XX. Patient should receive specific training and information leaflet on this issue. Fostair is also licensed for combined maintenance and reliever therapy (maximum 8 puffs per day). Any patient using this approach needs very careful counselling and monitoring. Eight puffs is equivalent to a daily dose of 2000mcg standard BDP. Fostair CFC-free MDI inhalers should be refrigerated until needed. Each inhaler has a 5 month shelf-life once removed from cold storage. Symbicort Turbohaler (Budesonide / Formoterol) Dry-powder inhaler 100/6mcg: £33.00 (120 doses) 200/6mcg: £38.00 (120 doses) 400/12mcg: £38.00 (60 doses) Some dosing flexibility is possible with Symbicort, it is still not as flexible as ICS and LABA prescribed separately. Symbicort is the preferred combination as Budesonide is equipotent to BDP and Formoterol has a faster onset of action. It is licensed in COPD. The 100/6 strength is now licensed in age >6 yrs. Symbicort Maintenance and Reliever Therapy (SMART). Patients over 18 years, at Step 3, who are poorly controlled may also use Symbicort 200/6 as a rescue medication (maximum 12 puffs per day), with no Salbutamol. This approach to treatment requires careful patient education and quantity of inhalers used should be monitored. Respiratory System – Inhaled Corticosteroids Page 52 Therapeutic Area Formulary Choices Cost per inhaler unless stated Rationale for decision / comments Seretide Evohaler (Fluticasone / Salmeterol 25mcg) CFC-free MDI 50mcg: £18.00 (120 doses) 125mcg: £35.00 (120 doses) 250mcg: non-formulary Seretide Evohaler 250mcg is non-formulary, due to cost and limited need for high dose Fluticasone in asthma (estimated only 1% asthma patients should need such high dose combination) 100mcg: £18.00 (60 dose) 250mcg: £35.00 (60 dose) 500mcg: £40.92 (60 dose) Seretide 500mcg Accuhaler is included for moderate to severe COPD where there is proven response to ICS. If no benefit after a trial period, stop treatment. Continued from previous page) Seretide Accuhaler (Fluticasone / Salmeterol 50mcg) Dry powder inhaler Spacer devices Medium volume: Large volume: Seretide 50mcg & 125mcg Evohalers included for asthma: for patients at Step 3 or above of the BTS / SIGN guidelines. Note that the 50mcg Evohaler is licensed for adults and children over 4 years and the 125mcg inhaler for adults and children over 12 years. This change is based on NICE guidance on inhaled corticosteroid for treatment of children with chronic asthma which states that the choice of product should be based on suitability for the individual child, licensed indication and cost. Patient‟s ability to use different devices varies; assessment of response to a prescribed treatment should include evaluation of inhaler technique as demonstrated by patient. First line recommended is MDI plus spacer on grounds of cost. AeroChamber Plus standard adult (blue) £4.69 (1) adult with mask (blue) £7.83 (1) infant with mask (orange) £7.83 (1) child with mask (yellow) £7.83 (1) Volumatic Respiratory System – Inhaled Corticosteroids £2.91 (1) The AeroChamber Plus is recommended as the spacer device of choice, in view of its portability and flexible inhaler orifice, which permits most MDIs to be used with it. MHRA advise that deposition and therefore effectiveness and adverse effects may differ from Volumatic AeroChamber Plus spacer devices should fit ALL MDI devices (inhaler mouthpiece fits into flexible gasket.) but prescribers should check SPC . ® Volumatic spacer device is only compatible with inhalers manufactured by GSK or if mouthpiece has same specifications as inhalers manufactured by GSK. Page 53 Asthma Step-down Guide: Combination MDIs: Note: all doses are for asthma maintenance therapy, not asthma maintenance and reliever therapy BTS/SIGN Step 4/5 Seretide Evohaler ® Flutiform® inhaler Seretide 250 Evohaler® 2 puffs bd Seretide 125 Evohaler® 2 puffs bd Seretide 50 Evohaler® 2 puffs bd *(2000mcg/100mcg salmeterol) NB. Non-formulary *(1000mcg/100mcg salmeterol) *(400mcg/100mcg salmeterol) Flutiform® 250mcg/10mcg 2 puffs bd *(2000mcg/40mcg formoterol) NB. Non-formulary BTS/SIGN Step 4 Fostair Inhaler® BTS/SIGN Step 3 Fostair® 100/6 Inhaler 2 puffs bd *(1000mcg/ 24mcg formoterol) Flutiform® 125mcg/5mcg 2 puffs bd Flutiform® 50mcg/5mcg 2 puffs bd *(1000mcg/20mcg formoterol) *(400mcg/20mcg formoterol) BTS/SIGN Step 3 Stepping down from Fostair is potentially problematic as there is only one strength. Therefore either the device has to be changed or the LABA dose reduced alongside the ICS. OPTION 1: Fostair 100/6 Inhaler 1 puff bd ® BTS/SIGN Step 2 Prescribe an MDI equivalent to 400500mcg BDP/day: Clenil Modulite® 100mcg 2 puffs bd OR Qvar Easi-Breathe® 50mcg 2 puffs bd OR ® Qvar MDI 50mcg 2 puffs bd OR Fluticasone 50 Evohaler® 2 puffs bd NB. Fluticasone inhalers are non-formulary but are included for comparison *(500mcg/12mcg formoterol) OPTION 2 Consider change to Flutiform® 50/5 2 puffs bd Key (for both pages of step-down guide): *(400mcg/20mcg formoterol) *Total daily dose of inhaled corticosteroid, in terms of beclometasone dipropionate (BDP) equivalent/ long acting beta-agonist OPTION 3 Consider change to separate corticosteroid and LABA inhalers Respiratory System – Inhaled Corticosteroids Page 54 Asthma Step-down Guide – combination DPIs: Note: all doses are for asthma maintenance therapy, not asthma maintenance and reliever therapy (e.g. not the SMART ® regime) BTS/SIGN Step 3 Symbicort Turbohaler ® 400/12 Symbicort Turbohaler ® 200/6 BTS/SIGN Step 2 Symbicort 400/12 Turbohaler® 1 puff bd Symbicort 100/6 Turbohaler® 2 puffs bd *(800mcg/ 24mcg formoterol) *(400mcg/24mcg formoterol Prescribe a DPI equivalent to 400500mcg BDP/day: Symbicort 200/6 Turbohaler® 2 puffs bd Symbicort 100/6 Turbohaler® 2 puffs bd Easyhaler® Beclometasone 200mcg 1 puff bd OR *(800mcg/ 24mcg formoterol) *(400mcg/ 24mcg formoterol) Easyhaler® Budesonide 200mcg 1 puff bd OR Symbicort 200/6 Turbohaler® 1 puff bd *(400mcg/ 12mcg formoterol) Symbicort Turbohaler ® 100/6 Symbicort 100/6 Turbohaler® 2 puffs bd ® BTS/SIGN Step 3 Seretide 500 Accuhaler® 1 puff bd Seretide 250 Accuhaler® 1 puff bd Seretide 100 Accuhaler® 1 puff bd *(2000mcg/100mcg salmeterol) *(1000mcg/100mcg salmeterol) *(400mcg/100mcg salmeterol) Respiratory System – Inhaled Corticosteroids ® Fluticasone 100 Accuhaler® 1 puff bd *(400mcg/ 24mcg formoterol) BTS/SIGN Step 4/5 Seretide Accuhaler Budesonide Turbohaler 200mcg 1 puff bd OR NB. Fluticasone Accuhaler® and budesonide Turbohaler® are non-formulary but are included here as some patients on Seretide Accuhale®r or Symbicort Turbohaler® may benefit from stepping down to the same device. Use formulary devices where possible. Page 55 Therapeutic Area Formulary Choices Cost per inhaler unless stated Rationale for decision / comments 3.3.2 Leukotriene receptor antagonists Leukotriene receptor antagonists Montelukast Chewable tablets Tablets Granules Zafirlukast Respiratory System – Inhaled Corticosteroids 4mg tablets: £25.69 (28) 5mg tablets: £25.69 (28) 10mg tablets: £26.97 (28) 4mg granules: £25.69 (28) Included for add-on therapy according to BTS & SIGN guidelines for the management of chronic asthma (BNF) and BTS/SIGN 2008 revised 2011 20mg tablets: £17.75 (56) Page 56 GUIDANCE FOR MANAGING COPD IN ACCORDANCE WITH NICE CLINICAL GUIDELINE CG101 (JUNE 2010) ADAPTED BY NHS SOMERSET MEDICINES MANAGEMENT TEAM FROM AN ORIGINAL PRODUCED BY SOMERSET LUNG CENTRE, MUSGROVE PARK, TAUNTON CONSIDERATIONS STOP SMOKING, VACCINATIONS (pneumococcal, and annual influenza), THINK PULMONARY REHAB (MRC >3), PATIENT EDUCATION Remember, COPD is generally NOT a steroid-responsive disease, but: There is evidence that some patients with more severe disease, or those who exacerbate frequently (more than twice a year), benefit from inhaled steroids. Trial data shows an improvement in both exacerbation frequency and health status of these groups but patients are at increased risk of contracting pneumonia. Do NOT use oral corticosteroids routinely for maintenance therapy Do NOT use oral corticosteroid reversibility tests to identify patients who will benefit from inhaled corticosteroids (ICS). Smoking cessation MUST be offered at every opportunity to people with COPD who still smoke, regardless of age. Combivent was discontinued in June 2008. Options are separate salbutamol/ipratropium inhalers (non-persistent symptoms), or a trial of tiotropium (persistent symptoms). Don‟t just assess on physiology. Use symptoms to determine inhaler benefit. Withdraw add on therapy if no benefit after trial. Determining disease severity Disability in COPD can be poorly reflected in the FEV1. A more comprehensive assessment should also include: degree of airflow obstruction and disability frequency of exacerbations prognostic factors such as breathlessness (assessed using the Medical Research Council (MRC) scale, carbon monoxide lung transfer factor (TLCO), health status, exercise capacity, BMI, partial pressure of oxygen in arterial blood (PaO2), and cor pulmonale. Severity of airflow obstruction Gold 1: Mild ≥ 80% predicted FEV1 Gold 2: Moderate 50-79% predicted FEV1 Gold 3: Severe 30-49% predicted FEV1 Symptoms should be present to diagnose COPD in people with mild airflow obstruction Symptoms Respiratory System – Inhaled Corticosteroids Gold 4: Very severe < 30% predicted FEV1 Or FEV1 < 50% with respiratory failure Choice of inhaled therapy in COPD Page 57 SABA e.g. salbutamol or terbutaline, OR SAMA e.g. ipratropium as required. SABA should continue through all stages of symptoms Breathlessness and/or exercise limitation FEV1 ≥ 50% Exacerbations or persistent breathlessness LABA e.g. Formoterol, Salmeterol, or Indacaterol FEV1 < 50% LAMA e.g. Tiotropium Aclidinium Glycopyrronium LABA + ICS in a combination inhaler Give LABA + LAMA if ICS is declined or not tolerated. Discontinue SAMA. Give LAMA in preference to regular SAMA. Persistent exacerbations or breathlessness LABA + ICS in a combination inhaler. Discontinue SAMA. Give LAMA in preference to regular SAMA LAMA + LABA + ICS in a combination inhaler. Consider LABA + LAMA if ICS is declined or not tolerated. Definition of terms LAMA e.g. Tiotropium Aclidinium Glycopyrronium Recommended product and daily dose SABA Short-acting beta2 agonist Salbutamol (as Ventolin) 100mcg PRN, or up to QDS (max: 400mcg daily) SAMA Short-acting muscurinic antagonist Ipratropium 20mcg PRN, up to QDS (max: 80mcg daily) LABA Long-acting beta2 agonist Formoterol 24mcg BD via Easyhaler or Turbohaler or Salmeterol 50mcg BD via MDI and spacer Recommended trial period Continue throughout Stop if LAMA introduced 2 weeks or Indacaterol 150-300mcg OD via Breezhaler LAMA Long-acting muscurinic antagonist Aclidinium 400mcg bd via DPI 6-8 weeks Glycopyrronium 50mcg daily via DPI Tiotropium 18mcg daily via Handihaler (when initiating, discontinue ipratropium). LABA + ICS Inhaled corticosteroid Symbicort Turbohaler 400/12: 1-2 actuations BD 3 months or Seretide Accuhaler 500/50: 1 actuation BD Respiratory System – Inhaled Corticosteroids Page 58 Delivery systems Inhalers Spacers Nebulisers Hand-held devices are usually best, with a spacer if appropriate If a person cannot use a particular device, try another Teach technique before prescribing and check regularly Ensure the spacer is compatible with the inhaler (aerochamber fits most inhaler devices) Individuals should make single actuations of the inhaler into the spacer, and inhale as soon as possible, repeating as needed Tidal breathing is as effective as single breaths Do not clean spacers more than once a month Clean with water and washing-up liquid and allow to air dry Consider a nebuliser for people with distressing or disabling breathlessness despite maximum therapy with inhalers Assess the individual and/or carers ability to use the nebuliser before prescribing and arrange appropriate support and maintenance of equipment Allow the patient to choose either a facemask or mouthpiece where possible Continue nebuliser treatment only if there is an improvement of symptoms, daily living activities, exercise capacity or lung function Oral therapies Corticosteroids are not normally recommended for maintenance therapy, but may be of use in some people with advanced COPD where corticosteroid treatment cannot be stopped after an exacerbation Keep dose as low as possible, monitor for osteoporosis and offer prophylaxis Theophylline should be considered only after trials of short- and long-acting bronchodilators, or in people who cannot use inhaled therapy Theophylline can be used in combination with inhaled beta 2 agonists and muscurinic antagonists Take care when prescribing to older people because of pharmacokinetics, comorbidities and interactions with other medications Reduce theophylline dose if macrolide or flouroquinolone antibiotics (or other drugs known to interact) are prescribed to treat an exacerbation Mucolytic therapy Mucolytic therapy can be considered in people with chronic productive cough, and continued if symptoms improve Do not routinely use to prevent exacerbations Not Recommended Anti-oxidant therapy (alpha-tocopherol and beta-carotene supplements) Anti-tussive therapy Prophylactic antibiotic therapy Corticosteroids Theophylline Respiratory System – Inhaled Corticosteroids Page 59 Assess symptoms or condition and manage as described below Breathlessness and exacerbations Frequent exacerbations Cor pulmonale Manage breathlessness and Fexercise limitation with inhaled therapy For exacerbations or persistent breathlessness: – use long-acting bronchodilators or LABA + ICS – consider adding theophylline if still symptomatic Offer pulmonary rehabilitation to all suitable people Refer patients who are breathless, have a single large bulla on a CT scan and an FEV1 less than 50% predicted for consideration of bullectomy Refer people with severe COPD for consideration of lung volume reduction surgery if they remain breathless with marked restrictions of their activities of daily living, despite maximal medical therapy (including rehabilitation), and meet all of the following: – FEV1 greater than 20% predicted – PaCO2 less than 7.3 kPa – upper lobe predominant emphysema – TLCO greater than 20% predicted Consider referring people with severe COPD for assessment for lung transplantation if they remain breathless with marked restrictions of their activities of daily living despite maximal medical therapy. Considerations include: – age – FEV1 – PaCO2 – homogeneously distributed emphysema on CT scan – elevated pulmonary artery pressures with progressive deterioration – comorbidities – local surgical protocols Optimise inhaled therapy Offer vaccinations and prophylaxis Give self-management advice Consider osteoporosis prophylaxis for people requiring frequent oral corticosteroids Consider in people who have peripheral oedema, a raised venous pressure, a systolic parasternal heave, a loud pulmonary second heart sound Exclude other causes of peripheral oedema Perform pulse oximetry, ECG and echocardiogram if features of cor pulmonale Assess need for LTOT Treat oedema with diuretic Angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers are not recommended Digoxin may be used where there is atrial fibrillation Respiratory System – Inhaled Corticosteroids Page 60 Assess symptoms or condition and manage as described below (continued) Respiratory failure Assess for appropriate oxygen Consider referral for assessment for long-term domiciliary NIV therapy Abnormal BMI Refer for dietetic advice Offer nutritional supplements if the BMI is low Pay attention to weight changes in older patients (especially > 3 kg) Chronic productive cough Consider mucolytic therapy Anxiety and depression Screen for anxiety and depression using validated tools in people who: – are hypoxic – are severely breathless or Refer to „Depression with a chronic physical health problem‟ (NICE clinical guideline 91). Alpha-1 antitrypsin deficiency Offer referral to a specialist centre to discuss the clinical management of this condition Alpha-1 antitrypsin replacement therapy is not recommended Palliative setting Opioids should be used when appropriate for the palliation of breathlessness in people with end-stage COPD unresponsive to other medical therapy Use benzodiazepines, tricyclic antidepressants, major tranquillisers and oxygen to treat breathlessness Provide access to multidisciplinary palliative care teams and hospices – have recently been seen or treated at a hospital for an exacerbation Respiratory System – Inhaled Corticosteroids Page 61 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 3.4.1 Antihistamines Non-sedating antihistamines For nasal allergy and treatment with corticosteroid nasal sprays, please see Chapter 15. First line: Loratadine 10mg tablets: £1.03 (30) 5mg/5ml solution: £2.26 (100ml) Loratadine is first line on basis of low rate of motor impairment and costeffectiveness. Loratadine is available OTC. Second line: Cetirizine 10mg tablets: £0.89 (30) 5mg/5ml solution: £1.78 (200ml) Cetirizine is second line as more likely to impair motor function than Loratadine. Cetirizine is available OTC. Chlorphenamine 4mg tablets: £0.91 2mg/5ml SF solution: £2.49 (150ml) Chlorphenamine is available OTC. Sedating antihistamines 3.7 Mucolytics Mucolytics Carbocisteine as Mucodyne ® Do not routinely use to prevent exacerbations. 375mg capsules: £18.98(120) 125mg/5ml liquid: £5.08 (300ml) 250mg/5ml liquid: £6.59 (300ml) Acetylcysteine Respiratory System – Inhaled Corticosteroids Carbocistine can be considered in patients with COPD with copious of tenacious sputum. Trial carbocysteine 750mg tds for 4 weeks and stop if ineffective. If effective reduce to bd. Dose: initially 2.25g daily in divided doses, then 1.5g daily in divided doses as condition improves Acetylcysteine is unlicensed and for specialist prescribing only. Erdocysteine is non-formulary Page 62 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments BNF Chapter 4: Central nervous system Top 4.1 Hypnotics and anxiolytics Hypnotics Temazepam 10mg tablets: £4.23 20mg tablets: £2.71 Patients should be advised to adopt better sleep hygiene and other lifestyle changes, where appropriate. A leaflet advising on sleep hygiene measures is available on PCT website. The National Prescribing Centre also produced a useful document, The Good Relaxation Guide, which contains information that can be printed off for patients. Initial prescriptions for hypnotics should be limited to 7-14 days supply and not transferred to repeat without re-assessment of the patient. Tolerance can develop within 3 to 14 days of continuous use and long term efficacy is not assured. Patients who do not benefit from a first Z-drug are unlikely to benefit from another. In line with the NICE guidance on hypnotics the formulary does not recommend the initiation of "Z" drugs, such as zopiclone and zolpidem. NB. Whilst "Z-drugs" will continue to be used within T&ST (as a result of CD issues), no patient will be discharged on these drugs unless prescribed them prior to admission. Different rules may apply to patients cared for by Somerset Partnership NHS Foundation Trust. Anxiolytics Diazepam 2mg tablets: £0.73 5mg tablets: £0.74 Treatment should be limited to lowest dose for the shortest period of time. Central Nervous System Page 63 Therapeutic Area 4.2 Formulary Choices Cost for 28 unless stated Rationale for decision / comments Drugs used in psychoses and related disorders Related guidance: NICE Clinical Guideline CG82 (2009): Schizophrenia (update) NICE Technology Appraisal TA213 (2011): Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years Antipsychotics Antipsychotics are usually initiated within secondary care, following Somerset Partnership guidelines. Prescribing responsibility may then be transferred to primary care in accordance with a Shared Care Agreement. Regular combined treatment with two or more antipsychotic agents is not recommended NICE CG82: When deciding on the most suitable medication: consider the relative potential of individual antipsychotics to cause extrapyramidal side effects (such as akathisia), metabolic side effects (such as weight gain), and other side effects (including unpleasant subjective experiences). Risperidone 1mg tablets: £0.83 (20) 2mg tablets: £1.61 (60) 3mg tablets: £1.84 (60) 4mg tablets: £1.79 (60) Risperidone long-acting injection ® (Risperdal Consta ) NB Cold chain must be maintained. 25mg: £79.69 (1) 37.5mg: £111.32 (1) 50mg: £142.76 (1) Olanzapine 2.5mg tablets: £1.17 5mg tablets: £1.82 7.5mg tablets: £2.17 10mg tablets: £2.67 15mg tablets: £3.54 20mg tablets: £4.81 Aripiprazole 5mg tablets: £96.04 10mg tablets: £96.04 15mg tablets: £96.04 30mg tablets: 192.08 Central Nervous System Risperidone is licensed for the short-term treatment, up to six-weeks, of persistent aggression in patients with moderate to severe Alzheimer‟s dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others. NB 6 week restriction does not apply where risperidone is being prescribed to treat acute or chronic psychoses or mania All other antipsychotics are unlicensed for use in dementia and should only be used when a person is a risk to themselves and others and all other methods have been tried. Prescribers are reminded that all antipsychotics are associated with an increased risk of serious adverse reactions in elderly patients with dementia, (mortality, stroke, TIA and possibly cognition). Aripiprazole is recommended as an option for the treatment of schizophrenia in people aged 15 to 17 years who are intolerant of risperidone, or for whom risperidone is contraindicated, or whose schizophrenia has not been adequately controlled with risperidone (NICE TA213). Page 64 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Quetiapine 25mg tablets: £2.62 (60) 100mg tablets: £5.82 (60) 150mg tablets: £7.76 (60) 200mg tablets: £6.61 (60) 300mg tablets: £10.50 (60) Where quetiapine is prescribed, the standard release formulation is preferred for long term use on cost grounds (approx. 15 x price difference). This approach is supported by Somerset Partnership Mental Health Directorate. 4.2.3 Antimanic drugs Bipolar Disorder Initiation of lithium therapy is the responsibility of Somerset Partnership NHS Foundation Trust after which care may be transferred to general practice under shared care guidance. All healthcare organisations in the NHS where lithium therapy is initiated, prescribed, dispensed and monitored are asked to ensure that by 31 December 2010: Patients prescribed lithium are monitored in accordance with NICE guidance. There are reliable systems to ensure blood test results are communicated between laboratories and prescriber. At the start of lithium therapy and throughout their treatment patients receive appropriate ongoing verbal and wrttten information and a record book to track lithium blood levels and relevant clinical tests. Prescribers and pharmacists check that blood tests are monitored regularly and is is safe to issue a repeat prescription and/or dispense the prescribed lithium. Systems are in place to identify and deal with medicines that might adversely interact with lithium therapy. Suplies of record books and alert cards are available from: Somerset Partnership Support Services, Mallard Court, Express Park, Bridgwater, TA6 4RN 01278 726964 Lithium Lithium carbonate Preparations vary widely in bioavailability: ® + For safety reasons inas Camcolit 250 250mg: £3.22 (100) Li 6.8mmol/tablet line with national ® 400mg: £4.30 (100) Modified-release. guidance lithium must as Camcolit 400 + Li 10.8mmol/tablet be prescribed by brand ® as Liskonium 450mg 450mg: £2.88 (60) Modified-release. + Li 12.2mmol/tablet ® 200mg: £2.30 (100) Modified-release. + Li 5.4mmol/tablet ® 400mg: £3.35 (100) Modified-release. + Li 10.8mmol/tablet as Priadel 200mg as Priadel 400mg Central Nervous System Page 65 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 4.3 Antidepressants Do not routinely prescribe antidepressants for initial treatment of mild depression or persistent subthreshold depressive symptoms. Do NOT initiate Dosulepin Selective serotonin re-uptake inhibitors (SSRI) Fluoxetine 20mg capsules: £0.84 (30) As Oxactin or 20mg capsules: £0.76 Fluoxetine, citalopram and sertraline are all included as first-line options for SSRI. The long half-life of fluoxetine is a benefit on withdrawal, but a drawback when switching drugs, e.g. to a TCA. In elderly or with reduced hepatic function maximum dose of citalopam is 20mg and maximum dose of escitalopram is 10mg. See flowchart p.67 & p68 for options Sertraline or 50mg tablets: £1.06 100mg tablets: £1.22 NB. SSRIs are known to increase risk of GI bleeds especially if co-prescribed with NSAIDs and in the very elderly. Citalopram 10mg tablets: £0.90 20mg tablets: £0.88 40mg tablets: £1.05 Prescribers are reminded of the risk of serotonin syndrome with SSRI when combined with other antidepressants, triptans, and opioids including tramadol. Tricyclic and related antidepressants TCAs should be avoided for the treatment of depression in the elderly, due to increased risk of adverse effects, e.g. cardiac especially in high doses. First-line: Lofepramine 70mg tablets: £11.71 (56) Second-line: Amitriptyline 10mg tablets: £0.73 25mg tablets: £0.74 50mg tablets: £0.82 Other antidepressants Mirtazapine 15mg tablets: £2.35 30mg tablets: £1.59 45mg tablets: £2.72 Oro-dispersible tablets: Lofepramine is the drug of choice in this group as it is safer and produces fewer adverse effects than traditional tricyclics. NB: Lofepramine is now more expensive than Fluoxetine. Mirtazapine is a second-line line option, sedating properties may be useful where insomnia is a problem. 15mg tablets: £1.99 (30) 30mg tablets: £1.83 (30) 45mg tablets: £2.30 (30) (Continued on next page) Central Nervous System Page 66 Central Nervous System Page 67 Central Nervous System Page 68 Therapeutic Area Formulary Choices Cost for 28 unless stated Other antidepressants Venlafaxine st 1 line: Immediate release 37.5mg tablets: £2.60 (56) 75mg tablets: £2.96 (56) Do not prescribe non M/R venlafaxine as Viepax brand (not cost-effective) 75mg tablets: £13.98 150mg tablets: £19.98 If modified release venlafaxine is prescribed, use tablets not capsules (on cost grounds) (Continued from page 66) Rationale for decision / comments See MHRA guidance ® nd 2 line: Venlafaxine modified-release as Viepax XL ® Viepax XL or Venlalic XL are cost-effective brands for modified release tablets as Venlalic XL as Depefex XL Central Nervous System 75mg tablets: £11.20 (30) 150mg tablets: £18.70 (30) 225mg tablets: £33.60 (30) There is no rationale for prescribing M/R products as a BD dose 75mg capsules: £10.40 (28) 150mg capsules: £17.40 (28) Page 69 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 120mg: £31.63 (84) Only to be prescribed in line with NICE guidance: 4.5 Drugs used in the treatment of obesity Lipid absorption inhibitors 4.7 Analgesics: Orlistat BMI > 30kg/m or > 28kg/m where other risk factors e.g. type 2 DM, hypertension or hypercholesterolaemia for patients who have lost ≥ 2.5kg by dietary control and increased physical activity during previous month only for individuals between 18 and 75 years arrangements should exist for primary care staff (mostly practice nurses) supported by community dieticians to offer advice, support and counselling on diet, physical activity and behavioural strategies treatment should continue beyond 3 months only if weight loss of >5% from start of treatment treatment should continue beyond 6 months only if weight loss is > 10% from start of treatment treatment should not usually continue beyond one year and never beyond two years 2 Related guidance: NICE Clinical Guideline CG59 (2008): Osteoarthritis 2 Osteoarthritis management p.132 Avoid soluble formulations of Paracetamol and Co-Codamol because of high sodium content (the equivalent of up to 9g of salt per day at full dose) which may contribute to or exacerbate hypertension or heart failure. These products are also more expensive. Medication Overuse Headache All medications for treating headache can cause MOH in patients with a pre-existing primary headache disorder, even if taking medicines for pain other than headache. Mean onest 1.7 years (triptans) to 4.8 years (analgesics) Non-opioid analgesics First-line Paracetamol 500mg tablets: £2.50 (100) First choice drug in acute and chronic pain. If treatment is not effective check that adequate dose is being used (i.e. 1g QDS) before adding other options. Available OTC. Paracetamol may be considered an option for treating agitation in people with dementia where pain may be a factor. Husebo et al. (2011) Br Med J 343: d4065; Husebo, Ballard, & Aarsland (2011) Int J Ger Psych 26: 1012-1018. Central Nervous System Page 70 Therapeutic Area Weak opioid analgesics Formulary Choices Cost for 28 unless stated Rationale for decision / comments Buprenorphine Patches should NOT be prescribed. They are non-formulary as not a cost-effective use of NHS resources. See note re effect of external heat sources p.70 The PCT strongly recommends that prescribers discuss the risk of addiction when initiating new patients on any opioid containing medication and also on review. This discussion should be recorded in the patient notes. Just three days of codeine or dihydrocodeine medicines can lead to addiction. Codeine 30mg x 8/day provides 240mg codeine equivalent to Morphine 30mg Codeine 15mg tablets: £1.19 30mg tablets: £1.49 60mg tablets: £2.40 Tramadol First-line: Immediate release capsules Weak opioid analgesics (continued) Second-line: Modified release as Marol (twice-daily dosing) as Tradorec XL (once-daily dosing) 50mg capsules: £3.20 (100) Note that around 10% of the caucasian population lack the enzyme to metabolize Codeine so derive little benefit from it, but still suffer the side effects Prescribing Paracetamol and Codeine separately enables more appropriate dose titration and enables patients to take more control of their own pain management, e.g. taking Paracetamol regularly and adding Codeine as required. Codeine alone is not considered a particularly effective analgesic. Combinations may be appropriate for patients where there is concern over risk of opiate abuse or where a fixed combination is known to be required regularly, is effective and tolerated. Tramadol may be considered as an alternative to Codeine where its efficacy or tolerability is poor. MHRA advise short-term or intermittent treatment; caution where history of addiction or seizure Tramadol is considered first line opiate for osteoarthritis when opiate therapy is appropriate NICE CG59 Tramadol may be most effective when given with full therapeutic doses of Paracetamol (i.e. NOT as Tramacet which contains only 375mg paracetamol). 100mg tablets: £6.98 (60) 150mg tablets: £10.48 (60) 200mg tablets: £14.28 (60) For patients with long term chronic pain responsive to tramadol but who suffer significant side effects from the immediate release capsules a modified release product may be prescribed. 100mg tablets: £14.10 (30) 200mg tablets: £14.98 (30) 300mg tablets: £22.47 (30) For patients suffering long term chronic night time pain and pain on early waking, Tradorec XL is a formulary option. Maintenance dose for majority of patients is 200mg IN THE EVENING Combination formulations that include tramadol as one of the ingredients (e.g. Tramacet) are non-formulary. Central Nervous System Page 71 Therapeutic Area Formulary Choices Combination analgesics The PCT strongly recommends that prescribers discuss the risk of addiction when initiating new patients on any opioid containing medication and also on review. This discussion should be recorded in the patient notes. Cost for 28 unless stated Rationale for decision / comments Just three days of codeine or dihydrocodeine medicines can lead to addiction. Co-Codamol (Codeine / Paracetamol) Co-codamol 30/500 x 8/day provides 240mg codeine equivalent to Morphine 30mg 8/500mg tablets: £3.30 (100) Evidence that Co-Codamol 8/500 offers significantly better analgesia than Paracetamol alone is poor and many patients, especially the elderly, experience troublesome constipation. Co-Codamol 8/500 is available OTC. 30/500mg tablets: £4.57 (100) Co-Codamol 30/500 is a potent analgesic carrying the full range of opioid side effects e.g. constipation and sedation, requiring particular care in the elderly – see BNF warning. Prescribe as separate components if possible. NB. Co-Codamol 30/500 tablets are >15% cheaper than capsules. Management of opioid overdosage may require use of Naloxone: refer to Chapter 15 of the current BNF Strong opioid analgesics First-line: Note: There is no evidence of superior clinical analgesic effect of other opioids over morphine Morphine Solution Strong opioid analgesics Modified release capsules as Zomorph Central Nervous System 10mg/5ml solution: £4.95 (100ml) 10mg capsules: £3.47 (60) 30mg capsules: £8.30 (60) 60mg capsules: £16.20 (60) 100mg capsules: £25.65 (60) 200mg capsules: £51.30 (60) Use oral solution for initial dose titration and breakthrough pain. Doses not to be given at intervals of less than one hour. Typical time to onset of therapeutic level – Oral morphine solution: 20 – 30 minutes Oxycodone solution: 60 minutes Morphine tablets: 90 minutes NB. Morphine 10mg/5ml is not subject to CD handwriting regulations. Zomorph is the recommended modified-release morphine formulation. Prescribe 12-hourly. Subject to CD regulations. Capsules can be opened and sprinkled on semi-solid food (e.g. yoghurt) or given in water via NG tube. Page 72 Therapeutic Area Formulary Choices Cost for 28 unless stated Strong opioid analgesics Morphine (continued) Modified release tablets as Morphgesic SR 10mg tablets: £3.85 (60) 30mg tablets: £9.24 (60) 60mg tablets: £18.04 (60) 100mg tablets: £28.54 (60) Fentanyl Fentanyl is only included for patients where morphine is contra-indicated or not tolerated or where there is specific need for a non-oral route. Patches as 12mcg £8.87 (5) 25mcg £12.68 (5) 50mcg £23.69 (5) 75mcg £33.03 (5) 100mcg £40.71 (5) See MHRA DSU Vol.2 Issue 2 (Sep-08): Fentanyl patches: serious and fatal overdose from dosing errors, accidental exposure, and inappropriate use. Increases in body temperature and external heat sources may lead to potentially fatal rises in serum fentanyl levels. 5mg capsules £11.43 (56) 10mg capsules £22.86 (56) 20mg capsules £45.71 (56) 5mg/5ml SF solution: £9.71 (250ml) Oxycodone is included only for patients where morphine is contra-indicated or not tolerated. Available data does not provide any evidence of oxycodone‟s superiority to morphine. 5mg tablets: £10.63 (28) 10mg tablets: £21.24 (56) 20mg tablets: £42.48 (56) 40mg tablets: £84.98 (56) 80mg tablets: £169.97 (56) Targinact is non-formulary: not a cost-effective use of NHS resources. No long-term data, no comparison with other opioids with/without regular laxatives. Second-line: Matrifen Third-line: Oxycodone Rationale for decision / comments MR tablets as Longtec Buprenorphine Patches should NOT be prescribed. They are non-formulary as not a cost-effective use of NHS resources. There is a lack of evidence of comparative efficacy with a clinically relevant treatment in the UK. The economic case has not been demonstrated. Like other transdermal products, increases in body temperature (eg after bathing) and external heat sources may lead to increased serum levels of active drug. Central Nervous System Page 73 OPIOID CONVERSION TABLE - St Margaret’s Hospice Guide to Opiod Dose Conversion This is an approximate guide, comprehensive data are lacking and there is inter-individual variation. In most cases, the calculated dose-equivalent of a new drug derived must be reduced by 25-50% to ensure safety. A dose reduction of at least 50% is recommended when switching at high doses (ie. morphine or equivalent doses of 1g/24 hours or more), in elderly or frail patients, or because of intolerable undesirable effects. A similar dose reduction is recommended when there has been a recent rapid escalation of the first opioid. NB Reduction may not be appropriate if the original opioid failed to control pain. The patient‟s clinical condition must be taken into account and breakthrough „prn‟ analgesia to make up any deficit while re-titrating to a satisfactory dose of the new opioid. (Converting from) Current opioid (Converting to) New opioid and/or new route of administration Divide 24 hour dose* of current opioid (col 1) by relevant figure below to calculate initial 24 hour dose of new opioid and/or new route (column 2) Example: 120mg oral morphine in 24 hours subcutaneous diamorphine Divide by 3 120mg/3 = 40mg subcutaneous diamorphine in 24 hours ORAL TO ORAL ROUTE CONVERSIONS oral codeine oral morphine oral tramadol oral morphine oral morphine oral oxycodone oral morphine oral hydromorphone ORAL TO TRANSDERMAL ROUTE CONVERSIONS oral morphine transdermal fentanyl oral morphine transdermal buprenorphine ORAL TO SUBCUTANEOUS ROUTE CONVERSIONS oral morphine subcutaneous morphine oral morphine subcutaneous diamorphine oral oxycodone subcutaneous morphine oral oxycodone subcutaneous oxycodone oral oxycodone subcutaneous diamorphine oral hydromorphone subcutaneous hydromorphone OTHER ROUTE CONVERSIONS (RARELY USED IN PALLIATIVE MEDICINE) subcutaneous or intramuscular morphine intravenous morphine subcutaneous alfentanil subcutaneous diamorphine subcutaneous oxycodone subcutaneous diamorphine intravenous morphine oral morphine * ** oral morphine intramuscular morphine Divide by 10 Divide by 7 Divide by 2 Divide by 7.5 Refer to manufacturer’s information** Seek specialist palliative care advice Divide by 2 Divide by 3 Divide by 1 Divide by 2 Divide by 1.5 Seek specialist palliative care advice Divide by 1 Divide by 10 (specialist palliative care input: amber drug) Divide by 1 – treat as equivalent up to doses of 60mg/24 hours – seek specialist advice Multiply by 2 Divide by 2 The same units must be used for both opioids or routes, eg mg morphine to mg oxycodone The conversion ratios of oral morphine : transdermal fentanyl specified by the manufacturer(s) vary from around 100:1 to 150:1 Central Nervous System Page 74 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 4.7.3 Neuropathic pain Related guidance: NICE Clinical Guideline CG96 (2010): Neuropathic pain – pharmacological management NICE recommendation for the pharmacological management of neuropathic pain depends on diagnosed origin of the pain. There is no need to change existing treatments for people whose neuropathic pain is well controlled Do not start treatment with opioids (such as morphine or oxycodone) other than tramadol without an assessment by a specialist pain service or a condition-specific service All pharmacological treatments should be started at a low dose & titrated to maximum effective or tolerated dose When switching to a new drug, consider overlapping treatments to avoid deterioration in pain control When withdrawing, taper the dose to avoid discontinuation symptoms If pain reduction is still unsatisfactory at maximum doses of first & second line treatments refer patient to a specialist pain and/or condition specific service Painful diabetic neuropathy ONLY First-line: Duloxetine 60mg capsules: £27.72 or Second-line: Amitriptyline 10mg tablets: £0.73 25mg tablets: £0.74 50mg tablets: £0.82 Use amitriptyline if duloxetine is contra-indicated or has not been found effective before using pregabalin. Pregabalin 25mg capsules: £64.40 (56) 50mg capsules: £96.60 (84) 75mg capsules: £64.40 (56) 100mg capsules: £96.60 (84) 150mg capsules: £64.40 (56) 200mg capsules: £96.60 (84) 225mg capsules: £64.40 (56) 300mg capsules: £64.40 (56) If pain reduction is unsatisfactory with first line options, offer treatment with another drug instead of, or in combination with the first drug, depending on outcome of informed discussion with patient. Capsules:100mg £2.83 (100) 300mg £3.87 (100) 400mg £4.62 (100) Pending review of CG96, gabapentin is included as an option. Gabapentin Central Nervous System Because of price structure for pregabalin, ensure dose optimisation is carried out. Page 75 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Amitriptyline 10mg tablets: £0.73 25mg tablets: £0.74 50mg tablets: £0.82 Amitriptyline should be considered as first option (unless C/I). If satisfactory pain reduction is obtained with amitriptyline but patient experiences adverse effects that cannot be tolerated, consider imipramine or nortriptyline as an alternative. If pain reduction is unsatisfactory with first line options, offer treatment with another drug instead of, or in combination with the first drug, depending on outcome of informed discussion with patient. Other neuropathic pain conditions First-line: or Imipramine 10mg tablets: £1.22 25mg tablets: £1.09 or Nortriptyline 10mg tablets: £34.51 25mg tablets: £56.11 or Pregabalin Prices as above Third-line: Tramadol capsules (immediate release) 50mg capsules: £3.20 (100) While awaiting referral tramadol may be considered instead of or in combination with other treatments. More potent opiates are not recommended. NB The combination of tramadol with amitriptyline, nortriptyline, imipramine or duloxetine is associated with a low risk of serotonin syndrome. Fourth-line: Lignocaine (Lidocaine) Patches 5% medicated plaster: £72.40 (pack 30) For the treatment of localised pain for people unable to take oral medication because of medical conditions and/or disability. All neuropathic pain Central Nervous System Page 76 Diagnosis of tension-type headache, migraine & cluster headache Adapted from „Headaches‟ (NICE clinical guideline 150), available from http://www.nice.org.uk/CG150 Headache feature Tension-type headache Migraine (with or without aura) Pain location1 Bilateral Unilateral or bilateral Pain quality Pressing/tightening (non-pulsating) Pain intensity Effect on activities Mild or moderate Not aggravated by routine activities of daily living None Other symptoms Pulsating (throbbing or banging in young people aged 12–17 years) Moderate or severe Aggravated by, or causes avoidance of, routine activities of daily living Cluster headache Unilateral (around the eye, above the eye and along the side of the head/face) Variable (can be sharp, boring, burning, throbbing or tightening) Severe or very severe Restlessness or agitation On the same side as the headache: sound or nausea and/or vomiting. Swollen eyelid without headache and; are fully reversible, develop over at least 5 minutes, last 5 - 60 minutes. Typical aura symptoms include visual symptoms such as flickering lights, spots or lines and/or partial loss of vision; sensory symptoms such as numbness and/or pins and needles; and/or speech disturbance. Duration of headache 30 minutes–continuous Frequency of headache < 15 days per month ≥ 15 days per month for more than 3 months Diagnosis Episodic tensiontype headache Chronic tensiontype headache2 eyelid 4–72 hours in adults 1–72 hours in 15–180 minutes young people aged 12–17 years < 15 days per month ≥ 15 days per month 1 every other day to 8 for more than 3 per day3, with months remission4 >1 month 1 every other day to 8 per day3 with a continuous remission4 <1 month in a 12-month period Chronic cluster headache Episodic migraine Chronic migraine Episodic cluster (with or without (with or without headache aura) aura) 1 Headache pain can be felt in the head, face or neck. 2 Chronic migraine and chronic tension-type headache commonly overlap. If there are any features of migraine, diagnose chronic migraine. 3 Frequency of recurrent headaches during a cluster headache bout. 4 The pain-free period between cluster headache bouts. Central Nervous System Page 77 Medication Recommendations from NICE CG 150: Headache (All recommendations - take account of preferences, comorbidities and risk of adverse events. * Formulary triptans: 1st line – sumatriptan; 2nd line – zolmitriptan. If these are consistently ineffective, try one or more alternative triptans. Tension Type Headache Acute treatment Aspirin (not for under 16 years association with Reye’s Syndrome) Paracetamol NSAID Migraine with or without aura Migraine associated with Menstrual Cycle Acute treatment Acute treatment oral triptan* + NSAID or When standard treatment is not effective: oral triptan* + aracetamol PLUS Frovatripan 2.5mg bd or Anti-emetic even in absence of nausea Zolmitriptan 2.5mg two or & vomiting three times a day on the days Consider nasal triptan for 12-17 year olds & migraine is expected non-oral anti-emetic Migraine in Pregnancy Cluster Headache Acute treatment Paracetamol Acute treatment Oxygen 100% at flow rate at least 12 litres/min with nonrebreathing face mask and/or subcutaneous or nasal triptan DO NOT OFFER Opioids DO NOT OFFER Ergots or derivatives Opioids DO NOT OFFER Routinely prescribe combined hormonal oral contraceptive DO NOT OFFER DO NOT OFFER Paracetamol NSAIDs Opioids Ergots Oral triptans Prophylaxis Prophylaxis: Review need to continue prophylaxis 6 months after starting Continue current regime for people on existing effective migraine prophylaxis. Propranolol or Topiramate (pts under 18) – ensure suitable contraception for females of child bearing age (risk of foetal malformation) Second line: Acupuncture: up to 10 sessions over 5-8 weeks Or Gabapentin – up to 1200mg daily Riboflavin 400mg once daily may be effective to reduce migraine frequency & intensity. Prophylaxis Prophylaxis Prophylaxis N/A Seek specialist advice Verapamil Seek specialist advice if cluster headache does not respond to verapamil Acupuncture: up to 10 sessions over 5-8 weeks Central Nervous System Consider triptan after discussing need for treatment and risks Seek specialist advice for cluster headache during pregnancy Use of medication in bold within this guidance is off-license for indication/age/dose given. These were all approved for prescribing in Somerset at Prescribing Forum November 2012. Prescribers should follow relevant professional guidance & patient (or parent or carer) should provide informed consent, which should be documented) Page 78 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Aspirin 300mg dispersible tablets: £4.00 (100) Evidence supports the efficacy of Aspirin at a dose of 900mg for acute migraine. Available OTC. Ibuprofen 200mg tablets: £3.01 (84) 400mg tablets: £3.01 (84) 600mg tablets: £6.57 (84) For severe headache 400mg dose recommended. 200mg and 400mg tablets available OTC. Paracetamol 500mg tablets: £2.50 (100) Soluble preparations may have a role for occasional use but have high sodium content. Available OTC. Recommended dose 1000mg. As above plus Price as above Analgesic plus anti-emetic combinations are the second line therapy option when simple analgesia alone has proved inadequate. Combination products eg. Migramax are significantly more expensive than separate prescriptions, one component of which is available OTC. Domperidone 10mg tablets: £1.04 (30) 30mg suppositories: £3.06 (10) Metoclopramide 10mg tablets: £0.86 Prochlorperazine 5mg tablets: £1.10 (28) 3mg buccal tabs:£5.89 (10) 4.7.4 Antimigraine drugs Acute management of migraine Simple analgesia Simple analgesia plus anti-emetic prescribed separately Triptans Metoclopramide causes more acute dystonic reactions than domperidone particularly in younger patients. 1st-line Sumatriptan 50mg tablets: £1.67 (6) 100mg tablets: £2.14 (6) Sumatripan is included as the most cost-effective triptan. Evidence suggests little additional benefit from doses above 50mg. If patients have been initiated on injectable forms, a trial of oral sumatriptan is recommended. 2.5mg tablets: £3.47 (6) 2.5mg orodispersible tabs: £3.65 (6) 5mg orodispersible tabs: £16.19 (6) Dose for migraine is 2.5mg – 5mg strength only for patients not achieving satisfactory relief with 2.5mg dose. nd 2 line: Zolmitriptan Central Nervous System There is no evidence that oro-dispersible formulations have a faster onset of action than conventional tablets. Page 79 Therapeutic Area Formulary Choices Prophylaxis of migraine Consider prophylaxis when more than one or two attacks occur per month. See BNF for details. The need for continuing migraine prophylaxis should be reviewed 6 months after starting. Induction of drug overuse headache is possible for all triptans. Risk becomes significant at 12 days per month of triptan intake, mean onest occurs after 1.7 years use. st 1 line: Propranolol Cost for 28 unless stated Rationale for decision / comments 10mg tablets: £0.78 40mg tablets: £0.79 80mg tablets: £1.07 Propranolol is the recommended first line prophylactic therapy for migraine. Avoid using Propranolol MR products as significantly higher cost: Inderal-LA (£1.91 pack of 28) and Half-Inderal LA (£5.40 pack of 28). nd Topiramate tablets 25mg tablets: £2.71 (60) 50mg tablets: £3.67 (60) 100mg tablets: £3.42 (60) 200mg tablets: £14.59 (60) Topiramate is effective for migraine prophylaxis. Advise women & girls of childbearing potential that topiramate is associated with a risk of foetal malformations & can impair the effectiveness of hormonal contraceptives. Ensure they are offered suitable contraception. Prescribe as tablet formulation not capsule because of large price difference. rd Amitriptyline 10mg tablets: £0.73 25mg tablets: £0.74 50mg tablets: £0.82 NICE CG150 states that people whose migraine is well controlled with amitriptyline should continue their current treatment. 2 line: 3 line: 4.8.1 Epilepsy Related guidance: NICE CG137 The Epilepsies: diagnosis and management in adults and children in primary and secondary care Brand Prescribing for Epilepsy Brand prescribing is advised for carbamazepine (Tegretol) and phenytoin (Epanutin; in September 2012 renamed Phenytoin Sodium Flynn Hard capsules) where there is evidence that bioavailability differences may have a clinical impact. For all other anti epileptics prescribing should be generic where one exists and the prescriber, in consultation with the child, young person, adult and their family and/or carers as appropriate, considers this not to be a concern. NICE CG137 recommends use of controlled release preparations when prescribing Carbamazepine. Central Nervous System Page 80 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 0.5ml syringe (2.5mg dose): £82 1ml syringe (5mg dose): £85.50 1.5ml syringe (7.5mg dose): £89.00 2ml syringe (10mg dose): £91.50 Note: Buccolamis currently the only licensed version of buccal midazolam and should be the preferred product for new patients. 4.8.2 Drugs used in status epilepticus Midazolam Buccal solution As Buccolam 10mg/2ml Therapeutic Area There may be a risk if existing patients are changed from „Epiststus‟ or other unlicensed specials to Buccolam unless there has been clear communication and training for the carer of the different strengths available As Epistatus (unlicensed product) Price variable Formulary Choices Cost (per pack as stated) Rationale for decision / comments Patches - various Gum - various Lozenges - various Nasal spray Prescribing for the management of nicotine addiction should be in line with NICE guidance Evidence for all aids to smoking cessation indicates that motivational support increase likelihood of successful quit attempt. Decisions around appropriate aids to smoking cessation should be made in agreement with the patient. Combinations of NRT, bupropion and varenicline for smoking cessation should not be used. Decisions around route of administration for NRT should be made in agreement with the patient. Combinations of NRT products should be considered for those with a high level of nicotine dependency or where previous attempts to stop smoking have been unsuccessful. Prescriptions should normally be for a sufficient to last until 2 weeks after the target stop date, subsequent prescriptions should only be given to people who demonstrate that their quit attempt is continuing. 4.10 Drugs used in substance dependence Smoking Cessation Nicotine Replacement Therapy (NRT) Quickmist Central Nervous System Page 81 Therapeutic Area Formulary Choices Cost for 28 unless stated Smoking Cessation Bupropion (Amfebutamone) 150mg tablets: £41.76 (60) (continued from previous page) Rationale for decision / comments Prescribers should consider prescribing Bupropion a month at a time to minimise waste and link with patients receiving ongoing behavioural support. Bupropion should not be prescribed in pregnancy, lactation or to patients aged <18 years Bupropion is contra-indicated in patients with history of seizures eating disorders CNS tumour experiencing acute symptoms of benzodiazepine or alcohol withdrawal Bupropion should not be prescribed to patients with other risk factors for seizures unless the potential benefits of smoking cessation clearly outweigh the risk. Factors increasing seizure risk include: Concomitant administration of drugs that lower seizure threshold eg. antidepressants, antimalarials, antipsychotics, quinolones, sedating antihistamines, systemic corticosteroids, theophylline and tramadol, stimulants and anorectics Alcohol abuse History of head trauma Diabetes Varenicline▼ Starter pack: £27.30 0.5mg tablets (11) 1mg tablets (14) 0.5mg tablets: £54.60 (56) 1mg tablets: £27.30 (28), £54.60 (56) Note: Varenicline (Champix) is a Black Triangle▼drug, consequently all adverse effects should be reported to the MHRA via the Yellow Card scheme. The MHRA have advised that following reports of depression and suicidal ideation: Smoking cessation with or without pharmacotherapy may be associated with an exacerbation of underlying psychiatric illness, including depression. Care should be taken in such patients, who should be advised of the risk Patients should be made aware of the possibility that trying to stop smoking might cause symptoms of depression Patients who are taking varenicline who develop suicidal thoughts should stop their treatment and contact their doctor immediately. There are some concerns about cardiovascular risk with a warning from FDA issued in June 2011. Patients should be instructed to notify their doctor of new or worsening cardiovascular symptoms. The risk appears to be similar with bupropion Central Nervous System Page 82 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Varenicline is approved for prescribing in Primary Care with the following advice Varenicline should only be prescribed within its licensed indications for smokers who have expressed a desire to quit smoking Varenicline should normally only be prescribed as part of a programme of behavioural support Varenicline should not be prescribed in pregnancy, lactation or to patients aged <18 years Prescribers should consider prescribing the 12 week course of Varenicline a month at a time to minimise waste in patients and link in with patients receiving ongoing behavioural support. Opioid dependence Oral methadone and buprenorphine are recommended by NICE for maintenance therapy in the management of opioid dependence. Patients should be committed to a supportive care programme including a flexible dosing regimen administered under supervision for at least three months, until compliance is assured. In Somerset substance misuse services are provided by Turning Point Somerset which offers a comprehensive program of supportive care through the central team and key workers. Selection of methadone or buprenorphine should be made on a case by case basis, but methadone should be prescribed (as ® Physeptone ) if both drugs are equally suitable. Primary care prescribing of methadone 1mg/ml mixture or buprenorphine sublingual tablets for the treatment or maintenance of opioid dependence is only recommended by GPs who undertaken the necessary RCGP training and in practices that have the relevant shared-care arrangements in place with Turning Point Somerset. Prescribing for the treatment or maintenance of drug addiction outside of shared-care arrangements is NOT recommended and could lead to medico-legal implications for the prescriber in some circumstances. Alcohol dependence Methadone 1mg/1ml mixture ® as Physeptone 1mg/ml: £6.42 (500ml) 1mg/ml sugar-free: £6.42 (500ml) Prescribing by brand is recommended as the most cost-effective option. NB: Sugar-free methadone liquid is thought to have more abuse potential, as it causes fewer complications if injected intra-venously by abusers. SF methadone mixture should be considered second-line. There is no evidence of SF preparations being beneficial in the prevention of dental problems in opioid dependence – dental decay is more likely to be attributed to lifestyle factors that effect dental hygiene and the depressant effect of opioids on salivary secretion. Buprenorphine sugar-free sublingual tablets ® as Subutex 0.4mg: £1.60 (7) 2mg:£6.35 (7) 8mg: £19.05 (7) Prescribing by brand is recommended as the most cost-effective option. Naltrexone 50mg tablets: £22.34 (28) For alcohol dependence, oral naltrexone is an AMBER drug, to be initiated at Turning Point and continued by general practice. Somerset Prescribing Forum approved use of generic naltrexone for this indication. Central Nervous System Page 83 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 4.11 Drugs for dementia Related guidance: NICE Technology Appraisal TA217 (2011): Donepezil, galantamine, rivastigmine and memantine for Alzheimer’s disease When assessing the severity of Alzheimer‟s disease and the need for treatment, healthcare professionals should not rely solely on cognition scores in circumstances in which it would be inappropriate to do so (see NICE TA217 for examples). When using assessment scales to determine the severity of Alzheimer‟s disease, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the results and make adjustments they consider appropriate. Healthcare professionals should also be mindful of the need to secure equality of access to treatment for patients from different ethnic groups, in particular those from different cultural backgrounds. These should only be initiated by specialists in the care of dementia (psychiatrists, neurologists and physicians specialising in the care of older people). Treatment should be continued only when it is considered to be having a worthwhile effect on cognitive, global, functional or behavioural symptoms. Patients who continue on treatment should be reviewed regularly by an appropriate specialist team, or according to the locally agreed Shared Care Protocol. Carer‟s views on the patients‟ condition should be sought at baseline and during follow-up. Acetylcholinesterase inhibitors Donepezil Galantamine Modified release Rivastigmine Transdermal patches NMDA-receptor antagonist Memantine Central Nervous System 5mg tablets: £1.69 (28) 10mg tablets: £1.98 (28) 8mg tablets: £59.29 (56) 12mg tablets: £74.10 (56) 8mg m/r capsules: £51.88 (28) 16mg m/r capsules: £64.90 (28) 24mg m/r capsules: £79.80 (28) 1.5mg capsules: £24.77 (28) 3mg capsules: £24.77 (28) 4.5mg capsules: £24.77 (28) 6mg capsules: £20.59 (28) 4.6mg/24hr patches: £77.97 (30) 9.5mg/24hr patches: £77.97 (30) 10mg tablets: £69.01 (28) 20mg tablets: £69.01 (28) The acetylcholinesterase (AChE) inhibitors: Donepezil, Galantamine and Rivastigmine are recommended as options for mild to moderate Alzheimer‟s disease. Treatment should be started with the drug of lowest acquisition cost. However, an alternative agent could be prescribed if considered appropriate when taking into account adverse event profile, expectations about adherence, medical co-morbidity, possibility of drug interactions and dosing profiles. Oral formulations should be used except where patient has poor swallow or experiences side effects with oral treatment which would lead to discontinuing treatment. Memantine is recommended as an option for people with; Moderate Alzheimer‟s disease who are intolerant or, or have a contraindication to AChE inhibitors, or Severe Alzheimer‟s disease. Page 84 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments BNF Chapter 5: Infections Related guidance: NHS Somerset Infection Management Guidance (2010) Top 5.1 Antibacterial drugs Penicillins Phenoxymethylpenicillin (Penicillin V) 250mg tablets: £1.17 (28) 125mg/5ml SF solution: £16.56 (100ml) 250mg/5ml SF solution: £16.56 (100ml) See Infection management guidance for appropriate clinical indications. Flucloxacillin 250mg capsules: £1.76 (28) 500mg capsules: £2.53 (28) 125mg/5ml suspension: £21.33 (100ml) 125mg/5ml SF suspension: £21.87 (100ml) 250mg/5ml suspension: £26.28 (100ml) 250mg/5ml SF suspension: £26.87 (100ml) See Infection management guidance for appropriate clinical indications. Amoxicillin 250mg capsules: £1.23 (21) 500mg capsules: £1.48 (21) 125mg/5ml SF suspension: £1.15 (100ml) 250mg/5ml SF suspension: £1.42 (100ml) See Infection management guidance for appropriate clinical indications. Co-amoxiclav 250/125mg tablets: £2.73 (21) 500/125mg tablets: £3.41 (21) 125/31mg SF suspension: £2.34 (100ml) 250/62mg SF suspension: £2.37 (100ml) See Infection management guidance for appropriate clinical indications. Management of infection Community use of Co-amoxiclav has been implicated in the causation of Clostridium difficile in Somerset. Page 85 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments Cephalosporins Cefalexin 250mg capsules: £1.97 (28) 500mg capsules: £2.10 (21) 125mg/5ml suspension: £1.50 (100ml) 250mg/5ml suspension: £1.79 (100ml) The Infection management guidance has a very limited role for cephalosporins first line. Cefalexin is indicated for second line use in UTIs where sensitivity is known and Trimethoprim or Nitrofurantoin are not appropriate. The spectrum of activity of Cefalexin and other oral cephalosproins means they are generally inappropriate for RTIs and skin and soft tissue infections. RESTRICTED USE ADVISED Cephalosporins are commonly implicated in Clostridium difficile infection Tetracyclines Doxycycline 100mg capsules: £1.03 (8) See Infection management guidance for appropriate clinical indications. Oxytetracycline has been removed from this section given probability of poor compliance with dosing requirements, together with clinical and costeffectiveness of Doxycycline as viable alternative. Macrolides Erythromycin 250mg e/c tablets: £1.78 (28) See Infection management guidance for appropriate clinical indications. ® NB. Erythromycin capsules (such as Erymax ) are approximately 10 times the price of the standard ec tablets. per 100ml suspension: 125mg/5ml: £2.46 sugar free £3.08 250mg/5ml: £3.60 sugar free £4.07 500mg/5ml: £5.80 sugar free £9.20 Clarithromycin Management of infection 250mg tablets: £3.73 (14) 500mg tablets: £3.27 (14) 125mg/5ml SF suspension:£6.68 (70ml) 250mg/5ml SF suspension:£13.28 (70ml) Erythromycin & Clarithromycin are known inhibitors of cytochrome P450 enzyme CYP3A4. Prescribers should be aware of the potential for drug interactions with other medicines. Click on these links for more information. See Infection management guidance for appropriate clinical indications. ® Clarithromycin MR tablets (Klaricid XL ) are non formulary on grounds of higher cost. Page 86 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments Azithromycin 250mg tablets: £3.39 (4) 500mg tablets: £2.34 (3) Azithromycin is recommended for treatment of Chlamydia where compliance with other options may be poor. AMBER (specialist initiation) for prevention of exacerbations of non-CF bronchiectasis. ECG required before initiation & if prescribed continuously for longer than 3 months, GP should consider periodic ECG to manage cardiac risks. Trimethoprim and sulphonamides Trimethoprim 100mg tablets: £1.05 (28) 200mg tablets: £0.93 (14) 50mg/5ml SF suspension: £2.16 (100ml) See Infection management guidance for appropriate clinical indications. Metronidazole and tinidazole Metronidazole 200mg tablets: £1.13 (21) 400mg tablets: £1.24 (21) 200mg/5ml suspension: £18.20 (100ml) See Infection management guidance for appropriate clinical indications. Quinolones Ciprofloxacin 250mg tablets: £0.82 (10) 500mg tablets: £0.97 (10) 750mg tablets: £8.59 (10) See Infection management guidance for appropriate clinical indications. Ciprofloxacin has very poor activity against common RTI pathogens and therefore should only be used on specialist advice for these indications. Quinolones are commonly implicated in Clostridium difficile infection. Urinary tract infections Nitrofurantoin 100mg tablets: £5.75 (28) 50mg capsules: £3.66 (30) 100mg capsules: £6.91 (30) 100mg capsules m/r: £5.87 (14) See Infection management guidance for appropriate clinical indications. Consider Nitrofurantoin as an alternative to Trimethoprim as first line treatment for uncomplicated UTIs. 50mg is associated with significantly less nausea than 100mg. Chapter 13: Skin 5.2 Antifungal drugs For topical antifungal preparations, please refer to Chapter 13: Skin Antifungals Fluconazole See Infection management guidance for appropriate clinical indications. Voriconazole – RED drug. NOT for primary care prescribing. 50mg capsules: £0.88 (7) 150mg capsule: £0.80 (1) Itraconazole 100mg capsules: £6.90 (15) See Infection management guidance for appropriate clinical indications. Management of infection Page 87 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments NB Transient or permanent hearing loss has been reported with itraconazole. Terbinafine 250mg tablets: £1.86 (28) See Infection management guidance for appropriate clinical indications. Measure LFTs before treatment & after 4-6 weeks. 5.3 Antiviral drugs For topical antivirals please refer to Chapter 13: Skin Antivirals Antiviral treatments for HIV, and Valganciclovir are RED drugs and not for primary care prescribing. Influenza vaccine First-line: Aciclovir Second- line: Valaciclovir First line: ® Fluvirin ® Enzira ® Influvac ® Fluarix Shingles Vaccine Management of infection See Infection management guidance for appropriate clinical indications. 200mg dispersible tablets: £2.58 (25) 400mg tablets: £5.12 (56) 800mg tablets: £6.00 (35) Famciclovir is non-formulary, based on cost. Famciclovir 750mg daily costs £148 per 7 day course i.e. around 16x higher than an equivalent course of Aciclovir 800mg. Valaciclovir is included in the formulary only for genital herpes for second line use when Aciclovir is not appropriate. 250mg tablets: £123.28 (60) 500mg tablets: £16.31 (10), £86.30 (42) £5.55 per dose £5.25 per dose £5.22 per dose £5.39 per dose Companies offer a range of deals & discounts depending on service package. The PCT has a duty to recommend that practices make best use of the available NHS resources and purchase a vaccine that is both cost effective and has a supplier who can provide sufficient practice support to ensure good uptake by patients. Given the choice of 4 different vaccines NHS Somerset see no reason for a practice to choose a vaccine with an NHS price > £5.55 Non-Formulary Supply is limited & prescribing not currently recommended on NHS. The DH has confirmed that it intends to run a national vaccination programme for those over 70 years of age, but until they have secured a sufficient supply of the Zostavax vaccine and is able to implement the JCVI‟s recommendations, GPs are currently advised not to give the vaccine. Page 88 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 Aims to provide a simple, empirical approach to the treatment of common infections to promote the safe, effective and economic use of antibiotics to minimise the emergence of bacterial resistance in the community Principles of Treatment 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. This guidance is based on best available evidence and should be used alongside references such as the BNF, BNFc , and SPCs Professional judgement should be used and patients should be involved in decisions about their treatment. Unless otherwise stated, a dose and duration of treatment for adults is usually suggested, but may need modification for age, weight and renal function. In severe or recurrent cases consider a larger dose or longer course. Prescribe an antibiotic only when there is likely to be a clear clinical benefit. Lower threshold for antibiotics in immunocompromised or those with multiple morbidities; consider culture and seek advice. Consider a no, or delayed, antibiotic strategy for acute self-limiting upper respiratory tract infections including sore throat, common cold, cough and sinusitis. (See No Antibiotic ‘Prescription’ Form) Limit prescribing over the telephone to exceptional cases. Use simple antibiotics prescribed generically whenever possible. Avoid broad spectrum antibiotics (e.g. co-amoxiclav, quinolones and cephalosporins) when narrow spectrum antibiotics remain effective, as they increase risk of Clostridium difficile, MRSA and resistant UTIs. Avoid widespread use of topical antibiotics (especially those agents also available as systemic preparations, e.g. fusidic acid). In pregnancy, AVOID tetracyclines, aminoglycosides, quinolones, high dose metronidazole (e.g. 2g STAT). In pregnancy, short-term use of trimethoprim (theoretical risk in first trimester in patients with poor diet or if taking another folate antagonist such as antiepileptic or proguanil), or nitrofurantoin (at term, theoretical risk of neonatal haemolysis) are unlikely to cause problems to the foetus. Clarithromycin is recommended in place of erythromycin (except in pregnancy) as it has less side-effects, greater compliance (as twice rather than four times daily), and generic tablets are similar cost. In children erythromycin may remain preferable as clarithromycin syrup is twice the cost. For further advice contact the Microbiologists at Musgrove Park Hospital, out of hours via MPH switchboard 01823 333444 Jump to the infection group you want by clicking on the link below UPPER RESPIRATORY TRACT INFECTIONS LOWER RESPIRATORY TRACT INFECTIONS MENINGITIS URINARY TRACT INFECTIONS GASTRO-INTESTINAL TRACT INFECTIONS ILLNESS GENITAL TRACT INFECTIONS SKIN INFECTIONS DENTAL INFECTIONS EYE INFECTIONS COMMENTS DRUG DOSE DURATION UPPER RESPIRATORY TRACT INFECTIONS: Consider delayed antibiotic prescriptions. Influenza HPA Influenza Acute Sore Throat CKS Annual vaccination is essential for all those at risk of influenza. For otherwise healthy adults antivirals not recommended. Treat ‘at risk’ patients ONLY within 48 hours of onset AND when influenza is circulating in the community or in a care home where influenza is likely. At risk: 65 years or over, chronic respiratory disease (including COPD and asthma) significant cardiovascular disease (not hypertension), immunocompromised, diabetes mellitus, chronic neurological, renal or liver disease. Use 5 days treatment with oseltamivir 75 mg bd or if there is resistance to oseltamivir use 5 days zanamivir 10 mg BD (2 inhalations by diskhaler). For prophylaxis, see NICE. (NICE Influenza). Patients under 13 years see HPA Influenza link. Avoid Antibiotics as 90% resolve in 7 days without, and pain only reduced by 16 hours If Centor score 3 or 4: (Lymphadenopathy; No Cough; Fever; Tonsillar Exudate) consider 2 or 3-day delayed or immediate antibiotics Antibiotics to prevent Quinsy NNT >4000 Antibiotics to prevent Otitis media NNT 200 Acute Otitis Media (child doses) CKS Optimise analgesia and Avoid Antibiotics 60% are better in 24 hours, and 80% are better in 4 days without. They only reduce pain at 2 days (NNT15) and do not prevent deafness Consider 2 or 3-day delayed or immediate antibiotics for pain relief if: < 2yrs with bilateral AOM NNT4 or bulging membrane & ≥ 4 marked symptoms All ages with otorrhoea NNT3 phenoxymethylpenicillin if allergic to penicillin: clarithromycin 500 mg QDS 1G BD (QDS when severe) 10 days 250-500mg BD 5 days Child doses amoxicillin if allergic to penicillin: erythromycin 40mg/kg/day in 3 doses (max. 3g daily) 5 days < 2yrs 125mg QDS 2-8yrs 250mg QDS 8-18yrs 250-500mg QDS 5 days Abx to prevent Mastoiditis NNT >4000 Management of infection Page 89 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 ILLNESS Acute Otitis Externa CKS COMMENTS First use aural toilet (if available) & analgesia CKS First line: acetic acid 2% DOSE DURATION 1 spray TDS 7 days Second line: neomycin sulphate with corticosteroid 3 drops TDS 7 days min to 14 days max Avoid Antibiotics as 80% resolve in 14 days without, and they only offer marginal benefit after 7 days (NNT15). phenoxymethylpenicillin 500mg QDS 7 days or amoxicillin 500mg TDS 1g if severe 7 days Use adequate analgesia if allergic to penicillin: doxycycline 200mg stat/100mg OD For persistent symptoms: co-amoxiclav 625mg TDS Cure rates similar at 7 days for topical acetic acid or antibiotic +/- steroid If cellulitis or disease extending outside ear canal, start oral antibiotics and refer Acute Rhinosinusitis DRUG Consider 7-day delayed or immediate antibiotic when purulent nasal discharge NNT8 In persistent infection use an agent with antianaerobic activity eg. co-amoxiclav 7 days 7 days LOWER RESPIRATORY TRACT INFECTIONS TOP Low doses of penicillins are more likely to select out resistance. Do not use quinolone (ciprofloxacin, ofloxacin) first line due to poor pneumococcal activity. Reserve all quinolones (including levofloxacin) for proven resistant organisms e.g. pseudomonas spp. Acute cough, Antibiotic little benefit if no co-morbidity amoxicillin 500 mg TDS 5 days bronchitis Symptom resolution can take 3 weeks. or doxycycline 200 mg stat/100 mg OD 5 days CKS Consider 7-14 day delayed antibiotic with NICE 69 symptomatic advice/leaflet Acute Treat exacerbations promptly with antibiotics amoxicillin 500 mg TDS exacerbation of if purulent sputum and increased shortness of or doxycycline 200 mg stat/100 mg OD COPD breath and/or increased sputum volume 7 days (14 days clarithromycin (if penicillin 500 mg BD NICE 12 for frequent Risk factors for antibiotic resistant organisms GOLD allergic exacerbators) include co-morbid disease, severe COPD, nd 2 line 960mg BD frequent exacerbations, antibiotics in last 3m co-trimoxazole CommunityUse CRB65 score to help guide and review: IF CRB65=0: amoxicillin 500 mg TDS 7 days acquired Each scores 1: Confusion (AMT<8); 500 mg BD 7 days pneumonia Respiratory rate >30/min; or clarithromycin treatment in BP systolic <90 or diastolic ≤ 60; 200 mg stat/100 mg OD 7 days or doxycycline the community Score 0: suitable for home treatment; BTS 2009 Guideline Score 1-2: hospital assessment or admission Score 3-4: urgent hospital admission Give immediate IM benzylpenicillin or D amoxicillin 1G po if delayed admission/life threatening, and seek risk factors for Legionella and Staph. aureus infection. If CRB65=1 & AT HOME amoxicillin 500 mg TDS AND clarithromycin 500 mg BD or doxycycline alone 200 mg stat/100 mg OD 7-10 days 7-10 days Mycoplasma infection is rare in over 65s MENINGITIS NICE fever guidelines TOP Transfer all patients to hospital immediately. IV or IM benzylpenicillin Age 10+ years: 1200 mg IF time before admission, give IV Children 1 - 9 yr: 600 mg (only give IM if benzylpenicillin, unless hypersensitive ie Or Children <1 yr: 300 mg vein cannot be history of difficulty breathing, collapse, loss of IV or IM cefotaxime Age 12+ years 1g found) HPA consciousness, or rash Child <12 yrs 50mg/kg Prevention of secondary case of meningitis: Only prescribe following advice from Somerset Health Protection Agency accessible on 01823 287817 (Fax: 01823 287819) or out of hours via Musgrove Park switchboard on 01823 333444 TOP URINARY TRACT INFECTIONS HPA UTI quick reference guide ESBLs CKS UTI Amoxicillin resistance is common, therefore ONLY use if culture confirms susceptibility. People > 65 years: do not treat asymptomatic bacteriuria; it is common (25% in ♀, 10% in ♂) but is not associated with increased morbidity Catheter in situ: antibiotics will not eradicate asymptomatic bacteriuria; only treat if systemically unwell or pyelonephritis likely Do not use prophylactic antibiotics for catheter changes unless history of catheter-change-associated UTI UTI in Women with severe or ≥ 3 symptoms: treat trimethoprim 200mg BD Women 3 days men & women Women with mild or ≤ 2 symptoms: use or nitrofurantoin (no fever or dipstick to guide treatment. Nitrite & 50-100mg QDS, or Men 7 days flank pain) blood/leucocytes has 92% positive predictive 100mg m/r BD HPA QRG value ; -ve nitrite, leucocytes, and blood has a 76% NPV Second line: perform culture in all treatment failures. SIGN Men: send pre-treatment MSU OR if Amoxicillin resistance is common; only use if susceptible CKS, CKS symptoms mild/non-specific, use –ve nitrite Community multi-resistant Extended-spectrum Beta-lactamase E. coli are and leucocytes to exclude UTI increasing, but often remain sensitive to nitrofurantoin. Fosfomycin may be an option on advice of microbiology,see guidance here Suspected meningococcal disease Management of infection Page 90 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 ILLNESS UTI in pregnancy HPA QRG CKS COMMENTS Send MSU for culture & sensitivity and start empirical antibiotics Short-term use of nitrofurantoin in pregnancy is unlikely to cause problems to the foetus Avoid trimethoprim if low folate status or on folate antagonist (eg antiepileptic or proguanil) UTI in children Child <3 mths: refer urgently for assessment HPA QRG CKS NICE Child ≥ 3 months: use positive nitrite to start antibiotics. Send pre-treatment MSU for all. Acute pyelonephritis CKS Recurrent UTI in women ≥ 3 UTIs/year Imaging: only refer if child <6 months or atypical UTI NICE HPA QRG CKS Symptomatic relapse Infectious diarrhoea CKS Clostridium difficile DH & HPA Travellers’ diarrhoea CKS First line: nitrofurantoin DOSE DURATION 50-100mg QDS, or 100 mg m/r BD or trimethoprim Second line: if susceptible, amoxicillin 200mg BD (off-label) Give folic acid if first trimester 500 mg TDS Third line: cefalexin 500 mg BD Lower UTI: trimethoprim or nitrofurantoin if susceptible, amoxicillin Second line: cefalexin See BNFc for dosage Upper UTI: co-amoxiclav Second line: cefixime All for 7 days Lower UTI 3 days Upper UTI 7-10 days If admission not needed, send MSU for culture & sensitivities and start antibiotics If no response within 24 hours, admit RCT data shows 7 days ciprofloxacin as good as 14 days co-trimoxazole. ciprofloxacin or co-amoxiclav If susceptible trimethoprim 500 mg BD 500/125 mg TDS 200mg BD 7 days 14 days 14 days Post-coital prophylaxis or standby antibiotic trimethoprim or nitrofurantoin 100 mg 50–100 mg Post coital stat (off-label) Prophylaxis OD at night Nightly: reduces UTIs but adverse effects nd Nitrofurantoin 2 line due to potential pulmonary toxicity. GASTRO-INTESTINAL TRACT INFECTIONS Eradication of Helicobacter pylori DRUG Eradication is beneficial in known DU, GU or low grade MALToma TOP PPI is either omeprazole capsules 20mg BD or lansoprazole capsules 30mg BD. H2RA is ranitidine 150mg BD or 300mg OD at night. First line: BD PPI plus 250 mg BD clarithromycin AND 400 mg BD metronidazole Consider test and treat in persistent All for OR uninvestigated dyspepsia 7 days PPI plus BD Do not offer eradication for GORD clarithromycin AND 500mg BD amoxicillin 1g BD Do not use clarithromycin or metronidazole if used in the past year for any infection Second line: Relapse PPI plus BD or MALToma ® DU/GU relapse: retest for H. pylori using bismuthate (De-nol tab ) 240 mg BD 14 days breath or stool test OR consider endoscopy for PLUS 2 unused antibiotics: culture & susceptibility 1 g BD amoxicillin 400 mg TDS NUD: Do not retest, offer PPI or H2RA metronidazole 500 mg QDS tetracycline Check travel, food, hospitalisation and antibiotic history (C. difficile is increasing). Fluid replacement is essential. Refer previously healthy children with acute painful or bloody diarrhoea to exclude E. coli 0157 infection. Antibiotic therapy not indicated unless systemically unwell. If the patient is systemically unwell, or if pregnant, initiate treatment on advice of microbiologist. If systemically unwell and campylobacter suspected (e.g. undercooked meat and abdominal pain), consider clarithromycin 250–500 mg BD for 5–7 days if treated early. Please send stool specimens from suspected cases of food poisoning and after antibiotic use. Please notify suspected cases of food poisoning to, and seek advice from, Somerset Health Protection Agency on 01823 287817 (Fax: 01823 287819) or out of hours via the Musgrove Park Hospital switchboard on 01823 333444. st nd Stop unnecessary antibiotics and/or PPIs 1 /2 episodes Triple therapy achieves an 85% eradication. For NUD, the NNT is 14 for symptom relief 70% respond to MTZ in 5days; 92% in 14days metronidazole (MTZ) 400 mg oral TDS 10-14 days rd Admit if severe: T >38.5; WCC >15, rising 3 episode/severe creatinine or signs/symptoms of severe colitis oral vancomycin 125mg oral QDS 10 -14 days Avoid anti-motility anti-diarrhoeal agents such as Loperamide or Codeine . Only consider standby antibiotics for remote areas or people at high-risk of severe illness with travellers’ diarrhoea If standby treatment appropriate give: ciprofloxacin 500 mg twice a day for 3 days (private Rx). If quinolone resistance high (e.g. south Asia): consider bismuth subsalicylate (Pepto Bismol) 2 tablets QDS as prophylaxis or for 2 days treatment Management of infection Page 91 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 ILLNESS COMMENTS Threadworms Treat all household contacts at the same time PLUS advise hygiene measures for 2 weeks (hand hygiene, pants at night, morning shower) PLUS wash sleepwear, bed linen, dust, and vacuum on day one. CKS DRUG DOSE DURATION > 6 months: mebendazole (off-label if < 2yrs) 100 mg stat 3-6 mths: piperazine+senna 2.5ml spoonful stat, repeat after 2 weeks < 3mths: 6 wks hygiene GENITAL TRACT INFECTIONS STI screening Chlamydia trachomatis SIGN BASHH HPA CKS Vaginal candidiasis TOP People with risk factors should be screened for chlamydia, gonorrhoea, HIV, syphilis. Refer individual and partners to GUM clinic or general practices with level 2 or 3 expertise in GUM. Risk factors: < 25y, no condom use, recent (<12mth)/frequent change of partner, symptomatic partner. Opportunistically screen all aged 15-25yrs doxycycline 100 mg BD 7 days Treat partners and refer to GUM service or azithromycin 1g stat Pregnancy or breastfeeding: azithromycin is Pregnant or breastfeeding: the most effective option. azithromycin 1g (off-label use) stat Due to lower cure rate in pregnancy, test for or erythromycin 500 mg QDS 7 days cure 6 weeks after treatment. or amoxicillin 500 mg TDS 7 days 1A+ All topical and oral azoles give 75% cure. clotrimazole 500 mg pess/ 10% cream stat 150 mg orally stat 100 mg pessary at night 5 g intravaginally BD 6 nights 7 days oral metronidazole 400 mg BD or 2 g 5 g applicatorful at night 5 g applicatorful at night 7 days BASHH HPA CKS Oral metronidazole (MTZ) is as effective as topical treatment but is cheaper. Less relapse with 7 day than 2g stat at 4 wks. Pregnant / breastfeeding: avoid 2g stat dose. Treating partners does not reduce relapse. Trichomoniasis Treat partners and refer to GUM service. metronidazole BASHH HPA, CKS Pregnant/ breastfeeding: avoid 2g stat dose. Consider clotrimazole for symptom relief (not cure) if MTZ declined. 400 mg BD or 2 g 5-7 days stat clotrimazole 100 mg pessary at night 6 nights 500 mg 400 mg BD 100 mg BD stat 14 days 14 days 400 mg BD 400 mg BD 14 days 14 days 500 mg BD 200 mg BD 100mg BD 28 days 28 days 28 days Pregnancy: avoid oral azole use intravaginal for 7 day. Bacterial vaginosis Pelvic Inflammatory Disease RCOG BASHH, CKS Acute prostatitis BASHH, CKS CKS Eczema CKS Erythema chronicum migrans CKS Cellulitis CKS 3A+ or MTZ 0.75% vag gel or clindamycin 2% crm 28% of gonorrhoea isolates now resistant to quinolones. If gonorrhoea likely (partner has it, severe symptoms, sex abroad) avoid ofloxacin regimen. If High Risk ceftriaxone PLUS metronidazole PLUS doxycycline or metronidazole PLUS ofloxacin Send MSU for culture and start antibiotics. 4-wk course may prevent chronic prostatitis. Quinolones achieve higher prostate levels. ciprofloxacin or trimethoprim or doxycycline Refer woman & contacts to GUM service. Always culture for gonorrhoea & Chlamydia. SKIN INFECTIONS Impetigo or oral fluconazole 1A+ clotrimazole 3A+ miconazole 2% cream BASHH HPA, CKS stat 5 nights 7 nights TOP For extensive, severe, or bullous impetigo, use oral flucloxacillin 500 mg QDS 7 days oral antibiotics. If penicillin allergic: Reserve topical antibiotics for very localised oral clarithromycin 250-500 mg BD 7 days lesions to reduce the risk of resistance. retapamulin Topically BD 5 days Reserve mupirocin for MRSA. mupirocin (MRSA only) Topically TDS 5 days If no visible signs of infection, use of antibiotics (alone or with steroids) encourages resistance and does not improve healing. In eczema with visible signs of infection, use treatment recommended in impetigo. Associated with Lyme disease. doxycycline 100mg BD 14 days Send clotted blood for Lyme serology and treat Second line: amoxicillin 500mg TDS 14 days empirically. Microbiology will advise on (especially for children, positive results. pregnancy & See BNFc for children breastfeeding) under 5 years. If patient afebrile and healthy other than cellulitis, use oral flucloxacillin alone. If river or sea water exposure, discuss with microbiologist. If febrile and ill, admit for IV treatment. Management of infection Flucloxacillin if allergic to penicillin: clarithromycin nd 500 mg – 1g QDS 500 mg BD 2 line: doxycycline 200mg stat, 100mg od facial: co-amoxiclav 500/125 mg TDS All for 7 days. If slow response or patient unable to take st nd 1 or 2 line options contact microbiology Page 92 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 Leg ulcers HPA QRG CKS Ulcers always colonized. Antibiotics do not improve healing unless active infection. If active infection, send pre-treatment swab. Review antibiotics after culture results. ILLNESS Diabetic Foot Infections PVL S. aureus HPA QRG Bites Human: CKS Cat or dog: Mastitis Scabies CKS Fungal infection – skin CKS body & groin CKS foot CKS scalp Fungal infection –fingernail or toenail CKS Varicella zoster/ chicken pox CKS & Herpes zoster/ shingles CKS Cold sores COMMENTS See PEDIS grading & Treatment Options Grade 1: No antibiotics Grade 2: treat as per guidelines Grade 2 + evidence of ischaemia, and above: refer to secondary care. Active infection if cellulitis/increased pain/pyrexia/purulent exudate/odour If active infection: Flucloxacillin if allergic to penicillin: or clarithromycin DRUG Flucloxacillin 500 mg – 1g QDS As for cellulitis 500 mg BD DOSE DURATION over 60kg 1g QDS Under 60kg (or problems with nausea) 500mg QDS As for cellulitis If no improvement or worse after 2 If allergic to penicillin weeks refer to If osteomyelitis is suspected, refer to Clarithromycin 500mg BD secondary care secondary care ASAP Panton-Valentine Leukocidin (PVL) is a toxin produced by 2% of S. aureus and is associated with persistent pustules and carbuncles or cellulitis. Can rarely cause severe invasive infections in healthy people. Send swabs if recurrent boils/abscesses. At risk: close contact in communities (e.g. nursing homes) or contact sport, sharing equipment, poor hygiene and eczema. Thorough irrigation is important. Prophylaxis or treatment: Assess risk of tetanus, HIV, hepatitis B&C. co-amoxiclav 625 mg TDS Antibiotic prophylaxis is advised. If penicillin allergic: Assess risk of tetanus and rabies. metronidazole PLUS 400 mg TDS All for 7 days Give prophylaxis if cat bite/puncture wound; doxycycline (cat/dog/man) 100 mg BD bite to hand, foot, face, joint, tendon, ligament; AND review at 24 & 48hrs Immunocompromised/diabetic/asplenic/ cirrhotic Antibiotics are not always required. Self-help flucloxacillin 500mg QDS 7 days measures e.g. continuation of breastfeeding or if allergic to penicillin: expressing will aid resolution of mastitis. 7 days 500mg QDS erythromycin Treat all home & sexual contacts within 24h. permethrin 5% cream 2 applications Treat whole body from ear/chin downwards If allergy: 1 week apart and under nails. malathion 0.5% aqueous liquid If under 2 or elderly, also face and scalp. Terbinafine is fungicidal, so treatment time Topical terbinafine BD 1-2 weeks shorter than with fungistatic imidazoles. or topical imidazole BD for 1-2 wks after If candida possible, use imidazole. healing If intractable: send skin scrapings. If infection (i.e. 4-6wks) confirmed, use oral terbinafine/itraconazole. Scalp: discuss with specialist. Take nail clippings: start therapy only if Superficial only amorolfine 1-2x/weekly fingers 6 months infection is confirmed by laboratory. 5% nail lacquer toes 12 months Terbinafine is more effective than azoles. First line: terbinafine 250 mg OD fingers 6 – 12 weeks Liver reactions rare with oral antifungals. toes 3 – 6 months If candida or non-dermatophyte infection Second line: itraconazole 200 mg BD 7 days monthly confirmed, use oral itraconazole. fingers 2 courses For children, seek specialist advice. toes 3 courses Pregnant/immunocompromised/neonate: seek If indicated: urgent specialist advice. aciclovir 800 mg five times a day 7 days Chicken pox: If started < 24h of rash & > 14y or severe pain or dense/oral rash or 2° household case or steroids or smoker consider aciclovir. Shingles: treat if > 50 yrs and within 72 hrs of rash (PHN rare if < 50yrs); or if active ophthalmic or Ramsey Hunt or eczema. Cold sores resolve after 7–10 days without treatment. Topical antivirals applied prodomally reduce duration by 12-24hrs. TOP DENTAL INFECTIONS Dental Infections Local guidance (Dental) The primary treatment of dental infections should be drainage of pus and removal of the source of infection. This will normally require attention by a dental practitioner. Urgent appointments (usually within 24 hours) can be obtained through the dental helpline 0845 7697691. Antibiotics are of limited use and should not be prescribed except for patients who are systemically unwell, or if there are signs of severe infection, e.g. fever, lymphadenopathy, cellulitis, or diffuse swelling. Patients to seek dental advice if possible. Dentists should follow local guidance. Acute dental-alveolar infections: amoxicillin 250mg TDS Up to 5 days If allergic to penicillin: metronidazole 200mg TDS Up to 3 days Pericoronitis: Management of infection metronidazole 200mg TDS 3 days Page 93 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 EYE INFECTIONS Conjunctivitis CKS TOP Most bacterial conjunctivitis is self-limiting. 65% resolve on placebo by day five. Red eye with yellow-white mucopurulent, not watery discharge. Usually unilateral but may spread. Management of infection If severe: chloramphenicol 0.5% drop and 1% ointment OR 1% ointment 2 hourly for 2 days then 4 hourly (whilst awake) at night All for 48 hours after resolution QDS Page 94 SOMERSET PCT - INFECTION MANAGEMENT GUIDANCE 2012/13 Appendix 1 Methicillin Resistant Staphylococcus Aureus (MRSA) Decolonisation Policy If clinical infection is suspected medical staff must discuss treatment options with a Consultant Microbiologist. Where there is clinical infection, decolonisation treatment should be undertaken in addition to any systemic treatment given. Topical decolonisation treatment must be commenced immediately, using nasal and skin preparations as below. This is used for 5 days then stopped for 2 days and the patient is re-screened on day 8 to determine if the patient is still MRSA positive Mupirocin (Bactroban) Nasal Ointment: Three times daily to nostrils PLUS Skinsan*: Once daily wash, include at least one hair wash daily OR Octenisan*: Once daily wash, include at least one hair wash daily * Although these may not be listed on all GP clinical system prescribing databases, they can be prescribed on FP10. If the patient remains positive after the first course of decolonisation a further course of topical treatment should be carried out as above, followed by a further screen. If the second course of decolonisation is unsuccessful, the Somerset PCT Infection Control Team must be contacted to discuss further options. The issues associated with the treatment for decolonising wounds is complex and should be discussed with a member of the Somerset PCT Infection Control Team. For patients in community hospitals, decolonisation therapy must be prescribed and staff must record decolonisation as per the Topical Therapy Chart. The Somerset PCT Infection Control Team can be contacted for further advice via the PCT switchboard on 01935 384000. Further advice (and documents, including topical therapy chart) is also available on the Infection control page of the Somerset PCT website nww.somersetpct.nhs.uk There is a separate pre-operative protocol for the management of patients attending Musgrove Park Hospital for elective orthopaedic surgery. For information, contact Taunton & Somerset NHS Trust Infection Prevention and Control team 01823 342611 Management of infection Page 95 BNF Chapter 6: Endocrine System 6.1 Drugs used in diabetes Top Related guidance: NICE Clinical Guideline CG87 (2009): Type 2 diabetes See summary chart on p.97 Before any pharmacological interventions are considered there should be a 3 month period of diet & lifestyle interventions. Education provide structured education to every patient and/or their carer at and around the time of diagnosis and review annually. Diet provide individualised and ongoing specialist nutritional advice. Lifestyle encourage weight loss and exercise. Blood Pressure Control Evidence from UKPDS indicates that control of blood pressure in people with hypertension & Type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity. Guidance on the use of Blood Glucose Testing Strips is on page 104 The VADT, ACCORD and ADVANCE trials show that tight control of blood glucose in long standing Type 2 diabetics (reducing HbA1c to below 7%) may be harmful. CG 87 agrees with this view and recommends: Involve the person in decisions about their individual HbA1c target which may be above the general target of 6.5% especially in long standing diabetes. Offer lifestyle advice and medication to help achieve and maintain the HbA1c target. Inform patients with a higher HbA1c that any reduction towards the agreed target is advantageous to their health. Avoid pursuing highly intensive management to levels of <6.5%. ♦ Self-monitoring of blood glucose should be offered to a patient newly diagnosed with T2DM only as an integral part of his/her self- management education. Its purpose should be discussed and there should be agreement how the results should be interpreted and acted upon. ♦ Eye and kidney damage should be screened annually. NB DH require that HbA1c should always be measured in millimoles per mol (mmol/mol) as well as by percentage. HbA1c of 6.5% is equivalent to 48 mmol/mol. Guide to HbA1c values expressed as mmol/mol Endocrine System - Diabetes DCCT- HbA1c % IFCC-HbA1c mmol/mol 6.0 42 6.5 48 7.0 53 7.5 58 8.0 64 9.0 75 Page 96 3 month trial of lifestyle interventions 97 HbA1c ≥ 6.5% METFORMIN with active dose titration and use of MR version if necessary to minimise incidence of GI side effects. HbA1c ≤ 6.5% Monitor for deterioration HbA1c ≥ 6.5% Metformin plus gliclazide HbA1c ≤ 7.5% Monitor for deterioration HbA1c ≥ 7.5% Insulin + metformin + gliclazide Adding insulin in preference to other oral rd hypoglycaemice should be normal 3 line option unless there is a strong reason not to, parrticularly if patient is markedly hyperglycaemic HbA1c ≤ 7.5% Monitor for deterioration HbA1c ≥7.5% Summary of NICE CG 87: Treatment of Type 2 diabetes Endocrine System - Diabetes Consider gliclazide if: i. Not overweight (tailor weight assessment to ethnic group) OR ii. Rapid therapeutic response is required owing to hyperglycaemic symptoms OR iii. Metformin CI or not tolerated Consider repaglinide before meals for people with erratic lifestyle. Consider substituting pioglitazone or gliptin for gliclazide if there is significant risk of hypoglycaemia (or its consequences) or if sulphonylurea is CI or not tolerated Consider adding pioglitazone or gliptin instead of insulin if insulin is not acceptable for (see note p.94) Consider adding exenatide or liraglutide if: BMI≥ 35 kg/m2 in people of European origin and there are problems associated with high weight BMI < 35 and insulin is unacceptable because of occupational implications andor weight loss would benefit other comorbidities Increase insulin dose and intensify regimen over time. Consider pioglitazone with insulin if: Pioglitazone has previously had a marked glucose-lowering effect or: Blood glucose control is inadequate with high-dose insulin For options i. and ii. consider Metformin plus gliclazide Gliclazide HbA1c < 6.5% Monitor for deterioration If metformin CI or not tolerated: Gliclazide + pioglitazone OR Gliclazide + gliptin Metformin + pioglitazone OR Metformin + gliptin HbA1c <7.5% Monitor for deterioration HbA1c ≥ 7.5% HbA1c ≥ 6.5% HbA1c <7.5% Monitor for deterioration HbA1c ≥7.5% Metformin + gliclazide + pioglitazone OR Start Insulin Metformin + gliclazide + gliptin OR Metformin + gliclazide + exenatide or liraglutide HbA1c < 7.5% Monitor for deterioration HbA1c ≥ 7.5% HbA1c ≥7.5% HbA1c <7.5% Monitor for deterioration Page 97 Insulin therapy in Type 2 Diabetes (based on NICE CG87, Type 2 Diabetes, May 2009) When other measures do not keep HbA1c to < 7.5% (or other higher level agreed with the individual), discuss the benefits and risks of insulin therapy. Start insulin therapy if the person agrees. Note: Insulin may be considered unacceptable for employment, social, recreational or other personal issues, or obesity. When starting insulin therapy, use a structured programme employing active insulin dose titration that encompasses: structured education continuing telephone support frequent self-monitoring dose titration to target dietary understanding management of hypoglycaemia management of acute changes in plasma glucose control support from an appropriately trained and experienced healthcare professional. First-line: Human NPH insulin (intermediate-acting insulin) at bedtime or twice daily OR: Long-acting insulin analogue (insulin detemir, glargine) once daily if: lifestyle and compliance factors make more frequent injections inappropriate the patient is unable to self-inject NPH insulin target HbA1c is not reached or lifestyle is restricted because of hypoglycaemia significant hypoglycaemia occurs with NPH insulin Alternative Options: Biphasic human insulin (pre-mix) once or twice-daily particularly where HbA1c is above 9.0%. Biphasic human insulin analogues (pre-mix) if: immediate injection before a meal is preferred, or hypoglycaemia is a problem, or blood glucose levels rise markedly after meals . Intensifying Insulin Therapy (HbA1c levels not controlled) Monitor patients on: NPH or long-acting insulin analogue to identify the need for injections of short-acting insulin before meals or pre-mixed insulin Pre-mixed insulin once or twice daily to identify the need for injections of short-acting insulin before meals or a change to mealtime plus basal insulin regime. Endocrine System - Diabetes Page 98 Therapeutic Area Formulary Choices Cost for 28 unless stated Insulin aspart (NovoRapid) 3ml cartridge: £28.31 (5) 10ml vial: £16.28 (1) Insulin lispro (Humalog) 3ml cartridge: £28.31 (5) 10ml vial: £16.61 (1) Soluble Insulin 10ml vial: £7.48 (1) Rationale for decision / comments Insulins Short acting: (Human Actrapid) Intermediate acting: Long acting: Needles Biphasic Insulin Aspart (NovoMix 30) 3ml cartridge: £28.84 (5) Biphasic Insulin Lispro (Humalog Mix25) 3ml cartridge: £29.46 (5) Isophane Insulin (Human Insulatard) 3ml cartridge: £22.90 (5) 10ml vial: £7.48 (1) Insulin Glargine (Lantus) 3ml cartridge: £41.50(5) 10ml vial: £30.68 (1) Insulin Detemir (Levemir) 3ml cartridge :£42.00 (5) Omnican Fine 6mm/31 gauge £6.65 (100) 8mm/31 gauge £6.65 (100) (10mm/30 gauge £6.65 (100) 12mm/29 gauge £6.65 (100)) Endocrine System - Diabetes Choice of needle & lancet may be governed by specific insulin prescribed and injection technique. There is no clinical reason for recommending needles longer than 8mm in adults or 6mm in children/adolescents. Omnican Fine represents a cost-effective choice of needle where appropriate. Page 99 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments This section specifically cover drugs used for management of blood glucose, however the majority of patients with diabetes should be considered to be at high risk of CVD and hence should also be prescribed Simvastatin 40mg for primary prevention (unless C/I). For secondary prevention guidance see page 41 ATT meta-analysis : Aspirin for primary prevention of CVD Aspirin is not licensed for the primary prevention of vascular events but there remains the possibility that for particular sub-groups of individuals at higher CV risk (including conditions such as diabetes) the risk:benefit of aspirin is favourable. Until more evidence is available, the use of Aspirin 75mg for patients with diabetes should be based on an individual risk assessment. Biguanides Metformin st 1 line: Immediaterelease Sachets Metformin should be; 500mg tablets: £0.77 (28) 850mg tablets: £1.11(56) First line in Type 2 DM because of cardioprotective effect unless not overweight, rapid therapeutic response required or metformin C/I introduced at low dose and given with or after food to minimise GI adverse effects e.g. 500mg daily and gradually titrated to 2g per day (or 3g under specialist supervision). continued in patients with Type 2 DM who require Insulin, as Metformin reduces insulin requirements. Use with caution in those at risk of a sudden deterioration in kidney function 500mg sachets: £6.58 (60) 1000mg sachets: £13.16 (60) Metformin sachets for patients with swallowing difficulties are much less expensive than „special‟ liquid formulation. 500mg m/r tablets: £5.32 750mg m/r tablets: £6.40 1000mg m/rtablets: £8.52 Metformin MR is approved for patients who would otherwise stop Metformin therapy due to GI side effects. 80mg tablets: £0.95 (28) 40mg tablets: £3.36 (28) NICE CG87 1.5.2.4 Prescribe a sulfonylurea with a low acquisition cost (but not glibenclamide) when a sulfonylurea is indicated. nd 2 line: Modified release Sulphonylureas Gliclazide Normal third line option, if HbA1c remains at ≥ 7.5% HbA1c (or level agreed with individual) is to initiate insulin therapy (see page 98 in addition to metformin and sulphonylurea (or other dual oral therapy) in preference to adding other drugs to control blood glucose unless there is strong justification not to. Endocrine System - Diabetes Page 100 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments Glitazones (thiazolidinediones) Prescribing of Pioglitazone should be in line with MHRA / EMEA advice (December 2007 & February 2008) and NICE guidance (May 2008): Pioglitazone should not be started in people who: The incidence of heart failure is increased when Pioglitazone is combined with insulin Inform patient of risk of oedema and what to do if this happens. Closely monitor patients during treatment with pioglitazone for signs and symptoms of fluid retention. Discontinue pioglitazone if heart failure develops. Following consideration at Somerset Prescribing Forum (Nov 2011) it was agreed that generic versions of pioglitazone may be used for all indications ○ ○ are at higher risk of fracture have evidence of heart failure Thiazolidinediones Pioglitazone DPP-4 inhibitors DPP-4 inhibitor may be preferable to a glitazone: Continue gliptin only if there is a reduction of ≥0.5% points in HbA1c in 6 months (between 5 and 6 mmol/mol) 15mg tablets: £4.28 30mg tablets: £5.31 45mg tablets: £6.61 The PROACTIVE trial showed improvements in secondary outcomes. Pioglitazone is licensed for use with insulin Continue only if there is a reduction ≥ 0.5% points in HbA1c in 6 months Pioglitazone might be preferable to a DPP-4 inhibitor if there is marked insulin insensitivity, or if DPP-4 inhibitor is contraindicated or not tolerated. To prevent weight gain If the patient has not responded to, or not tolerated or has a contraindication to a glitazone NB Group 2 (LGV/PCV) drivers are required to notify DVLA if taking combination of gliptin with sulphonylurea Dose Adjustment in Renal Impairment Sitagliptin Mild – no dose adjustment needed Moderate: creatinine clearance ≥30 to <50ml/min), use sitagliptin 50mg once daily. Saxagliptin Reduce dose to 2.5mg in moderate to severe renal impairment Linagliptin No dose reduction required for linagliptin for patients with renal impairment Vildagliptin Reduce dose to 50mg once daily when CrCl <50ml/min Endocrine System - Diabetes CrCl <30ml/min or with end-stage renal disease requiring haemodialysis or peritoneal dialysis, use sitagliptin 25mg once daily. Page 101 Therapeutic Area Formulary Choices Cost for 28 unless stated Linagliptin 5mg tablets: £33.26 (28) Rationale for decision / comments Saxagliptin 5mg tablets: £31.60 2.5mg tablets: £31.60 Saxagliptin is is licensed for triple therapy with metformin & sulphonylurea and with insulin +/- metformin 100mg tablets: £33.26 50mg tablets: £33.26 25mg tablets: £33.26 Sitagliptin is licensed for triple therapy with metformin & sulphonylurea and with insulin +/- metformin Vildagliptin 50mg tablets: £31.76 (56) In dual combination with a sulphonylurea, the recommended dose of vildagliptin is reduced to 50mg once daily administered in the morning. In this patient population, vildagliptin 100mg daily was no more effective than vildagliptin 50mg once daily Repaglinide 500mcg tablets: £11.76 (90) 1mg tablets: £11.76 (90) 2mg tablets: £5.60 (90) Repaglinide may have a role in patients who fail to achieve target HbA1c with Metformin +/- Sulphonylurea, or when either of these two classes of drug are contra-indicated or not tolerated. Consideration should be given to a trial of Repaglinide before initiating a glitazone. Repaglinide may have a particular role in patients with an erratic lifestyle / irregular eating pattern. Repaglinide should be given in the 30 minute period before a meal, up to TDS. Acarbose 50mg tablets: £7.00 (90) 100mg tablets: £12.87 (90) Acarbose may have a role for a person unable to use other oral glucose lowering medications (contra-indicated or not tolerated) or in patients who fail to achieve target HbA1c with Metformin +/- Sulphonylurea. Titrate dose slowly to reduce incidence of GI adverse effects. Sitagliptin Other options: Rapid acting insulin secretagogue Endocrine System - Diabetes Page 102 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments GLP-1 mimetic Exenatide 5 mcg pre-filled pen: £68.24 10mcg pre-filled pen: £68.24 (60 doses in each pen) Exenatide and Liraglutide administered either daily or weekly (at appropriate dose) may be considered for triple therapy in addition to metformin and a sulphonylurea in people whose HbA1c is above agreed level if; Dietary advice should be given before starting therapy with these agents. For all dose regimens of exenatide & liraglutide treatment should be continued only if there is a reduction of ≥ 1.0% points in HbA1c in 6 months (between 10 and 11 mmol/mol) AND 3% loss of initial body weight in 6 months. BMI ≥ 35 kg/m in those of European descent (with appropriate adjustment for other ethnic groups) & other specific psychological or medical problems associated with high body weight, or 2 BMI < 35 kg/m and insulin therapy would have significant occupational implications, or where weight loss would benefit other significant comobidities such as sleep apnoea. 2 2mg vial : £73.36 (4) NB Group 2 (LGV/PCV) drivers are required to notify DVLA if taking combination of exenatide with sulphonylurea. Liraglutide 6mg/ml pre-filled pens 3ml: £78.48 (2) 3ml: £117.72 (3) Somerset Prescribing Forum approved the use of exenatide as adjunctive therapy to basal insulin (with or without metformin and/or pioglitazone in adults with Type 2 diabetes) Patients are expected to show 0.5% (6mmol/mol) reduction in HbA1c after 6 months to justify continuation. The addition of insulin to basal exenatide was rejected, patients where weight & HbA1c reduction stipulated by NICE have not been achieved after 6 months on exenatide should have exenatide stopped as not cost-effective. Liraglutide 1.2mg daily can be considered for dual therapy (in combination with metformin or a sulphonylurea) only if either metformin or a sulphonylurea is contraindicated or not tolerated, and a DPP-4 inhibitor is contraindicated or not tolerated. The combination of liraglutide with insulin is currently not commissioned for prescribing in Somerset and any recommendation of this combination should remain the responsibility of secondary care. Endocrine System - Diabetes Page 103 Guidance on the use of Blood Glucose Testing Strips based on NICE CG87 NICE national guidelines for the management of blood glucose levels in people with type 2 diabetes May 2008 1. 2. 2. 4. 5. In line with NICE guidelines, regular HbA1c testing (every two to six months) is the standard measurement. Pathology services in Somerset currently allow a minimum interval of 3 months between tests. An individual target HbA1c should be set with every patient. Blood glucose testing strips are primarily intended for people with diabetes treated with insulin. The frequency of testing should be as agreed between the health professional and the individual with diabetes. (Those converting to insulin need to test more frequently during the dose titration phase, which is usually managed by diabetes specialist nurses. Those with type 1 diabetes may need to test 4 or more times daily). Self monitoring in patients with Type 2 diabetes, who are controlled by diet or oral hypoglycaemic agents, should only be instigated as an integral part of a patient‟s self-management plan. The purpose of self-monitoring should be discussed along with agreement about how the results should be interpreted and acted upon. eg: To provide information on hypoglycaemia To assess changes in glucose control resulting from medication and lifestyle changes To monitor changes during illness To ensure safety during activities such as driving Urine glucose monitoring is an option if blood glucose monitoring is not acceptable.I Frequency of self-testing is variable but is likely to be higher if a patient is unwell or titrating their medication. One pack of 50 strips will be sufficient for 6-12 months for most patients in this group. Practices should assess at least annually the continuing benefit of the intervention including: Appropriate frequency of testing Use made of results obtained Impact on quality of life Self-monitoring skills Blood Glucose testing for Drivers when on insulin or oral medication carrying the risk of hypoglycaemia (DVLA) Patients must not have had more than one episode of disabling hypoglycaemia within 12 months & must inform DVLA if they develop impaired awareness of hypoglycaemia. Cars & Motorcycles For patients on sulphonylureas & gliptins there is no absolute requirement to test blood glucose. It may be appropriate to monitor blood glucose regularly and at times relevant to driving depending on other patient factors. Vocational Driving (Bus, coach & lorries) Drivers should monitor blood glucose at least twice daily at times relevant to driving Endocrine System - Diabetes Page 104 Therapeutic Area Formulary Choices Cost for 28 unless stated Rationale for decision / comments 25mcg tablets: £2.77 50mcg tablets: £1.67 100mcg tablets: £1.63 Monitoring requirements are for TFTs annually 100micrograms/5ml oral solution sugar free: £80.05 (100ml) Liquid is lactose free Carbimazole 5mg tablets: £19.98 (100) 20mg tablets: £46.89 (100) New patients should be counselled regarding warning signs of haematological toxicity. Monitoring requirements are for FBC, LFTS and TFTs annually Propylthiouracil 50mg tablets: £53.83 (56) Propylthiouracil is included only for patients intolerant to Carbimazole. Monitoring requirements are for FBC, LFTS and TFTs annually 6.2 Thyroid and anti-thyroid drugs Thyroid hormones Anti-thyroid hormones Levothyroxine NB. Under no circumstances should Carbimazole and Propylthiouracil be combined. 6.3 Corticosteroids Glucocorticoid therapy Prednisolone Prescribers are advised to use plain prednisolone. Enteric coated prednisolone has slower onset of action, less consistent blood levels and no proven evidence of GI protective effect. 1mg tablets: £0.78 (28) 5mg tablets: £0.96 (28) Patients on long-term oral corticosteroids, should be provided with a steroid warning card, these are available for practices to requisition from supplies at: Somerset Partnership Support Services Mallard Court Express Park Bridgwater TA6 4RN 01278 726964 Thyroid and Anti-thyroid drugs Page 105 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments 6.4 Sex Hormones 6.4.1 Hormone Replacement Therapy (HRT) HRT should no longer be used a first line intervention to prevent osteoporosis. Preparations marked with an asterisk are those licensed for osteoporosis as well as relief of menopausal symptoms, all other preparations are only licensed for menopausal symptoms. In view of increasing evidence that HRT may have harmful effects on CVD, this should be carefully discussed with patients at commencement and annually at review. Oral preparations recommended 1st line on cost, although transdermal route may be more appropriate for some patients e.g. diabetics HRT should be prescribed by brand name to avoid confusion Unopposed 1mg tablets: £5.04 (84) Elleste Solo tablets are first line on cost grounds. Elleste Solo oestrogen 2mg tablets: £5.34* (84) Cyclical combined Continuous combined: Evorel 25mcg patch: £3.42 (8) 50mcg patch: £3.88* (8) 75mcg patch: £4.12* (8) 100mcg patch:£4.50* (8) Evorel is recommended where a patch formulation is required, due to lower cost, range of doses available and patient acceptability of matrix patches. Elleste Duet 1mg tablets: £9.19 (84) 2mg tablets: £9.72* (84) Elleste Duet tablets are first line on cost grounds. Femoston 1/10mg tablets: £13.47* (84) 2/10mg tablets: £13.47* (84) Femoston (Estradiol and Dydrogesterone) offers alternative with a C21 progestogen. Kliovance Tablets: £13.20* (84) Kliofem Tablets: £11.43* (84) Continuous combined products should not be used until 12 months after the menopause. Irregular bleeding patterns may occur for the first few months and may persist for some women, requiring a move back to cyclical preparations and/or investigation. Femoston Conti Tablets: £20.36* (84) Kliovance has identical composition to Elleste Duet Conti, but at a lower cost Tibolone is now non-formulary. It is expensive and benefits over HRT have not been demonstrated for menopausal symptoms. The MHRA have advised of increased risk of stroke in older women (LIFT study) and in February 2009 noted the increased risk of recurrent breast cancer when tibolone was used for vaso-motor symptoms in women with a history of breast cancer (LIBERATE trial). Sex Hormones Page 106 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments Progestogens Norethisterone 5mg tablets: £2.18 (30) Norethisterone (15mg/day from days 5 to 26 of menstrual cycle) is an option for management of heavy menstrual bleeding, however it is not recommended as first line by NICE Clinical Guideline No.44. Norethisterone may cause more androgenic effects than some other progestogens. Medroxyprogesterone 2.5mg tablets: £1.84 (30) 5mg tablets: £1.23 (10) 10mg tablets: £2.47 (10) Medroxyprogesterone may produce less androgenic adverse effects than Norethisterone. Sex Hormones Page 107 Therapeutic Area Formulary Choices Cost (per pack as stated) Rationale for decision / comments 250mg/ml amp: £2.45 (1ml) Sustanon 250 is the testosterone injection of choice on grounds of costeffectiveness. Second line is Testosterone Enantate 250mg given every 4 weeks. Trough testosterone should be measured on the day of the 3rd Enantate injection to make sure patients are not being overdosed – target is a testosterone in the lower quartile of reference range, 8-13 nmol/L. The Enantate dosing interval range of 3-6 weekly is longer than that for Sustanon, which is usually 3-4 weekly. 6.4.2 Male sex hormones and antagonists Testosterone Sustanon 250 ® Testosterone Enantate 250mg/ml amp: £13.33 (1ml) Nebido 250mg/ml amp: £80.00 (4ml) Testogel 50mg/5g gel sachet: £31.11 (30) 50mg/5g gel: £32.00 (30g) Testim Striant SR 2% testosterone gel (10mg per application): £26.67 (60g) 30mg Mucoadhesive buccal tablets: £28.00 (60) Restandol 40mg capsules: £8.55 (30) Tostran 5-Alpha Reductase Inhibitors (5-ARIs) ® If neither is available Nebido injection lasts for 10-14 weeks - measuring trough testosterone weekly from 10 weeks will enable the dosing interval to be determined using the target range above. Nebido should be given with the patient lying in prone position ALL Testosterone products are included (except Intrinsa) are included in the formulary for the duration of the national shortage of injectable formulations. For non-injectable alternatives please see BNF 62 6.4.2 or Choosing a Testosterone Preparation information sheet for details. Intrinsa for females remains NON-FORMULARY Cross refer to section 7.4.1 for further details on the management of Lower Urinary Tract Symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), for which 5-ARIs are indicated. Finasteride 5mg tablets: £1.69 (28) Finasteride is the only recommended 5-ARI, due to the weight of clinical evidence and cost-effectiveness. Dutasteride (Avodart) is non-formulary following rejection by the T&ST D&TC 6.5 Hypothalamic and pituitary hormones and anti-oestrogens 6.5.2 Posterior pituitary hormones and antagonists Posterior pituitary hormones Sex Hormones Desmopressin 200mcg tablets: £10.96 (30) Desmopressin tablets are included in the formulary only for the treatment of nocturnal enuresis in line with NICE CG111: Nocturnal enuresis. Page 108 6.6 Drugs affecting bone metabolism Lifestyle interventions: Investigations: Nutrition (especially Calcium and Vitamin D intake) FBC Weight bearing exercise Plasma viscosity, Smoking cessation Calcium, LFTs, creatinine, Avoid excess alcohol TSH, Gamma GT, ? radiology to exclude other # causes. Testosterone in males (sex hormone + SHBG) Guidance on primary prevention of osteoporosis in postmenopausal women is provided in NICE TAG 160 See summary table p111 Guidance on secondary prevention of osteoporosis in postmenopausal women is provided by NICE TAG 161. See summary table p113 The March 2012 Somerset Prescribing Forum debated and then approved the off license use of Bisphosphonates (alendronate (1st) , risedronate(2nd) rd or ibandronate(3 ): o Patients who have sustained fragility fractures but currently excluded by NICE criteria o Patients deemed by clinicians at high risk of fragility fractures (including patients with Osteopenia if at high # risk) The evidence of benefit from Bisphosphonate and Strontium therapy comes from trials which ensured patients had intake of therapeutic doses of Calcium and Vitamin D, supplementation with Calcium and Vitamin D is therefore recommended for patients prescribed these drugs. Where Calcium and Vitamin D is recommended, a formulation providing Calc.Carb. 1500mg and Vit D 400iu per tablet should be prescribed. A range of products is included all now of similar price; the product chosen should be made according to patient preference & encourage concordance. Preparations such as Calcichew D3 or Calcium & Ergocalciferol BP do not provide evidence-based doses of the constituents and should normally not be prescribed. Calcium and Vitamin D should be considered for all women over age of 75 yrs The optimal period of treatment with bisphosphonates is not known, evidence of benefit has been measured for up to 5 years. NICE recommends research into the long-term effects and prescribers should be aware of the possible adverse effects on bone quality when bisphosphonates are taken for extended periods. Bisphosphonate ‘drug holidays’ No formal guidance exists on this topic which is advocated by some secondary care centres. Local policy is to follow MHRA alert & assess people individually. The absolute numbers of atypical stress fractures in patients on long-term bisphosphonates is very low; it is not at all clear whether these are because of BPP therapy or simply random events. Drugs affecting Bone Metabolism Page 109 Patient group Primary prevention of osteoporosis in postmenopausal women Formulary product Cost (per pack as stated) Rationale for decision / comments 70mg tablets: £0.79 (4) 70mg/100ml solution: £22.80 (4x100ml) Weekly alendronate is recommended first line for the primary prevention of osteoporotic fracture in susceptible postmenopausal women where specified combinations of BMD; age; independent risk factors or other indicator of low bone mineral density apply. The flow chart on p74 summarises the conditions. Independent risk factors considered: st 1 line: Alendronic Acid nd See Summary of NICE TAG 160 on page 111 2 line Risedronate 35mg 35mg tablets: £1.19 (4) rd 3 line Denosumab January 2012 Somerset Prescribing Forum approved Denosumab as 3rd line treatment before strontium for both primary & secondary prevention of osteoporosis in women 4th line: Strontium Ranelate 60mg/ml prefilled syringe: £183.00 (1) 120mg Injection NOT for osteoporosis 2g sachets: £27.08 (28) All with calcium and vitamin D supplement: See p.129 for full choice Jan 2013 – costeffective product: Accrete D3 Drugs affecting Bone Metabolism Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: £2.95 (60) Parental history of hip fracture Alcohol intake > 3 units daily Rheumatoid arthritis Indicators of low bone mineral density : BMI < 22 kg/m2 Ankylosing spondylitis Crohn‟s disease Prolonged immobility Untreated premature menopause Osteoporosis confirmed by DEXA scan is expected except by local agreement for women over 75 with 2 independent risk factors or other indicator of low BMD. Risedronate and etidronate are recommended as alternatives where alendronate is contra-indicated or not tolerated and Strontium is recommended where treatment with a bisphosphonate is not appropriate and specified BMD, age & risk factors apply. Raloxifene is not recommended as a treatment option for primary prevention of osteoporotic fractures. Page 110 PRIMARY PREVENTION OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN Based on NICE TA160 and NICE TA204 Clinical risk factors for fracture: A. Parental history of # hip B. Alcohol > 3 units daily (> 4 units if considering Denosumab) C. Rheumatoid arthritis AGE < 70 and 0 risk factors DO NOT TREAT AGE 75 + Plus 2 risk factors from A, B, C or other indicator of low BMD AGE 70 - 74 Plus 1 or more risk factors A, B or C or indicator of low BMD AGE 65 - 69 Plus 1 or more risk factors A, B or C NO DEXA required Refer for DEXA T score – 2.5 or worse Initiate weekly generic ALENDRONATE Refer for DEXA T score – 2.5 or worse Initiate weekly generic ALENDRONATE Alendronate C/I, intolerant or unable to comply Alendronate C/I, intolerant or unable to comply Initiate weekly generic ALENDRONATE Alendronate C/I, intolerant or unable to comply – try risedronate or etidronate C/I, intolerant or unable to comply with bisphosphonates REFER FOR DEXA T score- 4.0 or worse OR -3.0 or worse and 2 risk factors try Denosumab, Zoledronate or Strontium NO risk factors ONE risk factor TWO risk factors T score better than - 3.5 DO NOT TREAT T score - 3.0 or worse try risedronate or etidronate T score - 2.5 or worse try risedronate or etidronate NO risk factors DO NOT TREAT T score - 3.5 or worse try risedronate or etidronate C/I, intolerant or unable to comply with bisphosphonates ONE risk factor T score -3.5 or worse try risedronate or etidronate NO risk factors and T score - 4.5 or worse try Denosumab, Zoledronate or Strontium TWO risk factors and T score - 3.5 or worse try Denosumab, Zoledronate or Strontium TWO risk factors T score -3.0 or worse try risedronate or etidronate C/I, intolerant or unable to comply with bisphosphonates NO risk factors and T score > - 4.5 DO NOT TREAT ONE risk factor and T score - 4.0 or worse try Denosumab, Zoledronate or Strontium AGE < 65 Plus 1 risk factor from A, B or C AND one additional indicator of low BMD NO risk factors DO NOT TREAT ONE risk factor and T score - 4.5 or worse try Denosumab, Zoledronate or Strontium REFER FOR DEXA T score – 2.5 or worse Initiate weekly generic alendronate Alendronate C/I, intolerant or unable to comply DO NOT TREAT The NHS Somerset Formulary allows consideration of monthly ibandronate where compliance issues would otherwise prevent patient taking bisphosphonates TWO risk factors and T score - 4.0 or worse try Denosumab, Zoledronate or Strontium Page 111 Patient group Formulary product Secondary prevention of osteoporosis in postmenopausal women (See Summary of NICE TAG 161 on p.113) 1st line: Alendronic Acid 2nd-line Risedronate 35mg Cost for 28 unless stated st 70mg tablets: £0.79 (4) 70mg/100ml solution: £22.80 (4x100ml) 35mg tablets: £1.19 (4) rd 3 line Denosumab January 2012 Somerset Prescribing Forum approved Denosumab as 3rd line treatment before strontium for both primary & secondary prevention of osteoporosis in women 4th-line Strontium Ranelate or Raloxifene 60mg All with calcium and vitamin D supplement: See p.128 for full choice Jan 2013 – costeffectice product: Accrete D3 Drugs affecting Bone Metabolism Rationale for decision / comments 60mg/ml prefilled syringe: £183.00 (1) nd rd Bisphosphonates (1 alendronate, 2 risedronate, 3 ibandronate) are recommended first line for the secondary prevention of osteoporotic fracture in women with confirmed osteoporosis who have also sustained a clinically apparent osteoporotic fracture. In addition, in March 2012, Somerset Prescribing Forum approved the off license use of Bisphosphonates in patients with previous fragility fractures or deemed by clinicians at high risk of fragility fractures for patients with Osteopenia. NB Local agreement for women over 75 – DEXA not required. 2g sachets: £27.08 (28) Where bisphosphonate is not appropriate, denosumab, strontium or raloxifene may be used again dependent on BMD, age & other risk factors. 60mg tablets: £17.06 Teriparetide is a treatment option following assessment in secondary care where other therapies are not appropriate. Teriparetide is a RED drug under the traffic light classification. This information is summarised in the flow chart on p113 Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: £2.95 (60) The FRAX algorithm is a tool to calculate 10 year probablilty of hip and other major osteoporotic fractures using the same risk factors as NICE plus glucocorticoid use and smoking status http://www.shef.ac.uk/FRAX/?lang=en Page 112 SECONDARY PREVENTION OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN Clinical risk factors for fracture: A. Parental history of # hip B. Alcohol > 4 units daily C. Rheumatoid arthritis Based on NICE TAG161 and NICE TAG204 (Denosumab) (1.6) Intolerance of alendronate, risedronate or etidronate is defined as persistent upper GI disturbance occuring even though instructions for administration have been followed correctly and sufficiently severe for treatment to be stopped. Weekly generic Alendronate is recommended for postmenopausal women who are confirmed to have osteoporosis (central T score -2.5 or worse). For women over 75 years DEXA not required. (1.7) Intolerance of strontium is defined as persistent nausea or diarrhoea, either of which warrants discontinuation of treatment. (1.8) An unsatisfactory response is defined by a women having another fragility fracture despite adhering fully to treatment for 1 year and there is evidence of a decline in BMD below her pre-treatment baseline If alendronate is not appropriate i.e. contraindicated, intolerant, unable to comply or unsatisfactory response to treatment, options depend on combination of age, T score and independent clinical risk factors. 50 – 54 55 – 59 60 – 64 65 – 69 70 – 74 75 and older Refer for DEXA Refer for DEXA Refer for DEXA Refer for DEXA Refer for DEXA DEXA not required Alendronate not option: Treat with risedronate or etidronate 0 risk factor 1 risk factor 2 risk factors Not recommended - 3.0 - 2.5 - 3.0 - 3.0 - 2.5 - 3.0 - 3.0 - 2.5 - 3.0 - 2.5 - 2.5 - 2.5 - 2.5 - 2.5 - 2.5 - 2.5 - 2.5 * DEXA not required if indicators for low BMD exist, including: Consider Denosumab or Zoledronic acid Age If T-score not available (2.6) A fragility fracture is defined as a fracture sustained as the result of a force equivalent to the force of a fall from a height equal to, or less than, the height of an ordinary chair. Alendronate, second bisphosphonate, and Denosumab or Zoledronic acid not option: Treat with strontium or raloxifene Strontium or raloxifene not option: refer to secondary care assessment for teriparatide 2 fragility fractures or less Not recommended Not recommended Not recommended 0 risk factors 1 risk factor 2 risk factors More than 2 fragility fractures Not recommended - 3.5 - 3.5 - 4.0 - 3.5 - 3.5 - 4.0 - 3.5 - 3.5 - 4.0 - 3.5 - 3.0 - 4.0 - 3.5 - 3.0 - 3.0 - 2.5 - 4.0 - 3.5 - 3.0* - 2.5 - 2.5 - 4.0 - 3.5 Not recommended - 4.0 - 4.0 2 Low BMI (< 22kg/m ), inflammatory conditions such as ankylosing spondylitis or Crohn‟s disease, Conditions resulting in prolonged immobility, and untreated early menopause. NHS Somerset Formulary allows consideration of monthly ibandronate where compliance issues would otherwise prevent patient taking bisphosphonates Drugs affecting Bone Metabolism Page 113 Patient group Formulary product Cost (per pack as stated) Rationale for decision / comments Steroid induced osteoporosis (6 months at >7.5mg Prednisolone equivalent) Alendronic Acid 70mg tablets: £0.79 (4) 70mg/100ml solution: £22.80 (4x100ml) To reduce the risk of osteoporosis doses of oral corticosteroids should be as low as possible and courses of treatment as short as possible. The risk of osteoporosis may be related to cumulative dose of corticosteroids; even intermittent courses can therefore increase the risk. The greatest rate of bone loss occurs during the first 6–12 months of corticosteroid use and so early steps to prevent the development of osteoporosis are important. Long-term use of high-dose inhaled corticosteroids may also contribute to corticosteroidinduced osteoporosis Patients taking (or who are likely to take) an oral corticosteroid for 3 months or longer should be assessed and where necessary given prophylactic treatment; those aged over 65 years are at greater risk. Patients taking oral corticosteroids who have sustained a low-trauma fracture should receive treatment for osteoporosis. The therapeutic options for prophylaxis and treatment of corticosteroid-induced osteoporosis are the same: Plus calcium and vitamin D supplement: See p.128 for full choice Jan 2013 – costeffectice product: Accrete D3 Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: £2.95 (60) a bisphosphonate calcitriol [unlicensed indication] hormone replacement: HRT in women, testosterone in men [unlicensed indication] Breast cancer treatment - induced bone loss: See: ‘Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK expert group (2008)’ Drugs affecting Bone Metabolism Page 114 Patient group Formulary product Cost (per pack as stated) Rationale for decision / comments Osteoporosis in Men Alendronic Acid 70mg tablets: £0.79 (4) 70mg/100ml solution: £22.80 (4x100ml) NB All young men with osteoporosis should be referred for specialist advice. Denosumab 60mg/ml prefilled syringe: £183.00 (1) In Nov 2011 Somerset Prescribing Forum agreed to approve use of denosumab in men when NICE criteria are fulfilled. Prescribers should ensure that patients are aware that the product is being used outside of its licence. Strontium 2g sachets: £27.08 (28) Licensed for use in men at increased of fracture, and approved for use in men with primary osteoporosis who cannot have, cannot tolerate or have failed oral bisphosphonate treatment. Plus calcium and vitamin D supplement: See p.128 for full choice Jan 2013 – costeffectice product: Accrete D3 Drugs affecting Bone Metabolism Alendronate 70mg is not licensed in men, but is used outside of license for this indication; prescribers should ensure that patients are aware of unlicensed nature. Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: £2.95 (60) Page 115 Patient group Formulary product Cost (per pack as stated) Rationale for decision / comments Primary Prevention of osteoporosis Frail elderly women Calcium and Vitamin D supplement See p.128 for full choice As above Indicated for those at increased fracture risk e.g. patients in Nursing or residential homes. Jan 2013 – costeffectice product: Accrete D3 Drugs affecting Bone Metabolism Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: £2.95 (60) Page 116 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 7: Obstetrics, gynaecology, and urinary-tract disorders Top 7.2 Treatment of vaginal and vulval conditions Preparations for vaginal atrophy Estradiol as Ovestin 0.1% cream £4.45 (15g) as Vagifem 10mcg pessaries £16.72 (24) Topical oestrogens should be used in the lowest effective amount to minimize systemic absorption. Patients should be reviewed at least annually to re-assess the need for continued treatment and to monitor for symptoms of endometrial hyperplasia or carcinoma in women with a uterus. Patients should have the opportunity to choose a product suited to them although there is no evidence of difference in effect. Long term treatment may be required as symptoms can recur on cessation of therapy Vagifem 25mcg pessaries being discontinued February 2013 Vaginal and vulval infections Fungal infections: First line: Fluconazole (oral) 150mg capsule: £0.80 (1) Fluconazole is recommended as first line due to ease of use and costeffectiveness. Available as a generic. Second line: Clotrimazole (intra-vaginal and/or topical) 500mg pessary: £3.38 (1) 2% cream / 500mg pessary combipack: £5.21 (1) 1% Cream: £1.41 (20g) Clotrimazole pessaries are second line due to higher cost. NB: available OTC, often at cost lower than the NHS prescription charge. Gynaecology and Urinary-tract Disorders Page 117 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 7.3 Contraceptives Women requiring contraception should be given information about and offered a choice of all methods including LARC (long-acting reversible contraception). Interactions The effectiveness of combined oral contraceptives, progestogen-only oral contraceptives, contraceptive patches, and vaginal rings can be considerably reduced by interaction with drugs that induce hepatic enzyme activity (e.g. carbamazepine, eslicarbazepine, modafinil, nelfinavir, nevirapine, oxcarbazepine, phenytoin, phenobarbital, primidone, ritonavir, St John’s Wort, topiramate, and, above all, rifabutin and rifampicin). Hormonal contraceptives and antibacterials that do not induce liver enzymes Advice on interactions between combined hormonal contraceptives and antibacterials that do not induce liver enzymes has been updated to take into account the recommendations of the Faculty of Sexual and Reproductive Healthcare Clinical Guidance: Drug Interactions with Hormonal Contraception (January 2011). Additional contraceptive precautions are no longer necessary when antibacterials that do not induce liver enzymes are taken with combined oral contraceptives, (unless diarrhoea or vomiting occurs), contraceptive patches or vaginal rings. Click here for more information. Some other interactions of hormonal contraceptives have been updated in Appendix 1 of the BNF: Interactions (under Oestrogens and Progestogens) Gynaecology and Urinary-tract Disorders Page 118 Therapeutic Area Formulary product Cost (per pack as stated) Low strength Loestrin 20 (Ethinylestradiol / norethisterone) 20mcg/1mg tablets: £2.70 (63) Standard strength: Ovranette (Ethinylestradiol / norgestrel) 30mcg/150mcg tablets: £2.20 (63) Rationale for decision / comments Combined hormonal contraceptives as Rigevidon ® Rigevidon is a cost-effective alternative to Ovranette. Cilest (Ethinylestradiol / norgestimate) 35mcg/250mcg tablets: £7.16 (63) Femodene (Ethinylestradiol / gestodene) 30mcg/75mcg tablets : £6.73 (63) NB: Third-generation COCs containing the progestogens gestodene or ® desogestrel (e.g. Femodene ) are associated with a higher risk of VTE. as Millinette 30/75 30mcg/75mcg tablets: £4.85 (63) Millinette 30/75 is a cost-effective alternative to Femodene ® ®Longtec Cerelle 75mcg is a cost-effective alternative to Cerazette Tri-Novum (triphasic) (Ethinylestradiol / norethisterone) 35mcg/500mcg, 35mcg/750mcg, & 35mcg/1mg: £3.46 (63) Micronor (Norethisterone 350mcg) Tablets: £2.11 (84) Femulen (Etyndiol acetate 500mcg) Tablets: £3.31 (84) ® Progestogen-only contraceptives (POPs) 30mcg/150mcg tablets: £1.89 (63) Gynaecology and Urinary-tract Disorders ® ® Pfizer is discontinuing Femulen (ethynodiol diacetate) tablets 500mg 3 x 28 once current stocks are exhausted, expected to be by the end of March 2013. Page 119 Therapeutic Area Formulary product Long-acting reversible contraception (LARC) Medroxyprogesterone ® as Depo-Provera Etonogestrel ® as Nexplanon Emergency Hormonal Contraception (EHC) Cost (per pack as stated) LARC methods are more cost-effective than COC pill even at one year. 150mg/ml prefilled syringe: £6.01 (1) ® ® 68mg implant: £79.46 Nexplanon is bioequivalent to Implanon (discontinued), it has the ® same release rate and 3-year duration of action. Nexplanon also has a different application device and insertion technique. Please visit http://www.nexplanontraining.co.uk/ or contact MSD directly for training. 1500mcg tablet: £5.20 (1) Available via PGD through many pharmacies across Somerset, free of charge to those who are exempt from prescription charges and at the standard prescription charge to those who are not exempt Levonorgestrol 1500mcg is the first-line oral preparation for patients presenting within 72 hours of UPSI or contraceptive failure. Levonorgestrel 1500mcg tablet as Levonelle 1500 Rationale for decision / comments DO NOT PRESCRIBE AS THE OTC PREPARATION: Levonelle OneStep (as over twice the cost of the POM product.) Pre-operative treatment of uterine fibroids Ulipristal acetate 30mg tablet ▼ as EllaOne 30mg tablet: £16.95 (1) Patients presenting between 72 hours and 120 hours may be offered the choice of ulipristal acetate or intrauterine device and the risks and benefits of each method should be discussed with the patient. Ulipristal is licensed for emergency contraception within 120 hours (5 days) after unprotected sexual intercourse (UPSI). Pregnancy should be excluded before ulipristal is taken. Ulipristal acetate 5mg tablet ▼ as Esmya 5mg tablet: £ 125.71 (28) Ulipristal acetate is indicated for pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age over the age of 18. Approved at Somerset Prescribing Forum as an AMBER drug for a maximum of 3 months treatment only with the acute trust to supply the first month. Pregnancy should be precluded prior to treatment and a non hormonal contraceptive method is recommended during treatment Gynaecology and Urinary-tract Disorders Page 120 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 7.4 Drugs for genito-urinary disorders 7.4.1 Drugs for urinary retention Related guidance: NICE Clincal Guideline CG97 (2010): Lower urinary tract symptoms Management of Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) involves: Alpha-blockers – as below, cross refer to CV section for recommendations on use of alpha-blockers in hypertension 5-alpha reductase inhibitors – cross refer to section 6.4.2. for details Evidence from the MTOPS study which combined Finasteride with Doxazosin showed that dual-therapy provides additional symptomatic benefit for patients and delays the progression of BPH, compared to monotherapy. Further guidance on management of LUTS associated with BPH is available on CD-ROM from the British Association of Urological Surgeons. Alpha-blockers First-line: Second-line: Doxazosin as modifiedrelease (m/r) (for initiation only Doxadura brand 4mg m/r tabs: £5.00 (28) as standard tablets for continuation) 4mg tablets: £1.35 (28) Doxadura brand 4mg tablets: £1.17 Tamsulosin MR capsules as Tabphyn MR ® Gynaecology and Urinary-tract Disorders Patients should be initiated on the 4mg MR preparation and then switched to the more cost-effective standard 4mg tablet once stabilised e.g. after one to two months therapy. 4mg m/r tabs £4.50 400mcg m/r capsules: £5.16 (30) Tamsulosin has greater selectivity for the alpha-receptors predominant in the urinary tract; however the clinical significance of this remains debateable. In view of this and its greater cost, Tamsulosin should only be used where there is intolerance to Doxazosin. Generic Tamsulosin capsules are now available. Available OTC. 400mcg m/r capsules: £4.39 (30) Tamsulosin MR tablets (Flomaxtra XL) are not included in the formulary Page 121 Therapeutic Area 7.4.2 Formulary product Cost (per pack as stated) Rationale for decision / comments Drugs for urinary frequency, enuresis, and incontinence Related guidance: NICE Clinical Guideline CG111 (2010): Nocturnal enuresis – the management of bedwetting in children and young people Before initiating treatment a thorough investigation of the underlying cause of incontinence should be carried out and drugtreatments should be reviewed 4 weeks after starting. If there is no or suboptimal improvement or intolerable adverse effects change the dose, or try an alternative antimuscarinic drug, and review again 4 weeks later. Thereafter, treatments should be reviewed annually. st 1 line: Oxybutynin (immediate release) Tolterodine (immediate release) 2.5mg tablets: £3.39 (56) 5mg tablets: £3.78 (56) 1mg tablets: £5.33 (56) 2mg tablets: £5.64 (56) As per NICE guidance Oxybutynin (non-MR) is recommended as the first line antimuscarinic for managing urinary incontinence as a result of detrusor instability on the basis of its good efficacy and low cost. Not recommended in frail, elderly women. Research has shown that concordance after 3 years is less than 10% regardless of class of drug use with little to differentiate treatment options (Shamliyan T, et al. Benefits and harms of pharmacologic treatment for urinary incontinence in women. A systemic review. Ann Intern Med 2012; 156:861-74) nd 2 line: Oxybutynin MR 5mg m/r tablets: £13.77 (30) 10mg m/r tablets: £27.54 (30) Tolterodine MR 4mg m/r capsules: £25.78 (28) Trospium (immediate release) as Flotros® 20mg tablets:£18.20 (60) TrospiumMR as Regurin XL® 60mg tablets: £23.05 Propiverine (immediate release) 15mg tablets: £18.00 (56) Darifenacin 5mg tablets: £20.90 (28) Gynaecology and Urinary-tract Disorders Oxybutynin MR, Trospium & Trospium MR, Solifenacin and Tolterodine MR are recommended as second line alternatives for use when antimuscarinic adverse effects such as dry-mouth have are problematic and affect patient compliance. Page 122 Therapeutic Area rd 3 line Non oral therapy Formulary product Cost (per pack as stated) Rationale for decision / comments Solifenacin 5mg tablets: £27.62 (30) 10mg tablets: £35.91 ( 30) Evidence indicated that higher dose of solifenacin is more likely to cause side effects than tolterodine MR or Trospium MR Fesoterodine 4mg m/r tablets: £25.78 (28) 8mg m/r tablets: £25.78 (28) Mirabegron 25mg tablets: £27.06 (28) 50mg tablets: £27.06 (28) To use as an option where antimuscarinic drugs are contra-indicated or clinically ineffective or side-effects are unacceptable, before surgery or botox therapy Lower dose used where hepatic or renal impairment exists Oxybutinin Patches Oxybutinin 3.9mg/24 hours: £27.20 (8) Oxybutinin patches remain an option at any stage for those unable to tolerate oral therapy or for patients with swallowing problems to avoid the need for unlicensed liquid formulations. Patches are applied twice weekly to clean, dry, unbroken skin on abdomen, hips or buttocks. For the use of desmopressin in the treatment of nocturnal enuresis, please refer to section 6.5.2 Posterior pituitary hormones and antagonists 7.4.5 Drugs for erectile dysfunction The drugs for the treatment of erectile dysfunction in men listed below are considered appropriate for initiation in general practice, where patients meet the following criteria for NHS prescribing and are endorsed as “SLS”: Diabetes mellitus Single gene neurological disease Multiple sclerosis Spina Bifida Parkinson's disease Spinal cord injury Poliomyelitis Dialysis for renal failure Prostate Cancer Radical pelvic surgery, prostatectomy or kidney transplant Severe pelvic injury Were receiving Caverject , Erecnos , MUSE , Viagra or Viridal for ED at NHS expense on 14-09-1998 First-line: Vardenafil Gynaecology and Urinary-tract Disorders 5mg tablets: £7.56 (4) 10mg tablets: £14.08 (4) 20mg tablets: £23.48 (4) ® ® ® ® ® NICE CG66 states that all PDE5‟s are effective and the evidence is not sufficient to distinguish between them. Vardenafil is first line as most cost effective option. Page 123 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Second-line Sildenafil 25mg tablets: £16.59 (4) 50mg tablets: £21.27 (4) 100mg tablets: £23.50 (4) All PDE5 inhibitors are contra-indicated in patients taking nitrates. Use after prostate surgery prophylactically: not considered to be in accordance with Health Service Circular 1999/148 therefore cannot to be prescribed on FP10 Treat as RED if recommended by a relevant specialist. Third-line: Tadalafil 10mg tablets: £26.99 (4) 20mg tablets: £26.99 (4) Tadalafil is offered as a third line option for patients who are intolerant or unresponsive to Sildenafil and Vardenafil. It should not be used in patients taking nitrates. Cialis Once Daily is non-formulary Gynaecology and Urinary-tract Disorders Page 124 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 8: Malignant disease and immunosupression Top 8.3 Sex hormones and hormone antagonists in malignant disease Hormone antagonists Anastrazole 1mg tablets: £1.94 (28) ® Prostate cancer & Gonadorelin analogues First-line: as Nastrosa 1mg tablets: £1.75 (28) Letrozole 2.5mg tablets: £2.20 (14) £84.68 (28) Anastrazole is recommended as an adjuvant to early oestrogen-receptorpositive breast cancer and is supported by a Shared Care Protocol. Monthly injections of triptorelin and goserelin were approved at the March 2010 meeting of the Somerset prescribing Forum for use within licensed indications re: Breast Cancer – endometriosis and uterine fibroids. Triptorelin as Decapeptyl SR Second-line: Anastrazole is recommended as an adjuvant to early oestrogen-receptorpositive breast cancer and is supported by a Shared Care Protocol. Goserelin Malignant Disease and Immunosuppression 3mg (4.2mg) vial: £69.00 (1) 11.25mg (15mg) vial: £207.00 (1) 22.5mg (28mg) vial: £414.00 (1) Decapeptyl SR is recommended as the first line GnRH anaologue within its licensed indications for prostate cancer. Patients with a life expectancy of >12 months who do not requiring 3monthly reviews should be considered for a switch from the 3-monthly (15mg) to the 6-monthly (28mg) preparation. 3.6mg PFS: £65.00 (1) 10.8mg PFS: £235.00 (1) Goserelin is considered as second line GnRH analogue for use within its licensed indications, where Decapeptyl is not appropriate. Page 125 BNF Chapter 9: Nutrition and blood Top 9.1 Anaemias and some other blood disorders Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Iron deficiency Ferrous fumarate 210mg tablets: £1.44 (100) 322mg tablets: £0.95 (28) 210mg Ferrous fumarate provides 68mg elemental iron, usual dose 210mg tds. 322mg Ferrous fumarate provides 100mg elemental iron, usual dose 322mg bd Ferrous sulphate is no longer included in the formulary as Ferrous fumarate provides equivalent at lower cost. For reference 200mg Ferrous sulphate tablets provide 65mg elemental iron. Syrup As Fersamal as Galfer Megaloblastic anaemia 140mg/5ml: £3.73 (200ml) 140mg/5ml £5.33 (300ml) Folic acid 400mcg tablets: £2.71 (90) 5mg tablets: £0.97 (28) Hydroxocobalamin 1mg/ml injection: £2.83 (5) 400mcg daily is indicated for prevention of neural tube defects 9.2 Fluids and electrolytes Potassium Salts Oral rehydration therapy Potassium chloride Electrolade 600mg m/r tablets: £1.90 (100) Sachets: £1.97 (6) Sachets: £4.99 (20) Electrolade offers a lower cost alternative to Dioralyte Chewable tablets: £7.25 (100) Evidence for efficacy of Calcium supplements is in combination with Vitamin D, there should be few situations where Calcium alone is indicated. 9.5 Minerals Calcium supplements Nutrition and Blood Calcium carbonate as Adcal Page 126 9.6 Vitamins Vitamin D Colecalciferol 800IU as Fultium as Desunin Nutrition and Blood 800IU capsules: £3.60 (30) Vitami D deficiency can occur in people whose exposure to sunlight is limited and in those whose diet is deficient in vitamin D but there is little agreement on what minimum blood levels should be and evidence base for supplementation is poor (except rickets). Levels will be reduced during winter months. Ergocalciferol or colecalciferol may be given in a dose of 20mcg (800IU daily by mouth. Higher doses may be necessary for severe deficiency.If recommended by secondary care there is an agreement that they will be responsible for supplying the supplement for its whole duration and primary care should not be asked to prescribe. Capsules contain arachis oil and must not be taken by people with peanut allergy, and gelatine 800IU tablets: £ 3.60 (30) Tablet version of colecalciferol – included for option to capsules which may be crushed for patients wih swallowing problems. Dose equivalent to 20microgram vitamin D3 Page 127 Vitamin D supplements with Calcium Calcium and vitamin D should be considered as an intervention to reduce fracture risk for all women over 75 yrs. Calcium and Vitamin D: Calcium & Ergocalciferol tablets BP are non-formulary as they provide an inadequate dosage for most patients. st 1 line: Accrete D3 Tablets: £2.95 (60) A range of Calcium and Vitamin D products are included to provide a range of flavours & formulation to encourage concordance. Accrete is currently the most cost-effective choice however a range of products is included for patient choice. Chewable tablets:£3.65 (56) £7.30 (112) Caplet: £3.65 (112) Dose AdCal D3 caplets is 2bd 2nd line: Adcal D3 or Adcal D3 Dissolve or Soluble tablets: £4.99 (56) Calcichew D3 Forte Chewable tablets: £4.24 (60) or Calceos Chewable tablets: £3.58 (60) ® Calcichew D3 Caplets: £7.43 (100) More costly than other products in the class & provides lower dose of colecalciferol. Vitamin K1 Phytomenadione 10mg/ml ampoule: £3.78 (10) 2mg/0.2ml ampoule: £4.71 (5) For use in the management of haemorrhage due to Warfarin, cross refer to anticoagulant section of formulary. MultiVitamin Preparations Dialyvit Nutrition and Blood Approved at May 2012 Prescribing Forum only for patients receiving renal dialysis. Unlicensed in UK – order supplies from USA Page 128 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 10: Musculoskeletal and joint diseases Top 10.1 Drugs used in rheumatic diseases and gout Related guidance: NICE Clinical Guideline CG59 (2008): Osteoarthritis (a summary of which can be found on page 132) Non-steroidal antiinflammatory drugs (NSAIDs) NICE recommends cytoprotection with PPIs for patients who require systemic NSAIDs. Recommended PPIs are: Lansoprazole 15mg capsules; Omeprazole 20mg capsules or Pantoprazole 20mg tablets. Risk of GI bleeds is higher for slow release formulations. Note that all NSAIDs should be prescribed at the minimum effective dose for the minimum period in order to limit cardiovascular, renal and GI toxicity. Consider trial of topical NSAIDs before moving to systemic NSAID for Osteoarthritis. First-line: Ibuprofen 200mg tablets: £3.01 (84) 400mg tablets: £3.01 (84) 600mg tablets: £6.57 (84) Ibuprofen is 1st choice on grounds of safety and cost Second-line: Naproxen 250mg tablets: £1.43 (28) 500mg tablets: £2.36 (28) Naproxen EC tablets are non-formulary, evidence that EC reduces GI events is poor and they are three times the price of standard tablets. Diclofenac sodium 25mg ec tablets: £0.78 (28) 50mg ec tablets: £0.80 (28) CV risks associated with diclofenac were statistically significantly increased at both high and low doses this included doses less than 100 mg/day (close to the maximum recommended dose for over-the-counter diclofenac products).If any NSAID is essential in patients with high CV risk consider Ibuprofen or Naproxen instead. Diclofenac MR preparations are non-formulary, on grounds of cost. Naproxen in a “bd” regime may be alternative. Note all standard generic Diclofenac sodium tablets are EC, there is no cost-premium for prescribing these. Third-line: COX-2 selective NSAIDs NICE recommends cytoprotection with PPIs for patients who require systemic COX-2s. Recommended PPIs are: Lansoprazole 15mg capsules or Omeprazole 20mg capsules Note that all NSAIDs including COX-2s should be prescribed at the minimum effective dose for the minimum period in order to limit cardiovascular, renal and GI toxicity. Consider trial of topical NSAIDs before moving to systemic COX-2 for Osteoarthritis. First-line: Meloxicam 7.5mg tablets: £1.25 (30) 15mg tablets: £1.48 (30) Note Etoricoxib and Celecoxib are non-formulary Musculoskeletal system Page 129 Therapeutic Area Formulary product Cost (per pack as stated) Rubefacients and topical NSAIDs Algesal Cream: £1.21 (50g) Transvasin Cream: £1.43 (40g) Ibuprofen as Fenbid 5% gel: £1.50 (100g) 10% gel £4.00 (100g) Piroxicam 0.5% gel: £5.06 (112g) Rationale for decision / comments NICE CG59 advises that Paracetamol and/or Topical NSAIDs should be considered AHEAD of oral NSAIDs for OSTEOARTHRITIS Topical NSAIDs should be considered for use in addition to core treatment for knee or hand inflammation. For patients using large volumes of topical NSAIDs, Fenbid 5%gel is the most cost-effective. Topical ketoprofen is no longer recommended following a Drug Safety Update warning about the risk of photosensitivity reactions after exposure to direct sunlight, uv lamps, etc. Felbinac (Traxam) and Diclofenac (Voltarol) gels / foams are nonformulary Capsaicin Musculoskeletal system 0.025% cream £17.71 (45g) 0.075% cream £14.58 (45g) Topical capsaicin should be considered as an adjunct to core treatment for knee or hand osteoarthritis Page 130 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Gout Guidelines on management of gout available from The British Society for Rheumatology and British Health Professionals in Rheumatology: http://rheumatology.oxfordjournals.org/cgi/reprint/kem056av1 Acute attacks: First-line: Second-line: Naproxen See p 129 for prices Oral NSAIDs at maximum doses are the drugs of choice where there are no contra-indications. NICE recommends cytoprotection with PPIs for patients who require systemic COX-2s. See above Colchicine can be an effective alternative to NSAIDs, but has a slower onset of action. To reduce risk of diarrhoea it should be used in doses of 500mcg bd to qds. Colchicine 500mcg tablets: £36.13 (100) First-line Allopurinol 100mg tablets: £1.00 (28) 300mg tablets: £1.06 (28) Allopurinol is first line therapy for lowering uric acid. In uncomplicated gout, therapy should be started if a second attack or further attacks occur within 1 year. Commence 1-2 weeks after inflammation of acute attack has settled. Treatment should be initiated with 50-100mg/day and increased at 50-100mg increments every few weeks, adjusted in necessary for renal function, until the therapeutic target (Serum Uric Acid < 300mol/litre) is reached. Maximum in severe conditions 900mg/day in divided doses. If mild/moderate renal impairment: seek further advice. Second-line: Febuxostat 80mg tablets: £24.36 (28) 120mg tablets: £24.36 (28) Febuxostat is recommended as an option for the management of chronic hyperuricaemia in gout only when allopurinol is not tolerated at an effective dose or for whom allopurinol is contra-indicated. NICE TA164 Sulfinpyrazone 100mg tablets: £41.25 (84) 200mg tablets: £79.00 (84) Uricosuric therapy with Sulfinpyrazone (usually 200-600mg/day) may be an appropriate second line option for patients with normal renal function who are under-excretors of uric acid and those resistant to, or intolerant of, Allopurinol. For those with mild/moderate renal impairment seek further advice. Long term control: Musculoskeletal system Page 131 Management of Osteoarthritis NICE CG59 (2008): quick reference summary Oral analgesics Therapy options for OA are summarised in the following: Healthcare professionals should consider offering paracetamol for pain relief in addition to core treatment (see figure 2); regular dosing may be required. Paracetamol and/or topical nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered ahead of oral NSAIDs, cyclo-oxygenase 2 (COX-2) inhibitors or opioids. oral NSAIDs including COX-2 inhibitors opioids capsaicin intra-articular corticosteroid injections paracetamol supports and braces topical NSAIDs education, advice, information access shockabsorbing shoes or insoles strengthening exercise aerobic fitness training assistive devices weight loss if overweight/obese TENS manual therapy (manipulation and stretching) Musculoskeletal system local heat and cold joint arthroplasty If paracetamol or topical NSAIDs are insufficient for pain relief for people with osteoarthritis, the addition of opioid analgesics should be considered with Tramadol considered first line. Risks and benefits should be discussed, particularly in elderly people. If a strong opioid is needed, its use should be relatively short term pending surgical or other specialist referral. Regular follow-up is needed to assess analgesic efficacy and minimise unwanted effects. Topical treatments Healthcare professionals should consider offering topical NSAIDs for pain relief in addition to core treatment (see figure 2) for people with knee or hand osteoarthritis. Topical NSAIDs and/or paracetamol should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids. Topical capsaicin should be considered as an adjunct to core treatment for knee or hand osteoarthritis. Rubefacients are not recommended for the treatment of osteoarthritis. Page 132 NSAIDs and highly selective COX-2 inhibitors Although NSAIDs and COX-2 inhibitors may be regarded as a single drug class of „NSAIDs‟, these recommendations continue to use the two terms for clarity, and because of the differences in side-effect profile. The recommendations in this section are derived from extensive health-economic modelling, which included December 2007 NHS drug tariff costs. This guideline replaces the osteoarthritis aspects only of NICE technology appraisal guidance 27. The guideline recommendations are based on up-to-date evidence on efficacy and adverse events, current costs and an expanded health-economic analysis of cost effectiveness. This has led to an increased role for COX-2 inhibitors, an increased awareness of all potential adverse events (gastrointestinal, liver and cardio-renal) and a recommendation to co-prescribe a proton pump inhibitor (PPI). Where paracetamol or topical NSAIDs are ineffective for pain relief for people with osteoarthritis, then substitution with an oral NSAID/COX-2 inhibitor should be considered. Where paracetamol or topical NSAIDs provide insufficient pain relief for people with osteoarthritis, then the addition of an oral NSAID/COX-2 inhibitor to paracetamol should be considered. Oral NSAIDs/COX-2 inhibitors should be used at the lowest effective dose for the shortest possible period of time. When offering treatment with an oral NSAID/COX-2 inhibitor, the first choice should be either a standard NSAID or a COX-2 inhibitor (other than etoricoxib 60 mg). In either case, these should be co-prescribed with a PPI, choosing the one with the lowest acquisition cost. All oral NSAIDs/COX-2 inhibitors have analgesic effects of a similar magnitude but vary in their potential gastrointestinal, liver and cardio-renal toxicity; therefore, when choosing the agent and dose, healthcare professionals should take into account individual patient risk factors, including age. When prescribing these drugs, consideration should be given to appropriate assessment and/or ongoing monitoring of these risk factors. If a person with osteoarthritis needs to take low-dose aspirin, healthcare professionals should consider other analgesics before substituting or adding an NSAID or COX-2 inhibitor (with a PPI) if pain relief is ineffective or insufficient. Nutraceuticals The use of glucosamine or chondroitin products is not recommended for the treatment of osteoarthritis. Intra-articular injections Intra-articular corticosteroid injections should be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with osteoarthritis. Intra-articular hyaluronan injections are not recommended for the treatment of osteoarthritis. Musculoskeletal system Page 133 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 11: Eye Top 11.3 Anti-infective eye preparations Antibacterials Chloramphenicol 0.5% drops: £1.65 (10ml) 1% ointment: £1.62 (4g) See Infection management guidance for appropriate clinical indications. Chloramphenicol drops and ointment are now both available OTC at a cost lower than NHS prescription charge but restrictions apply to sales. ® Fusidic acid (Fucithalmic ) is non-formulary Antivirals Aciclovir 3% ointment: £9.34 (4.5g) 11.4 Corticosteroids and other anti-inflammatory preparations Corticosteroids Other anti-inflammatory products As advised by secondary care Sodium cromoglicate 2% drops: £1.80 (13.5ml) Available OTC. Prescribe 13.5ml size. 5ml and 10ml pack sizes are OTC products, and are more expensive when being used regularly. 11.5 Mydriatics and cycloplegics Mydriatics and cyloplegics As advised by secondary care 11.6 Treatment of glaucoma Glaucoma As advised by secondary care First line: Latanoprost Eyes Where a prostaglandin analogue is indicated for reducing IOP, Latanoprost is the recommended first line agent on grounds of cost (generic form available) and ocular tolerability. Agreed by both T&S & YDH D&TC & Somerset Prescribing Forum Sept 2012. Patients currently using other forms of prostaglandin analogues may be reviewed when seen routinely by secondary care. Page 134 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 0.3% drops £1.12 0.5% drops: £0.81 (10ml) 1% drops: £0.94 (10ml) Treatment for dry eyes associated with tear deficiency should normally commence with the least viscous agent e.g. Hypromellose 0.3% drops and work through alternatives in increasing order of viscosity. 11.8 Miscellaneous ophthalmic preparations Dry eyes: Hypromellose Lubricant Carbomer 0.2% eye gel Brand Clinitas Presentation 10g tube Carmellose: 1% drops are significantly less expensive than 0.5% Carmize 1% 30 x 0.4ml single dose unit 60 x 0.4ml single dose unit £3.00 reuse up to 12 hrs £6.00 reuse up to 12 hrs For 0.5% cost is least using CARMIZE (£5.75) if patients are able to reuse vials for more than one drop. If not Optive becomes a cost-effective option. Carmize 0.5% 30 x 0.4ml single dose unit £5.75 reuse up to 12 hrs £15.53 reuse up to 12 hrs £7.49 up to 6 months Hypromellose 0.5% eye drops (Pres) Isopto Plain 90 x 0.4ml single dose unit 10ml 10ml (special container maintains contents) Hypromellose (Pres Free) Lumecare Hypromellose 0.3% Eye Drops Polyvinyl Alcohol 1.4% (Pres) Polyvinyl Alcohol 1.4% (Pres-Free) Sodium Hyaluronate (Pres) Sodium Hyaluronate (Pres-Free) Optive 0.5% Cost is least using Clinitas SDU (£5.70) if patients are able to reuse vials for more than one drop. If not VisMed Multi becomes a cost-effective option. White Soft Paraffin with Liquid Paraffin Cost £1.49 Expiry once open 28 days £0.81 28 days 30 x 0.5ml single dose unit £5.72 reuse up to 12 hrs Sno-Tears Liquifilm Tears 10ml 30 x 0.4ml £1.06 £5.35 28 days single use Blink Intensive Tears Clinitas 10ml 30 x 0.5ml single dose unit £4.98 £5.70 45 days 12 h Vismed Multi 10ml (special container maintains contents) £6.81 3m Lacrilube 3.5g £2.51 28 days Many of the preparations for dry eyes are classed as medical devices ie approved by private sector organisations called „Notified bodies‟, rather than medicines which are directly approved by the MHRA. When prescribing, the variation in cost of these preparations should be considered. Eyes Page 135 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 12: Ear, nose, and oropharynx Top 12.1 Drugs acting on the ear Otitis Externa also see Chapter 5 First line: Acetic acid ® as EarCalm 2% spray: £4.10 (5ml) Second line: Betamethasone with Neomycin Drops: £2.39 (10ml) See Infection management guidance for appropriate clinical indications. Available OTC Cure rates similar at 7 days for topical acetic acid or antibiotic +/- steroid. Otitis media Topical products not recommended for Otitis media Removal of wax For all preparations used in removal of ear wax patients should be advised to lie with affected ear uppermost for 5 minutes after administration to ensure penetration of the ear canal. Simple oils such as Olive (or Almond) oil should be used first line. Available OTC Olive Oil Docusate Sodium as Waxsol Ear, Nose and Throat See Infection management guidance for appropriate clinical indications. 0.5% drops: £1.81 (10ml) Available OTC Page 136 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 12.2 Drugs acting on the nose Nasal Allergy Nasal steroids First-line: Symptoms of nasal allergy are usually controlled with nasal corticosteroids and / or oral antihistamines. Beclometasone ® as Beconase 50mcg/spray: £2.19 (200 dose unit) Beclometasone nasal sprays are available OTC, unbranded versions at less than NHS prescription charge. Do Not prescribe Beconase Hayfever or Beconase 180 dose preparations as these are significantly more expensive. Second-line: Budesonide ® as Rhinacort Aqua 64mcg/spray: £3.49 (120 dose unit) Fluticasone Furoate 27.5mcg/spray: £6.44 (120 dose unit) Mometasone 50mcg/spray: £7.68 (140 dose unit) Triamcinolone 55mcg/spray: £7.39 (120dose unit) Anticholinergics Ipratropium 21mcg/spray: £3.99 (180 dose unit) Use Ipratropium only if rhinorhoea is main problem. Decolonisation of nasal MRSA Mupirocin Nasal ointment 2%: £3.54 (3g) For use in decolonisation of nasal MRSA, standard regime is TDS nasal application for 5 days. Where there is clinical infection, nasal decolonisation treatment should be undertaken in addition to any systemic treatment given Naseptin (Neomycin 0.5% / Chlorhexidine 0.1%) Nasal cream £1.90 (15g) Please refer to PCT Management of Infection Guidance and MRSA Policy for further details (page137). Ear, Nose and Throat Note: Fluticasone propionate nasal sprays are non-formulary. All patients currently prescribed Fluticasone propionate should be switched to ® Fluticasone furoate nasal spray Avamys as significantly more cost-effective. Page 137 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Benzydamine 0.15% mouthwash: £6.45 (300ml) May be diluted with water if stinging occurs. Available OTC Hydrocortisone 2.5mg pellets: £4.24 (20) Available OTC 12.3 Drugs acting on the oro-pharynx Oral ulceration and inflammation Oropharyngeal antiinfectives Preparations for oral candidiasis should be used after food and retained in the mouth for as along as is practical. Oral candidiasis is often associated with the use of inhaled corticosteroids, use of spacer devices and rinsing the mouth with water after using such inhalers may be helpful. Miconazole 0.2% gel: £2.97 (15g) £4.38 (80g) Nystatin ® as Nystan 100,000u/ml suspension: £1.80 (30ml) Mouthwashes Chlorhexidine 0.2% mouthwash: £3.32 (300ml) Available OTC. Dry mouth Bioxtra Spray: £3.94 (50ml) Approved for NHS prescribing where they fulfil the borderline substances criteria, for dry mouth caused by: Salivix Pastilles: £3.50 (50) Ear, Nose and Throat Miconazole gel is available OTC. Use with caution if patient taking warfarin. radiotherapy sicca syndrome Prescriptions should accordingly be endorsed as ACBS. All these products are available OTC, some at less than the NHS prescription charge Page 138 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 13: Dermatological preparations Related guidance: NICE Clinical Guideline CG57: Atopic eczema in children SIGN National Clinical Guideline 125: Management of atopic eczema in primary care Top 13.2 Emollient and barrier preparations Always ensure that sufficient quantities are prescribed: liberal twice daily application to the whole adult body will use at least 500g per week. Total quantity of emollient per week (based on “bd” application) for an adult: Face: 15-30g, Trunk: 400g, Both arms / legs: 100-200g, Both hands: 25-50g, Groins and genitalia: 15-25g, Scalp: 50-100g The more greasy an emollient the more effective it is but this needs to be balanced against cosmetic acceptability and compliance Emollient creams and emulsifying ointment can be used as soap substitutes as well as moisturisers Emollients should be applied by smoothing onto the skin in direction of any hairs (not by rubbing) Regular re-application, especially after washing, with drying by patting not rubbing, will increase the effectiveness of all emollient therapy 13.2.1 Emollients Gels Creams - soap substitute Creams Continued on next page Dermatology Doublebase Gel: Aquamax Wash Cream wash: £2.99 (250g) Non-foaming soap substitute. SLS & lanolin free. Aquamax Cream: £1.89 (100g) £3.99 (500g) SLS, Parabens & lanolin free. Most cost-effective preparation currently available but not available in pump packs. Cetraben Cream: £1.40 (50g) £3.98 (150g) £5.99 (500g) E45, Oilatum & Cetraben pump-packs are associated with less waste than other pump-packs presentations and are preferred first choice options on grounds of cost-effectiveness. E45 Cream: £1.61 (50g) £2915 (125g) £4.85 (350g) £5.96 (500g pump) However patients should be encouraged to find a product they will use regularly & achieve benefit from. Oilatum Cream: £2.46 (150g) £4.99 (500ml) Balneum Cream: £2.80 (50g) £9.80 (500g pump) £2.65 (100g) £5.83 (500g) Contains 5% urea Page 139 Therapeutic Area Emollients Formulary product Balneum Plus (Continued from previous page) Cost (per pack as stated) Rationale for decision / comments Cream: £3.29 (100g) £14.99 (500gpump) Contains 5% urea, 3% lauromacrogols Diprobase Cream: £1.28 (50g) £6.32 (500g pump) Hydromol Cream: £2.04 (50g) £3.80 (100g) £11.09 (500g) Emulsifying ointment or Ointment: £2.25 (500g) White soft paraffin Ointment: £2.85 (500g) Liquid paraffin / White soft paraffin 50/50 or Ointment: £2.44 (500g) Diprobase Ointment: £1.28 (50g) £5.99 (500g) Hydromol Ointment: £4.82 (500g) Ointments First-line: Second-line: Hydromol ointment has same ingredients as Epaderm and is cheaper. Epaderm is non formulary. Use preparations with antimicrobials only if infection present or strongly suspected Emollients with antimicrobials Eczmol ® Dermol Cream Dermol 500 Dermatology Cream: £3.70 (250ml) Eczmol cream contains 1% chlorhexidine gluconate. Cream £6.63 (500g) Lotion: £6.04 (500ml) Dermol contains 0.1% chlorhexidine dihydrochloride and 0.1% benzalkonium chloride. Page 140 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 13.2.1.1 Emollient bath additives and shower preparations Emollient bath preparations First-line: Based on current evidence bath emollients may offer little or no benefit. People who use them instead of directly applied emollients will unknowingly have substandard emollient therapy. Dermalo Bath emollient: £3.44 (500ml) Dermalo is recommended first line as a cost-effective fragrance-free liquid paraffin based bath additive. Dermalo has similar constituents to Oilatum and is less costly, Second-line: Doublebase Bath Emollient: £5.45 (500ml) Shower Gel: £5.21 (200g) Diprobath (lanolin-free) Bath emollient: £6.71 (500ml) E45 Emollient bath oil: £3.19(250ml) £5.11 (500ml) Hydromol Bath & Shower Emollient: £3.61 (350ml) £4.11 (500ml) £8.19 (1 litre) Oilatum Bath additive: £3.25 (250ml) £5.10 (500ml) Use preparations with antimicrobials only if infection present or strongly suspected Emollient bath / shower preparations with antimicrobials Dermol 200 Shower emollient: £3.55 (200ml) or Dermol 600 Bath emollient: £7.55 (600ml) Or Emulsiderm Liquid emulsion: £3.85 (300ml) Liquid emulsion: £12.00 (1ltr) or Oilatum Plus Dermatology Bath additive: £6.98 (500ml) Page 141 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 13.4 Topical corticosteroids Topical corticosteroids The Finger Tip Unit (FTU) is useful means of calculating approximate quantities required, as follows (1 FTU = 0.5g) Face and neck: 2.5 FTU , Trunk: 7 FTU (front) and 7 FTU (back), One arm: 3 FTU, One hand: 1 FTU, One leg: 6 FTU, One foot: 2 FTU Total quantities of topical steroids required per week based on “bd” application for an adult: Face and neck: 15-30g, Trunk: 100g, Both arms: 50g, both hands: 15-30g, Both legs: 100g, Groins and genitalia: 15-30g General note: Avoid prescribing dermatologicals that need to be made extemporaneously owing to the excessive costs of ‘special’ items. This does not apply to ready made dilutions such as Betnovate RD Topical corticosteroids Mild Moderate Most available as creams and ointments. Patients with atopic eczema should be advised to apply topical corticosteroids once daily (SIGN CG125). Twice weekly maintenance therapy should be considered in frequently relapsing moderate to severe atopic eczema (SIGN CG125). NB Potency of a steroid is a product of the formulation as well as the corticosteroid Hydrocortisone 1% Cream: £1.07 (15g) £2.14 (30g) Ointment: £2.54 (30g) Clobetasone butyrate 0.05% as Eumovate Cream/ointment: £1.86 (30g) £5.44 (100g) Betamethasone valerate 0.025% Cream/ointment: £3.15 (100g) Caution: Hydrocortisone butyrate is a potent steroid (Locoid) as Betnovate RD Fludroxycortide 0.0125% Cream/ointment: £3.26 (60g) as Haelan (Continued overleaf) Dermatology (Continued overleaf) Page 142 (Continued from previous page) Potent topical steroids should not be prescribed on repeat prescriptions. Potent First-line: Betamethasone valerate 0.1% Second-line: as Betnovate Hydrocortisone butyrate 0.1% as Locoid Mometasone furoate 0.1% Cream/ointment: £1.43 (30g) £4.05 (100g) Cream/ointment: £1.60 (30g) £4.93 (100g) as Elocon Cream: £4.36 (30g) £12.58 (100g) Ointment: £4.32 (30g) £12.44 (100g) Fluticasone propionate 0.05% as Cutivate Cream 0.05%/ointment 0.005%: £2.27 (15g) £4.24 (30g) Fluocinolone acetonide 0.025% Cream/ointment: £4.14 (30g) £11.75 (100g) as Synalar Very potent topical steroids should not be prescribed on repeat prescriptions. Very potent Clobetasol propionate 0.05% as Dermovate Dermatology Cream/ointment: £2.69 (30g) £7.90 (100g) Page 143 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 13.5 Preparations for eczema and psoriasis Vitamin D analogues Calcipotriol ® as Dovonex Ointment: £5.78 (30g) Dovonex Cream was discontinued on 01/10/11 with betamethasone ® as Dovobet Ointment: £61.43 (120g) Gel: £33.08 (60g) £61.43 (120g) For the treatment of stable plaque psoriasis on the body. For the treatment of mild to moderate scalp and “non-scalp” psoriasis in adults. The gel is licensed for body and scalp application. UK market research indicates the majority of patients prefer a gel formulation. Regular emollient use may be considered to reduce fall of scales and help with other symptoms, including itch. Department of Dermatology Musgrove Park Hospital Guidance for General Practitioners For patients prescribed calcipotriol / betamethasone dipropionate* preparations. The recommended treatment period for Dovobet® Gel is 4 weeks for use on the scalp and 8 weeks for use on “non-scalp”. The recommended treatment period for Dovobet® Ointment is 4 weeks. After these periods, treatment can be continued after medical review and under medical supervision. Dovobet Gel for body & scalp psoriasis Dovobet Ointment for body psoriasis Clearance is defined as no active psoriasis (flat, smooth, non-scaly & non-itchy). Patients should stop treatment at this point. Any residual redness will improve without further treatment. Dermatology Page 144 13.6 Acne and rosacea Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments 13.6.1 Topical preparations for acne Initial treatment should be based on whether the acne is predominantly inflammatory or comedonal, and its severity. Keratolytics Benzoyl Peroxide as PanOxyl Aquagel 2.5% gel: £1.76 (40g) 5% gel: £1.92 (40g) Benzoyl peroxide may be effective for both comedonal and inflammatory acne. Treatment should start with lower strength preparations, in an aqueous base. Topical antibacterials Clindamycin 1% with Zinc as Zindaclin Gel Gel: £8.66 (30g) Topical antibiotics are best reserved for patients with inflammatory acne who do not wish to take systemic antibiotics or who cannot tolerate them. Tretinoin Gel 0.01% gel: £5.28 (60g) 0.025% gel: £5.28 (60g) Retinoids are useful in treating comedonal acne. Skin irritation often occurs during the first few weeks of treatment. Retinoids are contra-indicated in pregnancy and women of child bearing age should take adequate contraceptive precautions. 100mg capsules: £1.03 (8) Oral antibiotic treatment should be reviewed after 3 months, however maximum benefit may only be seen after 4 to 6 months. Oxytetracycline has been removed from this section given the possibility of poor compliance with dosing requirements in long term use. Lymecycline 408mg capsules: £6.22 (28) £11.98 (56) Minocycline is not recommended owing to safety concerns requiring LFT monitoring when used >6 months, higher cost and lack of evidence of superiority over Lymecycline in acne. Co-Cyprindiol 2000/35mcg tablets: £4.82 (63) The risk of VTE with Co-Cyprindiol is higher than with conventional low-dose COCPs and recommend that: Retinoids 13.6.2 Oral preparations for acne Antibacterials Doxycycline or Hormonal it should only to be used after systemic antibiotics have failed or are not tolerated it should only be used in licensed indication it should not be used solely for contraception it should be discontinued 3-4 months after resolution of symptoms The evidence in favour of co-cyprindiol over other oral contraceptives in reducing acne lesion counts is limited. Dermatology Page 145 13.8 Photodamage Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Actinic keratosis Ingenol 0.0015% gel £65.00 (3 x 0.47g) Applied once daily to face or scalp for 3 days only 0.05% gel £65.00 (2 x 0.47g) Applied once daily to trunk or extremeties for 2 days only 13.10 Anti-infective skin preparations Avoid widespread use of topical antibiotics, especially those agents also available as systemic preparations. Refer to PCT Management of Infection guidelines for indications Antibacterials Antifungals Antivirals Dermatology Retapamulin 1% ointment: £7.89 (5g) Refer to PCT Management of Infection Guidance for indications. Mupirocin 2% cream/ointment: £4.38 (15g) Reserve for MRSA. For nasal use see Chapter 12. Amorolfine 5% nail paint: £11.35 (5ml) Refer to PCT Management of Infection Guidance for indications. Available OTC. Systemic treatment is more effective than topical for nail infections BNF 13.10.2 Clotrimazole 1% cream: £1.41 (20g) £3.53 (50g) Refer to PCT Management of Infection Guidance for indications. Available OTC Miconazole 2% cream: £1.82 (30g) Refer to PCT Management of Infection Guidance for indications. Available OTC Terbinafine 1% cream: £1.72 (15g) £3.44 (30g) Refer to PCT Management of Infection Guidance for indications. Available OTC Aciclovir 5% cream: £1.02 (2g) £5.10 (10g) For treatment of labial herpes simplex (cold sores), most effective if applied at prodromal phase. Use 5x/day for 5 days Available OTC Page 146 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments BNF Chapter 15: Anaesthesia Top 15.1.7 Antagonists for central and respiratory depression Opioid overdose Naloxone 400mcg/ml ampoule: £4.10 (1ml) 1mg/ml PFS: £8.36 (2ml) Antagonists for Central and Respiratory Depression Refer to Emergency treatment of poisoning section of current BNF for guidance on management of opioid overdose / respiratory depression. Page 147 Therapeutic Area Formulary product Cost (per pack as stated) Rationale for decision / comments Appendix 1 Borderline substances Food supplements Standard ACBS indications: shortbowel syndrome, intractable malabsorption, preoperative preparation of under-nourished patients, proven inflammatory bowel disease following total gastrectomy, bowel fistulas, or disease-related malnutrition and dysphagia General Practitioners are reminded that the ACBS recommends products on the basis that they may be regarded as drugs for the management of specified conditions. Gluten-free foods Top Assess nutritional status before starting use of food supplements and offer advice about enriching nutritional value of normal diet. Aim of treatment should be recorded and record of weight kept. Malnutrition Universal Screening Tool (MUST) is available on the Medicines Management section of the PCT intranet together with a guide to developing a Nutrition Support Care Pathway (p.132) for patients in community & Care Home Settings. A short leaflet produced by NHS Somerset dieticians is available advising on food fortification. NAGE (Nutrition Advisory Group for Elderly People) produce a range of advice leaflets & posters – details available at: www.bda.uk.com/Downloads/nage_updated_form_jan06.pdf or contact: NAGE, The British Dietetic Association, Cambertown House, Commercial Road, Goldthorpe Industrial, Estate, Goldthorpe, Rotherham, South Yorkshire, S63 9BL. Helpline Number: 01709 889900 Fax Number: 01709 881673 Fresubin Powder ® Extra Available in: Strawberry Vanilla Chocolate Original flavour ® Resource Thicken Up Clear £5.60 (7 x 62g sachets) (Sachets of powder requiring preparation with fresh whole milk.) For patients who are able to add whole milk to a powder, or have a carer / home staff. Not suitable for lactose intolerant patients. £8.46 (125g) Used to thicken food & liquid for patients with swallowing difficulties. The Prescribing Guide to Gluten Free foods indicating quantities of products appropriate for a range of people with coeliac disease is available on the Medicines Management section of the PCT intranet. (The Coeliac Society Nov 2011) Food supplements and Gluten-free foods Page 148 Complete MUST Nutritional Screening Develop a nutritional care plan considering the aims of the patient’s treatment Must = 0 - Low Risk Must = 1 - Medium Risk Continue screening monthly or at each review if patient is seen less than monthly. Continue screening (as for low risk) Ensure that patient has a tailored nutritional care plan in place which considers the patients preferences and nutritional needs to provide an optimal diet . Follow pathway detailed for MUST scoreof 1 for two weeks. Encourage regular meals and high energy puddings Encourage 2-3 high energy snacks per day Ensure patient receives food fortification. Fortify foods using butter, margarine, cream or grated cheese Offer 2-3 glasses of full cream milk/milky drinks (hot or cold) Screen more frequently should there be any clinical concerns, i.e. unplanned weight loss (loose fitting rings/clothes) impaired swallow, altered bowel habit, prolonged illness, ongoing poor appetite, apathy or depression. Improvement in nutritional status after 1 month If no improvement request a prescription for Ist line Fresubin Powder Extra twice a day in between meals for 1 month. Refer to Dietitian 2nd Line: ACBS approved 1.5kcal/ml milk based supplement or fruit juice based for patients who dislike or are intolerant to milk (seek advice from Somerset Community Dietitians 01278 447407) No improvement in nutritional status after 1 month Request a prescription for: st 1 Line: Fresubin Extra twice a day between meals 2nd Line: ACBS approved 1.5kcal/ml milk based supplement or fruit juice based for patients who dislike or are intolerant to milk (seek advice from Somerset Community Dietitians 01278 447407) Food supplements and Gluten-free foods Patient is unsafe and/or unable to feed orally then consider appropriateness of non-oral feeding e.g. Naso-gastric tube Must = 2 or more - High Risk If no improvement in nutritional status Referral to Somerset Community Dietiitans using the referral form and faxing to 01278 431384 or send to East Quay Medical Centre Bridgwater TA6 4GP Page 149 Suspicion of cow’s milk protein allergy (CMPA)– Breast fed infants Clinical assessment / findings Family History COLIC Suspicion of milk moderate CMPA Suspicion of severe CMPA Gastrointestinal: loose frothy diarrhoea +/general distress with colic (crying for more than 3 hours over more than 3 days over more than 3 weeks) One or more of the following: Gastrointestinal: frequent regurgitation, vomiting, diarrhoea, constipation, anaemia Dermatological: atopic dermatitis, General: persistent distress or colic more than 3 hours over more than 3 days over more than 3 weeks One or more of the following symptoms: Gastrointestinal: failure to thrive due to chronic diarrhoea, or vomiting, blood in stool, anaemia due to occult or macroscopic blood loss, protein losing enteropathy (hypoalbuminaemia), endoscopic or histologically confirmed enteropathy, severe ulcerative colitis Dermatological: exudative or severe atopic dermatitis Consider referral to breastfeeding specialist for feeding advice Maternal milk free diet whilst breast feeding continues for 2-4 weeks. Calcium supplement for mother will be required (1000mg/d calcium). eHF* formula for use in weaning e.g. Nutramigen (1 or 2) or Milupa Aptamil Pepti (1 or 2). Consider referral to Community Paediatric Dietetian No improvement Improvement *eHF – Extensively hydrolysed formula Reintroduce milk back into maternal diet If no symptoms develop return to normal diet No improvement Return to normal diet and consider paediatrician referral If symptoms return, restart maternal milk free diet. Or Consider eHF* for use with weaning solids and milk free weaning diet Consider maternal milk free diet with a 2 week trial of amino acid formula Neocate or Nutramigen AA for use with weaning solids Referral to paediatrician plus maternal milk free diet whilst breastfeeding continues. Calcium supplement for mother will be required (1000mg/d calcium). Amino acid formula for weaning e.g. Neocate LCP or Nutramigen AA Refer to paediatric dietitian for specialist advice. Specialist individual allergy and challenge plan to be developed. No improvement At 1 year of age or after 6 months symptom free undertake milk re-challenge at home as per written plan Food supplements and Gluten-free foods Page 150 Suspicion of cow’s milk protein allergy (CMPA)– Formula fed infants Clinical assessment / findings / Family History Suspicion of mild to moderate CMPA Suspicion of severe CMPA One or more of the following: One or more of the following symptoms: Gastrointestinal: frequent regurgitation, vomiting, diarrhoea, constipation, anaemia Dermatological: atopic dermatitis, urticarial (unrelated to acute infections or drugs) Gastrointestinal: failure to thrive due to chronic diarrhoea, or vomiting, blood in stool, anaemia due to occult or macroscopic blood loss, protein losing enteropathy (hypoalbuminaemia), endoscopic or histologically confirmed enteropathy, severe ulcerative colitis. Respiratory: runny nose, chronic cough, wheeze (all unrelated to infection) Dermatological: urticaria, swelling (angioedema), exudative or severe atopic dermatitis General: persistent distress or colic more than 3 hours over more than 3 days over more than 3 weeks) Respiratory: acute laryngoedema or bronchial obstruction with difficulty breathing Systemic reactions: anaphylactic shock needs immediate hospital management Elimination diet: Extensively hydrolysed formula (eHF) for 2-4 weeks e.g. Nutramigen 1 or 2, or Milupa Aptamil Pepti 1 or 2 Amino acid formula (AAF) e.g. Neocate LCP or Nutramigen AA and milk free diet for 2-4 weeks Improvement Open challenge back on cow‟s milk formula If no symptoms develop, return to normal diet. If symptoms return, restart eHF and continue to avoid milk for at least 6 months or until over 1 year. Give milk free dietary advice and consider referral to community paediatric dietitian At 1 year of age or after 6 months symptom free undertake milk re-challenge at home as per written plan Food supplements and Gluten-free foods No improvement 2 week trial of amino acid formula (AAF) Improvement No improvement Continue on AAF and avoid milk for at least 6 months or until over 1 year. Give milk free diet pack Return to normal diet and consider referral to paediatrician Improvement Refer to paediatric dietitian for specialist advice. Specialist individual allergy and challenge plan to be developed by hospital team No improvement Paediatric specialist diagnostic procedures eHF or AAF should be continued until the age of 1 year at which point the child can change onto ready to drink milk substitutes Alpro 1+ soya milk. If milk and soya allergy, eHF or AAF should be continued until the age of 2 years Page 151 Suggested feeding table. Birth-12 months PRODUCTS Amino acid formula (AAF) Preparation for single feeds Approximate age of baby Approx weight of baby Level scoops Cooled, freshly boiled water Feeds in 24 hours Neocate or Nutramigen AA Extensively hydrolysed formula (EHF) *Nutramigen 1 Nutramigen 2 *Aptamil Pepti 1 Birth to 6 months 6 months – 12 months Birth to 6 months Aptamil Pepti 2 6 months – 12 months 400g tins 900g tins 400g tins **400g tins 400g tins ml fl. oz. (approx) 3 90 3 6 6 6 Not suitable 6 Not suitable 9 1/4 4 120 4 6 8 8 Not suitable 8 Not suitable 4.7 10 1/4 5 150 5 5 8 8 Not suitable 8 Not suitable 4 months 6.5 14 1/4 7 210 7 5 11 11 Not suitable 11 Not suitable 6 months + 7.5 16 1/2 8 240 8 4 10 10 10 10 5 7 – 1 year - - 7 210 7 3 7 7 7 7 3 kg lb Birth - 2 wks 3.5 7 3/4 2 - 4 wks 4.2 2 months SUGGESTED NUMBER OF TINS NEEDED PER MONTH *Nutramigen 1 and Aptamil Pepti 1 may be used from birth – 1 year, although generally, once the child is 6 months old, they are moved to the appropriate follow-on formula, either Nutramigen 2 or Aptamil Pepti 2 respectively. ** Aptamil Pepti 1 is also available as a 900g tin, reduce number of tins accordingly. Appendix 2: Out of hours formulary Page 152 Appendix 2. OUT OF HOURS Appendix 2: Out of hours formulary Page 153 SOMERSET COMMUNITY PHARMACY ENHANCED SERVICE TO PROVIDE PALLIATIVE CARE DRUGS Bridgwater ASDA Pharmacy ASDA Superstore, East Quay, Bridgwater, TA6 5AZ 01278 720400 Pharmacy open: 8am – 10pm Monday to Friday 8am – 9pm Saturday 10am – 4pm Sunday Cheddar Tout’s Pharmacy Budgens Cheddar, Roynon Way, Cheddar, Somerset, BS27 3RB 01934 744546 Pharmacy open: 7am to 11pm Monday to Friday 8am to 10pm Saturday 10am to 4pm Sunday Frome Sainsbury’s Pharmacy Wessex Fields, Marston Road, Frome, BA11 4DH 01373 473284 Pharmacy open: 7am to 11pm Monday to Friday 7am to 10pm Saturday 10am to 4pm Sunday ASDA Pharmacy Warminster Road, Frome, BA11 5LA 01373 475200 Pharmacy open: 8am to 11pm Monday 7am to 11pm Tuesday to Saturday 10am to 4pm Sunday 01458 834986 Glastonbury Glastonbury Pharmacy Feversham Lane, Glastonbury, BA6 9LP Pharmacy open: 7am to 11pm Monday to Friday 7am to 7pm Saturday 9am to 1pm and 1.30pm to 5.30pm Sunday Appendix 2: Out of hours formulary Page 154 Minehead Boots the Chemist 14-16 The Parade, Minehead, TA24 5UG 01643 702004 Pharmacy open: 8.30am to 1.30pm and 2.30pm to 5.30pm Monday to Saturday 10am to 4pm Sunday South Petherton South Petherton Pharmacy (John Ware Ltd) Bernard Way, South Petherton, TA13 5EF 01469 242269 Pharmacy open: 7pm to 11.59pm Monday and Friday Midnight to 10pm Tuesday and Saturday 7am to 10pm Wednesday & Thursday Taunton ASDA Pharmacy Creechbarrow Road, Taunton, TA1 2AN 01823 448010 Pharmacy open: 9.45am to 12.30 and 2.30pm to 5pm Monday to Saturday. 11am to1pm and 2pm to 4pm Sunday Yeovil Asda Pharmacy Preston Road, Yeovil, BA20 2HB Pharmacy open: 7:30am to 11pm Monday - Friday 7am to 9pm Saturday 10am to 4pm Sunday Boots the Chemist 37, Middle Street, Yeovil BA20 1LG Pharmacy open: 8am to 1pm and 2pm to 10pm Monday - Sunday Appendix 2: Out of hours formulary 01935 709510 01935 426673 Page 155 Part 2: Dorset and Somerset Palliative Care Drug Stock List: Drug Cyclizine 50mg/ml Dexamethasone 4mg/ml Dexamethasone 2mg Diamorphine 10mg Diamorphine 100mg Diazepam 5mg/ml Diazepam 10mg Diclofenac 100mg Domperidone 30mg Fentanyl 25mcg Fentanyl 50mcg Fentanyl 75mcg Fentanyl 100mcg Glycopyrronium bromide 200mcg/ml Haloperidol 5mg/ml Hyoscine butylbromide 20mg/ml Hyoscine hydrobromide 400mcg/ml Levomepromazine 25mg Levomepromazine 25mg/ml Metoclopramide 5mg/ml Midazolam 5mg/ml Morphine sulphate 10mg/ml Morphine sulphate 30mg/ml Morphine sulphate (Oramorph) 10mg/5ml Morphine sulphate (Oramorph) 100mg/5ml Oxycodone 10mg/ml Prochlorperazine 25mg Sodium chloride 0.9% Water for Injection continued on next page Appendix 2: Out of hours formulary Form Injection Injection Tablets Injection Injection Injection Rectal Tubes Suppositories Suppositories Patches Patches Patches Patches Injection Injection Injection Injection Tablets Injection Injection Injection Injection Injection Oral Solution Concentrated Oral Solution Injection Suppositories Injection Injection Quantity 10 x 1ml 10 x 2ml 100 5 5 10 x 2ml 5 10 10 1x5 1x5 1x5 1x5 10 x 1ml 5 x 2ml 10 x 1ml 10 x 1ml 84 10 x 1ml 10 x 2ml 10 x 2ml 40 x 1ml 40 x 1ml 5 x 100ml 1 x 30ml 20 x 1ml 10 10 x 10ml 20 x 10ml Page 156 Drug Clexane 2000 units Clexane 4000 units Clexane 6000 units Clexane 8000 units Clexane 10000 units Tamiflu 30mg Tamiflu 45mg Tamiflu 74mg Tamiflu Relenza 5mg Appendix 2: Out of hours formulary Form Pre-Filled Syringes Pre-Filled Syringes Pre-Filled Syringes Pre-Filled Syringes Pre-Filled Syringes Capsules Capsules Capsules Suspension Dry Powder for inhalation Quantity 1 x 10 pfs 1 x 10 pfs 1 x 10 pfs 1 x 10 pfs 1 x 10 pfs 1 x 10 1 x 10 1 x 10 1 pack 1 pack Page 157 This page is intentionally blank