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Prescribing Formulary 17th Edition –March 2014 Last amendment: March 23rd 2015 The Somerset CCG allows all information provided to be re-used free of charge in its original context. This may only be done by non-commercial organisations/individuals using the information without profit. If you are a commercial, for profit organisation, or would like to re-use the information provided in a context other than which it was given, you must apply for a Re-Use of Information licence using the following contact details. Freedom of Information Team Somerset Clinical Commissioning Group Wynford House Lufton Way Yeovil Somerset BA22 8HR Email: [email protected] Somerset CCG - Prescribing Formulary 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. Generally we do not support the use of combination products for oral medicines, normally on cost grounds. However it is appreciated that patient choice and compliance may be the best option in some cases. 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 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: Provision of patient information on admissions from Primary Care Reconciliation of patient information post-discharge From Primary to Secondary Care 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 Chapter 1 Gastro-intestinal system Dyspepsia & gastro-oesophageal reflux disease Acute diarrhoea Antispasmodics Chronic bowel disorders Antisecretory drugs Guidance on assessing dehydration in children under 5 years Proton pump inhibitors (PPI) Laxatives Proton pump inhibitors (PPI) Local preparations for anal and rectal disorders Helicobacter pylori eradication Chapter 2 Cardiovascular system Positive inotropic drugs Guidelines for the Treatment of Chronic Stable Angina Pectoris Diuretics Oral anticoagulants Anti-arrhythmic drugs NOACs Beta-adrenoreceptor blocking drugs Stroke prevention in AF-patient decision aid Drugs affecting the renin-angiotensin system Summary of drug interactions for Dabigatran, Rivaroxaban & Apixaban Summary Drug Treatment for Hypertension Decision aid for patients requiring stroke prevention in AF NICE Care Pathway for Hypertension Implementation priorities for Dabigatran & Rivaroxaban Heart Failure Guidance Antiplatelet drugs Post MI secondary prevention Lipid regulation Calcium channel blockers – Dihydropyridines Secondary prevention of CVD Calcium channel blockers - Rate limiting Drug – statin interactions Other antianginal drugs Lipid regulating drugs Peripheral vasodilators Heart Failure prescribing Guidelines flowchart Nitrates, CCBs and potassium channel activators Table of contents Page 3 BNF Therapeutic Chapter Chapter 3 Page Page Respiratory system Safer use of inhaled corticosteroids Asthma Step-down Guide: Combination MDIs Bronchodilators Asthma Step-down Guide: Combination DPIs Corticosteroids Guidance for managing COPD Leukotriene receptor antagonists Antihistamines Adult and children asthma Inhaler pathway Mucolytics Chapter 4 Central nervous system Hypnotics and anxiolytics Neuropathic pain Drugs used in psychoses and related disorders Diagnosis of tension-type headache, migraine & cluster headache Antimanic drugs Medication Recommendations from NICE CG150: Headache Bipolar disorder Antidepressants Citalopram maximum dose guidance Escitalopram maximum dose guidance CNS stimulants and drugs for ADHD Antimigraine drugs Epilepsy Formulation switching of antiepileptic drugs Drugs used in status epilepticus Drugs used in substance dependence Drugs used in the treatment of obesity Smoking Cessation Traffic light system for identifying risk of serious illness in children Opioid dependence Analgesics Alcohol dependence Opioid Conversion Table Chapter 5 Drugs for dementia Infections Antibacterial drugs Infection Management Guidance Antifungal drugs MRSA Decolonisation Policy Antiviral drugs Guidance on the management & treatment of C. difficile infection Influenza vaccines Table of contents Page 4 BNF Therapeutic Chapter Chapter 6 Page Page Endocrine system Drugs used in diabetes Guidance on Type 2 diabetes management Sex Hormones Hormone Replacement Therapy Male sex hormones and antagonists Hypothalamic and pituitary hormones and anti-oestrogens Insulin therapy in Type 2 Diabetes Posterior pituitary hormones and antagonists HbA1c for Diagnosis of Diabetes Mellitus NHS England Interim Gender Dysphoria Protocol and Service Insulins Drugs affecting bone metabolism Hypodermic equipment Primary prevention of osteoporosis in post-menopausal women Drugs used in diabetes Secondary prevention of osteoporosis in post-menopausal women Guidance on the use of Blood Glucose Testing Strips Breast cancer treatment - induced bone loss Thyroid and anti-thyroid drugs Osteoporosis in Men Corticosteroids Chapter 7 Obstetrics, gynaecology, and urinary-tract disorders Treatment of vaginal and vulval conditions Management of LUTS associated with BPH Contraceptives Drugs for urinary frequency, enuresis, and incontinence Drugs for genito-urinary disorders Drugs for erectile dysfunction Anticholinergic load Chapter 8 Malignant disease and immunosuppression Sex hormones and hormone antagonists in malignant disease Hormone antagonists Chapter 9 Pre- or Postmenopausal women at high risk of breast cancer Prostate cancer & Gonadorelin analogues Nutrition and blood Anaemias and some other blood disorders Minerals Fluids and electrolytes Vitamins Table of contents Page 5 BNF Therapeutic Chapter Chapter 10 Page Musculoskeletal and joint diseases Drugs used in rheumatic diseases and gout Gout Chapter 11 Page Acute treatment and long-term management of gout Guidance on the management of Osteoarthritis Eye Anti-infective eye preparations Treatment of glaucoma Corticosteroids and other anti-inflammatory preparations Miscellaneous ophthalmic preparations Mydriatics and cycloplegics Ocular lubricants comparison table Chapter. 12 Ear, nose and oropharynx Drugs acting on the ear Drugs acting on the oro-pharynx Drugs acting on the nose Nasal Allergy Chapter 13 Skin Emollient and barrier preparations guidance Guidance on calcipotriol / betamethasone dipropionate use Emollients Topical preparations for acne Emollient bath additives and shower preparations Oral preparations for acne Topical corticosteroids Photodamage Preparations for eczema and psoriasis Anti-infective skin preparations Chapter 15 Anaesthesia Antagonists for central and respiratory depression Appendix 1 Borderline substances Food supplements Suspicion of cow’s milk protein allergy (CMPA)– Breast fed infants Gluten-free foods Suspicion of cow’s milk protein allergy (CMPA) – Formula fed infants MUST Nutritional Screening Suggested feeding for formula fed infants Table of contents Page 6 BNF Therapeutic Chapter Appendix 2 Page Page 184 Dorset & Somerset Out of Hours Service Somerset Community Pharmacies holding Palliative Care Drugs: Minehead Bridgwater South Petherton Cheddar Taunton Frome Yeovil Glastonbury Dorset and Somerset Palliative Care Drug Stock List 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 7 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) BNF Chapter 1: Gastro-intestinal system 1.1 Top Dyspepsia & gastro-oesophageal reflux disease Related guidance: NICE CG184 (2014):Dyspepsia NICE encourages people who need long-term management of dyspepsia symptoms to reduce their use of prescribed medication stepwise: by using the effective lowest dose, by trying 'as-needed' use when appropriate, and by returning to self-treatment with antacid and/or alginate therapy (unless there is an underlying condition or co-medication that needs continuing treatment). Advise people that it may be appropriate for them to return to self-treatment with antacid and/or alginate therapy (either prescribed or purchased over-thecounter and taken as needed). Antacids Mucogel Suspension: £1.71 (500ml) Low sodium and cost-effective treatment for dyspepsia. At dose of 10-20ml tds & at bedtime provides equivalent magnesium intake required for hypomagnesaemia as an alternative to magnesium glycerophosphate. Alginates Peptac 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 Gaviscon Advance Aniseed and peppermint Liquid: £5.12 (500ml) Chewable tablets: £3.07 (60) Recommended dose: 10ml. Contains 2.3mmol sodium & 1mmol potassium per 5ml dose 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. 1.2 Antispasmodics Antispasmodics Mebeverine Gastro-intestinal System 135mg tablets: £4.43 (100) Avoid prescribing as Colofac IBS® as this is the OTC pack and more expensive. Page 8 Therapeutic Area 1.3 Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Antisecretory drugs Related guidance: Related guidance: NICE CG184 (2014):Dyspepsia H2 - receptor antagonists 1.3.5 Ranitidine 150mg tablets: £1.96 Ranitidine is recommended as first line treatment for mild-moderate GORD in the (60) majority of patients. 300mg tablets: £1.63 Ranitidine is available OTC, but only as 75mg tablets (30) 75mg/5ml S/F oral solution: £7.79 (300ml) Proton pump inhibitors (PPI) Rebound acid hypersecretion and protracted dyspepsia may occur after stopping prolonged treatment with a PPI. Prescribed for appropriate indications at the lowest effective dose for the shortest period. Review the need for long-term treatment periodically. Severe hypomagnesaemia may occur 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 hydroxide (not suitable for patients with short bowel syndrome) or Mucogel (see previous page) Proton-pump inhibitors Lansoprazole capsules 15mg capsules: £1.20 30mg capsules: £1.61 Only use Lansoprazole orodispersible tablets (Zoton FasTabs®) as an alternative to costly special liquid formulations. NICE Dosage information on proton pump inhibitors Omeprazole capsules 10mg capsules: £1.27 20mg capsules: £1.26 As Mepradec® 10mg capsules: £1.13 (28) 20mg capsules: £1.13 (28) Only use Omeprazole dispersible tablets (Losec MUPS®) 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. Pantoprazole tablets 20mg tablets: £1.20 40mg tablets: £1.60 Pantoprazole has been included for circumstances where a tablet formulation is necessary. 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) Gastro-intestinal System Page 9 Therapeutic Area Helicobacter pylori eradication First line: or Second line: Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Please refer to Infection Management Guidance PPI (as opposite) + Metronidazole + Clarithromycin all for 7 days 400mg BD 250mg BD PPI (as opposite) + Amoxicillin + Clarithromycin all for 7 days 1g BD 500mg 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. 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. 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 tablets 2mg tablets: £2.15 (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: £1.27 30mg tablets: £1.41 Just three days of codeine containing medicines can lead to addiction – The CCG 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 10 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 1.5 Chronic bowel disorders Related guidance: NICE CG 166 Ulcerative colitis: management in adults, children and young people Aminosalicylates Patients receiving aminosalicylates should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasia. In line with national guidance it is recommended that Mesalazine is prescribed by brand, however recent data suggests that Asacol MR and Octasa MR have very similar biovailability and could be switched and patient monitored for changes in symptoms. UKMI For all mesalazine preparations monitor renal function as recommended in SmPC. First line: Second line: Mesalazine as Octasa MR 400mg tablets: £19.50 (90) as PentasacSR® 500mg tablets £30.74 (100) 1g tablets £36.89 (60) as Salofalk 500mg sachets: Salofalk sachets: 1.5g equivalent to 2g pentasa or 2.4g Octasa® or Asacol® £28.74 (100) 3g equivalent to 4g Pentasa or 4.8g Octasa® or Asacol® 1g sachets £28.74 (50) 1.5g sachets £48.85 (60) Oral therapy alone is not as effective as a topical salicylate alone or a combined 3g sachets £97.70 (60) oral/topical combined treatment 500mg suppositories £14.81 (28) 2g/59ml enema £29.92 (7) Mesalazine as Mezavant® XL Gastro-intestinal System Where 400mg tablets are required Octasa® tablets are recommended as first line as they are considered to be bioequivalent to the original product Asacol (see above) but at a lower cost. 800mg Octasa® cost more than 2 x 400mg so for cost-effective dose we recommend using 400mg tabs 1.2g tablets: £62.44 (60) Where 500mg tablets are required Pentasa® tablets are recommended. Consultant initiation only (AMBER prescribing). All patients should have evaluation of renal function prior to initiation and at least twice yearly whilst on treatment. Page 11 Therapeutic Area Corticosteroids Formulary Choices Cost for 28 Budesonide as Budenofalk Beclometasone dipropionate as Clipper® Gastro-intestinal System Rationale for decision / comments (unless otherwise stated) 3mg capsules £77.05 (100) 2mg/100ml Rectal Foam: £57.11 (14) 9mg GR granules sachets:£135 (60) 5mg tablets: £56.56 (30) 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. 9mg sachet dose is one per day spinkled onto tongue 30 mins before breakfast Budesonide (and conventional glucocorticosteroid) should not be used to maintain remission NICE CG152 On consultant recommendation only: To induce remission of left-sided or extensive ulcerative colitis as add-on therapy to 5-ASA containing drugs in accordance with NICE CG166 (Jun-13). Maximum course of treatment is four weeks. Page 12 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 13 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 1.6 Laxatives Related guidance: NICE Clinical Guideline CG99 (2010): Constipation in children and young people NICE Technical Appraisal TA211 Constipation (women) - prucalopride Bulk-forming laxatives Stimulant laxatives First line: Second line Ispaghula Husk 3.5g sachets: £2.20 (30) Prescribe generically. Available OTC. 3.4g sachets (e.g. Regulan) are more expensive at £2.44 per 30 Bisacodyl Senna Glycerol suppositories Osmotic laxatives Gastro-intestinal System 5mg tablets: £2.47 (60) 10mg suppositories: £3.52 (12) 7.5mg tablets: £12.64 (60) 7.5mg/5ml SF liquid: £2.69 (500ml) Available OTC. 1g: £0.88 (12) 2g: £0.88(12) 4g: £4.02 (12) All available OTC Glycerin suppository sizes: 1g = infant 2g = child 4g = adult Available OTC. 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. Page 14 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) First line: Macrogol as Laxido Orange Sugar-free as Cosmocol Orange sugarfree As sugar free lemon/lime alternative to Laxido orange as Cosmocol Paediatric Sachets £2.99 (30) For children 2-11 Lactulose 3.35g/5ml solution: £3.09 (500ml) 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. Prucalopride 1mg tablets:£38.69 (28) 2mg tablets:£59.52 (28) Lubiprostone 24mcg capsule: £29.68 (28) £53.48 (56) As per NICE TA211 2010, for chronic constipation in women only for whom treatment with at least two laxatives from different classes, at the highest tolerated recommended doses for at least 6 months, has failed to provide adequate relief and invasive treatment is being considered. Re-evaluate after 4 weeks treatment. As per NICE TA318 2014, for treating chronic idiopathic constipation, that is, for adults in whom treatment with at least 2 laxatives from different classes, at the highest tolerated recommended doses for at least 6 months, has failed to provide adequate relief and for whom invasive treatment for constipation is being considered.Re-examine after 2 weeks treatment. as Cosmocol Half Other drugs used in constipation Sachets £3.99 (30) Lemon/lime Sachets: £5.34 (30) Orange/lemon/lime:£3.99 (30) Sachets £2.99 (30) as Cosmocol Second line Sachets:£4.27 (30) NICE says prescribe oral macrogols as first-line treatment for children and young people with newly diagnosed idiopathic constipation. Gastro-intestinal System Half the dose of standard (minimum 12 years age) Page 15 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Pre-op Bowel Cleansing Solutions N/A Peripheral opioidreceptor antagonist Methylnaltrexone Injection 12mg/0.6ml Bowel cleansing medicine may modify the absorption of regularly prescribed medications. Urea and Electrolytes should be checked in all patients to minimise the risk of electrolyte imbalance particularly patients taking the following medications: Diuretics, corticosteroids, cardiac glycosides, NSAIDs, tricyclics, SSRIs, 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: £2.32 (23g) Ointment: £2.32 (25g) Suppositories: £2.14 (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: £39.30 (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 non-formulary. Acute trust commissioned to provide full treatment course. Gastro-intestinal System Page 16 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) BNF Chapter 2: Cardiovascular system Related guidance: NICE Clinical Guideline CG127 (2011): Hypertension: Clinical management of primary hypertension in adults NICE Clinical Guideline CG180 (2014): Atrial fibrillation NICE Clinical Guideline CG172 (2013): 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. 2.1 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 Positive inotropic drugs Cardiac glycosides Cardiovascular system Digoxin 62.5mcg tablets: £1.41 125mcg tablets: £1.05 250mcg tablets: £1.01 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. Doses of greater than 250mcg per day in adults and greater than 125mcg in patients over 70years should rarely be seen. Page 17 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.2 Diuretics Thiazides and related diuretics Indapamide 2.5mg tablets: £3.88 1.5mg MR tablets: £3.40 (30) Hypertension: indapamide 2.5mg daily is considered the optimal dose for hypertension. Low dose indapamide 1.5mg SR has been shown to control hypertension as effectively as 2.5mg (IR) with lower incidence of hypokalaemia. http://www.ncbi.nlm.nih.gov/pubmed/8572850 Bendroflumethiazide NB People treated with bendroflumethiazide whose blood pressure is stable & well controlled should continue on bendroflumethiazide 2.5mg tablets £0.82 Loop diuretics Aldosterone Antagonists Metolazone 2.5mg tablets 5mg tablets No longer marketed in UK but remains on formulary for consultant recommendation (Amber drug in the TLG.) Furosemide 20mg tablets:£0.82 40mg tablets: £0.82 Furosemide is included in the formulary for use Spironolactone Eplerenone Cardiovascular system Heart failure: bendroflumethiazide may have a limited role in mild heart failure or where patients are intolerant of loop diuretics. 25mg tablets: £1.33 50mg tablets: £1.80 25mg tablets: £42.72 50mg tablets: £42.72 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 18 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.3 Anti-arrhythmic drugs Drugs for arrythmias Amiodarone 100mg tablets: £1.36 200mg tablets: £1.77 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: 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 simvastatin is used. Dronedarone 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 What issues should be considered regarding drug induced QT prolongation? Prolongation of the QT interval can lead to a life threatening ventricular arrhythmia known as torsades de pointes which can result in sudden cardiac death. Recently there have been warnings relating to drug-induced QT prolongation for three commonly used drugs – citalopram, domperidone and ondansetron. There are also a number of other widely used drugs which are known to cause QT prolongation and there are a number of drug interactions which can increase the risk of this adverse effect occurring. Full list of medicines that prolong QT interval Cardiovascular system Page 19 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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: £1.23 2.5mg tablets: £1.18 3.75mg tablets: £1.81 5mg tablets: £0.98 7.5mg tablets: £4.32 10mg tablets: £1.06 25mg tablets: £0.92 50mg tablets: £0.95 100mg tablets: £1.12 50mg tablets: £1.03 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 20 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.5 Drugs affecting the renin-angiotensin system and other antihypertensives ACE-inhibitors (ACEIs) should be used in line with NICE / CCG 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: £1.15 5mg tablets: £1.12 10mg tablets: £1.11 20mg tablets: £1.15 1.25mg capsules:£1.06 2.5mg capsules: £1.14 5mg capsules: £1.22 10mg capsules: £1.45 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 21 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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 / CCG guidance for hypertension and heart failure. Angiotensin-II receptor blockers (ARBs) First line: 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) 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: £1.18 50mg tablets: £1.21 100mg tablets: £1.37 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:£2.72 (7) 4mg tablets:£0.89 (7) 8mg tablets:£1.72 16mg tablets: £2.12 32mg tablets: £3.05 Candesartan is included in the formulary for: 40mg capsules:£1.49 80mg capsules:£1.89 160mg capsules:£2.58 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 22 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Centrally acting antihypertensive drugs Methyldopa Moxonidine Alpha-blockers Doxazosin as Doxadura® Cardiovascular system 125mg tablets: £55.79 (56) 250mg tablets: £6.33 (56) 500mg tablets: £9.39 (56) Methyldopa is included in the formulary for: 200mcg tablets: £2.47 300mcg tablets: £2.67 400mcg tablets: £2.80 Moxonidine is included in the formulary for: 1mg tablets: £0.90 2mg tablets: £0.94 4mg tablets: £1.09 Doxazosin is included in the formulary for: 1mg tablets: £0.81 2mg tablets: £0.84 4mg tablets: £1.03 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: 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. Doxazosin MR 4mg one daily → Doxazosin 4mg one daily Doxazosin MR 8mg one daily → Doxazosin 4mg two daily Page 23 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) 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) + Thiazide-like diuretic + consider further diuretic or alphablocker or beta-blocker Consider seeking expert advice 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] Spironolactone does not have a UK marketing license for this indication. Informed consent should be obtained and documented Consider an α-blocker or β-blocker if further diuretic therapy is not tolerated, or contraindicated or ineffective Page 24 Cardiovascular system Page 25 Prescribing Guidelines for HEART FAILURE This guidance is not intended to replace NICE CG108 Chronic heart failure (Aug-10), 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 to 10mg ONCE DAILY Monitoring: serum urea, creatinine, electrolytes and eGFR at initiation and after each dose increment Cardiovascular system Page 26 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 27 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 28 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 Traffic Light Guidance (TLG). 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. (M. Tanaka et al. (2005) The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema. Clinical and Experimental Nephrology, 9: 122-126) Cardiovascular system Page 29 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 CG127 (Aug-11) 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 TA267 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. New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction who are in sinus rhythm with a heart rate of 75 beats per minute or more 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) with a left ventricular ejection fraction of 35% or less Initiation may be by GP with special interest (GPwSI) or heart failure specialist nurse. Cardiovascular system Page 30 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 CCG 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 31 Prescribing guideline post myocardial infarction -Drug therapy CG 172 secondary Prevention of MI Offer all people who have had an acute MI treatment with the following drugs: o ACE (angiotensin-converting enzyme) inhibitor o dual antiplatelet therapy (aspirin plus a second antiplatelet agent) o beta-blocker o statin. Offer an assessment of left ventricular function to all people who have had an MI. Titrate the ACE inhibitor dose upwards at short intervals (for example, every 12–24 hours) before the person leaves hospital until the maximum tolerated or target dose is reached. If it is not possible to complete the titration during this time, it should be completed within 4– 6 weeks of hospital discharge. Communicate plans for titrating beta-blockers up to the maximum tolerated or target dose – for example, in the discharge summary. Offer an ACEI and aspirin to patients who have had an MI >12 months ago and also a β blocker to patients with LVSD whether symptomatic or not (new for 2013) ACE intolerant should be offered an ARB. Statins are recommended for all patients with established cardiovascular disease. NICE does not specify preferred ACE and β blockers Medicines with licence post MI ACEI Target dose Max dose Cr Cl >60 ml/min Max dose CrCl 30-60ml/min Max dose CrCl 1030ml/min Ramipril (with or without heart 10mg 10mg 5mg 5mg Lisinopril 10mg Licensed for short term (6 week) use in Post MI Perindopril 8mg 4mg Captopril (only with LV failure) 100mg License is 4 weeks failure) 2mg 2mg alternate days No data No data ARB Valsartan Seek secondary care advice β blocker Bisoprolol 10mg Metoprolol,propranolol, timolol or atenolol Seek secondary care advice Cardiovascular system No data Page 32 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.6 Nitrates, calcium channel blockers and potassium channel activators Nitrates ISMN First line: ISMN second line: Glyceryl trinitrate (GTN) spray as Nitromin® Isosorbide mononitrate Instant release Glyceryl trinitrate is included in the formulary for: 400mcg: £3.44 (200 dose) 400mcg: £2.63 (180 dose) 10mg: £13.09 (56) 20mg: £14.08 (56) 40mg: £12.89 (56) Sustained-release as Tardisc XL 60mg tablets: £3.49 (28) Current generic price: £10.50 (28) Angina: for as required use for relief of symptoms Note that GTN tablets are now significantly more costly than spray 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 ISOSORBIDE DINITRATE is NON-FORMULARY except where initiated by a specialist for left ventricular failure Cardiovascular system Page 33 Primary Care Guidelines for the Drug Treatment of Chronic Stable Angina Pectoris Preventing and treating episodes of Angina Stable angina for medical management Short-acting sublingual spray or buccal nitrate prn Disp Aspirin 75mg od (+/- PPI) plus Atorvastatin 80mg. Target cholesterol as per any co-morbidity (eg diabetes) and relevant NICE guidance plus Contraindication (e.g. proven allergy to aspirin) Clopidogrel 75mg od (+/-) Pantoprazole Reduce dose of atorvastatin if any interactions or high risk of adverse effects or patient choice If patient is intolerant of atorvastatin, try simvastatin, pravastatin or rosuvastatin or (due to lack of evidence) final option is ezetimibe ACE (Ramipril or Lisinopril) in proven CVD titrated to max tolerated dose Treatment aimed at relief of symptoms Version 5 October 2014 1ST Line - Beta-blocker (bisoprolol) or Calcium antagonist (Amlodipine) titrate to maximum tolerated dose Symptoms not controlled 2nd Line Beta blocker AND calcium antagonist (amlodipine) Symptoms controlled do not offer a third drug Intolerant (e.g. fatigue) or contraindication to 1st drug Intolerant to both Beta-Blocker and Calcium Antagonist *Discontinue ivabradine if resting heart rate becomes too low <60 bpm or symptoms of bradychardia persist Consider 3rd drug ONLY when symptoms not controlled on 2 drugs AND the person is waiting for revascularisation or revascularisation is not considered appropriate or acceptable MR nitrate (Tardisc XL £3.49) or Nicorandil 20mg (£10.53) or Ivabradine* (£40.17) or Ranolazine (£48.98) based on CI, preference and cost Cardiovascular system DO NOT OFFER A 4th DRUG Consider switch of 3rd Line drug Switch to other option as monotherapy (Amlodipine) Symptoms not controlled MR nitrate (Tardisc XL £3.49) or Nicorandil 20mg (£10.53) or Ivabradine* (£40.17) or Ranolazine (£48.98) based on CI, preference and cost Symptoms controlled do not offer a third drug ANGINA not responded to treatment Re-evaluation and advice eg Skills to modify cognitions and behaviours associated with pain and self manage pain Review drug treatment and revascularisation Page 34 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Calcium channel blockers – Dihydropyridines First line: Amlodipine as Amlostin® Second line: Lercanidipine 5mg tablets: £0.89 10mg tablets: £0.94 NB. Avoid short-acting dihydropyridines in BP, CHD and CCF. Amlodipine is first line CCB, with lercanidipine as a second line option for: 5mg tablets: £0.80 10mg tablets: £0.85 Hypertension: in line with NICE guidance 10mg tablets: £1.55 20mg tablets: £1.86 Angina: as monotherapy where intolerance or C/I to use of a beta-blocker 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 Modified-release as Zemtard XL Once daily dose 120mg m/r capsules: £6.10 180mg m/r capsules: £6.20 240mg m/r capsules: £6.30 300mg m/r capsules: £6.70 Verapamil Immediaterelease Prescribe by brand Angina: as monotherapy where intolerance or C/I to use of a beta-blocker. 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 Zemtard XL brand ensures continuity of supply, as recommended nationally. Verapamil should not be combined with a beta-blocker for any indication due to high risk of bradycardia and heart-block 40mg tablets: £1.66 (84) 80mg tablets: £2.10 (84) Modified-release Half-Securon SR 120mg m/r tablets: £7.71 Securon SR 240mg m/r tablets: £5.55 Cardiovascular system Diltiazem XL (as Zemtard XL) is included in the formulary for: Verapamil is included in the formulary for: Angina: as monotherapy where intolerance or C/I to use of a beta-blocker. Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. Page 35 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.6.3 Other antianginal drugs Potassium Channel Activator Nicorandil 10mg: £3.73 (60) 20mg: £7.33 (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.34. AMBER for management of heart failure (see guidelines page 26) Other 2.6.4 Ranolazine 375mg: £48.98 (60) 500mg: £48.98 (60) 750mg: £48.98 (60) 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 substance-induced eg with potassium-depleting diuretics (thiazide diuretics and loop diuretics). Caution & careful monitoring is needed. *Ivabradine: MHRA alert June 2014 emerging clinical trial evidence of increased cardiovascular risk—carefully monitor for bradycardia Included for medical management of Stable angina: in line with NICE CG126 See guide p.34 Peripheral vasodilators and related drugs Related guidance: NICE Technology Appraisal TA223 (2011): Treatment of intermittent claudication in people with peripheral vascular disease Vasodilators Naftidrofuryl 100mg capsules: £6.58 (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. Cardiovascular system Page 36 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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 K 1) 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. 2.8.2 Oral anticoagulants Coumarins Management of patients on warfarin should be in line with the National Enhanced Service specification. Refer to National Patient Safety Agency (NPSA) guidance on safe practices around use of anticoagulants. Warfarin Continued overleaf Cardiovascular system 500mcg tablets: £1.40 1mg tablets: £0.89 3mg tablets: £0.93 5mg tablets: £0.98 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 37 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) New Oral Anticoagulants (NOACs) For primary care prescribing see NICE guidance on: Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation – TA249 Dabigatran for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism – TA327 Rivaroxaban – TA256, TA261, TA287 Apixaban – TA275 Primary prevention of venous thromboembolic events in adult patients after elective total hip replacement surgery or total knee replacement surgery is hospital prescribing only: (see NICE TA157 Dabigatran, NICE TA170 Rivaroxaban, and NICE TA245 Apixaban. 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. (RED Indication in TLG) Direct thrombin Inhibitor Cardiovascular system Dabigatran 75mg capsules: £65.90 (60) 75mg only for after elective knee & hip surgery in some patients – RED 110mg capsules:£65.90 (60) 150mg capsules:£65.90 (60) Dabigatran is included for Prevention of stroke & systemic embolism for people with non-valvular atrial fibrillation where patients fit the criteria in NICE TA249. See Implementation priorities. Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults. TA327 See note above for use post elective hip & knee replacement (NICE TA157). Page 38 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Direct inhibitor of activated Factor X Rivaroxaban 10mg tablets: £63.00 (30) 10mg only for after elective knee & hip surgery – RED 15mg tablets: £58.80 (28) 20mg tablets: £58.80 (28) For the prevention of stroke & systemic embolism for people with nonvalvular atrial fibrillation in accordance with NICE TA256. See p50 for implementation priorities and; For treating and preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults in accordance with NICE TA261 and; An option for treating pulmonary embolism and preventing recurrent deep vein thrombosis and pulmonary embolism in adults in accordance with NICE TA287 and; As an option to treat signs and symptoms of DVT and 15mg and 20mg strengths for prevention of cardiovascular disease in patients with atrial fibrillation undergoing cardioversion See note above for use post elective hip & knee replacement (NICE TA170) Apixaban Cardiovascular system 2.5mg tablets: £65.90 (60) 2.5mg only for after elective knee & hip surgery – RED 5mg tablets: £61.50 (56) 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, such as prior stroke or transient ischaemic attack (TIA); age ≥ 75 years; See note above for use post elective hip & knee replacement (NICE TA245). Apixaban has recently had licence extended to treatment of DVT and PE, and prevention of recurrent DVT and PE in adults. Awaiting NICE approval on this. Page 39 Drug interactions for Apixaban, Dabigatran & Rivaroxaban Drug Apixaban (APB) Dabigatran (DBG) Rivaroxaban (RVB) Any other anticoagulants Contraindicated (except when switching treatments) Contraindicated (except when switching treatments) Contraindicated (except when switching treatments) Antiplatelet agents – assess risk/need balance Increased risk of bleeding Increased risk of bleeding Increased risk of bleeding Strong CYP34A Inducer eg. Rifampicin, phenytoin, carbamazepine, St Johns Wort Caution ↓apixaban plasma levels and increased bleeding risk AVOID ↓dabigatran plasma levels CAUTION ↓rivaroxaban plasma levels Strong CYP34A and P-gp Inhibitors: 1. Systemic Azole-antimycotics (eg itraconazole, ketoconazole) Avoid ↑ bleeding risk Contra-indicated Avoid ↑ bleeding risk 2. HIV Protease Inhibitors Avoid ↑ bleeding risk Not studied – combination not recommended Avoid ↑ bleeding risk 3. Ciclosporin, tacrolimus Contra-indicated No data Strong CYP3A4 and moderate P-gp inhibitors 1. Clarithromycin, diltiazem, quinidine, amiodarone, verapamil No dose reduction. Caution ↑dabigatran plasma levels (especially in renal impairment) Verapamil – reduce dose (see SPC for detail) ↑rivaroxaban plasma levels, not considered clinically relevant but Caution if renal impairment 2. Dronedarone No data in SPC Contra-indicated Avoid – limited clinical data SSRIs/SNRIs/NSAID (including aspirin) Increased risk of bleeding Increased risk of bleeding Increased risk of bleeding All data sourced from SmPCs for APB, DBG, RVB Cardiovascular system Page 40 Decision aid for patients requiring stroke prevention in AF (there are no head-to-head trials between NOACS, and trials vs warfarin had different entry criteria)) Rivaroxaban▼ Apixaban ▼ 20mg OD 5mg BD FXa inhibitor FXa inhibitor Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Prevention of stroke and systemic embolism in adults with NVAF with ≥1 risk factor: Previous stroke, TIA, or systemic embolism (SEE) Left ventricular ejection fraction < 40 % Symptomatic heart failure, ≥ NYHA Class 2 Age ≥ 75 years Age ≥ 65 years with diabetes mellitus, coronary artery disease, or hypertension Treatment of DVT and PE Prevention of recurrent DVT and PE in adults Prevention of stroke and systemic embolism in adults with NVAF with ≥1 risk factor: congestive heart failure, hypertension age ≥ 75 years diabetes mellitus prior stroke or TIA. Prevention of cardiovascular disease in AF patients undergoing cardioversion Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Warfarin Dabigatran Dose Variable OD 110mg BD Class Vitamin K antagonists (VKA) Direct thrombin inhibitor Licensed indications (primary care prescribing) Prophylaxis of systemic embolism in rheumatic heart disease and AF Prophylaxis after insertion of prosthetic heart valves Prophylaxis and treatment of VTE and PE Transient attacks of cerebral ischaemia 150mg BD Prevention of stroke and systemic embolism in adults with NVAF, with ≥1 risk factor: prior stroke or TIA age≥ 75 years hypertension diabetes mellitus symptomatic heart failure ≥ NYHA Class 2 Comparator NICE TA249 NICE TA256 NICE TA275 VTE tx and prevention Comparator NICE TA327 NICE TA261 PE & recurrent VTE Comparator NICE TA327 NICE TA287 Stroke and systemic embolism Risk Comparator Non‐inferior Non‐inferior Superior Mortality Comparator No difference No difference Life‐ threatening bleed / ICH & major / minor bleeding Comparator Lower risk (both strengths) Lower risk All‐cause mortality 11% Lower risk Major bleed Comparator Lower risk Major GI bleeding Comparator No difference Must take with food? No No Dose frequency OD BD OD BD Initiation Variable Stroke & SEE: no change Stroke & SEE: no change DVT & PE: 15mg BD 21/7 Stroke & SEE: no change Elderly (>80 years) INR dependent as for other age groups No dose change. If also ≤ 60kg and / or serum creatinine ≥1.5mg/dl (133μmole/l): dose (2.5mg BD) Drug-drug interactions CYP2C9 CYP1A2 CYP3A4 inhibitors CYP3A4 P-glycoprotein CYP3A4 P-glycoprotein Bleeding risk NICE NVAF Stroke and SEE prevention Cardiovascular system Superior No difference No difference Higher risk Higher risk Yes dose (110mg BD) P-glycoprotein Lower risk No difference No Page 41 Dose Warfarin Dabigatran Variable OD 110mg BD 150mg BD Rivaroxaban▼ Apixaban ▼ 20mg OD 5mg BD Can be added to MDS compliance aids Can be added to MDS compliance aids Dietary vitamin K Monitored Dosage System (see RPS Guidance) Not suitable for MDS compliance aids Use with careful monitoring & specialist advice Contra‐indicated Increased bleeding risk (Plasma levels may be increased ( ~ 1.6x ) Renal Impairment CKD 4 and 5 Cr Cl <30ml/min Not suitable for MDS compliance aid inclusion unless NPSA guidance followed Cr Cl 15‐29ml/min –use with caution - reduce to 15mg OD Cr Cl 15‐29ml/min –reduce dose to 2.5mg bd Cr Cl <15ml/min –not recommended Cr Cl <15ml/min –not recommended Advisable to use warfarin if Cr Cl 15‐29ml/min and renal function expected to deteriorate further. CKD 3 Cr Cl 30- 49ml/min Safe to use: dose INR dependent Hepatic impairment Monitor INR more frequently Use 110mg dose if patient has a high bleeding risk Reduce the dose to 15mg od. No information available Contraindicated in hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B & C. Liver enzymes >2x ULN: not recommended No dose adjustment needed Contraindicated in hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Not recommended in patients with severe hepatic impairment Use with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B, no dose adjustment needed). Use with caution in patients with elevated liver enzymes (ALT / AST >2x ULN) or total bilirubin ≥1.5x ULN. Antidote for haemorrhage Vitamin K No antidote Supportive care only. Potential problem where emergency surgery is needed Not reversible. Early clinical trial data suggests bleeding effects completely reversed by Prothrombin Complex Concentrate (PCC). Supportive care only. Potential problem where emergency surgery needed. Not reversible. If bleeding is uncontrolled with supportive measures, administration of recombinant factor VIIa may be considered. Potential problem where emergency surgery needed. Prescriber guides & Patient alert cards Safety alerts NPSA: Actions that can make oral anticoagulant therapy safer NPSA management guidance Yellow books available via SBS (stationary order) Pradaxa® education resources Pradaxa® Patient Alert Card Xarelto® resources Xarelto® Patient Card Eliquis® resources. Eliquis® Patient Alert Card EHRA / ESC AF Oral Anticoagulation Card for non-vitamin K anticoagulants MHRA Drug Safety Update Oct 2013 - Revised contraindications for all NOACs AF = atrial fibrillation; BD = twice daily; DVT = deep vein thrombosis; GI = gastro-intestinal; ICH = intracranial haemorrhage; NYHA = New York Heart Association; NVAF = non-valvular atrial fibrillation; OD = once daily; PE = pulmonary embolism; SEE = systemic embolic event; TIA = transient ischaemic attack; ULN = upper limit of normal. Cardiovascular system Page 42 Reducing the risk of stroke in atrial fibrillation NICE CG180 Guide for health professionals The NICE guideline recommends that anticoagulation should be considered for men with a CHA2DS2-VASc score of 1 or more and offered to men and women with a CHA2DS2-VASc score of 2 or more, taking their bleeding risk into account. The guideline recommends that anticoagulation may be with apixaban, dabigatran etexilate, rivaroxaban or a vitamin K antagonist, and includes the relevant technology appraisals for apixaban, dabigatran etexilate and rivaroxaban. It recommends that the options for anticoagulation are discussed with the person and the choice based on their clinical features and preferences. The NICE guideline makes no recommendations for using one anticoagulant over another and no analysis compared the efficacy and safety of apixaban, dabigatran or rivaroxaban (the novel anticoagulants, or NOACs) with each other or with warfarin, so no similar comparisons have been made in this PDA. The NICE guideline recommends against the use of aspirin monotherapy solely for stroke prevention to people with atrial fibrillation and makes no recommendations about use of dual antiplatelet therapy, so these options are not discussed in the PDA. Assessment of stroke and bleeding risks Stroke risk Use the CHA2DS2-VASc stroke risk score to assess stroke risk in people with any of the following: symptomatic or asymptomatic paroxysmal, persistent or permanent atrial fibrillation atrial flutter a continuing risk of arrhythmia recurrence after cardioversion back to sinus rhythm. Bleeding risk Use the HAS-BLED score to assess the risk of bleeding in people who are starting or have started anticoagulation. Offer modification and monitoring of the following risk factors: uncontrolled hypertension poor control of international normalised ratio (INR) ('labile INRs') concurrent medication, for example concomitant use of aspirin or a non-steroidal anti-inflammatory drug (NSAID) harmful alcohol consumption. When discussing the benefits and risks of anticoagulation, explain to the person that: for most people the benefit of anticoagulation outweighs the bleeding risk for people with an increased risk of bleeding the benefit of anticoagulation may not always outweigh the bleeding risk, and careful monitoring of bleeding risk is important. Do not withhold anticoagulation solely because the person is at risk of having a fall. Cardiovascular system Page 43 Patient decision aid- please note this is not actual NICE guidance Cardiovascular system Page 44 Cardiovascular system Page 45 Cardiovascular system Page 46 Bleed risk-HAS-BLED There is little to support a patient decision aid with a HAS-BLED score of 0. The risk is very low whether they take an anticoagulant or not. Cardiovascular system Page 47 Cardiovascular system Page 48 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 All new and existing Non Valvular AF patients should discuss with their clinician the risks and benefits of dabigatran compared to warfarin before initiation or switching 1st 2nd 3rd 4th Patients newly diagnosed with Non Valvular AF – with good medicine compliance. Dabigatran is NOT suitable for most 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 49 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 All new and existing Non Valvular AF patients should discuss with their clinician the risks and benefits of rivaroxaban compared to warfarin before initiation or switching 1st Patients newly diagnosed with Non Valvular AF – with good medicine compliance. Rivaroxaban is suitable for patients using MDS systems Dose 20mg ONCE DAILY for all ages Dose 15mg ONCE DAILY if creatinine clearance 15-49 ml/min 2nd Patients fitting Criteria currently receiving no preventative treatment 3rd 4th Patients fitting Criteria receiving just aspirin – Aspirin offers little protection against stroke in AF compared to warfarin or rivaroxaban Patients with unstable INR on Warfarin or Phenindione. Start with those patients most commonly out of treatment range. House Bound patients requiring remote monitoring of INR If a dose is missed the patient should take rivaroxaban immediately and continue on the following day with the once daily intake as recommended. The dose should not be doubled within the same day to make up for a missed dose. Pregnancy Safety and efficacy of rivaroxaban have not been established in pregnant women. Studies in animals have shown reproductive toxicity and rivaroxaban passes the placenta. Contraindicated during pregnancy 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 50 Cardiovascular system Page 51 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.9 Antiplatelet drugs Related guidance: NICE Technology Appraisal TAG210 (2010): Clopidogrel and modified-release dipyridamole Anti-platelet drugs Aspirin 75mg dispersible tablets: £0.80 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 Clopidogrel Following consideration of available evidence at Somerset Prescribing Forum Sep-09 it was agreed that generic versions of clopidogrel may be used for all indications 75mg tablets: £1.74 (30) Clopidogrel is recommended by NICE as an option to prevent occlusive vascular events; for people who have had an ischaemic stroke or who have peripheral arterial disease or multivascular disease or TIA (by local agreement) Clopidogrel is also included in the formulary for: patients with true aspirin allergy who require secondary prevention of cardiac or vascular disease patients who have had an NSTEMI, regardless of treatment (up to 12 months) patients who have had a STEMI and received a bare-metal or drugeluting stent for up to 12 months (new for 2013) patients who have had a STEMI and medical management with or without reperfusion treatment with a fibrinolytic agent. [new 2013] (at least 1 month and up to 12 months) Continued on next page Cardiovascular system alternative to aspirin in people who also have other clinical vascular disease, in line with Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (NICE TA 210), and who have: had an MI and stopped dual antiplatelet therapy or had an MI more than 12 months ago. [new 2013] Page 52 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) (Continued from previous page) 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. 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, or if clopidogrel (unlicensed use) has been excluded Dipyridamole m/r (with Aspirin) as Asasantin Retard 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. Continued on next page Cardiovascular system Page 53 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Anti-platelet drugs Prasugrel (Continued from previous page) 5mg tablets: £47.56 10mg tablets:£47.56 Prescribers should ensure that all prescriptions for prasugrel have a stop date and that no repeats are issued after that date. Ticagrelor Prescribers should ensure that all prescriptions for ticagrelor have a stop date and that no repeats are issued after that date. Prasugrel 10mg in combination with aspirin is recommended as an option for preventing atherothrombotic events in adults 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 TA317: Acute coronary syndrome - prasugrel) £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. 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 54 2.12 Lipid-regulation Primary prevention of CVD (based on NICE Clinical Guideline CG181 (July 2014): 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 55 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 56 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 Eslicarbazepine No interaction No interaction Eslicarbazepine reduces systemic exposure to RSV when co administered Eslicarbazepine reduces systemic exposure to SMV when co-administered 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 Fusidic acid Contraindicated – suspend ATV 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 No interaction Contraindicated – suspend SMV No interaction 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 57 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 2.12 Lipid-regulating drugs. Related guidance: Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease 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 atftempts 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.57 Statins First line: Atorvastatin Simvastatin as Simvador® Continued on next page Cardiovascular system 10mg tablets: £1.13 20mg tablets: £1.41 40mg tablets: £1.99 80mg tablets: £2.73 10mg tablets: £0.77 20mg tablets: £0.86 40mg tablets: £1.04 80mg tablets: £1.78 10mg tablets: £0.77 20mg tablets: £0.86 40mg tablets: £1.04 80mg tablets: £1.78 Atorvastatin is first line statin for all new patients unless contraindicated. It is included in the formulary for: Hypercholesterolaemia Primary prevention of cardiovascular events (where 10year CVD risk ≥ 10%) Secondary prevention of CV events (give 80mg) 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)) Page 58 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Statins Continued from previous page 2nd line: Pravastatin 10mg tablets: £1.20 20mg tablets: £1.44 40mg tablets: £1.77 3rd line: Rosuvastatin 5mg tablets: £18.03 10mg tablets: £18.03 20mg tablets: £26.02 40mg tablets: £29.69 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. Pravastatin and Rosuvastatin have a different metabolic pathway so may be tolerated when Simvastatin or Atorvastatin are not. Cardiovascular system Page 59 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Other lipid lowering drugs 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. Ezetimibe 10mg tablets: £26.31 Ezetimibe is included in the formulary only for: monotherapy for patients intolerant to any statin 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 Local specialist advice is to also consider check triglyceride levels & consider fibrate. 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. Fibrates Fenofibrate micronized as Supralip brand 200mg capsules: £2.56 160mg capsules: £6.69 Nicotinic acid Bile acid sequestrants (Anionic exchange resins) Colestyramine (Questran®) Colesevelam Colestipol Specialist recommendation ONLY Consider use only in severe hypertriglyceridaemia. Do not routinely offer fibrates for the prevention of CVD to any of the following: people who are being treated for primary prevention people who are being treated for secondary prevention people with CKD people with type 1 diabetes people with type 2 diabetes. These lipid lowering drugs are usually initiated in secondary care by clinical biochemists for patients with complex dyslipidaemias. Nicotinic acid and bile acid sequestrants : do not use as for fibrates above Tredaptive (Nicotinic acid + laropiprant) withdrawn from market Jan 2013. HPS2-THRIVE trial failed to show reduced risk of CV events & incidence of serious adverse events in the treatment group was higher. Omega-3-acid ethyl esters (Omacor®) now non-formulary. NICE MI:secondary prevention (CG172) Nov 2013 says not to offer people omega 3 fatty acid capsules or supplemented foods to prevent another MI. Similarly NICE CG 181 Lipid modification July 2014 does not recommend using omega-3 fatty acids to help prevent CVD Cardiovascular system Page 60 Summary of NICE guidance on the use of statins and ezetimibe in adults This summary is intended only as a guide to certain aspects of the use of statins and ezetimibe. It is not a comprehensive guide to all aspects of care. See the relevant NICE guidance or NICE pathways for specific details, including who should be offered treatment, additional or alternative treatment options, referral and monitoring recommendations. Cardiovascular system Page 61 BNF Chapter 3: Respiratory System Related guidance: NICE Technology Appraisal TAG138 (2008): Asthma (in adults) - corticosteroids BTS / SIGN Guideline 141 (October 2014): British Guideline on the Management of Asthma Top 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.70/55 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 BDP = 400mcg BDP ® 400mcg budesonide (Pulmicort®/Symbicort®/Easyhaler®) ® ® ® 200mcg fluticasone (Flixotide /Seretide /Flutiform ) Respiratory System – Bronchodilators Page 62 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) 3.1 Bronchodilators Short acting beta-2 agonist bronchodilators (SABAs) First line: A salbutamol inhaler contains 25 days supply at full dose ( 8 puffs/day) Patients reliant on this dosage are poorly controlled and should be urgently reviewed. We would recommend that any patient using more than 2 reliever inhalers in a year have their technique and compliance checked. Salbutamol CFC-free MDI Second line: 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. 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 Respiratory System – Bronchodilators 100mcg/dose: £3.31 (200 dose) 200mcg/dose: £6.63 (200 dose) Page 63 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) Long acting Beta-2 agonist bronchodilators (LABAs) First line: 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 p70) In COPD, LABAs should be used in line with the local COPD guidance (page 57) If no benefit after trial period, stop treatment Formoterol Dry powder inhaler as Easyhaler 12mcg: £23.75 (120 dose) Formoterol is the first line LABA as Easyhaler. Maintenance dose is 12mcg once or twice daily. as Oxis Turbohaler 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 MDI as Atimos Second line: Salmeterol Salmeterol is the second line LABA as CFC-free MDI 25mcg: £29.26 (120 dose inhaler) as Accuhaler 50mcg: £29.26 (60 dose inhaler) Indacaterol as Breezhaler® Olodaterol 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. 300mcg: £29.26 (30 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. 2.5mcg:£26.35 (60 doses) Adults over 18, 2 puffs twice a day 150mcg: £29.26 (30 dose inhaler) as Striverdi Respimat® Respiratory System – Bronchodilators Page 64 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) Short acting anticholinergic bronchodilators Ipratropium as cfc-free MDI Long acting anticholinergic bronchodilators Aclidinium bromide Dry powder inhaler as Eklira Genuair▼ Glycopyrronium bromide Dry powder inhaler as Seebri Breezhaler® ▼ Tiotropium Dry powder inhaler as Handihaler Soft-mist inhaler as Respimat ▼ Umeclidinium Dry powder inhaler as Incruse Ellipta▼ Respiratory System – Bronchodilators 20mcg: £5.05 (200 dose inhaler) Do not co-prescribe Ipratropium with Tiotropium because of risk of increased anticholingeric adverse effects. 400mcg: £28.60 (60 dose pack) 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) 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 p. 80 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 2.5mcg: £33.50 (60 dose pack) Tiotropium Respimat (soft-mist inhaler) was included in the formulary for patient choice 55mcg:£27.50 (30 doses) The recommended dose in adults (also the maximum dose) is one inhalation of Incruse Ellipta once daily at the same time of the day each day. Page 65 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) Theophylline Reduce the dose of theophyline if macrolide or quinolones antibiotics (or other drugs known to interact) are prescribed to treat an exacerbation. Prescribe by brand. Theophylline MR as Nuelin SA® 175mg tablets: £6.38 (60) 250mg tablets: £8.92 (60) as Slo-Phyllin® 60mg capsules: £2.76 (56) 125mg capsules: £3.48 (56) 250mg capsules: £4.34 (56) as Uniphyllin Continus® 200mg tablets: £2.95 (56) 300mg tablets: £4.77 (56) 400mg tablets: £5.65 (56) 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. Aminophylline Aminophylline MR as Phyllocontin Continus® Respiratory System – Bronchodilators Offer theophylline only after trials of short- and long-acting bronchodilators, or to people who cannot use inhaled therapy. 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. Take care when prescribing theophylline to older people. Consider altered pharmacokinetics, comorbidities, and interactions with other medicines; 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. 225mg tablets: £2.40 (56) 350mg tablets: £4.22 (56) Page 66 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) 3.2 Corticosteroids (See advice on safer use of inhaled corticosteroids p 62) Inhaled corticosteroids (ICS) BTS / SIGN Guideline (141) 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 p62 CFC-free MDIs as Clenil Modulite as Qvar Budesonide 50mcg: £3.70 (200 dose) 100mcg: £7.42 (200 dose) 200mcg: £16.17 (200 dose) 250mcg: £16.29 (200 dose) Children up to age 15 should use these products with a Volumatic® 50mcg: £7.87 (200 dose) 100mcg: £17.21 (200 dose) Qvar is not licensed in patients under 12yrs. 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) as Easyhaler Respiratory System – Inhaled Corticosteroids 100mcg:£8.86 (200 dose) 200mcg £17.71 (200 dose) 400mcg: £17.71 (100 dose) Licensed from age 6 years. Page 67 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) 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 50mcg/5mcg £18.00 125mcg/5mcg £29.26 250mcg/10mcg: non-formulary 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 years. The 250mcg strength is non-formulary: licensed for over 18 years only and limited indications for high dose fluticasone in asthma (estimated only 1% asthma patients should need such a high dose combination.) Fostair (Beclomethasone / Formeterol) CFC-free MDI 100mcg/6mcg: £29.32 (120 dose inhaler) OVER 18 YEARS ONLY Fostair NEXThaler (Beclomethasone / Formeterol) ultrafine dry powder inhaler 100mcg/6mcg: £29.32. (Monthly cost of 1 puff bd= £14.63) (120 dose inhaler) WARNING: beclomethasone 100mcg in Fostair is equivalent to 250mcg of standard beclomethasone because of extra fine particle size. Patient should receive specific training and information leaflet on this issue. Asthma only. Fostair (MDI) is also licensed for use in COPD. Beclometasone-formoterol as maintenance and reliever therapy (MART): Patients over 18 years, at Step 3, who are poorly controlled may also use Fostair® as a rescue medication (maximum 8 puffs per day - equivalent 2000mcg standard BDP), with no Salbutamol. Careful patient education is required and quantity of inhalers used monitored. NEXThaler has same BDP equivalent as Fostair MDI Relvar® Ellipta® ▼ (Fluticasone furoate/vilanterol) Dry powder inhaler Respiratory System – Inhaled Corticosteroids 92mcg/22mcg: £27.80 (30 dose) 184mcg/22mcg: £33.50 (30 dose) Long acting once daily dosage due to the long acting furoate salt and LABA. Dose equivalent to 500mcg daily fluticasone proprionate (1000mcg BDP) Asthma: Both strengths licensed in adults and children >12years NOTE: Licensed for new patients uncontrolled at step 2 i.e no license for switching well controlled patients from another ICS/LABA combination. Individual components not available in separate inhalers so step-down could prove difficult Only 92/22 strength is licensed for COPD if FEV1<70% predicted normal (postbronchodilator) with an exacerbation history despite regular bronchodilator therapy. Page 68 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) Duoresp® Spiromax Budesonide/formoterol Dry powder inhaler Symbicort Turbohaler (Budesonide/formoterol) Dry-powder inhaler Seretide Evohaler (Fluticasone / Salmeterol 25mcg) CFC-free MDI Seretide Accuhaler (Fluticasone / Salmeterol 50mcg) Dry powder inhaler Respiratory System – Inhaled Corticosteroids 160mcg/4.5mcg: £29.97 (120 doses) 320mcg/9mcg: £29.97 (60 doses) 100mcg/6mcg: £33.00 (120 doses) 200mcg/6mcg: £38.00 (120 doses) 400mcg/12mcg: £38.00 (60 doses) Cost effective alternative to Symbicort Turbohaler. New legislation demands that delivered dose is stated. 160/4.5 is comparative to Symbicort 200/6 and 320/9 is comparative to 400/12. Can be used as maintenance or maintenance and reliever therapy. License in asthma and COPD (COPD 320/9mcg twice a day dose). Not licensed in 12-17 year olds unlike Symbicort. SPC for Duoresp suggests that stepdown from 160/4.5 may require separation into separate inhalers but does not preclude single daily dose regimen if considered clinically appropriate 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 years. 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. Careful patient education is required and quantity of inhalers used monitored. 50mcg: £18.00 (120 doses) 125mcg: £35.00 (120 doses) 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. 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. Page 69 Therapeutic Area Formulary Choices Cost per inhaler Rationale for decision / comments (unless otherwise stated) Combination long acting muscarinic antagonists (LAMA) and long acting β agonists (LABA) Anoro Ellipta▼ (Umeclidinium/vilanterol 55/22) Dry powder inhaler £32.50 (30 doses- one month) Once daily dose. Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD) Duaklir Genuair ▼ (aclidinium/formoterol 340/12) dry powder inhaler £32.50 (60 doses-one month) Twice daily dose. COPD only. Packaging is blue at present but will change to orange in September 2015 to avoid confusion with reliever therapies. £36.88 (30 doses –one month) Once daily dose. Indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with (COPD).Capsule has to be placed into device, needs certain dexterity. Ultibro Breezhaler▼ (glycopyrronium/indacat erol 110/54 mcg) dry powder inhaler Spacer devices Medium volume: Large volume: 3.3.2 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) £4.75 (1) adult with mask (blue) £7.92 (1) infant with mask (orange) £7.92 (1) child with mask (yellow) £7.92 (1) Volumatic £3.81 (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. Leukotriene receptor antagonists Leukotriene receptor antagonists Montelukast Chewable tablets Tablets Granules Zafirlukast Respiratory System – Inhaled Corticosteroids 4mg tablets: £2.21 (28) 5mg tablets: £2.37 (28) 10mg tablets: £2.52 (28) 4mg granules: £4.02 (28) Included for add-on therapy according to BTS & SIGN guidelines for the management of chronic asthma (BNF) and BTS/SIGN 141 October 2014 20mg tablets: £17.75 (56) Page 70 Summary of recently introduced inhalers and their equivalents (Yellow=new) Brand Name Device Drug Company Drugs Strength Adult Dose No. Puffs per inhaler Licens ed in Asthm a? License d in COPD? License d in Children ? Price Comments LABA Striverdi® Respimat®solution for inhalation BI Olodaterol 2.5mcg/puff 2 puffs OD 60 NO YES NO Ellipta® DPI GSK Umeclidinium 55mcg/puff 1 puffs OD 30 NO YES NO £26.35 COPD ONLY LAMA Incruse ® Spiriva® Respimat®solution for inhalation BI Tiotropium 2.5mcg/puff 2 puffs OD in asthma and COPD 60 YES YES NO £27.50 £33.50 Spiriva® Handihaler®DPI BI Tiotropium 18mcg /dose 1 Dose OD 30 NO YES NO Eklira® Genuair® DPI Almirall 400mcg/dose 1 Dose BD 60 NO YES NO Seebri® Breezhaler® DPI Pfizer Aclidinium Glycopyrroniu m £34.87 Handihal er £33.50 Refill 28.6 50 mcg /dose 1 Dose OD 30 NO YES NO 27.5 License recently extended to cover asthma. add-on maintenance bronchodilator treatment in adult patients with asthma who are currently treated with the maintenance combination of inhaled corticosteroids (≥800 µg budesonide/day or equivalent) and longacting β2 agonists and who experienced one or more severe exacerbations in the previous year COPD ONLY COPD ONLY COPD ONLY LABA/ ICS Respiratory System – Inhaled Corticosteroids Page 71 Fostair® Fostair® NEXThaler® DPI MDI Cheisi Cheisi Beclometason e/ formoterol Beclometason e/ formoterol 100/6mcg/puff 1-2 puffs bd 120 YES NO NO £29.32 100/6mcg/puff 1-2 puffs bd (max 8 puffs/d in maint and reliever therapy.) 120 YES YES NO 29.32 Relvar ® Ellipta® DPI GSK Fluticasone/ Vilanterol 92/22 mcg /puff 1 puff OD 30 YES YES Relvar ® Ellipta® DPI GSK Fluticasone/ Vilanterol 184/22 mcg /puff 1 puff OD 30 YES NO 160/4.5 mcg /puff Asthma 1-2 puffs BD. (max 8 puffs/d in maint and reliever therapy.) COPD 2puffs BD Duoresp ® Spiromax ® DPI TEVA Budesonide/ Formoterol Respiratory System – Inhaled Corticosteroids 120 YES YES YESAsthm a OVER 12 yrs ONLY YESAsthm a OVER 12 yrs ONLY NO 27.8 Patients not adequately ctrld with ICS + PRN SABA or those already ctrld on ICS + LABA. N.B. 200mcg. Fostair Equivalent to 500mcg BDP. NOT licensed to treat astma attacks. Patients not adequately ctrld with ICS + PRN SABA or those already ctrld on ICS + LABA. Maintenance and reliever therapy. N.B. 200mcg Fostair Equivalent to 500mcg BDP Recently licensed n COPD where FEV1 < 50% In COPD where FEV1 < 70% OR Asthma at STEP 3 38.87 Asthma ONLY 29.97 Equivalent to Symbicort Turbohaler 200/12mcg. Can be used for Maintenance and Reliever Therapy in asthma. In COPD where FEV1 < 50% Page 72 Duoresp ® Spiromax ® DPI Teva Budesonide/ Formoterol 320/9 mcg /puff Symbicort® Turbohaler® DPI GSK Budesonide/ Formoterol 100/6 mcg /puff Symbicort® Turbohaler® DPI GSK Budesonide/ Formoterol 200/6 mcg /puff Symbicort® Turbohaler® DPI GSK Anoro ® Ellipta ® DPI GSK Duaklir® Genuair® DPI Almirall Ultibro Breezhaler® DPI Pfizer Budesonide/ Formoterol Asthma 1-2 puffs BD (max 8 puffs/d in maint and reliever therapy.) COPD 1puff BD Asthma 1-2 puffs BD. (max 8 puffs/d in SMART therapy.) COPD 2puffs BD Asthma 1-2 puffs BD (max 8 puffs/d in SMART therapy.) COPD 1puff BD 60 YES YES NO 120 NO YES YESAsthm a OVER 6yrs ONLY 120 YES YES NO 29.97 Equivalent to Symbicort Turbohaler 200/12mcg. Asthma Maintenance ONLY- NOT LICENSED FOR Maintenance and reliever therapy) . In COPD where FEV1 < 50% 33 In COPD where FEV1 < 50% 38 In COPD where FEV1 < 50% 38 Maintenance ONLY- NOT LICENSED FOR Maintenance and reliever therapy) In COPD where FEV1 < 50% 400/12 mcg /puff Asthma 1 puff BD COPD 1puff BD 60 YES YES NO 55/22 mcg /puff 1 puff OD 30 NO YES NO £32.50 COPD ONLY 340/12 mcg/puff 1 puff BD 60 NO YES NO £32.50 COPD ONLY 85/43mcg/puff 1 puff od NO YES NO £36.88 COPD ONLY. Capsule has to be inserted into device LAMA/ LABA Umeclidinium / Vilanterol Aclidinium/for moterol Glycopyrroniu m/indacaterol Respiratory System – Inhaled Corticosteroids 30 Page 73 Adult asthma inhaler pathway December 2013 Daily BDP Dry powder Daily BDP MDI (beclometason e dipropionate) Step 1 Mild intermittent asthma Step 2 Mild persistent asthma preventer therapy SABA only when needed Reliever treatment with short acting bronchodilator (SABA) Salbutamol or terbutaline Salbutamol Easyhaler 100mcg/dose: £3.31 (200 dose) 200mcg/dose: £6.63 (200 dose) Inhaled steroid preventer treatment. Up to 400mcg BDP/day Beclometasone Easyhaler 200mcg: £14.93 (200 dose) 1puff bd - £4.18/28d Manufacturers vary in their recommended starting dose200mcg/day minimum Budesonide Easyhaler 200mcg £17.71 (200 dose) Or 100mcg if want to start lower £8.86 Step 3 Moderate persistent initial add on therapy Trial of LABA (4 weeks) No response Stop LABA Increase steroid to 800mcg Formoterol Easyhaler 12mcg 120 dose (£23.75) Beclometasone Easyhaler 200mcg (200 dose)(£14.93) Budesonide Easyhaler 200mcg £17.71 (200 dose) Respiratory System – Inhaled Corticosteroids 1 puff bd £4.96/28d 1 puff bd £2.48/28d 400mcg 200mcg - Clenil Modulite 200mcg: £16.17 (200 dose) One puff bd £4.53/28d 400mcg 50mcg 100mcg 2pbd £3.70/28d 1pbd £2.07/28d 200mcg Qvar 100mcg: £17.21 (200 dose) 1 puff bd £4.82/28d 2pbd £2.20/d 50mcg Plus spacer if necessary 800mcg Qvar 100 (£17.21) 200 dose 2puffs bd £9.64/28d 800mcg Clenil 200 (16.17) 200 dose 2puffs bd £9.05/28d 800mcg 800mcg Breath actuated MDIs available Airomir Autohaler Salamol EasiBreathe ~£6 each Breath actuated CFC-free MDI as Qvar Easibreathe 100mcg: £16.95 (200 dose) Consider adding trial of LABA BEFORE moving to a higher steroid strength Atimos licensed over 12 yrs only Straight to combination? Seretide 50 evohaler or Seretide 100 Accuhaler or Symbicort 100/6 all 2 puffs bd 200mcg 1puff bd £16.83/28d £8.36/28d 2puffs bd £9.92/28d Using TWO or more canisters of beta-2 agonist per year is an indicator of poor control 400mcg -------£11.08/28d 2puffs bd Ventolin Evohaler 100mcg/dose: £1.50 (200 dose inhaler) Formoterol 12mcg MDI (Atimos) (100 doses) £30.06 1puff bd Options (beclometason e dipropionate) Plus spacer if necessary 400mcg BTS/SIGN 141 October 2014 800mcgBDP = same effects on serum cortisol levels as 4mg oral prednisolone Breathactuated CFC-free MDI as Qvar Easibreathe Page 74 Good Response Partial Response Step 4 Persistent poor control Assess which type of inhaler (DPI or MDI) suits patient best, stop separate LABA and use combination inhaler Seretide 100 Accuhaler (60 dose) (£18) 1puff bd £16.80/28d 400mcg Symbicort 100/6 (120 dose) (£33) 2puffs bd £30.80/28d 400mcg Increase steroid to 800µg. Assess which type of inhaler (DPI or MDI) suits patient best Duoresp Spiromax 160/4.5(£29.97) 120 doses 2puffs bd £27.97/28d 800mcg Consider moving up to 2000µg BDP Seretide 250 Accuhaler (60 dose) £35 1 puff bd £32.67/28d Seretide 500 Accuhaler (60 dose) £40.92 1 puff bd £38.19/28d Oral steroid Maintain at 2000mcg/day as above Respiratory System – Inhaled Corticosteroids 2puffs bd £16.80/28d 400mcg Flutiform 50 (120 dose) £18 2puffs bd £16.80/28d 400mcg Fostair 100/6 (£29.32) 120 doses 2puffs bd £27.37/28d 1000mcg Flutiform 125 (120 dose) CFC-free MDI 125mg/5mcg £29.26 2 puffs bd £27.31/28d 1000mcg Seretide 125 (120 dose) £35 Non formulary Flutiform 250 2 puffs bd £32.67/28d 800mcg 1000mcg 2000mcg Step 5 Severe persistent/contin uous symptoms Refer to specialist Seretide 50 Evohaler) 120 dose £18 2 puffs bd £42.52/28d Seretide 2 puffs bd Evohaler 250 £55.51/28d Maintain at 2000mcg/day as above 1000mcg 2000mcg Symbicort 200/6 1puff bd would be more cost effective, but LABA dose would be sub therapeutic £17.73/28d. Fostair 100/6 could be used 1 p bd but again this may give sub therapeutic dose of LABA Fostair is licensed for over 18 yrs only. Fostair only lasts 5 months out of the fridge Seretide Accuhaler at 500mcg bd dose should be reserved for severe asthmatics only. Doses over 1000µg BDP equivalent/day require a steroid warning card. 2000mcg BDP=same effect on serum cortisol levels as 10mg oral prednisolone Note: 160mcg Duoresp is equivalent of 200mcg of BDP Addition of a fourth drug e.g leukotriene agonist, theophylline 2000mcg Page 75 Children age 5-12 asthma inhaler pathway Jan 2014 Dry powder Step 1 Mild intermittent asthma Salbutamol Easyhaler 100mcg/dose: £3.31 (200 dose) 200mcg/dose: £6.63 (200 dose) Age 4-11 up to 200mcg qds Reliever treatment with short acting bronchodilator (SABA) BDP - Options MDI BDP Ventolin Evohaler 100mcg/dose: £1.50 (200 dose inhaler) - Dose 100-200mcg up to qds (age 1 month-18yrs) Plus spacer always Step 2 Mild persistent asthma preventer therapy Inhaled steroid preventer treatment. 200400mcg BDP/day 200 is starting dose Budesonide Easyhaler 100mcg £8.86 200mcg £17.71 (200 dose) Age 6 and above 1 puff bd £2.48/28d 1 puff bd £4.96/28d 200mcg 400mcg SABA only when needed Step 3 Moderate persistent initial add on therapy Trial of LABA (4 weeks) No response Stop LABA Increase steroid to 400mcg Formoterol Easyhaler 12mcg 120 dose (£23.75) Age 6 and above Budesonide Easyhaler 100mcg £8.86 200mcg £17.71 (200 dose) Age 6 and above Respiratory System – Inhaled Corticosteroids 1puff bd -------£11.08/28d Clenil Modulite One puff bd 50mcg: £1.85/28d £3.70 (200 dose) 100mcg: £2.07/28d £7.42 (200 dose) Clenil Modulite One puff bd 200mcg: £4.53/28d £16.17 (200 dose) Plus spacer if necessary Salmeterol MDI 25mcg 2puffs bd (120 doses) £27.31/28d £29.26 Beclometasone Easyhaler not recommended for children 100mcg 200mcg Qvar not licensed under 12 years 400mcg Consider adding trial of LABA BEFORE moving to a higher steroid strength 400BDP = 2mg oral prednisolone Upto 2 puff bd £4.96/28d 1 puff bd £4.96/28d Clenil 100 (£7.42) 200 dose 2puffs bd £4.15/28d 400mcg Clenil 200 (16.17) 200 dose 1puffs bd £4.53/28d 400mcg 400mcg Page 76 Good Response Assess which type of inhaler (DPI or MDI) suits patient best, stop separate LABA and use combination inhaler Seretide 100 Accuhaler (60 dose) (£18) From 5 yrs 1puff bd £16.80/28d 1 puff daily £8.40/28d for maintenance only Symbicort 100/6 (120 dose) (£33) From 6yrs Max 2 puff bd £30.80/28d 1 puff bd £15.40/28d 400mcg Seretide 50 Evohaler(£1 8) 120 dose 2puffs bd £16.80/28d 400mcg Clenil 100 (£7.42) 200 dose 2puffs bd £4.15/28d 400mcg Clenil 200 (16.17) 200 dose 1puffs bd £4.53/28d 400mcg 200mcg 400mcg 200mcg 100mcg Partial Response Step 4 Persistent poor control Step 5 Severe persistent/conti nuous symptoms Refer to specialist Continue LABA and Increase steroid to 400mcg. Assess which type of inhaler (DPI or MDI) suits patient best Consider moving up to 800mcg BDP Oral steroid Symbicort 100/6 (£33) 120 doses From 6yrs Budesonide Easyhaler 200mcg £17.71 (200 dose) 1 puff od £7.70/28d for maintenance only 2puffs bd £30.80/28d 2 puff bd £9.91/28d 1 puff bd £4.96/28d Pulmicort Turbo 2 puff bd 200mcg £11.84 £13.26/28d (100dose) Age 6 and above Maintain at 800mcg/day as above Respiratory System – Inhaled Corticosteroids 400mcg 800mcg MDI Beclometasone only licensed upto 400mcg/day 400mcg Refer to respiratory paediatrician if uncontrolled at this level 800mcg Maintain at 800mcg/day as above Page 77 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 symbicort /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 78 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 Fluticasone 100 Accuhaler® 1 puff bd *(400mcg/ 24mcg formoterol) BTS/SIGN Step 4/5 Seretide Accuhaler® Budesonide Turbohaler® 200mcg 1 puff bd OR 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 NB. Fluticasone Accuhaler® and budesonide Turbohaler® are non-formulary but are included here as some patients on Seretide Accuhale® or Symbicort Turbohaler® may benefit from stepping down to the same device. Use formulary devices where possible. Page 79 GUIDANCE FOR MANAGING COPD IN ACCORDANCE WITH NICE CLINICAL GUIDELINE CG101 (JUNE 2010) ADAPTED BY SOMERSET CCG 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 Symptoms should be present to diagnose COPD in people with mild airflow obstruction Respiratory System – Inhaled Corticosteroids Gold 2: Moderate 50-79% predicted FEV1 Gold 3: Severe 30-49% predicted FEV1 Gold 4: Very severe < 30% predicted FEV1 Or FEV1 < 50% with respiratory failure Page 80 Symptoms Choice of inhaled therapy in COPD 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® or Olodaterol 2.5mcg 2puffs daily via Striverdi Respimat® 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). Umeclidinium 55mcg daily via DPI Respiratory System – Inhaled Corticosteroids Page 81 LABA/LAMA Combination of above Anoro Ellipta® 1 actuation daily (Umeclidinium/vilanterol) Duaklir Genuair® 1 actuation bd (Aclidinium/formoterol Ultibro Breezhaler® 1 actuation od (glycoprrronium / indacaterol) LABA + ICS Inhaled corticosteroid Duoresp Spiromax Symbicort Turbohaler® 400/12: 1-2 actuations BD or Relvar® Ellipta®92mcg/22mcg: 1 actuation daily (if FEV<70% expected) 3 months or Seretide Accuhaler® 500/50: 1 actuation BD or Fostair® 100/6: 2 actuations BD 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 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 Respiratory System – Inhaled Corticosteroids Page 82 Theophylline Mucolytic therapy Not Recommended 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 can be considered in people with chronic productive cough, and continued if symptoms improve Do not routinely use to prevent exacerbations Anti-oxidant therapy (alpha-tocopherol and beta-carotene supplements) Anti-tussive therapy Prophylactic antibiotic therapy Assess symptoms or condition and manage as described below Breathlessness and exacerbations 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 Frequent exacerbations Optimise inhaled therapy Offer vaccinations and prophylaxis Give self-management advice Consider osteoporosis prophylaxis for people requiring frequent oral corticosteroids Cor pulmonale 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 Respiratory System – Inhaled Corticosteroids Page 83 Angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers are not recommended Digoxin may be used where there is atrial fibrillation 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 - have recently been seen or treated at a hospital for an exacerbation Refer to ‘Depression with a chronic physical health problem’ (NICE CG91). 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 Respiratory System – Inhaled Corticosteroids Page 84 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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: £1.06 (30) 5mg/5ml solution: £2.06 (100ml) Loratadine is first line on basis of low rate of motor impairment and costeffectiveness. Loratadine is available OTC. Second-line: Cetirizine 10mg tablets: £1.02 (30) 5mg/5ml solution: £1.78 (200ml) Cetirizine is second line as more likely to impair motor function than Loratadine. Cetirizine is available OTC. Third-line: Desloratadine tablets 5mg tablets: £1.73 (30) As an option if first- and second-line choices are not tolerated or contra-indicated. Chlorphenamine 4mg tablets: £1.00 2mg/5ml SF solution: £2.60 (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: £6.99 (300ml) 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 in the UK and for specialist prescribing only.Red drug classification Erdocysteine is non-formulary Respiratory System – Inhaled Corticosteroids Page 85 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) BNF Chapter 4: Central nervous system Top 4.1 Hypnotics and anxiolytics Hypnotics First line Zaleplon 5mg tablets: £3.12 10mg tablets: £1.67 Zopiclone 3.75mg tablets: £1.32 7.5mg tablets:£1.32 2mg tablets: £0.86 5mg tablets: £0.89 Diazepam Second line Third line Anxiolytics 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 CCG 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. Zaleplon has a half life of just 1 hour. Zolpidem 2.5 hours, zopiclone 3.5-6.5 hours. Different rules may apply to patients cared for by Somerset Partnership NHS Foundation Trust. Diazepam may be considered as an alternative especially when using as a benzodiazepine withdrawal therapy. Melatonin As Circadin® 2mg P/R tablets £15.39 Zolpidem 10mg tablets: £3.76 5mg tablets:£1.64 Circadin® is indicated as monotherapy for the short-term treatment (up to 13 weeks) of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.Circadin may be of benefit to elderly patients at risk of falling, or to patients who drive and are susceptible to next-day drowsiness of z-drugs and benzodiazepines. MHRA warned in May 2014 of the risk of morning drowsiness and reduced driving ability with zolpidem.Link Temazepam 10mg tablets: £23.77 20mg tablets: £22.61 Treatment should be limited to lowest dose for the shortest period of time. Diazepam Central Nervous System 2mg tablets: £0.86 5mg tablets: £0.89 Treatment should be limited to lowest dose for the shortest period of time. Page 86 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.2 Drugs used in psychoses and related disorders Related guidance: NICE CG 178 (February 2014) Psychosis and schizophrenia in adults: treatment and management 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. All antipsychotics (except risperidone for short-term, <6 weeks, use – see below) 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). The choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees. Provide information and discuss the likely benefits and possible side effects of each drug, including: metabolic (including weight gain and diabetes) extrapyramidal (including akathisia, dyskinesia and dystonia) cardiovascular (including prolonging the QT interval) hormonal (including increasing plasma prolactin) other (including unpleasant subjective experiences). Regular combined treatment with two or more antipsychotic agents is not recommended Risperidone 1mg tablets: £0.99 (20) 2mg tablets: £2.06 (60) 3mg tablets: £2.35 (60) 4mg tablets: £2.26 (60) Risperidone 25mg: £79.69 (1 pfs) long-acting 37.5mg: £111.32 (1 pfs50mg: injection £142.76 (1 pfs) NB Cold chain must be maintained. 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 Six-week restriction does not apply where risperidone is being prescribed to treat acute or chronic psychoses or mania Two-weekly injection as part of a shared-care arrangement. Page 87 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Paliperidone long-acting injection ▼ 50mg: £183.92 (1 pfs) 75mg: £244.90 (1 pfs) 100mg: £314.07(1 pfs) 150mg: £392.59 (1 pfs) Maintenance in schizophrenia in patients previously responsive to paliperidone or risperidone in accordance with the shared care guidelines .Suitable for patients who require antipsychotic medication and can be given as a long acting injection for those patients that have not tolerated other typical depot medications because of EPSE. Paliperidone is an active metabolite of risperidone. Olanzapine 2.5mg tablets: £1.04 5mg tablets: £1.23 7.5mg tablets: £1.35 10mg tablets: £1.67 15mg tablets: £2.14 20mg tablets: £2.43 See below Aripiprazole 5mg tablets: £96.04 10mg tablets: £96.04 15mg tablets: £96.04 30mg tablets: £192.08 Aripiprazole is recommended as an option for the treatment of schizophrenia in people aged 15 to 17 years who are intolerant of risperidone, or where risperidone is contraindicated, or whose schizophrenia has not been adequately controlled with risperidone (NICE TA213). Generic aripiprazole is not licensed for bipolar disease. Use branded Abilify® Quetiapine 25mg tablets: £1.61 (60) 100mg tablets: £2.66 (60) 150mg tablets: £3.27 (60) 200mg tablets: £3.72 (60) 300mg tablets: £5.07 (60) 50mg tablets: £29.45 (60) 150mg tablets:£49.45 (60) 200mg tablets: £49.45 (60) 300mg tablets: £74.45 (60) 400mg tablets: £98.95 (60) Where quetiapine is prescribed, the standard release formulation is preferred for long term use on cost grounds (approx. 15 price differences). This approach is supported by Somerset Partnership NHS Foundation Trust Mental Health Directorate. General advice Offer people with psychosis or schizophrenia who smoke help to stop smoking, even if previous attempts have been unsuccessful. Be aware of the potential significant impact of reducing cigarette smoking on the metabolism of other drugs, particularly clozapine and olanzapine. [new 2014] Extended release as Biquelle XL® or Zaluron XL® Central Nervous System For patients unable to take immediate release quetiapine, a once daily dose XL preparation is available. Generically prescribed XL preparations are 50% or more expensive than brands stated. Page 88 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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: Lithium must be prescribed by brand for safety reasons (in-line with national guidance) as Camcolit 250® 250mg: £3.22 (100) Li+ 6.8mmol/tablet as Camcolit 400® 400mg: £4.30 (100) Modified-release. Li+ 10.8mmol/tablet as Liskonium® 450mg 450mg: £2.88 (60) Modified-release. Li+ 12.2mmol/tablet NPSA ‘Safer Lithium Therapy’ guidance must be followed as Priadel® 200mg 200mg: £2.30 (100) Modified-release. Li+ 5.4mmol/tablet as Priadel® 400mg 400mg: £3.35 (100) Modified-release. Li+ 10.8mmol/tablet Central Nervous System Page 89 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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) NB. SSRIs are known to increase risk of GI bleeds especially if co-prescribed with NSAIDs and in the very elderly. Prescribers are reminded of the risk of serotonin syndrome with SSRI when combined with other antidepressants, triptans, and opioids including tramadol. 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.91 & p93 for options Fluoxetine as Oxactin® as Olena® 20mg capsules: £1.10 (30) 20mg capsules: £0.92 (30) 20mg dispersible tablets £3.44 (28) Less expensive than fluoxetine liquid for patients unable to swallow capsules 50mg tablets: £3.26 100mg tablets: £5.78 Joint First-line SSRI for the pharmacological treatment of social anxiety disorder in accordance with NICE CG159. Or Sertraline Or Citalopram 10mg tablets: £0.97 20mg tablets: £0.96 40mg tablets: £1.11 Escitalopram 5mg tablets: £8.97 10mg tablets: £14.91 20mg tablets: £25.20 Joint First-line SSRI for the pharmacological treatment of social anxiety disorder in accordance with NICE CG159. See Somerset Partnership Guidance below (p.92) NB: Maximum dose restrictions – see MHRA DSU (Dec-11) for details. Central Nervous System Page 90 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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: £5.90 (56) Second-line: Amitriptyline 10mg tablets: £0.89 25mg tablets: £0.90 50mg tablets: £0.98 Other antidepressants Mirtazapine 15mg tablets: £2.13 30mg tablets: £1.75 45mg tablets: £2.44 Oro-dispersible tablets: Venlafaxine First-line: Immediate release Second-line: Modified-release as Vensir XL Central Nervous System 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: £1.65 (30) 30mg tablets: £1.66 (30) 45mg tablets: £2.32 (30) See MHRA guidance 37.5mg tablets: £2.37 (56) 75mg tablets: £2.69 (56) 75mg capsules: £2.60 (28) 150mg capsules: £3.90 (28) as Viepax XL 75mg tablets: £11.20 150mg tablets: £18.70 as Venlalic XL 75mg tablets: £11.20 (30) 150mg tablets: £18.70 (30) 225mg tablets: £33.60 (30) If modified release venlafaxine is prescribed, use tablets not capsules (on cost grounds) Viepax XL® or Venlalic XL® are cost-effective brands for modified release tablets (but NOT the non-MR formulation) There is no rationale for prescribing M/R products as a BD dose Page 91 Citalopram maximum dose (new guidance from MHRA) In October 2011 the MHRA issued new dose recommendations for citalopram due to the risk of dose-dependent QT prolongation: • The maximum dose of citalopram is now 40mg/day in adults and 20mg/day in the elderly and in patients with hepatic impairment. • Citalopram is contraindicated in known QT prolongation, congenital long QT syndrome or taking other QT-prolonging medicines (Click here for a full list) • Caution with pre-existing risk factors for QT prolongation - such as significant bradycardia, recent MI or decompensated heart failure.. Adult prescribed above 40mg/day: Reduce dose stepwise to 40mg/day Monitor for 3 months Remains stable If citalopram dose currently above new recommendations: Discuss with patient. Consider continued need for citalopram and alternative therapies; switch if also taking any other medicines likely to cause QTc prolongation Elderly or hepatic impairment prescribed above 20mg/day: Reduce dose stepwise to 20mg/day. Monitor for 3 months Consider risk:benefit with patient. Switch if possible Relapses or deteriorates If under 18 refer to CAMHS (unlicensed use). If all other options exhausted consider maintaining previously effective dose [document unlicensed dose and rationale in notes; evidence of informed consent from patients with capacity]. Reduce and monitor any risk factors. Monitor with regular ECG (e.g. initially, 6-monthly and after any medicine or dose changes), U&Es and ask patient to report any abnormal heart rate or rhythm. If significant QT prolongation detected, must seek specialist advice and/or switch Switch to different SSRI (other than escitalopram). Consider non-pharmacological therapies Escitalopram: Citalopram: The MHRA have also issued a warning that The MHRA have also issued a warning that escitalopram has also been associated with citalopram has also been associated with dose dependent QT prolongation. New dose dependent QT prolongation. New recommendations for maximum doses of recommendations for maximum doses of escitalopram (in the elderly or patients with citalopram, contraindications, cautions and hepatic impairment), contraindications, monitoring requirements have been issued cautions and monitoring requirements have (see separate flow chart). been issued (see separate flow chart). For further information please click here For further information please click here Medicine alternatives include: Sertraline (optimum alternative as similar indications, low interaction propensity, good tolerability, generic, NICE approved) Fluoxetine (beware of P450 interactions) Mirtazapine (depression indication only) Known to need above 40mg/day (adults) or 20mg/day (elderly or hepatic impairment) There is no comparative data available on QTc prolongation between other antidepressants/doses. There is no single switch method: Depending on citalopram dose, urgency, tolerability and other medicines then “reduce, stop and switch” is safest. Abrupt switching is not recommended. Please contact the pharmacy team on 01823 368265 with any questions. Somerset Partnership NHS Foundation Trust. Drug & Therapeutics Group. Dec 2011. Review date Dec 2014 Adapted from Norfolk & Waveney and Suffolk Mental Health Foundation Trusts Guidelines Central Nervous System Page 92 Escitalopram maximum dose (new guidance from MHRA) In December 2011 the MHRA issued new dose recommendations for escitalopram in the elderly or in patients with hepatic impairment, due to the risk of a dose-dependent QT prolongation: • The maximum dose in the elderly and patients with hepatic impairment has been reduced to 10mg daily. (The maximum dose for adults remains 20mg daily). • Escitalopram contraindicated in known QT prolongation, congenital long QT syndrome or taking other QT prolonging medicines (Click here for a full list). • Caution with pre-existing risk factors for QT prolongation - such as significant bradycardia, recent MI or decompensated heart failure. Central Nervous System Page 93 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.5 CNS stimulants and drugs used for attention defecit hyperactivity disorder Treatment of ADHD See NICE CG72 Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults (Sep-08; last modified Mar-13). AMBER prescribing only: Initiated by a suitable specialist for the treatment of ADHD in accordance with the shared care guideline. Methylphenidate Modified release as Concerta XL® as Equasym XL® as Medikinet XL® 5mg tablet: £3.03 (30) 10mg tablet: £5.49 (30) 20mg tablet: £10.92 (30) Brand as recommended by consultant: 18mg tablet: £31.19 (30) 27mg tablet: £36.81 (30) 36mg tablet: £42.45 (30) 10mg capsule: £25.00 (30) 20mg capsule: £30.00 (30) 30mg capsule: £35.00 (30) 5mg capsule: £24.04 (30) 10mg capsule: £24.04 (30) 20mg capsule: £28.86 (30) 30mg capsule: £33.66 (30) 40mg capsule: £57.72 (30) Atomoxetine 10mg capsule: £62.46 18mg capsule: £62.46 25mg capsule: £62.46 10mg capsule: £62.46 40mg capsule: £62.46 60mg capsule: £62.46 80mg capsule: £83.28 100mg capsule: £83.28 Dexamfetamine 5mg tablet: £18.90 Lisdexamfetamine 30mg capsule: £58.24 50mg capsule: £68.60 70mg capsule: £83.16 Central Nervous System 22% immediate-release + 78% modified release 30% immediate-release + 70% modified release 50% immediate-release + 50% modified release Prodrug of dexamfetamine. Unlicensed for treatment of adults over 18 years. Page 94 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.5.1 Drugs used in the treatment of obesity Lipid absorption inhibitors Orlistat Central Nervous System 120mg: £30.43 (84) Only to be prescribed in line with NICE guidance: BMI > 30kg/m2 or > 28kg/m2 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 Page 95 Traffic light system for identifying risk of serious illness in children* Colour Green Amber Red – low risk – intermediate risk – high risk Normal colour Pallor reported by parent/carer Pale / mottled / ashen / blue Responds normally to social cues Content/smiles Stays awake or awakens quickly Not responding normally to social cues No response to social cues No smile Appears ill to a healthcare professional (of skin, lips or tongue) Activity Strong normal cry/not crying Respiratory Wakes only with prolonged stimulation Decreased activity Does not wake or if roused does not stay awake Nasal laring Grunting Tachypnoea: - RR >50 breaths/ minute, age 6–12 months - RR >40 breaths/ minute, age >12 months Tachypnoea: RR >60 breaths/minute Weak, high-pitched or continuous cry Moderate or severe chest indrawing Oxygen saturation ≤95% in air Crackles in the chest Circulation and hydration Normal skin and eyes Moist mucous membranes Tachycardia: - >160 beats/minute, age <12 months - >150 beats/minute, age 12–24 months - >140 beats/minute, age 2–5 years Reduced skin turgor CRT ≥3 seconds Dry mucous membranes Poor feeding in infants Reduced urine output Other None of the amber or red symptoms or signs Age 3–6 months, temperature ≥39°C Age <3 months, temperature ≥38°C Fever for ≥5 days Rigors Non-blanching rash Swelling of a limb or joint Bulging fontanelle Non-weight bearing limb / not using an extremity Neck stiffness Status epilepticus Focal neurological signs Focal seizures CRT, capillary refill time; RR, respiratory rate * This traffic light table should be used in conjunction with the recommendations in the guideline on investigations and initial management in children with fever. See http://guidance.nice.org.uk/CG160 (update of NICE clinical guideline 47). ‘Feverish illness in children’, NICE clinical guideline 160 (May 2013) © National Institute for Health and Care Excellence 2013. All rights reserved Central Nervous System Page 96 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.7 Analgesics: Related guidance: CG177 Osteoarthritis: Care and management in adults Feb 2014 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: £2.78 (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. Weak opioid analgesics Buprenorphine Patches 5/10/20mg 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 CCG 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 Continued overleaf Central Nervous System 15mg tablets: £1.27 30mg tablets: £1.41 60mg tablets: £3.58 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. Page 97 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Continued from previous page Tramadol First-line: Immediate release capsules Second-line: Modified release Combination analgesics 50mg capsules: £3.67 (100) 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 may be most effective when given with full therapeutic doses of Paracetamol (i.e. NOT as Tramacet which contains only 375mg paracetamol). as Marol (twice-daily dosing) 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. as Tradorec XL (once-daily dosing) 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. The CCG 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. Co-codamol 30/500 x 8/day provides 240mg codeine equivalent to Morphine 30mg Co-Codamol (Codeine / Paracetamol) 8/500mg tablets: £3.97 (100) as Zapain 30/500mg tablets: £3.03 (100) (capsules are at >twice this price) 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. 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. Zapain is 40% cheaper than generic (£2/100) Management of opioid overdosage may require use of Naloxone: refer to Chapter 15 of the current BNF Strong opioid analgesics For non-cancer pain, strong opioids should be considered only when they are used as part of a programme of supported rehabilitation, with the goal of helping patients to manage pain-related disability. There is no evidence of superior clinical analgesic effect of other opioids over morphine Central Nervous System Page 98 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) First-line: Morphine Solution Strong opioid analgesics 10mg/5ml solution: £5.45 (100ml) Modified release capsules as Zomorph Modified release tablets as Morphgesic SR Second-line: Fentanyl 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) Continued overleaf Central Nervous System 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. 10mg tablets: £3.85 (60) 30mg tablets: £9.24 (60) 60mg tablets: £18.04 (60) 100mg tablets: £28.54 (60) 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. For non-cancer pain, 75mcg/hour should be the maximum dose, if ineffective other causes for lack of response should be considered (eg. Primary anxiety or unrealistic expectations of analgesia from patch). Patches as Matrifen 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. 12mcg / hour: £8.87 (5) 25mcg / hour: £12.68 (5) 50mcg / hour: £23.69 (5) 75mcg / hour: £33.03 (5) 100mcg / hour: £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. Page 99 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Continued from previous page Central Nervous System as Fencino® 12mcg / hour: £8.57(5) 25mcg / hour: £12.24 (5) 50mcg / hour: £22.87 (5) 75mcg / hour: £31.88 (5) 100mcg / hour: £39.29 (5) Buprenorphine patches as Hapoctasin® 35mcg/hr : £9.48 (4) 50mcg/hr: £14.23 (4) 70mcg/hr: £18.96 (4) As an option for patients with moderate to severe cancer pain for whom fentanyl may be too potent. Note: Hapoctasin® are 72 hour patches the same as fentanyl. Transtec® have the same rate of drug delivery as Hapoctasin® but are 96 hour patches. Table of approximate dose equivalents fro British Pain Society Page 100 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Third-line: Oxycodone 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. The CQC have issued guidance on prescribing, supply and administration: Safer Use of Controlled Drugs – Preventing Harm From Oral Oxycodone Medicines Instant release as Shortec® 5mg capsules £11.43 (56) 10mg capsules £22.86 (56) 20mg capsules £45.71 (56) 5mg/5ml SF solution: £9.71 (250ml) Modified release as Longtec Fourth-line: 5mg tablets: £10.00 (28) 10mg tablets: £19.99 (56) 20mg tablets: £39.98 (56) 40mg tablets: £79.98 (56) 80mg tablets: £159.98 (56) Tapentadol 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. Fourth-line strong opioid analgesic: Approved for relief of moderate to severe pain in adults as an alternative to oxycodone Instant release 50mg tablets: £12.46 (28) 75mg tablets: £18.68 (28) Note: instant release product only licensed for acute pain and the slow release preparation is only licensed for chronic pain. Modified release 50mg tablets: £12.46 (28) 100mg tablets: £49.82 (56) 150mg tablets: £74.73 (56) 200mg tablets: £99.64 (56) 250mg tablets: £124.55 (56) Procedures should be in place to prevent inadvertent prescribing errors 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 101 OPIOID CONVERSION TABLE - St Margaret’s Hospice Guide to Opioid 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 diamorphine subcutaneous alfentanil 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 102 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.7.3 Neuropathic pain Related guidance: CG173 Neuropathic pain - pharmacological management: NICE guideline November 2013 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 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 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 Neuropathic pain Amitriptyline Gabapentin Duloxetine Pregabalin 10mg tablets: £0.89 25mg tablets: £0.90 50mg tablets: £0.98 100mg capsules: £2.90 (100) 300mg capsules: £4.49 (100) 400mg capsules £4.77 (100) Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain (except trigeminal neuralgia) If the initial treatment is not effective or is not tolerated, offer one of the remaining 3 drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated. Consider tramadol only if acute rescue therapy is needed.Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments. 60mg capsules: £27.72 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) Because of price structure for pregabalin, ensure dose optimisation is carried out. Pregabalin dose spread over two daily doses proved non-inferior to three times a day dosing. http://www.update-software.com/BCP/WileyPDF/EN/CD007076.pdf . Central Nervous System Page 103 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Tramadol capsules (immediate release) 50mg capsules: £3.67 (100) Acute treatment as rescue, for short term use only NB The combination of tramadol with amitriptyline or duloxetine is associated with a low risk of serotonin syndrome. 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. Central Nervous System Page 104 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) Cluster headache Pain location1 Bilateral Unilateral or bilateral Pain quality Pressing/tightening (non-pulsating) Pain intensity Effect on activities Other symptoms Mild or moderate Not aggravated by routine activities of daily living None 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 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 Unusual sensitivity to light and/or sound or nausea and/or vomiting. Aura2: symptoms can occur with or without Duration of headache Frequency of headache 30 minutes–continuous < 15 days per month ≥ 15 days per month for more than 3 months headache and: o are fully reversible, o develop over at least 5 minutes, o 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. 4–72 hours in adults 1–72 hours in young people aged 12–17 years < 15 days per month ≥ 15 days per month for more than 3 months Diagnosis Episodic tensiontype headache Chronic tension-type headache2 Episodic migraine (with or without aura) Chronic migraine (with or without aura) On the same side as the headache: Red and/or watery eye Nasal congestion and/or runny nose Swollen eyelid Forehead and facial sweating Constricted pupil and/or drooping eyelid 15–180 minutes 1 every other day to 8 per day3, with remission4 >1 month Episodic cluster headache 1 every other day to 8 per day3 with a continuous remission4 <1 month in a 12-month period Chronic cluster headache 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. 5 Chronic migraine and chronic tension-type headache commonly overlap. If there are any features of migraine, diagnose chronic migraine. 6 NICE has developed technology appraisal guidance on Botulinum toxin type A for theprevention of headaches in adults with chronic migraine (headaches on at least 15 days permmonth of which at least 8 days are with migraine). Central Nervous System Page 105 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 Migraine with or without aura Acute treatment Acute treatment Aspirin (not for<16 years association with Reye’s Syndrome) Paracetamol NSAID Oral triptan* + NSAID or Oral triptan* + paracetamol plus Anti-emetic even in absence of nausea & vomiting Consider nasal triptan for 1217 year olds & non-oral antiemetic DO NOT OFFER DO NOT OFFER Migraine associated with Menstrual Cycle Acute treatment When standard treatment is not effective: Frovatripan 2.5mg bd or Zolmitriptan 2.5mg two or three times a day on the days migraine is expected Migraine in Pregnancy Cluster Headache Acute treatment 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 DO NOT OFFER DO NOT OFFER Prophylaxis Paracetamol NSAIDs Opioids Ergots Oral triptans Prophylaxis Paracetamol Consider triptan after discussing need for treatment and risks Opioids Prophylaxis Prophylaxis Review need to continue N/A Verapamil Seek specialist advice prophylaxis 6 months after Seek specialist advice if starting cluster headache does not Continue current regime for respond to verapamil people on existing effective Seek specialist advice for migraine prophylaxis. cluster headache during Propranolol or Topiramate pregnancy (patients <18) – ensure suitable contraception for females of child bearing age (risk of foetal malformation) Second line: o Acupuncture: up to 10 sessions over 5-8 weeks or Use of medication in bold within this guidance is off-license for indication/age/dose given. These o Gabapentin – up to 1200mg were all approved for prescribing in Somerset at Prescribing Forum November 2012. daily Prescribers should follow relevant professional guidance & patient (or parent or carer) should o Riboflavin 400mg once daily provide informed consent, which should be documented) may be effective to reduce migraine frequency & intensity. Acupuncture: up to10 sessions over 5-8 weeks Central Nervous System Ergots or derivatives Opioids Routinely prescribe combined hormonal oral contraceptive Prophylaxis Page 106 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.7.4 Antimigraine drugs Acute management of migraine Simple analgesia Aspirin 300mg dispersible tablets: £11.90 (100) Evidence supports the efficacy of Aspirin at a dose of 900mg for acute migraine. Available OTC. Ibuprofen 200mg tablets: £3.40 (84) 400mg tablets: £3.19 (84) 600mg tablets: £6.91 (84) For severe headache 400mg dose recommended. 200mg and 400mg tablets available OTC. Paracetamol 500mg tablets: £2.78 (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: £1.13 (30) 30mg suppositories: £3.06 (10) Affects QT .Maximum dose10mg tds (30mg) in adults and adolescents weighing 35k or more. Avoid in moderate-severe liver function and in patients with severe underlying heart problems http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON409258 Metoclopramide 10mg tablets: £0.94 Metoclopramide causes more acute dystonic reactions than domperidone particularly in younger patients. Maximum 5 day treatment period. MHRA warning Prochlorperazine 5mg tablets: £1.02 (28) 3mg buccal tabs: £6.49 (10) Simple analgesia plus anti-emetic prescribed separately Triptans First-line Sumatriptan 50mg tablets: £1.55 (6) 100mg tablets: £1.90 (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. Second-line: Central Nervous System Page 107 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Zolmitriptan Prophylaxis of migraine First-line 2.5mg tablets: £1.42 (6) 2.5mg orodispersible tabs: £1.74 (6) 5mg orodispersible tabs: £12.88 (6) Dose for migraine is 2.5mg – 5mg strength only for patients not achieving satisfactory relief with 2.5mg dose. There is no evidence that oro-dispersible formulations have a faster onset of action than conventional tablets. Zolmitriptan orodispersible a good cost effective alternative to rizatriptan melts 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. Propranolol 10mg tablets: £0.96 40mg tablets: £1.19 80mg tablets: £1.66 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). Second-line: Topiramate tablets 25mg tablets: £2.77 (60) 50mg tablets: £3.11 (60) 100mg tablets: £3.16 (60) 200mg tablets: £15.73 (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. Third-line Amitriptyline 10mg tablets: £0.89 25mg tablets: £0.90 50mg tablets: £0.98 NICE CG150 states that people whose migraine is well controlled with amitriptyline should continue their current treatment. Central Nervous System Page 108 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.8.1 Epilepsy Related guidance: NICE CG137 The Epilepsies: diagnosis and management in adults and children in primary and secondary care Formulation switching of antiepileptic drugs See MHRA / CHM Guidance on antieplileptic drugs issued Jul-13. AED Categorisation Problems related to small differences in bioavailability of different manufacturers products (branded, generic) are of concern for some drugs (most notably phenytoin) but not for some others that have a wider therapeutic index and/or high solubility and permeability. In broad terms, three groups of AEDs are identified regarding concerns of the potential risk related to switching between products: Category Guidance AEDs affected Category 1 For these drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product. Phenytoin, carbamazepine, phenobarbital, primidone Category 2 For these drugs the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with patient and/or carer taking into account factors such as seizure frequency and treatment history. Valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine, zonisamide, topiramate Category 3 For these drugs it is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns such as patient anxiety, and risk of confusion or dosing errors. Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin NICE CG137 recommends use of controlled release preparations when prescribing Carbamazepine. 4.8.2 Drugs used in status epilepticus Midazolam Buccal solution as Buccolam 10mg/2ml 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. Licensed in patients 18yrs and under. There may be a risk if existing patients are changed from ‘Epistatus®’ or other unlicensed specials to Buccolam unless there has been clear communication and training for the carer of the different strengths available As Epistatus® Price variable (unlicensed product) Central Nervous System Page 109 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 4.10 Drugs used in substance dependence Related information: NICE Tobacco Harm Reduction PH45 June 2013 Smoking Cessation Nicotine Replacement Therapy (NRT) Patches - various Gum - various Lozenges - various Nasal spray Inhalator Quickmist Bupropion (Amfebutamone) 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. 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 150mg tablets: £41.76 (60) Central Nervous System 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 seizure, eating disorders, CNS tumour, or thoser experiencing acute symptoms of benzodiazepine or alcohol withdrawal Page 110 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Smoking Cessation (continued from previous page) Varenicline▼ Varenicline (Champix) is a Black Triangle▼drug, consequently all adverse effects should be reported to the MHRA via the Yellow Card scheme. Following reports of depression and suicidal ideation the MHRA advise: 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 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) Varenicline is approved for prescribing in Primary Care with the following advice. Varenicline should: Special advice for certain patients Offer people with psychosis or schizophrenia who smoke help to stop smoking, even if previous attempts have been unsuccessful. Be aware of the potential significant impact of reducing cigarette smoking on the metabolism of other drugs, particularly clozapine and olanzapine. [new 2014] Link only be prescribed within its licensed indications for smokers who have expressed a desire to quit smoking normally only be prescribed as part of a programme of behavioural support 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. Page 111 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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. Methadone 1mg/1ml mixture as Physeptone® Alcohol dependence 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 0.4mg: £1.60 (7) 2mg: £2.13 (7) 8mg: £3.94 (7) Prescribing generically 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 112 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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 Orodispersible Galantamine 5mg tablets: £1.31 (28) 10mg tablets: £1.71 (28) 5mg tablets: £7.05 (28) 10mg tablets: £9.42 (28) 8mg tablets: £59.29 (56) 12mg tablets: £74.10 (56) Modified release as Gatalin XL or Luventa XL® Rivastigmine Transdermal patches as Alzest Central Nervous System 8mg m/r capsules: £25.94 (28) 16mg m/r capsules: £32.45 (28) 24mg m/r capsules: £39.90 (28) 8mg m/r capsules: £25.42 (28) 16mg m/r capsules: £31.80 (28) 24mg m/r capsules: £39.10 (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 comorbidity, 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. Avoid anticholinergic (antimuscarinic) drugs with acetylcholinesterase inhibitors which have the potential to reverse their effects 1.5mg capsules: £4.38 (28) 3mg capsules: £4.44 (28) 4.5mg capsules: £17.86 (28) 6mg capsules: £17.62 (28) 4.6mg/24hr patch: £35.10 (30) 9.5mg/24hr patch: £35.10 (30) Considered bioequivalent to Exelon Page 113 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) NMDA-receptor antagonist Memantine 10mg tablets: £12.43 (28) 20mg tablets: £42.27 (28) 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. Central Nervous System Page 114 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) BNF Chapter 5: Infections Related guidance: Somerset CCG Infection Management Guidance (2013/14) Top 5.1 Antibacterial drugs Penicillins Phenoxymethylpenicillin (Penicillin V) 250mg tablets: £1.44 (28) 125mg/5ml SF solution: £14.73 (100ml) 250mg/5ml SF solution: £14.66 (100ml) See Infection management guidance for appropriate clinical indications. Flucloxacillin 250mg capsules: £1.66 (28) 500mg capsules: £2.48 (28) 125mg/5ml suspension: £21.37 (100ml) 125mg/5ml SF suspension: £21.87 (100ml) 250mg/5ml suspension: £26.03 (100ml) 250mg/5ml SF suspension: £26.87 (100ml) See Infection management guidance for appropriate clinical indications. Amoxicillin 250mg capsules: £1.46 (21) 500mg capsules: £1.65 (21) 125mg/5ml SF suspension: £1.33 (100ml) 250mg/5ml SF suspension: £1.59 (100ml) See Infection management guidance for appropriate clinical indications. Co-amoxiclav 250/125mg tablets: £2.18 (21) See Infection management guidance for appropriate clinical indications. 500/125mg tablets: £3.38 (21) Community use of Co-amoxiclav has been implicated in the causation of 125/31mg SF suspension: Clostridium difficile in Somerset. £1.73 (100ml) 250/62mg SF suspension: £1.88 (100ml) Management of infection Page 115 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Cephalosporins Cefalexin RESTRICTED USE ADVISED 250mg capsules: £1.83 (28) 500mg capsules: £2.05 (21) 125mg/5ml suspension: £1.40 (100ml) 250mg/5ml suspension: £2.22 (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. Cephalosporins are commonly implicated in Clostridium difficile infection Tetracyclines Doxycycline 100mg capsules: £1.11 (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: £1.74 (28) per 100ml suspension: 125mg/5ml: £2.75 sugar free £3.18 250mg/5ml: £4.13 sugar free £4.31 500mg/5ml: £7.14 sugar free £12.05 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. 250mg tablets: £1.90 (14) 500mg tablets: £2.74 (14) 125mg/5ml SF suspension:£4.51 (70ml) 250mg/5ml SF suspension:£7.97 (70ml) See Infection management guidance for appropriate clinical indications. 250mg tablets: £2.88 (4) 500mg tablets: £1.89 (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. Clarithromycin Azithromycin Management of infection 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. Clarithromycin MR tablets are non formulary on grounds of higher cost. Page 116 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Trimethoprim and sulphonamides Trimethoprim 100mg tablets: £1.01 (28) 200mg tablets: £0.99 (14) 50mg/5ml SF suspension: £1.96 (100ml) See Infection management guidance for appropriate clinical indications. Metronidazole and tinidazole Metronidazole 200mg tablets: £1.26 (21) 400mg tablets: £1.31 (21) 200mg/5ml suspension: £25.11 (100ml) See Infection management guidance for appropriate clinical indications. Quinolones Ciprofloxacin 250mg tablets: £0.91 (10) 500mg tablets: £1.10 (10) 750mg tablets: £8.00 (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 (UTI) First-line: Nitrofurantoin 100mg tablets: £8.81 (28) 50mg capsules: £13.92 (30) 100mg capsules: £6.50 (30) 100mg capsules MR: £9.50 (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. Second-line: Trimethoprim As above Uncomplicated UTI: 200mg BD for 3 days (women) or 7 days (men). See Infection management guidance for UTI with complicating factors. Catheter associated UTI (CAUTIS) Do not use prophylactic antibiotics for catheter changes unless history of catheter-change-associated UTI or trauma during catheterisation. Clostridium difficile Stop unnecessary antibiotics and/or PPIs. Seek Microbiology advice. First-line: Metronidazole As above Mild and moderate CDI: 400mg TDS for 10-14 days Second-line: Vancomycin 125mg capsules: £132.47 Severe or 3rd episode of CDI: 125mg (oral) QDS for 10-14 days Fidaxomicin 200mg tablets: £1350.00 (20) Approved for primary care use on the advice of a consultant microbiologist ( AMBER ) in accordance with Public Health England (PHE) guidance to the management of Clostridium difficile. Treatment restricted to 10 days (licensed treatment duration.) Management of infection Page 117 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Bacterial vaginosis For treatment only. Preventative should be via self-care - Lactic Acid Gel as Balance Activ BV® 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: £1.12 (7) 150mg capsule: £1.08 (1) Itraconazole 100mg capsules: £4.89 (15) See Infection management guidance for appropriate clinical indications. NB Transient or permanent hearing loss has been reported with itraconazole. Terbinafine 5.3 250mg tablets: £1.65 (28) See Infection management guidance for appropriate clinical indications. Measure LFTs before treatment & after 4-6 weeks. 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. First-line: Aciclovir Second- line: Valaciclovir Management of infection See Infection management guidance for appropriate clinical indications. 200mg dispersible tablets: £2.09 (25) 400mg tablets: £4.89 (56) 800mg tablets: £4.81 (35) 250mg tablets: £123.28 (60) 500mg tablets: £6.86 (10), £86.30 (42) 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. Page 118 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Influenza vaccine Tri-valent intramuscular injection 2013-14 season 2014-15 season For active immunisation against the influenza infection as part of the UK national immunisation programme Companies offer a range of deals & discounts depending on service package. The CCG 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 the different vaccines Somerset CCG sees no reason for a practice to choose a vaccine with an NHS price > £5.50 The Joint Committee on Vaccination and Immunisation states that vaccines should only be administered within the licensed age range: First line: Fluvirin® Enzira® Influvac® Fluarix® £5.55 per dose £5.25 per dose £5.22 per dose £5.39 per dose - First line: Enzira® Influvac® £5.25 per dose (2013 price) £5.22 per dose (2013 price) - Licensed for adults and children from 5 years of age - Licensed for adults and children from 6 months of age Licensed for adults and children from 4 years of age Licensed for adults and children from 5 years of age Licensed for adults and children from 6 months of age Licensed for adults and children from 6 months of age Fluarix Tetra®▼ (tetravalent vaccine) is not recommended. Nasal vaccine Fluenz Tetra®▼ £180.00 (10) For active immunisation against the influenza infection as part of the UK national immunisation programme: All infants aged two years and three years (but not four years or older) on 1 September 2013, or; Children aged 4 to 17 years who are in a clinical risk group category listed in Chapter 19 of the Immunisation Against Infectious Disease Shingles Vaccine (Varicella zoster Vaccine) Management of infection Zostavax® is recommended for active immunisation of individuals aged 70 year or 79 years for the prevention of herpes zoster (“zoster” or shingles) and herpes zoster-related post-herpetic neuralgia (PHN) as part of the UK national immunisation programme: Supply is limited & prescribing not currently recommended on NHS FP10. Page 119 Management of Infection-Guidance for Primary Care -February 2015 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. This guidance is based on best available evidence and should be used alongside references such as the BNF, BNFc , and SPCs. 2. Professional judgement should be used and patients should be involved in decisions about their treatment. 3. 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. Please refer to BNF for further dosing and interaction information (e.g. interaction between macrolides and statins) if needed and please check for hypersensitivity. 4. Prescribe an antibiotic only when there is likely to be a clear clinical benefit. 5. Lower threshold for antibiotics in immunocompromised or those with multiple morbidities; consider culture and seek advice. 6. Consider a NO, or back-up / delayed, antibiotic strategy for acute self-limiting mild UTI symptoms and upper respiratory tract infections including sore throat, common cold, cough and sinusitis. (See No Antibiotic ‘Prescription’ Form). 7. Limit prescribing over the telephone to exceptional cases. 8. Use simple antibiotics prescribed generically whenever possible. 9. 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. 10. Avoid widespread use of topical antibiotics (especially those agents also available as systemic preparations, e.g. fusidic acid). 11. In pregnancy take specimens to inform treatment; where possible avoid tetracyclines, aminoglycosides, quinolones, high dose metronidazole (2 g STAT) unless benefit outweighs risks. Short-term use of nitrofurantoin (at term, theoretical risk of neonatal haemolysis) is not expected to cause fetal problems. Trimethoprim is also unlikely to cause problems unless poor dietary folate intake or taking another folate antagonist e.g. antiepileptic. 12. 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. 13. For further advice (i.e. empirical therapy failure, special circumstances, etc.) contact the Microbiologists at Musgrove Park Hospital, out of hours via MPH switchboard 01823 333444. 14. This guidance should not be used in isolation, it should be supported with patient information about back-up/delayed antibiotics, infection severity and usual duration, clinical staff education, and audits. Materials are available on the RCGP TARGET website. Jump to the infection group you want by clicking on the link below UPPER RESPIRATORY TRACT INFECTIONS GENITAL TRACT INFECTIONS LOWER RESPIRATORY TRACT INFECTIONS SKIN INFECTIONS MENINGITIS DENTAL INFECTIONS URINARY TRACT INFECTIONS EYE INFECTIONS GASTRO-INTESTINAL TRACT INFECTIONS ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) DURATION OF TREATMENT UPPER RESPIRATORY TRACT INFECTIONS: Consider delayed antibiotic prescriptions Annual vaccination is essential for all those at risk of influenza. Influenza Allowed on FP10 as SLS (winter season); status change to: treat ‘at risk’ patients, when influenza is circulating in the PHE Influenza community and ideally within 48 hours of onset (do not wait for lab report) or in a care home where influenza is likely. At risk: NICE Influenza pregnant (including up to two weeks post partum), 65 years or over, chronic respiratory disease (including COPD and asthma) Treatment significant cardiovascular disease (not hypertension), immunocompromised, diabetes mellitus, chronic neurological, renal or liver NICE Influenza disease, morbid obesity (BMI>=40). Use 5 days treatment with oseltamivir 75mg bd. If resistance to oseltamivir or severe Prophylaxis immunosuppression, use zanamivir 10mg BD (2 inhalations by diskhaler for up to 10 days) and seek advice. See PHE Influenza guidance for treatment of patients under 13 years or in severe immunosuppression (and seek advice). Acute Sore Avoid Antibiotics as 90% resolve in 7 days Phenoxymethylpenicillin 500 mg QDS 10 days Throat without, and pain only reduced by 16 hours 1G BD (QDS when severe) CKS If Centor score 3 or 4: (Lymphadenopathy; No Cough; Fever; Tonsillar Exudate) consider 2 or if allergic to penicillin: 3-day delayed or immediate antibiotics. Clarithromycin 250-500mg BD 5 days Antibiotics to prevent Quinsy NNT >4000 Antibiotics to prevent Otitis media NNT 200 10d penicillin lower relapse vs 7d in RCT in <18yrs Acute Otitis Optimise analgesia and Target Antibiotics Child doses Media 60% are better in 24 hours, and 80% are better Amoxicillin Neonate 7-28 days (child doses) in 4 days without antibiotics. They only reduce 30mg/kg (max. 125mg) pain at 2 days (NNT15) and do not prevent TDS CKS deafness. 1mth-1yr 125mg TDS BNFc Consider 2 or 3-day delayed or immediate 1-5yrs 250mg TDS All for antibiotics for pain relief if: 5-18yrs 500mg TDS 5 days < 2yrs with bilateral AOM (NNT4) or Penicillin allergy: bulging membrane & ≥ 4 marked symptoms < 2yrs 125mg QDS Erythromycin All ages with otorrhoea NNT3 2-8yrs 250mg QDS Abx to prevent Mastoiditis NNT >4000 8-18yrs 250-500mg QDS Management of infection Page 120 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) Acute Otitis Externa CKS Acute Rhinosinusitis CKS First use aural toilet (if available) & analgesia 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. Avoid Antibiotics as 80% resolve in 14 days without, and they only offer marginal benefit after 7 days (NNT15). Use adequate analgesia Consider 7-day delayed or immediate antibiotic when purulent nasal discharge NNT8. In persistent infection use an agent with antianaerobic activity e.g. co-amoxiclav First line: Acetic acid 2% Second line: Neomycin sulphate with corticosteroid Phenoxymethylpenicillin or Amoxicillin DURATION OF TREATMENT 1 spray TDS 7 days 3 drops TDS 7 days min to 14 days max 500mg QDS 500mg TDS 1g if severe Penicillin allergy: Doxycycline 200mg stat/100mg OD All for 7 days For persistent symptoms: Co-amoxiclav 625mg TDS 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 All for 5 days bronchitis Consider 7 days delayed antibiotic with or Doxycycline 200 mg stat/100 mg OD CKS symptomatic advice/leaflet. NICE 69 Symptom resolution can take 3 weeks. Consider immediate antibiotics if > 80yr and ONE of: hospitalisation in past year, oral steroids, diabetic, congestive heart failure OR > 65yrs with 2 of above. Acute Treat exacerbations promptly with antibiotics if Doxycycline 200mg stat/100mg OD purulent sputum and increased shortness of exacerbation of or Amoxicillin 500mg TDS breath and/or increased sputum volume. COPD NICE 101 Penicillin allergy: All for 5-7 days Risk factors for antibiotic resistant organisms Gold Clarithromycin 500 mg BD include co-morbid disease, severe COPD, frequent exacerbations, antibiotics in last 2nd line/ if resistance 3months. Co-trimoxazole 960mg BD CommunityUse CRB65 score to help guide and review: IF CRB65=0: Amoxicillin 500 mg TDS 7 days acquired Each CRB65 parameter scores 1: or Clarithromycin 500 mg BD 7 days pneumonia or Doxycycline 200 mg stat/100 mg OD 7 days Confusion (AMT8); treatment in the Respiratory rate ≥ 30/min; community BP systolic <90 or diastolic ≤ 60; Age ≥65; If CRB65=1 & AT HOME BTS 2009 Score 0: suitable for home treatment; Guideline Score 1-2: hospital assessment or admission Amoxicillin 500 mg TDS 7-10 days CKS Score 3-4: urgent hospital admission AND Clarithromycin 500 mg BD NICE Give immediate IM Benzylpenicillin if delayed or Doxycycline alone 200 mg stat/100 mg OD 7-10 days admission/life threatening, and seek risk factors for Legionella and Staph. aureus infection. Mycoplasma infection is rare in over 65s. MENINGITIS NICE fever guidelines Suspected meningococcal disease PHE Meningococcal disease Transfer all patients to hospital immediately. IF time before admission, give IV Benzylpenicillin or Cefotaxime, unless hypersensitive i.e. history of difficulty breathing, collapse, loss of consciousness, or rash. TOP IV or IM Benzylpenicillin Or (only give IM if vein cannot be found) Age 12+ years 1g Child <12 yrs 50mg/kg Prevention of secondary case of meningitis: Only prescribe following advice from Devon, Cornwall and Somerset Health Protection Team, Tel: 0344 225 3557or out of hours via the Musgrove Park Hospital switchboard on 01823 333444. URINARY TRACT INFECTIONS - refer to PHE UTI guidance for diagnosis information TOP As E. coli bacteraemia in the community is increasing ALWAYS safety net and consider risks for resistance Amoxicillin resistance is common, therefore ONLY use if culture confirms susceptibility. People > 65 years: do not treat asymptomatic bacteriuria as 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 or trauma (NICE & SIGN guidance). Treat women with severe/or ≥ 3 symptoms. Uncomplicated UTI (no UTI in Women mild/or ≤ 2 symptoms AND admission risk): men & women a) Urine NOT cloudy 97% negative predictive 1st line (no fever or value, do not treat unless other risk factors for flank pain) Trimethoprim 200mg BD infection. PHE UTI Alternatives b) If cloudy urine use dipstick to guide treatment. SIGN Nitrofurantoin or 100mg m/r BD Nitrite plus blood or leucocytes has 92% positive CKS Women Pivmecillinam (3 days only) 400mg STAT then predictive value; nitrite, leucocytes, blood all CKS Men 200mg TDS Management of infection IV or IM Cefotaxime Age 10+ years: 1200 mg Children 1 - 9 yr: 600 mg Children <1 yr: 300 mg Page 121 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) RCGP UTI Clinical module SAPG UTI negative 76% NPV4Ac) Consider a back-up / delayed antibiotic option. Men: Consider prostatitis and send pretreatment MSU1,5C OR if symptoms mild/nonspecific, use negative dipstick to exclude UTI.6C Always safety net. In treatment failure: always perform culture. Pivmecillinam is only licensed for a 72 hour course and cannot be used in Penicillin allergy. Amoxicillin resistance is common; only use if susceptible (usual dose 500mg TDS, 3 days for women and 7 days for men). Pivmecillinam is first option for community multi-resistant Extended-spectrum Betalactamase E. coli and Fosfomycin (women: 3g stat; men: 3g stat plus 2nd 3g dose 72 hours later) may be an option on advice of microbiology, see Fosfomycin proforma (YDH & MPH). Recurrent UTI in women (not pregnant) ≥ 3 UTIs/year UTI in pregnancy PHE UTI CKS UTI in children PHE UTI CKS NICE Review at 6 months or more often. To reduce recurrence first advise simple measures including hydration. Then standby or post-coital antibiotics. Nightly prophylaxis reduces UTIs but adverse effects and long term compliance poor. Nitrofurantoin 2nd line due to potential pulmonary toxicity. Methenamine hippurate (Hiprex™) has been locally approved as an option. Note: patients already taking prophylactic antibiotics should only be switched if failure/ resistance in urinary isolate/ drug intolerance or complication. 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 (e.g. antiepileptic or proguanil) Child <3 moths: refer urgently for assessment Child ≥ 3 months: use positive nitrite to guide. Start antibiotics, also send pre-treatment MSU for all. Imaging: only refer if child <6 months, or recurrent or atypical UTI. Acute pyelonephritis CKS If previous or current MRGNO/ ESBL discuss with microbiology or consider admission. If admission not needed, send MSU for culture & susceptibility and start antibiotics. If no response within 24 hours, admit. If ESBL risk and with microbiology advice consider IV antibiotic via outpatients (OPAT). GASTRO-INTESTINAL TRACT INFECTIONS Treat all positives in known DU, GU or low grade Eradication of MALToma. In Non-Ulcer NNT is 14. Helicobacter Management of infection Frail vulnerable with associated comorbidity GFR˃45ml/min: 1st line Nitrofurantoin Alternatives Pivmecillinam (3 days only) or Trimethoprim Frail vulnerable with associated comorbidity GFR<45ml/min: 1st line Pivmecillinam (3 days only) Alternative Trimethoprim DURATION OF TREATMENT Women 3 days Men 7 days 100mg m/r BD 400mg STAT then 200mg TDS 200mg BD (except Pivmecillinam licensed for 3 days) 400mg STAT then 200mg TDS 200mg BD Pivmecillinam is first option if previous history of Trimethoprim resistance. Second line: perform culture in all treatment failures. Risk factors for increased resistance include: care home resident, recurrent UTI, hospitalisation >7d in the last 6 months, unresolving urinary symptoms, recent travel to a country with increased antimicrobial resistance (outside Northern Europe and Australasia) especially health related, previous known UTI resistant to trimethoprim, cephalosporins or quinolones. If increased resistance risk, send culture for susceptibility testing & give safety net advice. Post coital stat Trimethoprim 100 mg (off-label) or Nitrofurantoin (note: as 50–100 mg per December 2014 100mg Prophylaxis (non-MR) 1x nocte is the OD at night most cost-effective option for prophylaxis with Nitrofurantoin. or consider: Methenamine hippurate First line: Nitrofurantoin or Trimethoprim Give folic acid if first trimester Second line: if susceptible, Amoxicillin Third line: Cefalexin Lower UTI: Trimethoprim or Nitrofurantoin If susceptible, Amoxicillin Second line: Cefalexin Upper UTI: Co-amoxiclav Second line: Cefixime Ciprofloxacin or Co-amoxiclav If susceptible: Trimethoprim 1g 100 mg m/r BD 200mg BD (off-label) Give folic acid if first trimester BD (may be increased to TDS if catheterised) All for 7 days 500 mg TDS 500 mg BD Lower UTI 3 days See BNFc for dosage Upper UTI 7-10 days 500 mg BD 500/125 mg TDS 7 days 14 days 200mg BD 14 days TOP Always use PPI TWICE DAILY: Esomeprazole 20mg, Lansoprazole 30mg, Omeprazole 20-40mg, Pantoprazole 40mg or Rabeprazole 20mg Page 122 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) pylori NICE Dyspepsia NICE PPI doses NICE H.Pylori PHE H.Pylori CKS Do not offer eradication for GORD. First line treatment: choose the treatment regimen with the lowest acquisition cost, and take into account previous exposure to clarithromycin or metronidazole. Do not use Clarithromycin, Metronidazole or Quinolone if used in past year for any infection. Retest for H. pylori post DU/GU or relapse after second line therapy: using breath or stool test OR consider endoscopy for culture and susceptibility. Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment. First line PPI & Amoxicillin + either Clarithromycin OR Metronidazole 1g BD 500mg BD 400mg BD First line - Penicillin allergy PPI & Amoxicillin & Clarithromycin 1g BD 500mg BD First line - Penicillin allergy with previous exposure to Clarithromycin PPI & Bismuthate (De-nol tab®) & Metronidazole & Tetracycline Second line (still have symptoms after 1st line eradication): PPI & Amoxicillin + either Clarithromycin OR Metronidazole (whichever was not first line) Second line - previous exposure to Clarithromycin & Metronidazole PPI & Amoxicillin + either Tetracycline OR Levofloxacin Second line - Penicillin allergy without previous exposure to Quinolone PPI & Metronidazole & Levofloxacin Infectious diarrhoea CKS Clostridium difficile DoH PHE Travellers’ diarrhoea CKS Threadworm CKS DURATION OF TREATMENT 240mg BD 400mg BD 500mg QDS All for 7 days 1g BD 500mg BD 400mg BD 1g BD 500mg QDS 250mg BD (MALToma 14 days) 400mg BD 250mg BD Second line - Penicillin allergy with previous exposure to Quinolone 240mg BD PPI & Bismuthate (De-nol tab®) & 400mg BD Metronidazole & 500mg 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 usually 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 (within 3 days). 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, Devon, Cornwall and Somerset Health Protection Team, Tel: 0344 225 3557or out of hours via the Musgrove Park Hospital switchboard on 01823 333444. Stop unnecessary antibiotics and/or PPIs. 1st episode 70% respond to MTZ in 5 days; 92% in 14days metronidazole (MTZ) 400 mg oral TDS 10-14 days Admit if severe: T >38.5; WCC >15, rising 2nd episode/severe/type 027 creatinine or signs/symptoms of severe colitis. oral vancomycin 125mg oral QDS 10 -14 days Avoid anti-motility anti-diarrhoeal agents such as Recurrent disease consider: Loperamide or Codeine. Fidaxomicin (AMBER on the 200mg oral BD 10 days recommendation of a microbiologist) 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 Treat all household contacts at the same time > 6 months: Mebendazole 100mg stat PLUS advise hygiene measures for 2 weeks (‘off-label’ if < 2yrs) (hand hygiene, pants at night, morning shower) PLUS wash sleepwear, bed linen, dust, and < 6mths: six weeks hygiene vacuum on day one. GENITAL TRACT INFECTIONS Contact UKTIS (Tel. 0844 892 0909 or use TOXBASE®), for information on foetal risks if TOP patient is pregnant STI screening People with risk factors should be screened for chlamydia, gonorrhoea, HIV, syphilis. Refer individual and partners to GUM clinic or Sexual Health Clinic. Risk factors: < 25yrs, no condom use, recent (<12mth)/frequent change of partner, symptomatic partner, BASHH area of high HIV. Management of infection Page 123 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) Chlamydia trachomatis/ urethritis SIGN BASHH PHE CKS Opportunistically screen all aged 15-25yrs. Treat partners and refer to GUM service. Pregnancy or breastfeeding: Azithromycin is the most effective option. Due to lower cure rate in pregnancy, test for cure 6 weeks after treatment. For suspected epididymitis in men ˃ 35 years with low risk of STI (High risk, refer to GUM). Vaginal candidiasis BASHH PHE CKS All topical and oral azoles give 75% cure. Bacterial vaginosis BASHH PHE 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 BASHH PHE CKS Treat partners and refer to GUM service. Pregnant/ breastfeeding: avoid 2g stat dose MTZ. Consider Clotrimazole for symptom relief (not cure) if MTZ declined. Pelvic Inflammatory Disease BASHH CKS Refer woman & contacts to GUM service. Always culture for gonorrhoea & chlamydia. 28% of gonorrhoea isolates now resistant to quinolones. If gonorrhoea likely (partner has it, severe symptoms, sex abroad) use ceftriaxone regimen or refer to GUM. Low risk only Metronidazole PLUS Ofloxacin If high risk or likely gonorrhoea Ceftriaxone PLUS Metronidazole PLUS Doxycycline Send MSU for culture and start antibiotics. 4-wk course may prevent chronic prostatitis. Quinolones achieve higher prostate levels. Ciprofloxacin Acute prostatitis CKS Pregnancy: avoid oral azole and use intravaginal for 7 days. Doxycycline or Azithromycin Pregnant or breastfeeding: Azithromycin or Erythromycin or Amoxicillin Epididymitis: low STI risk: Ofloxacin Clotrimazole OR oral Fluconazole Pregnant: Clotrimazole OR Miconazole 2% cream 3A+ oral Metronidazole OR MTZ 0.75% vag gel OR Clindamycin 2% cream OR Lactic Acid Gel (Balance Activ BV®) used in place of clindamycin for treatment only (self-care and buy OTC for prophylaxis) Metronidazole (MTZ) Clotrimazole DURATION OF TREATMENT 100mg BD 1g 7 days stat 1g (off-label use) 500mg QDS 500mg TDS stat 7 days 7 days 200mg BD 500mg pessary OR 10% cream 150mg orally 14 days stat 10 mg pessary at night 5g intravaginally BD 6 nights 7 days 7 days stat 5 nights 7 nights 7 nights 400 mg BD or 2g 5 g applicatorful at night 5 g applicatorful at night one single use tube at night stat 400 mg BD or 2g 5-7 days stat 100mg pessary at night 6 nights 400mg BD 400mg BD 14 days 14 days 500mg IM 400mg BD 100mg BD 500 mg BD stat 14 days 14 days All for 28 days 2nd line Trimethoprim 200mg BD SKIN INFECTIONS Scarlet Fever PHE CKS TOP Suspected scarlet fever can be confirmed by taking a throat swab for culture of GAS, although a negative throat swab does not exclude the diagnosis. Consider taking a throat swab in patients with clinically suspected scarlet fever and in children with an undiagnosed febrile illness without an obvious focus of infection. Prescribe antibiotics without waiting for the culture result if scarlet fever is clinically suspected. Advise exclusion from nursery / school / work for 24 hours after the commencement of appropriate antibiotic treatment. Notify Devon, Cornwall and Somerset Health Protection Team, Tel: 0344 225 3557 or out of hours via the Musgrove Park Hospital switchboard on 01823 333444. First line: Penicillin V Alternative for children who are unable to swallow tablets, or where compliance is a concern Amoxicillin Second line (If penicillin allergy) Azithromycin Impetigo PHE CKS Eczema CKS For extensive, severe, or bullous impetigo, use oral antibiotics. Reserve topical antibiotics for very localised lesions to reduce the risk of resistance. Reserve Mupirocin for MRSA. <1mth 12.5mg/kg (max. 62.5mg) QDS 1mth-<1yr 62.5mg QDS 1-<6yrs 125mg QDS 6-<12yrs 250mg QDS 12-<18yrs 250-500mg QDS Adults 500mg QDS 10 days 50 mg/kg OD (max 1000 mg) or alternatively 25 mg/kg (max 500 mg) BD 6mths-<12yrs ‘off-label’ 12mg/kg (max. 500mg) OD ˃12yrs 500mg OD 500 mg QDS 5 days oral Flucloxacillin 7 days If penicillin allergic: oral Clarithromycin 250-500 mg BD 7 days Retapamulin Topically BD 5 days Mupirocin (MRSA only) Topically BD 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. Management of infection Page 124 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) Erythema chronicum migrans CKS PHE Associated with Lyme disease. Send clotted blood for Lyme serology and treat empirically. Microbiology will advise on positive results. Cellulitis CKS “Guidelines for the Management of Cellulitis in Adults in Somerset” (Appendix 1) Leg ulcer PHE CKS If patient afebrile and healthy other than cellulitis, use oral flucloxacillin alone. If river or sea water exposure, discuss with microbiologist. Refer to local guidance “Guidelines for the Management of Cellulitis in Adults in Somerset” (Appendix 1 to this document). MRSA Diabetic Foot Infections PVL S. aureus PHE Bites Human: CKS Cat or dog: Mastitis CKS Scabies CKS Fungal infection – skin CKS body & groin CKS foot CKS scalp Ulcers always colonized. Antibiotics do not improve healing unless active infection. If active infection, send pre-treatment swab. Review antibiotics after culture results. Do not use Clindamycin. For active MRSA infection, confirmed by lab results. Use antibiotic sensitivities to guide treatment. If severe infection or no response to monotherapy after 24-48 hours, seek advice from microbiologist. For cellulitis refer to local guidance “Guidelines for the Management of Cellulitis in Adults in Somerset” (Appendix 1 to this document). 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. Doxycycline Second line: Amoxicillin (especially for children, pregnancy & breastfeeding) Flucloxacillin if allergic to penicillin: Clarithromycin (caution in elderly with heart disease) or Doxycyline facial: Co-amoxiclav DURATION OF TREATMENT 100mg BD All for 14 days 500mg TDS See BNFc for children under 5 years. 1g QDS (reduce to 500mg QDS if intolerant) 500 mg BD 200mg STAT followed by 100mg OD 500/125 mg TDS All for 7 days (review days 4872hrs or as appropriate) Active infection if cellulitis/increased pain/pyrexia/purulent exudate/odour For MRSA screening and suppression, see PHE MRSA Quick Reference Guide 1g QDS (reduce to Flucloxacillin All for 7 days 500mg QDS if intolerant) (If severe if allergic to penicillin: 500 mg BD infection or no Clarithromycin (caution in response to elderly with heart disease) monotherapy or Doxycyline 200mg STAT followed after 24-48 hours, by 100mg OD seek advice from 500/125 mg TDS facial: Co-amoxiclav microbiologist.) Flucloxacillin 500mg - 1G QDS If allergic to penicillin Doxycycline All for 7-14 days 200mg STAT followed by 100mg OD If osteomyelitis is suspected, refer to secondary care Panton-Valentine Leukocidin (PVL) is a toxin produced by 4.9% of S. aureus from boils/abscesses. Can rarely cause severe invasive infections in healthy people; if found suppression therapy should be given. 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 All for 7 days Antibiotic prophylaxis is advised. If penicillin allergic: Assess risk of tetanus and rabies. Metronidazole PLUS 400 mg TDS Doxycycline (cat/dog/man) Give prophylaxis if cat bite/puncture wound; bite 100 mg BD to hand, foot, face, joint, tendon, ligament; immunocompromised/diabetic/asplenic/ AND review at 24 & 48hrs cirrhotic/presence of prosthetic valve or prosthetic joint. Antibiotics are not always required. Self-help Flucloxacillin 500mg - 1G QDS measures e.g. continuation of breastfeeding or expressing will aid resolution of mastitis. If allergic to penicillin: Clarithromycin (if not 500mg BD All for 14 days breastfeeding) OR Doxycycline 200mg stat then 100mg OD 2 applications Treat all home & sexual contacts within 24h. Permethrin 5% cream 1 week apart Treat whole body from ear/chin downwards and If allergy: 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, oral therapy indicated. Management of infection Page 125 Management of Infection-Guidance for Primary Care -February 2015 ILLNESS COMMENTS DRUG ADULT DOSE (unless otherwise stated) Fungal infection – fingernail or toenail CKS Varicella zoster/ chicken pox CKS PHE & Herpes zoster/ shingles CKS Cold sores Topical treatment for most fungal skin and nail infections are low priority and suitable for self care. Take nail clippings: start therapy only if infection is confirmed by laboratory. Terbinafine is more effective than azoles. Liver reactions rare with oral antifungals. If candida or non-dermatophyte infection confirmed, use oral itraconazole. For children, seek specialist advice. Pregnant/immunocompromised/neonate: seek urgent specialist advice. Chicken pox: IF onset of rash < 24hrs & > 14years 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. Superficial only Amorolfine 5% nail lacquer First line: Terbinafine Second line: Itraconazole If indicated: Aciclovir 1-2x/weekly DURATION OF TREATMENT fingers toes 6 months 12 months fingers toes 6 – 12 weeks 3 – 6 months fingers toes 7 days monthly 2 courses 3 courses 250 mg OD 200 mg BD 800 mg five times a day 7 days Cold sores resolve after 7–10 days without treatment. Topical antivirals applied prodromally reduce duration by 12-24hrs. DENTAL INFECTIONS Dental Infections TOP 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 0300 123 7691. 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 500mg TDS Up to 5 days If allergic to penicillin: Metronidazole 200mg TDS Up to 3 days Pericoronitis: metronidazole Most bacterial conjunctivitis is self-limiting. Treat if severe, as most viral or self-limiting. 65% resolve on placebo by day five. Red eye with yellow-white mucopurulent, not watery discharge. Usually unilateral but may spread. If severe: 1st line Chloramphenicol 0.5% drops 200mg TDS EYE INFECTIONS Conjunctivitis CKS 3 days TOP Fusidic acid gel eye drops has less Gramnegative activity than Chloramphenicol and is not recommended locally due to rising resistance and in cost. If treatment failure with Chloramphenicol consider referral to specialist. Ofloxacin (Exocin®) is a cost-effective option in severe conjunctivitis only when Chloramphenicol not tolerated. Management of infection and 1% ointment OR 1% ointment 1 drop 2 hourly for 2 days then 4 hourly (whilst awake) at night All for 48 hours after resolution QDS Page 126 Management of Infection-Guidance for Primary Care -February 2015 Appendix 2 Methicillin Resistant Staphylococcus Aureus (MRSA) Decolonisation Policy (WG 05/08/14) 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 (if using Naseptin® then this nasal cream must be continued for an additional 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: twice daily to nostrils for at least 5 days (if Mupirocin nasal treatment is unavailable the second line treatment is Neomycin sulphate & chlorhexidine dihydrochloride (Naseptin®) Nasal Cream four times daily for 10 days) 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 NHS Somerset CCG 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 CCG 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 NHS Somerset CCG Infection Control Team can be contacted for further advice via the CCG switchboard on 01935 384000. Further advice (and documents, including topical therapy chart) is also available on the Infection control page of the NHS Somerset CCG website http://www.somersetccg.nhs.uk Management of infection Page 127 Public Health England Updated guidance on the management and treatment of Clostridium difficile infection (Jun-13) Algorithm 1. 1st episode of Clostridium difficile infection (CDI) Diarrhoea AND one of the following: Positive C. difficile toxin test OR Results of C. difficile toxin test pending AND clinical suspicion of CDI If clinically appropriate discontinue non-C. difficile antibiotics to allow normal intestinal flora to be re-established Suspected cases must be isolated Symptoms/signs: not severe CDI (None of: WCC >15, acute rising creatinine and/or colitis) Oral metronidazole 400mg 8-hourly 10-14 days Symptoms/signs: severe CDI WCC >15, acute rising creatinine and/or colitis Oral vancomycin 125 mg 6-hourly 10-14 days. Consider oral fidaxomicin 200 mg 12-hourly 10 days in patients with multiple co-morbidities who are receiving concomitant antibiotics DAILY ASSESSMENT DAILY ASSESSMENT Symptoms improving Diarrhoea should resolve in 1-2 weeks st Recurrence occurs in ~20% after 1 episode; 50-60% after 2nd episode Symptoms not improving or worsening Should not normally be deemed a treatment failure until day 7 of treatment. However, if evidence of severe CDI continues or worsens Symptoms not improving or worsening Should not normally be deemed a treatment failure until until day 7 of treatment. However, if evidence of severe CDI: WCC >15, acute rising creatinine and/or signs/symptoms of colitis Switch to oral vancomycin 125 mg 6-hourly 10-14 days Antimotility agents should not be prescribed in acute CDI Management of infection Surgery / GI / Micro / ID consultation AND, depending on degree of ileus/prior treatment EITHER Vancomycin 125-500 mg PO/NG 6-hourly +/- Metronidazole 500 mg IV 8-hourly x 10 days OR Fidaxomicin 200 mg PO 12-hourly PLUS CONSIDER Intracolonic vancomycin (500 mg in 100–500 ml saline 4–12-hourly) given as retention enema: 18 gauge Foley catheter with 30 ml balloon inserted per rectum; vancomycin instilled; catheter clamped for 60 minutes; deflate and remove (Apisarnthanarak et al., 2002) Further Surgery/GI/Micro/ID consultation Depending on choice of therapy (see above) consider: 1. High dose oral/NG vancomycin (500mg PO 6-hourly) 2. IV Immunoglobulin 400mg/kg 1 dose, consider repeat Page 128 Updated guidance Algorithm on the management 2 Recurrent and treatment Clostridium of Clostridium difficile difficile infection infection (CDI) Recurrent CDI occurs in ~15-30% of patients treated with metronidazole or vancomycin Recurrence of diarrhoea (at least 3 consecutive type 5-7 stools) within ~30 days of a previous CDI episode AND positive C. difficile toxin test Must discontinue non- C. difficile antibiotics if at all possible to allow normal intestinal flora to be re-established Review all drugs with gastrointestinal activity or side effects (stop PPIs unless required acutely) Suspected cases must be isolated Symptoms/signs: not life-threatening CDI Oral fidaxomicin 200 mg 12-hourly for 10 days (efficacy of fidaxomicin in patients with multiple recurrences is unclear) Depending on local cost-effectiveness decision making, Oral vancomycin 125 mg 6-hourly 10-14 days is an alternative Daily Assessment (include review of severity markers, fluid/electrolytes) Symptoms improving Diarrhoea should resolve in 1-2 weeks IF MULTIPLE RECURRENCES ESPECIALLY IF EVIDENCE OF MALNUTRITION, WASTING, etc. 1. Review ALL antibiotic and other drug therapy (consider stopping PPIs and/or other GI active drugs) 2. Consider supervised trial of anti-motility agents alone (no abdominal symptoms or signs of severe CDI) Also consider on discussion with microbiology: 3. Fidaxomicin (if not received previously) 200 mg 12-hourly for 10 days 4. Vancomycin tapering/pulse therapy (4-6 week regimen) 5. (Am J Gastroenterol 2002;97:1769-75) 6. IV immunoglobulin, especially if worsening albumin status (J Antimicrob Chemother 2004:53:882-4) 7. Donor stool transplant (Clin Infect Dis 2011;53:994-1002.Van Nood et al., NEJM 2013) Management of infection Page 129 BNF Chapter 6: Endocrine System Top 6.1 Drugs used in diabetes Related guidance: NICE Clinical Guideline CG87 (2009): Type 2 diabetes See summary chart on p.Error! Bookmark not defined. Before any pharmacological interventions are considered there should be a 3 month period of diet & lifestyle interventions. Education Diet provide individualised and ongoing specialist nutritional advice. Lifestyle encourage weight loss and exercise. provide structured education to every patient and/or their carer at and around the time of diagnosis and review annually. 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 144 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 48mmol/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 130 3 month trial of lifestyle interventions Error!HbA1c Bookmark not defined. ≥48mmol/mol METFORMIN with active dose titration and use of MR version if necessary to minimise incidence of GI side effects. 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 HbA1c <48mmol/mol Monitor for deterioration Metformin HbA1c ≤48mmol/mol Monitor for deterioration HbA1c ≥48mmol/mol Metformin plus gliclazide HbA1c ≤58mmol/mol Monitor for deterioration HbA1c ≥58mmol/mol Insulin + metformin + gliclazide Adding insulin in preference to other oral hypoglycaemics should be normal 3rd line option unless there is a strong reason not to, parrticularly if patient is markedly hyperglycaemic HbA1c ≤58mmol/mol Monitor for deterioration HbA1c ≥58mmol/mol Consider repaglinide before meals for people with erratic lifestyle. Consider substituting pioglitazone (1st line) or gliptin/gliflozin 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.132) Consider adding exenatide, lixisenatide 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 Insulin+gliptin Insulin+cana/dapa/empaglliflozin Insulin+lixa/exenatide(bd dose only)/liraglutide Endocrine System - Diabetes For options i. and ii. consider Metformin plus gliclazide Gliclazide HbA1c ≥48mmol/mol + pioglitazone If metformin CI or not tolerated: Gliclazide + pioglitazone or Metformin + gliptin (alogliptin 1st line) or Metformin + canagliflozin/dapagliflozin/empagliflozin HbA1c <58mmol/mol Monitor for deterioration HbA1c ≥58mmol/mol or Gliclazide + gliptin (Alogliptin 1st line) HbA1c <58mmol/mol Monitor for deterioration HbA1c ≥58mmol/mol Metformin + gliclazide + pioglitazone or Metformin + gliclazide + gliptin or Start Insulin Metformin + gliclazide + cana/dapa/empag Or Metformin +pioglitazone + canagliflozin or Metformin + gliclazide + lixisenatide or exenatide or liraglutide (use injections last) HbA1c <58mmol/mol Monitor for deterioration HbA1c ≥58mmol/mol HbA1c ≥58mmol/mol HbA1c <58mmol/mol Monitor for deterioration Page 131 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 132 HbA1c for Diagnosis of Diabetes Mellitus Alogrithm as approved by Somerset Clinical Commissioning Group HbA1c is recognised by the WHO for the diagnosis of diabetes. The specialist diabetes services in Somerset (Taunton, Yeovil and Bath) have recommended that the following algorithm is adopted. More detail on the evidence and reasoning for this are given below. This is for use in ADULT patients in NON-URGENT situations. NICE Guidance on Prevention of Type 2 Diabetes http://www.nice.org.uk/nicemedia/live/13791/59951/59951.pdf Endocrine System - Diabetes Page 133 Until recently, type 2 diabetes has been diagnosed using the following criteria: 2. In symptomatic individuals, a single diagnostic test is sufficient – either random (RBG) or fasting glucose (FBG), or an oral glucose tolerance test (OGTT) 3. In asymptomatic individuals (the majority), a two-step process is performed. A screening test, typically random or fasting glucose (but could be OGTT), is performed and in individuals testing positive, a follow up test on a different day, typically FBG or OGTT. These tests and criteria still apply; HbA1c is an additional diagnostic test. HbA1c (glycated haemoglobin) has long been used as tool for assessing blood glucose control in individuals with diabetes. As a measure of integrated plasma glucose levels over 2-3 months it was felt to have utility in the diagnosis of diabetes. This has been studied, and in 2011, the WHO produced a report recommending the use of HbA1c in the diagnosis of diabetes http://www.who.int/diabetes/publications/reporthba1c_2011.pdf. The primary recommendations were: 1. HbA1c can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. 2. An HbA1c of 48 mmol/mol (6.5%) is recommended as the cut point for diagnosing diabetes. A value of less than 48 mmol/mol does not exclude diabetes diagnosed using glucose tests. The algorithm for diagnosis of diabetes is based on one developed by the Association of British Clinical Diabetologists (ABCD) and reflects joint national guidance (http://www.acb.org.uk/docs/Article%20Summary%20Use%20of%20HbA1c%20WHO%20gu idance%20251111[1].pdf). Somerset Clinical Commissioning Group has approved HbA1c funding for primary care within their priority setting process in August 2013. Clinical information provided by Paul Lambert Consultant Diabetologist Taunton and Somerset NHS Foundation Trust September 2013 Version 5 Endocrine System - Diabetes Page 134 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 6.1.1 Insulins Insulin Passport Insulin Passports and patient information booklets should be offered to patients receiving insulin. The Insulin Passport provides a record of the patient’s current insulin preparations and contains a section for emergency information. The patient information booklet provides advice on the safe use of insulin. They are suppled either from the insulin manufacturers, or via the Somerset partnership. Eli Lilly – Russell Pearce – 07825 990332 / Debbie Gilmore 07714 308537 Novo Nordisk – 01293 613555 Sanofi – Rob Bartlett [email protected] 07841 321709 Sompar team administrator on 01823 346191 Please read code patients Insulin passport given 8CE02 Insulin passport completed 8BAi. Informed dissent not to carry insulin passport 8BAj Short acting: Insulin aspart NovoRapid 3ml cartridge: £28.31 (5) 10ml vial: £14.08 (1) Prefilled pens are around £2-3 more expensive per 5 and should be used only when patient choice demands. Insulin lispro Humalog 3ml cartridge: £28.31 (5) 10ml vial: £16.61 (1) Soluble insulin Human Actrapid Insuman Rapid® 10ml vial: £7.48 (1) 3ml cartridge: £17.50 (5) Insulin glulisine Apidra Continued on next page Endocrine System - Diabetes Solostar 3ml pf inj. device: £28.30 (5) 3ml cartridge: £28.30 (5) 10ml vial: £16.00 (1) Page 135 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Intermediate acting: Biphasic insulin aspart NovoMix 30 3ml cartridge: £28.79 (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) ® 3ml pf inj. device: £19.80 (5) Insuman Basal 3ml cartridge: £17.50 (5) 5ml vial: £5.61 (1) Biphasic isophane insulin Insuman Comb 15® 3ml cartridge: £17.50 (5) Insuman Comb 25® 3ml pf inj. device: £19.80 (5) 3ml cartridge: £17.50 (5) 5ml vial: £5.61 (1) ® Insuman Comb 50 3ml cartridge: £17.50 (5) Long acting: Insulin glargine Lantus 3ml cartridge: £41.50(5) 10ml vial: £30.68 (1) Insulin detemir Levemir Endocrine System - Diabetes 3ml cartridge :£42.00 (5) Page 136 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Hypodermic equipment Choice of needle & lancet may be governed by specific insulin prescribed and injection technique. Insulin pen needles There is no clinical reason for recommending needles longer than 8mm in adults or 6mm in children or adolescents. GlucoRx FinePoint® 4mm/31 gauge: £5.95 (100) 5mm/31 gauge: £5.95 (100) 6mm/31 gauge: £5.95 (100) 8mm/31 gauge: £5.95 (100) Omnican Fine 4mm/31gauge:£5.95 (100) 6mm/31 gauge: £5.95 (100) 8mm/31 gauge: £5.95 (100) BD Autoshield DUO ® 5mm/30 gauge: £30.08 (100) GlucoRx FinePoint® represents a cost-effective choice of needle where appropriate. Only for patients who have their insulin administered by healthcare assistants, nurses, carers etc to help prevent needlestick injuries: Shield automatically locks after injection to help prevent accidental needlesticks Metal tabs provide visual confirmation that the safety feature is activated 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 56 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. Endocrine System - Diabetes Page 137 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 6.1.2 Drugs used in diabetes Biguanides Metformin Metformin should be: First-line: Immediate-release 500mg tablets: £0.90 850mg tablets: £1.30 (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 Sachets Metformin sachets now discontinued, so for patients with swallowing difficulties a ‘special’ liquid formulation is an expensive option Second-line: Modified release as Diagemet XL Generic Sulphonylureas Gliclazide 500mg m/r tablets: £1.75 Metformin MR is approved for patients who would otherwise stop metformin therapy due to GI side effects. 750mg m/r tablets: £6.40 1000mg m/rtablets: £8.52 80mg tablets: £1.04 40mg tablets: £3.36 NICE CG87 recommends prescribing a sulfonylurea with a low acquisition cost (but not glibenclamide) when a sulfonylurea is indicated. Normal third line option, if HbA1c remains at ≥ 58mmol/mol HbA1c (or level agreed with individual) is to initiate insulin therapy (see page 132 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 138 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Glitazones (thiazolidinediones) Prescribing of Pioglitazone should be in line with MHRA/EMEA advice (Oct-07, Dec-07, Jan-11, Aug-11) and NICE guidance (TA63 Aug-03, CG66 May-08, CG87 May-09) 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 (Gliptins) 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: £1.49 30mg tablets: £1.92 45mg tablets: £2.33 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 Alogliptin Reduce dose to 12.5mg once daily when CrCl <50ml/min, 6.25mg once daily when CrCl <30ml/min CrCl <30ml/min or with end-stage renal disease requiring haemodialysis or peritoneal dialysis, use sitagliptin 25mg once daily. Continued overleaf Endocrine System - Diabetes Page 139 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) DPP-4 inhibitors First line Alogliptin 6.25mg tablets:£26.60 12.5mg tablets:£26.60 25mg tablets: £26.60 Second line Linagliptin 5mg tablets: £33.26 Monotherapy if metformin intolerant or C/I.Dual therapy with metformin. Triple therapy with SU and metformin. Can use with insulin with or without metformin Saxagliptin 5mg tablets: £31.60 2.5mg tablets: £31.60 Saxagliptin is is licensed for triple therapy with metformin & sulphonylurea and with insulin +/- metformin Sitagliptin 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 Caution >75years Vildagliptin 50mg tablets: £31.76 (56) Twice daily dosing.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: £8.67 (90) 1mg tablets: £9.10 (90) 2mg tablets: £5.71 (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: £9.02 (90) 100mg tablets: £15.48 (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. Other options: Rapid acting insulin secretagogue Endocrine System - Diabetes As a dual therapy add-on to other agents including insulin. Please note that the licence for alogliptin does not preclude any particular combination including triple therapy with metformin and a sulphonylurea (SU), and the use within this specific combination is not contraindicated. The safety and efficacy of alogliptin when used as triple therapy with metformin and a sulphonylurea have not been fully established. Monotherapy would be considered “off license” Page 140 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Sodium-glucose cotransporter-2 (SGLT-2) inhibitor Dapagliflozin▼ 5mg tablets: £36.59 10mg tablets: £36.59 SGLT-2 drugs are recommended by NICE as an add-on to metformin in a similar way to DDP-4. So continue only if there is a reduction of ≥0.5% points in HbA1c in 6 months (between 5 and 6 mmol/mol) For the improvement of glycaemic control treatment of type 2 diabetes mellitus of in adults in accordance with NICE TA288 (Jun-13): Dapagliflozin in a dual therapy regimen in combination with metformin is recommended as an option for treating type 2 diabetes, only if it is used as described for DPP-4 inhibitors in NICE CG87 Mar-09 (Updated Mar-10) Dapagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option for treating type 2 diabetes Age limit 75 years Not recommended with concurrent pioglitazone or eGFR <60ml/min/1.73m2 Quadruple therapy with metformin, SU and DPP-4 has not been studied so remains non-formulary Canagliflozin▼ Endocrine System - Diabetes 100mg tablets:£39.20 (30) 300mg tablets:£49.99 (30) Monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications. Add-on therapy with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control Age limit 85 years Can be used as per NICE TA288 (Jun-13) No initiatition if eGFR <60ml/min/1.73m2 Page 141 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Empagliflozin▼ Endocrine System - Diabetes 10mg tablet: £36.59 25mg tablet: £36.59 Monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance. Add on with other glucose–lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control No age limit Can be used as per NICE TA288 (Jun-13) No initiatition if eGFR <60ml/min/1.73m2 Page 142 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) GLP-1 mimetic (Glucagon-like peptide-1 analogue) First-line: Dietary advice should be given before starting therapy with these agents. For all dose regimens of lixisenatide, 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. Lixisenatide▼ Treatment initiation pack: £54.14 Once-daily dosing 10mcg prefilled pen: £27.07 (14 doses) 20mcg prefilled pen: £54.14 (2 14 doses) Second-line: or Exenatide Twice-daily dosing 5mcg pre-filled pen: £68.24 (60 doses) 10mcg pre-filled pen: £68.24 (60 doses) Modified-release▼ Once-weekly 2mg vial : £73.36 (4) dosing 2mg prefilled pen £73.36 (4) Lixisenatide, 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; BMI ≥ 35 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) & other specific psychological or medical problems associated with high body weight, or BMI < 35 kg/m2 and insulin therapy would have significant occupational implications, or where weight loss would benefit other significant comobidities such as sleep apnoea. NB Group 2 (LGV/PCV) drivers are required to notify DVLA if taking combination of exenatide with sulphonylurea. Somerset Prescribing Forum approved the use of lixisenatide and exenatide as adjunctive therapy to basal insulin (with or without metformin and/or pioglitazone in adults with Type 2 diabetes) i.e. within the respective licensed indications. Patients are expected to show 0.5% (6mmol/mol) reduction in HbA1c after 6 months to justify continuation. 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. or Liraglutide Once-daily dosing 6mg/ml pre-filled pen: £78.48 (2 3ml), £117.72 (3 3ml) 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. For triple therapy see above Endocrine System - Diabetes Page 143 Guidance on the use of Blood Glucose Testing Strips based on NICE CG87 NICE national guidelines for the management ofblood glucose levels in people with type 2 diabetes (May-08) 1. 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. 2. 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). 2. 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 e.g.: 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. 4. 5. 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 twice daily on their driving days, at times relevant to the driving they do. Endocrine System - Diabetes Page 144 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 6.2 Thyroid and anti-thyroid drugs Thyroid hormones Anti-thyroid hormones Levothyroxine 25mcg tablets: £2.83 50mcg tablets: £1.96 100mcg tablets: £1.95 100micrograms/5ml oral solution sugar free: £77.03 (100ml) Monitoring requirements are for TFTs annually Carbimazole 5mg tablets: £41.93 (100) 20mg tablets: £103.62 (100) New patients should be counselled regarding warning signs of haematological toxicity. Monitoring requirements are for FBC, LFTS and TFTs annually Propylthiouracil 50mg tablets: £53.94 (56) Propylthiouracil is included only for patients intolerant to Carbimazole. Monitoring requirements are for FBC, LFTS and TFTs annually Liquid is lactose free. Liothyronine (T3) is classified as not recommended for primary care initiation and considered red when consultant requested 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. Thyroid and Anti-thyroid drugs 1mg tablets: £0.95 (28) 5mg tablets: £1.13 (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 Page 145 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 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: £5.06 (84) Elleste Solo tablets are first line on cost grounds. Elleste Solo oestrogen 2mg tablets: £5.06* (84) Cyclical combined Continuous combined: Transdermal patches 25mcg patch: £3.42 (8) 50mcg patch: £3.88* (8) as Evorel 75mcg patch: £4.12* (8) 100mcg patch:£4.28* (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: £9.20 (84) 2mg tablets: £9.20* (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) 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. Kliovance has identical composition to Elleste Duet Conti, but at a lower cost Kliofem Tablets: £11.43* (84) Femoston Conti Tablets: £20.36* (84) 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 146 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) Progestogens Sex Hormones Norethisterone 5mg tablets: £2.24 (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. Page 147 Therapeutic Area Formulary Choices Cost for 28 Rationale for decision / comments (unless otherwise stated) 6.4.2 Male sex hormones and antagonists Testosterone First-line: Sustanon 250 ® 250mg/ml amp: £2.45 (1ml) Second-line: Testosterone Enantate 250mg/ml amp: £58.86 (1ml) Third-line: Nebido® 250mg/ml amp: £80.00 (4ml) Fourth-line: Testogel® 50mg/5g gel sachet: £31.11 (30) Testim® 50mg/5g gel: £32.00 (30g) Tostran® 2% gel (10mg per application): £26.67 (60g) Striant SR® 30mg Mucoadhesive buccal tablets: £28.00 (60) Restandol® 40mg capsules: £8.55 (30) (Temporary formulary inclusion) 5-Alpha Reductase Inhibitors (5-ARIs) Hypothalamic and pituitary hormones and anti-oestrogens 6.5.2 Posterior pituitary hormones and antagonists Sex Hormones 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. 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: £1.54 (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 Posterior pituitary hormones Intrinsa® for females remains NON-FORMULARY 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. If neither is first- or second-line choices are 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 Desmopressin 200mcg tablets: £9.84 (30) Desmopressin tablets are included in the formulary only for the treatment of nocturnal enuresis in line with NICE CG111: Nocturnal enuresis. Page 148 NHS England Interim Gender Dysphoria Protocol and Service Protocol Flowchart Hormone Therapy as part of Gender Reassignment: NHS England expects GPs to co-operate with their commissioned Gender Identity Clinics (GICs) and to prescribe hormone therapy recommended for their patients by the GIC. They are also expected to co-operate with GICs in patient safety monitoring, by providing basic physical examinations (within the competence of GPs) and blood tests recommended by the GIC. The GIC is expected to assist GPs by providing relevant information and support, including the interpretation of blood test results. Hormone therapy should be monitored at least 6 monthly in the first 3 years and yearly thereafter, dependant on clinical need. From: NHS England. Interim Gender Dysphoria Protocol and Service Guideline 2013/14 (Oct-13) Sex Hormones Page 149 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) DEXA scanning: Fractures over the age of 75 should be treated without DEXA Guidance on primary prevention of osteoporosis in postmenopausal women is provided in NICE TAG 160 See summary table p154 Guidance on secondary prevention of osteoporosis in postmenopausal women is provided by NICE TAG 161. See summary table p157 The March 2012 Somerset Prescribing Forum debated and then approved the off license use of Bisphosphonates (alendronate (1st) , risedronate(2nd) or ibandronate(3rd): 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 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 150 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Primary prevention of osteoporosis in postmenopausal women First-line: See Summary of NICE TA160 on page 154 Somerset Prescribing Forum (Jan-12) approved Denosumab as third-line treatment for primary prevention of osteoporotic fractures in women Raloxifene is not recommended as a treatment option for primary prevention of osteoporotic fractures. Alendronic Acid 70mg tablets: £0.90 (4) 70mg/100ml solution: £22.80 (4x100ml) Risedronate 35mg 35mg tablets: £1.16 (4) Second-line: Ibandronate 150mg 150mg tablet: £3.02 (1) Third-line: Denosumab* 60mg/ml prefilled syringe: £183.00 (1) 120mg Injection (Xgeva®) is NOT for treatment of osteoporosis Bisphosphonates - 1st alendronate, 2nd risedronate & 3rd ibandronate (where compliance would otherwise prevent patients taking bisphosphonate) are 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 p142 summarises the conditions. Independent risk factors considered: 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. Osteopenia: Only the lowest cost bisphosphonates are approved for patients with osteopenia. This is an off-licence use & patients’ informed consent is required. *Also for men at increased risk of fracture Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. Drugs affecting Bone Metabolism Page 151 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Fourth line Strontium Ranelate All with calcium and vitamin D supplement Sachets 2G: £27.08 (28) Strontium should be considered only for patients with severe osteoporosis in post-menopausal women and men with a high risk of fracture, and only prescribed to patients who do not have a history of heart problems and if the patient is unable to take any of the above medicines http://www.mhra.gov.uk/home/groups/commspo/documents/news/con382707.pdf Calcium carbonate 1500 mg and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: See p.129 for full choice ThieCal D3 chewable tablets 1000mg/880IU £2.95 (30 tablets) Once daily dose with or without food Accrete D3 tablets 600mg/800IU £2.95 (60) Twice daily tablet Drugs affecting Bone Metabolism Page 152 Drugs affecting Bone Metabolism Page 153 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 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 DO NOT TREAT TWO risk factors and T score - 3.5 or worse try Denosumab, Zoledronate 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 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 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 Page 154 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Secondary prevention of osteoporosis in postmenopausal women First-line: See Summary of NICE TA161 on p.157) Somerset Prescribing Forum approved Zoledronic acid annual infusion (Sep-10) & Denosumab (Jan-12) as third-line treatments for secondary prevention of osteoporosis Raloxifene is not recommended as a treatment option for primary prevention of osteoporotic fractures. Alendronic Acid 70mg tablets: £0.90 (4) 70mg/100ml solution: £22.80 (4x100ml) Risedronate 35mg 35mg tablets: £1.16 (4) Second-line: Ibandronate 150mg 150mg tablet: £3.02 (1) Third-line: Denosumab* 60mg/ml prefilled syringe: £183.00 (1) 120mg Injection (Xgeva®) is NOT for treatment of osteoporosis Bisphosphonates (1st alendronate or risedronate, 2nd 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. Where an oral bisphosphonate is not appropriate, denosumab and annual infusion of zoledronic acid are approved by Somerset Prescribing Forum as 3rd line treatments or raloxifene (subject to BMD, age & other risk factors). 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 p 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 NB Local agreement for women aged over 75 years: DEXA not required. *Also for men at increased risk of fracture Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. Drugs affecting Bone Metabolism Page 155 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Raloxifene 60mg 60mg tablets: £14.15 or All with calcium and vitamin D supplement Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: See p.129 for full choice Accrete D3 Drugs affecting Bone Metabolism £2.95 (60) Jan 2013 – cost-effective product Page 156 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. contra- indicated, 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 other bisphosphonate 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. Bisphosphonate and Denosumab or Zoledronic acid not option: Treat with raloxifene 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 Low BMI (< 22kg/m2), 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 157 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Steroid induced osteoporosis (6 months at >7.5mg Prednisolone equivalent) Plus calcium and vitamin D supplement: Alendronic Acid 70mg tablets: £0.90 (4) 70mg/100ml solution: £22.80 (4x100ml) Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: See p.178 for full choice Accrete D3 £2.95 (60) cost-effective product: 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: 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)’ Algorithm 1: Women who experience premature menopause – The development of treatment-induced menopause or planned ovarian suppression before the age of 45 years are indications for evaluation of BMD by DEXA. c and any type of concomitant endocrine treatment. Any patient with a documented vertebral fragility fracture or previous low trauma hip fracture should receive prophylactic bisphosphonate treatment irrespective of baseline BMD (p.19 in consensus guidance) Algorithm 2: Postmenopausal women – The use of an aromatase inhibitor is an indication for evaluation of BMD by DEXA. Monitoring and treatment thereafter depends on baseline BMD, age & presence of any major risk factors for osteoporotic fracture. For women over the age of 75 years with one or more major risk factors, bone protection therapy with a bisphosphonate treatment is recommended irrespective of baseline BMD (p.21 in consensus guidance) Drugs affecting Bone Metabolism Page 158 Patient group Formulary Choices Cost Rationale for decision / comments (per pack size stated) Osteoporosis in Men First-line: Second-line: NB All young men with osteoporosis should be referred for specialist advice. Alendronic Acid 70mg tablets: £0.90 (4) 70mg/100ml solution: £22.80 (4x100ml) Risedronate 35mg 35mg tablets: £1.16 (4) Denosumab 60mg/ml prefilled syringe: £183.00 (1) Somerset Prescribing Forum (Nov-11) approved 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. Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. Plus calcium and vitamin D supplement: Calcium and vitamin D supplement Accrete D3 Primary Prevention of osteoporosis: Frail elderly women See p.178 for full choice £2.95 (60) As above Calcium and Vitamin See p.178 for full choice D supplement Accrete D3 Drugs affecting Bone Metabolism Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: Indicated for those at increased fracture risk e.g. patients in Nursing or residential homes. Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets £2.95 (60) Page 159 Therapeutic Area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 7: Obstetrics, gynaecology, and urinary-tract disorders 7.2 Top 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 reassess 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 were discontinued February 2013 Vaginal and vulval infections Fungal infections: First line: Fluconazole (oral) 150mg capsule: £1.08 (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 combi-pack: £5.21 (1) 1% Cream: £1.34 (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 160 Therapeutic Area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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 161 Therapeutic Area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 7.3.1 Combined hormonal contraceptives Low strength Ethinylestradiol / norethisterone as Loestrin 20 Standard strength: Ethinylestradiol / norgestrel as Rigevidon® as Ovranette 20mcg/1mg tablets: £2.70 (63) 30mcg/150mcg tablets: £1.89 (63) 30mcg/150mcg tablets: £2.20 (63) Rigevidon® is a cost-effective alternative to Ovranette®. Ethinylestradiol / norgestimate as Cilest Ethinylestradiol / gestodene as Millinette® 30/7 as Femodene 5 35mcg/250mcg tablets: £7.16 (63) NB: Third-generation COCs containing the progestogens gestodene or desogestrel (e.g. Femodene®) are associated with a higher risk of VTE. 30mcg/75mcg tablets: £4.85 (63) 30mcg/75mcg tablets : £6.73 (63) Millinette® 30/75 is a cost-effective alternative to Femodene® Ethinylestradiol / norethisterone (tri-phasic) as Tri-Novum Gynaecology and Urinary-tract Disorders 35mcg/500mcg, 35mcg/750mcg, & 35mcg/1mg: £3.46 (63) Page 162 Therapeutic Area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 7.3.2 Progestogenonly contraceptives (POPs) Norethisterone 350mcg 7.3.2.3 Intra uterine POP system Mirena® as Micronor Jaydess® Long-acting reversible contraception (LARC) T-shaped plastic frame levonorgestrel 20 micrograms/24 hours, net price = £88.00 13.5mg: £69.22 Five year use license Smaller frame and smaller reservoir. Approved for use in the CASH service where a coil is appropriate but Mirena is not suitable or not tolerated. Three year life license. Contraception only LARC methods are more cost-effective than COC pill even at one year. Please see NICE guidance on Features of the larc methods to discuss with women (Sept 14) and Choice of method for different groups of women (Sept 14) Medroxyprogesterone as Depo-Provera® Etonogestrel as Nexplanon® 7.3.5 Emergency Hormonal Contraception (EHC) Tablets: £2.11 (84) Progestogens gestodene or desogestrel (e.g. Cerelle® ) are associated with a higher risk of VTE. Cerelle® 75mcg is a cost-effective alternative to Cerazette® Levonorgestrel 1500mcg tablet as Upostelle® 150mg/ml prefilled syringe: £6.01 (1) 68mg implant: £79.46 1500mcg tablet: £5.20 (1) 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. Available via PGD through many pharmacies across Somerset, free of charge to all. Levonorgestrol 1500mcg is the first-line oral preparation for patients presenting within 72 hours of UPSI or contraceptive failure. DO NOT PRESCRIBE AS THE OTC PREPARATION: Levonelle One Step (as over twice the cost of the POM product.) Gynaecology and Urinary-tract Disorders Page 163 Therapeutic Area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Ulipristal acetate 30mg tablet ▼ as EllaOne Pre-operative treatment of uterine fibroids Ulipristal acetate 5mg tablet as Esmya Gynaecology and Urinary-tract Disorders 30mg tablet: £16.95 (1) 5mg tablet: £ 113.14 (28) 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 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 Page 164 Consilient Pill Equivalences and VTE risk There is an increased risk of venous thromboembolic disease in users of combined hormonal contraceptives particularly during the first year and possibly after restarting combined hormonal contraceptives following a break of four weeks or more. This risk is considerably smaller than that associated with pregnancy (about 60 cases of venous thromboembolic disease per 100 000 pregnancies). In all cases the risk of venous thromboembolism increases with age and in the presence of other risk factors, such as obesity. The risk also varies depending on the type of progestogen, see the chart below for details.Provided that women are informed of the relative risks of venous thromboembolism and accept them, the choice of oral contraceptive is for the woman together with the prescriber jointly to make in light of her individual medical history and any contra-indication Gynaecology and Urinary-tract Disorders Page 165 Gynaecology and Urinary-tract Disorders Page 166 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: Doxazosin as Modifiedrelease (MR) for initiation only as Doxadura® 4mg m/r tabs: £5.00 (28) 4mg m/r tabs £4.50 Instant-release tablets for continuation as Doxadura® 4mg tablets: £1.09 (28) 4mg tablets: £1.03 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. Page 167 Second-line: Tamsulosin MR capsules as Tabphyn MR® 400mcg m/r capsules: £5.71 (30) 400mcg m/r capsules: £4.39 (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. Tamsulosin MR tablets (Flomaxtra XL) are not included in the formulary Gynaecology and Urinary-tract Disorders Page 168 7.4.2 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 NICE Clinical Guideline CG171 (2013): The management of urinary incontinence in women Before initiating treatment a thorough investigation of the underlying cause of incontinence should be carried out and drug treatments 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. First-line: Second-line: Oxybutynin (immediate release) 2.5mg tablets: £1.97 (56) 5mg tablets: £3.17 (56) Tolterodine (immediate release) 1mg tablets: £2.94 (56) 2mg tablets: £3.07 (56) Darifenacin (once daily) 7.5mg tablets: £25.48 (28) 15mg tablets: £25.48 (28) Oxybutynin MR 5mg m/r tablets: £13.77 (30) 10mg m/r tablets: £27.54 (30) Tolterodine MR as Neditol XL® 4mg m/r capsules: £12.89 (28) Trospium (immediate release) as Flotros® As per NICE guidance immediate release Oxybutynin 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) NICE advises thatsome adverse effects are indications that treatment is having effect and that they may not see full benefits for 4 weeks. If first treatment for OAB or mixed UI is not effective or not tolerated, offer another drug with the lowest acquisition cost. Aim to avoid additional antimuscarinic drugs particularly in elderly and patients with dementia due to risk of delirium. See muscarinic load below. 20mg tablets:£18.20 (60) TrospiumMR as Regurin XL® 60mg tablets: £23.05 (28) Propiverine (immediate release) Propiverine MR 15mg tablets: £18.00 (56) 30mg capsules: £24.45 (28) Continued overleaf Gynaecology and Urinary-tract Disorders Page 169 Continued from previous page Third-line Non oral therapy Solifenacin 5mg tablets: £27.62 (30) 10mg tablets: £35.91 ( 30) Fesoterodine 4mg m/r tablets: £25.78 (28) 8mg m/r tablets: £25.78 (28) Mirabegron 25mg tablets: £29.00 (28) 50mg tablets: £29.00 (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. Evidence indicated that higher dose of solifenacin is more likely to cause side effects than tolterodine MR or Trospium MR For the use of desmopressin in the treatment of nocturnal enuresis, please refer to section 6.5.2 Posterior pituitary hormones and antagonists Gynaecology and Urinary-tract Disorders Page 170 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 Were receiving Caverject®, Erecnos®, MUSE®, Viagra® or Viridal® for ED at NHS expense on 14-09-1998 Severe pelvic injury Prescriptions need to be annotated “SLS” with the exception of sildenafil from August 1st 2014 First-line Sildenafil 25mg tablets: £1.24 (4) 50mg tablets: £1.41 (4) 100mg tablets: £1.45 (4) All PDE5 inhibitors are contra-indicated in patients taking nitrates. Prophylactic use after prostate surgery to improve recovery. Not licenced for this indication, therefore treat as RED if recommended by a relevant specialist for this indication. Second-line: Vardenafil 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. Avanafil Gynaecology and Urinary-tract Disorders 50mg tablets: £10.94 (4) £19.70 (8) 100mg tablets: £14.08 (4) £26.26 (8) 200mg tablets: £21.90 (4) £39.40 (8) Page 171 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 Non oral therapy 7.4.6 Alprostadil as Vitaros®cream 4 doses: £40 An alternative to oral medication 30mg tablets: £14.71 (3) 30mg tablets: £26.48 (6) 60mg tablets: £19.12 (3) 60mg tablets: £34.42 (6) Dapoxetine is a short-acting selective serotonin re-uptake inhibitor licensed for use in the treatment of premature ejaculation in men (18 to 64 yrs) who meet all the following criteria: poor control over ejaculation, a history of premature ejaculation over the past 6 months, marked distress or interpersonal difficulty as a consequence of premature ejaculation, and an intravaginal ejaculatory latency time of less than two minutes. Maximum 6 tablets per month. Drugs for premature ejaculation Dapoxetine Anticholinergic load Gynaecology and Urinary-tract Disorders Page 172 Gynaecology and Urinary-tract Disorders Page 173 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 8: Malignant disease and immunosupression 8.3 Top Sex hormones and hormone antagonists in malignant disease Hormone antagonists Anastrazole 1mg tablets: £1.93 (28) Anastrazole is recommended as an adjuvant to early oestrogen-receptorpositive breast cancer and is supported by a Shared Care Protocol. Letrozole 2.5mg tablets: £1.76 (14), £84.68 (28) Anastrazole is recommended as an adjuvant to early oestrogen-receptorpositive breast cancer and is supported by a Shared Care Protocol. Use of an aromatase inhibitor is an indeication for evaluation of BMD by DEXA Pre- or Postmenopausal women at high risk of breast cancer Tamoxifen 10mg tablets: £21.19 (30) 20mg tablets: £2.39 (30) 40mg tablets: £16.16 (30) 10mg/5ml oral solution: £29.61 (150ml) NICE CG164 Jun-13: for 5 years to premenopausal women at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer for 5 years to postmenopausal women with or without a uterus and at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer Local agreement: Tamoxifen is approved for longterm use (>5 years) Raloxifene 60mg tablets: £14.15 (28), £59.59 (84) Raloxifene (unlicensed use) for 5 years to postmenopausal women with a uterus and at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer (NICE CG164 Jun-13) Prostate cancer & Monthly injections of triptorelin and goserelin were approved at the March 2010 meeting of the Somerset prescribing Forum for use Gonadorelin analogues within licensed indications re: Breast Cancer – endometriosis and uterine fibroids. First-line: Triptorelin as Decapeptyl SR 3mg (4.2mg) vial: £69.00 (1) 11.25mg (15mg) vial: £207.00 (1) 22.5mg (28mg) vial: £414.00 (1) Second-line: Leuprorelin as Prostap Malignant Disease and Immunosuppression 3.75mg PFS: £75.24 11.25mgPFS:£225.72 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 3-monthly reviews should be considered for a switch from the 3-monthly (15mg) to the 6monthly (28mg) preparation. Administered every 13 weeks rather that 12 making it more cost effective than goserelin Page 174 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Third line: Goserelin Malignant Disease and Immunosuppression 3.6mg PFS: £65.00 (1) 10.8mg PFS: £235.00 (1) Goserelin is considered as third line GnRH analogue for use within its licensed indications, where Decapeptyl and Triptorelin are not appropriate. Goserelin is used in young women with breast cancer. It is used either to protect their ovaries during chemotherapy or to suppress their ovaries following treatment to reduce the chance of recurrence. The 10.8 mg 3 monthly implant is not licensed in breast cancer so the 3.6 mg injection is given on a monthly basis - usually for 18m to 2 years Page 175 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 9: Nutrition and blood 9.1 Top Anaemias and some other blood disorders Iron deficiency Ferrous fumarate 210mg tablets: £2.30 (100) 322mg tablets: £0.95 (28) Syrup as Fersamal as Galfer Megaloblastic anaemia 9.2 140mg/5ml: £3.73 (200ml) 140mg/5ml £5.33 (300ml) Folic acid 400mcg tablets: £2.71 (90) 5mg tablets: £0.99 (28) Hydroxocobalamin 1mg/ml injection: £2.83 (5) 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. 400mcg daily is indicated for prevention of neural tube defects Fluids and electrolytes Potassium Salts Potassium chloride 600mg m/r tablets: £1.90 (100) Oral rehydration therapy Electrolade Sachets: £1.97 (6) Sachets: £4.99 (20) Nutrition and Blood Electrolade offers a lower cost alternative to Dioralyte Page 176 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 9.5 Minerals Calcium supplements 9.6 Calcium carbonate Chewable tablets: £8.25 (100) Evidence for efficacy of Calcium supplements is in combination with Vitamin D, there should be few situations where Calcium alone is indicated. 800IU capsules: £3.60 (30) There is no national guidance on use of plain Vit D. Vitamin 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. Capsules contain arachis oil and must not be taken by people with peanut allergy, and gelatine as Desunin 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 as Fultium D3 3200IU capsules £13.32 (30) £39.96 (90) 20000IU capsules £17.04(15) Fultium D3 3200IU is included in formulary for Vitamin D deficiency in adults and the elderly (serum levels <25 nmol/l (<10 ng/ml)) for up to 12 weeks. For higher doses see below. Treatment, 40,000iu weekly for 7 weeks, preferably with food, then reduce to maintenance dose equiv to 1400—2000iu/day (2—3 caps per month). Prevention, 20,000iu every 4 weeks. Agreed as an option when recommended and initiated by a consultant as Adcal Vitamins Vitamin D Colecalciferol 800IU as Fultium D3 £29.00 (30) as InVita D3 25,000IU Oral solution 3x1ml ampoule: £4.45 High dose unlicensed Vitamin D (e.g. 20,000IU Dekristol® Capsules) remain non-formulary. 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 (i.e. considered RED under the TLG)and primary care should not be asked to prescribe. When concordance is an issue there should be no restriction of choice Nutrition and Blood Page 177 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Vitamin D supplements with Calcium Calcium and vitamin D should be considered as an intervention to reduce fracture risk for all women over 75 years. Calcium and Vitamin D: Calcium & Ergocalciferol tablets BP are non-formulary as they provide an inadequate dosage for most patients. A range of Calcium and Vitamin D products are included to provide a range of flavours & formulation to encourage concordance. First-line: Accrete D3 Tablets: £2.95 (60) Accrete D3is currently the most cost-effective choice however a range of products is included for patient choice. Second-line: Adcal D3 Chewable tablets:£3.65 (56), £7.30 (112) Caplet: £3.65 (112) Dose Adcal D3® caplets is 2bd or Adcal D3 Dissolve or Soluble tablets: £4.99 (56) Calcichew D3 Forte Chewable tablets: £4.24 (60) or Chewable tablets: £3.58 (60) Calceos Calcichew D3® Caplets: £7.43 (100) Vitamin K1 Phytomenadione 10mg/ml ampoule: £3.78 (10) For use in the management of haemorrhage due to Warfarin, cross refer to 2mg/0.2ml ampoule: £4.71 (5) anticoagulant section of formulary. MultiVitamin Preparations Dialyvit Renavit Nutrition and Blood More costly than other products in the class & provides lower dose of colecalciferol. Approved at May-12 Prescribing Forum only for patients receiving renal dialysis. Unlicensed in UK – order supplies from USA Tablets: £12.50 (100) Preparation of Vitamins B1, B2, B6, B12, C, Biotin, Folic acid, Nicotinamide, and Pathothenic acid. Approved at Nov-13 Prescribing Forum only for patients receiving renal dialysis. Page 178 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 10: Musculoskeletal and joint diseases 10.1 Top Drugs used in rheumatic diseases and gout Related guidance: CG177 Osteoarthritis: Care and management in adults Feb 2014 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: £3.40 (84) 400mg tablets: £3.19 (84) 600mg tablets: £6.91 (84) Ibuprofen is 1st choice on grounds of safety and cost Second-line: Naproxen 250mg tablets: £1.22 (28) 500mg tablets: £1.70 (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 is now non-formulary after the EMEA / MHRA added new contraindications and warnings after a Europe-wide review of cardiovascular safety (Jun-13). 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: £1.04 (30) 15mg tablets: £1.33 (30) NB: Etoricoxib & celecoxib are non-formulary (Celecoxib exception below) Celecoxib (named-patient basis only – see comment right) Musculoskeletal system 100mg capsules: £21.55 (60) 200mg capsules: £21.55 (30) Named-patient basis only when recommended by Consultant Rheumatologist when ibuprofen, naproxen and meloxicam are ineffective. Consider risk-benefit compared to diclofenac. Page 179 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Rubefacients and topical NSAIDs Algesal Cream: £1.21 (50g) Transvasin Cream: £1.55 (40g) Ibuprofen as Fenbid Piroxicam 5% gel: £1.50 (100g) 10% gel £4.00 (100g) 0.5% gel: £5.77 (112g) 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 non-formulary 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 180 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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: Naproxen 250mg tablets: £1.22 (28) 500mg tablets: £1.70 (28) Oral NSAIDs at maximum doses are the drugs of choice where there are no contra-indications. NICE recommends gastroprotection with PPIs for patients who require systemic COX-2s. See above Second-line: Colchicine 500mcg tablets: £36.23 (100) 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. First-line Allopurinol 100mg tablets: £0.97 (28) 300mg tablets: £1.08 (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 181 1,2 Consider risk factors and clinical presentations GOUT TREATMENT ALGORITHM Likely diagnosis of gout (exclude septic arthritis) Typical 1st MTP joint involvement ACUTE TREATMENT Suppress pain and reduce inflammation until acute flare has subsided. Use one of the following Full-dose NSAID Colchicine* (500 microgram 3-4 times daily reducing course) Avoid if eGFR<30 ml/min Corticosteroid (intra-articular, intramuscular) oral (0.5mg/Kg for 5-10 days) Advise patient to use an ice-pack 6-week appointment: sUA ≥ 360 micro mol per litre Reduce risk factors: Switch thiazide/indapamide/loop diuretic to ACE or Losartan (uricosuric) if possible Reduce alcohol intake (beer especially) Reduce intake fructose/corn syrup in food and drinks Check fasting lipids LONG-TERM TREATMENT Initiate sUA-lowering therapy if patient has had ≥2 flares per year, based on patient preference and clinical judgement. Allopurinol 100mg - 200mg od AND Add prophylactic low-dose colchicine (500 microgram twice daily) for up to the first six months of treatment (3 months may be sufficient). Alternatives NSAID (but not aspirin) if no contraindications or Prednisolone 10 mg od Patient education - increased fluid intake 6-week appointment: sUA ≥ 0.36 mmol per litre 6-week appointment: sUA < 360 micro mol per litre RECONSIDER DIAGNOSIS Persistent symptoms without definitive diagnosis should be discussed with secondary care 6-week appointment: sUA < 0.36 mmol per litre Increase allopurinol depending upon sUA Continue with sUA-lowering therapy Moderately severe 300mg – 600mg Retest sUA every six months to one year Severe 700mg – 900mg Stop colchicine 1 month after hyperuricaemia corrected prophylactic colchicine (500 microgram Maintain If allopurinol intolerant (side effects sufficient to warrant discontinuation) or allergic to allopurinol initiate twice daily) . Febuxostat 80 mg od. If sUA >0.36mmol/l after 2-4 weeks increase to 120MG od Gout flares while taking sUA lowering therapy Suppress pain and reduce inflammation. Do not interrupt sUA lowering therapy unless there is a clinical reason In stable gout uric acid levels should be checked annually *Colchicine is the preferred treatment for patients who have concomitant conditions and who are taking medications that contraindicate the use of NSAIDs + Allopurinol dosage reduction in renal failure:/elderly: start low (1.5 mg per unit of eGFR) or 50 mg od 1. Zhang W, Doherty M, Pascual E et al. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65: 1301–11. Part II: Management. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT), Ann Rheum Dis 2006; 65: 1312–24. 2. Jordan KM, Cameron JS, Snaith M et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology 2007; 46: 1372-4. This treatment algorithm has been produced as an educational service by A. Menarini Pharma UK SRL. Musculoskeletal system Management of Osteoarthritis Therapy options in CG177 Feb 2014 are unchanged from 2008 guidance Therapy options for OA are summarised in the following: 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 Oral analgesics strengthening exercise aerobic fitness training local heat and cold assistive devices weight loss if overweight/obese 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. 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 TENS manual therapy (manipulation and stretching) Musculoskeletal system joint arthroplasty 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 183 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 184 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 11: Eye 11.3 Anti-infective eye preparations Antibacterials Chloramphenicol 0.5% drops: £1.59 (10ml) 1% ointment: £1.60 (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 11.4 Aciclovir 3% ointment: £9.34 (4.5g) Corticosteroids and other anti-inflammatory preparations Corticosteroids As advised by secondary care Other anti-inflammatory products Sodium cromoglicate 11.5 As advised by secondary care Treatment of glaucoma Glaucoma As advised by secondary care First line: 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. Patients currently using other forms of prostaglandin analogues may be reviewed when seen routinely by secondary care. Latanoprost Preservative-free single use as Monoprost® Eyes Prescribe 13.5ml size. 5ml and 10ml pack sizes are OTC products (and non-formulary), and are more expensive when being used regularly. Mydriatics and cycloplegics Mydriatics and cyloplegics 11.6 2% drops: £1.61 (13.5ml) 50mcg/ml: £1.99 (2.5ml) 50mcg/ml: £8.49 (30x0.2ml) For the reduction of elevated intra-ocular pressure in patients with open-angle glaucoma and ocular hypertension who have proven sensitivity to benzalkonium chloride Page 185 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 11.8 Miscellaneous ophthalmic preparations Dry eyes: Hypromellose Preservative-free single use as Lumecare® Eyes 0.3% drops £1.21 (10ml) 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. 0.3% drops: £5.72 (30x0.5ml) Treatment for dry eyes associated with tear deficiency in patients who have proven sensitivity to benzalkonium chloride Page 186 Lubricant Carbomer 0.2% eye gel Brand Clinitas Presentation 10g tube Cost Preservative free Xailin Gel 10g tube £3.25 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 £1.49 Expiry once open 28 days Carmellose: 1% drops are less expensive than 0.5% If patients are able to re-use vials for more than one drop Xailin® Fresh is best option. If not Optive becomes a cost-effective option. Xailin® Fresh (0.5%) 30 x 0.4ml single dose units £3.84 Carmize 0.5% 30 x 0.4ml single dose unit £5.75 reuse up to 12 hrs 90 x 0.4ml single dose unit £15.53 reuse up to 12 hrs Optive 0.5% (special container maintains contents) 10ml £7.49 up to 6 months Hypromellose 0.5% eye drops (Pres) Isopto Plain 10ml £0.81 28 days Hypromellose (Pres Free) Lumecare Hypromellose 0.3% Eye Drops 30 x 0.5ml single dose unit £5.72 reuse up to 12 hrs Polyvinyl Alcohol 1.4% (Pres) Polyvinyl Alcohol 1.4% (Pres-Free) Sno-Tears Liquifilm Tears 10ml 30 x 0.4ml £1.06 £5.35 28 days single use Sodium Hyaluronate (Pres) Blink Intensive Tears Clinitas (where units are resealed after use later that day) 10ml £4.98 45 days 30 x 0.5ml single dose unit £5.70 reuse up to 12 hrs Sodium Hyaluronate (Pres-Free) 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. Vismed Multi (special container maintains contents) 10ml £6.81 3m Soft white paraffin 57.3% w/w, White mineral oil 42.5% w/w, Lanolin alcohols 0.2% w/w Xailin Night 5g £2.49 28 days White Soft Paraffin with Liquid Paraffin VitaPos 5g £2.75 6m 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 187 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) BNF Chapter 12: Ear, nose, and oropharynx 12.1 Top 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 See Infection management guidance for appropriate clinical indications. 0.5% drops: £1.81 (10ml) Available OTC as Waxsol Ear, Nose and Throat Page 188 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 12.2 Drugs acting on the nose Nasal Allergy Nasal steroids First-line: Second-line: Symptoms of nasal allergy are usually controlled with nasal corticosteroids and / or oral antihistamines. Beclometasone as Beconase® Budesonide as Rhinacort Aqua® 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. 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: £5.45 (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 BD 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 CCG Management of Infection Guidance and MRSA Policy for further details (page189). 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 189 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 12.3 Drugs acting on the oro-pharynx Oral ulceration and inflammation Oropharyngeal antiinfectives Benzydamine 0.15% mouthwash: £6.46 (300ml) May be diluted with water if stinging occurs. Available OTC Hydrocortisone 2.5mg pellets: £4.24 (20) Available OTC 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: £3.43 (300ml) Available OTC. Dry mouth BioXtra Gel Mouthspray: £3.94 (50ml) Saliva replacement. Neutral pH. Gluten and sugar-free. Contains fluoride (4.2mg/l). Contains porcine-derived gastric mucin. Approved for NHS prescribing where they fulfil the borderline substances criteria, for dry mouth caused by: Miconazole gel is available OTC. Use with caution if patient taking warfarin. radiotherapy sicca syndrome Prescriptions should accordingly be endorsed as ACBS. Available OTC Salivix Toothpastes Ear, Nose and Throat Pastilles: £3.50 (50) Saliva stimulation. Available OTC. No longer subject to ACBS criteria. Toothpastes should be considered as self care and are therefore nonformulary Page 190 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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 13.2 Top 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 Doublebase Gels Doublebase Dayleve Creams - soap substitute Gel: £2.65 (100g) £5.83 (500g pump) £2.65 (100g) £5.83 (500g pump) Contains povidone which inhibits water evaporation, so should need to be used less frequently Epimax Cream: £0.75 (100g) £2.49 (500g tub) Non-foaming soap substitute. SLS & lanolin free. Aquamax Wash Cream wash: £2.99 (250g) Non-foaming soap substitute. SLS & lanolin free. Aqueous cream is non-formulary: may cause skin irritation, particularly in children with eczema, possibly due to sodium lauryl sulfate content. (MHRA DSU Mar-13) Creams First line Second line Epimax Aquamax Ultrabase Dermatology Cream: £0.75 (100g) £2.49 (500g tub) Cream: £1.89 (100g) £3.99 (500g) Cream: £1.40 (50g) £4.80 (500g pump) SLS, Parabens & lanolin free. Most cost-effective preparation currently available but not available in pump packs. Page 191 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Cetraben Cream: £1.40 (50g) £3.98 (150g) £5.99 (500g) pump 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) £2.91 (125g) £4.85 (350g) £5.62 (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: £2.85 (50g) £9.97 (500g pump) Contains 5% urea Balneum Plus Cream: £3.29 (100g), £14.99 (500g pump) 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: £2.31 (500g) White soft paraffin Ointment: £3.11 (500g) Liquid paraffin / White soft paraffin 50/50 or Ointment: £2.39 (500g) Diprobase Ointment: £1.28 (50g) £5.99 (500g) Hydromol Ointment: £4.82 (500g) Continued on next page Emollients (Continued from previous page) Ointments First-line: Second-line: Dermatology Hydromol ointment has same ingredients as Epaderm and is cheaper. Epaderm is non formulary. Page 192 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Emollients with antimicrobials Use preparations with antimicrobials only if infection present or strongly suspected Eczmol® Dermol Cream Dermol 500 13.2.1.1 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. 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: Dermatology Doublebase Bath Emollient: £5.45 (500ml) Shower Gel: £5.21 (200g) 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: £2.75 (250ml) £4.57 (500ml) Page 193 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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 (1000ml) or Oilatum Plus Dermatology Bath additive: £6.98 (500ml) Page 194 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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: £1.12 (15g), £2.24 (30g) Ointment: £2.54 (30g) Caution: Hydrocortisone butyrate is a potent steroid (Locoid) Clobetasone butyrate 0.05% as Eumovate Cream/ointment: £1.86 (30g), £5.44 (100g) Betamethasone valerate 0.025% as Betnovate RD Cream/ointment: £3.15 (100g) Fludroxycortide 0.0125% as Haelan Dermatology Cream/ointment: £3.26 (60g) Page 195 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Potent First-line: Potent topical steroids should not be prescribed on repeat prescriptions. Betamethasone valerate 0.1% as Betnovate Second-line: Cream/ointment: £1.43 (30g), £4.05 (100g) Hydrocortisone butyrate 0.1% as Locoid Cream/ointment: £1.60 (30g), £4.93 (100g) Mometasone furoate 0.1% 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% as Synalar Very potent Very potent topical steroids should not be prescribed on repeat prescriptions. Clobetasol propionate 0.05% as Dermovate Dermatology Cream/ointment: £4.14 (30g), £11.75 (100g) Cream/ointment: £2.69 (30g) £7.90 (100g) Page 196 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 13.5 Preparations for eczema and psoriasis Vitamin D analogues Calcipotriol as Dovonex® with betamethasone as Dovobet® Ointment: £5.78 (30g) Ointment: £61.55 (120g) Gel: £33.08 (60g), £61.43 (120g) Dovonex® Cream was discontinued on Oct-11. 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 197 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 13.6 Acne and rosacea 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 Topical antibacterials Retinoids Clindamycin 1% with Zinc as Zindaclin Gel Tretinoin Gel 2.5% gel: £1.76 (40g) 5% gel: £1.92 (40g) Gel: £8.66 (30g) Benzoyl peroxide may be effective for both comedonal and inflammatory acne. Treatment should start with lower strength preparations, in an aqueous base. Topical antibiotics are best reserved for patients with inflammatory acne who do not wish to take systemic antibiotics or who cannot tolerate them. 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: £1.11 (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: 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: requires LFT monitoring when used >6 months. Higher cost and lack of evidence of superiority over Lymecycline in acne. Co-Cyprindiol 2000/35mcg tablets: £5.37 (63) The risk of VTE with Co-Cyprindiol is higher than with conventional low-dose COCPs and recommend that: 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 198 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 13.8 Photodamage Actinic keratosis Ingenol 0.0015% gel £65.00 (3x0.47g) Applied once daily to face or scalp for 3 days only 0.05% gel £65.00 (2x0.47g) 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 CCG Management of Infection guidelines for indications Antibacterials Antifungals Antivirals Dermatology Retapamulin 1% ointment: £7.89 (5g) Refer to CCG Management of Infection Guidance for indications. Mupirocin 2% cream: £4.38 (15g) Ointment £5.09 (15g) Reserve for MRSA. For nasal use see Chapter 12. Amorolfine 5% nail paint: £15.55(5ml) Refer to CCG 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: £1.34 (20g), £3.35 (50g) Refer to CCG Management of Infection Guidance for indications. Available OTC Miconazole 2% cream: £1.82 (30g) Refer to CCG Management of Infection Guidance for indications. Available OTC Terbinafine 1% cream: £1.89 (15g), £3.78 (30g) Refer to CCG Management of Infection Guidance for indications. Available OTC Aciclovir 5% cream: £0.99 (2g), £4.95 (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 199 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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: £16.50 (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 200 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) 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 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 CCG intranet together with a guide to developing a Nutrition Support Care Pathway (p.196) 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 Food supplements and Gluten-free foods Page 201 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) gastrectomy, bowel fistulas, or diseaserelated 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. Aymes Shake Available in: Strawberry Vanilla, Chocolate, Banana Neutral Fresubin Powder Extra® Available in: Strawberry Vanilla Chocolate Original flavour Ensure Shake® Available in: Strawberry Vanilla, Chocolate Banana Food supplements and Gluten-free foods £5.46 (7x57g) Can be made with milk or water £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. £5.46 (7x57g sachets) (Sachets of powder requiring preparation with fresh whole milk.) Page 202 Therapeutic area Formulary Choices Cost Rationale for decision / comments (per pack size stated) Resource ®Thicken Up Clear £8.46 (125g) Used to thicken food & liquid for patients with swallowing difficulties. Easier to use & more palatable than starch based thickeners. Main features are: Remains fully transparent in clear liquids No change in odour or taste; helps to maintain appetite Thickens rapidly and does not continue to thicken over time Dissolves readily without lumps. Less powder required than conventional thickeners as has greater water binding properties. Gluten-free foods 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 CCG intranet. (The Coeliac Society ) Food supplements and Gluten-free foods Page 203 Complete MUST Nutritional Screening Develop a nutritional care plan considering the aims of the patient’s treatment Must = 1 - Medium Risk Must = 0 - Low 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 Must = 2 or more - High Risk If no improvement request a prescription for Ist line Fresubin Powder Extra or Aymes Shake twice a day in between meals for 1 month. Refer to Dietitian 2nd Line: Fresubin 2KCAL or Fresubin Jucy Drink for patients who dislike or are intolerant to lactose. For patients who have end stage kidney disease or Dysphagia please seek advice from Somerset Community Dietitians. Tel: 01278 447407. No improvement in nutritional status after 1 month Request a prescription for: 1st Line: Fresubin Extra or Aymes Shake twice a day between meals 2nd Line: Fresubin 2KCAL or Fresubin Jucy Drink for patients who dislike or are intolerant to lactose. For patients who have end stage kidney disease or Dysphagia please seek advice from Somerset Community Dietitians. Tel: 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 Monitor patient’s compliance for 6 weeks. Monitor progress and 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 204 Suspected cow’s milk protein allergy (CMPA) – Breast fed infants (January 2015) Clinical assessment and family history of Cow’s milk allergy (CMPA) Suspected mild to moderate CMPA Suspicion of severe CMPA 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 Maternal milk free diet whilst breast feeding for 2-4 weeks. Maternal calcium supplement will be required (1000mg calcium/day). Baby may require Extensively Hydrolysed Formula (eHF) for use with weaning foods e.g. Similac Alimentum OR Milupa Aptamil Pepti 1 or 2 OR Nutramigen 1 or 2 OR Althera (see overleaf). Soya Infant formula not recommended for babies under 6 months of age. Improvement? YES Challenge by reintroducing milk back into maternal diet (or in weaning foods) and check symptoms If no symptoms develop return to normal diet Referral to paediatrician plus maternal milk free diet whilst breastfeeding continues. Calcium supplement for mother will be required (1000mg calcium/day). Amino acid formula on weaning e.g. Neocate LCP or Alfamino or Nutramigen AA. Refer to paediatric dietitian for specialist advice. NO Check maternal diet for sources of dairy. If weaning, consider a 2-4 week trial of amino acid formula (instead of eHF) such as Neocate LCP or Alfamino or Nutramigen AA for use with milk free weaning solids. If symptoms return, restart maternal milk free diet. Or Consider eHF* for use with weaning solids and milk free weaning diet Improvement? YES NO Return to normal diet and consider paediatrician referral Specialist individual allergy and challenge plan to be developed. After 12 months of age, may continue to breast feed on a maternal milk free diet or use over the counter Alpro soya Junior 1+ as main ‘milk’ drink if cow’s milk still not tolerated. Continue on milk free diet and at 1 year of age or after 6 months symptom free undertake milk rechallenge at home as per written plan Food supplements and Gluten-free foods Page 205 Suspicion of cow’s milk protein allergy (CMPA) – Formula fed infants (January 2015) Clinical assessment and family history of CMPA 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 Respiratory: runny nose, chronic cough, wheeze (all unrelated to infection) 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. General: persistent distress or colic more than 3 hours over more than 3 days over more than 3 weeks) Dermatological: urticaria, swelling (angioedema), exudative or severe atopic dermatitis Dermatological: atopic dermatitis, urticarial (unrelated to acute infections or drugs) Respiratory: acute laryngoedema or bronchial obstruction with difficulty breathing Trial of extensively hydrolysed formula (eHF) for 2-4 weeks e.g. Similac Alimentum or Milupa Aptamil Pepti 1 or 2 or Nutramigen Lipil 1 or 2 or Althera (See notes overleaf). Soya infant formula is not recommended as a first line treatment for babies under 6 months of age. Improvement? YES NO Open challenge back on cow’s milk formula Consider trial of different eHF e.g. Similac Alimentum, Milupa Aptamil Pepti 1 or 2, Nutramigen Lipil 1 or 2 or Althera If no improvement on alternative eHF, try 2-4 week trial of amino acid formula (AAF) such as Neocate LCP or Nutramigen AA or Alfamino Improvement? YES NO If no symptoms develop, return to normal diet. Systemic reactions: anaphylactic shock needs immediate hospital management Continue on eHF and avoid milk for at least 6 months or until over 1 year. Give milk free dietary advice and consider referral to community paediatric dietitian Improvement? YES Re-challenge with eHF after 2-4 week trial on AAF Improvement? YES 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 NO Amino acid formula (AAF) e.g. Neocate LCP or Nutramigen AA or Alfamino (and strict milk free diet if weaning) for 2-4 weeks Improvement? YES NO Unlikely to be CMPA. Return to normal infant formula and consider referral to paediatrician. Refer to hospital paediatric dietitian and hospital paediatrician for specialist advice. Specialist individual allergy and challenge plan to be developed by hospital team Continue on AAF and avoid milk for at least 6 months or until over 1 year. Give milk free diet pack 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 concurrent milk and soya allergy, extrensively hydrolysed formula or amino acid should be continued until the age of 2 years Paediatric specialist diagnostic procedures Page 206 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 Extensively hydrolysed formula (EHF) Nutramigen *Nutramigen 1 Nutramigen 2 *Similac or Puramino Alimentum Birth to 6 6 months – 12 months months Birth to 6 months 400g tins 400g tins 400g tins 400g tins Similac Alimentum 6 months – 12 months 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 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 Similac Alimentum Appendix 2: Out of hours formulary Page 207 Appendix 2. OUT OF HOURS Appendix 2: Out of hours formulary Page 208 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 209 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 210 Part 2: Dorset and Somerset Palliative Care Drug Stock List: Drug Form Quantity Cyclizine 50mg/ml Injection 10 x 1ml Dexamethasone 4mg/ml Injection 10 x 2ml Dexamethasone 2mg Tablets 100 Diamorphine 10mg Injection 5 Diamorphine 100mg Injection 5 Diazepam 5mg/ml Injection 10 x 2ml Diazepam 10mg Rectal Tubes 5 Diclofenac 100mg Suppositories 10 Domperidone 30mg Suppositories 10 Fentanyl 25mcg Patches 1x5 Fentanyl 50mcg Patches 1x5 Fentanyl 75mcg Patches 1x5 Fentanyl 100mcg Patches 1x5 Glycopyrronium bromide 200mcg/ml Injection 10 x 1ml Haloperidol 5mg/ml Injection 5 x 2ml Hyoscine butylbromide 20mg/ml Injection 10 x 1ml Hyoscine hydrobromide 400mcg/ml Injection 10 x 1ml Levomepromazine 25mg Tablets 84 Levomepromazine 25mg/ml Injection 10 x 1ml Metoclopramide 5mg/ml Injection 10 x 2ml Midazolam 5mg/ml Injection 10 x 2ml Morphine sulphate 10mg/ml Injection 40 x 1ml Morphine sulphate 30mg/ml Injection 40 x 1ml Morphine sulphate (Oramorph®) 10mg/5ml Oral Solution 5 x 100ml Morphine sulphate (Oramorph®) 100mg/5ml Concentrated Oral Solution 1 x 30ml Oxycodone 10mg/ml Injection 20 x 1ml Prochlorperazine 25mg Suppositories 10 Sodium chloride 0.9% Injection 10 x 10ml Water for Injection Injection 20 x 10ml Clexane® 2000 units Pre-Filled Syringes 1 x 10 pfs Clexane® Pre-Filled Syringes 1 x 10 pfs Clexane 6000 units Pre-Filled Syringes 1 x 10 pfs Clexane® 8000 units Pre-Filled Syringes 1 x 10 pfs Clexane ®10000 units Pre-Filled Syringes 1 x 10 pfs Tamiflu® 30mg Capsules 1 x 10 Tamiflu® 45mg Capsules 1 x 10 Tamiflu® 75mg Capsules 1 x 10 Tamiflu® 30mg/5ml Oral Suspension 1 pack Relenza® Dry Powder for inhalation 1 pack 4000 units 5mg Appendix 2: Out of hours formulary Page 211 Version 16 (Version date: XX January 2014)