Back. Thiazide diuretics Drug Indication Formulation Notes on prescribing Bendroflumethiazide Hypertension, oedema Tablets

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1 Cardiovascular System General information Diuretics and related drugs Anti-arrhythmic drugs Drugs affecting the renin - angiotensin system Calcium channel blockers α-adrenoreceptor blocking drugs β-adrenoreceptor blocking drugs Vasodilator anti-hypertensive drugs Centrally acting anti-hypertensive drugs Antianginal drugs Drugs for Peripheral Vascular disease Antiplatelets Anticoagulants Antifibrinolytic drugs Lipid regulating drugs Updated:

2 General Information

3 There are both local and national guidance for the management of various cardiovascular conditions. Please refer to the following for further information: Clinical Effectiveness Group. Cardiovascular Disease Summary Guidelines. National Institute for Health and Clinical Excellence: - Hypertension: management of hypertension in adults in primary care. Clinical Guidance 34. June Management of chronic heart failure in adults in primary and secondary care. Clinical Guidance 5. July Secondary prevention in primary and secondary care for patients following a myocardial infarction. Clinical Guidance 48. May Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease. Technology Appraisal 94. January Clopidogrel and dipyridamole for the prevention of artherosclerotic events. Technology Appraisal 90. May Management of atrial fibrillation. Clinical Guideline 36. June All available from: The Coronary Heart Disease National Service Framework outlines the commitment of the Department of Health to reduce the death rate from coronary heart disease, stroke and related diseases. For more information visit the Department of Health website: Thiazide diuretics Bendroflumethiazide Hypertension, oedema Doses greater 2.5mg offer no advantage and cause more electrolyte disturbance. Indapamide MR is not recommended for prescribing as it is Indapamide Hypertension, stroke expensive with no evidence of improved efficacy. The branded indapamide / perindopril combination product (Coversyl Arginine Plus ) is not recommended for prescribing. Metolazone Oedema, hypertension Used mostly as an adjunct in congestive cardiac failure.

4 Loop Diuretics Furosemide Oedema, oral solutions Some oral solutions contain alcohol. (Frusol liquid brand has 10% alcohol). Bumetanide Oedema Tablet, oral solution May be better where furosemide is less effective (e.g. severe CCF/ oedema /ascites). Note: 1mg bumetanide = 40mg furosemide. Potassium-sparing diuretics and combinations Amiloride Oedema, potassium conservation with thiazide and loop diuretics Oral solution available (sugar free) Co-amilofruse (amiloride & furosemide) Oedema Generic tablets only Renal function and serum potassium levels should be monitored. Can interfere with tests for parathyroid function. Stop 3 days before giving a glucose tolerance test. Not generally needed as most low dose diuretics do not need additional potassium sparing diuretic. Renal function and serum potassium levels should be monitored. Can interfere with tests for parathyroid function. Stop 3 days before giving a glucose tolerance test. Aldosterone antagonists Aldosterone antagonists may cause hyperkalaemia and / or renal failure (particularly in the elderly; avoid potassium supplements and other potassium sparing diuretics). Monitor closely if prescribed concurrently with ACEIs and AIIRAs. Spironolactone Congestive heart failure, oedema and ascites in cirrhosis, malignant ascites, nephrotic syndrome, primary hyperaldosteronism Solution available Gynaecomastia is usually related to both dose and duration and is normally reversible on discontinuation.

5 Eplerenone [Inspra ] Adjunct in left ventricular dysfunction with evidence of heart failure after a myocardial infarction to reduce risk of CV mortality and morbidity in stable patients TNDG: for heart failure; hypertension; primary hyperaldosteronism. To be initiated in hospital, by consultants only Requires close monitoring to avoid hyperkalaemia. In hypertension, prescribing and monitoring will remain with the hospital due to its unlicensed status. Anti-arrhythmic Drugs Amiodarone Treatment of severe rhythm disorders not responding to other therapies or when other treatments cannot be used Required monitoring: Thyroid disorders: 6 monthly TFT monitoring required. Seek specialist advice if clinical signs of thyroid disease or severe TFT abnormalities develop. Hepatotoxicity: 6 monthly LFT monitoring and seek specialist advice if clinical signs of liver disease or severe LFT abnormalities develop. Corneal microdeposits may cause drivers to be dazzled by headlights at night. If vision is impaired or other ophthalmic problems occur seek expert advice urgently as amiodarone may need to be stopped to prevent blindness. Pneumonitis should be suspected if new or progressive SOB or cough develops. Peripheral neuropathy should be suspected if new neurological symptoms arise. Patient advice: Slate grey or bluish pigmentations of light-exposed skin, particularly the face, may occur in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.

6 Photosensitisation is common - patients should be advised to avoid exposure to direct sunlight. Amiodarone has a half-life of several weeks: amiodarone related adverse effects and interactions may occur several months after stopping therapy. Toxicity can occur within therapeutic range. Signs of toxicity include nausea, vomiting, diarrhoea, abdominal pain, visual disturbances, confusion, drowsiness and headache. Hypokalaemia predisposes to toxicity. Digoxin Supraventricular arrhythmias (atrial fibrillation), also used in heart failure, oral solution Routine monitoring is not necessary however it may be useful to assess compliance or toxicity. TDM: Target serum concentration: 1 2 micrograms/litre Sample time: 6 8 hours post dose Notes: Sample needed on days of treatment Bioavailability tablet elixir: 62.5mcg tablet = 50mcg elixir. Disopyramide Flecainide Sotalol Ventricular arrhythmias, especially post MI; supraventricular arrhythmias Arrythmias see current BNF for further information Ventricular arrhythmias/ prophylaxis of supraventricular arrhythmias only MR tablets, immediate release tablets Renal function is the most important determinant of dosage. Has antimuscarinic effects: ocular hypertension with narrow angle glaucoma, acute urinary retention with prostatic enlargement, aggravation of myasthenia gravis. CSM: It should no longer be used for hypertension, angina, thyrotoxicosis, or secondary prevention of MI. When stopping sotalol for these indications, reduce the dose gradually.

7 Verapamil Supraventricular arrhythmias Immediate release talets, oral solution The combination of verapamil with a β-blocker should only be initiated by a specialist. Drugs affecting the renin-angiotensin system Before starting an ACE inhibitor (ACEI) or an angiotensin-ii receptor antagonist (AIIRA) check urea and electrolytes, and renal function (preferably the estimated glomerular filtration rate [egfr]). Re-check the urea, electrolytes, and the egfr within 2 weeks of starting or increasing the dose: A rise in serum creatinine concentration of more than 20% or a fall in the egfr of more than 15% after initiation or a dose increase should be followed by further measurements within 2 weeks. If deterioration in kidney function is confirmed, seek specialist advice on whether to stop drug treatments or to investigate for renal artery stenosis. If serum potassium levels rise to above 6.0 mmol/l (hyperkalaemia): o Stop nephrotoxic drugs (e.g. nonsteroidal anti-inflammatory drugs) o Stop or reduce the dose of potassium-retaining diuretics (amiloride, triamterene, spironolactone) If hyperkalaemia persists, despite appropriate adjustments to other drug treatments, the ACEI or AIIRA should be stopped. Note: severe hyperkalaemia (> 8 mmol/l) can cause cardiac arrest and death with very few warning symptoms. Urea and electrolytes and egfr should be monitored every 12 months (unless required more frequently due to impaired renal function). Angiotensin-converting enzyme inhibitors (ACEI) Lisinopril Diabetic nephropathy in normotensive insulin-dependent and hypertensive non-insulin-dependent diabetes mellitus, hypertension, heart failure, short-term post MI. Ramipril Perindopril Erbumine / tert- Hypertension, Congestive Cardiac Failure, post MI with HF, prevention of MI / stroke Hypertension, symptomatic heart failure, prophylaxis of cardiac events following MI or re-vascularisation in stable coronary artery disease. Capsules Advise patient of first dose hypotension particularly if also taking diuretics. Advise patient of first dose hypotension particularly if also taking

8 butylamine diuretics. Perindopril should only be prescribed as generic perindopril (as erbumine or tert-butylamine) and not as Coversyl Arginine or perindopril arginine. The branded indapamide / perindopril combination product (Coversyl Arginine Plus ) is not recommended for prescribing. Angiotensin-II receptor antagonists (AIIRA) Candesartan Hypertension, HF with impaired left ventricular systolic function Irbesartan Losartan Hypertension, renal disease in hypertensive type 2 diabetes mellitus. Hypertension (inc. reduction of stroke risk in hypertension with left ventricular hypertrophy); diabetic nephropathy in type 2 diabetes mellitus. Indicated ONLY if patient intolerant to an ACEI (persistent dry cough, angiooedema). ACEI + AIIRA combinations Danger of hyperkalaemia. To be prescribed under specialist advice only. Renin inhibiors Aliskiren [Rasilez ] Essential hypertension TNDG: Aliskiren is approved for initiation by cardiology specialist services:

9 For patients with resistant level 3 or 4 hypertension who fail to achieve / tolerate optimal doses of combination medication to provide the required control. All prescribing and monitoring to be carried out by the cardiology specialist services for 3 6 months after initiation. All patients should be reviewed after 1 month and aliskerin stopped if there is no significant benefit. After 3-6 months of treatment for those patients who respond well to aliskerin and require long-term treatment, GPs may prescribe under a Shared Care agreement. It is estimated the specialist team would see approximately patients only per year who may fit the criteria for aliskerin. Aliskerin is likely to be used in addition to current medication, rather than being substituted. As a newly licensed (black triangle) drug, any adverse drug reactions should be reported to the MHRA. Calcium Channel Blockers Amlodipine Hypertension, prophylaxis of angina Diltiazem Verapamil Hypertension, prophylaxis and treatment of angina Supraventricular arrhythmias, angina, hypertension. MR preparations, immediate release MR tablets, immediate release tablets MR brands are not interchangeable. Some dose forms are not appropriate for initial dose titration in elderly, hepatic & renal impairment. See current BNF. These should be prescribed by brand. MR preparation should be prescribed by brand. α-adrenoceptor blocking drugs

10 Doxazosin Phenoxybenzamine Hypertension Hypertension in phaechromocytoma Immediate release tablets Capsules Considered as 4 th line in the management of hypertension. May be useful for patients with concomitant Benign Prostatic Hypertrophy. NB: The immediate release preparation is preferred for prescribing as the maximum licensed dose is 16mg per day. (XL formulation has a maximum licensed dose of 8mg). The XL version is contra-indicated in those with a history of gastro-intestinal obstruction or stricture. Micturition syncope: can increase the risk of micturition syncope in susceptible individuals especially on starting treatment. β-adrenoreceptor Blocking Drugs (prescribed according to new NICE guidelines June 2006) β-blockers are no longer considered as first line treatment for hypertension. CSM: β blockers should not be given to people with a history of asthma or bronchospasm. Atenolol Angina, hypertension, liquid Bisoprolol Heart failure, hypertension, Usually reserved for treatment of heart failure. Carvedilol angina Hypertension; angina; adjunct to diuretics, digoxin, or ACE inhibitors in symptomatic chronic heart failure Labetalol Hypertension in pregnancy Propranolol Migraine prophylaxis & Usually reserved for treatment of heart failure. Caution in liver damage: severe hepatocellular damage reported after both short-term and long-term treatment. Laboratory testing is needed at first sign of liver dysfunction and if there is evidence of damage (or if jaundiced) labetalol should be stopped and not restarted.

11 panic /anxiety attacks, thyrotoxicosis Vasodilator anti-hypertensive drugs Moderate to severe hypertension, heart failure in Normally used with β-blockers as use alone can cause tachycardia & Hydralazine combination with a long acting nitrate, hypertensive crisis fluid retention. Doses should be kept below 100mg to reduce incidence of side-effects (including Systemic lupus erythematosus). Centrally acting anti-hypertensive drugs Methyldopa Hypertension in pregnancy Moxonidine Mild to moderate hypertension FBC & LFT are required prior to treatment and at intervals during the first 6 12 weeks or if unexplained fever occurs as methyldopa can cause haemolytic anaemia, leucopenia, thrombocytopenia, hepatitis and pancreatitis. Can cause somnolence and dizziness. Anti-anginals Glyceryl Sublingual tablets, Requires a minimum 4 hour nitrate free period to Prophylaxis and treatment of angina trinitrate spray, patches reduce tolerance particularly for transdermal patch. Many patients on long-acting nitrates rapidly develop Isosorbide Prophylaxis of angina, adjunct in congestive MR tablets, tablets tolerance. Reduction of blood-nitrate concentrations for 4 mononitrate heart failure to 8 hours each day usually maintains effectiveness.

12 Dosing for conventional formulation: Maximum twice daily, with the second dose taken approximately 8 hours after the first. Nicorandil Prophylaxis and treatment of angina Ivabradine [Procoralan ] Ranolazine [Ranexa ] Treatment of angina in patients in normal sinus rhythm chronic stable angina As adjunctive therapy in the treatment of stable angina in patients inadequately controlled or intolerant of first-line antianginal therapies MR tablets Dosing for MR formulation: Once daily Patients should be warned not to drive or operate machinery until it is established that their performance is unimpaired. Prescribe quantities in whole packs. TNDG: for hospital initiation in patients with chronic stable angina as an alternative to nicorandil, when β- blockers or calcium channel blockers are contraindicated or not tolerated. TNDG: for hospital initiation by a consultant cardiologist in patients with unstable angina who fit the following criteria: Have a controlled heart rate A course of all other approved drugs have been demonstrated to be ineffective, or not tolerated, and the patient is still suffering ischaemic attacks. All prescribing and monitoring to be carried out by the hospital team for the first 3 months. All patients to be educated by the hospital team and given a Patient Information Card to minimise the risks associated with drug interactions. The hospital team to produce some guidance for safe continuation of prescribing of ranolazine before asking GPs to continue prescribing

13 Drugs for Peripheral Vascular Disease Cilostazol intermittent claudication in patients without rest pain and no peripheral tissue necrosis TNDG: for hospital initiation only. GP to prescribe under a shared care agreement. Specialist to send treatment guideline to GPs when transferring the prescribing. Cilostazol is a liver enzyme inhibitor and could therefore increase levels and side effects of drugs metabolised by this route. Anti-platelet Drugs NICE: Treatment of non-st segment- elevation acute coronary syndrome Clopidogrel, in combination with low-dose aspirin, is recommended for use in the management of non-st-segment-elevation acute coronary syndrome (ACS) for up to 12 months after the most recent acute episode in people who are at moderate to high risk of myocardial infarction or death. Thereafter, standard care, including treatment with low-dose aspirin alone, is recommended. NICE: Prevention of occlusive vascular events The combination of modified-release (MR) dipyridamole and aspirin is recommended for people who have had an ischaemic stroke or a transient ischaemic attack (TIA) for a period of 2 years from the most recent event. Thereafter, or if MR dipyridamole is not tolerated, preventative therapy should revert to standard care (including long-term treatment with low-dose aspirin) Clopidogrel alone (within its licensed indications) is recommended for people who are intolerant of low-dose aspirin and either have experienced an occlusive vascular event or have symptomatic peripheral arterial disease, (long term treatment instead of aspirin) Aspirin intolerance is defined as either of the following: proven hypersensitivity to aspirin-containing medicines history of severe dyspepsia induced by low dose aspirin BLT SCG: Clopidogrel with low dose aspirin in Acute Coronary Syndromes and Coronary Artery Stenting The current recommended treatment duration is 1 month following a bare metal stent (BMS) or 12 months following insertion of a drug eluting

14 stent (DES). There are occasions where at the consultant s discretion dual antiplatelet therapy is required indefinitely and will be documented as such. Patients prescribed clopidogrel and aspirin indefinitely should still be reviewed on a regular basis. Age, renal function and gender do not have an effect on the therapeutic outcome of the drug and clopidogrel is not licensed for use in children. NICE technology appraisal guidance 182: 1. Prasugrel in combination with aspirin is recommended as an option for preventing atherothrombotic events in people with acute coronary syndromes having percutaneous coronary intervention, only when: immediate primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction is necessary or stent thrombosis has occurred during clopidogrel treatment or the patient has diabetes mellitus. 2. People currently receiving prasugrel for treatment of acute coronary syndromes whose circumstances do not meet the criteria in 1 should have the option to continue therapy until they and their clinicians consider it appropriate to stop. Clopidogrel/ prasugrel card All patients discharged from the Barts and The London NHS Trust following Percutaneous Coronary Intervention having been commenced on clopidogrel or prasugrel therapy, will be given a clopidogrel/prasugrel card. This provides patients with written information on the reason why clopidogrel or prasugrel has been started, their daily dose, the drug s concurrent use with aspirin and the planned duration of therapy. The card also provides details on possible adverse effects and potential interactions with other medicines, and highlights the need to consult a doctor before any surgical procedures. Failure to communicate adequately the intended duration of combination therapy to the patient and the primary care physician can result in: Inappropriate continuation of combination therapy increasing the risk of bleeding Inappropriate early discontinuation of treatment, increasing the risk of intra-stent thrombosis and subsequent myocardial infarction Aspirin Prophylaxis of cerebrovascular There is no evidence that EC or MR preparations reduce the Dispersible tablets disease / MI risk or GI side effects and are consequently not recommended. Clopidogrel Secondary prevention of atherosclerotic events in ACS, PAD, See above MI, ischaemic stroke Dipyridamole Secondary prevention of ischaemic stroke and TIA MR capsules See above. Prescribe quantities in whole packs.

15 Prasugrel [Efient ] In combination with aspirin for the prevention of atherothrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention Film coated tablets NICE: The combination course length is 12 months as for clopidogrel. After 12 months, aspirin would continue alone. Oral anticoagulants NPSA Patient Safety Alert 18 (March 2007) Ensure all members of staff dealing with patients on anticoagulant therapy are aware of the risks associated with anticoagulation Procedures are in place to reflect safe prescribing practice of anticoagulants Appropriate information about their anticoagulant should be given to patients throughout the course of their treatment, ensuring they understand how to take their dose and when to seek help Promote safe practice for prescribers to check blood clotting is being monitored regularly and the INR is safe before reissuing repeats prescriptions ensure that patient has an updated Yellow (anticoagulation) book The Yellow Book should be checked by the prescriber before supplying any repeat prescription for anticoagulants to ensure that it is safe to do so Promote safe practice for co-prescribing of clinically significant interacting drugs In Tower Hamlets, this alert is being implemented via the GP and Community Pharmacy Incentive schemes. Anticoagulant treatment booklets available from RR Donnelley Global Document Solutions , or Women of child-bearing age should be warned oral anticoagulants are teratogenic and should not be given in the first trimester of pregnancy. Warfarin Prophylaxis & treatment of VT&PE, prophylaxis of embolisation in rheumatic heart disease, AF or after insertion of

16 Phenindione prosthetic heart valve Prophylaxis of embolisation in rheumatic heart disease / AF, prophylaxis after insertion of prosthetic heart valve, prophylaxis and treatment of VT&PE For warfarin allergic patients. Antifibrinolytic Drugs Prevention / treatment of Tranexamic bleeds, menorrhagia, local Acid fibrinolysis, angioedema, epistaxis CSM: Lipid regulating drugs advice (muscle effects) The CSM has advised that rhabdomyolysis associated with lipid-regulating drugs such as the fibrates and statins appears to be rare (approx. 1 case in every treatment years) but may be increased in those with renal impairment and possibly in those with hypothyroidism. Concomitant treatment with drugs that increase plasma-statin concentration increase the risk of muscle toxicity; concomitant treatment with a fibrate and a statin may also be associated with an increased risk of serious muscle toxicity. Statins Primary and Secondary CEG: Use first line at a dose of 40mg daily. 10mg not advocated. Simvastatin prevention of See CEG CVD guidelines for more information. cardiovascular disease; NB: Max. 10 mg daily with concomitant ciclosporin, danazol, fibrate or lipid-lowering primary prevention if CVD dose of nicotinic acid. Max. 20 mg daily with concomitant amiodarone or verapamil.

17 Pravastatin Atorvastatin risk >20% Primary and Secondary prevention of cardiovascular disease; primary prevention if CVD risk >20% Secondary prevention of cardiovascular disease; primary prevention if CVD risk >20% Max. 40 mg daily with diltiazem. NICE May 08: Treatment for the primary or 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. For patients with renal impairment, interacting drugs e.g. ciclosporin or cholesterol levels not controlled by simvastatin 40mg. See CEG CVD guidelines for more information. Fibrates MHRA: Fibrates should be considered as first-line therapy only in patients with isolated severe hypertriglyceridaemia For patients with mixed hyperlipidaemia, fibrates may be used only when a statin or other effective treatments are contraindicated or not tolerated Combination therapy with a statin and a fibrate should be used with caution and only when the benefits are expected to outweigh potential risks Myotoxicity: Special care is needed in patients with renal disease as progressive increases in Bezafibrate Hyperlipidaemia MR tablets serum creatinin concentration or failure to follow dosage guidelines may result in myotoxicity. Discontinue if myotoxicity suspected or creatine kinase concentration increases significantly. Other lipid regulating drugs Adjunct to diet and TNDG & NICE: Ezetimibe statin treatment in 1 & As monotherapy for patients in whom statins are not appropriate (i.e. true [Ezetrol ] homozygous familial intolerance or contraindication) e.g. patients with significant liver dysfunction. hypercholesterolaemia In combination with atorvastatin, where a course of 80mg daily of atorvastatin

18 (ezetimibe alone if statin not appropriate) failed to achieve the required targets. Patients with significantly raised triglycerides should continue to receive a fibrate, either alone where there is a pure hypertriglyceridaemia or in combination where the picture was mixed. References: Joint Formulary Committee. British National Formulary. 58 th Ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain Barts and The London & Queen Mary s School of Medicine and Dentistry. Clinical Effectiveness Group.Summary Gidelines: Cardiovascular Disease. October Available from: Accessed CKS. Antiplatelet treatment. October Accessed from on MeReC. Prescribing antiplatelet drugs in primary care Accessed from on MHRA. ACE inhibitors and angiotensin II receptor antagonists: not for use in pregnancy.. Drug Safety Update: Volume 1, Issue 5, December Accessed from: on MHRA. Fibrates: new prescribing advice. Drug Safety Update: Volume 1, Issue 4, November Accessed from: on MHRA. Statins: class effects identified. Drug Safety Update: Volume 1, Issue 7, February Accessed from: on National Institute for Clinical Excellence. Hypertension: management of hypertension in adults in primary care. Clinical Guidance 34. June Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Management of chronic heart failure in adults in primary and secondary care. Clinical Guidance 5. July Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Secondary prevention in primary and secondary care for patients following a myocardial infarction. Clinical Guidance 48. May Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease. Technology Appraisal 94. January Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Clopidogrel in the treatment of non-stsegment- elevation acute coronary syndrome. Technology Appraisal 80. July Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Clopidogrel and dipyridamole for the prevention of artherosclerotic events. Technology Appraisal 90. May Available from: Accessed 10/03/08 National Institute for Clinical Excellence. Ezetimibe for the treatment of primary (hetrozygous familial and non-familial) hypercholesterolaemia. Technology Appraisal 132. November Available from: Accessed 04/04/08 National Prescribing Centre. Ezetimibe in hypercholesterolaemiae. MeReC Extra Issue 32. March Accessed from

19 on Tower Hamlets Shared Care Guidelines Available from National Institute for Clinical Excellence. Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. Technology Appraisal 182. October Accessed