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.
ACE inhibitors and ARBs can cause hyperkalaemia, particularly if co-prescribed with potassium sparing diuretics (eplerenone, spironolactone, triamterene, bumetanide, amiloride) and certain antibiotics (trimethoprim,co-trimoxazole. Section 12 of the UK Renal Council’s Clinical practice guidelines treatment of acute hyperkalaemia in adults(2014) is especially relevant to primary care. It recommends that all patients with severe hyperkalaemia (K+ ≥ 6.5 mmol/L) are referred to secondary care for immediate assessment and treatment but that patients with mild (K+ ≥ 5.5-5.9 mmol/L) or moderate (K+ 6.0-6.4 mmol/L) hyperkalaemia have a review of their medication and diet and regular monitoring of serum potassium; the urgency of assessment and frequency of potassium monitoring will depend on individual circumstances.
NHS Somerset recommends Losartan as the first choice for people with a history of gout and cardiac comorbidity who need an Angiotensin-converting enzyme inhibitor or Angiotensin II Receptor Blocker;
Losartan demonstrated statistically significant reductions in serum uric acid levels or increases in fractional excretion of uric acid in all studies, whereas no other ARB reached statistical benefit. The effect of ARBs on the occurrence of gout attacks or other clinical outcomes were not represented. Four studies evaluated safety effects of these agents indicating abnormalities such as minor changes in lab values. In conclusion, losartan is the only ARB that has consistently demonstrated a significant reduction in serum uric acid levels, although the significance of impacting clinical outcomes remains unknown. Losartan appears to be a safe and efficacious agent to lower serum uric acid levels in patients with hyperuricemia.The effect of angiotensin II receptor blockers on hyperuricemia. Therapeutic Advances in Chronic Disease (2015).See ARBs in formulary.
See NHS Somerset formulary Useful links for NHS Somerset sick day rules.
| Therapeutic Area | Formulary Choices | Cost for 28 (unless otherwise stated) | Rationale for decision / comments | |
|---|---|---|---|---|
| Angiotensin-converting enzyme inhibitors (ACEi) | Lisinopril | 2.5mg tablet: £0.66 | For hypertension. Adult: initially 10 mg once daily; usual maintenance 20 mg once daily; maximum 80 mg per day. For secondary prevention following myocardial infarction. Adult: titrate to maximum tolerated/target dose and continue indefinitely. Maintenance 5-10 mg once daily. For heart failure. Adult: titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached. Maximum 35 mg per day. For diabetic nephropathy. Adult: initially 2.5–5 mg once daily, adjusted according to response; usual dose 10–20 mg once daily. | Measure serum sodium and potassium, and assess renal function, before and 1 to 2 weeks after starting an ACE inhibitor, and after each dose increment. Measure blood pressure before and after each dose increment of an ACE inhibitor. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. Once the target or maximum tolerated dose of an ACE inhibitor is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. ACE inhibitors should be avoided in pregnancy unless essential. They may adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohydramnios have also been reported. |
| 5mg tablet: £0.75 | ||||
| 10mg tablet: £0.86 | ||||
| 20mg tablet: £0.88 | ||||
| 5mg/5ml oral solution sugar free: £218.00 (150ml) | ||||
| Ramipril | 1.25mg capsule: £1.09 | For hypertension. Adult: initially 1.25–2.5 mg once daily, increased if necessary up to 10 mg once daily, dose to be increased at intervals of 2–4 weeks. For secondary prevention following myocardial infarction. Adult: titrate to maximum tolerated/target dose and continue indefinitely. Maintenance dose 5 mg twice daily. For heart failure. Adult: titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached (10 mg daily in 1–2 divided doses, daily dose preferably taken in 2 divided doses). For diabetic nephropathy. Adult: initially 1.25 mg once daily for 2 weeks, then increased to 2.5 mg once daily for 2 weeks, then increased if tolerated to 5 mg once daily. |
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| 2.5mg capsule: £1.03 | ||||
| 5mg capsule: £1.03 | ||||
| 10mg capsule: £1.11 | ||||
| 2.5mg/5ml oral solution sugar free: £196.00 (150ml) | ||||
| Perindopril erbumine | 2mg tablet: £0.95 (30) | Prescribe as Perindopril erbumine. Perindopril arginine is not cost effective. For hypertension. Adult: initially 4 mg once daily for 1 month, dose to be taken in the morning, then, adjusted according to response; maximum 8 mg per day. For secondary prevention following myocardial infarction. Adult: titrate to maximum tolerated/target dose and continue indefinitely. Maintenance dose 8 mg once daily. For heart failure. Adult: titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached (4 mg once daily). |
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| 4mg tablet: £1.09 (30) | ||||
| 8mg tablet: £1.41 (30) | ||||
| NHS Somerset classify Fosinopril sodium as not recommended as per Traffic light guidance. | ||||
| NHS Somerset classify Enalapril maleate and hydrochlorothiazide as not recommended as per Traffic light guidance. | ||||
| Advise patients taking hydrochlorothiazide-containing products of the cumulative, dose-dependent risk of non-melanoma skin cancer, particularly in long-term use, and the need to regularly check for (and report) any suspicious skin lesions or moles. Counsel patients to limit exposure to sunlight and UV rays and to use adequate sun protection. See MHRA (November 2018) for Hydrochlorothiazide: risk of non-melanoma skin cancer, particularly in long-term use. | ||||
| Therapeutic Area | Formulary Choices | Cost for 28 (unless otherwise stated) | Rationale for decision / comments |
|---|---|---|---|
| Angiotensin-II receptor blockers (ARB) | Patients exhibiting ACEi cough should trial a second 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. |
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| Losartan | 25mg tablet: £0.77 | For hypertension for people of African or Caribbean origin and those intolerant to ACEi. Adult: initially 25-50 mg once daily for several weeks, then increased if necessary to 100 mg once daily. For heart failure for people intolerant to ACEi. Adult: initially 12.5 mg once daily, increased if tolerated to up to 150 mg once daily, doses to be increased at weekly intervals. For diabetic nephropathy for people intolerant to ACEi. Adult: initially 25-50 mg once daily for several weeks, then increased if necessary to 100 mg once daily. |
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| 50mg tablet: £0.86 | |||
| 100mg tablet: £0.96 | |||
| Candesartan | 2mg tablet: £0.76 (7) | For hypertension for people intolerant to ACEi. Adult: initially 8 mg once daily, increased if necessary up to 32 mg once daily, dose to be increased at intervals of 4 weeks; usual dose 8 mg once daily. For heart failure for people intolerant to ACEi. Adult: initially 4 mg once daily, increased to up to 32 mg once daily, dose to be increased at intervals of at least 2 weeks to 'target' dose of 32 mg once daily or to maximum tolerated dose. |
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| 4mg tablet: £0.57 (7) | |||
| 8mg tablet: £1.02 | |||
| 16mg tablet: £1.16 | |||
| 32mg tablet: £1.35 | |||
| Valsartan | 40mg capsule: £5.51 | Third line for secondary prevention following myocardial infarction for people intolerant to ACEi. Adult: initially 20 mg twice daily, increased if necessary up to 160 mg twice daily, doses to be increased over several weeks if tolerated. Third line for heart failure for people intolerant to ACEi or in conjunction with an ACEi when a beta-blocker cannot be used. Adult: initially 40 mg twice daily, increased to up to 160 mg twice daily, doses to be increased at intervals of at least 2 weeks. |
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| 80mg capsule: £7.58 | |||
| 160mg capsule: £6.85 | |||
| Sacubitril and valsartan as Entresto® | 24mg/26mg tablet: £45.78 | For treating symptomatic chronic heart failure with reduced ejection fraction, only in people: • with New York Heart Association (NYHA) class II to IV symptoms and • with a left ventricular ejection fraction of 35% or less and • who are already taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or ARBs. Adult: initially 24/26 mg to 49/51mg twice daily for 2–4 weeks, increased if tolerated to 97/103 mg twice daily. |
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| 49mg/51mg tablet: £91.56 (56) | |||
| 97mg/103mg tablet: £91.56 (56) | |||
| Centrally acting antihypertensive drugs | Methyldopa | 125mg tablet: £94.69 (56) | For hypertension in pregnancy Adult: initially 250 mg 2–3 times a day, dose should be increased gradually at intervals of at least 2 days; maximum 3 g per day. |
| 250mg tablet: £22.19 (56) | |||
| 500mg tablet: £16.62 (56) | |||
| Moxonidine | 200mcg tablet: £5.15 | For treatment of resistant hypertension as per NICE guidance at Step 4 where BP remains sub-optimally controlled despite standard therapies. Adult: 200 micrograms once daily for 3 weeks, dose to be taken in the morning, then increased if necessary to 400 micrograms daily in 1–2 divided doses (max. per dose 400 micrograms), maximum daily dose to be given in 2 divided doses; maximum 600 micrograms per day. |
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| 300mcg tablet: £4.26 | |||
| 400mcg tablet: £3.95 | |||
| Alpha-blockers | Doxazosin | 1mg tablet: £0.76 | Alpha blocker monotherapy is not recommended. Doxazosin is included in the formulary for: • Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. • Benign prostatic hyperplasia: See section 7 NB. Doxazosin MR (Cardura XL®) tablets are specifically not recommended for maintenance in hypertension and maximum licensed dose for other indications is 8mg. Stabilised hypertensive patients on Doxazosin MR tablets should be switched to standard 4mg tablets: • Doxazosin MR 4mg one daily → Doxazosin 4mg one daily • Doxazosin MR 8mg one daily → Doxazosin 4mg two daily |
| 2mg tablet: £0.78 | |||
| 4mg tablet: £0.86 | |||