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 | Lisinopril | 2.5mg tablet: £0.74 | 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: Start ACE inhibitor therapy at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the optimal tolerated or target dose is achieved • 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 |
| 5mg tablet: £0.82 | |||
| 10mg tablet: £0.92 | |||
| 20mg tablet: £1.04 | |||
| 5mg/5ml oral solution sugar free: £198.00 (150ml) | |||
| Ramipril | 1.25mg capsule: £1.19 | 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: Start ACE inhibitor therapy at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the optimal tolerated or target dose is achieved |
|
| 2.5mg capsule: £1.13 | |||
| 5mg capsule: £1.08 | |||
| 10mg capsule: £1.22 | |||
| 2.5mg/5ml oral solution sugar free: £179.00 (150ml) | |||
| Perindopril erbumine | 2mg tablet: £0.95 (30) | Ensure Perindopril is prescribed as Perindopril erbumine, rather than Perindopril arginine, which is more expensive. Perindopril Erbumine is included in the formulary for: Hypertension:Treatment of hypertension Heart failure:Treatment of symptomatic heart failure. Start ACE inhibitor therapy at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the optimal tolerated or target dose is achieved Stable Coronary Artery Disease: Reduction of risk of cardiac events in patients with a history of myocardial infarction and/or revascularisation. |
|
| 4mg tablet: £1.09 (30) | |||
| 8mg tablet: £1.41 (30) | |||
| NHS Somerset classify Enalapril maleate and hydrochlorothiazide as a Black drug (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 (ARBs) | 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 CG106 (2018): Chronic heart failure) |
||
| First line: | Losartan | 25mg tablets: £3.07 50mg tablets: £3.64 100mg tablets: £4.64 | Losartan is included in the formulary for: • Hypertension: (where intolerant to ACEI except for people of African or Caribbean origin at step 2 where ARB are preferred 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. |
| Second line: | Candesartan | 2mg tablets: £2.17 (7) 4mg tablets: £0.93 (7) 8mg tablets: £4.72 16mg tablets: £5.37 32mg tablets: £4.02 | Candesartan is 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. |
| Third line: | Valsartan | 40mg capsules: £6.09 80mg capsules: £7.79 160mg capsules: £10.92 | Valsartan is included in the formulary for: • Essential hypertension in adults and hypertension in children and adolescents 6-18 yrs of age • Recent MI-Treatment of clinically stable patients with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction after a recent (12 hours-10 days) myocardial infarction. Heart failure - Treatment of adult patients with symptomatic heart failure when (ACE) inhibitors are not tolerated or in beta-blocker intolerant patients as add-on therapy to ACE inhibitors when mineralocorticoid receptor antagonists (spironolactone, eplenerone) cannot be used. |
| Sacubitril and valsartan as Entresto® | 24mg/26mg tablet: £45.78 | Sacubitril valsartan is recommended as an option 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 ACE inhibitors or ARBs. |
|
| 49mg/51mg tablet: £45.78, £91.56 (56) | |||
| 97mg/103mg tablet: £91.56 (56) | |||
| Centrally acting antihypertensive drugs | Methyldopa | 125mg tablets: £112.95 (56) 250mg tablets: £5.37 (56) 500mg tablets: £9.57 (56) | Methyldopa is included in the formulary for: • Hypertension in pregnancy |
| Moxonidine | 200mcg tablets: £1.26 300mcg tablets: £1.36 400mcg tablets: £1.31 | Moxonidine is included in the formulary for: • Hypertension: For treatment of resistant hypertension at Step 4 where BP remains sub-optimally controlled despite standard therapies. |
|
| Alpha-blockers | Doxazosin | 1mg tablets: £0.76 2mg tablets: £0.77 4mg tablets: £0.88 | 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 |