Eplerenone

Eplerenone is a selective mineralocorticoid receptor antagonist with little effect on androgen or progesterone receptors, so gynaecomastia and menstrual disturbance are uncommon. It reduces death after myocardial infarction with left ventricular dysfunction and in heart failure with reduced ejection fraction, and lowers blood pressure. It costs more than spironolactone and is limited in East Africa.

Classification. Selective aldosterone antagonist; potassium sparing diuretic.

Mechanism. Competitively blocks the mineralocorticoid receptor in the distal nephron, heart and vessels, reducing sodium retention, potassium loss and myocardial fibrosis.

Pharmacodynamics. Onset of blood pressure effect within 2 weeks, full effect at 4 weeks. Raises serum potassium.

Pharmacokinetics. Oral bioavailability about 69%; food has no effect. Half life 4 to 6 hours. Metabolised mainly by CYP3A4 to inactive metabolites; about 67% excreted in urine.

Heart failure after myocardial infarction with left ventricular dysfunction, adult.

• Start 25 mg once daily (can begin 3 to 14 days after infarction).

• Increase to 50 mg once daily within 4 weeks, as potassium allows.

• Target and maximum 50 mg once daily.

Heart failure with reduced ejection fraction, NYHA class II, adult. Start 25 mg once daily; increase to 50 mg once daily after 4 weeks if potassium is under 5.0 mmol/L.

Hypertension, adult (where licensed). Start 50 mg once daily; increase to 50 mg twice daily after 4 weeks; maximum 100 mg daily.

Dose adjustment with kidney impairment. eGFR 30 to 50 mL/min: start 25 mg on alternate days and increase to 25 mg once daily, then 50 mg only with monitoring.

Children. Not established.

Contraindications. Potassium above 5.0 mmol/L at the start; eGFR under 30 mL/min; severe hepatic impairment; concurrent potassium sparing diuretics or potassium supplements; strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir); in hypertension, type 2 diabetes with microalbuminuria or creatinine clearance under 50 mL/min, and concurrent angiotensin converting enzyme inhibitor or angiotensin receptor blocker; hypersensitivity.

Warnings. Hyperkalaemia; kidney function decline; hypotension; caution with moderate CYP3A4 inhibitors (erythromycin, verapamil, diltiazem, fluconazole): limit to 25 mg daily. Sick day rule applies.

Adverse effects. Hyperkalaemia, dizziness, creatinine rise, diarrhoea, nausea, hypotension, raised triglycerides and cholesterol; gynaecomastia is rare.

Interactions. Strong CYP3A4 inhibitors: contraindicated. Moderate CYP3A4 inhibitors: maximum 25 mg daily. CYP3A4 inducers (rifampicin, carbamazepine, St John's wort): lower levels. Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, trimethoprim and potassium supplements: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: raised levels.

Special groups.

• Pregnancy: avoid unless essential; no good data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change; check potassium closely.

• Older adults: start 25 mg; monitor potassium.

• Kidney impairment: avoid with eGFR under 30 mL/min; start 25 mg on alternate days at eGFR 30 to 50 mL/min.

• Liver impairment: mild to moderate: no change; severe: avoid.

Formulations. Tablets 25 and 50 mg.

Administration. Oral once daily with or without food. Avoid grapefruit juice.

Baseline. Potassium, sodium, creatinine and eGFR, blood pressure, drug history for CYP3A4 interactions.

Monitoring. Potassium and creatinine within the first week, at 1 month, then every 3 to 6 months and after any dose change or new interacting drug. Halve the dose if potassium is above 5.5 mmol/L; stop if above 6.0 mmol/L.

Stopping. No taper. Hold on sick days with vomiting or diarrhoea.

Common prescribing errors. Starting when potassium is 5.0 mmol/L or higher; combining with a strong CYP3A4 inhibitor; combining with spironolactone; omitting the first week check; using it in kidney impairment without adjustment.