Eplerenone

Mineralocorticoids cause salt and water retention and increase K+ and H+ excretion by binding to specific mineralocorticoid receptors. Eplerenone is a specific antagonist for the mineralocorticoid receptor (MR). It binds to cytosolic MRs in epithelial cells of the late distal tubule and collecting duct, inhibiting aldosterone's effects, thereby reducing NaCl transport and preventing increased driving force for K+ and H+ secretion.

Adult

Initially 25 mg daily, then increased to 50 mg daily, increased within 4 weeks of initial treatment.

Renal adjustment

Avoid if eGFR less than 30 mL/minute/1.73 m2. Initially 25 mg on alternate days if eGFR 30–60 mL/minute/1.73 m2, adjust dose according to serum-potassium concentration—consult product literature. Close monitoring required due to increased risk of hyperkalaemia.

Hepatic adjustment

Manufacturer advises avoid in severe impairment (no information available).

Geriatric

For aldosterone antagonists, prescription potentially inappropriate with concurrent potassium-conserving drugs without monitoring of serum potassium (risk of dangerous hyperkalaemia).

Max dose

50 mg daily; manufacturer advises max. dose 25 mg daily with concurrent use of amiodarone or moderate inhibitors of CYP3A4.

• Hyperkalaemia
• Renal impairment (eGFR less than 30 mL/minute/1.73 m2)
• Severe hepatic impairment
• Concurrent potassium-conserving drugs without monitoring of serum potassium (risk of dangerous hyperkalaemia)
• hyperkalemia
• patients at increased risk of developing hyperkalemia (e.g., renal failure)
• creatinine clearance ≤30 mL/min
• strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole)
• renal insufficiency with creatinine clearance <30 mL/min
• combination with other K+-sparing diuretics
• renal insufficiency
• Significant renal dysfunction (creatinine ≥2.5 mg/dL in men and ≥2.0 mg/dL in women)
• Hyperkalemia (potassium ≥5.0 mEq/L)