What is the recommended eperenone dosing regimen for adults and children, and how should the dose be adjusted in patients with hepatic or renal impairment?

Eplerenone Dosing

Standard Adult Dosing

For hypertension, start eplerenone at 50 mg once daily and increase to 50 mg twice daily (100 mg total) if blood pressure remains uncontrolled after 4 weeks. 1

• The usual dose range is 50-100 mg daily, given once or twice daily 1
• Eplerenone often requires twice-daily dosing for adequate blood pressure lowering 1
• Doses of 50-200 mg/day lower systolic blood pressure by approximately 9 mmHg and diastolic by 4 mmHg compared to placebo 2
• There is no clinically important dose-response difference between 50-200 mg daily 2

Heart Failure Dosing

For heart failure with reduced ejection fraction (LVEF ≤35-40%), start at 25 mg once daily and titrate to 50 mg once daily after 4 weeks if potassium remains ≤5.0 mEq/L. 1

• Initial dose: 25 mg once daily 1
• Check potassium and creatinine at 1 week and 4 weeks after starting 1
• Target maintenance dose: 50 mg once daily 1
• Do not increase dose if potassium >5.5 mEq/L or worsening renal function develops 1

Post-Myocardial Infarction Dosing

Start eplerenone 25 mg once daily within 3-14 days post-MI in patients with LVEF ≤40% and heart failure symptoms or diabetes, then increase to 50 mg once daily after 4 weeks. 1

• Requires adequate renal function (eGFR >30 mL/min/1.73 m²) and potassium <5.0 mEq/L 1

Renal Impairment Adjustments

Eplerenone is contraindicated when eGFR <30 mL/min/1.73 m² or creatinine >2.0 mg/dL in women or >2.5 mg/dL in men. 1

• For eGFR 30-49 mL/min/1.73 m²: Start at 25 mg every other day, maximum 25 mg once daily 1
• For eGFR ≥50 mL/min/1.73 m²: Standard dosing applies 1
• If creatinine rises to 220-310 µmol/L (2.5-3.5 mg/dL), reduce dose to 25 mg every other day and monitor closely 1
• If creatinine exceeds 310 µmol/L (3.5 mg/dL), stop eplerenone immediately 1

Hepatic Impairment

No specific dosing adjustments are provided in guidelines, but use with caution and start at lower doses. 3

• Eplerenone undergoes hepatic metabolism, requiring dose reduction in hepatic impairment 3
• Close monitoring of potassium and renal function is essential 3

Pediatric Dosing

Eplerenone is not approved for use in children, and no pediatric dosing guidelines exist.

• All clinical trials and guidelines focus exclusively on adult populations 1

Critical Monitoring Requirements

Check potassium and creatinine at baseline, 3 days, 1 week, monthly for 3 months, then every 3 months if stable. 1, 4

• If potassium 5.5-6.0 mEq/L: Reduce dose to 25 mg every other day 1
• If potassium ≥6.0 mEq/L: Stop eplerenone immediately and monitor closely 1, 4
• Discontinue all potassium supplements when starting eplerenone 1, 4

Essential Drug Interactions and Contraindications

Avoid combining eplerenone with potassium supplements, other potassium-sparing diuretics, or NSAIDs. 1, 4

• Do not use with ACE inhibitors or ARBs without very close monitoring due to severe hyperkalemia risk 1, 4
• Avoid NSAIDs and COX-2 inhibitors, which worsen renal function and cause hyperkalemia 4
• Contraindicated in pregnancy 1

Common Pitfalls to Avoid

The highest risk period for hyperkalemia and renal complications is the first few weeks after initiation—do not delay monitoring. 1, 4

• Do not uptitrate if potassium >5.5 mEq/L or creatinine is rising 1
• Counsel patients to avoid high-potassium foods (bananas, oranges, tomatoes, salt substitutes) 1, 4
• If gynecomastia develops on spironolactone, eplerenone 25-50 mg daily is preferred due to lower risk of sexual side effects 1, 4
• Reassess volume status if hypotension develops, as eplerenone combined with other antihypertensives increases hypotension risk 4