What is the recommended dosing for eplerenone (generic name) in patients with heart failure or hypertension?

Eplerenone Dosing in Heart Failure and Hypertension

For patients with heart failure or hypertension, eplerenone should be initiated at 25 mg once daily and titrated to a target dose of 50 mg once daily, with dose adjustments based on renal function and serum potassium levels. 1, 2

Heart Failure Dosing

Initial Dosing

• Starting dose: 25 mg once daily 1, 2
• Target dose: 50 mg once daily, preferably titrated within 4 weeks as tolerated 1, 2
• Renal function considerations:
  • For patients with eGFR ≥50 mL/min/1.73 m²: Target 50 mg once daily 3
  • For patients with eGFR 30-49 mL/min/1.73 m²: Limit to ≤25 mg once daily 3

Dose Titration

• Assess for dose up-titration after 4-8 weeks 1
• Do not increase dose if worsening renal function or hyperkalemia occurs 1
• Re-check renal function and serum electrolytes 1 and 4 weeks after increasing dose 1

Dose Adjustment Based on Potassium Levels

• Serum K+ <5.0 mEq/L: May increase from 25 mg every other day to 25 mg daily, or from 25 mg daily to 50 mg daily 2
• Serum K+ 5.0-5.4 mEq/L: No adjustment needed 2
• Serum K+ 5.5-5.9 mEq/L: Reduce from 50 mg daily to 25 mg daily, or from 25 mg daily to 25 mg every other day 1, 2
• Serum K+ ≥6.0 mEq/L: Withhold medication and restart at 25 mg every other day when potassium falls below 5.5 mEq/L 1, 2

Hypertension Dosing

• Starting dose: 50 mg once daily 2
• Maximum dose: 50 mg twice daily (100 mg/day) if blood pressure response is inadequate 2
• Note: Doses higher than 100 mg/day are not recommended as they provide no additional blood pressure reduction and increase hyperkalemia risk 2, 4

Monitoring Requirements

Before Initiation

• Check renal function (creatinine should be <2.5 mg/dL in men, <2.0 mg/dL in women) 5
• Check baseline serum potassium (should be normal) 1

After Initiation

• Check renal function and serum electrolytes at 1 and 4 weeks after starting treatment 1, 5
• After achieving maintenance dose, monitor at 1,2,3, and 6 months, then every 6 months thereafter 1, 5
• More frequent monitoring for patients with risk factors for hyperkalemia 5

Special Considerations

Drug Interactions

• For patients receiving moderate CYP3A inhibitors (e.g., erythromycin, verapamil, fluconazole):
  • Heart failure patients: Do not exceed 25 mg once daily 2
  • Hypertension patients: Start at 25 mg once daily, maximum 25 mg twice daily 2

Contraindications and Cautions

• Avoid triple therapy with ACE inhibitor, ARB, and eplerenone due to increased hyperkalemia risk 5
• Use with caution in elderly patients (higher risk of hyperkalemia) 5
• Avoid NSAIDs when possible 5

Clinical Evidence

Eplerenone has demonstrated significant mortality benefits in heart failure patients:

• In EPHESUS trial, eplerenone 25-50 mg daily reduced mortality by 15% in post-MI patients with LVEF ≤40% and heart failure 1
• In patients with LVEF ≤30%, eplerenone reduced all-cause mortality by 21% and sudden cardiac death by 33% 6
• In EMPHASIS-HF, lower doses (25 mg daily) in patients with eGFR 30-49 mL/min/1.73 m² were as effective as higher doses (50 mg daily) in patients with better renal function 3

For hypertension, eplerenone 50-200 mg/day lowers systolic blood pressure by approximately 9.21 mmHg and diastolic by 4.18 mmHg compared to placebo 4.

Adverse Effects Management

• Hyperkalemia: Most common serious adverse effect; follow potassium-based dose adjustment protocol 1, 2
• Worsening renal function: If creatinine rises to >220 μmol/L (2.5 mg/dL), halve the dose; if >310 μmol/L (3.5 mg/dL), stop eplerenone 1
• Gynecomastia: Less common with eplerenone than spironolactone; consider switching from spironolactone to eplerenone if this occurs 1, 7