What is the recommended dose of Eplerenone for heart failure?

Eplerenone Dosing for Heart Failure

The recommended dose of eplerenone for heart failure is 25 mg once daily initially, titrated to a target dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient. 1, 2

Dosing Protocol

Initial Dosing

• Start with 25 mg once daily for patients with heart failure with reduced ejection fraction (HFrEF) 1
• For patients with impaired renal function (eGFR 30-49 mL/min/1.73 m²), use 25 mg once daily or 25 mg every other day 1, 3
• For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), eplerenone is contraindicated 1

Dose Titration

• Increase to target dose of 50 mg once daily after 4-8 weeks if tolerated 1, 2
• Do not increase dose if worsening renal function or hyperkalemia occurs 1
• Recheck renal function and serum electrolytes 1 and 4 weeks after increasing dose 1

Dose Adjustment Based on Serum Potassium

• If potassium <5.0 mEq/L: Maintain or increase dose to target 2
• If potassium 5.0-5.4 mEq/L: No adjustment needed 2
• If potassium 5.5-5.9 mEq/L: Reduce dose (50 mg daily to 25 mg daily, or 25 mg daily to 25 mg every other day) 2
• If potassium ≥6.0 mEq/L: Withhold medication and restart at 25 mg every other day when potassium <5.5 mEq/L 2

Monitoring Requirements

• Check renal function and serum electrolytes before initiating therapy 1
• Recheck within 2-3 days and again at 7 days after initiation 1
• Monitor monthly for the first 3 months and every 3 months thereafter 1, 4
• More frequent monitoring is needed in patients at higher risk for hyperkalemia 1
• New cycle of monitoring should be initiated if ACE inhibitors or ARBs are added or doses increased 1

Special Considerations

Renal Function

• Eplerenone is effective at lower doses (25 mg daily) in patients with eGFR 30-49 mL/min/1.73 m² 3
• Despite lower doses, patients with impaired renal function experience more adverse events 3
• Do not use if serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 1

Drug Interactions

• When used with moderate CYP3A inhibitors (e.g., erythromycin, verapamil, fluconazole), do not exceed 25 mg once daily 2
• Discontinue potassium supplements when initiating eplerenone 1
• Use caution when combining with ACE inhibitors or ARBs due to increased risk of hyperkalemia 1

Clinical Evidence

• The EMPHASIS-HF trial demonstrated that eplerenone reduced mortality and hospitalization in patients with mild heart failure symptoms (NYHA class II) and LVEF ≤30% or between 30-35% with QRS duration >130 ms 1, 5
• The EPHESUS trial showed that eplerenone reduced mortality by 15% in post-MI patients with HF and LVEF <40% 5, 6
• Eplerenone has fewer anti-androgenic side effects (gynecomastia, breast pain) compared to spironolactone 4

Contraindications and Precautions

• Do not initiate if baseline serum potassium >5.0 mEq/L 1
• Avoid triple combination of ACE inhibitor, ARB, and aldosterone antagonist 1
• Instruct patients to stop eplerenone during episodes of diarrhea, dehydration, or when loop diuretic therapy is interrupted 1
• Counsel patients to avoid foods high in potassium and NSAIDs 1

Remember that close monitoring of potassium and renal function is essential to minimize the risk of hyperkalemia, which is the most common serious adverse effect of eplerenone therapy 4.