What is the recommended conversion dose from spironolactone to eplerenone?

Conversion of Spironolactone to Eplerenone

When converting from spironolactone to eplerenone, use a 1:2 ratio, meaning 25 mg of spironolactone is equivalent to 50 mg of eplerenone daily. 1

Dosing Conversion Algorithm

The standard conversion follows this equivalence:

• Spironolactone 25 mg daily = Eplerenone 50 mg daily 1
• Spironolactone 50 mg daily = Eplerenone 100 mg daily 1

This 1:2 ratio reflects the fact that eplerenone is less potent than spironolactone as a mineralocorticoid receptor antagonist, requiring approximately double the dose to achieve similar blood pressure reduction and clinical effects. 2, 3

Initiation Protocol After Conversion

Start eplerenone at 25 mg once daily for the first week, then increase to the target maintenance dose (typically 50 mg daily) after checking electrolytes. 4, 2

• Do not initiate eplerenone if serum potassium is >5.5 mEq/L or creatinine clearance is ≤30 mL/min 4
• After approximately 1 week on 25 mg daily, recheck potassium levels before dose escalation 4
• If potassium remains <5.0 mEq/L, increase to the target maintenance dose 4
• Target dose titration should preferably occur within 4 weeks 2

Mandatory Monitoring Requirements

Check renal function and serum electrolytes before conversion, at 1 week after starting eplerenone, then at 1,2,3, and 6 months, followed by every 6 months thereafter. 1

Potassium Management During Conversion:

• If K+ is 5.0-5.4 mEq/L: Maintain current eplerenone dose 4
• If K+ is 5.5-5.9 mEq/L: Reduce eplerenone dose (from 50 mg daily to 25 mg daily, or from 25 mg daily to 25 mg every other day) 4
• If K+ is ≥6.0 mEq/L: Stop eplerenone immediately; can restart when potassium falls below 5.5 mEq/L 4

Key Advantages of Conversion

The primary reason to convert from spironolactone to eplerenone is to avoid anti-androgenic side effects, particularly gynecomastia in men, which occurs in approximately 10% of male patients on spironolactone but is minimal with eplerenone. 1, 2, 5

• Eplerenone is more selective for the mineralocorticoid receptor, resulting in fewer progestational and anti-androgenic effects 2, 6
• In clinical studies, patients who developed painful gynecomastia on spironolactone 400 mg had complete resolution after switching to eplerenone 150 mg while maintaining blood pressure control 5
• Sexual side effects such as erectile dysfunction and breast tenderness are significantly reduced with eplerenone 7, 2

Special Populations and Dose Adjustments

For patients with moderate renal impairment (eGFR 30-49 mL/min/1.73 m²), start eplerenone at 25 mg every other day rather than daily. 1, 8

• Eplerenone is contraindicated when eGFR <30 mL/min/1.73 m² 1, 8
• Consider sex-specific factors: males are more prone to gynecomastia with spironolactone, making conversion more beneficial 1

Critical Precautions

Discontinue all potassium supplements when converting to eplerenone due to its potassium-sparing effects. 8

• Avoid concurrent use of potent CYP3A4 inhibitors with eplerenone 4
• Do not combine with both an ACE inhibitor and angiotensin receptor blocker simultaneously 4
• Monitor for side effects including nausea, diarrhea, dizziness, or headache, which can occur in up to 10% of patients 4

Clinical Efficacy Comparison

Both medications demonstrate equivalent blood pressure reduction and clinical outcomes in heart failure, with no significant differences in mortality or hospitalization rates. 5, 9

• In patients with idiopathic hyperaldosteronism, eplerenone normalized blood pressure in 82.4% of patients compared to 76.5% with spironolactone (p=1.00) 5
• A nationwide cohort study of 7,479 HFrEF patients found no differences in the composite outcome of death and heart failure hospitalization between eplerenone and spironolactone (HR 1.02,95% CI 0.82-1.27) 9
• Treatment withdrawal was significantly lower with eplerenone (34%) compared to spironolactone (53%, p<0.001), suggesting better tolerability 9

Common Pitfalls to Avoid

Do not use a 1:1 conversion ratio—this is the most common error and will result in underdosing. The correct ratio is 1:2 (spironolactone:eplerenone). 1

• Do not skip the initial 1-week period at 25 mg eplerenone before dose escalation, as this allows for electrolyte monitoring 4
• Do not forget to discontinue potassium supplements, which can lead to dangerous hyperkalemia 8
• Do not assume hyperkalemia risk is lower with eplerenone—both drugs carry similar hyperkalemia risk and require identical monitoring 2, 5