What is the equivalent dose of spironolactone (aldosterone antagonist) and eplerenone (selective aldosterone receptor antagonist)?

Equivalent Dosing of Spironolactone and Eplerenone

The equivalent dosing ratio between spironolactone and eplerenone is approximately 1:2, with 25 mg of spironolactone being equivalent to 50 mg of eplerenone in terms of mineralocorticoid receptor antagonism. 1

Dosing Equivalence and Clinical Applications

• The standard maintenance dose of spironolactone is 25-50 mg once daily, which is equivalent to eplerenone 50-100 mg once daily 1
• In heart failure treatment, the target dose for both medications is spironolactone 50 mg once daily or eplerenone 50 mg once daily 1
• Initial dosing typically starts at spironolactone 25 mg daily or eplerenone 25 mg daily, with subsequent titration based on clinical response and laboratory parameters 1
• For patients with renal impairment (eGFR 30-49 mL/min/1.73 m²), the starting dose should be reduced to spironolactone 12.5-25 mg once daily or eplerenone 25 mg every other day 1

Comparative Efficacy

• Spironolactone demonstrates greater antihypertensive efficacy compared to eplerenone at equivalent doses, with studies showing a 6.9 mmHg greater reduction in diastolic blood pressure with spironolactone 2
• In resistant hypertension, spironolactone has been established as the more effective add-on therapy compared to eplerenone 3
• The greater potency of spironolactone is likely due to its non-selective binding profile and longer half-life compared to eplerenone 4, 3

Side Effect Profiles and Considerations

• The primary advantage of eplerenone over spironolactone is its improved side effect profile, particularly regarding anti-androgenic effects 4, 5
• Spironolactone is associated with significant rates of:
  • Gynecomastia in men (10-21% vs. 4.5% with eplerenone) 1, 2
  • Breast tenderness in women (21% vs. 0% with eplerenone) 2
  • Sexual dysfunction 3
• Eplerenone is specifically indicated as an alternative when patients develop breast discomfort or enlargement on spironolactone 1
• Both medications carry similar risks of hyperkalemia and renal dysfunction, requiring the same monitoring protocols 1, 4

Monitoring Requirements (Same for Both Medications)

• Check renal function and serum electrolytes before initiation 1
• Recheck renal function and electrolytes at 1 and 4 weeks after starting treatment 1
• Monitor monthly for the first 3 months, then every 3-6 months thereafter 1
• Discontinue or reduce dosage if:
  • Potassium rises above 5.5 mmol/L 1
  • Creatinine exceeds 2.5 mg/dL in men or 2.0 mg/dL in women 1

Clinical Pearls

• When switching from spironolactone to eplerenone due to side effects, double the dose (e.g., spironolactone 25 mg to eplerenone 50 mg) to maintain equivalent efficacy 4, 3
• Eplerenone has fewer drug interactions due to its more selective receptor binding profile 5
• Both medications should be avoided in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or baseline potassium >5.0 mmol/L 1
• The routine triple combination of ACE inhibitors, ARBs, and aldosterone antagonists should be avoided due to increased risk of hyperkalemia 1