Eplerenone Dosing for Primary Aldosteronism
For primary aldosteronism, eplerenone should be initiated at 50-100 mg daily and titrated up to 100-300 mg daily based on blood pressure response and potassium levels. 1, 2
Initial Dosing Strategy
- Start eplerenone at 50-100 mg once daily for bilateral primary aldosteronism (idiopathic hyperaldosteronism), which represents the majority of cases requiring medical management 1, 3
- This starting dose is substantially higher than the 25 mg daily used for heart failure, reflecting the different pathophysiology and treatment goals in primary aldosteronism 4, 1
- The lower heart failure doses (25-50 mg daily) are inadequate for treating the autonomous aldosterone excess seen in primary aldosteronism 4, 2
Dose Titration and Target
- Titrate eplerenone up to 100-300 mg daily using a titration-to-effect approach based on blood pressure control and potassium normalization 2
- In clinical trials specifically for primary aldosteronism, eplerenone was dosed at 100-300 mg once daily to achieve adequate mineralocorticoid receptor blockade 2
- Maximum doses may reach 300 mg daily in refractory cases, though most patients respond to 100-200 mg daily 2
Important Clinical Context
Spironolactone is generally more effective than eplerenone for primary aldosteronism. In a head-to-head trial, spironolactone reduced diastolic blood pressure by 12.5 mmHg compared to only 5.6 mmHg with eplerenone (P<0.001), despite using higher doses of eplerenone 2. However, eplerenone causes significantly less gynecomastia in men (4.5% vs 21.2%) and breast pain in women (0% vs 21.1%) 2.
- Eplerenone is primarily reserved for patients who cannot tolerate spironolactone due to sexual side effects, not as first-line therapy 1, 2
- Spironolactone remains the preferred first-line agent at 50-100 mg daily, titrated up to 300-400 mg daily if necessary 1, 3
Monitoring Requirements
- Check potassium and creatinine within 2-3 days and again at 7 days after initiation or dose increases 4
- Continue monthly monitoring for the first 3 months, then every 3 months thereafter 4
- If potassium rises above 5.5 mEq/L, halve the dose or switch to alternate-day dosing 4
- Discontinue if potassium exceeds 6.0 mEq/L or creatinine rises above 2.5 mg/dL in men or 2.0 mg/dL in women 4
Critical Pitfall to Avoid
Do not use heart failure dosing protocols for primary aldosteronism. The 25-50 mg daily doses recommended for heart failure are insufficient to overcome the autonomous aldosterone production in primary aldosteronism and will result in inadequate blood pressure control 4, 1, 2. Primary aldosteronism requires 2-6 times higher doses to achieve therapeutic effect 2.