What is the best approach to switching from spironolactone (Aldactone) to eplerenone (Inspra) in a patient with idiopathic hyperaldosteronism currently taking 100mg twice daily (BID) of spironolactone with concomitant potassium dosing?

Switching from High-Dose Spironolactone to Eplerenone in Idiopathic Hyperaldosteronism

For a patient with idiopathic hyperaldosteronism on spironolactone 100mg BID (200mg total daily), switch to eplerenone 100mg BID (200mg total daily) as the equivalent dose, discontinue concomitant potassium supplementation immediately, and monitor serum potassium and creatinine at 1 week and 4 weeks post-switch. 1, 2

Dose Conversion Strategy

The conversion ratio is approximately 1:1 for total daily dose in idiopathic hyperaldosteronism. 2

• In the only prospective randomized trial comparing these agents specifically in idiopathic hyperaldosteronism, patients received spironolactone 25mg BID or eplerenone 25mg BID as starting doses, with titration up to 400mg spironolactone or 200mg eplerenone daily 2
• This 2:1 maximum dose ratio reflects eplerenone's lower mineralocorticoid receptor binding affinity, but in clinical practice for idiopathic hyperaldosteronism, a 1:1 conversion from your current 200mg spironolactone to 200mg eplerenone (100mg BID) is appropriate 2
• Eplerenone demonstrated equivalent blood pressure control (82.4% vs 76.5% achieving BP <140/90) with faster systolic BP reduction in idiopathic hyperaldosteronism patients 2

Critical Pre-Switch Requirements

Check baseline potassium and creatinine before initiating eplerenone. 3, 1

• Eplerenone is contraindicated if serum potassium >5.5 mEq/L or creatinine clearance ≤30 mL/min 3
• For hypertension indication specifically, eplerenone is contraindicated if creatinine >2.0 mg/dL in males or >1.8 mg/dL in females 3
• Discontinue all potassium supplements immediately when switching, as eplerenone maintains potassium-sparing effects 1, 4

Dosing Schedule

Start eplerenone at 100mg twice daily (your equivalent dose) if renal function and potassium are acceptable. 2

• The FDA label indicates eplerenone often requires twice-daily dosing for adequate BP lowering, making BID dosing appropriate for your high total daily requirement 5
• If eGFR is 30-49 mL/min/1.73m², consider starting at 50mg BID and titrating up 1, 3
• Maximum approved dose is 100mg daily for heart failure, but up to 200mg daily has been studied in idiopathic hyperaldosteronism 2

Monitoring Protocol

Follow intensive early monitoring to detect hyperkalemia or renal dysfunction. 1, 6

• Check potassium and creatinine at 1 week and 4 weeks after the switch 1
• After achieving stable dosing, monitor at 1,2,3, and 6 months, then every 6 months thereafter 1
• In the idiopathic hyperaldosteronism trial, mild hyperkalemia occurred in 3/17 patients on eplerenone (at 150mg daily) versus 2/17 on spironolactone (at 400mg daily), showing similar risk profiles 2

Management of Hyperkalemia

If potassium rises to >5.5 mmol/L, reduce eplerenone dose by 50% (to 50mg BID). 1, 5

• If potassium reaches >6.0 mmol/L, stop eplerenone immediately and monitor closely 1, 5
• Consider increasing any concomitant loop diuretic dose if volume status permits 4
• Never combine eplerenone with ACE inhibitor + ARB together, as this dramatically increases hyperkalemia risk 5, 7

Management of Worsening Renal Function

If creatinine rises to >220 μmol/L (2.5 mg/dL), halve the eplerenone dose to 50mg BID. 5, 7

• If creatinine rises to >310 μmol/L (3.5 mg/dL), stop eplerenone immediately 5, 7
• Conversely, if creatinine is stable or decreasing, no dose adjustment is needed 7

Advantages of Switching

Eplerenone eliminates the anti-androgenic side effects that occur with spironolactone. 2, 6

• In the idiopathic hyperaldosteronism trial, 2 patients developed bilateral painful gynecomastia on spironolactone 400mg, which resolved after switching to eplerenone 150mg daily while maintaining BP control 2
• Eplerenone's selectivity for the mineralocorticoid receptor (versus spironolactone's cross-reactivity with androgen and progesterone receptors) reduces risk of gynecomastia, erectile dysfunction, and menstrual irregularities 6, 8
• Efficacy for blood pressure control and potassium normalization is equivalent between the two agents in idiopathic hyperaldosteronism 2

Common Pitfalls to Avoid

Do not continue potassium supplements after switching to eplerenone. 1, 4

• Continuing potassium supplementation with eplerenone creates severe hyperkalemia risk, as both are potassium-sparing 1
• Avoid NSAIDs and COX-2 inhibitors, which worsen renal function and increase hyperkalemia risk with aldosterone antagonists 7
• Do not use strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin) concomitantly with eplerenone, as this is contraindicated 3
• With moderate CYP3A inhibitors (verapamil, erythromycin, fluconazole), do not exceed eplerenone 50mg daily 3, 5
• Instruct the patient to temporarily stop eplerenone during episodes of diarrhea, vomiting, or dehydration 7

Special Considerations for Idiopathic Hyperaldosteronism

Idiopathic hyperaldosteronism typically requires higher aldosterone antagonist doses than heart failure indications. 2, 9

• Your current 200mg daily spironolactone dose is within the therapeutic range of 25-400mg daily for idiopathic hyperaldosteronism 9
• Eplerenone up to 200mg daily has been studied specifically in this population 2
• If BP remains uncontrolled on maximum eplerenone monotherapy, consider adding hydrochlorothiazide 12.5mg daily rather than further increasing eplerenone 2
• The combination of aldosterone antagonist with thiazide diuretic maximizes efficacy and paradoxically reduces hyperkalemia risk by enhancing potassium excretion 10