Can a patient be switched from spironolactone to eplerenone?

Switching from Spironolactone to Eplerenone

Yes, patients can be switched from spironolactone to eplerenone, particularly when patients experience side effects like gynecomastia or breast discomfort from spironolactone. 1

Indications for Switching

• Male patients treated with spironolactone who develop breast discomfort or gynecomastia should be considered for switching to eplerenone 1
• Eplerenone is specifically designed to avoid the hormone-associated side effects of spironolactone due to its selective binding to mineralocorticoid receptors 2, 3
• Spironolactone has been associated with gynecomastia in approximately 10% of male patients (compared to placebo in RALES trial), while this side effect is infrequent with eplerenone 1, 4

Conversion Protocol

• When switching, start eplerenone at 25 mg once daily as the equivalent starting dose to spironolactone 25 mg 1, 5
• The target dose for eplerenone is 50 mg once daily, similar to the target dose of spironolactone 1
• Consider dose up-titration after 4-8 weeks, aiming for the evidence-based target dose of eplerenone 50 mg once daily 1

Monitoring Requirements

• Check renal function and serum electrolytes before initiating eplerenone 6
• Re-check renal function and serum electrolytes at 1 and 4 weeks after starting treatment 1
• Continue monitoring at 1,2,3, and 6 months after achieving maintenance dose, and every 6 months thereafter 1
• If potassium rises above 5.5 mmol/L, halve the dose and monitor blood chemistry closely 1
• If potassium rises to >6.0 mmol/L or creatinine to >310 μmol/L (3.5 mg/dL), stop eplerenone immediately 1

Efficacy Considerations

• Both medications have demonstrated efficacy in treating heart failure, though there may be some differences in potency 7, 8
• In the EPHESUS trial, eplerenone led to a 15% relative risk reduction in death, while in RALES, spironolactone showed a 30% relative risk reduction 1, 4
• For resistant hypertension, spironolactone may have greater antihypertensive effects than eplerenone at comparable doses 7, 8

Contraindications and Cautions

• Eplerenone is contraindicated in patients with:
  • Serum potassium >5.5 mEq/L at initiation 6
  • Creatinine clearance ≤30 mL/min 6
  • Concomitant use of strong CYP3A inhibitors 6
• For hypertension treatment, additional contraindications include:
  • Type 2 diabetes with microalbuminuria 6
  • Serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females 6
  • Creatinine clearance <50 mL/min 6
• Importantly, spironolactone and eplerenone should not be used concomitantly as this is specifically contraindicated 9

Common Pitfalls to Avoid

• Failure to monitor potassium and renal function after switching can lead to hyperkalemia 10, 4
• The risk of hyperkalemia is higher in patients with impaired renal function, diabetes, and those concomitantly treated with ACE inhibitors or ARBs 10, 6
• Patients should be advised to avoid NSAIDs not prescribed by a physician and salt substitutes high in potassium 1
• The triple combination of an ACE inhibitor, ARB, and mineralocorticoid receptor antagonist is NOT recommended due to increased risk of hyperkalemia 1