When to choose Aldactone (spironolactone) over spironolactone?

When to Choose Eplerenone Over Spironolactone

Eplerenone should be chosen over spironolactone in men who experience breast discomfort and/or enlargement (gynecomastia) while on spironolactone therapy. 1

Understanding the Difference

Both spironolactone (Aldactone) and eplerenone are mineralocorticoid receptor antagonists (MRAs) that block aldosterone's actions. While they have similar clinical efficacy in treating heart failure and hypertension, they differ in their side effect profiles due to their pharmacological properties:

• Spironolactone: Has higher affinity for progesterone, androgen, and glucocorticoid receptors 2
• Eplerenone: Has lower affinity for these non-mineralocorticoid receptors 2

Specific Indications for Choosing Eplerenone

1. Hormone-Related Side Effects

• Primary indication: Men experiencing breast discomfort and/or enlargement (gynecomastia) on spironolactone 1
• Gynecomastia occurs in approximately 10% of men taking spironolactone compared to placebo 1
• This side effect is infrequent with eplerenone due to its greater selectivity for mineralocorticoid receptors 2

2. Post-Myocardial Infarction

• Eplerenone has specific evidence in patients 3-14 days after acute MI with LVEF ≤40% and heart failure or diabetes 1
• The EPHESUS trial demonstrated a 15% relative risk reduction in death with eplerenone in this population 1

Monitoring Requirements

Both medications require identical monitoring:

• Check renal function and serum electrolytes before starting
• Recheck at 1 and 4 weeks after initiation
• Monitor at 1,2,3, and 6 months after achieving maintenance dose
• Continue monitoring every 6 months thereafter 1

Potential Adverse Effects Management

For Both Medications:

Hyperkalemia

• If K+ >5.5 mmol/L: Halve dose and monitor closely
• If K+ ≥6.0 mmol/L: Stop medication immediately 1

Worsening Renal Function

• If creatinine rises to >220 μmol/L (2.5 mg/dL): Halve dose
• If creatinine rises to >310 μmol/L (3.5 mg/dL): Stop medication 1

Dosing Considerations

• Starting dose for both: 25 mg once daily
• Target dose for both: 50 mg once daily 1
• Eplerenone often requires twice-daily dosing for adequate blood pressure lowering 1
• For spironolactone, doses >50 mg/day do not appear to produce further reductions in blood pressure 3

Common Pitfalls and Caveats

1. Hyperkalemia risk: Both medications can cause hyperkalemia, which appears more frequent with spironolactone at recommended doses 2

2. Real-world side effects: Side effects in clinical practice are more common than reported in clinical trials. In one study, spironolactone withdrawal rate was 25%, with hyperkalemia (17.1%) and renal function deterioration (14.5%) being the most common reasons 4

3. Cost considerations: Eplerenone is typically more expensive than spironolactone, which may affect medication adherence

4. Monitoring frequency: Inadequate monitoring of electrolytes and renal function is a common pitfall that can lead to serious complications

5. Dosing frequency: Eplerenone may require twice-daily dosing for optimal blood pressure control, potentially affecting adherence 1

By following these guidelines, clinicians can make appropriate decisions about when to choose eplerenone over spironolactone to optimize patient outcomes while minimizing adverse effects.