What are the clinical differences between Eplerenone (generic name) and Spironolactone (generic name), both mineralocorticoid receptor antagonists (MRAs)?

From the Guidelines

Eplerenone and spironolactone are both potassium-sparing diuretics and mineralocorticoid receptor antagonists, but they differ in several important clinical aspects, with eplerenone being preferred in men concerned about gynecomastia or sexual dysfunction, and in women experiencing menstrual irregularities with spironolactone, due to its more selective binding to mineralocorticoid receptors and lower risk of hormonal side effects 1. The main differences between eplerenone and spironolactone lie in their selectivity for mineralocorticoid receptors and their side effect profiles. Spironolactone is more potent and less selective, binding to androgen and progesterone receptors, which leads to its common side effects of gynecomastia, breast tenderness, menstrual irregularities, and decreased libido 1.

• Eplerenone is more selective for mineralocorticoid receptors, resulting in fewer hormonal side effects but requiring higher doses (typically 25-50 mg daily compared to spironolactone's 12.5-100 mg daily) 1.
• Spironolactone is generally less expensive and more widely available, making it a first-line choice for many conditions including heart failure, resistant hypertension, and hyperaldosteronism 1.
• Both medications require monitoring of potassium levels and renal function, with similar contraindications in severe renal impairment (eGFR <30 mL/min) and hyperkalemia 1. The choice between these medications should be based on patient-specific factors including sex, comorbidities, cost considerations, and potential side effect profiles, with eplerenone being a better option for patients who are concerned about the hormonal side effects associated with spironolactone 1.

From the Research

Clinical Differences

The clinical differences between Eplerenone and Spironolactone, both mineralocorticoid receptor antagonists (MRAs), are as follows:

• Eplerenone is a more selective blocker of the mineralocorticoid receptor than Spironolactone, which results in fewer antiandrogenic side-effects 2, 3, 4, 5.
• Spironolactone has a greater antihypertensive effect than Eplerenone in patients with hypertension associated with primary aldosteronism 2.
• Eplerenone is associated with a lower incidence of male gynaecomastia and female mastodynia compared to Spironolactone 2, 3, 6, 5.
• Both agents can cause hyperkalemia, but the effect appears to be greater with Spironolactone when administered at recommended doses 3, 4, 5.

Efficacy and Tolerability

The efficacy and tolerability of Eplerenone and Spironolactone are:

• Eplerenone has been shown to be beneficial in treating hypertension and post-myocardial infarction heart failure, with a similar antihypertensive efficacy to other agents 3, 4.
• Spironolactone is established as the most effective add-on anti-aldosterone therapy in resistant hypertension, but Eplerenone is a promising alternative, especially for patients who develop anti-androgenic side effects 6.
• The choice of agent should be based on individual patient issues, such as the nature of heart failure and patient concerns about adverse events 5.

Side Effects

The side effects of Eplerenone and Spironolactone are:

• Spironolactone is associated with dose-dependent sexual side effects, including gynecomastia and menstrual irregularities 2, 3, 6, 5.
• Eplerenone has a lower incidence of sexual side effects compared to Spironolactone, but can still cause hyperkalemia 3, 4, 5.
• Both agents require close monitoring of potassium levels and renal function during administration 6, 4, 5.