Eplerenone: Selective Mineralocorticoid Receptor Antagonist
Eplerenone (Inspra) is a selective mineralocorticoid receptor antagonist (MRA) with high selectivity for aldosterone receptors compared to spironolactone. Its selectivity reduces the sex-hormone-related side effects (gynaecomastia, menstrual irregularities) that limit spironolactone use.
Approved for heart failure after myocardial infarction (EPHESUS trial) and as add-on therapy in hypertension. Also used in primary hyperaldosteronism and resistant hypertension.
Mechanism of Action
Eplerenone competitively blocks aldosterone at the mineralocorticoid receptor, preventing sodium retention, potassium loss, and fibrotic cardiac/vascular remodelling. Unlike spironolactone, it has minimal affinity for androgen and progesterone receptors.
Indications & Use
Heart failure with reduced ejection fraction (HFrEF) following acute myocardial infarction (with ACE inhibitor or ARB), stable chronic HFrEF, hypertension (add-on), primary hyperaldosteronism.
Dosage
Post-MI heart failure: start 25 mg once daily, titrate to 50 mg/day if tolerated. Hypertension: 50 mg once daily (or twice daily if insufficient). Contraindicated if GFR <30 mL/min or K+ >5.5 mmol/L.
Side Effects
Hyperkalaemia (most important — potentially life-threatening). Dizziness, fatigue, diarrhoea. Unlike spironolactone: no gynaecomastia or menstrual irregularities.
Drug Interactions
ACE inhibitors/ARBs: additive hyperkalaemia risk. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): contraindicated — markedly increase eplerenone levels. NSAIDs: reduce antihypertensive effect.
Contraindications
K+ >5.0 mmol/L at initiation, GFR <30 mL/min (post-MI HF) or <50 mL/min (hypertension), type 2 diabetes with proteinuria, concomitant strong CYP3A4 inhibitors, hypersensitivity.
Frequently Asked Questions
Why is potassium monitoring so important with eplerenone?
Eplerenone blocks aldosterone, increasing potassium retention. Hyperkalaemia (K+ >5.5 mmol/L) is a serious complication that can cause fatal cardiac arrhythmias. Check potassium before starting and regularly during treatment.
How does eplerenone differ from spironolactone?
Eplerenone is more selective for mineralocorticoid receptors with minimal anti-androgenic activity, so it does not cause gynaecomastia or sexual side effects. However, it is less potent and more expensive than spironolactone.
Can eplerenone be combined with ACE inhibitors?
Yes — this is the recommended combination for HFrEF. However, close potassium monitoring is essential, as the combination significantly increases hyperkalaemia risk.
References
- EPHESUS Trial (eplerenone post-MI)
- ESC Heart Failure Guidelines 2021
- EMA product information Inspra
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.