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Selective Mineralocorticoid Receptor Antagonist Pregnancy: Avoid — limited data. Animal studies suggest fetal harm at high doses. Seek specialist advice.

Eplerenone

Brand names: Inspra

Adult dose

Dose: Post-MI heart failure (NICE-approved): 25mg OD initially; increase to 50mg OD within 4 weeks if tolerated and potassium <5.0 mmol/L. Primary hyperaldosteronism (Conn's syndrome — pre-surgical or inoperable): 25–100mg OD, titrated to blood pressure and potassium. Heart failure with reduced ejection fraction (HFrEF): 25mg OD increasing to 50mg OD.
Route: Oral
Frequency: Once daily
Max: 50mg OD (cardiac indications); 100mg OD (hyperaldosteronism under specialist supervision)
More selective than spironolactone — fewer anti-androgenic and progestogenic side effects (no gynaecomastia, menstrual disturbance). Preferred over spironolactone in men (avoids gynaecomastia) and post-MI. Check potassium before starting and within 1 week of initiation — hyperkalaemia risk.

Paediatric dose

Route: Oral
Frequency: Once daily
Max: Not applicable
Not licensed under 18 years. Seek specialist paediatric cardiology/endocrinology opinion.

Dose adjustments

Renal

eGFR <30: avoid (hyperkalaemia risk). eGFR 30–50: use with extreme caution, close potassium monitoring. Post-MI indication: do not initiate if serum creatinine >220 micromol/L (men) or >177 micromol/L (women).

Hepatic

Severe hepatic impairment: avoid.

Clinical pearls

  • EPHESUS trial: eplerenone 50mg OD reduced all-cause mortality by 15% post-MI with LV dysfunction — now standard of care in this setting (NICE)
  • Hyperkalaemia is the key risk — potassium >5.5 mmol/L: halve dose; >6.0 mmol/L: stop immediately
  • Advantage over spironolactone: no gynaecomastia, no menstrual irregularity (highly selective for mineralocorticoid receptor vs. androgen/progesterone receptors)
  • Primary hyperaldosteronism (Conn's): eplerenone or spironolactone used pre-operatively or if unilateral adrenalectomy not possible — controls hypertension and hypokalaemia

Contraindications

  • eGFR <30
  • Potassium >5.0 mmol/L at initiation
  • Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir — markedly increase eplerenone exposure)
  • Concomitant potassium-sparing diuretics or potassium supplements

Side effects

  • Hyperkalaemia (most important — potentially fatal)
  • Hypotension
  • Dizziness
  • Diarrhoea
  • Elevated creatinine (mild)
  • Gynaecomastia (much less than spironolactone — <1%)

Interactions

  • Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) — contraindicated; 5-fold increase in eplerenone AUC
  • ACE inhibitors, ARBs — additive hyperkalaemia; monitor potassium closely
  • NSAIDs — reduce antihypertensive effect; increase renal impairment risk
  • Lithium — eplerenone may increase lithium levels

Monitoring

  • Potassium (before starting; 1 week after initiation or dose change; then monthly for 3 months; then 3–6 monthly)
  • eGFR and creatinine
  • Blood pressure

Reference: BNFc; BNF 90; NICE TA254 (Eplerenone post-MI); EPHESUS Trial (NEJM 2003). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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