Generic Name

Eplerenone

Mechanism

Eplerenone is a *selective mineralocorticoid receptor antagonist* (MRA).
• It competitively blocks aldosterone binding to the mineralocorticoid receptor in the distal nephron and vasculature.
• This inhibition reduces sodium reabsorption, potassium excretion, and fibrotic/collagen deposition.
• Resulting actions: lower blood pressure, decreased preload/afterload, and attenuation of cardiac remodeling in heart failure (HF).
• Because of minimal affinity for androgen or progesterone receptors, eplerenone rarely causes endocrine side effects that are common with spironolactone.

Pharmacokinetics

• Bioavailability: ~40‑45 % after oral dosing (rapid absorption).
• Peak plasma concentration (Tmax): 1–2 h post‑dose.
• Half‑life: 4–6 h (steady‑state achieved within 10–14 days).
• Metabolism: Primarily hepatic via CYP3A4 and CYP2C9 → polar metabolites.
• Elimination: Renal (≈35 %) and biliary; not a substrate for P‑glycoprotein.
• Drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) ↑ plasma levels; strong inducers (e.g., rifampicin) ↓ efficacy.

Indications

• Heart failure (post‑myocardial infarction): Adjunct to ACEI/ARB + diuretic; improves survival.
• Hypertension: Add-on therapy when ACEI/ARB alone is insufficient.
• Secondary hyperaldosteronism: e.g., in chronic kidney disease (CKD) or cirrhosis.
• Persistent hyperkalemia risk mitigation in patients on MRAs when combined with ACEI/ARB.

Contraindications

• Contraindications:
• Severe hyperkalemia (serum K⁺ > 5.0 mmol/L).
• Advanced renal dysfunction (CrCl 5.5 mmol/L.
• Renal function deterioration: Dose adjustment required; avoid in CrCl < 30 mL/min unless closely monitored.
• Drug interactions: Avoid concomitant use with other potassium‑sparing agents or CYP3A4 inhibitors.

Dosing

• Take with or without food; food does not alter absorption.
• Avoid excessive alcohol consumption due to additive hypotensive effect.

Adverse Effects

Common (≥ 1 %):
• Hyperkalemia (most serious).
• Hypotension, dizziness (especially after the first dose).
• Headache, fatigue, nausea, diarrhea.
• Mild renal function alteration (serum creatinine rise ≤ 0.3 mg/dL).

Serious adverse events (rare):
• Life‑threatening hyperkalemia (K⁺ > 6.5 mmol/L).
• Acute renal failure (esp. in pre‑existing CKD).
• Severe hypotension with syncope.
• Allergic reactions (rash, angioedema).

Monitoring

• Baseline: Serum K⁺, creatinine, BUN, electrolytes, BP, HR.
• During therapy:
• Serum K⁺ & creatinine: every 3–4 wk for first 3 mo, then 3 mo intervals.
• BP & weight: bi‑weekly first month, then monthly.
• Electrolyte panels if patient develops GI losses or on diuretics.
• Adverse effect signs: Report sudden weakness, palpitations, or visual changes.

Clinical Pearls

• Gynecomastia Myth: Because eplerenone lacks affinity for sex hormone receptors, it is 5–10× safer than spironolactone for endocrine side‑effect avoidance.
• Heart‑failure “Triple‑combination”: When added to ACEI/ARB + diuretic, eplerenone confers mortality benefit regardless of baseline ejection fraction (< 35 %).
• Dose Splitting in CKD: Splitting the daily dose (e.g., 25 mg bid) can mitigate peak‑tolerability issues while maintaining efficacy.
• Drug‑Drug Interaction Safety Net: Pairing eplerenone with ketoconazole or clarithromycin *must* trigger a 50 % dose reduction or temporary hold due to CYP3A4 inhibition.
• Pregnancy Caution: Though a category C drug, some clinicians use eplerenone for maternal hypertension when no alternatives exist; discuss off‑label risks thoroughly.

--
• Remember: Regular potassium checks are the single most critical safety check when prescribing eplerenone.