This page describes pharmacological agents that may have legal restrictions, side effects, and drug interactions in your jurisdiction. Information is for educational research only — consult a clinician before considering any compound.
Eplerenone
Selective mineralocorticoid receptor antagonist — blocks aldosterone's effects on the kidney and vasculature without spironolactone's…
Aliases (5)
Overview
What is Eplerenone?
Eplerenone (Inspra) is a selective mineralocorticoid receptor antagonist FDA-approved for heart failure post-MI and resistant hypertension. More selective than spironolactone with fewer antiandrogen side effects.
Key Benefits
Reduces mortality in heart failure, lowers blood pressure in resistant hypertension, reduces fibrosis and cardiac remodeling. Alternative to spironolactone when gynecomastia or sexual side effects are concerns.
Mechanism of Action
Selectively blocks the mineralocorticoid (aldosterone) receptor in renal tubules, vasculature, and myocardium. Reduces sodium retention and counteracts aldosterone-mediated fibrotic and inflammatory signaling.
Pharmacokinetics
▸Brand options2 known
StatusRx (US), POM (UK), Rx most jurisdictions; not scheduled
Peptide Interactions
Standard HF/HTN backbone. RAS blockade above MR + MR antagonism = strong combined effect. Hyperkalemia risk is real — need K+ monitoring. EPHESUS and EMPHASI…
Standard HF triple-therapy with MRA and ACEi/ARB. Not directly synergistic with eplerenone but the combination is the evidence-based HF regimen.
Useful in volume-overloaded HF; eplerenone offsets loop-induced K+ wasting nicely.
New HF/CKD pillar; combine cleanly with MRA in modern HF protocols.
Mild additive BP drop. Generally fine in healthy users; watch for orthostasis if both started near-simultaneously.
Eplerenone plasma levels can rise 5-10x → severe hyperkalemia / hypotension risk. Contraindicated with strong CYP3A4 inhibitors per FDA label.
Redundant K+-sparing diuresis → hyperkalemia. Don't stack.
additive hyperkalemia.
blunt the antihypertensive effect, increase AKI risk in volume-depleted users, and slightly raise hyperkalemia risk.
Hyperkalemia and AKI risk multiply. Not recommended outside specialist HF settings.
Quality Indicators
Pharmacy-dispensed, intact packaging
Prescription tablets in original sealed packaging from a licensed pharmacy.
Generic vs branded
Generics are usually fine but bioavailability can vary slightly; track if you switch.
Unbranded blister or counterfeit risk
Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.
What to Expect
- Day 1PK-driven acute peak per administration. Verify dose tolerated.
- Week 1Steady-state reached for most daily-dosed pharma.
- Week 2-4Therapeutic effect established; titration window if needed.
- Long-termPeriodic monitoring per drug class (labs, BP, ECG as applicable).
Side Effects & Safety 8
Side Effects
- 1(None reach >10% in standard-dose trials in non-HF populations. In HF trials, hyperkalemia >5.5 mEq/L showed up in ~5-10% depending on baseline renal function and concomitant ACEi/ARB.)
- 2Hyperkalemia (mild, K+ 5.0-5.5) — the headline electrolyte concern, especially with ACEi/ARB co-use, NSAIDs, K+ supplements, or impaired renal function.
- 3Dizziness / mild orthostatic hypotension (first 1-2 weeks)
- 4Increased serum creatinine (small, usually 10-15% rise reflecting hemodynamic effect; not true AKI in most cases)
- 5Mild fatigue
- 6Headache
- 7Diarrhea (uncommon)
- 8Cough (rare; not a class effect like ACEi cough)
When to Stop
- Severe hyperkalemia (K+ >6.0) — especially with renal impairment, ACEi/ARB combination, K+ supplements, or NSAIDs. Can precipitate arrhythmia. Most preventable adverse event in MRA use.
- Acute kidney injury — rare; risk concentrates in volume-depleted patients, bilateral renal artery stenosis, or NSAID co-use.
- Severe hypotension in volume-depleted users.
- Angioneurotic edema — extremely rare; not a typical class effect.
- No fetal toxicity data as severe as ARBs/ACEi but generally avoided in pregnancy.
- Week 1-2: orthostasis, mild dizziness; resolves as volume status stabilizes.
- Week 4 (and after each dose increase): check K+ and creatinine. This is non-negotiable in HF-dose use.
- Ongoing: K+/creatinine every 6-12 months once stable.
- Any new ACEi/ARB/NSAID/K+ supplement added: recheck K+ within 2-4 weeks.
References
EPHESUS 2003 — NEJM, Pitt et al.
n=6,632 post-MI HF, eplerenone 25-50 mg/day; 15% all-cause mortality reduction; the foundational outcome trial.
View StudyEMPHASIS-HF 2011 — NEJM, Zannad et al.
n=2,737 mild HFrEF (NYHA II), eplerenone 25-50 mg/day; 27% reduction in CV death or HF hospitalization.
View StudyInspra (eplerenone) FDA prescribing information
PK, CYP3A4 metabolism, dose-response, contraindications, K+ monitoring schedule.
View StudyTOPCAT 2014 — NEJM, Pitt et al.
spironolactone in HFpEF; primary endpoint missed; relevant context for the MRA-in-HFpEF debate.
View StudyGarthwaite & McMahon 2004 — Eur J Pharmacol, eplerenone selectivity profile
receptor selectivity data underpinning the "no gyno, no anti-androgen" profile vs spironolactone.
View StudyPitt et al. 2008 — review, MRA selectivity and clinical implications
synthesis of eplerenone vs spironolactone clinical trade-offs.
View StudyWADA Prohibited List 2026
confirms K+-sparing MRAs are not currently prohibited (loop and thiazide diuretics ARE; verify class annually).
View StudyHow was your experience with this compound?
Anonymous · one vote per session · results below at 5+ votes.
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