Spironolactone (Aldactone, CaroSpir)
Spironolactone is a widely used steroidal MRA with major cardiovascular, renal, endocrine, and dermatologic applications. The RALES trial established survival benefit in HFrEF; PATHWAY-2 supported its role in resistant hypertension.
- Mechanism of action
- Steroidal MR antagonist with additional androgen-receptor and progesterone-receptor activity; blocks aldosterone-mediated sodium retention and potassium secretion.
- Administration route
- Oral, once or twice daily
FDA-approved indications (2026)
Heart failure with reduced ejection fraction
Reduction of morbidity and mortality in NYHA class III–IV HFrEF (RALES).
Resistant hypertension
4th-line add-on per ACC/AHA 2017 hypertension guideline (PATHWAY-2).
Primary hyperaldosteronism
Medical therapy when surgery is not appropriate.
Edema
Cirrhosis, nephrotic syndrome, and refractory CHF.
Off-label
PCOS hirsutism, acne vulgaris in women, transgender feminizing hormone therapy.
Dosing: adult, renal, and hepatic
| Population | Dose |
|---|---|
| HFrEF | Start 12.5–25 mg PO daily; titrate to 25–50 mg daily with potassium ≤5.0 and eGFR ≥30. |
| Resistant hypertension | 25–50 mg PO daily. |
| Edema | 25–200 mg/day in divided doses. |
| Renal impairment | Avoid if eGFR <30 or K+ >5.0. Conservative dosing and close monitoring in eGFR 30–60. |
| Hepatic impairment | Use cautiously; monitor electrolytes and consider dose reduction. |
Contraindications and boxed warnings
Contraindications
- Hyperkalemia.
- Addison disease.
- Concurrent eplerenone.
- Anuria / acute renal insufficiency.
2026 guideline and pivotal trial position
ACC/AHA/HFSA 2022/2026 guidelines retain MRAs as one of the four HFrEF pillars. In resistant hypertension, 2017 ACC/AHA recommendations with PATHWAY-2 data support spironolactone as 4th-line add-on. Endocrine Society (2016, reaffirmed) and AACE guidance support spironolactone for medical therapy of primary aldosteronism.
RALES
30% relative risk reduction in all-cause mortality in severe HFrEF.
TOPCAT
Neutral overall in HFpEF; regional analyses suggest benefit in selected populations.
PATHWAY-2
Spironolactone superior to doxazosin or bisoprolol as 4th-line in resistant hypertension.
Cross-system reasoning
Spironolactone's anti-androgenic activity makes it a bridge across cardiology, endocrinology, dermatology, and gender-affirming care. The same prescription protects a patient with HFrEF, lowers BP in resistant hypertension, and treats hirsutism in PCOS. Safety monitoring is dominated by potassium and creatinine; gynecomastia is a common reason for switching to finerenone or eplerenone in male patients. Combine cautiously with ACE-I/ARB, trimethoprim-sulfamethoxazole, and NSAIDs.
Key references
- FDA Label — Aldactone
- Pitt B, et al. RALES (NEJM 1999)PMID: 10471456
- Williams B, et al. PATHWAY-2 (Lancet 2015)PMID: 26414968
Related clinical reading
Explore Spironolactone in Ailva
Ailva is a free clinical intelligence platform for NPI-verified US physicians. Get evidence-based answers with verified citations from 16M+ indexed papers — plus free CME credits.
This reference is for US-licensed physicians and is not a substitute for the full FDA prescribing information. Dosing in special populations, drug interactions, and emerging safety information should be verified against the current manufacturer label and society guidelines before prescribing.