Spironolactone is an oral drug that blocks the hormone aldosterone. Aldosterone tells the kidney to hold on to sodium and water and to excrete potassium, so blocking it makes the kidney lose salt and water while retaining potassium. That makes spironolactone a “potassium-sparing” diuretic. Pfizer sells it as Aldactone, first approved by the FDA in 1960, and it is widely available as a generic.
It is approved for heart failure, hypertension, edema from cirrhosis or nephrotic syndrome, and primary hyperaldosteronism. It also blocks the androgen receptor, which is why it is used off-label for acne and excess hair growth in women, and why men taking it can develop breast enlargement (gynecomastia). Its single most important risk is a high blood potassium level (hyperkalemia), which can cause dangerous heart rhythms.
This page summarizes what the FDA label, the major clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Mineralocorticoid (aldosterone) receptor antagonist; potassium-sparing diuretic |
| Brands / approval | Aldactone (Pfizer), NDA 012151, approved January 21, 1960; CaroSpir oral suspension, NDA 209478; generics |
| Route | Oral (tablets; suspension) |
| Strengths | 25, 50 and 100 mg tablets; suspension 25 mg/5 mL |
| Labeled doses | 25–50 mg/day (heart failure) up to 100–400 mg/day (before surgery for primary hyperaldosteronism) |
| Half-life (label) | Parent drug 1.4 h; active metabolites 13.8–16.5 h (canrenone 16.5 h) |
| Key off-target effect | Binds the androgen receptor (antiandrogen) |
| Main risk | Hyperkalemia; gynecomastia is the most common adverse reaction |
| US status | Prescription only |
| WADA status | Prohibited at all times (S5, diuretics and masking agents) |
What it is
Spironolactone is a synthetic steroid. Its chemical name is 17-hydroxy-7α-mercapto-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone acetate (FDA label). Its formula is C₂₄H₃₂O₄S and its molecular weight is 416.6 g/mol (PubChem). It is practically insoluble in water.
The label describes its main mechanism this way: spironolactone and its active metabolites compete with aldosterone for its receptor at the sodium-potassium exchange site in the distal part of the kidney tubule. The result is more sodium and water lost in the urine while potassium is kept. This one mechanism explains both its diuretic and blood-pressure-lowering effects, and its main danger, high potassium.
The antiandrogen effect
Spironolactone also binds the androgen receptor, the receptor that testosterone and dihydrotestosterone (DHT) act on. In tissue from human prostate and foreskin, spironolactone competitively blocked DHT binding with an affinity about 10 times lower than DHT’s own (Rifka et al., JCEM 1978). Rat studies found the same: spironolactone was about 20 times less effective than DHT at displacing it from the receptor, and it did not inhibit 5α-reductase (Corvol et al., Endocrinology 1975).
A 1976 clinical conference reviewed several mechanisms that may combine to cause its estrogen-like side effects, such as impotence and gynecomastia in men and menstrual irregularity in women (Ann Intern Med 1976):
- blocking androgens at the target tissue;
- effects on steroid production in the testes and adrenal glands;
- raised gonadotropin (LH and FSH) levels, shown in children.
The current label confirms the receptor effect in a practical way: spironolactone “binds to the androgen receptor and may increase prostate-specific antigen (PSA) levels” in men on abiraterone for prostate cancer, so the two are not recommended together.
Pharmacokinetics
Spironolactone itself is short-lived. Most of its effect comes from metabolites that last much longer. From the Aldactone label:
| Parameter | Value |
|---|---|
| Time to peak, spironolactone | 2.6 h |
| Time to peak, canrenone | 4.3 h |
| Effect of food | AUC (total exposure) about 95% higher with food |
| Protein binding | Over 90% (parent and metabolites) |
| Half-life, spironolactone | 1.4 h |
| Half-life, canrenone | 16.5 h |
| Half-life, 7-α-thiomethyl spirolactone (TMS) | 13.8 h |
| Half-life, 6-β-hydroxy-TMS (HTMS) | 15 h |
| Excretion | Mainly urine, then bile |
Because food nearly doubles absorption, the label says it may be taken with or without food but consistently in the same way. In people with cirrhosis and ascites, the half-life is longer and clearance of the drug and its metabolites is reduced.
The CaroSpir suspension is not interchangeable with tablets. Its label states that, for the same dose, it gives 15–37% higher serum concentrations than Aldactone tablets, and that it should not be used for doses above 100 mg (CaroSpir label).
Approved medical use
The Aldactone label lists four indications and starting doses:
| Indication | Labeled dosing |
|---|---|
| Heart failure (NYHA class III–IV, reduced ejection fraction), to increase survival and reduce hospitalization | 25 mg once daily if potassium is ≤5.0 mEq/L and eGFR is over 50 mL/min/1.73 m²; may increase to 50 mg/day; 25 mg every other day if eGFR is 30–50 mL/min/1.73 m² or if hyperkalemia occurs |
| Hypertension, as add-on therapy | 25–100 mg/day, single or divided; titrate at 2-week intervals; doses over 100 mg/day generally add no further benefit |
| Edema from cirrhosis or nephrotic syndrome | Usually 100 mg/day (range 25–200 mg); in cirrhosis, start in hospital and titrate slowly |
| Primary hyperaldosteronism | 100–400 mg/day before surgery; lowest effective dose for long-term use when surgery is not suitable |
Acne and hirsutism (excess body and facial hair in women) are not FDA-labeled uses. The trial evidence for them is summarized below.
What the research shows
Severe heart failure (RALES)
RALES was the trial that made spironolactone a standard heart failure drug. It randomized 1,663 patients with severe heart failure and an ejection fraction of 35% or less, who were being treated with an ACE inhibitor and a loop diuretic, to spironolactone 25 mg/day or placebo (Pitt et al., NEJM 1999). It was stopped early, after a mean of 24 months, because of a clear benefit. The mean dose at study end was 26 mg/day.
| Outcome | Spironolactone | Placebo | Relative risk (95% CI) |
|---|---|---|---|
| Death from any cause | 35% (284 of 822) | 46% (386 of 841) | 0.70 (0.60–0.82) |
| Hospitalization for worsening heart failure | — | — | 0.65 (0.54–0.77) |
| Gynecomastia or breast pain in men | 10% | 1% | P under 0.001 |
The lower death rate came from fewer deaths from progressive heart failure and fewer sudden cardiac deaths.
Heart failure with preserved ejection fraction (TOPCAT)
TOPCAT tested spironolactone 15–45 mg/day in 3,445 patients with heart failure and an ejection fraction of 45% or more, followed for a mean of 3.3 years (Pitt et al., NEJM 2014):
| Outcome | Spironolactone | Placebo | Hazard ratio (95% CI) |
|---|---|---|---|
| Primary composite (cardiovascular death, aborted cardiac arrest, heart failure hospitalization) | 18.6% | 20.4% | 0.89 (0.77–1.04), not significant |
| Heart failure hospitalization | 12.0% | 14.2% | 0.83 (0.69–0.99) |
| Hyperkalemia | 18.7% | 9.1% | — |
The main result was negative. Hyperkalemia roughly doubled, although with frequent monitoring there was no difference in serious adverse events or dialysis.
Resistant hypertension (PATHWAY-2)
PATHWAY-2 enrolled 335 people whose blood pressure stayed high despite three drugs at maximal doses (Williams et al., Lancet 2015). In a double-blind crossover design, each person rotated through 12 weeks each of spironolactone 25–50 mg, bisoprolol 5–10 mg, doxazosin 4–8 mg and placebo, added to their usual drugs.
| Comparison | Difference in home systolic blood pressure (95% CI) |
|---|---|
| Spironolactone vs placebo | −8.70 mm Hg (−9.72 to −7.69) |
| Spironolactone vs doxazosin | −4.03 mm Hg (−5.04 to −3.02) |
| Spironolactone vs bisoprolol | −4.48 mm Hg (−5.50 to −3.46) |
Spironolactone was the most effective add-on drug. Serum potassium went above 6.0 mmol/L on one occasion in 6 of 285 patients on spironolactone.
Acne in women (SAFA)
The SAFA trial randomized 410 women aged 18 and over with persistent facial acne to spironolactone (50 mg/day for 6 weeks, then 100 mg/day to week 24) or placebo (Santer et al., BMJ 2023):
| Outcome | Spironolactone | Placebo | Effect (95% CI) |
|---|---|---|---|
| Acne quality-of-life symptom score, week 12 (primary) | 19.2 | 17.8 | +1.27 (0.07–2.46) |
| Acne quality-of-life symptom score, week 24 | 21.2 | 17.4 | +3.45 (2.16–4.75) |
| Self-reported improvement, week 24 | 82% | 63% | OR 2.72 (1.50–4.93) |
| Investigator-rated treatment success, week 12 | 19% | 6% | OR 5.18 (2.18–12.28) |
| Headache | 20% | 12% | P = 0.02 |
The benefit was small at 12 weeks and larger at 24 weeks. No serious adverse reactions were reported. The investigators concluded it is a useful alternative to oral antibiotics for women with acne.
Hirsutism
A 2009 Cochrane review found 9 small randomized trials, mostly on hirsutism (Brown et al., Cochrane 2009). In the two trials comparing 100 mg/day with placebo, women were more likely to report subjective improvement in hair growth (OR 7.18, 95% CI 1.96–26.28). The reviewers concluded there is some evidence that it reduces hirsutism, but that studies in this area are scarce and small. At that time, they found no evidence of benefit for acne; SAFA was published later.
Side effects and risks
The current Aldactone label has no boxed warning. Its warnings are hyperkalemia, low blood pressure and worsening kidney function, electrolyte and metabolic changes, and gynecomastia.
Hyperkalemia
Spironolactone raises potassium by design. The risk is higher with kidney impairment, potassium supplements, potassium-containing salt substitutes, and drugs that also raise potassium. The label names:
- ACE inhibitors and angiotensin receptor blockers;
- NSAIDs;
- heparin and low-molecular-weight heparin;
- trimethoprim.
The label advises checking potassium within one week of starting or changing the dose and regularly after that.
What happens without that care was shown in Ontario after RALES was published (Juurlink et al., NEJM 2004). Among older heart failure patients on ACE inhibitors:
| Measure | 1994 | 2001 |
|---|---|---|
| Spironolactone prescriptions per 1,000 patients | 34 | 149 (late 2001) |
| Hospitalizations for hyperkalemia per 1,000 patients | 2.4 | 11.0 |
| Hyperkalemia-related deaths per 1,000 patients | 0.3 | 2.0 |
The authors estimated 560 extra hyperkalemia admissions and 73 extra hospital deaths in 2001 alone, with no matching drop in heart failure readmissions or overall deaths. By contrast, RALES had excluded patients with creatinine over 2.5 mg/dL or potassium over 5.0 mEq/L and checked labs every 4 weeks for the first 12 weeks (per the label).
Gynecomastia and sexual side effects
Gynecomastia is the label’s most common adverse reaction. In RALES, at a mean dose of 26 mg/day, about 9% of men developed it, per the label. The risk rises with dose, onset ranges from 1–2 months to over a year, and it is usually reversible. The label also lists decreased libido, erectile dysfunction, breast and nipple pain, and irregular or absent menstrual periods.
Other electrolyte, kidney and metabolic effects
Besides high potassium, the label lists low sodium, low magnesium, low calcium, hypochloremic alkalosis, high blood glucose and raised uric acid (rarely gout). Excess fluid loss can cause dehydration, low blood pressure and worse kidney function, especially with ACE inhibitors, ARBs or nephrotoxic drugs. In cirrhosis with ascites, sudden fluid and electrolyte shifts can trigger hepatic encephalopathy and coma, which is why the label says to start in hospital.
Rare reactions in postmarketing reports include low white cell and platelet counts, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS), and a very few cases of liver injury, including one death.
Other interactions
- Lithium: reduced lithium clearance and a risk of lithium toxicity.
- NSAIDs and aspirin: may blunt the diuretic and blood-pressure effects.
- Digoxin: spironolactone interferes with some digoxin blood tests.
- Cholestyramine: hyperkalemic metabolic acidosis has been reported.
- Abiraterone: may raise PSA; combination not recommended.
- Mitotane: lowers mitotane levels; avoid together.
Who should not use it
The label contraindicates spironolactone in people with:
- hyperkalemia;
- Addison’s disease (adrenal insufficiency);
- concurrent use of eplerenone, another aldosterone blocker.
In pregnancy, the label advises avoiding it because, in rats, high doses feminized male fetuses. Human data from case reports have not shown a link with major birth defects. In 18- and 24-month studies in rats, it increased benign and some malignant tumors of the liver, thyroid and testes at high doses; this is animal data.
Use outside medicine and anti-doping status
Spironolactone is listed by name under class S5, diuretics and masking agents, on the WADA 2026 Prohibited List. It is prohibited in and out of competition and is a “specified substance.”
Bodybuilders have used diuretics to try to increase muscle definition before contests, and case reports describe the harm. A 27-year-old professional bodybuilder who combined diuretics, potassium supplements and diet restriction developed life-threatening hyperkalemia, ECG changes and mild muscle breakdown (Sturmi and Rutecki, Phys Sportsmed 1995). A 31-year-old bodybuilder taking anabolic steroids, amphetamines, a furosemide-amiloride combination and potassium supplements had a heart attack with potassium of 6.7 mmol/L and ventricular tachycardia (Appleby et al., Int J Cardiol 1994). Neither case involved spironolactone specifically, but amiloride is also a potassium-sparing diuretic, and the label warns that combining spironolactone with potassium supplements “may lead to severe hyperkalemia.”
Its antiandrogen action also means it works against the androgen receptor, the same receptor anabolic steroids act on. For comparison, see bicalutamide, a dedicated androgen receptor blocker, and the other diuretics furosemide and hydrochlorothiazide, which do not spare potassium; the Aldactone label notes spironolactone may be useful when other diuretics have caused low potassium.
Key takeaways
- An aldosterone blocker that spares potassium. It makes the kidney lose sodium and water while keeping potassium. The parent drug lasts about 1.4 h, but its active metabolites have half-lives of 13.8–16.5 h.
- Proven in severe heart failure. In RALES, 25 mg/day cut the risk of death by 30% in patients with an ejection fraction of 35% or less. It did not significantly improve the main outcome in heart failure with preserved ejection fraction.
- Hyperkalemia is the key danger. Combined with ACE inhibitors, ARBs, NSAIDs, potassium supplements or kidney impairment, it can push potassium to life-threatening levels. Hospitalizations for hyperkalemia rose more than fourfold in Ontario after RALES.
- It is also an antiandrogen. It blocks the androgen receptor, which underlies its use for acne and hirsutism in women and its main side effect in men, gynecomastia (about 9–10% in RALES).
- Banned in sport. WADA lists it by name as a prohibited diuretic and masking agent, at all times.
Sources
- Pfizer. Aldactone (spironolactone) tablets, prescribing information, NDA 012151. DailyMed; Drugs@FDA.
- CMP Pharma. CaroSpir (spironolactone) oral suspension, prescribing information, NDA 209478. DailyMed.
- National Center for Biotechnology Information. Spironolactone, PubChem CID 5833. PubChem.
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- Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–1392. PubMed.
- Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059–2068. PubMed.
- Santer M, Lawrence M, Renz S, et al. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ. 2023;381:e074349. PubMed.
- Brown J, Farquhar C, Lee O, Toomath R, Jepson RG. Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev. 2009;(2):CD000194. PubMed.
- Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543–551. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.
- Sturmi JE, Rutecki GW. When competitive bodybuilders collapse. Phys Sportsmed. 1995;23(11):49–53. PubMed.
- Appleby M, Fisher M, Martin M. Myocardial infarction, hyperkalaemia and ventricular tachycardia in a young male body-builder. Int J Cardiol. 1994;44(2):171–174. PubMed.