Spironolactone & Eplerenone: Independent Evidence, Risks, Funding

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Key takeaways
  • Spironolactone and eplerenone are aldosterone-blocking "potassium-sparing" diuretics. Spironolactone is licensed for heart failure, hypertension add-on use, fluid retention from cirrhosis or nephrotic syndrome, and primary hyperaldosteronism (US Aldactone label). In the UK, eplerenone is licensed only for heart failure after a heart attack and for mild (NYHA II) heart failure (UK Inspra SmPC).
  • The strongest publicly funded evidence is for stubborn high blood pressure. In PATHWAY-2, a UK crossover trial of 335 people funded by the British Heart Foundation and NIHR, spironolactone lowered home systolic pressure 8.70 mm Hg more than placebo (95% CI 7.69 to 9.72) and about 4 mm Hg more than doxazosin or bisoprolol (PATHWAY-2, Lancet 2015; NIHR Evidence).
  • The heart-failure survival evidence comes mainly from manufacturer-sponsored trials. RALES (spironolactone, severe heart failure) was funded by Searle, the maker of Aldactone: deaths fell from 46% to 35% (RR 0.70, 95% CI 0.60 to 0.82) (RALES summary). EMPHASIS-HF (eplerenone, mild heart failure) was sponsored by Pfizer: HR 0.63 (0.54 to 0.74) for heart-failure death or admission (ACC summary). The publicly funded TOPCAT trial in preserved ejection fraction missed its main target (HR 0.89, 0.77 to 1.04) (ACC summary).
  • High potassium is the main danger. In TOPCAT, 18.7% of people on spironolactone had hyperkalaemia versus 9.1% on placebo (ACC). After RALES, Ontario hyperkalaemia admissions among older heart-failure patients on ACE inhibitors rose from 2.4 to 11.0 per 1,000 (BMJ news report of Juurlink 2004). The MHRA warns that combining spironolactone with an ACE inhibitor or ARB raises the risk of severe hyperkalaemia (MHRA 2016).
  • Breast enlargement or pain affected about 10% of men on spironolactone in RALES versus 1% on placebo (ACC). Eplerenone lists gynaecomastia only as "uncommon" (UK SmPC), but we found no head-to-head trial.
  • For acne in women, the NIHR-funded SAFA trial (410 women) found a small, statistically significant gain on the main quality-of-life score at 12 weeks (1.27 points, 95% CI 0.07 to 2.46) and a larger one at 24 weeks (SAFA, BMJ 2023). Acne is not a listed indication on the labels we read.
  • Money trail: Aldactone is Pfizer's brand (UK SmPC); the UK Inspra SmPC now names Viatris, "formerly Mylan or Upjohn" (emc). Of the 12 sources we graded, 3 are tier 1, 4 tier 2, 2 tier 3 and 3 tier 4.
  • Evidence grade: Strong for lowering blood pressure in resistant hypertension and for survival in reduced-ejection-fraction heart failure (but mostly maker-funded). Moderate for primary aldosteronism and acne. Risk for hyperkalaemia and kidney function.

Independent evidence review · Prescription medicine

Spironolactone and eplerenone are useful, cheap-to-moderate-cost medicines whose benefits are well established and whose main danger, high blood potassium, is predictable and testable. Spironolactone has the best publicly funded evidence as a fourth add-on drug for resistant high blood pressure; both drugs cut deaths in reduced-ejection-fraction heart failure, though those landmark trials were paid for by the makers. Confidence is high for blood pressure and heart failure, moderate for primary aldosteronism and women's acne, and low for anything else. The harm is mostly about monitoring: potassium and kidney tests, and avoiding stacked potassium-raising drugs. Spironolactone adds hormonal effects such as breast enlargement in men; eplerenone is more selective but is licensed for fewer uses.

Best evidence for resistant hypertension (PATHWAY-2), reduced-ejection-fraction heart failure (RALES, EMPHASIS-HF, EPHESUS), primary aldosteronism
Main risks hyperkalaemia and kidney injury; breast enlargement (spironolactone); harm to a male fetus in animal studies
Key rule blood tests for potassium and creatinine soon after starting or any dose change, and no potassium supplements or salt substitutes unless a prescriber says so
Safety first
Spironolactone and eplerenone are prescription-only. Do not start, stop or change the dose without the prescriber who monitors your blood tests. High potassium can be fatal and may cause dangerous heart rhythms (UK Aldactone SmPC). Seek urgent medical help for muscle weakness, palpitations, an irregular or very slow pulse, fainting, or passing very little urine, especially if you are also taking an ACE inhibitor, an ARB, an anti-inflammatory painkiller, trimethoprim or a potassium supplement. Do not use potassium-containing salt substitutes unless a prescriber has approved them (US label).

Table of contents

Evidence summary

Claim Evidence Source Funding / conflict Strength
Spironolactone is the best fourth add-on drug for resistant hypertension 335 people enrolled, 230 completed all cycles. Home systolic pressure −8.70 mm Hg vs placebo (95% CI −9.72 to −7.69); −4.03 vs doxazosin (−5.04 to −3.02); −4.48 vs bisoprolol (−5.50 to −3.46). PATHWAY-2; NIHR British Heart Foundation and NIHR; several authors declared pharma honoraria Strong
Spironolactone cuts deaths in severe heart failure 1,663 patients, EF 35% or less. Death 46% vs 35% (RR 0.70, 95% CI 0.60 to 0.82). Stopped early. RALES summary; ACC Funded by Searle, maker of Aldactone Strong (maker-funded)
Eplerenone cuts death or heart-failure admission in mild (NYHA II) heart failure 2,737 patients. Primary HR 0.63 (0.54 to 0.74); all-cause death HR 0.76 (0.62 to 0.93). EMPHASIS-HF (ACC) Sponsored by Pfizer Strong (maker-funded)
Eplerenone reduces death after a heart attack with left-ventricular dysfunction 6,632 patients. All-cause death 14.4% vs 16.7% (RR 0.85). EPHESUS (ACC) Sponsor not stated on the summary we read Moderate
Spironolactone helps heart failure with preserved ejection fraction 3,445 patients. Primary outcome HR 0.89 (0.77 to 1.04), not significant. Admissions for heart failure 12.0% vs 14.2%. TOPCAT (ACC) NHLBI (US government) Weak
Spironolactone improves acne in women 410 women. ASQ symptom score +1.27 at 12 weeks (0.07 to 2.46), +3.45 at 24 weeks (2.16 to 4.75). Investigator-rated success 19% vs 6% at 12 weeks (OR 5.18, 2.18 to 12.28). SAFA NIHR HTA programme; one author declared skin-care and pharma ties Moderate
Medicine is preferred for bilateral primary aldosteronism Guideline says lifelong MRA treatment is usually offered for bilateral disease, suggests spironolactone over other MRAs, and suggests MRAs over amiloride-type drugs (conditional; certainty graded very low on the page we read). Endocrine Society 2025 Funding not stated on the page we read Moderate
Hyperkalaemia is common and can be serious TOPCAT 18.7% vs 9.1%. EMPHASIS-HF potassium above 5.5 mmol/L in 11.8% vs 7.2%. Ontario admissions 2.4 to 11.0 per 1,000 after RALES. ACC; SmPC; BMJ news Mixed: NHLBI, Pfizer-sponsored, Ontario data Risk
Breast enlargement or pain in men on spironolactone About 10% vs 1% in RALES. The US label reports about 9% and says risk rises with dose; usually reversible. ACC; US label Searle-funded trial; Pfizer-written label Risk

Independent evidence and credibility scorecard

Independence tiers: 1 = regulator or government body; 2 = academic or Cochrane team with no declared commercial funding for the work; 3 = independent authors analysing mostly manufacturer-run trials, or minor declared industry ties; 4 = manufacturer-funded or manufacturer-authored. Credibility runs from A (highest) to D. Labels are written by the maker and approved by a regulator, so we place them at tier 3.

Source Who funds it Country Independence tier (1–4) Credibility (A–D) Why it would tell the truth / residual bias
NIHR Evidence summary of PATHWAY-2 UK government (NIHR) UK 1 A A public body with no product; its reputation rests on plain summaries. Residual bias: it summarises a trial that NIHR also helped fund.
MHRA Drug Safety Update, Dec 2016 UK government (regulator) UK 1 A Legal duty to protect patients and no product to sell. Residual bias: caution tends to favour warnings over benefits; after feedback that the February 2016 wording was inconsistent with heart-failure guidelines, the MHRA clarified in December 2016 that it did not mean the drugs cannot be combined.
TOPCAT (read via ACC summary) NHLBI, US National Institutes of Health US 1 B Public funding with no stake in the drug; a neutral result was still reported. Residual bias: we read a society summary, not the paper, and the ACC's own funding was not traced.
PATHWAY-2, Lancet 2015 British Heart Foundation (charity) and NIHR UK 2 B Public and charity funders, double-blind crossover, funders had no role in analysis. Residual bias: several authors declared honoraria from drug makers, including Pfizer; academics are rewarded for positive findings.
SAFA, BMJ 2023 NIHR Health Technology Assessment programme; sponsor University of Southampton UK 2 B Public funder, placebo-controlled, open-access results. Residual bias: one author declared advisory or consultancy ties with skin-care and drug companies (including Mylan); the primary result is modest.
Endocrine Society primary aldosteronism guideline, 2025 Not stated on the page we read; co-sponsored by six medical societies US (society); international panel 2 B Professional society whose standing depends on defensible guidance; recommendations we read are conditional, with low to very low certainty. Residual bias: panel members' industry ties not checked.
Juurlink et al. 2004 (read via BMJ news report and appraisal) Not stated on either page we read Canada (Ontario data) 2 B Population data from older adults, no drug to sell. Residual bias: observational; funding not verified; we did not open the NEJM paper.
Aldactone labels, US (Pfizer) and UK (Pfizer Ltd) Written by Pfizer; approved by FDA and MHRA US / UK 3 B Legally required warnings and monitoring schedules; liability rewards completeness. Residual bias: a maker writes the efficacy framing.
Inspra UK SmPC (Viatris) Written by Viatris; approved by the MHRA UK 3 B Contraindications and potassium rules are regulator-checked. Residual bias: the sponsor summarises its own trials (EPHESUS, EMPHASIS-HF).
RALES (read via summaries) Searle, maker of Aldactone International 4 C Peer-reviewed, double-blind, stopped early for benefit and later echoed by independent evidence. Residual bias: the maker paid, and we read secondary summaries.
EMPHASIS-HF (read via ACC summary) Pfizer International; sponsor US 4 C Large double-blind trial with hard endpoints. Residual bias: sponsor-run, stopped early, hyperkalaemia checked every 4 months per protocol.
FINEARTS-HF secondary analysis, JAMA Cardiology 2024 Bayer; Bayer staff among the authors International 4 C Transparent about funding and about higher hyperkalaemia. Residual bias: the maker of finerenone designed and funded it.

Country clustering: the cleanest sources on hypertension and acne (PATHWAY-2, SAFA, NIHR, MHRA) are all from the UK, so the blood-pressure and acne verdicts reflect a UK lens. The heart-failure survival trials are international but sponsored by US or German companies, and no independent trial of the original RALES or EMPHASIS-HF question has replaced them. Where sources with opposing interests agree, we say so: the maker-written labels, the MHRA, the public trials and the Ontario data all agree that hyperkalaemia is the key hazard.

What spironolactone and eplerenone are

Spironolactone is an aldosterone antagonist and potassium-sparing diuretic (UK Aldactone SmPC). It is sold as Aldactone by Pfizer and as many generics. The US label lists tablets in 25, 50 and 100 mg strengths and the UK SmPC lists the brand as 25 mg film-coated tablets (US label).

Eplerenone (Inspra) is a related aldosterone antagonist with strengths of 25 mg and 50 mg and a maximum daily dose of 50 mg (UK Inspra SmPC).

Finerenone is a related nonsteroidal mineralocorticoid-receptor antagonist made by Bayer. It was tested in FINEARTS-HF (6,001 adults with heart failure at 37 countries), where it cut the combined outcome of total worsening heart-failure events and cardiovascular death (rate ratio 0.84, 95% CI 0.74 to 0.95) while raising potassium above 5.5 mmol/L in 14.6% versus 7.1% on placebo (ACC feature). The trial was funded by Bayer, which also took part in design and conduct (JAMA Cardiology analysis). We have not reviewed finerenone's labelling in this article and do not recommend it over either drug.

How they work

Both drugs block the receptor for aldosterone, a hormone that makes the kidney hold on to sodium and lose potassium. RALES began from the reasoning that ACE inhibitors do not fully suppress aldosterone, so blocking its receptor might add benefit (RALES summary). The PATHWAY-2 authors read the result as supporting a primary role for sodium retention in resistant hypertension (PATHWAY-2).

The UK Aldactone SmPC says animal studies show reproductive toxicity linked to "anti-androgenic effects" (emc). That is the likely reason spironolactone causes breast enlargement and is used in acne, but we did not find a source that proves the mechanism in people, so we treat it as proposed, not proven. Evidence from trials, not mechanism, is what the sections below rest on.

What they are prescribed for

  • Spironolactone, US label: heart failure with reduced ejection fraction (NYHA III to IV), add-on hypertension treatment, oedema from cirrhosis or nephrotic syndrome, and primary hyperaldosteronism (Pfizer label).
  • Spironolactone, UK SmPC: heart failure, cirrhosis with ascites and oedema, malignant ascites, nephrotic syndrome, and diagnosis and treatment of primary aldosteronism (emc). Resistant hypertension is covered by NICE: the 2011 guideline recommended spironolactone for resistant hypertension that did not respond to three other drugs, with an alpha- or beta-blocker if it is not tolerated (NIHR Evidence).
  • Eplerenone, UK SmPC: lowering cardiovascular death and illness in stable patients with left-ventricular dysfunction and heart-failure signs after a recent heart attack, and NYHA class II chronic heart failure with ejection fraction of 30% or less (emc).
  • Off-label: acne in women is not listed in either label we read. See the acne section below.

What works and what does not

Claimed benefit Verdict Evidence Key caveat
Lower blood pressure when three drugs fail WORKS −8.70 mm Hg vs placebo (PATHWAY-2). Three-month exposure; potassium above 6.0 mmol/L in 2% of those on spironolactone.
Fewer deaths in reduced-EF heart failure WORKS RALES RR 0.70; EMPHASIS-HF HR 0.76 for death (RALES; ACC). Both maker-funded; trials ran with close potassium checks.
Heart failure with preserved EF MIXED TOPCAT missed its primary endpoint; admissions were lower (ACC). The ACC page calls the admission and women-only findings hypothesis-generating.
Primary aldosteronism (bilateral) WORKS Guideline prefers MRAs (Endocrine Society). Conditional recommendations with very low certainty for the drug comparisons; no large placebo trials were found in this review.
Acne in adult women MIXED SAFA ASQ +1.27 at 12 weeks, +3.45 at 24 weeks (SAFA). Women only, 6-month trial; the 12-week difference had a lower confidence limit close to zero.
Hirsutism or hair loss INSUFFICIENT We did not open a trial or review on this. No verdict can be given from sources we read.

Benefits by claim

Resistant hypertension

PATHWAY-2 was a double-blind crossover trial: each person took spironolactone, bisoprolol, doxazosin and placebo in turn on top of three existing drugs. Of 335 enrolled, 230 completed all cycles. Spironolactone gave the largest fall in home systolic pressure: 8.70 mm Hg below placebo, 4.03 below doxazosin and 4.48 below bisoprolol (PATHWAY-2). In plain terms, that is a clinically meaningful extra drop for people whose pressure is stuck high. Dosing was 25 mg then 50 mg, and the funders were the British Heart Foundation and NIHR support (NIHR Evidence). Any adverse event occurred in 19% on spironolactone versus 15% on placebo; potassium above 6.0 mmol/L occurred in 6 of 285 (2%), reaching 6.5 mmol/L at most (PATHWAY-2). Before this stage, treatment resistance should be confirmed and secondary causes ruled out; see our articles on resistant hypertension and secondary hypertension.

Primary aldosteronism

The 2025 Endocrine Society guideline suggests screening everyone with hypertension (a conditional recommendation that depends on resources), and suggests spironolactone over other MRAs mainly because it is low cost and widely available (very low certainty). It also suggests MRAs rather than amiloride-type drugs (very low certainty), and says lifelong MRA treatment is usually offered for bilateral disease (Endocrine Society). The Aldactone label gives primary hyperaldosteronism as an indication (US label).

Heart failure with reduced ejection fraction

In RALES, 1,663 people with severe heart failure took spironolactone or placebo on top of standard care for a mean of 24 months. Deaths were 46% on placebo versus 35% on spironolactone (RR 0.70, 95% CI 0.60 to 0.82), admissions for worsening heart failure fell by 35%, and the trial stopped early (RALES summary; ACC). In EMPHASIS-HF, 2,737 people with mild symptoms took eplerenone or placebo: cardiovascular death or heart-failure admission fell from 25.9% to 18.3% (HR 0.63, 0.54 to 0.74) and all-cause death from 15.5% to 12.5% (HR 0.76, 0.62 to 0.93) (ACC). After a heart attack with left-ventricular dysfunction, EPHESUS found death in 14.4% on eplerenone versus 16.7% on placebo (RR 0.85) (ACC). Both RALES and EMPHASIS-HF were paid for by the makers, so we label them as such. Our fuller discussion is in heart failure with reduced ejection fraction.

Heart failure with preserved ejection fraction

TOPCAT, funded by the US NHLBI, randomised 3,445 people with symptomatic heart failure and ejection fraction of 45% or more to spironolactone or placebo. The main outcome occurred in 18.6% versus 20.4% (HR 0.89, 95% CI 0.77 to 1.04, not significant); heart-failure admission was lower (12.0% versus 14.2%) but the page flags that as hypothesis-generating (ACC). See HFpEF for the wider picture. The nonsteroidal MRA finerenone had a positive result in a Bayer-funded trial in a similar group (see above).

Acne and other off-label uses

SAFA randomised 410 women (201 spironolactone, 209 placebo) with persistent facial acne. The dose started at 50 mg daily and rose to 100 mg from week 6 (SAFA; University of Southampton). Mean age was 29.2 years, and 98% increased to the higher dose. The main outcome, the Acne-Specific Quality of Life symptom score, differed by 1.27 points at 12 weeks (95% CI 0.07 to 2.46) and 3.45 at 24 weeks (2.16 to 4.75). Investigator-rated treatment success at 12 weeks was 19% versus 6% (OR 5.18, 2.18 to 12.28). Any adverse reaction affected 64% versus 51% of women, with headache at 20% versus 12%; breast tenderness was similar at 20% versus 18%, and potassium was checked only at baseline (SAFA, BMJ). Women able to become pregnant had to use contraception. For the wider acne evidence see our acne article. We did not open evidence on hirsutism or hair loss and make no claim there.

Risks and all side effects

Serious: high potassium and kidney injury
Hyperkalaemia was twice as frequent on spironolactone in TOPCAT (18.7% vs 9.1%), and creatinine and kidney failure also rose (ACC). In EMPHASIS-HF, potassium above 5.5 mmol/L occurred in 11.8% on eplerenone versus 7.2% on placebo (UK SmPC), and in people with eGFR 30 to 59 the rates were 16.6% versus 9.3% (ACC). Outside trials, Ontario hyperkalaemia admissions among older heart-failure patients on ACE inhibitors rose from 2.4 to 11.0 per 1,000 and related deaths from 0.3 to 2.0 per 1,000 as spironolactone prescribing climbed from 34 to 149 per 1,000 (BMJ news report; Canadian Family Physician appraisal). The study is observational, so it shows association, not proof of cause.

Monitoring (label rules)

  • Spironolactone, US: check potassium within one week of starting or adjusting the dose, then regularly; more often with kidney impairment or other potassium-raising drugs (US label).
  • Spironolactone, UK, heart failure: potassium and creatinine at one week, monthly for three months, quarterly for a year, then six-monthly; interrupt if potassium exceeds 5 mEq/L (UK SmPC).
  • Eplerenone, UK: potassium before starting, within the first week and at one month, then periodically; the SmPC steps the dose down at 5.5 to 5.9 mmol/L and withholds at 6.0 mmol/L or above (UK SmPC).
  • MHRA: combined use with an ACE inhibitor or ARB raises severe hyperkalaemia risk, especially in marked renal impairment, and should be used with caution; the same applies to eplerenone in heart failure (MHRA, 13 December 2016).

Other effects

  • Breast enlargement or pain: about 10% of men in RALES versus 1% on placebo (ACC). The US label says risk rises with dose, onset ranges from one to two months to over a year, and it is usually reversible (US label). PATHWAY-2 saw no gynaecomastia, which the authors put down to three months' exposure (PATHWAY-2). Occasionally enlargement persists (UK SmPC).
  • Eplerenone: gynaecomastia is listed as uncommon; other reactions include renal impairment, cough, insomnia, diarrhoea, dizziness, hypotension, rash and raised urea or creatinine (UK SmPC). Different trials, different groups: this is not a head-to-head comparison.
  • Metabolic acidosis and urea: reversible hyperchloraemic metabolic acidosis in decompensated cirrhosis, and reversible rises in blood urea (UK SmPC).
  • Acne dose effects: headache and dizziness were more common than on placebo (SAFA).
  • Long-term animal studies: at high doses in rats, spironolactone increased benign and malignant tumours in several organs (US label). We did not review human cancer data.

All interactions

  • Potassium-raising drugs: ACE inhibitors, ARBs, NSAIDs, heparins, trimethoprim and co-trimoxazole, potassium supplements and potassium-containing salt substitutes (US label; UK SmPC). See our pages on ramipril and losartan.
  • Lithium: reduced clearance and higher toxicity risk; monitor levels (US label). See lithium.
  • NSAIDs and aspirin: may blunt the diuretic and blood-pressure effect; NSAIDs also raise acute kidney injury risk with eplerenone (US label; UK Inspra SmPC).
  • Digoxin: spironolactone can falsely raise digoxin readings on some immunoassays; eplerenone modestly raises exposure (about 16%) (US label; UK Inspra SmPC).
  • Other spironolactone interactions: cholestyramine (reported hyperkalaemic acidosis), abiraterone (may raise PSA, combination not recommended), mitotane (avoid), carbenoxolone (avoid) (US label; UK SmPC).
  • Eplerenone and CYP3A4: contraindicated with strong inhibitors (itraconazole, ketoconazole, ritonavir, clarithromycin); do not exceed 25 mg daily with amiodarone, diltiazem or verapamil; strong inducers such as rifampicin, carbamazepine and St John's wort are not recommended; avoid ciclosporin and tacrolimus; ACE inhibitor plus ARB plus eplerenone is contraindicated (UK Inspra SmPC). See also our page on supplements and heart medicines.
  • Each other: concomitant eplerenone is a contraindication on the spironolactone labels (US label).
  • Other blood-pressure drugs and anaesthesia: effects may be enhanced, and spironolactone reduces the vascular response to noradrenaline (UK SmPC).

Who should avoid them

  • Raised potassium or Addison's disease: both are contraindications for spironolactone (US label).
  • Severe kidney disease: the UK Aldactone SmPC lists acute renal insufficiency, significant renal compromise or anuria as contraindications. Eplerenone is contraindicated at eGFR below 30 and when potassium is above 5.0 mmol/L at the start, and in severe liver impairment (Child-Pugh C) (UK Aldactone SmPC; UK Inspra SmPC). See chronic kidney disease and the heart.
  • Pregnancy: the US label says animal data suggest spironolactone may feminise male fetuses, advises avoiding use or informing the patient of the risk, and notes human case data have not shown a clear rise in major malformations (US label). The UK SmPC says data are limited and use only if benefit justifies risk (UK SmPC). Eplerenone has no adequate human data (UK Inspra SmPC). SAFA required usual contraception for women able to become pregnant, and seven pregnancies occurred (SAFA). Pregnancy planning in heart disease is covered in heart disease during pregnancy.
  • Breastfeeding: the UK SmPC says spironolactone should not be used while breastfeeding, because its metabolite canrenone passes into milk; the US label says a decision should weigh breastfeeding against need (UK SmPC; US label). The regulators differ; this is for a clinician to decide.
  • Children: use is limited and should be supervised by a paediatric specialist (UK SmPC).
  • Cirrhosis: the US label advises starting in hospital and titrating slowly (US label). See cirrhosis.
  • Older people and diabetes: the eplerenone SmPC lists older age, renal impairment and diabetes as higher-risk for hyperkalaemia (UK Inspra SmPC).

Dosage and how to take them

These are label doses and trial doses, not personal advice.

  • Spironolactone, US label: heart failure starting dose 25 mg once daily if potassium is 5.0 mEq/L or lower and eGFR above 50, may increase to 50 mg; hypertension 25 to 100 mg daily, titrated at two-week intervals; oedema usually 100 mg daily (range 25 to 200); primary hyperaldosteronism 100 to 400 mg daily before surgery (US label).
  • Spironolactone, UK SmPC: should be taken once daily with a meal; severe heart failure starting dose 25 mg daily (UK SmPC).
  • Eplerenone, UK SmPC: start at 25 mg daily, aim for 50 mg daily within about four weeks; 25 mg every other day if creatinine clearance is 30 to 60 mL/min (UK Inspra SmPC).
  • Trial doses: RALES 25 mg rising to 50 mg (RALES summary); TOPCAT 15 to 45 mg (mean 25 mg at 8 months) (ACC); SAFA 50 mg then 100 mg (SAFA).

Follow the money: who makes them and who funded the evidence

Who makes and sells them

  • Spironolactone originator: Aldactone is a Pfizer product. The US label is issued by Pfizer Laboratories (revised November 2025) (Pfizer label) and the UK marketing-authorisation holder is Pfizer Limited, Sandwich, Kent (emc). RALES was funded by Searle, which the RALES summary names as the maker of Aldactone (summary). Pfizer completed its acquisition of Pharmacia on 16 April 2003 (SEC 8-K); we could not open a document that ties Searle to that deal, so the Searle-to-Pfizer chain is not verified here.
  • Eplerenone originator: EMPHASIS-HF was sponsored by Pfizer (ACC). The UK Inspra SmPC today names Viatris, "formerly Mylan or Upjohn" (emc), so the brand has changed hands from the trial sponsor. We did not open a document explaining the transfer, and we do not state its terms.
  • Generics: many generic spironolactone and eplerenone products exist. We could not retrieve the current NHS Drug Tariff price or market-share figures, so we give no price or revenue figures.
  • Finerenone: made by Bayer, which funded and helped run FINEARTS-HF (JAMA Cardiology).
Follow the money

Research funding at a glance

Funding & backersSource & studyClaim & limits

12 sources graded. The counts below are the independence tiers assigned in the scorecard above. They count sources, not funding amounts or evidence quality.

Tier 13Independent
Tier 24Indirect ties
Tier 32Interested party
Tier 43Self-interested

Public funding alone does not prove independence, and commercial funding alone does not prove a claim false. Named funders, countries and relationships are in the scorecard and source notes.

Who funded the trials

  • Public and charity: PATHWAY-2 (British Heart Foundation, NIHR), SAFA (NIHR Health Technology Assessment programme, sponsor University of Southampton), TOPCAT (US NHLBI) (PATHWAY-2; SAFA; TOPCAT).
  • Maker-funded: RALES (Searle), EMPHASIS-HF (Pfizer), FINEARTS-HF (Bayer) (see links above).
  • Author ties: PATHWAY-2 authors declared honoraria from Novartis, Boehringer Ingelheim, Servier, Daiichi Sankyo and Pfizer, one is a board member of the MHRA, and another is president of the British Hypertension Society and chief investigator on Pfizer-funded outcome studies (PATHWAY-2 declarations). In SAFA, author AML declared relationships with Almirall, Eucerin, Galderma, GSK, La Roche-Posay, LEO Pharma, L'Oreal, Mylan, Origimm and Procter & Gamble (SAFA). One FINEARTS-HF author holds a patent related to site-specific eplerenone delivery (JAMA Cardiology).

Documented integrity events

We did not identify a regulatory ban, recall or enforcement action specific to spironolactone or eplerenone in the sources we opened. We did not run a litigation-database search, so this is an absence in what we read, not proof that none exists. Regulatory safety actions we did find are the MHRA's 2016 hyperkalaemia warning and its clarification (MHRA) and the New Zealand regulator's similar reminder, which noted five local cases over 12 years (Medsafe 2016).

Frequently asked questions

How is eplerenone different from spironolactone?

Both block aldosterone. In the UK, eplerenone is licensed for heart failure (after a heart attack, and NYHA II) and has a 50 mg daily maximum, while spironolactone has a broader list of uses (Inspra SmPC; Aldactone SmPC). Eplerenone lists gynaecomastia as uncommon, but we found no head-to-head trial.

Why do I need so many blood tests?

Because high potassium can be fatal and often has no early warning. The labels set a schedule of tests after starting and after any dose change (US label; UK SmPC).

Does spironolactone cause breast growth in men?

It can. About 10% of men in RALES versus 1% on placebo had breast enlargement or pain (ACC). It is usually reversible after stopping (US label).

Is spironolactone safe in pregnancy?

It is generally avoided. The US label cites animal data that it may feminise male fetuses (US label), and the UK SmPC says use only if benefit justifies risk (UK SmPC). Pregnancy plans should be discussed before starting.

Is spironolactone approved for acne?

Acne is not among the indications in the labels we read (US; UK). The NIHR-funded SAFA trial found benefit in women over 12 to 24 weeks (SAFA).

Can I use a salt substitute while taking it?

Not without checking. Potassium-containing salt substitutes can raise potassium (US label; UK SmPC).

Does spironolactone work for heart failure with a normal ejection fraction?

Not clearly. TOPCAT missed its primary target (HR 0.89, 95% CI 0.77 to 1.04), though admissions were lower (ACC).

What about finerenone?

It is a nonsteroidal MRA from Bayer. In a Bayer-funded trial it reduced worsening heart-failure events and cardiovascular death (RR 0.84, 0.74 to 0.95) but still raised potassium above 5.5 mmol/L (14.6% vs 7.1%) (ACC; JAMA Cardiology).

Sources and funding notes

What we could not verify: NICE's current hypertension (NG136) and heart-failure (NG106) pages blocked our access, so we relied on the NIHR Evidence summary for NICE's earlier resistant-hypertension advice and could not confirm current NICE potassium thresholds. PubMed and NEJM pages were rate-limited or blocked, so RALES, EMPHASIS-HF, EPHESUS, TOPCAT and Juurlink were read through secondary summaries (ACC, a trial-summary site, a BMJ news report and a Canadian Family Physician appraisal), not the original papers. We could not confirm EPHESUS's sponsor or the funding of the Endocrine Society guideline and Juurlink study. We did not trace the ACC's own funding. We found no Drug Tariff price, market-share figure, or documented ownership chain from Searle to Pfizer or from Pfizer to Viatris for Inspra. We opened no source on hirsutism, hair loss or PCOS, and we did not review the finerenone label.

  1. US Aldactone prescribing information (Pfizer, revised November 2025) — regulator-approved label; manufacturer-written; Pfizer
  2. Aldactone 25 mg film-coated tablets, UK SmPC (emc) — MHRA-approved; Pfizer Limited
  3. Inspra 25 mg film-coated tablets, UK SmPC (emc) — MHRA-approved; Viatris
  4. PATHWAY-2, Lancet 2015 (Williams et al.) — trial; British Heart Foundation and NIHR
  5. NIHR Evidence: spironolactone for resistant hypertension — summary; UK government
  6. SAFA, BMJ 2023 (Santer et al.) — trial; NIHR HTA programme
  7. University of Southampton news on SAFA — press release; sponsor University of Southampton
  8. Endocrine Society primary aldosteronism guideline page (2025) — guideline; funding not stated on the page
  9. MHRA Drug Safety Update, December 2016 — regulator; UK government
  10. Medsafe Prescriber Update, September 2016 — regulator; New Zealand government
  11. RALES summary (WikiJournalClub) — secondary summary of the Searle-funded trial
  12. ACC summary of RALES — society summary; sponsor not stated on the page
  13. ACC summary of EMPHASIS-HF — society summary; trial sponsor Pfizer
  14. ACC summary of EPHESUS — society summary; sponsor not stated
  15. ACC summary of TOPCAT — society summary; trial sponsor NHLBI
  16. ACC feature on finerenone (FINEARTS-HF) — society article; sponsor not stated on the page
  17. Finerenone, serum potassium and outcomes, JAMA Cardiology 2024 — secondary analysis; Bayer
  18. BMJ news report on Juurlink et al. (2004) — news; funding not stated
  19. Canadian Family Physician appraisal of Juurlink et al. — appraisal; funding not stated
  20. Pfizer Form 8-K on Pharmacia merger (2003) — corporate filing; Pfizer

Educational research reviewed 6 October 2026. This article is not medical advice; talk to a qualified clinician or pharmacist before starting, stopping or combining treatments.

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