Spironolactone

Is spironolactone safe?

Spironolactone is one of the drugs that changed heart failure care, and for most people it is safe with simple checks. In the RALES trial, published in 1999, adding 25 mg a day to standard treatment in severe heart failure cut deaths from 46% to 35% over two years. It is also widely used for high blood pressure, fluid in liver disease, and, off-label, for acne in women. In 2024 it filled about 13.4 million US prescriptions (ClinCalc).

The danger is potassium. Spironolactone makes the kidneys hold on to it, and in someone with weak kidneys or on an ACE inhibitor or ARB, levels can climb high enough to stop the heart. We score it 76, above furosemide (70) but below hydrochlorothiazide (83). A lower score is not a reason to stop it; for heart failure it saves lives.

High potassium: who is really at risk

What happened after RALES shows the danger. Doctors in Ontario started prescribing spironolactone to many more older heart failure patients, often without the careful blood tests used in the trial. A 2004 NEJM study of people aged 66 and over on ACE inhibitors found:

That was an estimated 73 extra hospital deaths in one Canadian province in a single year. In 2016 the MHRA warned again after a coroner's case in which a patient with heart failure, diabetes and kidney disease died of high potassium days after a low-dose ACE inhibitor was added.

The risk is very different in healthy people. A 2015 study of 974 young women taking spironolactone for acne found high potassium in 0.72% of blood tests, the same as the 0.76% rate in similar women not taking it.

The current US label says to check potassium within a week of starting or raising the dose and regularly after that. In heart failure it should only be started if potassium is 5.0 or below, and at a lower dose (25 mg every other day) when kidney function is reduced.

Hormonal side effects

Spironolactone blocks male hormones as well as aldosterone. That is why it helps hormonal acne in women, and why it causes trouble in men.

• Breast growth in men: about 9% of men in RALES on an average of 26 mg a day. The label says it rises with dose, can take from one or two months to over a year to appear, and is usually reversible.
• Erection problems and lower libido in men.
• Irregular periods, breast tenderness and bleeding after the menopause in women.

Breast cancer is a common worry, and the evidence is reassuring. A UK study following more than a million women over 55 found no difference in breast cancer rates (hazard ratio 0.99).

For acne, the UK SAFA trial in 410 women found that 82% on spironolactone reported improvement at 24 weeks against 63% on placebo. Headaches were more common (20% against 12%), and there were no serious reactions.

Interactions to check

Most of the dangerous interactions are about potassium:

• ACE inhibitors and ARBs such as lisinopril and losartan: often used together in heart failure on purpose, but only with regular blood tests.
• Potassium supplements and salt substitutes like Lo-Salt: the label says to stop potassium supplements in heart failure patients starting spironolactone.
• NSAIDs, heparin and trimethoprim (a common antibiotic for urinary infections): all can raise potassium.
• Eplerenone: contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary together.
• Lithium: levels rise; monitor.
• Abiraterone for prostate cancer: not recommended, as spironolactone can raise PSA.

It also distorts some blood tests for digoxin, so labs need to use a different method.

Who should be careful

• People with kidney disease, diabetes or heart failure, especially over 65.
• Anyone with high potassium or Addison's disease, in whom it is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary.
• People with cirrhosis: the label says to start it in hospital, as sudden fluid shifts can bring on confusion or coma.
• Pregnant women: in rats it feminised male fetuses, and the label says to avoid it. The NHS says it is not usually recommended in pregnancy.

Get urgent help for a slow or irregular heartbeat, muscle weakness or numbness, which can be signs of high potassium. Talk to your doctor or pharmacist before stopping or changing the dose, and before starting any new medicine or supplement.

How we scored it

Dependence (98), track record (95) and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (85) are strong. Interactions (52) is the weakest factor, because so many common drugs and supplements push potassium up. Serious side effects (66) reflect the potentially fatal high-potassium risk in older, sicker patients, while regulatory warnings (75) reflect the MHRA alert without a current boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary.