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Drug Reference

spironolactone

potassium-sparing diuretic· Brands: Aldactone, CaroSpir, Spiractin, VerospironPO

Mechanism of action
Spironolactone is a competitive antagonist at the mineralocorticoid (aldosterone) receptor in the late distal tubule and collecting duct of the nephron. By blocking aldosterone binding, it reduces the expression of the epithelial sodium channel (ENaC) and Na+/K+-ATPase, which decreases sodium reabsorption and potassium secretion. This produces mild natriuresis and potassium retention. Spironolactone also has antiandrogenic activity: it antagonises the androgen receptor, inhibits 5-alpha-reductase, and increases sex hormone-binding globulin. These effects explain its use in acne, hirsutism, and its adverse effects such as gynaecomastia and menstrual irregularity.
Pharmacokinetics
Spironolactone is given orally and is well absorbed, with bioavailability around 90 percent, increased by food. It undergoes extensive first-pass hepatic metabolism, mainly by CYP3A4, to active metabolites including canrenone, 7-alpha-thiomethylspirolactone, and 6-beta-hydroxy-7-alpha-thiomethylspirolactone. The parent drug has a short half-life of about 1.4 hours, but active metabolites have longer half-lives (canrenone roughly 16 hours), so the diuretic effect is delayed, with onset over days and peak effect after several days to weeks. Protein binding exceeds 90 percent. Elimination is primarily renal and biliary. In renal impairment, metabolite accumulation occurs, and hyperkalaemia risk rises, so dose reduction or avoidance may be needed.
Indications & dosing

Heart failure with reduced ejection fraction (NYHA class II to IV)

Add-on to an ACE inhibitor, ARB or ARNI plus a beta-blocker. Check potassium and renal function at baseline, at 1 week and after each dose change.

  • adult · PO: 12.5–25 mg once daily · Add-on to an ACE inhibitor, ARB or ARNI plus a beta-blocker. Check potassium and renal function at baseline, at 1 week and after each dose change.

Resistant hypertension, as a fourth-line add-on

Low potassium or an incidental adrenal mass should prompt assessment for primary hyperaldosteronism. Avoid combining with potassium supplements or other potassium-retaining drugs.

  • adult · PO: 25–50 mg once daily · Low potassium or an incidental adrenal mass should prompt assessment for primary hyperaldosteronism. Avoid combining with potassium supplements or other potassium-retaining drugs.

Primary hyperaldosteronism, medical management

Titrate against potassium, renin and blood pressure. Higher daily doses are sometimes needed under specialist supervision. Surgery is preferred for a unilateral adenoma.

  • adult · PO: 25–100 mg once daily · Titrate against potassium, renin and blood pressure. Higher daily doses are sometimes needed under specialist supervision. Surgery is preferred for a unilateral adenoma.

Ascites and peripheral oedema in cirrhosis

Often combined with furosemide in a 100 mg to 40 mg ratio. Monitor weight, electrolytes and renal function; avoid rapid diuresis.

  • adult · PO: 100–400 mg once daily · Often combined with furosemide in a 100 mg to 40 mg ratio. Monitor weight, electrolytes and renal function; avoid rapid diuresis.

Hypokalaemia and potassium depletion when supplements are inadequate

Licensed use varies by region; check the local formulary. Avoid in renal impairment and with other potassium-retaining drugs.

  • adult · PO: 25–100 mg once daily · Licensed use varies by region; check the local formulary. Avoid in renal impairment and with other potassium-retaining drugs.

Hirsutism and acne in women with polycystic ovary syndromeoff-label

Response takes 3 to 6 months. Contraindicated in pregnancy and requires effective contraception. Monitor potassium with combined hormonal treatment.

  • adult · PO: 50–100 mg once daily · Response takes 3 to 6 months. Contraindicated in pregnancy and requires effective contraception. Monitor potassium with combined hormonal treatment.

Oedema or heart failure in children

Dose per local paediatric guidance; some regimens use up to 6 mg/kg/day in specialist care. Monitor potassium, creatinine and growth.

  • pediatric · PO: 1–3 mg/kg/day once or twice daily · Dose per local paediatric guidance; some regimens use up to 6 mg/kg/day in specialist care. Monitor potassium, creatinine and growth.
Contraindications & precautions
  • Hyperkalaemia (serum potassium above the upper limit of normal at baseline) · Spironolactone is a competitive aldosterone antagonist and raises serum potassium. Starting treatment in an already hyperkalaemic patient can precipitate life-threatening arrhythmia.
  • Severe renal impairment, anuria, or acute kidney injury · Reduced renal potassium excretion markedly increases hyperkalaemia risk. The exact eGFR threshold for avoiding the drug varies by formulary; many local protocols advise against initiation below an eGFR of about 30 mL/min/1.73 m2.
  • Addison's disease or other adrenal insufficiency · Aldosterone deficiency is already present, so blocking the receptor causes severe and unpredictable hyperkalaemia and hyponatraemia.
  • Concurrent potassium supplements, potassium-sparing diuretics (for example amiloride, triamterene), or eplerenone · Additive potassium retention. Combination therapy is occasionally used under specialist supervision with close monitoring, but is not routine practice.
  • Hypersensitivity to spironolactone or other components of the formulation · Rare; consider excipient allergy with liquid and compounded preparations.
  • Pregnancy · Antiandrogenic activity is a theoretical risk to a male fetus. Avoid unless the indication is compelling after specialist review. Practice varies by region.
  • Breastfeeding · The active metabolite canrenone appears in breast milk in small amounts. Weigh the benefit against the possibility of effects on the infant.
  • Check serum potassium and renal function (eGFR or creatinine) before starting, within about one week, at one month, and then periodically, and after any dose change or acute illness.
  • Avoid potassium supplements, potassium-containing salt substitutes, and unnecessary NSAIDs. Review concurrent ACE inhibitors, angiotensin receptor blockers, trimethoprim and heparin, all of which raise potassium further.
  • Spironolactone raises serum lithium concentrations and can interfere with some digoxin assays; monitor if these drugs are co-prescribed.
  • Take with or after food to improve absorption and reduce gastrointestinal upset.
  • Use with care in older adults and in people with diabetes or mild to moderate renal impairment, where hyperkalaemia develops more readily.
  • In cirrhosis with ascites, monitor electrolytes, renal function and for signs of hepatic encephalopathy, since treatment is usually continued only while ascites persists.
Adverse effects
  • Hyperkalaemiaserious
  • Acute kidney injury or a rise in serum creatinineserious
  • Hyponatraemiaserious
  • Gynaecomastia (dose-related, more frequent at higher doses)
  • Breast tenderness and enlargement
  • Menstrual irregularity, metrorrhagia, or postmenopausal bleeding
  • Reduced libido and erectile dysfunction
  • Nausea, vomiting, or abdominal discomfort
  • Blood dyscrasias such as agranulocytosis or thrombocytopeniaserious
  • Severe cutaneous reactions such as Stevens-Johnson syndrome or DRESSserious
Interactions
  • potassium chloridecontraindicatedCo-prescription is contraindicated. If the combination is considered essential, it must be used only under specialist supervision with frequent monitoring of serum potassium, electrolytes, and renal function. Stop the potassium supplement and seek immediate medical attention if hyperkalaemia develops. Consider alternative potassium-sparing strategies or non-potassium-sparing diuretics.
  • trimethoprimmajorAvoid co-prescription if possible. If the combination is necessary, monitor serum potassium and renal function at baseline and within 5 to 7 days after starting therapy, and periodically thereafter. Advise patients to avoid potassium supplements and salt substitutes. Consider alternative antibiotics without potassium-sparing effects.
  • ramiprilmajorPrescribers may use this combination in selected patients (e.g., heart failure) with close monitoring. Measure serum potassium and creatinine before starting, then within 1 week, and regularly thereafter, especially after dose changes. Avoid in patients with significant renal impairment, baseline hyperkalaemia, or high risk of worsening renal function. Consider alternatives such as eplerenone or loop diuretics if risk is high.
  • digoxinmajorMonitor serum digoxin concentrations, serum potassium and renal function before starting spironolactone and at regular intervals thereafter. Adjust the digoxin dose as needed to maintain therapeutic levels. Consider alternative diuretics if the patient is at high risk of hyperkalaemia or digoxin toxicity. Advise patients to report symptoms of toxicity such as nausea or palpitations.
  • perindoprilmajorUse with caution. Monitor serum potassium and creatinine within 1 to 2 weeks of starting or changing the combination, and regularly thereafter. Avoid in patients with severe renal impairment (eGFR < 30 mL/min) or baseline potassium > 5.0 mmol/L. If combined, use lower doses and consider stopping if potassium rises above 5.5 mmol/L.
  • lisinoprilmajorUse together with caution. Monitor serum potassium and creatinine at baseline, within 1-2 weeks after starting or changing doses, and then periodically. Avoid in patients with significant renal impairment or baseline potassium above 5.0 mmol/L. Consider alternative antihypertensive or renin-angiotensin system blocker, or use lower doses.
  • ibuprofenmajorAvoid concomitant use when possible, especially in patients with renal impairment or risk factors for hyperkalaemia. If co-prescription is necessary, use the lowest effective dose of ibuprofen for the shortest duration. Monitor serum potassium and renal function (creatinine, eGFR) at baseline, within 3 to 5 days of starting therapy, and regularly thereafter. Consider alternative analgesics such as paracetamol. Adjust the spironolactone dose if renal function or potassium changes.
Renal & hepatic adjustment
  • eGFR 60+: No specific dose adjustment. Monitor potassium and creatinine at baseline and within 1 week of initiation or dose change, then periodically.
  • eGFR 30–59: Use with caution. Start at a low dose (e.g., 12.5 to 25 mg daily) and titrate slowly. Monitor potassium and creatinine closely, within 1 week of initiation and after each dose change.
  • eGFR 0–29: Avoid unless under specialist supervision. Risk of severe hyperkalaemia and worsening renal function. If used, start at a very low dose (e.g., 12.5 mg daily or alternate days) with frequent monitoring. (avoid)
  • Hepatic impairment (mild): No specific dose adjustment. Monitor electrolytes and renal function.
  • Hepatic impairment (moderate): No specific dose adjustment. Use with caution; monitor electrolytes and renal function, and watch for signs of hepatic encephalopathy.
  • Hepatic impairment (severe): Use with caution. Spironolactone is metabolised hepatically and may accumulate. Monitor electrolytes, renal function and mental state closely. Specialist supervision advised.
Monitoring, pregnancy & toxicity
  • Serum potassium · Baseline, within 1 week of starting or dose change, then at 1, 3 and 6 months; more often if eGFR <60 or on ACE inhibitor/ARB.
  • Serum creatinine and eGFR · As for potassium.
  • Blood pressure and heart rate · Baseline and at each clinical review.
  • Weight and fluid status · Daily during initiation or titration in heart failure or ascites; otherwise at each review.
  • Serum sodium · Baseline and periodically, especially if at risk of hyponatraemia.
  • Gynaecomastia, breast tenderness, menstrual irregularities · Ask at each review; may require dose reduction or discontinuation.
  • Pregnancy: Spironolactone is not recommended in pregnancy, especially during the first trimester, because of its anti-androgenic effects and the risk of feminisation of a male fetus. It should only be used if clearly necessary, under specialist supervision. Alternative antihypertensives such as labetalol, nifedipine or methyldopa are preferred for hypertension in pregnancy.
  • Toxicity: Hyperkalaemia (may be delayed due to slow onset of action). Features include muscle weakness, paraesthesia, palpitations, ECG changes (peaked T waves, widened QRS, arrhythmias). · Stop spironolactone. Monitor potassium and ECG. Treat hyperkalaemia with calcium gluconate for cardiac protection, insulin/dextrose infusion, nebulised salbutamol, and potassium binders. Dialysis for refractory cases.
  • Toxicity: Hyponatraemia and dehydration: confusion, lethargy, seizures, reduced skin turgor, hypotension. · Stop drug. Correct fluid and electrolyte balance with careful IV fluids. Monitor sodium and neurological status.
  • Toxicity: Hypotension and tachycardia: dizziness, syncope, shock. · Stop drug. Supportive care with IV fluids and, if necessary, vasopressors. Monitor haemodynamics.
  • Toxicity: Acute renal impairment: oliguria, rising creatinine, fluid overload. · Stop drug. Monitor renal function and urine output. Supportive care; consider renal replacement therapy if severe.
Clinical notes
Spironolactone is used for heart failure with reduced ejection fraction to reduce mortality and hospitalisation, for resistant hypertension, for primary hyperaldosteronism, and for ascites in cirrhosis. It is also used for hypokalaemia and, off-label, for acne and hirsutism. Typical teaching doses: heart failure 25 mg once daily, titrated to 50 mg; hypertension 25 to 100 mg daily; ascites 100 to 400 mg daily; these are examples only and must be verified. Key adverse effects include hyperkalaemia, hyponatraemia, renal impairment, gynaecomastia, breast tenderness, impotence, reduced libido, menstrual disturbances, and gastrointestinal upset. Monitor serum potassium and creatinine at baseline, within one week, at four weeks, and after any dose change or intercurrent illness. Avoid or use with caution alongside other potassium-sparing agents, ACE inhibitors, angiotensin receptor blockers, potassium supplements, and NSAIDs. Contraindicated in hyperkalaemia, severe renal impairment, Addison's disease, and pregnancy. Practice varies by region and formulary, especially for heart failure and cirrhosis dosing.

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BNF; local formulary; summary of product characteristics; current heart failure and hepatology guidelines.