Spironolactone Drug Interactions
Also known as: Aldactone, CaroSpir
Spironolactone is a potassium-sparing diuretic and aldosterone antagonist used to treat heart failure, hypertension, edema, and hyperaldosteronism. It blocks aldosterone receptors in the kidney, reducing sodium retention and potassium excretion.Spironolactone has 1 documented drug interaction in our database, including 0 contraindicated, 1 major, 0 moderate, and 0 minor interactions.
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Contraindicated
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Major
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Moderate
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Minor
Concurrent use of losartan and spironolactone significantly increases the risk of hyperkalemia (elevated serum potassium). Both drugs reduce potassium excretion through complementary mechanisms — losartan blocks aldosterone secretion via AT1 receptor blockade, while spironolactone directly antagonizes aldosterone receptors in the kidney. The combination can cause life-threatening hyperkalemia, particularly in patients with renal impairment, diabetes, or heart failure.
Mechanism
Losartan reduces angiotensin II-mediated aldosterone secretion from the adrenal cortex (via AT1 receptor blockade), decreasing renal potassium excretion. Spironolactone competitively antagonizes aldosterone at the mineralocorticoid receptor in the collecting duct, further reducing potassium excretion. The additive effect on potassium retention can cause serum potassium to rise to dangerous levels (>6 mEq/L).
Clinical Management
Use with caution; avoid in patients with eGFR <30 mL/min/1.73m² or baseline potassium >5.0 mEq/L. Monitor serum potassium and renal function within 1–2 weeks of initiating the combination and periodically thereafter. Instruct patients to avoid potassium-containing salt substitutes and high-potassium foods. Consider reducing the spironolactone dose or switching to a loop diuretic if hyperkalemia develops. This combination is used intentionally in heart failure (RALES trial) but requires careful monitoring.
For complete prescribing information:
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