Concomitant use of drugs known to cause hyperkalemia with spironolactone may result in severe hyperkalemia.
Spironolactone may have an additive effect when given concomitantly with other diuretics and antihypertensive agents. The dose of such drugs may need to be reduced when spironolactone is added to the treatment regimen.
Spironolactone reduces vascular responsiveness to norepinephrine. Caution should be exercised in the management of patients subjected to anesthesia while they are being treated with spironolactone.
Spironolactone has been shown to increase the half-life of digoxin.
Non-steroidal anti-inflammatory drugs such as aspirin, indomethacin and mefenamic acid may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins and have been shown to attenuate the diuretic effect of spironolactone.
Spironolactone enhances the metabolism of antipyrine.
Spironolactone can interfere with assays for plasma digoxin concentrations.
Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with ammonium chloride or cholestyramine.
Co-administration of spironolactone with carbenoxolone may result in decreased efficacy of either agent.