ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.
Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Pressor Amines (e.g., Norepinephrine): Spironolactone reduces the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with Spironolactone.
Skeletal Muscle Relaxants, Nondepolarizing (e.g., Tubocurarine): Possible increased responsiveness to the muscle relaxant may result.
Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing and thiazide diuretics. Combination of NSAIDs, e.g., indomethacin, with potassium-sparing diuretics has been associated with severe hyperkalemia. Therefore, when Spironolactone and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Digoxin: Spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and digitalization doses when Spironolactone is administered, and the patient should be carefully monitored to avoid over or under digitalization.