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 (eg, norepinephrine): Spirolactone 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 Aldactone.
Skeletal muscle relaxants, nondepolarizing (eg, 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, eg, indomethacin, with potassium-sparing diuretics has been associated with severe
hyperkalemia. Therefore, when Aldactone and NSAIDs are used concomitantly, the patient should be observed closely to
determine if the desired effect of the diuretic is obtained.
Digoxin: Spirolactone 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 underdigitalization.
Drug/Laboratory Test Interactions
Several reports of possible interference with digoxin radioimmunoassays by spironolactone, or its metabolites,
have appeared in the literature. Neither the extent nor the potential clinical significance of its interference
(which may be assay-specific) has been fully established.