ALDACTONE (Spironolactone Tablets, USP) 9 Drug Interactions

9.4 Drug-Drug Interactions

The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).

Table 4 - Established or Potential Drug-Drug Interactions ALDACTONE Source of Evidence Effect Clinical comment
ALDACTONE	Source of Evidence	Effect	Clinical comment
Legend: CS = Case Study; CT = Clinical Trial; T = Theoretical
Alcohol, barbiturates or narcotics	T	Potentiation of orthostatic hypotension may occur.	Avoid alcohol, barbiturates or narcotics, especially with initiation of therapy.
Antipyrine	T	Spironolactone enhances the metabolism of antipyrine.
Cholestyramine/ Ammonium Chloride	CS	Hyperchloremic metabolic acidosis, frequently associated with hyperkalemia, has been reported in patients given spironolactone concurrently with ammonium chloride or cholestyramine.
Corticosteroids, and adrenocorticotropic hormone (ACTH)	T	Intensified electrolyte depletion, particularly hypokalemia, may occur.	Monitor serum potassium, and adjust medications, as required.
Diuretics and Antihypertensives	CS	Although ALDACTONE may be administered concomitantly with diuretics and antihypertensives, the effect of ALDACTONE is additive. Hyperkalemia has been associated with the use of angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, angiotensin II antagonists and aldosterone blockers in combination with spironolactone.	It is advisable to reduce the dose of these drugs. In particular, the dose of ganglionic blocking agents should be reduced by at least 50% when ALDACTONE is added to the regimen.
Eplerenone	CT	Severe hyperkalemia has been associated with the use of aldosterone blockers in combination with spironolactone.
Heparin, low molecular weight heparin	CT	Concomitant use of spironolactone with heparin, low molecular weight heparin may lead to severe hyperkalemia.
Drugs known to cause hyperkalemia	T	Concomitant use of drugs known to cause hyperkalemia with spironolactone may result in severe hyperkalemia
Lithium	T	Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.	Lithium generally should not be given with diuretics.
Norepinephrine	CT	ALDACTONE reduces the vascular responsiveness to norepinephrine.	Caution should be exercised in the management of patients subjected to regional or general anaesthesia while being treated with spironolactone.
Digoxin	CS	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 dose of digoxin when spironolactone is administered, and the patient should be carefully monitored to avoid over‑ or underdigitalization.
Non‑Steroidal Anti‑Inflammatory Drugs	CS	Nonsteroidal anti-inflammatory drugs such as ASA, mefenamic acid, and indomethacin may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins and have been shown to attenuate the diuretic action of spironolactone. Hyperkalemia has been associated with the use of indomethacin in combination with potassium‑sparing diuretics.	However, it has been shown that ASA does not alter the effect of spironolactone on blood pressure, serum electrolytes, urea nitrogen, or plasma renin activity in hypertensive patients. If combination use is necessary, monitor renal function, serum potassium, and blood pressure closely. Dose adjustment may be required.
Abiraterone	CS	Spironolactone binds to the androgen receptor and may increase prostate-specific antigen (PSA) levels in abiraterone-treated prostate cancer patients.

9.5 Drug-Food Interactions

In a 9 subject study, statistically significant increases of approximately 2-fold in spironolactone AUC(_0-24) and greater than 2-fold in C_max were reported after food co-administration. At the same time, increases of approximately 1.4-fold were seen in C_max and AUC(_0-24) of canrenone.

The clinical importance of this finding is not known.

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 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.

Spironolactone has been shown to increase the half life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity (see 9.4 Drug-Drug Interactions).