ALDACTONE (Spironolactone Tablets, USP) Drug Interactions

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Drug-Drug Interactions

Table 1. Established or Potential Drug-Drug Interactions

Aldactone Drug Interaction

Effect

Clinical comment

Alcohol, barbiturates or narcotics

Potentiation of orthostatic hypotension may occur.

Avoid alcohol, barbiturates or narcotics, especially with initiation of therapy.

Antipyrine

Spironolactone enhances the metabolism of antipyrine.

Cholestyramine/ Ammonium Chloride

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)

Intensified electrolyte depletion, particularly hypokalemia, may occur.

Monitor serum potassium, and adjust medications, as required.

Diuretics and Antihypertensives

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

Severe hyperkalemia has been associated with the use of aldosterone blockers in combination with spironolactone.

Heparin, low molecular weight heparin

Concomitant use of spironolactone with heparin, low molecular weight heparin may lead to severe hyperkalemia.

Drugs known to cause hyperkalemia

Concomitant use of drugs known to cause hyperkalemia with spironolactone may result in severe hyperkalemia

Lithium

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

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

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

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.

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 Cmax were reported after food co-administration.  At the same time, increases of approximately 1.4-fold were seen in Cmax and AUC(0-24) of canrenone.

The clinical importance of this finding is not known.

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 Drug-Drug Interactions).