Because eplerenone metabolism is predominantly mediated via CYP3A4, do not use INSPRA with drugs that are strong inhibitors of CYP3A4. [See CONTRAINDICATIONS and CLINICAL PHARMACOLOGY.]
In patients with hypertension taking moderate CYP3A4 inhibitors, reduce the starting dose of INSPRA to 25 mg once daily. [See DOSAGE AND ADMINISTRATION (2.3, 2.4) and CLINICAL PHARMACOLOGY.]
ACE Inhibitors and Angiotensin II Receptor Antagonists
Congestive Heart Failure Post-Myocardial Infarction
In EPHESUS [see CLINICAL STUDIES], 3020 (91%) patients receiving INSPRA 25 to 50 mg also received ACE inhibitors or angiotensin II receptor antagonists (ACEI/ARB). Rates of patients with maximum potassium levels >5.5 mEq/L were similar regardless of the use of ACEI/ARB.
In clinical studies of patients with hypertension, the addition of INSPRA 50 to 100 mg to ACE inhibitors and angiotensin II receptor antagonists increased mean serum potassium slightly (about 0.090.13 mEq/L). In a study in diabetics with microalbuminuria, INSPRA 200 mg combined with the ACE inhibitor enalapril 10 mg increased the frequency of hyperkalemia (serum potassium >5.5 mEq/L) from 17% on enalapril alone to 38%.
A drug interaction study of eplerenone with lithium has not been conducted. Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors. Serum lithium levels should be monitored frequently if INSPRA is administered concomitantly with lithium.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
A drug interaction study of eplerenone with an NSAID has not been conducted. The administration of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Therefore, when INSPRA and NSAIDs are used concomitantly, patients should be observed to determine whether the desired effect on blood pressure is obtained and monitored for changes in serum potassium levels.