Drug Interactions between eplerenone and miconazole

MONITOR: Coadministration with inhibitors of CYP450 3A4 including azole antifungal agents may increase the plasma concentrations of eplerenone, which is primarily metabolized by the isoenzyme. In pharmacokinetic studies, administration of eplerenone (100 mg single dose) with the potent inhibitor ketoconazole (200 mg twice a day) resulted in a 1.7-fold increase in eplerenone peak plasma concentration (Cmax) and a 5.4-fold increase in systemic exposure (AUC), while administration with other 3A4 inhibitors (erythromycin 500 mg twice daily; verapamil 240 mg once daily; saquinavir 1200 mg three times daily; fluconazole 200 mg once daily) resulted in increases in eplerenone Cmax ranging from 1.4- to 1.6-fold and AUC from 2.0 to 2.9-fold. The interaction has not been studied with miconazole buccal tablets. Although systemic absorption following mucous membrane exposure is limited, the potential for interaction with drugs metabolized by CYP450 3A4 such as eplerenone cannot be ruled out.

MANAGEMENT: Caution is advised if eplerenone is prescribed in combination with miconazole mucous membrane preparations. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever miconazole is added to or withdrawn from therapy.