Drug Interactions between aminoglutethimide and aprepitant

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of aprepitant, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of a single 375 mg dose of aprepitant on day 9 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg/day for 14 days) resulted in an 11-fold decrease in aprepitant systemic exposure (AUC) and 3-fold decrease in the mean terminal half-life.

MANAGEMENT: The possibility of diminished therapeutic response to aprepitant should be considered during coadministration with CYP450 3A4 inducers, particularly potent ones like carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifampin, and St. John's wort. Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.