Drug Interaction Report

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 Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.