Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 2C8 and/or 3A4 may decrease the plasma concentrations of dabrafenib, which is primarily metabolized by these isoenzymes. Administration of rifampin (600 mg once a day), a potent CYP450 3A4 and moderate CYP450 2C8 inducer, with dabrafenib (150 mg twice a day) for 10 days resulted in a decreased dabrafenib AUC (34%) and Cmax (27%). The AUC of the metabolite hydroxy-dabrafenib was not affected; however, the AUC increased by 73% for the metabolite carboxy-dabrafenib and decreased by 30% for desmethyl-dabrafenib.

MANAGEMENT: Concomitant use of dabrafenib with potent CYP450 2C8 or 3A4 inducers should generally be avoided. Otherwise, patients should be closely monitored for potential loss of efficacy of dabrafenib.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.