Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with dabrafenib may decrease the plasma concentrations and efficacy of contraceptive hormones. The mechanism is dabrafenib induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones.

MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with dabrafenib. Because use of dabrafenib may cause fetal harm, it is particularly important that patients not become pregnant during treatment. Female patients of reproductive potential should use a highly effective, non-hormonal method of contraception during treatment and for 4 weeks after treatment. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Intrauterine systems are unlikely to be significantly affected because of their local action.

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.