Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentrations of tucatinib, which is primarily metabolized by CYP450 2C8 and to a lesser extent by CYP450 3A4. When rifampin (600 mg once daily), a potent CYP450 3A4 and moderate CYP450 2C8 inducer, was administered with a single tucatinib dose of 300 mg, tucatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 50%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of tucatinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

Food does not appear to have a clinically significant effect on the oral bioavailability of sotorasib. When a 960 mg dose of sotorasib was administered to study patients with a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), sotorasib peak plasma concentration (Cmax) did not change while systemic exposure (AUC 0-24 hours) increased by 25% compared to administration under fasted conditions. Sotorasib can be administered with or without food at approximately the same time each day.