Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of sotorasib, which is partially metabolized by the isoenzyme. According to the prescribing information, the main metabolic pathways of sotorasib are non-enzymatic conjugation and oxidative metabolism via CYP450 3A isoenzymes. When a single dose of sotorasib was coadministered with multiple doses of rifampin, a potent CYP450 3A4 inducer, sotorasib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 51%, respectively. Reduced therapeutic efficacy of sotorasib may occur. No clinically significant effect on sotorasib exposure was observed following coadministration with a single dose of rifampin.

MANAGEMENT: Concomitant use of sotorasib with potent CYP450 3A4 inducers should generally be avoided.

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.