Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may 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. No clinically significant effect on sotorasib exposure was observed following coadministration with a single dose of rifampin. The interaction has not been studied with other, less potent inducers.

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

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.

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.