Drug Interaction Report

MONITOR: Theoretically, coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of darifenacin, which has been shown to be a substrate of the isoenzyme.

MANAGEMENT: Pharmacologic response to darifenacin should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the darifenacin dosage adjusted if necessary.

The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown.

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.