Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ixazomib, which is a substrate of the isoenzyme. When ixazomib was administered with the potent CYP450 3A4 inducer rifampin, ixazomib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 54% and 74%, respectively.

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

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of ixazomib. A food effect study found that administration of a single 4 mg dose of ixazomib with a high-fat meal decreased ixazomib peak plasma concentration (Cmax) by 69% and systemic exposure (AUC) by 28%.

MANAGEMENT: Ixazomib should be taken at least one hour before or two hours after eating. On days when both ixazomib and dexamethasone are administered, advise patients to separate dosing times, since dexamethasone should be taken with food while ixazomib should be taken on an empty stomach.

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.