Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly 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. The therapeutic efficacy of ixazomib may be reduced.

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

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.

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.