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 use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

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.