Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may decrease the plasma concentrations and therapeutic efficacy of olutasidenib, which is primarily metabolized by the isoenzyme. When coadministered with multiple doses of rifampin, a potent CYP450 3A4 inducer, olutasidenib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 43% and 80%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: Concomitant use of olutasidenib with potent or moderate CYP450 3A4 inducers should be avoided.

ADJUST DOSING INTERVAL: Coadministration with a high-fat meal may increase the plasma concentrations of olutasidenib. According to the product labeling, administration of a single 150 mg dose with a high-fat meal (approximately 800 to 1000 calories, with approximately 50% of those calories from fat) increased olutasidenib peak plasma concentration (Cmax) and systemic exposure (AUC) by 191% and 83%, respectively, in healthy subjects.

MANAGEMENT: Olutasidenib should be administered at about the same time each day, on an empty stomach at least 1 hour before or 2 hours after a meal.

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.