Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of olutasidenib, which is primarily metabolized by the isoenzyme. When coadministered with 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: The potential for diminished pharmacologic effects of olutasidenib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

MONITOR: Isolated case reports have suggested that the ingestion of alcohol during griseofulvin therapy may rarely cause disulfiram-like reactions, flushing, tachycardia, or increased effects of alcohol. The mechanism is unknown.

MANAGEMENT: Patients should be advised of the possibility of increased adverse effects or a disulfiram-like reaction.

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.