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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.