Drug Interaction Report

MONITOR: Coadministration with olutasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4. Based on in vitro studies, olutasidenib may increase clearance via induction of CYP450 3A4, resulting in decreased plasma concentrations of agents that are metabolized by the isoenzyme. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if olutasidenib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information for olutasidenib recommends avoiding coadministration with CYP450 3A4 substrates for which minimal concentration changes may lead to therapeutic failure. If coadministration is required, clinical and laboratory monitoring may be appropriate whenever olutasidenib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including buprenorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Patients taking buprenorphine should not consume alcohol or use medications that contain alcohol on days of buprenorphine dosing. In general, potent narcotics such as buprenorphine should not be combined with alcohol.

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.