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is required, clinical and laboratory monitoring may be appropriate whenever olutasidenib is added to or withdrawn from therapy.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.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

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.