Drug Interaction Report

GENERALLY AVOID: Concomitant use with multiple doses of vorasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A. Vorasidenib is predicted to be an inducer of CYP450 3A resulting in decreased plasma concentrations of agents that are metabolized by the isoenzyme. The interaction may be significant for sensitive CYP450 3A substrates or those that demonstrate a narrow therapeutic index. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Concomitant use of vorasidenib with substrates of CYP450 3A should be avoided due to the potential for reduced efficacy

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

GENERALLY AVOID: Due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of vorasidenib, smoking tobacco during treatment with vorasidenib may decrease its plasma concentrations and anti-tumor effect. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Patient should be advised to avoid smoking tobacco during treatment with vorasidenib because it may reduce efficacy of the therapy.