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 3A4 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: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.

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.