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

GENERALLY AVOID: Coadministration of protein-bound sirolimus intravenous suspension with grapefruit juice may increase the systemic exposure to sirolimus. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of sirolimus by certain compounds present in grapefruit. However, grapefruit juice primarily inhibits CYP450 3A4-mediated first-pass metabolism in the gut wall and may have limited effects on medications that are not administered orally. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with protein-bound sirolimus.

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.