Drug Interaction Report

GENERALLY AVOID: Coadministration with vimseltinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The proposed mechanism, based on in vitro data, involves decreased clearance due to inhibition of P-gp by vimseltinib. Based on model-informed drug interaction studies, coadministration of the P-gp substrate dabigatran with vimseltinib (30 mg twice weekly) is predicted to increase the systemic exposure (AUC) and peak plasma concentration (Cmax) of dabigatran by 2 to 3-fold. However, if dabigatran is administered 4 hours after vimseltinib (30 mg twice weekly), the AUC and Cmax are predicted to increase by only up to 1.3-fold. Clinical data are not available.

MANAGEMENT: Concomitant use of vimseltinib with P-gp substrates should generally be avoided. If coadministration is considered necessary, vimseltinib should be taken at least 4 hours prior to the P-gp substrate. The individual product labeling of the P-gp substrate should be consulted for further guidance.

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.