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.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of silodosin. The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies. The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated. Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.