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 with large amounts of certain fruit juices, including grapefruit, orange and apple, may decrease the oral bioavailability of fexofenadine. The proposed mechanism is inhibition of drug efflux via intestinal organic anion transporting polypeptides (e.g., P-glycoprotein), of which fexofenadine is a substrate. In a five-way crossover study with 10 healthy volunteers, 1/4-strength grapefruit juice, grapefruit juice, orange juice and apple juice (300 mL with drug administration and 150 mL every 1/2 hour for up to 3 hours, total volume 1.2 L) reduced the mean area under the plasma concentration-time curve (AUC) of a 120 mg dose of fexofenadine by 23%, 67%, 72% and 77%, respectively, compared to water. Mean peak plasma concentration (Cmax) was similarly affected. The clinical significance of these changes is unknown. However, results from studies using histamine-induced skin wheals and flares found that the size of wheal and flare was significantly larger when fexofenadine was administered with either grapefruit or orange juices compared to water.

MANAGEMENT: To maximize plasma levels and therapeutic effects, fexofenadine should be taken with water. In addition, patients should refrain from consuming large amounts of grapefruit, orange, or apple juice.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.