Drug Interaction Report

GENERALLY AVOID: Coadministration with risdiplam may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of multidrug and toxin extrusion 1 and 2K (MATE1 and MATE2K) proteins. Based on in vitro data, risdiplam and its metabolite are MATE1 and MATE2K transport inhibitors. The proposed mechanism is decreased clearance due to risdiplam-mediated inhibition of MATE1 and/or MATE2K.

MANAGEMENT: Coadministration of risdiplam with drugs that are substrates of MATE1 and/or MATE2K should generally be avoided. However, if concomitant use is unavoidable, monitor for drug-related toxicities and consider dosage reduction of the MATE1 or MATE2K substrate (based in the labeling of that drug) as needed.

ADJUST DOSING INTERVAL: Administration of trifluridine-tipiracil with a standardized high-fat, high-calorie meal has been shown to decrease trifluridine peak plasma concentration (Cmax) as well as tipiracil Cmax and systemic exposure (AUC) by approximately 40% compared to administration in a fasting state in patients with cancer given a single 35 mg/m2 dose. No change in trifluridine AUC was observed.

MANAGEMENT: Based on the observed correlation between increases in the Cmax of trifluridine and decreases in neutrophil counts, trifluridine-tipiracil should be taken within one hour after completion of the morning and evening meals.