Drug Interaction Report

MONITOR: Coadministration with asciminib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. In vitro, asciminib is a substrate and inhibitor of P-gp, an efflux transporter expressed in the gastrointestinal tract, liver, and kidney. However, drug interaction studies with P-gp substrates have not been conducted.

MANAGEMENT: Caution is advised when asciminib is used concomitantly with drugs that are substrates of P-gp, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy. The prescribing information recommends closely monitoring for the development of adverse reactions in patients receiving asciminib therapy with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. In addition, the prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a P-gp inhibitor like asciminib and for any dosage adjustments that may be required.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.