Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and efflux transporter. When apixaban was coadministered with the moderate CYP450 3A4 and P-gp inhibitor diltiazem (360 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.4-fold, respectively. Likewise, coadministration with the P-gp inhibitor naproxen (500 mg single dose) increased the mean apixaban Cmax and AUC by approximately 1.6- and 1.5-fold, respectively.

MANAGEMENT: No dosage adjustment for apixaban is required during concomitant therapy with lone inhibitors of CYP450 3A4 or P-gp, or moderate or weak dual inhibitors of both CYP450 3A4 and P-gp. However, caution may be advisable. Closer monitoring of the pharmacologic effects of apixaban may be appropriate whenever a CYP450 3A4 or P-gp inhibitor is added to or withdrawn from therapy. Patients should be routinely evaluated for signs and symptoms suggesting blood loss such as a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress (in pregnant women).

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.