Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the systemic exposure to indacaterol following oral inhalation, as it is a substrate of both the isoenzyme and efflux transporter. When a single 300 mcg dose of indacaterol inhalation powder was administered in combination with the potent dual CYP450 3A4/P-glycoprotein inhibitor, ketoconazole (200 mcg twice daily for 7 days), indacaterol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.9-fold, respectively. These changes probably reflect the impact of maximal combined inhibition. Similarly, verapamil 80 mg three times a day for 4 days increased indacaterol Cmax by 1.5-fold and AUC by 2-fold, while erythromycin 400 mg four times a day for 7 days increased indacaterol Cmax by 1.2-fold and AUC by 1.4-fold. Ritonavir 300 mg twice daily for 7.5 days had no effect on the Cmax of indacaterol, but increased its AUC by 1.7-fold. Indacaterol oral inhalation powder has been evaluated in clinical trials for up to one year at doses up to 600 mcg. No dosage adjustment is necessary at the 75 mcg dose when used with CYP450 3A4 and P-glycoprotein inhibitors.

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.