Drug Interaction Report

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of afatinib, which is a substrate of the efflux transporter. In study subjects, oral administration of the P-gp inhibitor ritonavir (200 mg twice daily) one hour before afatinib dosing resulted in a 48% increase in afatinib systemic exposure. There was no change in afatinib exposure when ritonavir was administered simultaneously with, or 6 hours after, the afatinib dose.

MANAGEMENT: Caution is advised if afatinib is used in combination with P-gp inhibitors. Patients should be monitored for potentially increased adverse effects such as diarrhea, which may lead to dehydration with or without renal impairment; cutaneous reactions including rash, erythema, and bullous, blistering, or exfoliating lesions; interstitial lung disease such as lung infiltration, pneumonitis, acute respiratory distress syndrome, and allergic alveolitis; hepatotoxicity, which may be life-threatening or fatal; keratitis characterized by acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye, and/or ulceration; and left ventricular dysfunction. The manufacturer recommends reducing the daily dose of afatinib by 10 mg if not tolerated. The previous dose may be resumed after discontinuation of the P-gp inhibitor as tolerated.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of afatinib. According to the product labeling, administration of afatinib with a high-fat meal decreased peak plasma concentration (Cmax) by 50% and systemic exposure (AUC) by 39% compared to administration in the fasted state.

MANAGEMENT: Afatinib should be taken at least 1 hour before or 2 hours after a meal.

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.