Drug Interaction Report

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of telisotuzumab vedotin. Telisotuzumab vedotin is an antibody-drug conjugate (ADC) that releases MMAE via proteolytic cleavage, and MMAE has been shown in vitro to be primarily metabolized by CYP450 3A4. MMAE systemic exposure (AUC) is predicted to increase by 1.4-fold following concomitant administration of telisotuzumab vedotin with the potent CYP450 3A4 inhibitor ketoconazole.

MANAGEMENT: Caution is advised when telisotuzumab vedotin is used concomitantly with potent CYP450 3A4 inhibitors. Patients should be closely monitored for development or exacerbation of toxicities such as ocular surface disorders (e.g., dry eyes, keratitis, blurred vision), peripheral neuropathy, interstitial lung disease/pneumonitis, and peripheral edema. If serious adverse reactions occur, the dosing of telisotuzumab vedotin should be adjusted or withheld as necessary in accordance with the product labeling.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.