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 may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.