Drug Interaction Report

MONITOR: Coadministration with mosunetuzumab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Initiation of mosunetuzumab treatment causes transient release of cytokines that may suppress CYP450 isoenzymes, although the potential for interaction has not been studied. According to the manufacturer, the highest drug-drug interaction risk would be after the first dose of the first cycle, up to 14 days after the second 60 mg dose on the first day of the second cycle, as well as during and after cytokine release syndrome.

MANAGEMENT: Caution is advised when mosunetuzumab is prescribed to patients receiving drugs that are metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic index such as carbamazepine, colchicine, cyclosporine, disopyramide, phenytoin, quinidine, theophylline, warfarin, macrolide immunosuppressants, vinca alkaloids, and some narcotic analgesics. Clinical laboratory monitoring are recommended following the initiation of mosunetuzumab, and the individual dosage of the concomitant agents adjusted as needed.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.

MANAGEMENT: Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.