Drug Interaction Report

MONITOR CLOSELY: Coadministration of loncastuximab tesirine with antineoplastic, immune-modulating, immuno- or myelosuppressive therapies may potentiate the risk of severe infections, myelosuppression, and/or other unintended additive immunosuppressive effects. Serious and fatal infections, including opportunistic infections, as well as myelosuppression, including neutropenia, thrombocytopenia, and anemia have been reported with the use of loncastuximab tesirine. Concomitant use may potentiate these risks. However, clinical data are not available.

MANAGEMENT: The safety and efficacy of loncastuximab tesirine use in combination with other immuno- or myelosuppressive agents have not been evaluated. Patients receiving loncastuximab tesirine should be monitored closely for the development of signs and symptoms of infection and/or myelosuppression. The manufacturers' recommendations and institutional protocols for dosage, treatment regimens, monitoring, and management of toxicities should be consulted.

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.