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.

GENERALLY AVOID: Theoretically, coadministration with grapefruit juice may increase the plasma concentrations of pacritinib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, clarithromycin. In a clinical drug interaction study, a single dose of pacritinib (400 mg) was administered following treatment with clarithromycin (500 mg twice daily for 5 days). The peak plasma concentration (Cmax) and systemic exposure (AUC) of pacritinib increased by 30% and 80%, respectively, compared to pacritinib administered alone. Longer treatment with clarithromycin that results in maximal CYP450 3A4 inhibition may increase pacritinib exposure even higher. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to pacritinib may increase the risk of adverse effects such as diarrhea, thrombocytopenia, infection, and QT prolongation.

Pacritinib pharmacokinetics were not significantly affected when administered with a high-fat meal.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid consumption of grapefruit or grapefruit juice during treatment with pacritinib. Pacritinib may be administered with or without food.