Drug Interaction Report

GENERALLY AVOID: Coadministration of dinutuximab or dinutuximab beta with corticosteroids may potentiate the risk of infections due to additive immunosuppressive activity. Infections, including sepsis, pneumonia, herpes virus infection, myelitis, and encephalomyelitis as well as hematologic toxicities, including thrombocytopenia and neutropenia, have been reported with both dinutuximab and dinutuximab beta therapy.

MANAGEMENT: The manufacturer of dinutuximab beta recommends that, except for life threatening conditions, concomitant use of dinutuximab beta and corticosteroids should be avoided for 2 weeks prior to the first course of dinutuximab beta and for 1 week after the last course (UK). If concomitant use is required, close clinical and laboratory monitoring for the development of systemic infections and severe hematologic adverse effects is recommended both during and after discontinuation of therapy.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of 21-desdeflazacort, the active metabolite of deflazacort that is formed by esterases after oral administration and further metabolized by CYP450 3A4 to several inactive metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. 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 systemic exposure to 21-desdeflazacort may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Deflazacort should not be administered with grapefruit juice.