Drug Interaction Report

MONITOR CLOSELY: The use of the CD20-directed cytolytic antibody ublituximab with other immune-modulating or immunosuppressive therapy, including immunosuppressant doses of corticosteroids may increase the risk of infections. Adverse events most commonly reported with ublituximab alone included upper respiratory tract infections and urinary tract infections. However, serious and life-threatening infections, such as hepatitis B virus (HBV) reactivation have been reported in relapsing multiple sclerosis (RMS) controlled clinical trials with ublituximab, as well as fatal infections. In addition, Progressive Multifocal Leukoencephalopathy (PML) due to JC virus infection, fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have been reported in patients treated with other anti-CD20 antibodies; however, these adverse events were not reported in RMS controlled clinical trials with ublituximab.

MANAGEMENT: The increased risk of additive immunosuppression should be considered if coadministering ublituximab with other immunosuppressive therapy. In addition, the prolonged immunosuppressant effects and mode of action of other immunosuppressant drugs such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone should be considered prior to starting ublituximab therapy. Patients should be advised to immediately notify their doctor if they develop signs or symptoms of infection, including HBV reactivation, upper or lower respiratory tract infection, urinary tract infections, herpes-related infection, or PML.

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.