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.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.