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 pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.