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: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.