Ofatumumab (Arzerra®) and Rituximab (Rituxan®)
October 2, 2013
A boxed warning will be added to the label of ofatumumab (Arzerra®) and the boxed warning will be revised in the label of rituximab (Rituxan®) to include the risk of reactivation of hepatitis B virus (HBV). The Warnings and Precautions sections of the labels of ofatumumab and rituximab already include information about the risk of HBV reactivation, but cases of fatal liver injury have occurred. Additional recommendations to reduce the risk of reactivation of HBV have been added to both labels.
Ofatumumab is FDA-approved for chronic lymphocytic leukemia (CLL) and rituximab is FDA-approved for non-Hodgkin’s lymphoma, CLL, rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis. Ofatumumab and rituximab are both CD20-directed cytolytic monoclonal antibodies.
Clinically resolved hepatitis B infections can reactivate during therapy with ofatumumab or rituximab. Hepatitis and fatal liver injury can occur following HBV reactivation. Patients are at risk for HBV reactivation if hepatitis B core antibody (anti-HBc) or hepatitis B surface antigen (HBsAg) is positive. Hepatitis B surface antigen (anti-HBs) is positive in patients with protective antibodies following immunization against HBV and does not indicate HBV reactivation unless anti-HBc or HBsAg is also positive.
According to the Adverse Event Reporting System database, 32 cases of fatal liver injury due to confirmed HBV reactivation have occurred in patients taking ofatumumab (1 case since FDA-approval in October 2009) or rituximab (31 cases since FDA-approval in November 1997). Cases occurred between 63 days after initiating therapy and up to 12 months after the final dose. All cases occurred in patients who received other chemotherapy in addition to ofatumumab or rituximab. Most patients were male (n=21) with a mean age of 62 years. Seventy-seven additional cases of fatal liver injury were reported in patients taking ofatumumab (2 cases) or rituximab (75 cases), but HBV reactivation was not confirmed.
The new recommendations to decrease the risk of HBV reactivation in patients treated with ofatumumab or rituximab include:
- Measure anti-HBc and HBsAg prior to initiating therapy to identify patients with previous HBV infection.
- In patients with positive anti-HBc or HBsAg, consult a hepatitis specialist to determine appropriate monitoring and antiviral therapy.
- Monitor patients for signs of HBV infection or reactivation during therapy and for several months after discontinuing ofatumumab or rituximab.
- Immediately discontinue ofatumumab or rituximab in patients who develop HBV infection and begin treatment. Discontinue all other chemotherapy until resolution of the HBV infection.
- It is not known if patients who develop HBV reactivation hepatitis can safely restart treatment with rituximab or ofatumumab.
Additional information is available at:
- FDA Medwatch Alerts – September 25, 2013:
- FDA Drug Safety Communication – September 25, 2013:
October 2, 2013, University of Utah, Drug Information Service. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.