Arzerra (ofatumumab) and Rituxan (rituximab): Drug Safety Communication - New Boxed Warning, Recommendations to Decrease Risk of Hepatitis B Reactivation

[Posted 09/25/2013]

AUDIENCE: Oncology, Pharmacy, Rheumatology, Patient

ISSUE: FDA approved changes to the prescribing information of the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab) to add new Boxed Warning information about the risk of reactivation of hepatitis B virus (HBV) infection. The revised labels also will include additional recommendations for screening, monitoring, and managing patients on these drugs to decrease this risk.

In patients with prior HBV infection, HBV reactivation may occur when the body’s immune system is impaired. HBV reactivation has occurred in patients with prior HBV exposure who are later treated with drugs classified as CD20-directed cytolytic antibodies, including Arzerra (ofatumumab) and Rituxan (rituximab). Some cases have resulted in fulminant hepatitis, hepatic failure, and death.

See the FDA Drug Safety Communication for additional information, including a Data Summary.

BACKGROUND: Arzerra is used to treat chronic lymphocytic leukemia (CLL) in patients who have further disease after treatment with the anti-cancer drugs fludarabine and alemtuzumab. Rituxan is used to treat non-Hodgkin’s lymphoma and CLL. It is also used to treat other medical conditions, including rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

RECOMMENDATIONS: To decrease the risk of HBV reactivation, FDA recommends that health care professionals:

• Screen all patients for HBV infection before starting treatment with Arzerra or Rituxan by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
• Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection.
• Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during Arzerra or Rituxan therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy with these drugs.
• In patients who develop reactivation of HBV while on Arzerra or Rituxan, immediately discontinue the drug and start appropriate treatment for HBV. Also discontinue any chemotherapy the patient is receiving until the HBV infection is controlled or resolved.  Because of insufficient data, no recommendation can be made regarding the resumption of Arzerra or Rituxan in patients who develop HBV reactivation hepatitis.

For Patients:

• Before receiving Arzerra or Rituxan, tell your health care professional if you have or have had any severe infections, including HBV.
• If you have had HBV infection, your health care professional should monitor you for HBV infection during treatment and for several months after you stop treatment with Arzerra or Rituxan.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[09/25/2013 - Drug Safety Communication - FDA]