Arzerra, Rituxan Could Reactivate Hepatitis B Virus, FDA Warns

Federal health regulators are warning that the leukemia drugs Arzerra and Rituxan may reactivate hepatitis B virus infections in users, after more than 100 suspected deaths have been identified in connection with the issue.  

The FDA issued a drug safety communication on September 25, announcing new black box label warnings for the immune-suppressing and anti-cancer drugs. Black box warnings are the strongest label warning the FDA can require a drug to carry.

According to the FDA, use of side effects Rituxan or Arzerra may reactivate the hepatitis B virus (HBV) in patients with prior HBV infections, due to their impairment of the immune system. This can lead to fulminant hepatitis, liver failure, and death. Both drugs belong to a class known as CD20pdirected cytoytic antibodies.

Following a review of the FDA’s Adverse Event Reporting System, health officials found at least 109 cases of patients taking the drugs who later died of HBV-related acute liver injury. Virtually all (106) of the cases were associated with Rituxan use. Only three were linked to Arzerra. The FDA found 32 of the cases had enough data for a diagnosis, and 22 of those were confirmed as being linkted to HBV reactivation.

The FDA is recommending that doctors screen all patients for HBV infection before beginning treatment with either drug. The agency recommends that patients showing evidence of prior HBV infection be sent to consult with physicians with experience in managing hepatitis B. The doctors should consider monitoring their hepatitis B and placing them on HBV antiviral therapy.

The monitoring should during the entirety of Rituxan and Arzerra therapy and for several months after, since some patients have shown HBV reactivation up to a year after completion of therapy, the FDA warns.

Patients who show signs of HBV reactivation should be taken off the drugs immediately and given HBV treatment.

Rituxan Brain Infections

Rituxan (rituximab) is a chimeric monoclonal antibody drug that helps the immune system fight specific types of cells, like lymphoma cancer cells. The drug, which is manufactured jointly by Genentech, Inc. and Biogen Idec, Inc., was approved by the FDA in 1997 for treatment of non-Hodgkin’s lymphoma and rheumatoid arthritis, generating annual sales of about $2.3 billion. Like Arzerra, it is also approved for the treatment of chronic lymphocytic leukemia (CLL).

There are concerns about Rituxan’s connection to the deadly brain virus, progressive multifocal leukoencephalopathy (PML), and whether the long-term use of Rituxan, without interrupting the treatment, may be a potential factor increasing the risk of PML. Some experts have suggested that having patients take time away from the drug’s use, referred to as “drug holidays” may give their body the opportunity to fight off the virus that causes the infection and reduce the risk of progressive multifocal leukoencephalopathy from Rituxan. There is a black box warning on the label about the possible link between Rituxan and PML.

Progressive multifocal leukoencephalopathy is a viral infection that causes inflammation at multiple locations in the brain, leading to potentially life-threatening brain damage. Symptoms could include loss of vision, impaired speech, paralysis, cognitive decline and weakness. There is no known cure for PML, but the disease can sometimes be slowed or stopped by reducing immunosuppression.

Arzerra (ofatumumab) is a relatively new drug from GlaxoSmithKline first approved in 2009 for the treatment of CLL in patients who have already been treated with the anti-cancer drugs fludarabine and alemtuzumab.