Rituxan Fatal Infections Lead FDA to Review Risk of Side Effects

Following reports that link side effects of Rituxan to fatal brain infections, the FDA is reviewing whether users of the cancer-fighting drug should use the medication for shorter periods of time or take “drug holidays” to reduce the risk.

According to a Wall Street Journal report, FDA officials indicate that they are discussing the potential changes and looking at whether the long-term use of Rituxan, without interruptions in treatment, may be a potential factor increasing the risk of a rare brain infection, known as progressive multifocal leukoencephalitis (PML).

The discussions come in the wake of a recent study published in the May 14 issue of the medical journal Blood, which linked 57 cases of PML brain infections to Rituxan side effects, with a 90% fatality rate. Although the risk of developing the fatal infection is still extremely rare in comparison to the drug’s use, the PML occurrence rate was found to be much higher than first thought.

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 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. The drug makers are currently petitioning the FDA to expand the approved uses for Rituxan to include treatment of chronic lymphocytic leukemia together with chemotherapy.

Progressive multifocal leukoencephalitis, which is also referred to as progressive multifocal leukoencephalopathy or PML, is a rare brain disease that attacks the central nervous system. Symptoms could include confusion, blurred vision, speech difficulties, movement problems, dizziness and loss of balance. There is no known cure and it can worsen over time, usually resulting in death.

Although the causal connection between PML and Rituxan has not been proven, it is possible that Rituxan suppresses the immune system enough so that the virus that causes PML runs unchecked by the body’s natural defenses. FDA officials are reviewing whether temporarily stopping use of the drug may give the immune system a chance to fight off the virus before it becomes PML.

Taking a “drug holiday” from Rituxan may decrease the risk of the fatal infection, but the tactic also has its own risks. Taking a break in treatment could potentially cause the underlying cancer to recur more severely. Genentech officials told the Wall Street Journal that there is no evidence at this time that the tactic would help.

Rituxan is not the only drug that has been linked to an increased risk of the fatal brain infection. A Raptiva recall was issued by Genentech on April 8, 2009 for their psoriasis medication after reports surfaced of several users developing PML. It was found that the risk of patients developing the PML side effects outweighed the benefits provided by the treatment.

In 2004, a link between PML and Tysabri, an injection used to treat multiple sclerosis and Chron’s disease, led to a temporary recall of the medication. Tysabri was reintroduced in 2006 with more stringent usage guidelines, but at least six new Tysabri PML infections have been reported since the drug’s return.

Rituxan currently has a “black box” label warning regarding the possibility of a link to PML, which is the strongest warning that can be placed on a prescription medication.