FDA Drug Safety Communication

The U.S. Food and Drug Administration (FDA) has 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. Both Arzerra and Rituxan are used to treat certain cancers of the blood and lymph system. Rituxan is also approved to treat other medical conditions, including rheumatoid arthritis. Both drugs suppress the body's immune system.

In patients with prior HBV infection, HBV reactivation may occur when the body's immune system is impaired. This infection can cause serious liver problems, including liver failure and death. Reactivation can occur in patients who previously had HBV infection that was clinically resolved, but who later require therapy for a condition such as cancer. When a treatment is given that can impair the body's immune system, the previous HBV infection can again become an active infection. The initial HBV infection may occur without obvious signs of liver disease, and it may remain dormant in liver tissue. Therefore, screening for evidence of prior exposure is necessary to reliably assess the risk of HBV reactivation.

The risk of HBV reactivation is already described in the Warnings and Precautions section of the labels for both drugs; however, cases continue to occur, including deaths, prompting FDA to examine this risk further for current evidence that may aid in recognition and reduction in the risk. HBV reactivation is being added to the existing Boxed Warning of the Rituxan label, and a new Boxed Warning is being created for the Arzerra label to describe the risk. The Warnings and Precautions section also is being revised for each drug to express new recommendations.

To decrease the risk of HBV reactivation, we recommend 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.

Health care professionals and patients should discuss the risks of serious infections, including HBV, before starting treatment with Arzerra or Rituxan. Patients should talk to their health care professional if they have any questions or concerns about these drugs.

View the full FDA Drug Safety Communication on FDA.gov