Welcome to FDA Drug Safety Podcasts from the Division of Drug Information. On September 25, 2013, the FDA issued a Drug Safety Communication announcing that the FDA has approved changes to the prescribing information of the immune-suppressing and anti-cancer drugs Arzerra (or ofatumumab) and Rituxan (or rituximab) to add new Boxed Warning information about the risk of reactivation of hepatitis B virus (or 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 is also 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 (or HBsAg) and hepatitis B core antibody (or 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.
At this time, FDA recommends that Health Care Professionals be aware of the following:
- HBV reactivation has occurred in patients with prior HBV exposure who are later treated with drugs classified as CD20-directed cytolytic antibodies, including Arzerra and Rituxan. Some cases have resulted in fulminant hepatitis, hepatic failure, and death.
- HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis (i.e., increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death).
- Cases of HBV reactivation have been reported in patients who are HBsAg positive.
- Cases have also been reported in patients who are HBsAg negative, but test positive for anti-HBc. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [or anti-HBs] positive).
- Screen all patients for HBV infection before initiating treatment with Arzerra or Rituxan by measuring HBsAg and anti-HBc.
- Note that patients who have protective antibodies due to immunization will test positive only for anti-HBs.
- For patients who show evidence of prior HBV exposure by testing positive for HBsAg or anti-HBc, consult with physicians with expertise in managing hepatitis B regarding monitoring and considerations for HBV antiviral therapy.
- Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following Arzerra or Rituxan therapy. HBV reactivation has been reported up to 12 months following completion of therapy.
- In patients who develop reactivation of HBV while on Arzerra or Rituxan, immediately discontinue the drug and institute appropriate HBV treatment. Also discontinue any concomitant 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.
- Report adverse events involving Arzerra or Rituxan to the FDA MedWatch program at www.fda.gov/MedWatch.
Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. A link to this communication and the complete data summary can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at email@example.com.
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FDA Drug Safety Podcast: Boxed Warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab) mp3(MP3 - 6.9MB) [ARCHIVED] FDA Drug Safety Communication: Boxed Warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab)