THOUSAND OAKS, California, and PHILADELPHIA, Pennsylvania—Amgen, Inc and Wyeth Pharmaceuticals have agreed to add a “black box” notice to prescribing information for Enbrel® (etanercept) regarding drug-associated infection risk. According to a Food and Drug Association Medwatch safety alert, “The revisions include a boxed warning about infections, including serious infections leading to hospitalization or death, which have been observed in patients treated with Enbrel. Infections have included bacterial sepsis and tuberculosis (TB).1 The information had previously been a bold-face warning regarding the risk of infections and TB but was upgraded to the more serious black box due to new postmarketing surveillance data.

“The revisions include a boxed warning about infections, including serious infections leading to hospitalization or death, which have been observed in patients treated with Enbrel.”—Food and Drug Association
The heightened warning notice advises physicians to
  • test all patients for latent TB infection before beginning treatment
  • complete treatment of latent TB before beginning treatment
  • educate patients about symptoms of infection such as bacterial sepsis and TB
  • monitor patients closely for signs and symptoms of infection during and after treatment with Enbrel
  • monitor all patients receiving the drug for signs and symptoms of active TB, including those who initially tested negative for latent TB


The updated “adverse reactions” section of the labeling states, “In global clinical studies of 20,070 patients (28,308 patient-years of therapy), TB was observed in approximately 0.01% of patients. In 15,438 patients (23,524 patient-years of therapy) from clinical studies in the US and Canada, TB was observed in approximately 0.007% of patients.”

However, a letter from Amgen-Wyeth to healthcare professionals also states, “Data from clinical trials and preclinical studies suggest that the risk of reactivation of latent TB infection is lower with Enbrel than with TNF-blocking monoclonal antibodies.”2

The FDA warning adds, “Patients who develop an infection should be evaluated for appropriate antimicrobial treatment and, in patients who develop a serious infection, Enbrel should be discontinued.”

References

1. 2008 safety alerts. FDA Website. http://www.fda.gov/medwatch/safety/2008/safety08.htm#Enbrel.
2. Harper SE, Freundlich B. Tuberculosis and infections with Enbrel (entanercept) [letter]. FDA Website. http://www.fda.gov/medwatch/safety/2008/safety08.htm#Enbrel.