FDA Mandates Package Label Changes for TNF Blockers

The FDA announced last month that it would require manufacturers of tumor necrosis factor, or TNF, blockers to strengthen their products' package label warnings to highlight potential risks for opportunistic fungal infections that can result in death.

TNF blockers, which suppress the immune system, are approved to treat various conditions, including rheumatoid arthritis, plaque psoriasis, ankylosing spondylitis and Crohn's disease. Four TNF blockers currently are marketed in the United States: certolizumab pegol, sold as Cimzia; etanercept, sold as Enbrel; adalimumab, sold as Humira; and infliximab, sold as Remicade.

"Patients taking TNF blockers should be aware they are more susceptible to serious fungal infections," the FDA said in a Sept. 4 news release. "Those who develop a persistent fever, cough, shortness of breath and fatigue should promptly seek medical attention."

In an alert to health care professionals, the FDA stated that histoplasmosis and other fungal infections are not always promptly identified in patients taking TNF blockers, a situation the agency said has led to "delays in appropriate treatment, sometimes resulting in death." Deaths from coccidioidomycosis and blastomycosis also have been reported, according to the alert.

For patients taking TNF blockers who present with signs and symptoms indicating a possible fungal infection, said the alert, "health care professionals should ascertain if patients live in or have traveled to areas of endemic mycoses. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified. ... As with any serious infection, consider stopping the TNF blocker until the infection has been diagnosed and adequately treated."

As always, FDA officials encourage clinicians to report any unexpected adverse or serious events associated with the use of these drugs to the FDA's MedWatch program; such reports can be filed online.