On September 4, the FDA announced that the manufacturers of all TNF-α blockers must strengthen existing warnings in the product labeling regarding development of invasive fungal and other opportunistic infections.21 At least 12 patients who developed invasive fungal infections while receiving anti-TNF agents have died. Medication Guides are now also required upon medication dispensing.22 It has come to the attention of the FDA that healthcare professionals are not reliably identifying cases of histoplasmosis and other invasive fungal infections, leading to treatment delays and deaths. The FDA has reviewed over 240 reports of histoplasmosis, of coccidioidomycosis and blastomycosis in patients on TNF blockers. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified. When possible, an infectious disease consult should be obtained. As with any serious infection, consider stopping the TNF blocker until the infection has been diagnosed and adequately treated. The Boxed Warning and the Warnings and Precaution of the drug labels were updated and the drug manufacturers were also required to educate prescribers about these risks.
On October 16, the FDA announced a new “boxed warning” regarding life-threatening infections and PML associated with efalizumab (Raptiva, Genentech) treatment.23,24 This decision was based on the FDA’s postmarket surveillance, which identified a case of PML in a 70-year-old who received efalizumab for over four years.25 This patient was not receiving any other immunosuppressants and did not appear immune compromised. Physicians and other healthcare professionals treating patients with efalizumab need to be alert to new onset neurologic symptoms and provide consultation with a neurologist, brain MRI, and lumbar puncture, as clinically indicated.
