FDA Orders Additional Warnings on TNF-alpha Blockers
The FDA has announced that the makers of four TNF-alpha drugs (Enbrel, Remicade, Humira, and Cimzia) must strengthen warnings about fungal infection. Warnings already exist on TNF-alpha drugs regarding serious infection, including fungal infection, but the FDA fears fungal infection is going unnoticed in too many patients.
The "emphasized" warning will appear in the Boxed Warnings, the Warnings and Precaution sections of the prescribing information that is included with each of the drugs, and in the Medication Guides for patients. The warning will emphasize the risk of developing an opportunistic fungal infection with TNF-alpha use. The drug makers will also have to educate prescribers about the risk.
Indications for the TNF-alpha Blockers
Enbrel has been approved to treat moderate to severe rheumatoid arthritis, moderate to severe juvenile rheumatoid arthritis, psoriatic arthritis.ankylosing spondylitis, and chronic moderate to severe plaque psoriasis.
Remicade has been approved to treat moderate to severe rheumatoid arthritis and active psoriatic arthritis. Other conditions which have benefited from Remicade infusions include juvenile rheumatoid arthritis, ankylosing spondylitis, uveitis, psoriasis, sarcoidosis, and Crohn's disease.
Humira has been approved to treat rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.
Cimzia was approved on April 22, 2008 to treat moderate to severely active Crohn's disease in adults who have not been helped by usual treatments. On May 14, 2009, Cimzia was approved for adults who have moderately to severely active rheumatoid arthritis.
The Reason for "Beefing-up" the Existing Fungal Infection Warning
Based on reports that were reviewed by the FDA, health care professionals (doctors) are not recognizing cases of histoplasmosis and other fungal infections consistently -- leading to delayed treatment. The FDA reviewed 240 reports of histoplasmosis, an infection caused by the fungus Histoplasma capsulatum, in patients treated with Enbrel, Remicade, or Humira. The majority of those reports came from an area where H. capsulatum is commonly found (the Ohio River and Mississippi River valleys). In at least 21 of those cases, histoplasmosis was not diagnosed initially, leading to delayed treatment -- and ultimately 12 of those patients died.
The FDA also reviewed a case of histoplasmosis in a patient taking Cimzia. There were also reports of patients who took TNF blockers and developed coccidioidomycosis and blastomycosis -- some resulting in death.
Symptoms of Possible Systemic Fungal Infection
Patients should be monitored and observed for symptoms of systemic fungal infection during and after treatment with TNF blockers. Patients should immediately report the following symptoms to their doctor if they occur:
- fever
- malaise
- weight loss
- sweats
- cough
- dyspnea (shortness of breath)
- pulmonary infiltrates on x-ray
- serious systemic illness including shock
Also, be sure to tell your doctor if you already have or if you are planning to travel to any region where certain fungi are more common. The awareness of the risk of fungal infection with the use of TNF-alpha blockers, as well as awareness of symptoms associated with fungal infection, is very important so patients can receive timely, appropriate treatment.
Sources:
FDA: Manufacturers of TNF-Blocker Drugs Must Highlight Risk of Fungal Infections. FDA News. September 4, 2008.
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01879.html
Information for Healthcare Professionals. Cimzia, Enbrel, Humira, and Remicade. FDA. September 4, 2008.
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124185.htm
