Drugs for Rheumatoid Arthritis Must Warn of Fungal
Infection Risk
FDA invokes new authorities to alert patients and
prescribers to risk of Humira, Cimzia, Enbrel, and Remicade
Sept.
5, 2008 Millions of senior citizens fight against their own immune
systems. Four of the drugs used by many in this battle against some
autoimmune diseases, primarily rheumatoid arthritis, have been
identified by the Food and Drug Administration as a possible risk factor
in deadly fungal infections.
The FDA announced that the manufacturers of Humira,
Cimzia, Enbrel, and Remicade must strengthen the existing warnings, in
the Warnings and Precaution sections of the drugs' prescribing
information and Medication Guides, on the risk of developing
opportunistic fungal infections. Some patients with invasive fungal
infections have died.
The four drugs, known as tumor necrosis factor
alpha blockers (TNF-alpha blockers), which suppress the immune system,
are approved to treat a variety of conditions which may include
rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic
arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn's
disease.
FDA today exercised its new authority under the
Food and Drug Administration Amendments Act of 2007 to require
manufacturers of TNF inhibitors to make safety-related changes to
prescribing information, or labeling.
Under the FDA's new authorities, we can require
safety label changes and a risk evaluation and mitigation strategy,
known as REMS, when the agency becomes aware of new safety information,
said Bob Rappaport, M.D., director of the Division of Anesthesia,
Analgesia and Rheumatology Products, Center for Drug Evaluation and
Research. Requiring the risks to be highlighted will help health care
professionals be more vigilant in watching for these adverse events, and
is necessary to ensure that the benefits of these drugs outweigh their
risks.
Since the initial approval of the four TNF
blockers, the prescribing information for these drugs has included
information about the risk of serious infections, including fungal
infections. However, based on reports reviewed by FDA, health care
professionals are not consistently recognizing cases of histoplasmosis
and other invasive fungal infections, leading to delays in treatment.
Patients taking TNF blockers should be aware that
they are more susceptible to serious fungal infections. Those who
develop a persistent fever, cough, shortness of breath, and fatigue
should promptly seek medical attention. To assist in the diagnosis,
those being treated with TNF blockers should tell their health care
professionals where they live and what areas they have recently visited.
Patients who develop a fungal infection may be advised to stop the TNF
blocker until they recover.
FDA has reviewed 240 reports of histoplasmosis, an
infection caused by the fungusHistoplasma capsulatum, in patients being
treated with Enbrel, Humira, or Remicade. The majority of the reports
involved people in the Ohio River and Mississippi River valleys (the
fungus is commonly found in those areas). In at least 21 of the reports,
histoplasmosis was initially not recognized by health care
professionals, and antifungal treatment was delayed. Twelve of those
patients died.
The FDA reviewed one reported case of
histoplasmosis in a patient taking Cimzia. The FDA also has received
reports of cases of coccidioidomycosis and blastomycosis, including
deaths, in patients treated with TNF blockers.
TNF blocker manufacturers are required to submit
safety labeling changes, including strengthened warnings and revisions
to the Medication Guides to the FDA within 30 days or to provide a
reason why they do not believe labeling changes are necessary.
If they do not submit new language, or if the FDA
disagrees with the new language the company proposes, the Food and Drug
Administration Amendments Act of 2007 provides strict timelines for
resolving the labeling changes and allows the agency to issue an order
directing the labeling change as deemed appropriate to address the new
safety information.
Medication Guides will become part of a REMS for
Humira and Remicade and are already part of a REMS for Enbrel and
Cimzia. The manufacturers for all four of these drugs will also be
required to educate prescribers about the risks.
For more information:
http://www.fda.gov/cder/drug/InfoSheets/HCP/TNF_blockersHCP.htm
