FDA Demands Tougher Warnings on Immunosuppressive Drugs

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FDA Demands Tougher Warnings on Immunosuppressive Drugs

09.03.08

Forbes - NY*

http://www.forbes.com/forbeslife/health/feeds/hscout/2008/09/04/hscou

t619099.html

THURSDAY, Sept. 4 (HealthDay News) -- Federal health authorities

have asked the manufacturers of four widely used immunosuppressive

drugs to bolster safety warnings on the risk of developing

opportunistic fungal infections.

The drugs, Humira, Cimzia, Enbrel and Remicade, belong to a class of

medications known as tumor necrosis factor alpha blockers (TNF-alpha

blockers), which suppress the immune system and are approved to

treat several conditions including rheumatoid arthritis, juvenile

idiopathic arthritis, psoriatic arthritis, plaque psoriasis,

ankylosing spondylitis and Crohn's disease.

All four drugs already carry black-box warnings related to different

safety issues, including fungal infections.

" FDA has asked the manufacturers of these four drug products to

highlight existing warnings of fungal infections, " Dr.

Siegel, clinical team leader in the division of anesthesia,

analgesia and rheumatology products at the FDA's Center for Drug

Evaluation and Research, said at a Thursday news conference. " The

box warning, which is the most serious warning in the labeling, must

be upgraded to strongly warn doctors to consider the occurrence of

histoplasmosis and other fungal infections. "

Histoplasmosis is caused by the fungus Histoplasma capsulatum and

can cause flu-like symptoms. The FDA reviewed 240 reports of

histoplasmosis in patients taking Enbrel, Humira or Remicade, most

of whom reside in the Ohio River and Mississippi River valleys,

where the fungus is endemic.

Twenty-one of these patients had delayed diagnoses and therefore

delayed treatment. Of these, 12 died. Overall, among the 240

patients reviewed, 45 died.

" These infections need to be identified early enough so that

treatment is not delayed, " Siegel said. " In a number of cases,

treatment was delayed and resulted in prolonged hospitalization and

death. "

Authorities also looked at one reported case of histoplasmosis in a

patient taking Cimzia. There have also been reports of other fungal

infections, notably coccidioidomycosis and blastomycosis, some

fatal, in patients taking these drugs.

The FDA is already in the middle of a safety review of TNF blockers,

including an investigation into whether or not the drugs are linked

with the development of cancer, particularly lymphoma, in children

and young adults. " We have a six-month timeline for that review, and

we intend to meet that timeline, " Siegel said.

All the drug labels already include information about possible

fungal infections, but authorities expressed concern that the issue

wasn't highlighted appropriately.

" We've been concerned about the possibility of serious infectious

since we initially approved these drugs, and it has been in the

labeling since the beginning, " Siegel said. " Warnings about serious

infections have included fungal infections. What's new is that we

became aware that some physicians may not be considering the

possibility of fungal infections early enough, so we want to raise

awareness. So far, companies have been fully cooperating with

efforts here. "

" We don't want to give the impression that these conditions were

neglected, " Siegel continued. " They're hard to diagnose, and they

can mimic other conditions. We think the new message is that people

weren't aware that this might happen but that it is under-diagnosed

and important to identify. "

The manufacturers are required to submit labeling changes within 30

days or to outline reasons as to why labeling changes are not

necessary.

Doctors and patients should be on the lookout for persistent fever,

cough, shortness of breath and fatigue. Any patients experiencing

these symptoms, especially if they live or have traveled to areas

where the fungus is endemic, should seek medical attention

immediately.

" What we're trying to do here is help patients own their own health

care, and our advice is don't hesitate to contact their doctor if

they feel any of these key symptoms related to these kinds of

infections, " Siegel said.