In a highly unusual step, a major medical organization -- the American Academy of Dermatology -- is protesting the FDA action.
"The AAD is very disappointed with this ruling by the FDA," AAD spokeswoman Abby Van Voorhees, MD, tells WebMD. "We don't think the science supports this harsh labeling. The link to cancer was not proven, and the data shows these medications to be quite safe."
Eczema patients -- and their doctors -- are going to be frightened by the warning, says Van Voorhees, assistant professor and director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.
"Eczema patients have a lot of pain and suffering, and we worry they might not get these medicines due to unwarranted fear," she says. "This is a medication that can be very helpful for patients. We would hate to see them be inadequately treated as a consequence."
Novartis, which makes Elidel, will fully comply with the FDA's ruling. But in an unusual move -- drug companies don't like to anger the FDA -- the company is publicly critical of the agency's action.
"We want to make it very, very clear that this action is not substantiated by scientific or clinical evidence," Novartis spokeswoman Megan Humphrey tells WebMD. "Based on 21,000 patients in clinical trials, and based on postmarketing use of Elidel in more than 6 million patients, there is no evidence of a causal relationship between Elidel and cancer."
FDA spokeswoman Crystal Rice says the FDA is merely warning that nobody knows whether the long-term use of Elidel and Protopic is safe.
"We acknowledge that there are different approaches and differences of opinion, but in the end, the major finding FDA wanted to convey was the report of cancer cases in patients," Rice says.
The FDA action was prompted by its Pediatric Advisory Committee. This group of independent experts in February 2005 voted 15-1 to recommend the black box warning.
P. Joan Chesney, MD, of St. Jude Children's Research Hospital in Memphis, Tenn., chaired the advisory panel. She declined to be interviewed for this article. However, she spoke to the issue at the February 2005 panel meeting. Verbatim transcripts of FDA advisory panel meetings appear on the FDA web site.
"There is a risk to long-term use [of Elidel and Protopic]," Chesney said in summing up the panel's deliberations. "There should be increased emphasis on use of the product only as second-line therapy because of the potential risk. ... Use in children under 2 years of age should be minimized, again because of unknown risk. ... It should not be used in immunosuppressed patients or those with an increased risk for cancer [because the drugs' immune-suppressing effects] in some cases may result in cancer."
Van Voorhees argues that there is very little evidence that either Elidel or Protopic has caused any cancers. The fact that the drugs' long-term risk is unknown, she says, is not enough reason to discourage their use.
"There are unknown risks with any medicine that is fairly new on the market," Van Voorhees says. "But currently there is really no evidence demonstrating that cancer was caused by Elidel or Protopic -- even in the rare cases among people using these drugs. Providing information about a theoretical concern is important. But we don't feel placing a black box warning on the label was the best way to do it."
Inappropriate Use or Good Clinical Practice?
Panel member Norman Fost, MD, MPH, is professor of pediatrics at the University of Wisconsin, Madison. He said during the panel discussion that he was alarmed at how many Elidel and Protopic prescriptions were being written as first-line treatments or for children under the age of 2 years.
"A black box warning may be excessive, may be overshoot, may be unduly inhibiting [to patients who need the drugs]," Fost said. "[But] it may be that's the only tool left to stop millions of prescriptions that are inappropriate. ... That may be the only way to do it."
Van Voorhees says that doctors have to be able to treat patients as best they can. Sometimes, she says, this means using drugs in ways that aren't yet officially approved. Such "off-label use" is common for a wide variety of medicines.
"It is very nice when caring for patients to have as many drugs at your disposal as possible," Van Voorhees says. "Rulings that limit the number of drugs that patients can access is not very helpful to doctors on the front line of caring for patients."
The FDA, she says, has made it clear that it would like to see Elidel and Protopic reserved only for patients for whom conventional steroidal medications don't work. And the FDA would prefer to see the drug prescribed only for short-term treatment. But there are real-world reasons to use the drugs in these ways, Van Voorhees says.
"There are specific situations, based on medical problems or locations of rash, that could make first-line treatment with Elidel or Protopic very appropriate," she says. "And the FDA is trying to encourage people to use these drugs for a shorter period. That can be very challenging, because eczema is painful and itchy and long lasting. We want to be able to maintain patients' skin with good rash control over a long time."