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."