Two relatively new and very popular prescription creams used to treat eczema (search) in children and adults may soon carry a "black box" warning — indicating the drugs represent a cancer risk for some.

In an FDA meeting, a distinguished nationwide panel of experts reviewed medical data that linked Elidel (search) and Protopic (search) with an increased risk of skin cancer and lymphoma.

Their recommendation: That both medications carry a warning that the drugs may increase the risk of cancer. They continue to back the original FDA ruling that the drugs should not be used in children under the age of two.

"We made our recommendation based on animal data and biologic plausibility combined with the fact that the use of these products is increasing tremendously," says Dianne Murphy, MD, committee member and FDA director of the Office of Pediatric Therapeutics.

Both drugs are currently approved for the treatment of eczema, an inflammatory condition of the skin which affects some 15 million Americans, 20 percent of whom are children. The condition causes dry, red, itchy skin that can blister or develop scaly patches.

The majority of patients develop their first bout of eczema before they are 12 months old. Both Elidel and Protopic are currently approved for use in children aged two and up.

While the FDA committee recommends a stern warning for all those who use the drug, Murphy stresses that there were no human clinical trials that indicated cancer was a risk.

However, she tells WebMD that the committee reviewed numerous animal studies that did indicate a risk, including one monkey study that showed an increasing risk of developing tumors as doses increased.

"The greater the dose the greater the number of tumors — and with the highest dose we saw seven out of eight monkeys develop tumors," says Murphy.

Equally important was the "biologic plausibility of the drugs” — meaning, the way in which the medications work. These medications suppress the immune system, which may be a precipitating factor in the development of cancer.

"It depends greatly on what other precipitating factors may be present in an individual patient's profile, but this could certainly be a contributing factor under certain circumstances," says Murphy.

Adding more fuel to the fire was a series of isolated adverse events voluntarily reported by consumers and their doctors to the FDA.

Since Protopic was approved in 2000, the FDA has received 10 reports of serious adverse events in children under age 2, and 17 cancers in all age groups. These included non-Hodgkin's lymphoma and skin cancer. Published reports say three of these cancer patients have died.

Elidel, which was approved in 2001, appears to have a similar profile. According to FDA records, from approval in December 2001 through September 2004, there were 54 serious adverse events reported in children under the age of 2, and eight cancers in all age groups, including four in children over the age of 2. The majority of the noncancer events were skin related, and resulted in hospitalization for 15 children.

Creams Used When Steroids Fail

While the number of tumors detected is significant, experts point out it is still small compared with the millions of people using these medications. According to the FDA, nearly 9 million prescriptions were written for Elidel since its approval, with 12.7 percent prescribed for children between 1 and 2 years old. Although Protopic was on the market sooner, prescriptions for this drug climbed to just 3.5 million, with about 8 percent given to younger patients, says the FDA.

Other drugs used to treat eczema include steroid medications (search), which are normally the initial treatment. Experts say both Elidel and Protopic are considered second-string drugs, recommended only when steroid medications fail.

If you are currently using either Protopic or Elidel, Murphy says be certain you are using them only for the conditions for which they have been approved, and only if there are no other treatment options. Experts also say you should talk to your doctor about whether or not you are at increased risk for cancer due to other precipitating factors, including personal and family history of disease.

The FDA is expected to rule on the "black box" warning soon, though it is likely they will take the committee’s recommendation.

Published reports indicate both drug manufacturers say there is no clinical evidence of increased cancer risk in humans with either medication. Both companies agree monitoring should continue. Published reports say the companies also plan to review safety data and are planning to continue studies on their own.

By Colette Bouchez, reviewed by Michael W. Smith, MD

SOURCES: Diane Murphy, MD, director, Office of Pediatric Therapeutics, FDA. FDA advisory committee briefing, Feb. 15, 2005. Questions and Answers on Atopic Dermatitis, American Academy of Dermatology.