Several popular remedies for diaper rash and other skin problems contain an active ingredient that has been found to cause severe nerve and liver damage in research animals, according to a petition delivered to the Food and Drug Administration yesterday.
An FDA spokesman said the agency has no reports of serious side effects in humans from the skin products. "We will respond to the petition, as we do to all of them," he said.
The petition, from a group of scientists and health activists, asked the FDA to remove the products containing the ingredient from the market.
The ingredient, iodochlorhydroxyquin, is found in the over-the-counter product Vioform and the prescription product Vioform-Hydrocortisone, both manufactured by Ciba-Geigy as skin cream, ointment and lotion. The skin products are used for fungal and bacterial infections in children and adults, including diaper rash, athlete's foot and infected cases of eczema.
The same ingredient in those products formerly was marketed by Ciba-Geigy as Entero-Vioform, an oral remedy for travelers' diarrhea. It was suspected of causing more than 10,000 cases of a serious neurological disorder before its manufacture ceased in 1982.
A spokesman for Ciba-Geigy said, "We don't feel that the petition is justified based on the safety record of the product." Asked about the findings of nerve and liver damage in animals, he said there had been "no reports of an adverse reaction of that nature."
Drug industry surveys indicate that over 740,000 prescriptions were filled in the United States in 1984 for products containing iodochlorhydroxyquin, including over 600,000 for the Ciba-Geigy version. Other products containing the ingredient are Pricort Cream and Lotion (Arlo), HCV Creme (Saron), Nystaform Ointment (Miles Pharmaceuticals), Pedi-Cort V Creme (Pedinol) and generic versions.
In addition, approximately 175,000 tubes of Vioform cream and ointment were sold as a non-prescription skin remedy. No data are available on what proportion of the products sold are used on infants.
The petition, submitted to the FDA by Public Citizen's Health Research Group, was cosigned by researchers at the University of Nebraska who studied the drug's toxic effects, and by two Boston pediatricians and a New York medical student. It concludes, "the FDA should remove from the market all OTC [over-the-counter] and prescription drug products containing iodochlorhydroxyquin."
In the Nebraska study, scientists applied cream containing 3 percent iodochlorhydroxyquin (the concentration found in most versions on the market) to the skin of five dogs twice a day for 28 days, then covered the skin with plastic to simulate skin under a disposable diaper.
"All treated dogs lost weight," and "became lethargic and less responsive to stimuli," according to the petition. One dog died, and another developed paralysis of its hind legs.
When the treated dogs were killed and examined, "all had liver damage -- in some cases, really quite severe," said Sidney J. Stohs, chairman of the university's Department of Biomedicinal Chemistry and the study's author.
In a separate study, Stohs measured blood levels of iodochlorhydroxyquin in adults several hours after applying cream containing the drug to their skin and covering it with plastic wrap. He found 40 percent of the drug was absorbed into the bloodstream, almost as much as the 46 percent absorbed from the digestive tract when the drug is taken orally. Levels of the drug in the bloodstream were comparable to those found in the dogs.
When given as the oral drug Entero-Vioform, iodochlorhydroxyquin was suspected of causing more than 10,000 cases of a neurologic disorder called subacute myelo-optic neuropathy (SMON), whose symptoms included abdominal pain, weakness or paralysis of the legs, muscle twitching and blindness. Entero-Vioform was banned in Japan, where most of the cases occurred, in 1970, and removed from the U.S. market in 1972.
Stohs said that based on his findings, the same symptoms might occur in a baby with diaper rash who had the cream applied two or three times daily for two or three weeks.