Can Doxylamine, A Sleep Aid Ingredient, Cause Cancer

by: Marian Segal

In 1978, FDA approved a new drug application providing for OTC marketing of doxylamine succinate for nighttime sleep-aid use.

Subsequently, the National Cancer Institute found that methapyrilene, an antihistamine similar to doxylamine, was a potent cancer-causing agent in rats. As a result, methapyrilene was removed from the market in 1979. This prompted FDA's National Center for Toxicological Research to study doxylamine for carcinogenicity and chronic toxicity.

The scientists gave mice and rats variable doses of doxylamine in their feed for two years and then examined their tissues.

"We got the study results in 1991, and they were inconclusive," says FDA microbiologist Katharine Freeman. "There were no significant differences in survival in the treated or nontreated rats or mice, and it was impossible to say if the changes seen in some animals--like tumors and liver toxicity--were species-specific, or if the findings were relevant to human use. We were left with the problem of how to deal with such nebulous findings."

At FDA's request, the Pulmonary-Allergy Drugs Advisory Committee evaluated the data and concluded doxylamine would not likely cause cancer in humans. It recommended OTC status, but suggested the rodent findings be included in the product labeling.

Concerned about how to present the information in a way that would be useful to consumers, FDA in 1993 asked its newly formed Nonprescription Drugs Advisory Committee for recommendations about doxylamine and its labeling.

This committee agreed with the pulmonary-allergy panel that doxylamine is unlikely to cause cancer in humans and is safe for OTC use. It recommended, however, that there be no statement about tumors in the labeling, but that FDA present the information in an agency talk paper and FDA Consumer article. In January 1994, FDA amended the monograph for OTC antihistamine drug products to include doxylamine succinate.

This article was published in FDA Consumer magazine several years ago. It is no longer being maintained and may contain information that is out of date.

About the Author

Marian Segal