Study knocks popular cough and cold medication ingredient off the market

A study by Yale investigators of phenylpropanolamine, or PPA, one of the most frequently used ingredients in many cough and cold medications, found that it leads to increased risk of hemorrhagic stroke in women. Men may also be at a lesser risk. The findings provoked the Food and Drug Administration (FDA) in October to advise ending the marketing and distribution of PPA, prompting manufacturers to withdraw many of the most popular over-the-counter (OTC) products using PPA, such as Alka-Seltzer Plus, Dimetapp Elixir and Robitussin.

The study took place at four research centers and was coordinated by the Yale investigators under a grant from two manufacturers of PPA. The results made front-page headlines worldwide because of the popularity of the products affected. Walter N. Kernan, M.D., associate professor of medicine, one of four co-investigators at Yale, says of the OTC products, “They’re essentially gone.”

The paper detailing the five-year, $5 million study did not appear in the New England Journal of Medicine until Dec. 14, but the results were released earlier on the journal’s Web site because of their importance to public health. “I think the FDA decision was cautious but very appropriate,” says Kernan. “There are alternative OTC medications for relief of cough and cold symptoms.”

The study was undertaken because of case reports associating PPA with hemorrhagic stroke—bleeding between the cerebral lobes or around the edges of the brain—an uncommon form of stroke, especially in the 18- to 49-year-old age group that was the focus of the study. The study did not look at ischemic stroke, by far the most common form of stroke.

The investigators examined 702 people who had suffered a hemorrhagic stroke and compared them to twice that number of control subjects who had not had a stroke. That database is the largest of its kind. The investigators are now using it to study other risk factors for stroke. “We expect to find new and more precise information about other risk factors for hemorrhagic stroke, including other drug products,” says Kernan. “These additional analyses may have important public health implications as well.”