Yale study sparks FDA review of cold drugs

A recent Yale study has prompted a Food and Drug Administration (FDA) committee to recommend banning a common ingredient in non-prescription medicines because it has been found to increase the risk of strokes.

FILE PHOTOS These drugs contain the chemical PPA, recently associated with strokes in young women.

Last week, the FDA advisory committee on nonprescription drugs recommended that the FDA remove phenylpropanolamine (PPA) from over-the-counter medicines. The FDA has up to 90 days to decide whether to ban PPA based on the suggestion of the committee, which consists of physicians, statisticians, epidemiologists, and other experts.

PPA is widely used in many over-the-counter decongestants, including Dimetapp and Robitussin, as well as several appetite suppressants. The Yale researchers found an increase in the risk of hemorrhagic stroke associated with PPA use, according to a Wed., May 10 report on the study's overall findings.

Associate Professor of Medicine Dr. Walter Kernan, who conducted the study, said the FDA will base its conclusions on the Yale team's research. "Our study will be used by the FDA in making a final decision on how PPA [is presented to the public]," he said.

FDA press officer Jason Brodsky said that the FDA is considering the Yale study's results seriously. "We think the study is very important [for establishing a link] between the use of PPA and the risk of hemorrhagic stroke," Brodsky said. "The study has given us important information because of the extensive use of PPA in over-the-counter products. We are now evaluating whether the use of PPA in these products should be discontinued."

The risk of hemorrhagic stroke resulting from PPA use is low, however, according to Professor of Neurology Dr. Lawrence Brass, a stroke specialist who also led the research. "The risks are fairly small, although the relative risk [of PPA use versus another chemical] is high," Brass said. While the relative risk is about 16 times higher, the overall risk of hemorrhagic stroke is "perhaps 1 in 500,000," he added.

The five-year, $5 million dollar study was funded by the Consumer Healthcare Products Association (CHPA), but the organization is critical of the study's findings. "Evidence from clinical trials and adverse-event tracking, when taken together, overwhelmingly support the safety and effectiveness of PPA when used as directed on product labeling," Dr. William Soller, CHPA senior vice president and director of science and technology, told the FDA in a letter reviewing the Yale study.

Eight billion doses of PPA are administered yearly, and it is the eighth-most common chemical found in over-the-counter medicines. Brass said that of the 750,000 strokes that occur annually, only 15 percent are hemorrhagic in nature, where bleeding occurs inside the brain.

Interest in the potential effects of PPA use initially came from case reports of hemorrhagic strokes during the late 1970s and early 1980s. In the early1990s, Congress became involved, and as a result the FDA started to look into the issue.

The FDA then requested that PPA manufacturers perform research, and in 1992, they asked Brass to propose an independent study of the risks of PPA. "The manufacturers contacted me to ask what I thought about the existing data and how I would address getting more definitive data," Brass said. Brass was chosen because he had experience in stroke analysis from writing several reports on strokes associated with factors such as cocaine use.

Yale faculty members Dr. Ralph Horwitz, chairman of the Department of Medicine, and Dr. Catherine Viscoli, an associate research scientist, worked with Brass to design the research proposal, and Kernan joined the group shortly after. The only prior research conducted on PPA was published in 1984, when scientists found no association between PPA use and hemorrhagic stroke.

Begun in 1994, the Yale study, which is the largest ever on the health effects of PPA, involved 702 patients aged 18 to 49 who suffered hemorrhagic strokes and 1,376 control subjects. The study found that the rate of stroke in women was 16.58 times higher after taking an appetite suppressant within three days before the stroke, and about three times higher in women who had their first ever dose of PPA. Too few men were observed who used PPA and subsequently suffered a stroke to draw conclusive inferences, the study found.

Until the FDA makes a final decision on whether to ban PPA, it will remain available to the public in over-the-counter medications. "I would advise consumers to pay close attention to the final ruling of the FDA," Kernan said. "In the meantime, it is appropriate for consumers to be aware of our study [when making personal choices about using PPA]."

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