Ingredient in 400 Cold Drugs May Cause Strokes in Young Women, FDA Warns

      New York Times WASHINGTON -- Some of the nation''s largest pharmacy chains and drug manufacturers Monday began withdrawing cold remedies and appetite suppressants, including some that have been staples in American medicine cabinets for decades, after federal regulators announced they would take steps to ban all use of the active ingredient in the products.

      The ingredient is phenylpropanolamine, or PPA, which scientists have recently linked to a slight risk of stroke in young women. Officials at the Food and Drug Administration said they would seek to remove PPA from both prescription and nonprescription drugs and warned consumers against taking any product containing the chemical.

      The FDA said its warning covered 400 products. Certain formulations of Alka-Seltzer, Dimetapp, Robitussin, Contac and Triaminic, use phenylpropanolamine, as do many generic cold remedies, some prescription decongestants and some products for children. Acutrim and Dexatrim, both appetite suppressants, also contain PPA.

      In issuing the sweeping public health advisory, FDA officials asked the manufacturers of all PPA products, 100 companies in all, to stop marketing them voluntarily while the agency drafted new regulations that would effectively ban the ingredient from all pharmaceuticals.

      The request sent drug store and pharmaceutical executives scrambling to respond, and it was not immediately clear if all would comply.

      But already, officials at the Walgreens, CVS and Rite-Aid pharmacy chains are removing phenylpropanolamine products from their shelves. And the drug makers SmithKline Beecham and Bristol-Myers Squibb said Monday that they would no longer market cold products containing the chemical.

      "We have a brand that has been out there for 49 years," said Nancy Lovre, a spokeswoman for SmithKline Beecham, which until Monday marketed one version of Contac, its 12-hour formulation, which contains PPA. "Our customers are very important to us. We want to avoid confusion."

      A spokesman for Bristol-Myers Squibb, which sells the cold remedies Comtrex and Naldecon, said it was already moving to reformulate its products. "We do believe that PPA had a demonstrated record for 50 years of market use," said the spokesman, Patrick Donohue. "But nevertheless the FDA has made a decision. We fully intend to comply with it."

      Phenylpropanolamine, which is similar in structure to amphetamine, has been on the market for more than 50 years, although there have long been concerns about its safety. Until now, however, the FDA has said not enough scientific evidence existed to justify removing it from the market.

      The action Monday was based on a five-year study by scientists at Yale, who recently reported that PPA was associated with a small, but significant, increase in the risk of stroke among young women.

      The study, posted on the Web site of The New England Journal of Medicine on Monday, found that women ages 18 to 49 who took PPA as an appetite suppressant were as much as 15 times as likely as other women to suffer hemorrhagic stroke, a type of stroke characterized by bleeding in the brain. First-time users of the ingredient were three times as likely to suffer a stroke.

      On Oct. 19, a panel of scientific experts reviewed the study and, in a series of votes, recommend overwhelmingly that the FDA remove phenylpropanolamine from over-the-counter products. The panel did not consider whether the ingredient should be permitted in prescription drugs.

      But the recommendation has proved hugely controversial. The Consumer Healthcare Products Association, a drug industry trade group that paid $5 million for Yale to conduct the study, has disavowed it, saying the findings are flawed. Drug manufacturers have insisted that PPA products are safe and effective when used as directed.

      On Monday, the trade group said it would let each company decide how to handle the FDA request.

      "CHPA members continue to stand by the safety of PPA-containing products when used according to label directions," said R. William Soller, the trade group''s senior vice president. "However, our members acknowledge the FDA''s action and its decision to initiate a new regulation to address PPA''s safety."

      To enact a permanent ban, the agency must issue a new regulation governing over-the-counter products and seek public comment. It must also initiate separate proceedings to remove the ingredient from prescription drugs.

      These regulatory moves could take months. But the FDA has calculated that between 200 and 500 strokes each year may be attributable to phenylpropanolamine. So it decided to issue an immediate warning to consumers.

      "We are not here to be alarmist," said Charles Ganley, director of the divisions of over-the-counter drugs at the agency. "We recognize that that this is a rare occurrence." But, he said, "We felt it was important to alert consumers of what position we are taking."

      Ganley noted that for patients taking decongestants, there was an alternative ingredient, pseudoephedrine. And while PPA is the only ingredient permitted by the FDA to be sold as an over-the-counter weight loss drug, the agency concluded that the drug was not effective enough to be worth even a small risk.

      Safety concerns about phenylpropanolamine first emerged in the early 1980s, when the FDA began receiving reports that some people taking the chemical had suffered hemorrhagic stroke. In 1990, Sen. Ron Wyden, D-Ore., then a congressman, held hearings about the ingredient, and the following year the FDA held a public meeting to examine the risks.

      The Yale study grew out of that meeting. Had the drug industry not agreed to conduct it, said Ganley of the FDA, regulators would likely have removed phenylpropanolamine from the market as early as 1994.

     

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