WASHINGTON, Nov. 6 - Some of the nation's largest pharmacy chains and drug manufacturers today 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 today that they would seek to remove PPA from both prescription and nonprescription drugs and warned consumers against taking any product containing the chemical.
The F.D.A. 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 the ingredient.
In issuing the sweeping public health advisory, officials at the drug agency went one step beyond the recommendation of an outside panel of experts, which recently called for PPA to be removed from over-the- counter drugs. Instead, the agency asked the manufacturers of all PPA products, 100 companies in all, to stop marketing them voluntarily while regulators draft new rules that would effectively ban the ingredient. The request sent drugstore and pharmaceutical executives scrambling to respond, and it is not immediately clear whether all will comply.
Already, officials at the Walgreens, CVS and Rite-Aid chains are removing phenylpropanolamine products from their shelves. And the drug makers SmithKline Beecham and Bristol-Myers Squibb said today that they would no longer market cold remedies 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 today marketed one version of Contac, its 12-hour formulation, that 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 the company was moving to reformulate its products.
We do believe that PPA had a demonstrated record for 50 years of market use, said the spokeman, Patrick Donohue. But nevertheless the F.D.A. 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 F.D.A. has said there was not enough scientific evidence to justify removing it from the market.
Today's action was based on a five-year study by scientists at Yale University, who recently reported that PPA was associated with a small, but significant, increase in the risk of stroke among young women.
The study, which was posted today on the Web site of The New England Journal of Medicine, found that women ages 18 to 49 who took phenylpropanolamine as an appetite suppressant were as much as 15 times more likely than 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, said phenylpropanolamine could no longer be generally recognized as safe and effective, the agency's standard for over-the- counter products. It did not consider whether the ingredient should be allowed in prescription drugs.
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 makers insist that PPA products are safe and effective when used as directed. Today, the trade group said it would let each company decide how to handle the F.D.A.'s request. C.H.P.A. members continue to stand by the safety of PPA-containing products when used according to label directions, said Dr. R. William Soller, the trade group's senior vice president. However, our members acknowledge the F.D.A.'s action and its decision to initiate a new regulation to address PPA's safety.
To enact a permanent ban, the food and drug 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 F.D.A. has calculated that 200 to 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 Dr. Charles Ganley, director of the divisions of over-the-counter drugs at the agency. We recognize that this is a rare occurence. But, Dr. Ganley said, we felt it was important to alert consumers of what position we are taking.
Dr. Ganley noted that for patients taking decongestants, there was an alternative ingredient, pseudoephedrine. And while PPA is the only ingredient permitted by the F.D.A. to be sold as an over-the-counter weight loss drug, the agency concluded that the drug is not effective enough to be worth even a small risk. Safety concerns about phenylpropanolamine first emerged in the early 1980's, when the food and drug agency began receiving reports that some people taking the chemical had suffered hemorrhagic stroke. In 1990, Senator Ron Wyden, Democrat of Oregon, then a congressman, held hearings about the ingredient, and the following year the F.D.A. 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, Dr. Ganley of the F.D.A. said, regulators would probably have removed phenylpropanolamine from the market as early as 1994, the same year it issued a regulation for other cold products that do not contain it. Consumer health advocates lauded the agency's decision. Good riddance to PPA, said Dr. Sidney M. Wolfe, the director of Public Citizen's Health Research Group, an advocacy organization in Washington.
But debate among pharmacologists continued. Dr. Raymond Woosley, chairman of the pharmacology department at Georgetown University, said the F.D.A.'s decision was correct. Excellent move, Dr. Woosley said. If you look at any textbook of pharmacology that goes back 40, 50 years, there were concerns about stroke with these amphetaminelike compounds.
But Dr. John P. Morgan, a professor of pharmacology at City University of New York who has conducted studies of PPA for the industry, disagreed, saying: I do not think this was the right thing. The data propelling this are so weak, and flawed.
Despite Dr. Morgan's contention, The New England Journal of Medicine announced today that it would formally publish the Yale study on Dec. 21 - an important imprimatur, because it means the study has passed On its Web site, the journal's editors said the potential public health implications warranted early distribution.
The journal also released a study of the risks of ephedra, an ingredient that is in natural appetite suppressants that are classified as dietary supplements, and therefore escape regulation by the F.D.A. The article reviewed reports of 140 patients who suffered serious side effects, including stroke and seizures, after taking ephedra products. Ten died, and 13 percent were permanently disabled.
Some public health experts, including Dr. Woosley, fear that if phenylpropanolamine is removed from the over-the-counter weight-loss drugs, consumers will begin turning to products containing ephedra. But Dr. Soller, of the drug industry trade group, said ephedra was safe and beneficial when used properly.
Source: New York Times on the Web