November 29, 2000

Skipper Chong Warson

By Leah Shafer

he recent U.S. Food and Drug Administration (FDA) report that phenylpropanolamine (PPA), a chemical found in some cold medicines and diet pills, may cause hemorrhagic stroke has resulted in hundreds of products being pulled from pharmacy shelves. And despite claims by manufacturers and even some medical professionals that the study the FDA advisory is based on is inconclusive, the fact remains that it's a good idea to remove these products from your medicine cabinet as well.

The FDA warning applies to 400 products, both prescription and over the counter -- there were billions of doses of PPA taken in 1999 alone. The only sure way to avoid PPA is to carefully read the label of a medication before taking it.

Strokes related to PPA are estimated to occur in 200 to 500 people a year; they most commonly happen to young women. This kind of stroke has been raising red flags since the 1970s; the FDA commissioned a major study to investigate the connection in the early 1990s. As Bob Sherman, a regulatory review biologist for the FDA, comments, "When we began receiving reports of strokes in young women, it signaled that there could be a problem, because young people very rarely have strokes." The final results of the study came in November 2000 and caused the FDA to conclude that PPA cannot be considered safe. The FDA issued a public health advisory, calling for manufacturers to discontinue marketing products with the chemical.

The Hemorrhagic Stroke Project

Manufacturers have used PPA for more than 50 years, but scientists still can't say why PPA might cause hemorrhagic stroke in young women. There have been concerns about the incidence of stroke with PPA for years, however. Its effect on blood pressure may be the key.

"PPA raises blood pressure initially, but then the body develops a tolerance to it and blood pressure goes back down quickly," Sherman says. "In most individuals, it raises blood pressure no more than a normal activity like going up the stairs [would]. But in some individuals, it is suspected that PPA raises blood pressure to a greater degree, and high blood pressure is a risk for stroke."

The typical victim of a PPA-induced stroke is a healthy young woman, frequently a first-time user of PPA with no other stroke risks. Without any warning, such women have suffered hemorrhagic stroke within a few days of taking PPA; such a stroke leads to permanent disability or even death.

The typical victim of a PPA-induced stroke is a healthy young woman, frequently a first-time user of PPA with no other stroke risks.

After years of speculation about the risks of PPA, the FDA commissioned the five-year, $5 million study at Yale University School of Medicine. The Hemorrhagic Stroke Project is the largest case-controlled study of its kind ever done. It compared 702 people who were admitted to hospitals with hemorrhagic stroke -- which may or may not have been related to PPA -- with 1,376 control subjects. The researchers asked detailed questions about each patient's history and medication use, and then calculated what a patient's risk for stroke was after taking products containing PPA.

In general, the study determined that people taking any form of PPA were almost one-and-a-half times more likely to have a stroke within three days than were control subjects.

The researchers then looked at stroke risk based on the form of PPA taken. The risk of stroke was slightly lower than the average for people taking cough and cold remedies. But the shocker of the study was in regard to people taking diet pills: These people were almost 17 times as likely to have a stroke than a control subject.

Scientists don't understand why diet-pill users are at higher risk, but there are many theories. "One of the possibilities is that the population using weight-control products might tend to use more than the recommended dose," Sherman points out. "Also, overweight people -- a likely group to take weight-control products -- might have high blood pressure anyway and be at greater risk for stroke." There's also the possibility that overweight people somehow metabolize PPA differently, Sherman says.

The controversy

But not everyone agrees on the outcome of the study or on the interpretation given by the Yale researchers and the FDA. Manufacturers point out that the risk for stroke is minimal and say the situation is overblown.

Charles H. Hennekens, M.D., an epidemiologist and consultant to Consumer Healthcare Products Association (CHPA), a national trade association that represents manufacturers of over-the-counter medicines, reviewed the Yale study and found it unconvincing. "Some of the most outstanding medical experts in the field of epidemiology concur that this study showed no overall link between PPA and hemorrhagic stroke," said Dr. Hennekens in a statement. "The study showed that so few hemorrhagic stroke patients reported having used PPA that the study results could be rendered inconclusive." Experts also point out that the risk is minimal. "The number of strokes is very small considering that there are billions of doses of PPA taken a year," Sherman says.

But even so, another representative of the CHPA said that its members are reviewing the safety issues, and many are pulling the plug on manufacturing products with PPA. Drug makers SmithKlein Beecham and Bristol-Meyers Squibb said in November 2000 that they would no longer sell cold-remedy products containing PPA. Other sellers of products containing PPA -- such as Walgreens, CVS, Albertsons, Kroger, Rite Aid, Eckerd Corporation, and Rx.com -- are already removing them from their shelves.

An alternative drug used in cough and cold medications, pseudoephedrine, does not have reports of stroke associated with its use, says Laura Bradbard, an FDA spokesperson. There are no alternative weight-loss pills, however. Every appetite suppressant sold over the counter contains PPA.

Better safe than stroke

The FDA is in the process of writing rules that will ban PPA from over-the-counter products; until then, some stores have participated in a voluntary moratorium on the sale of products containing the chemical. Because PPA doesn't meet the FDA's criteria for a recall, the FDA simply called for manufacturers to discontinue marketing such products.

"Our only option was to put out an alert to consumers," Bradbard says. And it seems a consumer's only option is to pay attention to the list of ingredients in the products stocking the home medicine cabinet.

Send feedback on this article.