November 29, 2000
Danger in the Medicine Cabinet?
FDA warns about stroke risk from chemical in cold medicine, diet
By Leah Shafer
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
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
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.
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
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
"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
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