This summary is to provide additional information to health care professionals in
conjunction with the Food and Drug Administration (FDA) public health advisory concerning
the risk of hemorrhagic stroke associated with phenylpropanolamine hydrochloride. FDA is
taking steps to remove phenylpropanolamine from all drug products and has requested that
all drug companies discontinue marketing products containing phenylpropanolamine.
Phenylpropanolamine has been marketed for many years. During the early 1970's, FDA
initiated a scientific review of OTC drug products to determine the safety and
effectiveness of products marketed in the United States. That review included
phenylpropanolamine. In 1976, one expert panel recommended that phenylpropanolamine be
generally recognized as safe and effective as a nasal decongestant, and in 1982 another
expert panel recommended that phenylpropanolamine be generally recognized as safe and
effective for weight control. FDA did not finalize a safe and effective status for
phenylpropanolamine because of concerns about occasional reports of hemorrhagic stroke
associated with using this drug.
Because of continued reports of hemorrhagic stroke potentially associated with
phenylpronalamine, FDA asked the pharmaceutical industry to conduct a study that evaluated
the risk of hemorrhagic stroke from taking phenylpropanolamine. The drug was allowed to be
marketed while this study was being done based on the previous recommendations of the
expert panels. The results of that study (entitled "Phenylpropanolamine & Risk of
Hemorrhagic Stroke: Final Report of the Hemorrhagic Stroke Project") were provided to
FDA earlier this year. (http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3647b1_tab19.doc)
The study was a case-control study of men and women 18 to 49 years old who were
hospitalized with a subarachnoid or intracerebral hemorrhage. Case subjects selected had
no prior history of stroke and were able to participate in an interview within 30 days of
their event. For each case subject, two control subjects (no stroke) were identified
(matched based on age, gender, and race).
The final study comprised 702 case subjects and 1,376 control subjects. Age matching
occurred for 1,367 controls (99%) and ethnicity matching occurred for 1,321 controls
(96%). Subjects were classified as exposed to phenylpropanolamine if they reported use of
this drug within 3 days of the stroke event for case subjects, or a corresponding date for
control subjects. Reported exposures were verified by the study investigators.
The study reported an association between phenylpropanolamine use and hemorrhagic
stroke in women. The increase in risk of hemorrhagic stroke was found for women using
phenylpropanolamine for weight control in the 3 days after starting use of the drug and
for women using phenylpropanolamine as a nasal decongestant product in the first day of
use. Although the study showed that the risk of hemorrhagic stroke was found mostly in
women, men may also be at risk.
On October 19, 2000, FDAs Nonprescription Drugs Advisory Committee (NDAC)
discussed this report and other information on phenylpropanolamine. NDAC determined that
there is an association between phenylpropanolamine and hemorrhagic stroke and recommended
that phenylpropanolamine not be considered generally recognized as safe for OTC use as a
nasal decongestant or for weight control.
FDA has reviewed the report and believes there is an association between
phenylpropanolamine use and hemorrhagic stroke. Although this risk of hemorrhagic stroke
is very low, FDA has significant concerns because of the seriousness of this adverse event
(the irreversible outcome) and the inability to predict who is at risk. FDA does not
consider the conditions for which phenylpropanolamine is used as justifying the risk of
this serious event. FDA agrees with NDACs recommendation that phenylpropanolamine
not be considered generally recognized as safe for use in OTC drug products. FDA also has
concerns about the safe use of phenylpropanolamine in prescription drug products.
Alternate nasal decongestants which do not contain phenylpropanolamine are available both
OTC and by prescription.
FDA plans to act to remove phenylpropanolamine as an ingredient in OTC and prescription
drug products. FDA has notified all manufacturers, repackers, and distributors of any
prescription or OTC drug product containing phenylpropanolamine of this new information
and requested that they discontinue marketing drug products containing
phenylpropanolamine. If applicable, products may be reformulated without