REPLY

The dentist should report ADEs. (adverse drug events):

Heart fluttering goes away within minutes. Feeling ill hours later requires
further investigation. Please note that many of the Fen-Phen prescriptions
were written long after this report. Physicians were parties to legal
action, were sued, and lost. One of the more famous ones was Dr. Abby
Landzberg.

Joel M. Eichen DDS

PLEASE note the date on this report and what happened AFTER.

***

http://www.fda.gov/medwatch/SAFETY/dexfen.htm

IMPORTANT UPDATE ON REDUX
(DEXFENFLURAMINE HYDROCHLORIDE CAPSULES) C-IV
August 22, 1996

Dear Health Care Professional:

Wyeth-Ayerst Laboratories and Interneuron Pharmaceuticals, Inc. would like
you to be aware that a section of the Redux prescribing information is being
updated.

Based on the final report of the International Primary Pulmonary
Hypertension Study (IPPHS), an epidemiologic study that looked at the
relationship between anorexigens and a rare, serious, and life-threatening
cardiopulmonary disorder, primary pulmonary hypertension (PPH), the
companies and the U.S. Food and Drug Administration (FDA) have met to
evaluate the data and discuss labeling revisions.

Based on a preliminary evaluation of the IPPHS data, provided by the
investigators and reviewed prior to the approval of Redux, the risk of PPH
in persons who have used anorexigens for 3 or more months was about 9 times
higher than in non-users. PPH is estimated to occur in the general
population at 1 to 2 cases per million adults per year, and the current
labeling for Redux estimates the risk at 18 cases per million for persons
using the drug longer than 3 months. In the final report, the risk was
calculated to be about 23 times higher for patients using anorexigens for 3
or more months compared to non-users. The incidence of PPH for patients
taking anorexigens, including Redux, is now estimated to be between 23 and
46 cases per million patients per year.

There are no new data in the IPPHS final report. The preliminary report
differed from the final report because investigators reclassified and
included 10 previously excluded cases: some where compounded mixtures of
anorexigens were used, and some where information about anorexigens was
incomplete.

Although the incidence of PPH for patients taking anorexigens remains small,
PPH is a serious disorder with an estimated 4-year mortality rate of 45%.
Therefore, it is very important that Redux not be prescribed for cosmetic
weight loss. Redox is indicated for use only in those patients who have a
body mass index (BMI) of at least 30 kg/m squared (which is approximately 30
percent over desirable weight) or a BMI of at least 27 kg/m squared (which
is approximately 20 percent over desirable weight) in the presence of other
risk factors (e.g., hypertension, diabetes or hyperlipidemia).

In order for the labeling of Redux to be consistent with the final IPPHS
report and to allow you to counsel your patients with accurate information,
we are working with FDA to revise product labeling appropriately. In the
interim, this letter provides an overview of the IPPHS data to use as a
reference in treating your obese patients.

As indicated in the current labeling, patients should be advised to report
immediately any deterioration in exercise tolerance. Treatment should be
discontinued in patients who develop new, unexplained symptoms of dyspnea,
angina pectoris, syncope, or lower extremity edema. These patients should be
evaluated for the etiology of these symptoms and the possible presence of
PPH.

Obesity is a serious medical problem in the United States. Redux, combined
with a reduced-calorie diet, is indicated for the management of obesity,
including weight loss and maintenance of that weight loss. In clinical
trials, Redux helped produce a significant reduction in weight during the
first 4 to 6 months, and that loss was maintained during the year-long
therapy. The safety and effectiveness of Redux beyond one year have not been
determined.

Contraindications, Warnings, and Side Effects
Redux (dexfenfluramine hydrochloride capsules) C-IV should not be used in
patients hypersensitive to dexfenfluramine or related compounds; in patients
with diagnosed pulmonary hypertension; or in patients taking (or within 14
days of discontinuing) monamine oxidase (MAO) inhibitors. Redux should not
be administered to patients using other serotonergic drugs. Redux is not
recommended for women who are pregnant or nursing or for pediatric patients.
In animals receiving high doses of Redux for short periods of time resulting
in brain concentrations approximately 10 times those seen in humans,
neurochemical changes were observed. The dose and brain serotonin
concentration of dexfenfluramine may affect reversibility. The relevance of
these findings to humans is not known. The most commonly reported adverse
effects are diarrhea, dry mouth, and somnolence. The adverse effects were
generally mild and transient.

Additional Information
Enclosed for your information is the current product insert regarding Redux.
We will forward to you the revised version once our discussions with the FDA
are complete.

The medical community can further our understanding of adverse events by
reporting all cases to Wyeth-Ayerst at 1-800-934-5556 or to the FDA
MedWatchprogram by phone 1-800-FDA-1088, by fax at 1-800-FDA-0178 or modem
1-800-FDA-7737 or by mail:

MedWatch, HF-2
FDA
5600 Fishers Lane
Rockville, MD 20857

For information regarding Redux, please don't hesitate to contact your
Wyeth-Ayerst sales representative or call the company's medical information
line at 1-800-934-5556.

Sincerely,