September 15, 1997

Dear Health Care Provider:

Wyeth-Ayerst Laboratories today announced a voluntary and immediate withdrawal of the weight loss medications PONDIMIN (fenfluramine hydrochloride) tablets C-IV and Redux (dexfenfluramine hydrochloride) capsules C-IV from the market.

The company is taking this action based on new, preliminary information regarding abnormal heart valve findings in patients using these medications.

Even though this new information is not derived from a thorough clinical study and is difficult to evaluate, the company is taking the most prudent course of action. Wyeth-Ayerst is committed to safeguarding the health and well-being of patients and ensuring that health care providers have the latest medical information.

Owing to the unanswered questions prompted by the emerging findings, the company today also announced that is forming an expert panel of leading physicians and researchers to thoroughly evaluate the data and recommend additional actions to address this situation. The company will work closely with this panel, as well as with the U.S. Food and Drug Administration (FDA), to better understand these findings.

Based on postmarketing reports from the Mayo Clinic of 24 cases of heart valve disease in some patients treated with the combination of phentermine and fenfluramine, the company advised you in our letter of July 24, 1997, of the addition of boxed warnings concerning heart valve disease to the labeling for Pondimin and Redux. The company also announced a joint effort with the Mayo Clinic to initiate a comprehensive study to examine the possible association of unusual valvular disorders with these products. The Mayo Clinic cases were subsequently reported in an article appearing in the August 28, 1997, issue of The New England Journal of Medicine. This article was accompanied by a letter to the editor from the U.S. Food and Drug Administration (FDA) reporting additional cases of heart valve disease in 28 patients taking the combination of phentermine and fenfluramine, two patients taking fenfluramine alone, four patients taking dexfenfluramine alone, and two patients taking dexfenfluramine and phentermine.

Additional adverse event reports of abnormal heart valve findings in patients using dexfenfluramine or fenfluramine alone or in combination with other weight loss agents continue to be received by the company and the FDA. These reports have included dyspnea, chest pain, syncope, lower extremity edema, or a new heart murmur.

On Friday afternoon, September 12, 1997, the FDA provided the company with new summary information concerning abnormal echocardiogram findings in asymptomatic patients seen in five centers. These patients had been treated with fenfluramine or dexfenfluramine for up to 24 months, most often in combination with phentermine. Abnormal echocardiogram findings were reported in 92 of 291 subjects evaluated, including 80 reports of aortic regurgitation (mild or greater) and 23 reports of mitral regurgitation (moderate or greater). These observations reflect a preliminary analysis of pooled information rather than results of a formal clinical investigation and are difficult to evaluate because of the absence of matched controls and pretreatment baseline data for these patients. Nevertheless, the company believes it is prudent, in light of this information, to withdraw these products from the market at this time.

The company and FDA will continue to work together to further evaluate these reports. If you need additional medical information, please contact the Wyeth-Ayerst Medical Affairs Department at 1-800-513-7897.

Sincerely,

Marc W. Deitch, M.D.
Senior Vice President, Medical Affairs
Global Medical Director

N.B. A full-page notice will appear in leading national and regional newspapers this week announcing this decision and providing a toll-free telephone number (1-800-892-2718) for those requiring further information. Patients will be advised to contact their physicians. Please direct patients who want to return their unused medication to call this number. Please follow your normal procedures for return of product. If you have questions about returning product, please call 1-800-666-7248.

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