History
Fenfluramine as a single drug was first introduced in the 1970s, but was not popular because it only temporarily reduced weight. A 1984 study found a weight loss of 7.5 kg on average in 24 weeks, as compared to 4.4 kg under placebo. It sold modestly until the 1990s, when it was combined with phentermine and heavily marketed. A similar drug, aminorex, had caused severe lung damage and "provided reason to worry that similar drugs ... could increase the risk of a rare but often fatal lung disease, pulmonary hypertension." In 1994, Wyeth official Fred Wilson expressed concerns about fenfluramine's labeling containing only four cases of pulmonary hypertension when a total of 41 had been observed, but no action was taken until 1996. In 1995, Wyeth introduced dexfenfluramine (the dextro isomer, marketed as Redux), which it hoped would cause fewer adverse effects. However, the medical officer of the Food and Drug Administration (FDA), Leo Lutwak, insisted upon a black box warning of pulmonary hypertension risks. After Lutwak refused to approve the drug, the FDA management had someone else sign it and approved the drug with no black box warning for marketing in 1996. European regulators required a major warning of pulmonary hypertension risks.
In 1996, a paper in the New England Journal of Medicine (NEJM) from the Mayo Clinic discussed clinical findings in 24 patients who had taken fen-phen. The authors noted that their findings suggested a possible correlation between mitral valve dysfunction and the use of these anorectic agents. Later in 1996, a 30-year-old woman developed heart problems after a month of using it; when she died in February 1997, the Boston Herald devoted a front page article to her. The FDA alerted medical doctors that it had received nine additional reports of the same type, and requested all health care professionals to report any such cases to the agency’s MedWatch program, or to their respective pharmaceutical manufacturers. The FDA subsequently received over a hundred additional reports of valvular heart disease in patients taking fen-phen, fenfluramine alone or dexfenfluramine alone. The FDA requested that the manufacturers of fenfluramine and dexfenfluramine stress the potential risk to the heart in the drugs' labeling and in patient package inserts. As of 1997, the FDA was continuing to receive reports of valvular heart disease in persons who had taken these drugs. This disease typically involves the aortic and mitral valves.
After reports of valvular heart disease and pulmonary hypertension, primarily in women who had been undergoing treatment with fen-phen or (dex)fenfluramine, the FDA requested its withdrawal from the market in September 1997.
The action was based on findings from doctors who had evaluated patients taking these two drugs with echocardiograms, a procedure that can test the functioning of heart valves. The findings indicated that approximately 30 percent of evaluated patients had abnormal echocardiograms, even though they had no symptoms. This percentage of abnormal test results was much higher than would be expected from a comparatively sized sample of the population who had not been exposed to either fenfluramine or dexfenfluramine.
Read more about this topic: Fenfluramine/phentermine
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