Fen-phen was an anti-obesity treatment that utilizes two anorectic drugs, fenfluramine and phentermine. Fenfluramine, and later, a related drug, dexfenfluramine, was marketed by American Home Products, now known as Wyeth, but were shown to cause potentially fatal pulmonary hypertension and heart valve problems, which eventually led to their withdrawal and legal damages of over $13 billion.[1] Phentermine was not shown to cause harmful effects.[1] Wyeth made drugs marketed as Redux and Pondimin, which were used as the fenfluramine half of the fen-phen combination formula.[2]
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Fenfluramine was first introduced in the 1970s, but was not popular because it only temporarily reduced weight by a few pounds.[1] It sold modestly until the 1990s, when it was combined with phentermine and heavily marketed.[1] 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."[1] 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.[1] In 1995, Wyeth introduced Redux (dexfenfluramine, the dextro isomer), which it hoped would cause fewer adverse effects. However, the FDA's medical officer, Leo Lutwak, insisted upon a black box warning of pulmonary hypertension risks. After Lutwak refused to approve the drug, FDA management had someone else sign it and approved the drug with no black box warning for marketing in 1996.[1] European regulators required a major warning of pulmonary hypertension risks.[1]
In 1996, a paper in the New England Journal of Medicine from the Mayo Clinic discussed the 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.[3] Later in 1996, a 30-year-old woman developed heart problems after only a month of using it; when she died in February 1997, the Boston Herald devoted a front page article to her.[4] 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 66 additional reports of heart valve disease, all primarily associated with fen-phen. There were also reports of documented heart-valve problems in patients taking only either fenfluramine or dexfenfluramine. 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 cardiac valvular disease in persons who had taken these drugs. This valvular 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, the Food and Drug Administration (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.
Upon the release of the information regarding Fen-phen's cardiac risks, the Association of Trial Lawyers of America formed a large trial lawyer group to seek damages from American Home Products, the distributor of Pondimin and Redux.[5]
As of 2004[update], Fen-phen is no longer widely available. In April 2005, American Lawyer magazine ran a cover story on the wave of Fen-phen litigation, reporting that more than 50,000 product liability lawsuits had been filed by alleged fen-phen victims. Estimates of total liability ran as high as $14 billion. As of February 2005, Wyeth was still in negotiations with injured parties, offering settlements of $5,000 to $200,000 to some of those who had sued, and stating they might offer more to those who were most seriously injured.[2] One plaintiff's attorney claimed that "the payments [were] not going to be large enough to cover medical expenses."[6] Thousands of injured persons rejected these offers.[2] At the time, Wyeth announced it has set aside $21.1 billion (U.S.) to cover the cost of the lawsuits.[2]