Fenfluramine Redux

After many health problems and deaths, the FDA removed Pondimin and Redux from market. Since then, there have been 200 reported cases of primary pulmonary hypertension relating to fen-phen and dexfen-phen. Of those cases, 40 have resulted in death. The FDA has received more than 100 reports of heart valve damage directly related to fen-phen or fenfluramine therapy there are no reports from individuals taking phentermine alone for weight loss. 

On September 15,1997, FDA asked the manufacturers of dexfenfluramine (Redux manufactured for Intemeuron Pharmaceuticals by Wyeth-Ayerst) and fenfluramine (Pondimin Wyeth-Ayerst) to voluntarily withdraw both treatments from the market because of findings that indicate approximately 30% of patients taking the combined drugs had abnormal echocardiograms, even if they had no symptoms. Both companies agreed. FDA is not requesting the withdrawal of phentermine, the third widely used medication for obesity. 

Off-label use during the 1990s became an issue after doctors in the United States and other countries began prescribing fenfluramine (Pondimin) or dexfenfluramine (Redux) in combination with phentermine. The combinations known informally as fen-phen (sometimes also written as phen-fen ) or fen-dex had not been approved by the FDA, a process that involves research and hearings. 

Fenfluramine, a racemic chemical more closely related to amphetamine than to serotonin, affects brain levels of serotonin and its metabolites at relatively low doses. It was introduced as an anorexigenic drug almost 20 years ago. Its d- isomer, J-fenfluramine (dexfenfluramine, Redux) was about twice as potent as fenfluramine. After several controlled clinical trials demonstrated that dexfenfluramine could help patients maintain weight loss for at least a year, it was quickly introduced into the market in the USA and became a best-selling drug overnight. 

The amphetamine analogue fenfluramine, whose synthesis you designed while you were reading Chapter 31, used to be marketed as an anorectic (appetite-suppressant)—it stimulates the production of the hormone serotonin and makes the body feel satisfied—until it became clear that some undesirable side-effects could be avoided by administering it solely as the (S)-enantiomer. Fenfluramine relaunched as the enantiomerically pure dexfenfluramine, and was reputedly a turning point for your overweight patients —was available in the USA as a component of the slimming pill Redux. 

Fenfluramine Canal , Ponderal , Ponderax , Pondimin , Redux ... 

Fenfluramine (approved in 1973, withdrawn in 1997) and phentermine (appetite suppressant approved in 1959 and still available). Wyeth-Ayerst Laboratories, a subsidiary of American Home Products Corp. of Madison, New Jersey, manufactured and marketed fenfluramine under the brand name Pondimin. Wyeth-Ayerst also marketed Redux (dexfenfluramine), which was manufactured for Interneuron Pharmaceuticals. See http //www.fda.gov/cder/news/phen/fenphenpr81597.htm... 

New pharmacological treatments have been developed for the treatment of obesity. These include the combination of phentermine and fenfluramine (phen-fen) and, alternatively, dexfenfluramine (Redux). Phentermine (Fastin, lonamin) is a stimulant and fenfluramine (Pondimin) is a serotonin agonist. In combination they have persistent appetite suppression and weight loss effects. These medications can cause anxiety and insomnia and must be used with extreme caution if taken with antidepressants, especially SSRIs. Dexfenfluramine works similarly, but avoids the side effect of increased anxiety, and instead tends to cause diarrhea, dry mouth, and somnolence. There have also been reports of pulmonary hypertension, a potentially fatal condition, especially when taken for longer than three months. Some researchers (Ricuarte et al. 1991 McCann et al. 1994) have expressed concern because rats given these medications showed evidence of neuronal toxicity. Thus, they are effective medications, but must be used with caution. 

The Fen-Phen combination regimen started in 1992 after the publication of an article that showed dramatic weight loss when both drugs were taken together. In 1995, the FDA was asked to approve a new diet drug, dexfenfluramine or Redux. Developed by Interneuron Pharmaceuticals Inc., a Massachusetts company, Redux is a purified form of fenfluramine. However, prior reports had linked fenfluramine use with primary pulmonary hypertension (PPH), a rare but potentially fatal cardiopulmonary disease. The FDA finally approved fenfluramine and Redux went on the market in April 1996. In July 1997, the Mayo Clinic released results from a study that found 24 cases of heart... 

The debate regarding the appropriateness of obesity pharmacotherapy remains heated, fueled by the recognized national need to treat a growing epidemic, the lack of longterm outcomes studies, and the medical and litigious fallout from the failed use of fen-phen (fenfluramine-phentermine) and dexfenfluramine (Redux). 

Withdrawals from the market of ethically approved drugs in recent years [e.g., Pon-dimin (fenfluramine hydrochloride) and its sister compound Redux (dexfenflura-mine hydrochloride) for reasons of abnormal heart valve effects in 1996 Baycol/Li-pobay (cerivastatin) for occurrence of fatal rhabdomyolysis in 2001 Serzone (nefazo-dine) for associated Hver failure in 2003]... 

S)-(+) Dexfenfluramine (Redux ) 21, a serotonin reuptake inhibitor, has been marketed in Europe and the United States as a very effective anti-obesity drug. This isomer, obtained by resolution of racemic fenfluramine using d-camphoric acid, exhibits a greater anorectic effect than die (R)-(-) and racemic forms, since it is more selective on serotonin as a 5-HT agonist (22). As a result of reports of imdesirable side effects, e.g., valvular heart disease, Redux has been wididrawn from the market, while further studies continue. Racemic fluoxetine (Prozac ) (22) is widely used for treatment of major depression and is one of the most commonly prescribed medications. It is also approved for treatment of obsessive compulsive disorder and bulimia. Non-racemic fluoxetine and its intermediates have been prepared by chemical, enzymatic. 

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