Dexfenfluramine market

For instance, in September 2004, Bayer settled 2861 product liability cases for 1.09 billion for its cholesterol medicine cerivastatin (Baycol), which was linked to 100 deaths and withdrawn from market in 2001. In July 2004, the company settled 2771 cases for 1.06 billion. Bayer still has 7577 additional cases to settle (see Section 28.4.4.5 for additional information). In another example, a 1 billion jury verdict was upheld against Wyeth for its fenfluramine or dexfenfluramine and phentermine (Fen-Phen) drug combination, which was linked to primary pulmonary hypertension (PPH). Wyeth has set aside 16.6 billion to cover future liability on the drug (see Section 28.4.4.2 for more on this case). ... 

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. 

Fenfluramine has not been systematically studied in the treatment of BN, but dexfenfluramine has been evaluated with disappointingly mixed results. Due to an association with the development of heart valve abnormalities and pulmonary hypertension, particularly when coadministered with phentermine (lonamin) in the so-called Fen-Phen strategy, these medications have recently been removed from the U.S. market. 

In 1997, the manufacturers withdrew fenfluramine and dexfenfluramine from the market. Phentermine is still sold because no cases of heart valve disease were reported when that drug was taken alone, according to the FDA report. 

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 (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... 

The S enantiomer was sold independently under the name dexfenfluramine. Which enantiomer is dexfenfluramine (Fen-Phen was withdrawn from the market in 1997, after it was shown to damage heart valves in some patients.) ... 

Dexfenfluramine, the dextrorotatory isomer, was previously widely marketed as an appetite suppressant in the management of obesity. It appears to be a pure serotonin receptor agonist without the dopaminergic and sympathetic activity of the racemic mixture. 

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... 

In September 1997, the FDA requested the manufacturers of fenfluramine and dexfenfluramine to voluntarily withdraw their products from the market. This was done following case reports of valvular heart disease in patients taking either medication as monotherapy or in combination with another anorexic agent, phentermine. Because no association has been found between phentermine alone and valvular heart disease, it is still available. Isolated case reports of pulmonary hypertension and phentermine monotherapy have been reported, but present data do not support an association. Although fenfluramine and phentermine were both approved by the FDA to be used as anorectic agents, the combination therapy, fen-phen, was never approved. 

Two halogenated amphetamines, fenfluramine and dexfenfluramine, have been used to reduce appetite these drugs were withdrawn from the U.S. market after reports of cardiac toxicity associated with their use. The mechanism of action of this class of drugs is controversial. A profound reduction in levels of 5-HT in the brain lasts for weeks and is accompanied by a loss of proteins (5-HT transporter and tryptophan hydroxylase) selectively localized in 5-HT neurons, suggesting that the halogenated amphetamines have a neurotoxic action, although neuroanatomical signs of neuronal death are not readily apparent. 

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. 

As a result of research performed by different groups dexfenfluramine was introduced as a drug for obesity treatment in the USA in 1995. Whole body calorimetry contributed to this approach. Evidence has been found later for dF being involved in generating valvular insufficiency. So in 1997 it was (at least) temporarily withdrawn from the market. 

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