Dexfenfluramine pulmonary hypertension with

Common adverse reactions seen with phentermine use include heart palpitations, tachycardia, elevated blood pressure, stimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, dry mouth, constipation, and diarrhea. Phentermine should be avoided in patients with unstable cardiac status, hypertension, hyperthyroidism, agitated states, or glaucoma. In combination with fenfluramine or dexfenfluramine, pulmonary hypertension and valvular heart disease have been reported. The risk of developing either serious adverse effect cannot be ruled out with use of phentermine alone. Since phentermine is related to the amphetamines, the... 

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. 

A 30-year-old woman who had taken dexfenfluramine for 7 months developed pulmonary hypertension and right heart failure during late pregnancy. She died of septicemia with multiorgan failure 4 days after a cesarean section (60). 

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 principal side effects of phentermine are insomnia, restlessness, and euphoria. Some patients rapidly develop toleranee to this agent, resulting in discontinuation of therapy. The combination of phentermine with fenfluramine or dexfenfluramine was as-soeiated with inereased incidences of both primary pulmonary hypertension (PPH) and ear-diae valvulopathy, but it is unlikely that phentermine alone causes these same problems. Phentermine, nonetheless, contains a warning label listing PPH and cardiac valve lesions as possible adverse events. 

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 factors leading to the development of pulmonary hypertension are unclear, although associations with portal hypertension and pregnancy have been detected. Obesity by itself may double the risk of pulmonary hypertension. Additionally, the use of cocaine or oral contraceptives, infection with the human immunodeficiency virus (HIV), the use of anorexic agents, hepatic cirrhosis, genetic susceptibility, and female sex in the third to fourth decades of life also have been implicated as predisposing factors. Exposure of patients to fenfluramine or dexfenfluramine has been associated with 20% of all diagnosed cases of pulmonary hypertension. ... 

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. 

Fenfluramine and dexfenfluramine have generally been withdrawn worldwide because of the occurrence of serious and sometimes fatal valvular heart disease (aortic, mitral, tricuspid or mixed valve disease). Pulmonary hypertension has also sometimes been seen. These serious adverse effects occurred when these drugs were taken alone, and when combined with phenter-mine as Fen-phen and Dexfen-phen, but not with phentermine alone. ... 

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