Phentermine pulmonary hypertension with

Phentermine, possessing two methyl groups on the a position, retains the indirect-acting sympathomimetic properties and is also used for the short-term treatment of obesity. The association of primary pulmonary hypertension with certain anorectics, including phentermine, has led to reduced prescription and removal from the market in several countries. The usual adult dose of phentermine hydrochloride is 15 to 30 mg once daily before breakfast and 8 mg three times daily has also been recommended. 

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. 

The amphetamines were replaced by amphetamine analogs—substances somewhat less potent than amphetamines. Fen-Phen, the combination of fenfluramine and phentermine, was a popular appetite suppressant in the 1990s, but was associated with severe health problems such as pulmonary hypertension, heart valve dysfunction, and nerve damage. As a result, both drugs were withdrawn from the market. 

Tomita T, Zhao Q. Autopsy findings of heart and lungs in a patient with primary pulmonary hypertension associated with use of fenfluramine and phentermine. Chest 2002 121 649-652. 

Mark EJ, Patalas ED, Chang HT, Evans RJ, Kessler SC. Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl... 

Strother J, Fedullo P, Yi ES, Masliah E. Complex vascular lesions at autopsy in a patient with phentermine-fenfluramine use and rapidly progressing pulmonary hypertension. Arch Pathol Lab Med 1999 123 539-540. 

The autopsy findings in the heart and lungs of a patient with pulmonary hypertension associated with fenfluramine and phentermine have been described (13). 

Pulmonary hypertension and multivalvular damage after prolonged use of fenfluramine with phentermine have been reported in a 70-year-old Israeh woman (61). 

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. 

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. 

E. Prolonged use (usually 3 months or longer) of fenfluramine or dexfenflu-ramine in combination with phentermine ( fen-phen ) has been associated with an increased risk of pulmonary hypertension and of fibrotic valvular heart disease (primarily aortic, mitral, and tricuspid regurgitation). The pathology of the valvular disease is identical to that seen with carcinoid syndrome. 

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. ... 

Cardiovascular Pulmonary hypertension has been associated with phentermine in a 29-year-old woman [88 ]. 

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