Fenfluramine cardiac valvulopathies

Savage, J.E., Rauser, L., McBride, A., Hufeisen, S.J. and Roth, B.L. (2000) Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic... 

The Chairman of FDA s Advisory Committee commented on the risk of death from developing PPH. "We have had what 1 think appears to be a reasonable estimate of the risk of deaths from pulmonary hypertension. We need to understand clearly that if a million patients take this drug, at least a couple dozen of them will die annually as a result of this complication. That seems the best estimate. This is something that has to be weighed seriously." The appearance of heart valvulopathies in otherwise asymptomatic people in their thirties or forties was unexpected and caught patients and practitioners by surprise. Both fenfluramine and phentermine cause an increase in the amount of serotonin available in the body, which can cause cardiac valvulopathies. 

Cardiac valvulopathy associated with exposure to fenfluramine or dexfenflu-ramine U.S. Department of Health and Human Services interim public health recommendations, November 1997. Morb Mortal Wkly Rep 1997 46 1061-1066. 

Anorectic drugs, which are structurally related to the amphetamines, act mainly on the satiety centre in the hypothalamus and also increase general physical activity (1). All of them, except fenfluramine, stimulate the central nervous system and can cause restlessness, nervousness, irritabihty, and insomnia. Adverse effects also occur through sympathetic stimulation and gastrointestinal irritation. Drug interactions can occur with monoamine oxidase inhibitors. Dexamfetamine, phenmetrazine, and benzfetamine can cause dependence. Some of them have been associated with cardiac valvulopathy and primary pulmonary hypertension (2). 

The fenfluramines and phentermine can cause valvular heart disease (8-10), and this has been reviewed (11). Fenfluramine was voluntarily withdrawn by the manufacturers on 15 September 1997, and the US Department of Health and Human Services issued interim recommendations for people previously exposed to fenfluramine or dexfenfluramine with cardiac valvulopathies (SEDA-22, 3). 

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. 

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