Fenfluramine

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Friday, July 08, 2005 11:49 am Email this article

​Fenfluramine was the original "fen" in phen-fen (also called fen-phen). Fenfluramine binds to the serotonin transporter protein on cells and blocks the reuptake of serotonin just as Prozac does, but fenfluramine binds to a different domain compared to Prozac and is actually taken up into cells. The resulting high intracellular concentration of fenfluramine stimulates the fibrosis cascade resulting in primary pulmonary hypertension (PPH) or heart valve disease, just as with aminorex, phenformin and Sansert (Rothman et al Circulation 1999;100:869). There is no doubt that fenfluramine altered the heart valves in approximately one-third of the patients taking fenfluramine while they took the drug. A few patients progressed to actual valve failure. In the other patients, after the drug was stopped, the valves reverted to a functionally normal state. There is no further need to do echocardiograms in asymptomatic patients who took fenfluramine.

Ironically, while the original package insert for fenfluramine advised against combining fenfluramine with SSRI drugs, it is now clear that such a combination would have prevented the development of heart valve disease or PPH (Abenhaim et al NEJM 1999;340:482). Warnings in the PDR against combining phentermine with SSRI drugs were never based on real data, but instead on the paranoia of the legal department of pharmaceutical companies. Such warnings are obsolete and harmful and should be withdrawn, but sadly once text is in the PDR, it is seldom removed. Be advised: the PDR is NOT the standard of care in America. The standard is "the average practice of reasonably competent physicians", and no physician can be judged competent who does not treat obesity effectively.

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• Fenfluramine