Fenfluramine: Back From the Dead

• Published in: Clinical therapeutics 2018-08, Vol.40 (8), p.1420-1422
• Main Authors: Wurtman, Richard J., Wurtman, Judith
• Format: Article
• Language: English
• Subjects: Antidepressants; Buttresses; Carbohydrates; Enantiomers; Epilepsy; Fenfluramine; Inhibitors; Obesity; Physicians; Prescription drugs; Serotonin
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2018.07.009

[...]each mole contains presumably equal quantities of two pharmacologically distinct compounds: the d-enantiomer, which promotes serotonin-mediated neurotransmission,1 and the l-enantiomer, which lacks serotoninergic potency but can suppress dopaminergic transmission.2 d,l-Fenfluramine (marketed as Pondimin® [American Home Products, Madison, New Jersey]) and its d-enantiomer (marketed as Redux® [Wyeth-Ayerst Pharmaceuticals, Collegeville, Pennsylvania] and Adifax [Servier Laboratories, Rivonia, South Africa]) had been widely used to treat obesity.3 The racemic mixture is now proposed for treating Dravet syndrome and other epileptic encephalopathies.4,5 Whether d,l-fenfluramine's utility for this latter purpose resides in its d-enantiomer or the l-enantiomer, or perhaps both, is apparently unknown at present. Physicians must also be certain that their patients with epilepsy, who often are treated with multiple drugs, are not concurrently receiving a monoamine oxidase (MAO) inhibitor, as was the situation (described later) when obese patients who were taking d,l-fenfluramine, a serotonin uptake blocker, also received phentermine,6,7 an unrecognized MAO inhibitor (ie, as “fen-phen”). [...]buttressed by rare reports of similar lesions in patients taking d-fenfluramine, the US Food and Drug Administration ordered that all fenfluramines—both d,l-fenfluramine itself and the d-isomer—be withdrawn from the market.