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Fenfluramine-like cardiovascular side-effects of benfluorex

¹ Université Paris-Sud11, UPRES EA 2705, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique des Hôpitaux de Paris, Clamart, and ² Groupe HTAP de Bretagne Occidentale, GETBO EA 3878, Hôpital Universitaire de la Cavale Blanche, Brest, France.

CORRESPONDENCE: K. Boutet, Département de Médecine Interne et Pneumologie, Hôpital du Sacré-Cœur de Montréal, 5400 boul Gouin ouest, Montreal, Quebec, H4J 1C5, Canada. Fax: 1 5143383699. E-mail: kim.boutet{at}umontreal.ca

Keywords: Anorexigen, norfenfluramine, pulmonary arterial hypertension, valvular heart disease

Received: June 6, 2008
Accepted October 16, 2008

Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects.

The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2–49 kg·m^–2.

No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.