Benfluorex


Benfluorex, sold under the brand name Mediator, is an anorectic and hypolipidemic agent that is structurally related to fenfluramine. It may improve glycemic control and decrease insulin resistance in people with poorly controlled type-2 diabetes.
It was on the market between 1976 and 2009, and is thought to have caused between 500 and 2,000 deaths. It was patented and manufactured by the French pharmaceutical company Servier. However, Servier is suspected of having marketed benfluorex at odds with the drug's medical properties.

Drug withdrawn

On 18 December 2009, the European Medicines Agency recommended the withdrawal of all medicines containing benfluorex in the European Union, because their risks, particularly the risk of heart valve disease, are greater than their benefits. Thus Frachon et al. showed a higher rate of unexplained valvular heart disease in people taking benfluorex. Weill et al. looked at over 1 million people with diabetes demonstrating a higher hospitalization rate in benfluorex takers for valvular heart disease.
In France, the medication had been marketed as by Servier as an adjuvant antidiabetic under the name Mediator. The drug was on the market between 1976 and 2009, and is thought to have caused between 500 and 2,000 deaths. The drug was also used in Spain, Portugal, and Cyprus.
Fenfluramine, a related drug, had been withdrawn from the market in 1997 after reports of heart valve disease, pulmonary hypertension, and development of cardiac fibrosis. This side effect is mediated by the metabolite norfenfluramine on 5HT2B receptors of heart valves, leading to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the tricuspid valve. Both fenfluramine and benfluorex form norfenfluramine as a metabolite. This side effect led to the withdrawal of fenfluramine as an anorectic drug worldwide, and later to the withdrawal of benfluorex in Europe.