Benfluorex
Encyclopedia
Benfluorex is an anorectic
and hypolipidemic agent
that is structurally related to fenfluramine
. Two clinical studies have shown it may improve glycemic control and decrease insulin resistance
in people with poorly controlled type 2 diabetes
; However Servier is suspected of having marketed Mediator (benfluorex) at odds with the drug's medical properties.
In France the medication had been marketed as Mediator by Servier as an adjuvant antidiabetic
; it was on the market between 1976 and 2009 and is thought to have caused between 500 - 2,000 deaths. The drug was also used in 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, a related drug, had been withdrawn from the market in 1997 after reports of heart valve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.
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
and hypolipidemic agent
Hypolipidemic agent
Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of hyperlipidemias. They are called lipid-lowering drugs or agents.- Classes of hypolipidemic drugs :...
that is structurally related to fenfluramine
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
. Two clinical studies have shown it may improve glycemic control and decrease insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
in people with poorly controlled type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
; However Servier is suspected of having marketed Mediator (benfluorex) at odds with the drug's medical properties.
Drug withdrawn
On 18 December 2009 the European Medicines Agency (EMEA) recommended the withdrawal of all medicines containing benfluorex in the European Union, because their risks, particularly the risk of heart valve disease (fenfluramine-like cardiovascular side-effects), are greater than their benefits. Thus Frachon et al. showed a significantly higher prevalence of unexplained valvular heart disease in patients taking benfluorex compared to controls. and Weill et al. looked at over 1 million diabetic patients demonstrating a higher hospitalization rate in benfluorex takers for valvular heart disease.In France the medication had been marketed as Mediator by Servier as an adjuvant antidiabetic
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
; it was on the market between 1976 and 2009 and is thought to have caused between 500 - 2,000 deaths. The drug was also used in Portugal and Cyprus.
Fenfluramine
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
, a related drug, had been withdrawn from the market in 1997 after reports of heart valve
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
disease, pulmonary hypertension
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
, and development of cardiac fibrosis
Cardiac fibrosis
Cardiac fibrosis refers to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts.Fibrocyte cells normally secrete collagen, and function to provide structural support for the heart...
. This side effect is mediated by the metabolite norfenfluramine
Norfenfluramine
Norfenfluramine is a psychoactive drug which functions as a serotonin releasing agent and potent 5HT2B receptor agonist. The action of norfenfluramine on 5HT2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the...
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.