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;[1][2] However Servier is suspected of having marketed Mediator (benfluorex) at odds with the drug's medical properties.[3]
[edit] Drug withdrawn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.[4] Thus Frachon et al. showed a significantly higher prevalence of unexplained valvular heart disease in patients taking benfluorex compared to controls.[5] and Weill et al. looked at over 1 million diabetic patients demonstrating a higher hospitalization rate in benfluorex takers for valvular heart disease.[6]
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.[7] 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Fenfluramine, a related drug, had been withdrawn from the market in 1997 after reports of heart valve disease,[8][9] pulmonary hypertension, and development of cardiac fibrosis.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.
[edit] References
- ^ Moulin P, Andre M, Alawi H et al (2006). "Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18-week, randomized, double-blind study". Diabetes Care 29 (3): 515–20. doi:10.2337/diacare.29.03.06.dc05-1439. PMID 16505498. Free full text
- ^ Roger P, Auclair J, Drain P (1999). "Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo". J Diabetes Complications 13 (2): 62–7. doi:10.1016/S1056-8727(98)00004-X. PMID 10432168.
- ^ Mullard A (March 2011). "Mediator scandal rocks French medical community". Lancet 377 (9769): pp. 890–892. PMID 21409784. http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611603346.pdf.
- ^ Press Release European Medicines Agency recommends withdrawal of benfluorex from the market in European Union [1]
- ^ Frachon, I. �N.; Etienne, Y.; Jobic, Y.; Le Gal, G. �G.; Humbert, M.; Leroyer, C.; Lexchin, J. (2010). Lexchin, Joel. ed. "Benfluorex and Unexplained Valvular Heart Disease: A Case-Control Study". PLoS ONE 5 (4): e10128. Bibcode 2010PLoSO...510128F. doi:10.1371/journal.pone.0010128. PMC 2853566. PMID 20405030. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2853566. edit
- ^ Weill, A.; Païta, M.; Tuppin, P.; Fagot, J. P.; Neumann, A.; Simon, D.; Ricordeau, P.; Montastruc, J. L. et al (2010). "Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus". Pharmacoepidemiology and Drug Safety 19 (12): 1256–1262. doi:10.1002/pds.2044. PMID 20945504. edit
- ^ France braced for diabetic drug scandal report - BBC News - 11 January 2011
- ^ Connolly HM, Crary JL, McGoon MD et al (1997). "Valvular heart disease associated with fenfluramine-phentermine". N. Engl. J. Med. 337 (9): 581–8. doi:10.1056/NEJM199708283370901. PMID 9271479. http://content.nejm.org/cgi/content/full/337/9/581.
- ^ Weissman NJ (2001). "Appetite suppressants and valvular heart disease". Am. J. Med. Sci. 321 (4): 285–91. doi:10.1097/00000441-200104000-00008. PMID 11307869.
Over 1300 deaths in Mediator scandal in France. Lisa Nainggolan - theheart.org ; Feb 9, 2012.
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