Cessation of the marketing of Mediaxal® in Singapore

In May 2009, the French Medicines Agency (AFSSAPS) identified very rare cases of cardiac valvular disorders associated with the use of benfluorex (Mediaxal®, Servier) during its routine post-marketing surveillance. This prompted the re-evaluation of the benefit-risk ratio of the product by the AFSSAPS, which led to the agency's decision to suspend the marketing authorisation of Mediaxal® in France on 24November 2009 and cease exportations of the product from 30November 2009. Servier Laboratories has also stopped the marketing of Mediaxal® in Singapore as a consequence of the AFSSAPS' decision.

Background

Benfluorex is an antihyperlipidaemic agent that is used for decreasing the intestinal absorption of triglycerides, decrease lipid synthesis and also facilitate the cellular penetration and utilisation of glucose. It is a derivative of fenfluramine with an appetite suppressant action, which is the reason for its preferential use in overweight type 2 diabetic patients.

Mediaxal® has been marketed in France for at least 30 years as an adjuvant to dietary control in the treatment of overweight type 2 diabetic patients.

Cases of cardiac valve disease

Between its launch in 1976 and September 2009, a total of 45 cases of cardiac valve disease in patients exposed to benfluorex had been reported to the French national pharmacovigilance system. At the end of September 2009, the AFSSAPS was informed of the preliminary results of the REGULATE Study, carried out by Servier laboratories, which had been initiated before the emergence of the safety signal. The objective was to compare the efficacy and safety of two antidiabetic agents, benfluorex and pioglitazone, as adjuncts to sulphonylurea therapy over a 52-week period. A total of 847 type 2 diabetic patients were included. The preliminary results, based on the comparison of echocardiographic examinations at baseline and after 1 year of treatment, showed the emergence of functional valvular abnormalities that were trivial but occurred more frequently with benfluorex than with pioglitazone (26.5% vs. 10.9%; p<0.0001). Morphological valve abnormalities were also observed twice as often with benfluorex than with the comparator (2.6% vs. 1.3%; p<0.264).

Regulatory actions taken

The French Marketing Authorisation Committee examined all data related to the benefit and risk of benfluorex in its current use conditions as “adjuvant to appropriate diet in overweight diabetics” and concluded that the modest efficacy data in the management of type 2 diabetes does not outweigh the risk of cardiac valve disease. The French Committee hence suspended the marketing authorisation for proprietary medicinal products containing benfluorex with effect from 30 November 2009.

Local situation

Mediaxal® has been registered in Singapore since June 1990 for the treatment of abnormalities of lipid metabolism, which is a different indication from that in France. To date, HSA has not received any adverse reaction reports associated with the use of Mediaxal®.

In view that the cessation of exportation of Mediaxal® from France will affect the supply of Mediaxal® to Singapore, Servier has voluntarily ceased the marketing of this product locally with effect from 30^th November 2009. Physicians who have prescribed Mediaxal® to their patients were advised to re-evaluate the treatment of their patients and to switch to appropriate alternative therapies.