Isomeride (dexfenfluramine) marketed by the Servier laboratory was an appetite suppressant drug indicated to treat obesity. It was withdrawn from sale in 1997 after causing adverse effects of pulmonary arterial hypertension and cardiac consequences. Summary of the case.
Isomeride® (dexfenfluramine) produced by the Servier laboratory East marketed in France on November 15, 1985 (in 1996 under the Redux brand in the United States). It’s a anorectic drug (appetite suppressant) indicated in case of obesity. He is withdrawn from sale on September 15, 1997 due to complications of pulmonary arterial hypertension and heart valve abnormalities. “7 to 10 million French people took Isomeride between 1985 and 1997” estimates the Association of assistance to the victims of Isoméride® and Mediator® (AVIM). Early reports of treatment side effects by Isomeride® have been reported as early as 1991. What are the consequences taking Isomeride? What are the key dates in the case? What replaces isomeride?
What are the side effects of Isomeride?
Isoméride® is withdrawn from the French and American markets after the announcement ofserious side effects : of the heart valve disease and of thepulmonary arterial hypertension caused by dexfenfluramine (active ingredient of the medicine). I’pulmonary arterial hypertension where PAH is a rare and serious disease which results in a increased pressure within the pulmonary arteries, responsible for bringing blood to the lungs to be charged with oxygen. This disease is manifested by shortness of breath on exertion, sometimes accompanied by signs of heart failure such as lower limb edema. “Pulmonary arterial hypertension including risk is multiplied by 3 after 3 months of use of Isomeride® And by 23 after 12 months of use” indicates the Association for the Assistance of Victims of Isoméride®. Valvular heart disease includes heart valve diseases. According to a French study made public on March 10, 2006 by the AFSSAPS (ex-ANSM), Isoméride ® causes serious side effects up to five years after stopping treatment.
Why the withdrawal of Isomeride caused a scandal?
In 1991, the Antoine-Béclère hospital in Clamart observed a link between Isoméride® and the occurrence of pulmonary arterial hypertension. In 1993, Mariane Ewalenko, a Belgian cardiologist, noticed heart valve disease under treatment with Isomeride®. She warns the Servier laboratory. “We reported the cases to the Belgian Pharmacovigilance Agency and I heard nothing more. In total I reported 14 cases of valve disease between 1993 and 1995” she reports to the authors of the book The black book of medicine. Another Belgian doctor, Dr. Jean Malak tries to warn against the risks of Isoméride®, without success. In March 1994, a survey carried out by the Professor Lucien Abenhaim emphasizes the risks of pulmonary arterial hypertension associated with Isoméride®. Yet the drug hits the US market in April 1996.”The laboratory will then seek to minimize the importance of this information to the Food and Drug Administration (FDA). On the sheets sent to the FDA, these cardiac pathologies will be qualified as “non-serious” so as not to arouse the attention of the American health authorities.” report it Figaro in an article published in June 2011. It will not be withdrawn from the French and American markets until 1997, several years after the first reports complications of pulmonary arterial hypertension and heart valve abnormalities.
The active substance of Mediator® is the benfluorex. That of Isoméride® is the dexfenfluramine. The 2 molecules belong to the family of fenfluramines. Unlike isomeride, Mediator® is not positioned on the market as anorectic but as an adjunct to diet in overweight diabetics.
What replaces Isomeride?
Isoméride® cannot be replaced in France by another medicine. The marketing authorizations (AMM) of anorectic drugs were suspended in France from 1999 and then withdrawn in 2006. No medicine can be prescribed to lose weight.
Key dates in the Isomeride case
► November 15, 1985. Isoméride® is marketed in France by the Servier laboratory. It is indicated to fight against obesity but it is also used as an appetite suppressant by people wishing to lose weight.
► 1991 : The doctors at the Antoine-Béclère hospital in Clamart observe a link between isomeride® and the occurrence of pulmonary arterial hypertension.
► 1993 : Mariane Ewalenko, a Belgian cardiologist, notices heart valve disease under treatment with Isomeride®. She warns the Servier laboratory. “We reported the cases to the Belgian Pharmacovigilance Agency and I have had no more news. In total I reported 14 cases of valve disease between 1993 and 1995” she reports to the authors of the book The Black Book of Medicine. Another Belgian doctor, the Dr. Jean Malak also points out the risks of Isoméride®, without success.
► March 1994. Pr Lucien Abenhaïm, director of the Center for Clinical Epidemiology and Public Health Research at McGill University in Montreal, publishes a study requested by Servier laboratories in the National Library of Medicine highlighting the risks of pulmonary arterial hypertension linked to Isomeride®.
► May 10, 1995. The Ministry of Health publishes A stopped prohibiting the execution and supply of magistral preparations containing dexfenfluramine.
►April 1996. Isoméride® is launched in the United States as Redux by the American laboratory American Home Products, which bought the rights to it from the Servier laboratory.
► August 29, 1996. A study published in the New England Journal Of Medicine reports that “the use of anorexic drugs including Isomeride® was associated with an increased risk of primary pulmonary hypertension“.
► March 1997. Anna Paulos, a 39-year-old woman files complaint against Isomeride® for causing his pulmonary arterial hypertension. In December 2000the first civil chamber of the Tribunal de Grande Instance (TGI) of Nanterre declares the guilty Servier laboratoryreports The echoes.
► September 15, 1997. Isoméride® is withdrawn from the market in France and in the United Statesdue to complications of pulmonary arterial hypertension and heart valve abnormalities.
► July 7, 2006. The TGI of Nanterre condemns the Servier laboratory to pay 130,500 to the family of one deceased victim after taking Isomeride® treatment. The victim, aged 47, mother, died on October 31, 1995. The laboratory appealed against the judgment but the January 20, 2011, the Court of Appeal of Versailles condemns the Servier laboratory by increasing the sum to be paid to the family to 145,500 euros.
– Appetite suppressants and the risk of primary pulmonary hypertension, August 29, 1996, New England Journal Of Medicine
– International study on primary pulmonary hypertension, March 1994, Pr L. Abenhaim, National Library of Medicine