The European Medicines Agency ( EMEA ) has completed a review of Acomplia ( Rimonabant ) at the request of the European Commission, following concerns over the medicine’s psychiatric safety.
The Agency’s Committee for Medicinal Products for Human Use ( CHMP ) has concluded that the benefits of Acomplia no longer outweigh its risks, and that its marketing authorisation should be suspended across the European Union ( EU ).

Acomplia is a medicine containing the active substance Rimonabant. It is used together with diet and exercise to reduce weight in adult patients who are: obese with a body mass index ( BMI ) greater or equal to 30 kg/m 2 , or overweight ( BMI greater or equal to 27 kg/m 2 ) and also have other risk factors, such as type 2 diabetes or dyslipidaemia.

The active substance in Acomplia, Rimonabant, is a cannabinoid receptor antagonist. It acts by blocking a specific type of receptor called cannabinoid type 1 ( CB1 ) receptors that are found in the nervous system and are part of the system that the body uses to control food intake. By blocking the receptors, Rimonabant can help patients to reduce food intake and to lose weight. The receptors are also found in adipocytes.

Acomplia has been authorised in the European Union since June 2006 and is marketed in 18 EU Member States 2 . Rimonabant is also authorised as Zimulti, but this product is not marketed in the EU.

The CHMP has been aware that Acomplia can cause psychiatric side effects, especially depression, since its initial assessment. Warnings about psychiatric safety have been included in Acomplia’s product information since its first authorisation. Since then, the CHMP has been monitoring the medicine closely and changes to the product information have been introduced as new data have become available.

The ongoing review of the medicine led to the CHMP’s recommendation in July 2007 to restrict the medicine’s use. This resulted in the addition of a contraindication for patients with ongoing major depression or taking antidepressants. A warning was also added to the prescribing information, stating that treatment with Acomplia should be stopped if a patient develops depression.

The CHMP recommended a further update in May 2008 to reflect new information on psychiatric reactions and to advise prescribers to monitor patients for signs and symptoms of psychiatric disorders, particularly depression, after the start of treatment.

Because of new data showing increasing concern over the psychiatric safety of Acomplia, the CHMP decided to ask a group of experts in diabetes, cardiovascular disease and psychiatry to review the medicine. The group met in June 2008, and looked at all of the available data on the benefits and risks of Acomplia. The experts were concerned that the margin of benefits over risks for Acomplia had narrowed since the medicine’s approval, but agreed that more data were needed before a conclusion could be reached.

As the assessment of the latest data from the company continued to raise concerns over the safety of Acomplia, the European Commission issued a formal request.
This enabled the CHMP to prepare an opinion on whether the marketing authorisation for Acomplia should be maintained, changed, suspended or withdrawn across the EU.

This review included all available information on the benefits and risks of Acomplia, focusing on its psychiatric side effects in patients taking the medicine, including new information that had become available after the expert meeting in June 2008. The information came both from the company’s monitoring of the use of the medicine from its launch until September 2008, and from studies conducted by the company that have been completed since Acomplia was granted marketing authorisation.

The CHMP confirmed that Acomplia is moderately effective in helping patients to lose weight. It also confirmed that the medicine has some benefits in terms of its effects on blood fats and blood glucose control. However, the new data show that in real life, patients tend to stop their treatment early. This short-term treatment with Acomplia may not bring the benefits expected on the basis of the clinical trials. There is also no evidence that Acomplia prevents cardiovascular disease.
The Committee confirmed that the risk of psychiatric side effects, including depression, sleep disorders, anxiety and aggression, is approximately doubled in patients taking Acomplia, compared to obese or overweight patients taking placebo. The new data from ongoing studies and post-marketing reports indicated that serious psychiatric disorders may be more common than in the clinical trials used in the initial assessment of the medicine.

Since the medicine has been on the market, an increasing number of cases of serious psychiatric disorders, including suicide, have been reported. In addition, between June and August 2008, five cases of suicide were reported in patients taking Acomplia in ongoing studies, compared with one case in patients taking placebo. These were seen in a total of around 36,000 patients. The Committee was also concerned that some patients taking antidepressants were still being prescribed Acomplia despite the introduction of the contraindication for these patients in 2007.

Because patients at an elevated risk of developing psychiatric disorders could not be identified, the Committee concluded that introducing further restrictions to the use of the medicine would be unlikely to reduce the risk to an acceptable level.
Therefore, the Committee concluded that the benefits of Acomplia no longer outweigh its risks, and recommended that the marketing authorisation for the medicine should be suspended across the EU.

Source: EMEA, 2008

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