Sibutramine is an anti-obesity agent, which inhibits the reuptake of norepinephrine and serotonin.
On 4 October 1999, sibutramine containing medicinal products were subjected to a referral under Article 12 of Council Directive 75/319/EEC, as amended triggered by Belgium, who considered that sibutramine gave rise to increased blood pressure and heart rate in a substantial number of users and that the long-term consequences of these effects were not sufficiently documented. Belgium requested the CPMP to reassess the benefit/risk of sibutramine containing medicinal products.
Subsequently, the CPMP reviewed the safety and efficacy of sibutramine containing medicinal products and after considering the commitment from the Marketing Authorisation Holder, adopted an opinion on 16 November 2000, recommending the maintenance of the Marketing Authorisations for sibutramine containing medicinal products in accordance with an amended Summary of Product Characteristics (SPC) and under certain conditions, such as the performance of a clinical study to evaluate the impact of sibutramine on the cardiovascular risk and the submission of six-monthly Periodic Safety Update Reports (PSURs) for review by the CPMP. On the basis of the Opinion adopted by the CPMP, the European Commission issued a decision on 26 March 2001.
On 6 March 2002 the Italian Authorities circulated a Rapid Alert to all MS, EMEA and EC, informing all parties of their decision to temporarily suspend the Marketing Authorisations for sibutramine containing medicinal products in Italy. This suspension was mainly due to safety concerns, based on a number of reports of serious adverse reactions associated with sibutramine in Italian patients, including two fatal cases. Subsequently, Italy triggered on 19 March 2002 a referral to the EMEA, under Article 31 of Directive 2001/83/EC (formerly Article 12 of Council Directive 75/319/EEC, as amended), requesting the CPMP to give an opinion on whether the marketing authorisations for sibutramine containing medicinal products, in the current approved therapeutic indications, should be maintained, changed, suspended or withdrawn, on the basis of reported serious adverse reactions associated with these medicinal products. Italy considered that for public health protection, a reassessment of the efficacy and safety of sibutramine containing medicinal products was necessary.
The referral procedure started on 21 March 2002. Written explanations were provided by the Marketing Authorisation Holders (MAHs) on 12 April and 5 June 2002.
On the basis of the available data on sibutramine, the CPMP considered that the benefit/risk balance of sibutramine containing medicinal products is favourable, and therefore adopted on 27 June 2002, an Opinion recommending the maintenance of the Marketing Authorisations for sibutramine containing medicinal products referred in Annexes IA and IB of the Opinion, as amended in accordance with the SPC set out in Annex III and under the conditions set out in Annex IV of the Opinion.
A summary of the scientific conclusions is provided in the Annex II.
The final opinion was converted into a Decision by the European Commission on 15 October 2002.
|International non-proprietary name (INN) or common name||
Article 31 referrals
This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.
European Commission final decision
|EC decision date||
Opinion following an Article 31 referral for Sibutramine International Non-Proprietary Name (INN): Sibutramine: Background information and Annexes I, II, III (PDF/252.55 KB)Adopted
First published: 03/12/2002
Last updated: 03/12/2002
Sibutramine - Article 31 referral - Annex III (PDF/156.91 KB)Adopted
First published: 14/12/2002
Last updated: 14/12/2002
- Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
- Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
- List of the medicines affected by the referral (Annex I)
- Scientific conclusions of the Committee (Annex II)
The following two documents are sometimes available:
- Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes havebeen recommended by the Committee
- Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be takenfor the marketing authorisation(s) such as safety measures or extra studies