- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Table of contents
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medicinal products, in the current approved therapeutic indications, should be maintained, changed, suspended or withdrawn, on the basis of reported serious adverse reactions associated with these medicinal products.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.
About this medicine
About this procedure
European Commission final decision
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.
Key dates and outcomes
|CHMP opinion date||
|EC decision date||
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
- Overview - lay-language summary of the stage of the procedure
- Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
- Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
- List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
- Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
- List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
- List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
- Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
- Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
- Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
- Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
- Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
- Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
- Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
- Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)
Note that older documents may have different titles.