- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Sertindole is an atypical antipsychotic agent. It has affinity for dopamine receptors, especially D2 and for serotinergic receptors: 5HT2A and 5HT2C. It also inhibits α1-adrenergic receptors, but has almost no affinity to histaminergic or cholinergic receptors. Sertindole, indicated for the treatment of schizophrenia, was authorised in the United Kingdom in May 1996 and then subsequently in other European Member States through the Mutual Recognition procedure.
On 2 November 1998 the Netherlands presented to the EMEA a referral under article 36 of Directive 2001/83/EC, further to the suspension of the marketing of sertindole containing medicinal products in the Netherlands. The Netherlands considered that sertindole containing medicinal products presented a risk for public health due to an increased risk of sudden or cardiac death. The referral was considered by the CPMP at the November 1998 meeting and the referral procedure started on 18 November 1998. The Marketing Authorisation Holders (MAHs) provided written explanations on 18 January and 25 May 1999 and oral explanations at the June 1999 CPMP meeting.
On 23 June 1999, the CPMP adopted an Opinion (CPMP/1784/99) recommending that the Marketing Authorisations for all sertindole containing medicinal products should be suspended for a one-year period. On the basis of the CPMP opinion, the European Commission adopted on 20 January 2000 a Decision suspending the Marketing Authorisations concerning medicinal products containing sertindole until 31 December 2000.
Subsequently, the CPMP, having reviewed the evidence submitted by the MAHs and having reassessed the benefit/risk profile of sertindole containing medicinal products, adopted an opinion on 19 October 2000 recommending the renewal of the suspension of the Marketing Authorisations for all sertindole containing medicinal products for a further year. On 22 February 2001, the European Commission adopted a Decision suspending the Marketing Authorisations for medicinal products containing sertindole until 31 December 2001.
Supplementary information was provided by the MAHs on 18 May 2001 and on 31 May 2001. On 28 June 2001, an Ad-Hoc Expert Group was convened to review the available clinical and preclinical data related to the cardiovascular activity of sertindole and to consider whether such data support the current marketing authorisation status of sertindole.
Supplementary information was provided by the MAHs on 15 august 2001, 28 September 2001 and 11 October 2001. Oral explanations were given by the MAHs on 16 October 2001.
Based on re-evaluation of all available data including additional data submitted by the MAHs on sertindole, it has been concluded that further clinical safety data, strong safeguards including extensive contraindications and warnings for patients at risk of cardiac dysrhythmias, a recommended reduction in maximum dose from 24 mg to 20 mg in all but exceptional cases, and extensive ECG monitoring requirement before and during treatment would permit the re-introduction of sertindole containing medicinal products to the market. In the first instance, reintroduction should be limited to patients participating in two new post-marketing studies. The MAHs are committed to perform these two postmarketing studies to further investigate the cardiovascular safety concern. Therefore, the CPMP considered that, on the basis of the currently available information, the benefit/risk balance of sertindole containing medicinal products is now favourable and recommended on 18 October 2001, the lifting of the suspension of the Marketing Authorisations for all medicinal products referred in Annex I of the CPMP Opinion on the following conditions:
- Amendment of the Summary of Product Characteristics as set out in Annex III of the CPMP Opinion.
- The CPMP requirements and the conditions of the marketing authorisations as set out in Annex IV of the CPMP Opinion.
On the basis of the CPMP Opinion, the European Commission issued a Decision on 26 June 2002 concerning the lifting of the suspension of the Marketing Authorisations for sertindole containing medicinal products.
|International non-proprietary name (INN) or common name||
Article 36 referrals (prior to July 2012)
This type of referral applied for a marketing authorisation that were granted via the mutual-recognition or decentralised procedure. It was triggered when a Member State considered that action (variation, suspension or withdrawal) was needed on the grounds of the need to protect public health. This referral has been replaced by Articles 107i and 31.
European Commission final decision
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Opinion following an Article 36 referral for Sertindole International Non-Proprietary Name (INN): Sertindole: Background information and Annexes I, II (English) and Annex III (all languages) (PDF/234.92 KB)Adopted
First published: 13/09/2002
Last updated: 13/09/2002
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.