Prozac - referral

Current status

European Commission final decision

Overview

The Committee for Medicinal Products for Human Use (CHMP) has completed its arbitration review of Prozac (fluoxetine) and associated names¹, and gave a positive opinion to extend its use in the treatment of children suffering from depression, provided that the marketing authorisation holder (MAH), Eli Lilly, carries out additional studies to ensure that the safety profile of Prozac remains acceptable. The new indication is as follows:

Children and adolescents aged 8 years and above: Moderate to severe major depressive episode, if depression is unresponsive to psychological therapy after 4-6 sessions. Antidepressant medication should be offered to a child or young person with moderate to severe depression only in combination with a concurrent psychological therapy.

For further information, please refer to the Product Information for Prozac as adopted by the CHMP on 1 June 2006. The document is published for information on the EMEA website, pending formal endorsement by the European Commission

¹ Prozac is marketed also under the names of Fluctin, Fluctine, Fluoxétine Lilly, Fluoxétine RPG Prozac, Fontex, Ladose.

Why did the CHMP review this medicine?

Prozac is currently authorised for use in adults to treat depression, obsessive-compulsive disorders and bulimia nervosa (an eating disorder) within the European Union.

Following a request from the UK, the MAH for Prozac submitted an application for the extension of the indications to treat depression in children and adolescents, via the mutual recognition procedure². The review was initiated by France on the basis of safety and efficacy concerns on the use of Prozac in this age group.

² This is a procedure whereby Member States mutually recognise marketing authorisations within the European Union. In case of disagreement during the procedure, the issue is referred to the CHMP for arbitration.

What data has the CHMP reviewed?

The CHMP reviewed data submitted by the MAH, which included data from experimental models, clinical studies and information published in scientific journals.

Efficacy was supported by three main studies, involving over 750 children and adolescents. All studies compared the efficacy of Prozac in the treatment of depression with that of a placebo (dummy treatment) over 9 to 12 weeks. The CHMP also reviewed safety data from experimental and clinical studies on growth, sexual development and suicide-related behaviour (suicide attempt and suicidal thoughts).

What are the conclusions of the CHMP?

• The studies in children and adolescents showed a positive effect.
• The medicine should only be used together with psychological therapy in patients non-responding to such therapy alone after 4 to 6 sessions.
• The starting dose should be 10 mg per day (given as 2.5ml of the oral solution) and it may be increased to 20 mg per day after one to two weeks.
• If no clinical benefit is seen within 9 weeks, treatment should be reconsidered.
• The significance of the observations in experimental studies on sexual development, emotional behaviour and testicular toxicity will be further investigated. The MAH will also put in place a system to obtain safety data in treated children, in particular regarding sexual development.
• The CHMP confirmed that doctors and parents should carefully monitor children and adolescents for suicidal behaviour, particularly at the beginning of treatment.

Overall, the CHMP concluded that the benefits of Prozac are greater than its potential risks for the treatment of moderate to severe major depressive episode in children and adolescents.

For further information, please refer to the Product Information for Prozac as adopted by the CHMP on 1 June 2006. The document is published for information on the EMA website, pending formal endorsement by the European Commission is available under the "All documents" tabs.

Questions and answers on the review of Prozac for use in children and adolescents

Adopted Reference Number: EMEA/198323/2006

Key facts

About this medicine

• Approved name:
  Prozac
• International non-proprietary name (INN) or common name:
  fluoxetine

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/46089/06
• Type:
  Article 6(12) referrals (prior to January 2010)

  This type of referral was triggered for a medicine that had been authorised by mutual recognition or via the decentralised procedure when there was disagreement between Member States on a variation (type II). This referral has been replaced by Article 13 referrals.

Key dates and outcomes

• CHMP opinion date:
  01/06/2006
• EC decision date:
  21/08/2006

All documents

Prozac- Article 6 (12) referral - Annex I, II, III

Adopted

Opinion following an Article 6(12) referral for Prozac and associated names International Non-Proprietary Name (INN): Fluoxetine: Background information

Adopted Reference Number: EMEA/311654/2006

Questions and answers on the review of Prozac for use in children and adolescents

Adopted Reference Number: EMEA/198323/2006

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.