Seroquel / Seroquel XR and associated names - referral

Current status

European Commission final decision

Overview

On 22 May 2014, the European Medicines Agency completed a review of Seroquel and Seroquel XR. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for these medicines in the European Union (EU).

What are Seroquel and Seroquel XR?

Seroquel and Seroquel XR are antipsychotic medicines that contain the active substance quetiapine. They are used in patients with schizophrenia, a mental illness with a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (false beliefs). They are also used for the prevention and treatment of bipolar disorder, a mental illness in which patients have manic episodes (periods of abnormally high mood), alternating with periods of normal mood, as well as episodes of depression. Seroquel XR can also be used as add-on treatment in major depression.

The exact mechanism of action of quetiapine is unknown, but it attaches to several receptors on the surface of nerve cells in the brain, including the receptors for the neurotransmitters dopamine and serotonin. As neurotransmitters are chemicals that allow nerve cells to communicate with each other, this affects signals transmitted between brain cells. Since these neurotransmitters are involved in schizophrenia, bipolar disorder and major depression, quetiapine helps to normalise the activity of the brain, reducing the symptoms of these diseases.

Seroquel is available as tablets (25, 100, 150, 200 and 300 mg) while Seroquel XR is available as prolonged-release tablets (50, 150, 200, 300 and 400 mg). Prolonged-release means that the active substance is released slowly from the tablet over a few hours. Seroquel and Seroquel XR are also marketed under other trade names. The company that markets these medicines is Astra Zeneca.

Why were Seroquel and Seroquel XR reviewed?

Seroquel and Seroquel XR are authorised in the EU via national procedures. This has led to divergences across Member States in the way the medicines can be used, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets in the countries where the medicines are marketed.

Seroquel and Seroquel XR were identified by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) as needing harmonisation.

On 12 June 2013, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Seroquel and Seroquel XR in the EU.

What are the conclusions of the CHMP?

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications

After reviewing the available data supporting the use of the medicines, the CHMP agreed that Seroquel and Seroquel XR can continue to be used for the treatment of schizophrenia and treatment and prevention of bipolar disorder, but recommended harmonised wordings for these indications as follows:

• treatment of schizophrenia;
• treatment of moderate to severe manic episodes in bipolar disorder and major depressive episodes in bipolar disorder;
• prevention of recurrence of manic or depressed episodes in patients with bipolar disorder who previously responded to quetiapine treatment.

Seroquel XR can also continue to be used as add-on to ongoing treatment for major depressive episodes in patients with major depressive disorder who have had sub-optimal response to treatment with other antidepressants.

4.2 Posology and method of administration

The CHMP also harmonised the dosing recommendations, particularly how to increase the dose and the recommended daily dose.

4.6 Fertility, pregnancy and lactation

Having reviewed the data available on the use of quetiapine during pregnancy, the CHMP concluded that no definite conclusion can be drawn on the risk of malformations in the unborn child when the medicine is used during early pregnancy (first trimester). Therefore, quetiapine should only be used during pregnancy if the benefits justify the potential risks. Additionally, the data available show that newborns who were exposed to antipsychotics (including quetiapine) during late pregnancy (third trimester) are at risk of side effects including agitation, somnolence, breathing and feeding problems. Consequently, newborns should be monitored carefully.

Other changes

The CHMP also harmonised other sections of the SmPC including sections 4.4 (special warnings and precautions for use) and 4.8 (undesirable effects).

The amended information to doctors and patients is available in the 'All documents' tab.

The European Commission issued a decision on 6 August 2014.

Questions and answers on Seroquel, Seroquel XR and associated names (quetiapine)

Reference Number: EMA/301727/2014

Key facts

About this medicine

• Approved name:
  Seroquel / Seroquel XR and associated names
• International non-proprietary name (INN) or common name:
  quetiapine

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1362
• Type:
  Article 30 referrals

  This type of referral is triggered when Member States have adopted different decisions over the years for some medicines (e.g. different indications, contraindications or posology) and there is a need to harmonise across the EU.

Key dates and outcomes

• CHMP opinion date:
  22/05/2014
• EC decision date:
  06/08/2014

All documents

Opinion provided by Committee for Medicinal Products for human Use

Seroquel, Seroquel XR and associated names Article-30 referral - Annex III

Questions and answers on Seroquel, Seroquel XR and associated names (quetiapine)

Reference Number: EMA/301727/2014

European Commission final decision

Seroquel, Seroquel XR and associated names Article-30 referral - Assessment report

Reference Number: EMA/CHMP/489245/2014

Seroquel, Seroquel XR and associated names Article-30 referral - Annex I

Seroquel, Seroquel XR and associated names Article-30 referral - Annex II

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.