Retinoid-containing medicinal products

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status
European Commission final decision

Overview

 

Updated measures for pregnancy prevention during retinoid use

Warning on possible risk of neuropsychiatric disorders also to be included for oral retinoids

On 22 March 2018, the European Medicines Agency (EMA) completed its review of retinoid medicines, and confirmed that an update of measures for pregnancy prevention is needed. In addition, a warning on the possibility that neuropsychiatric disorders (such as depression, anxiety and mood changes) may occur will be included in the prescribing information for oral retinoids (those taken by mouth).

Retinoids include the active substances acitretin, adapalene, alitretinoin, bexarotene, isotretinoin, tazarotene and tretinoin. They are taken by mouth or applied as creams or gels to treat several conditions mainly affecting the skin, including severe acne and psoriasis. Some retinoids are also used to treat certain forms of cancer.

The review confirmed that oral retinoids can harm the unborn child and must not be used during pregnancy. In addition, the oral retinoids acitretin, alitretinoin and isotretinoin, which are used to treat conditions mainly affecting the skin, must be used in accordance with the conditions of a new pregnancy prevention programme by women able to have children.

Topical retinoids (those applied to the skin) must also not be used during pregnancy, and by women planning to have a baby.

More information is available below.

Regarding the risk of neuropsychiatric disorders, the limitations of the available data did not allow to clearly establish whether this risk was due to the use of retinoids. However, considering that patients with severe skin conditions may be more vulnerable to neuropsychiatric disorders due to the nature of the disease, the prescribing information for oral retinoids will be updated to include a warning about this possible risk. Available data suggest that topical retinoids do not carry a risk of neuropsychiatric side effects, and therefore no additional warnings need to be added to the prescribing information.

The review of retinoids was carried out by EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which assessed the available data including published literature, post-marketing reports of side effects and additional information collected from stakeholder meetings and written submissions.

The EMA's Committee for Medicinal Products for Human use (CHMP) then endorsed the PRAC recommendations and adopted the Agency's final opinion. The CHMP opinion was sent to the European Commission, which issued a final legally binding decision valid across the EU.

Key facts

About this medicine
Approved name
Retinoid-containing medicinal products
International non-proprietary name (INN) or common name
  • acitretin
  • adapalene
  • alitretinoin
  • bexarotene
  • isotretinoin
  • tretinoin
  • tazarotene
Associated names
  • Targretin
  • Panretin
Class
dermatological agents
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1446
Type
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.

Authorisation model
Centrally and nationally authorised products (mixed)
Decision making model
PRAC-CHMP-EC
Key dates and outcomes
Procedure start date
07/07/2016
PRAC recommendation date
08/02/2018
CHMP opinion/CMDh position date
22/03/2018
EC decision date
21/06/2018
Outcome
Risk minimisation measures

All documents

Procedure started

Under evaluation

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    Retinoid Article-31 referral - Updated measures for pregnancy prevention during retinoid use (PDF/95.28 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018
    EMA/254364/2018

  • List item

    Retinoid Article-31 referral - Annex I (PDF/325.15 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018

  • List item

    Retinoid Article-31 referral - Divergent position (PDF/38.49 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018

  • List item

    Retinoid Article-31 referral - PRAC assessment report (PDF/282.63 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018
    EMA/254364/2018

  • List item

    Retinoid Article-31 referral - Annex II (PDF/42.68 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018

  • List item

    Retinoid Article-31 referral - Annex IV (PDF/27.24 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018

  • List item

    Retinoid Article-31 referral - Annex III (PDF/154.44 KB)


    First published: 02/07/2018
    Last updated: 02/07/2018

  • 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.

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