Valproate and related substances

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
European Commission final decision

Overview

New measures to avoid valproate exposure in pregnancy endorsed

Member State representatives agree new restrictions and pregnancy prevention programme

On 21 March 2018 the CMDh1 endorsed new measures to avoid exposure of babies to valproate medicines in the womb, because exposed babies are at high risk of malformations and developmental problems.

Valproate-containing medicines have been approved nationally in the EU to treat epilepsy and bipolar disorder and in some countries for prevention of migraine. The new measures include a ban on the use of such medicines for migraine or bipolar disorder during pregnancy, and a ban on treating epilepsy during pregnancy unless there is no other effective treatment available.

Further, the medicines must not be used in any woman or girl able to have children unless the conditions of a new pregnancy prevention programme are met. The programme is designed to ensure that patients are made fully aware of the risks and the need to avoid becoming pregnant.

A visual warning of the pregnancy risks (in the form of boxed text with other possible elements such as a warning symbol) must also be placed on the packaging of the medicines and warnings be included on patient cards attached to the box and supplied with the medicine each time it is dispensed.

The CMDh agreed with EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which carried out a review and recommended the new measures, that despite previous recommendations aimed at better informing patients of the risks with these medicines, women were still not always receiving the right information in a timely manner. The new measures endorsed by CMDh therefore strengthen previous restrictions on valproate use and requirements to inform women of the risk.

Companies marketing these medicines are also required to carry out additional studies on the nature and extent of the risks and to monitor valproate use and the long-term effects from affected pregnancies.

Because the CMDh position was agreed by majority vote it was sent to the European Commission, which issued a final legally binding decision valid across the EU.


1 The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.

Key facts

About this medicine
Approved name
Valproate and related substances
International non-proprietary name (INN) or common name
sodium valproate, valproate magnesium, valproate semisodium, valproic acid, valpromide
Associated names
  • Absenor
  • Convival Chrono
  • Convulex
  • Delepsine
  • Depakin
  • Depakine
  • Depakote
  • Depamag
  • Depamide
  • Deprakine
  • Diplexil
  • Dipromal
  • Epilim
  • Episenta
  • Epival
  • Ergenyl
  • Espa-Valept
  • Hexaquin
  • Kentlim
  • Leptilan
  • Micropakine L.P.
  • Orfiril
  • Petilin
  • Valepil
  • Valhel PR
  • Valpal
  • Valpro and Valprolek
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1454
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.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
09/03/2017
PRAC recommendation date
08/02/2018
CHMP opinion/CMDh position date
21/03/2018
EC decision date
31/05/2018
Outcome
Risk minimisation measures

Public hearing

EMA's Pharmacovigilance Risk Assessment Committee (PRAC) held a public hearing on this topic on 26 September 2017 at the Agency's premises in London:

The hearing was broadcast live on 26 September from 12:45-18:00 UK time.

The video recording is now available.

At the public hearing, the PRAC sought input on a list of specific questions. These are set out in the document below, together with a summary of the safety concerns with this medicine:

The application deadline to take part in the public hearing was 25 August 2017.

For more information on the PRAC meeting where the public hearing took place, see: PRAC: 25-29 September 2017.

For more information about public hearings at EMA, see Public hearings.

All documents

Procedure started

Under evaluation

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Position provided by CMDh

  • List item

    Valproate Article-31 referral - PRAC assessment report (PDF/837.15 KB)

    Adopted

    First published: 07/06/2018
    Last updated: 07/06/2018
    EMA/198940/2018

  • List item

    Valproate Article-31 referral - Annex II (PDF/79.87 KB)


    First published: 07/06/2018
    Last updated: 07/06/2018

  • List item

    Valproate Article-31 referral - Annex IV (PDF/34.36 KB)


    First published: 07/06/2018
    Last updated: 07/06/2018

  • List item

    Valproate Article-31 referral - Annex I (PDF/904.04 KB)


    First published: 07/06/2018
    Last updated: 07/06/2018

  • List item

    Valproate Article-31 referral - New measures to avoid valproate exposure in pregnancy endorsed (PDF/191.71 KB)


    First published: 23/03/2018
    Last updated: 23/03/2018
    EMA/145600/2018

  • List item

    Valproate Article-31 referral - Annex III (PDF/120.98 KB)


    First published: 23/03/2018
    Last updated: 07/06/2018

  • European Commission final decision

  • List item

    Valproate Article-31 referral - New measures to avoid valproate exposure in pregnancy endorsed (PDF/94.49 KB)

    Adopted

    First published: 07/06/2018
    Last updated: 07/06/2018
    EMA/375438/2018

  • List item

    Valproate Article-31 referral - Divergent position (PDF/28.45 KB)


    First published: 07/06/2018
    Last updated: 07/06/2018

  • List item

    Valproate Article-31 referral - New measures to avoid valproate exposure in pregnancy endorsed (PDF/94.49 KB)

    Adopted

    First published: 07/06/2018
    Last updated: 07/06/2018
    EMA/375438/2018

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

    News

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