Valproate and related substances

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Summary

 

New review of valproate use in pregnancy and women of childbearing age

EMA to consider if risks of these medicines require further restrictions of use

The European Medicines Agency (EMA) has started a review looking at the use of valproate-containing medicines in the treatment of women and girls who are pregnant or of childbearing age. These medicines are approved nationally in the EU to treat epilepsy, bipolar disorder and in some countries, migraine, and have been previously reviewed by the Agency.

An EMA review in 20141 resulted in measures to strengthen the warnings and restrictions on the use of valproate medicines in women and girls, due to the risk of malformations and developmental problems in babies who are exposed to valproate in the womb. Although sometimes there may be no alternative to using valproate, these measures aimed to ensure that patients are aware of the risks of doing so, and that they take valproate only when clearly necessary. The 2014 review also recommended studies at EU level to measure how effective the proposed measures were.

Some EU member states have since carried out additional assessments of the impact of the measures at national level and concerns have been raised about how effective the measures have been in increasing awareness and reducing valproate use appropriately in its various indications. The French medicines regulator, ANSM, therefore asked EMA to review the effectiveness of the measures and to consider whether further EU-wide action should be recommended to minimise the risks in women who are pregnant or of childbearing age.

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) will examine the available evidence and will consult with relevant stakeholder groups. This will include holding a public hearing about their concerns. While the review is ongoing, patients prescribed valproate who have any concerns about their medication should discuss them with their healthcare professionals.


1Valproate and related substances

More about the medicine

Valproate medicines are used to treat epilepsy and bipolar disorder. In some EU Member States they are also authorised to prevent migraine headaches.

The active ingredient in these medicines may be valproic acid, magnesium valproate, sodium valproate, valproate semisodium or valpromide.

Valproate medicines have been authorised via national procedures in all EU Member States and in Norway and Iceland. They are marketed under several brand names including: 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.

More about the procedure

The review of valproate was initiated on 9 March 2017 at the request of the French medicines regulator ANSM, under Article 31 of Directive 2001/83/EC.

The review will be carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. The PRAC recommendations will then be sent to Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

Name Language First published Last updated
Valproate Article-31 referral - Review started (English only) 2017-03-10  

Key facts

About this medicine

Approved nameValproate and related substances
International non-proprietary name (INN) or common name

sodium valproate, valproate magnesium, valproate semisodium, valproic acid, valpromide

Associated namesAbsenor, 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
Class

About this procedure

Current statusUnder evaluation
Reference numberEMEA/H/A-31/1454
TypeArticle 31 referrals

This type of referral is triggered when the interest of the Community is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Decision making modelPRAC-CMDh
Authorisation modelNationally authorised product(s)

Key dates and outcomes

Procedure start date09/03/2017

Public hearing

EMA's Pharmacovigilance Risk Assessment Committee (PRAC) will hold a public hearing on this topic on 26 September 2017 at the Agency's premises in London. The hearing will start at 13:00 (UK time). 

EU citizens are invited to share their experiences with these medicines, so that these can be heard before the committee’s recommendation. 

The PRAC is seeking input from the public 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:

If you are considering taking part, please read the full guidance on how to participate:

public_hearings_guidance_thumbnail

Public hearings - guidance for participants

The guidance describes the process and practical arrangements for public hearings, including how to participate either as a speaker or an observer

EMA has also made an information video

 


To register your interest in taking part, please complete and return the application form to publichearings@ema.europa.eu EMA by 25 August 2017:
 

public_hearings_form_thumbnail

Application form to attend the public hearing on valproate on 26 September 2017

EMA will write to all applicants within two weeks after the application deadline to confirm whether they can attend. 

 

 


The hearing will also be broadcast live on 26 September 2017 on EMA's website. 

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

For more information on the PRAC meeting where the public hearing will take place, see: PRAC: 25-28 September 2017.

All documents

Procedure started

Name Language First published Last updated
Valproate Article-31 referral - PRAC list of questions EN = English 2017-03-10  
Valproate Article-31 referral - Timetable for the procedure EN = English 2017-03-10 2017-06-09
Valproate Article-31 referral - Annex I EN = English 2017-03-10 2017-04-11
Valproate Article-31 referral - Review started EN = English 2017-03-10  
Valproate Article-31 referral - Notification EN = English 2017-03-10  

Document description:

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) or Coordination Group for Mutual Recognition and Decentralised Procedures - Human (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 / CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

Current status:
Under evaluation

Public hearing

  • The PRAC will hold a public hearing on this topic on 26 September 2017. For more information, click on the 'Public hearing' tab.