Valproate and related substances
- Procedure started
- Under evaluation
- PRAC recommendation
- CMDh position
- European Commission final decision
Table of contents
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 |
|
Associated names |
|
About this procedure
|
|
---|---|
Current status |
European Commission final decision
|
Reference number |
EMEA/H/A-31/1454
|
Type | |
Authorisation model |
Nationally authorised product(s)
|
Decision making model |
PRAC-CMDh
|
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.
A video recording is available below.
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
Valproate Article-31 referral - Notification (PDF/115.59 KB)
First published: 10/03/2017
Last updated: 10/03/2017
EMEA/H/A-31/1454
Valproate Article-31 referral - Review started (PDF/78.3 KB)
First published: 10/03/2017
Last updated: 10/03/2017
EMA/144306/2017
Valproate Article-31 referral - Annex I (PDF/461.98 KB)
First published: 10/03/2017
Last updated: 11/04/2017
EMEA/H/A-31/1454
Valproate Article-31 referral - PRAC list of questions (PDF/85.24 KB)
First published: 10/03/2017
Last updated: 10/03/2017
EMA/PRAC/154222/2017
Under evaluation
Recommendation provided by Pharmacovigilance Risk Assessment Committee
Position provided by CMDh
Valproate Article-31 referral - PRAC assessment report (PDF/837.15 KB)
First published: 07/06/2018
Last updated: 07/06/2018
EMA/198940/2018
Valproate Article-31 referral - Annex II (PDF/79.87 KB)
First published: 07/06/2018
Last updated: 07/06/2018
Valproate Article-31 referral - Annex IV (PDF/34.36 KB)
First published: 07/06/2018
Last updated: 07/06/2018
Valproate Article-31 referral - Annex I (PDF/904.04 KB)
First published: 07/06/2018
Last updated: 07/06/2018
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
Valproate Article-31 referral - Annex III (PDF/120.98 KB)
First published: 23/03/2018
Last updated: 07/06/2018
European Commission final decision
Valproate Article-31 referral - Divergent position (PDF/28.45 KB)
First published: 07/06/2018
Last updated: 07/06/2018
Valproate Article-31 referral - New measures to avoid valproate exposure in pregnancy endorsed (PDF/94.49 KB)
First published: 07/06/2018
Last updated: 07/06/2018
EMA/375438/2018
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.
News
-
23/03/2018
-
09/02/2018
-
09/02/2018
-
12/01/2018
-
29/09/2017
-
07/07/2017
-
09/06/2017
-
10/03/2017