Guidance

Valproate use by women and girls

Information about the risks of taking valproate medicines during pregnancy.

From:
Medicines and Healthcare products Regulatory Agency
Published
23 March 2018
Last updated
30 January 2024 — See all updates

See also Collection of information and guidance for patients and for healthcare professionals on the reproductive risks of valproate and new safety measures introduced to reduce these risks.

Valproate (Epilim, Depakote and other generic brands) is associated with a significant risk of birth defects and developmental disorders in children born to women who take valproate during pregnancy. Since 2018 any use of valproate in patients of childbearing potential has to be within the terms of the Pregnancy Prevention Programme. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant.

This page describes the risks associated with valproate use in pregnancy and the measures in place to reduce harm.

It is important patients don’t stop taking valproate without first discussing it with their specialist.

Information about the risks if valproate is taken during pregnancy  

If valproate is taken during pregnancy, up to 4 in 10 babies are at risk of developmental disorders, and approximately 1 in 9 are at risk of birth defects.

In women who take valproate while pregnant, around 1 in 9 babies (11%) will have a birth defect.

Birth defects seen when mothers take valproate during pregnancy include:

  • spina bifida (where the bones of the spine do not develop properly)
  • facial and skull malformations (including cleft lip and palate, where the upper lip or facial bones are split)
  • malformations of the limbs, heart, kidney, urinary tract and sexual organs

In women who take valproate while pregnant, about 3–4 children in every 10 may have developmental problems, and these disorders can be seriously debilitating and permanent.

The effects on development can include:

  • being late in learning to walk and talk
  • lower intelligence than other children of the same age
  • poor speech and language skills
  • memory problems.

Children exposed to valproate in the womb are more likely to have autism or autistm spectrum disorders. There is also some evidence children may be more likely to be at risk of developing symptoms of attention deficit hyperactivity disorder (ADHD).

Valproate should not be used in pregnancy

Valproate must not be used in any woman or girl able to have children unless there is a Pregnancy Prevention Programme (PPP) in place. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant.

These regulatory measures, announced following a large-scale review of the risk in 2018, also include a ban on the use of valproate for migraine or bipolar disorder during pregnancy, and a ban on the use of valproate to treat epilepsy during pregnancy unless there is no other effective treatment available.

No one should stop taking valproate without advice from their specialist.

Responsibilities of healthcare professionals for the PPP

Healthcare professionals who seek to prescribe or dispense valproate to their female patients must make sure this is within the terms of the PPP. This includes the completion of a signed risk acknowledgement form when their treatment is reviewed by a specialist, at least annually.

These regulatory changes are further supported by:

  • smaller pack sizes to encourage monthly prescribing
  • a pictogram/warning image on valproate labelling
  • rules introduced in 2023 to ensure all patients receive the whole pack of valproate with the warnings on the box

The Commission on Human Medicines has reviewed the available safety data relating to the use of other key antiepileptic drugs in pregnancy, including the risk of major congenital malformations and of adverse neurodevelopmental outcomes. The review’s findings should help inform discussions on treatment options with women with epilepsy at initiation and at routine recommended annual reviews and with women who are planning to become pregnant.

Working together, across the health sector, these measures will help reduce the number of pregnancies exposed to valproate medicines to an absolute minimum and will make sure all women and girls of childbearing potential are aware of the risks.

Materials and resources

A statutory patient information leaflet should always be provided with a medicine containing valproate.

Additional copies of the patient information leaflet of valproate-containing medicines are available to download.

View the Patient guide

View the Patient card

View the Annual Risk Acknowledgement Form

View the Healthcare Professional Guide

Video to support healthcare professionals

The below video is to help healthcare professionals in implementing the new 2018 regulatory measures, including the pregnancy prevention programme and regular patient reviews.

Valproate – pregnancy prevention programme

Patient support networks

If you have questions or concerns about the risks associated with valproate and pregnancy, please speak to your doctor, pharmacist or other healthcare professional.

You can also contact a patient support network such as:

Bipolar UK - 0333 323 3880

Epilepsy Action - 0808 800 5050

Epilepsy Society - 01494 601 400

Mind - 0300 123 3393

If you are taking valproate and think you might be pregnant or know you are pregnant, contact your doctor at once so that you can talk through your options.

If you have experienced any side effects to this medicine you can report these to MHRA using the Yellow Card Scheme.

If you or your child has been affected by valproate medicines, you can also contact a support network such as:

OACS - 07904 200364

INFACT/FACSA - 01253 799161

Clinical resources

The following resources are available to support healthcare professionals understand their clinical responsibilities for valproate:

Monitoring impact

We have been monitoring trends in the prescribing of sodium valproate to assess the impact of evolving regulatory recommendations and introduction of the pregnancy prevention programme using primary care data from the Clinical Practice Research Datalink GOLD database.

Version 4 - CPRD study monitoring the use of valproate in girls and women in the UK: report from January 2010 to December 2019 (PDF, 277 KB, 8 pages)

Version 3 - CPRD study monitoring the use of valproate in girls and women in the UK: report from January 2010 to June 2019 (PDF, 243 KB, 5 pages)

Version 2 - CPRD study monitoring the use of valproate in girls and women in the UK – report from January 2010 to December 2018 (PDF, 200 KB, 5 pages)

Version 1 - CPRD study monitoring the use of valproate in girls and women in the UK - report from January 2010 to June 2018 (PDF, 145 KB, 4 pages)

We will continue to monitor these and other data sources, including clinical audits and patient surveys, and will take action as necessary to protect public health.

Valproate registry

We have launched a valproate registry in partnership with NHS Digital, that will help prevent pregnancy in women taking valproate and make it easier for healthcare professionals to monitor the issue. The registry brings together data from the NHS Business Services Authority (BSA), Maternity Services Data Set (MSDS) and Hospital Episode Statistics (HES).

First Published 23 March 2018

Last updated 28 November 2023

Updates to this page

Published 23 March 2018
Last updated 30 January 2024 + show all updates

  1. Updated the 'Materials and resources' and 'Clinical resources' sections

  2. TBC

  3. Added information on the valproate registry

  4. Updated link to - Royal College of General Practitioners and Association of British Neurologists and Royal College of Physicians – Clinical guidance to support healthcare professionals involved in the care of women on valproate

  5. Uploaded new versions of the patient card, patient booklet, and healthcare professionals booklet (dated November 2020)

  6. Updated the current advice section to include the advice from CHM's review

  7. Added a link to new guidance on Valproate Pregnancy Prevention Programme: temporary advice for management during coronavirus (COVID-19).

  8. We have added a new version of the CPRD study monitoring the use of valproate in girls and women in the UK: report from January 2010 to December 2019

  9. Uploaded new versions of the patient card, patient booklet, healthcare professionals booklet and the Annual Risk Acknowledgement Form.

  10. December 2019 Addition of links to clinical resources to support healthcare professionals.

  11. Addition of version 3 of CPRD study monitoring the use of valproate in girls and women in the UK – report from January 2010 to June 2019

  12. Addition of version 2 of CPRD study monitoring the use of valproate in girls and women in the UK – report from January 2010 to December 2018

  13. Added updated annual risk acknowledgement form which must be completed as part of the pregnancy prevention programme.

  14. Added analysis of primary care prescribing data.

  15. Provided new link to Patient Information Leaflets

  16. Added a new video for healthcare professionals covering use of valproate by women and girls.

  17. Added the patient card, patient booklet, and booklet for healthcare professionals

  18. Updated with information about the strengthened regulatory position on valproate.

  19. First published.

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