Medicines Healthcare Products Regulatory Agency
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 dont 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 34 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 hasreviewed the available safety datarelating to the use of other key antiepileptic drugs in pregnancy, including the risk of major congenital malformations and of adverse neurodevelopmental outcomes. The reviews 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
These materials will be replaced with new versions in early 2024. Until then they should be used to support the Pregnancy Prevention Programme.
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 areavailable to download.
View thePatient card
View thePatient booklet
View theBooklet for healthcare professionals
View theAnnual Risk Acknowledgement Form
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 theYellow 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:
- NICE Summary of guidance and safety advice
- 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.
- British Paediatric Neurology Association (BPNA) and the Royal College of Paediatrics and Child Health (RCPCH) Joint guidance to provide recommendations about the use of valproate in female patients under 18 years of age.
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 D