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.
Valproate is a treatment for epilepsy and bipolar disorder and is prescribed to thousands of women. Since its introduction in 1974, the product information for doctors has included a warning about the possible risk of birth defects. As the risks to unborn children have been increasingly understood, the warnings have been strengthened.
In March 2018 the CMDh endorsed a strengthened regulatory position on valproate medicines. Valproate must no longer be used in any woman or girl able to have children unless she has a pregnancy prevention programme in place. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant.
It is important women don’t stop taking valproate without first discussing it with their doctor.
If valproate is taken during pregnancy, up to 4 in 10 babies are at risk of developmental disorders, and approximately 1 in 10 are at risk of birth defects.
In women who take valproate while pregnant, around 1 in 10 babies 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. The long-term effects are not known.
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 autistic 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 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.
Healthcare professionals who seek to prescribe valproate to their female patients must make sure they are enrolled in the PPP. This includes the completion of a signed risk acknowledgement form when their treatment is reviewed by a specialist, at least annually.
An updatedis available to support the Valproate Pregnancy Prevention Programme (version dated March 2019).
These regulatory changes are further supported by:
- smaller pack sizes to encourage monthly prescribing
- a pictogram/warning image on valproate labelling
All women and girls who are prescribed valproate should contact their GP and arrange to have their treatment reviewed.
No woman or girl should stop taking valproate without first discussing it with their doctor.
These regulatory measures are supported across the NHS with other authorities also making changes – such as GP system computer alerts and amended NICE guidelines – to make sure changes in prescribing behaviour take place promptly.
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.
Patient Information Leaflets
A statutory patient information leaflet should always be provided with a medicine containing valproate, even if dispensed in a pharmacy box.
Additional copies of the patient information leaflet of valproate-containing medicines are available to download.