Valproate – reproductive risks
Information about the reproductive risks of taking valproate medicines and the measures in place to reduce potential harm.
Information about valproate
Valproate is prescribed for some patients with epilepsy or bipolar disorder. Valproate-containing medicines include sodium valproate, valproic acid and valproate semisodium, so you may see these names on the box. Products may also be referred to using various brand names which include Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell.
Valproate should only be prescribed to patients (male or female) aged under 55 years when two specialists have agreed that your condition does not respond to other treatments and the benefits of treatment outweigh the risks.
If you are concerned about the risks of valproate, talk to your doctor, nurse, pharmacist or another healthcare professional.
No one should stop taking valproate without advice from a specialist because of the importance of keeping their condition well managed.
Information for female patients
Valproate must not be prescribed to any woman or girl able to have children unless the conditions of the Pregnancy Prevention Programme (PPP) are followed. The PPP is designed to make sure female patients are fully aware of the reproductive risks and the need to avoid becoming pregnant while taking valproate. Healthcare professionals should discuss the risks with patients and guides are provided to support those discussions before both the patient and healthcare professional sign the Annual Acknowledgement of Risk Form.
The risks of women taking valproate during pregnancy
In women who take valproate while pregnant, around 1 in 9 babies (11%) will have a birth defect.
Birth defects 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
- eye malformations in association with other birth defects that may affect vision
- hearing problems or deafness
In women who take valproate while pregnant, about 3 or 4 children in every 10 may have developmental problems. These disorders can be seriously debilitating and permanent.
The effects on development can include:
- difficulties learning to walk and talk
- lower intellectual ability than other children of the same age
- poor speech and language skills
- memory problems
Children of mothers who take valproate during pregnancy:
- are more likely to have autism or autism spectrum disorders
- may have a lower weight than expected for their age at birth
There is also some evidence children may be more likely to be at risk of developing symptoms of attention deficit hyperactivity disorder (ADHD).
If you are taking valproate, do not stop taking it without first discussing it with your specialist.
If you are taking valproate and you are planning a family, think you might be pregnant, or you know you are pregnant, contact your doctor at once so you can talk through your options.
Information for male patients
All male patients should be made aware of the risks and benefits of being prescribed valproate and there are guides to support these discussions as well as a patient card and information leaflet supplied with the medicine.
Male patients aged under 55 years being started on valproate are required to complete a Risk Acknowledgement Form with a healthcare professional.
Valproate can potentially cause:
- Male infertility (which may be reversible after treatment is stopped or the dose is reduced in some patients)
- Toxic effects on the testes (testicles) of animals, such as reduction in testes weight - it is currently unclear what this means for humans
The risks of men taking valproate around the time of conception
In men who take valproate in the 3 months before conception, about 5 children in every 100 may have neurodevelopmental conditions (problems with early childhood development).
Due to limitations in the data it is not clear if the increased risk for neurodevelopmental conditions is caused by valproate or other factors. Unfortunately, there is not enough data to show which particular type of disorder children may be at risk of developing.
If you are taking valproate, do not stop without first discussing it with your specialist.
If you are taking valproate and you are planning a family, contact your doctor so you can talk through your options.
Patient support networks
If you have questions or concerns about the risks associated with valproate, 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
- Young Epilepsy
- SUDEP Action - 0123772852
If you or your child has been affected by valproate medicines, you can also contact a support network such as:
- Independent Fetal Anticonvulsant Trust (INFACT) - 01253 799161
- Organisation for Anti-Convulsant Syndrome (OACS) - 07904 200364
Information for healthcare professionals
In addition to a significant risk of birth defects and developmental disorders in children born to women who take valproate during pregnancy, there is evolving evidence of reproductive harms in male patients. A number of recent changes to the regulatory position have been communicated to healthcare professionals:
| November 2023 | A National Patient Safety Alert asked organisations to prepare for new regulatory measures for increased oversight of prescribing of valproate to new patients and existing female patients. A Public Assessment Report presents the evidence and expert discussions which led to the new measures. |
| January 2024 | An article in Drug Safety Update announced the introduction of the new measures and provided new safety and educational materials to support their implementation. |
| September 2024 | An article in Drug Safety Update advised that as a precaution, men taking valproate and their partners should use effective contraception. A Public Assessment Report presents the evidence and expert discussions which led to the new measures. |
| February 2025 | An article in Drug Safety Update advised that whilst two specialist review is required for male patients under 55 years initiating valproate, two specialist review is not required for males already taking valproate given the availability of updated male patient guide and the information for male patients on the card on the box of valproate containing medicines. A Public Assessment Report presents the expert advice which led to the regulatory decision. Three infographics describe circumstances where review by two specialists may be required: - for female patients under 55 years old - for male patients under 55 years old - for male and female patients 55 years and older |
| June 2025 | An article in Drug Safety Update provided updated safety and educational materials to support discussions on reproductive risks (see below). |
Materials and resources
Safety and educational materials
To support the implementation of these measures for valproate, the following safety and educational materials are available:
- Patient guides for female and male patients: Provides those taking valproate (or their parent, caregiver, or responsible person) with information on the risks of valproate in pregnancy and the risks to male patients and what they need to do.
- Healthcare professionals Guide: Provides updated information for healthcare professionals on the risks of valproate in pregnancy and the risks for male patients, the new conditions for valproate prescribing and key points for patient discussions.
- Annual Risk Acknowledgement Form: For female patients under 55 years starting valproate and at annual review. Used to support and record the discussion between the patient and specialist prescriber on the risks associated with valproate in pregnancy and to record the decision of the countersigning specialist. At subsequent annual reviews only one specialist is required.
- Male Risk Acknowledgement Form: Used to support and record the discussion between the patient and specialist prescriber of the risks associated with valproate in males under 55 years when starting treatment with valproate and to record the decision of the countersigning specialist. This is only to be completed at initiation of valproate.
- Patient Card: Provides key information for female patients receiving valproate on contraception and pregnancy prevention and precautionary advice for me and their female partner to use effective contraception.
- Pharmacy Poster: Provides important actions for pharmacists dispensing valproate to patients.
Rules introduced in 2023 to ensure all patients receive the whole pack of valproate with the warnings on the box.
See Product Information for valproate medicines, including the Patient Information Leaflet.
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.
Second Specialist Signatories
To support the measures introduced in January 2024, the Commission of Human Medicines (CHM) advised that the second specialist signatory could include the following however it should be noted that this determination should be made at a local level:
- Consultant adult or paediatric neurologists
- Consultant psychiatrists
- Speciality and associate specialist doctors in psychiatry and neurology
- Speciality doctors in psychiatry
- Paediatrician with special interest in epilepsy
- Paediatrician who regularly manages complex epilepsy or bipolar disorder
- Epilepsy nurse consultant
- Specialist nurses in relevant disciplines
- Specialist pharmacists
Clinical resources
The following resources are available to support healthcare professionals understand their clinical responsibilities for valproate:
- NICE – Summary of guidance and safety advice
- NHS – Decision support tool: is valproate the right epilepsy treatment for me?
- Association of British Neurologists – ABN guidelines for valproate prescribing in adult (16 or over) neurology
- 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
- BPNA, OPEN UK, RCPCH prescribing guidance document (PDF, 227 KB, 5 pages)
Monitoring impact
Medicines and Pregnancy Registry
We have launched a Medicines and Pregnancy Registry in partnership with NHS England (formerly NHS Digital). This provides six-monthly reports to help monitor the effectiveness of the valproate pregnancy prevention plan. It includes age-stratified prescribing data, and numbers of those starting or stopping antiepileptic drugs – including valproate – as well as prescribing in and around pregnancy over time.
We have been monitoring trends in the prescribing of sodium valproate to assess the impact of evolving regulatory recommendations and introduction of the PPP 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.