Issued by: Medicines and Healthcare products Regulatory Agency

Men taking valproate and their partners are being advised by the Medicines and Healthcare products Regulatory Agency (MHRA) to use effective contraception because of new data suggesting a potential small increased risk of harm to children if valproate is used by a father at conception. Valproate is licensed for epilepsy and bipolar disorder.

This precautionary advice follows the analysis of a retrospective observational study which reports a possible association between valproate use by men and a small increased risk of a range of neurodevelopmental disorders in their children (aged 0 to 11 years) when compared to men prescribed lamotrigine or levetiracetam.

The study, carried out in some of the Scandinavian countries where valproate is used, showed that around 5 out of 100 children had a neurodevelopmental disorder when born to fathers treated with valproate compared with around 3 out of 100 when born to fathers treated with lamotrigine or levetiracetam.

Whilst this study does not prove that valproate use in men increased the risk of problems in children, it is an important safety issue that warrants action on a precautionary basis.

Though the risk is much lower than the risk of neurodevelopmental disorders in children born to mothers who take valproate during pregnancy, the MHRA advice, which has been introduced as a precautionary measure, recommends that male patients and their partner use effective contraception during valproate treatment and for at least three months after stopping valproate.

Patients should not donate sperm during treatment with valproate and for three months after stopping valproate.

Healthcare professionals should inform male patients about this newly identified risk at their next routine treatment review, offer them a discussion about how it impacts their current treatment and other potential treatment options available. For those patients wishing to change their treatment the MHRA recommends that priority be given to male patients who are planning to father a child in the next year.

The MHRA encourages patients to attend their next routine appointment to discuss their treatment plan and to talk to a healthcare professional if they have any questions.

No one should stop taking valproate without advice from a specialist because of the importance of keeping their condition under control.

Anyone with questions should speak to a healthcare professional. Any suspected side effects associated with valproate should be reported via the Yellow Card scheme.

Dr Alison Cave, Chief Safety Officer at the MHRA, said:

"Valproate is an effective medicine in the treatment of epilepsy and bipolar disorder. Men taking valproate should be aware that there is now evidence of a potential small increased risk of their child having a neurodevelopmental disorder if their partner becomes pregnant while they are on valproate.

"While the risk to a child is lower than the risk associated with a mother taking valproate in pregnancy, we recommend that men taking valproate and their partners follow the updated guidance and use effective contraception.

"Patients on valproate should not stop taking their medicine unless advised to do so by a healthcare professional. It is important to attend your next appointment in order to discuss your treatment plan."

This new advice comes in addition to measures introduced in January this year which stated that from January 2024 (https://www.gov.uk/guidance/valproate-use-by-women-and-girls) valproate must not be started in new patients (male or female) younger than 55 years unless two specialists independently consider and document that there is no other effective or tolerated treatment, or unless there are compelling reasons that the reproductive risks do not apply. For the majority of patients, other effective treatment options are available.

Although valproate is associated with male infertility, the results of this study show that if a child is conceived while their father is taking valproate there is a potential small increased risk of neurodevelopmental disorders.

ENDS

Notes to editors

- The Commission on Human Medicines has advised on the safety of valproate on a number of occasions and has sought views from patients and other representatives regularly since the Valproate Stakeholders’ Network was formed by the MHRA in 2016.

- The risk estimates for children exposed to valproate taken by the mother during pregnancy is up to 30 to 40 babies in 100 for developmental disorders, and approximately 11 in 100 for major birth defects.

- Neurodevelopmental disorders are conditions that affect how the brain functions. They range from minor limitations allowing those affected to live fairly normal lives, to disorders that require lifelong care. Neurodevelopmental disorders encompass a broad range of conditions, including Intellectual Disorders, Communication Disorders, Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorders, Motor Disorders, Tic Disorders and Other Neurodevelopmental Disorders.

- The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe. All our work is underpinned by robust and fact-based judgements to ensure that the benefits justify any risks.

- The MHRA is an executive agency of the Department of Health and Social Care (DHSC).

- For media enquiries, please contact the newscentre@mhra.gov.uk, or call on 020 3080 7651.

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