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Men who take valproate, and their partners, should use effective contraception, the Medicines and Healthcare products Regulatory Agency (MHRA) has said.
The advice, issued on 5 September 2024, follows a study that revealed a possible connection between the use of valproate in men and a small increased risk of neurodevelopmental disorders in their children.
The Scandinavian study found that around 5 out of 100 children born to men who were taking valproate at the time of conception had a neurodevelopmental disorder, compared with 3 out of 100 children when the fathers were taking lamotrigine or levetiracetam — two other drugs used to treat epilepsy.
“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,” the MHRA said.
Noting that the risk of neurodevelopmental disorders in children is much lower compared with mothers who take the valproate during pregnancy, the MHRA said it was advising males and any partners to “use effective contraception during valproate treatment and for at least three months after stopping valproate”.
The regulator also advises that patients should not donate sperm during valproate treatment and for three months after stopping the medicine.
The use of valproate by pregnant women has been associated with a high risk of congenital malformations and neurodevelopmental disorders in their children.
In 2018, the MHRA announced that the medicine must not be prescribed to women or girls of child-bearing potential unless they are on a pregnancy prevention programme (PPP).
In January 2024, new regulatory measures were introduced to reduce harms associated with valproate, including a requirement for two specialist doctors to sign off new valproate prescriptions.
Alison Cave, chief safety officer at the MHRA, commented: “Valproate is an effective medicine in the treatment of epilepsy and bipolar disorder.
“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.”
Alison Fuller, director of health improvement and influencing at Epilepsy Action, said: “We know there are around 65,000 boys and men currently on sodium valproate in the UK. The measures are precautionary, meaning they will not require two signatories to stay on their medication. That said, they will still need to have an in-depth conversation with a healthcare professional.
She added that Epilepsy Action was aware the advice would raise questions within the epilepsy community.
“We are concerned people with epilepsy will feel confused at best, and very worried about what this means for their treatment at worst.”
Claire Anderson, president of the Royal Pharmaceutical Society, said: “Pharmacists already play a vital role in providing clear guidance and accompanying printed patient safety information on the safe use of valproate for women as part of the PPP.
“It is imperative to note that patients must not stop taking valproate without advice from a specialist, due to the importance of keeping their condition under control.
“Pharmacists are well placed to support patients with this new safety advice and will continue working with prescribers to ensure patient safety is maintained when taking valproate.”
In March 2024, a study published in JAMA Neurology reported that the declining use in women of valproate and carbamazepine, another epilepsy medicine, had led to a reduction in major congenital malformations in children.
