Men taking valproate and their partners advised to use effective contraception

Men taking valproate and their partners are being advised by the Medicines and Healthcare products Regulatory Agency (MHRA) to use effective contraception as new data suggests 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 and is prescribed to around 60,000 men aged 13-54 in England, with a further 5,000 under the age of 12. It is  prescribed under brand names including Epilim, Belvo, Convulex and Depakote and has been linked with male infertility. 

However, the 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. 
 

Results of the valproate study

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.

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

The risk is much lower than the risk of neurodevelopmental disorders in children born to mothers who take valproate during pregnancy. 

Up to 40 per cent of babies exposed to valproate in the uterus are born with a physical or neurodevelopmental disorder.
 

New advice for men

The new MHRA advice, which has been introduced as a precautionary measure, recommends that:

• men and their partners use effective contraception while taking valproate and for at least three months after stopping treatment 
• they should not donate sperm during treatment with valproate and for three months after stopping valproate. 

Healthcare professionals are asked to inform men about the 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 men 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 men 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.
 

Effective contraception

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.’’

This new advice comes in addition to measures introduced in January this year which stated that from January 2024 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. 
 

Epilepsy Society responds

Clare Pelham, Chief Executive at the Epilepsy Society said: “It is right for the MHRA to be vigilant as more information becomes available about the risks of epilepsy medication; and to bring this to public attention.  They have not always done so.  

“People with epilepsy must be able to make informed choices about the drugs they wish to take.  This will include for some people coming to a view about whether to use contraception or to decide to start a family and, if so, what anti-seizure medication they wish to take.  This is a personal decision which can only be taken in consultation with your own doctor or consultant.  

“People’s choices will vary dependent on their health, their lifestyle, and any religious views.  The overriding factor is that every person must have good, reliable and expert information to inform their decision.”  

You can listen to Clare Pelham talking about the new safety measures on BBC Radio 4 (scroll to 15:39-17:31 Released on 6 September, available for 29 days)

You can also read more at BBC News online.