Study suggests risk of harm for babies fathered by men taking valproate
The medicines regulator is re-examining evidence from a study which suggests there may be an increased risk of neurodevelopmental disorders in children fathered by men on valproate in the three months prior to conception. This is compared with men on other anti-seizure medicines.
IMPORTANT: No one should stop taking valproate without advice from their healthcare professional. Anyone who has concerns should talk to their healthcare professional.
In the study, around 5 children in 100 born to fathers treated with valproate around conception were diagnosed with a neurodevelopmental disorder. This is compared to 3 in 100 children whose fathers were taking lamotrigine or levetiracetam during the same timeframe.
While this risk is much smaller than that associated with valproate in pregnancy, the Medicine and Healthcare products Regulatory Agency (MHRA) is rigorously examining the results and will seek independent expert advice from the Commission on Human Medicines.
Further guidance will be issued, but in the meantime, the MHRA is advising any men on valproate who are planning a family in the next year to talk to their healthcare professional about their treatment.
The review of paternal risk does not alter the recently announced new regulations around the prescribing of valproate.
New measures around valproate
The new measures mean that valproate must not be started in new patients (both male and female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply.
You can read more about the new measures here.
The population-based study was commissioned by the European Medicines Agency and reviewed data from more than 4,000 paternal valproate exposures from national registries across Norway, Denmark and Sweden.
The study was resubmitted owing to possible errors in the original version. The MHRA is analysing the resubmitted results.
Risks versus benefits
Ley Sander, Medical Director at the Epilepsy Society, commented on the announcement: “This highlights the challenges faced when prescribing medication for epilepsy. Valproate is a very effective drug in controlling seizures in some types of epilepsy but it also carries risks during pregnancy and, the study suggests, prior to conception.
"It is very important to consider all evidence which helps determine the safety of a medication, but the risks must be proportionately weighed against the benefits. We must always keep in mind that seizures are not benign events and can, in extreme circumstances, prove fatal.
“The MHRA have already introduced new prescribing practices around valproate for men, but it is vital that we go further and use our scientific knowledge and expertise to understand at a molecular level why some drugs elevate risk in some men and women while others don’t.
"We are asking the Government and industry to actively invest in genomic research that would enable us to identify at an individual level which person will be vulnerable to which medication, so that drugs can be prescribed according to a person’s individual genome.
“This is the only way forward. If we don’t invest now, we will continue to face these challenges across more and more drugs. When valproate was first prescribed five decades ago, we didn’t have the expertise to understand drug response at an individual level, but we do now. We have a duty to people with epilepsy in our care to ensure we use that expertise for their health and the health of their children.”