EMA Reviews Data on Paternal Exposure to Valproate

On Aug. 16, 2023, the European Medicines Agency (EMA) released a press statement to announce that their Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on the possible risk of neurodevelopmental disorders (NDDs) developing in children because of paternal use of valproate medicines. The data being assessed is from a retrospective observational study conducted by companies as an obligation after a previous review of valproate use during pregnancy. The study compared the development of NDDs (including autism spectrum disorder) in children from men taking valproate with the development in children from men taking lamotrigine or levetiracetam (other epilepsy treatments). It was conducted in multiple registry databases in Denmark, Sweden, and Norway.

The results may indicate an increased rate of NDD development in children born to men taking valproate three months from conception, but PRAC found several important limitations with the data from the study. It had questions about the definition of NDDs used in the study, and the specific type of epilepsy the fathers had, as higher dosages of valproate can be prescribed more frequently for certain types of epilepsy associated with NDDs. Additionally, after the results were submitted, the companies also informed PRAC on errors in the Norwegian database.

Because of these limitations, PRAC requested the companies to submit analyses of corrected data as well as more information as soon as possible. PRAC will review the new data when it is available before it makes an EU-wide recommendation. In the meantime, some Member States are using interim national recommendations. EMA reminded male patients taking valproate to not stop taking their medicine without consulting their doctor, as symptoms from their epilepsy or bipolar disorder could worsen, and sudden discontinuation could trigger seizures. Previous recommendations of women during pregnancy to avoid exposure to valproate remain in place.

Source: EMA