The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) is currently evaluating the results of a post-authorization safety study (PASS), relating to the risk of neurodevelopmental disorders and congenital malformations in children whose fathers were treated with valproate in the three months preceding conception.

This study was requested following the review of the safety of valproate in women of childbearing potential and pregnant women in 2018 and was conducted by a consortium of marketing authorization holders of valproate-containing medicines using data from several registry databases in Norway, Sweden and Denmark (The study is registered in the ENCEPP database with the code number EUPAS34201).

The retrospective analysis of these registries compared children whose fathers had been treated with valproate in the three months prior to conception with children whose fathers had been treated with lamotrigine or levetiracetam (other medicines for the treatment of epilepsy and/or bipolar disorder).
The study has some limitations that make it difficult to unequivocally interpret the results.

Further investigations are therefore needed to evaluate the strength of this evidence. Therefore, the PRAC has requested the consortium of marketing authorization holders to provide additional information and additional data analyzes as soon as possible, in order to ensure that the study is carefully reviewed and the results fully trustworthy. The outcome of this evaluation will be communicated to patients and healthcare professionals as soon as it is available.

Male patients being treated with valproate should not stop taking the medicine without talking to their doctor, as abrupt discontinuation exposes epileptic patients to recurrence of seizures and patients with mood disorder to clinical worsening.

The ongoing evaluation of these new study results does not impact current recommendations for women of childbearing potential and restrictions in place to avoid exposure to valproate during pregnancy that are available at the following link.