The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) has concluded that there may be a causal association between paternal exposure to valproate and related substances and neurodevelopmental disorders in offspring, according to a signal assessment report adopted on 11 June 2026 and published on 20 July 2026. The report, which updates a previous PRAC recommendation from November 2025, is based on additional data submitted by marketing authorisation holders and study authors, and recommends updating product information to reflect the potential risk.
The signal was first validated by the Dutch medicines agency (NL) on 26 June 2025, and PRAC appointed Liana Martirosyan (NL) as rapporteur. After an initial assessment, PRAC adopted its first recommendation on 10 July 2025, followed by a second recommendation on 20 November 2025 after reviewing marketing authorisation holder submissions. The current assessment incorporates further data received in March and April 2026, including study authors' responses and additional marketing authorisation holder submissions, leading to the final recommendation adopted on 11 June 2026.
The report covers valproate and related substances (sodium valproate, valproic acid, valproate semisodium, valpromide, valproate magnesium) used for epilepsy, bipolar disorder, and migraine. The PRAC recommendation is expected to lead to updated warnings in the product information for healthcare professionals and patients, potentially affecting prescribing practices for men of reproductive age. The decision impacts patients and healthcare providers who rely on valproate for these conditions, as well as marketing authorisation holders such as Sanofi, which holds the innovator authorisation. While the update may improve informed decision-making and reduce potential risks to children, it could also limit treatment options for men with epilepsy or bipolar disorder who have limited alternatives.