New side effect of valproic acid.

At the beginning of April 2023, a letter was published on the website of Roszdravnadzor for healthcare professionals about new data on the safety of drugs with an international non-proprietary name (INN) – valproic acid. This letter is based on a notice from Sanofi Russia regarding a higher risk of developing neurodevelopmental disorders (NDPD), including autism spectrum disorders, in children whose fathers received valproic acid therapy before and at the time of conception.

Valproic acid preparations are used to treat epilepsy and to treat and prevent bipolar disorder in adults. Valproic acid is also used to treat epilepsy and prevent high fever seizures in children under 6 years of age.

The basis for signaling about a new side effect was the results of a retrospective observational study conducted in three Nordic countries, according to which the risk of developing NDPD in the valproic acid group ranged from 5.6 % to 6.3 % compared with a risk of 2.5 % – 3.6 % in the lamotrigine/levetiracetam combination group.

Back in May 2018, the European Commission approved some recommendations of the Pharmacovigilance Risk Assessment Committee. These included a preclinical epigenetic study and six post-marketing safety studies (PASS), including one to assess the association between paternal exposure to valproic acid and the risk of NDPD.

Sanofi Russia plans to make appropriate changes to the instructions for medical use, as well as the development of new educational materials to inform medical professionals and patients about the possible risk.

The State Register of Medicines (GRLS) contains 20 valproic acid products with valid registration certificates, more than half of which are manufactured in Russia. According to AlphaRM and the Pharmvestnik portal, drugs with the active ingredient valproic acid occupy more than 11 % of the market of all antiepileptic drugs on the Russian pharmaceutical market.