During its June 2026 meeting, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency completed its review of a safety signal for valproate and related substances and recommended New safety information for healthcare professionals regarding the chikungunya vaccine Ixchiq.
Valproate and related substances
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) completed evaluation of new data regarding potential risk of neurodevelopmental disorders in children born to men treated with valproate and concluded that evidence of potential risk of neurodevelopmental disorders in children born to men treated with valproate is contradictory. The PRAC recommends updating product information to reflect available data.
The PRAC completed its review of a safety signal for valproate and related substances, and concluded that based on the evaluation of new data, the evidence on neurodevelopmental disorders in children born to men treated with valproate is contradictory and the causal role of valproate is uncertain. In light of this uncertainty, the Committee recommended maintaining existing precautionary measures for male patients. These measures were put in place in 2024 to address a potential increased risk of neurodevelopmental disorders (NDDs) in children born to men treated with valproate during the three months before conception.
In addition, the PRAC recommended that the medicine’s product information be updated to reflect the most recent data related to NDDs.
Valproate medicines are used to treat epilepsy and bipolar disorder. In some EU Member States they are also authorised to prevent migraine headaches. NDDs are problems with development that begin in early childhood, such as autism spectrum disorders, intellectual disability, communication disorders, attention deficit/hyperactivity disorders and movement disorders.
In January 2024, the assessment of the findings of a post authorisation safety study (PASS), which used data from multiple registry databases in Denmark, Norway and Sweden suggested an increased risk of NDDs in children born to men treated with valproate in the three months before conception compared with men treated with the epilepsy medicine lamotrigine or levetiracetam. At that time, while the committee acknowledged that the PASS data had limitations, the PRAC concluded that NDDs are a potential risk in children born to men treated with valproate during the three months before conception, and the PRAC recommended precautionary measures for men taking the medicine.
At the time, the PRAC requested the marketing authorisation holders carry out a larger study, specifically designed to address some of the limitations of the PASS study. This study is currently ongoing and is expected to conclude in 2028.
The latest safety signal was started in July 2025 after the publication of a Danish nationwide registry-based study,study which did not suggest an increased risk of NDDs in children born to men treated with valproate. In assessing this signal, the PRAC reviewed all the latest evidence. While findings from one study suggested a possible link between NDDs and valproate, most studies (so-called retrospective observational studies) investigating this issue have not found an increased risk of NDDs. Differences in how these studies were designed, such as the patients that were included and how patients’ underlying health conditions were accounted for, may explain why findings vary.
Overall, the PRAC could not conclude whether a potential risk of NDDs in children of fathers treated with valproate before conception is due to valproate or other factors, such as the fathers’ underlying medical condition. The committee concluded that the available evidence is contradictory, and a causal link with the medicine is uncertain.
In light of remaining uncertainties and pending the results of the ongoing study in 2028, the PRAC agreed that the precautionary measures introduced in 2024 should remain in place. The Committee also recommended updating the product information, as well as the healthcare professional guide and the patient guide for male patients, to ensure that healthcare professionals and patients have access to the most up-to-date information.
Further information can be found in the assessment report which will be published in due course on the EMA website.
In Belgium, there are medicines authorised that contain valproate. They are sold under the following names:
- Depakine;
- Valproate Desitin.
New safety information for healthcare professionals regarding Ixchiq : the chikungunya vaccine should be restricted to people at high risk of infection
The PRAC recommends that the Ixchiq vaccine should be restricted to individuals with a high risk of becoming infected with the chikungunya virus.
The Committee also endorsed a direct healthcare professional communication (DHPC) to inform healthcare professionals of the updated recommendations.
Ixchiq is a live-attenuated vaccine used to protect people 12 years of age and older against chikungunya disease. It contains a strain of the chikungunya virus that has been attenuated.
This restriction of the indication follows a routine EMA review of available safety data which evaluated the impact of serious adverse events reported with the vaccine (including aseptic meningitis) on the benefit-risk balance of Ixchiq. Some of these events resulted in hospitalisation and death.
Known serious side effects linked to the vaccine mainly occur in people aged 65 years and older and in people with multiple underlying chronic medical conditions, although young otherwise healthy adults have also been affected.
In these persons, serious or prolonged chikungunya-like adverse reactions have been observed, sometimes leading to a deterioration of the person’s general condition, including malaise and decreased appetite, exacerbation of pre-existing diseases, brain disorders like encephalopathy and encephalitis, aseptic meningitis (inflammation of the membranes around the brain and spinal cord) or confusion.
Healthcare professionals are reminded that the vaccine should only be given to individuals 12 years of age and older who are at high risk of acquiring chikungunya infection and after careful consideration of the potential benefits and risks. It is contraindicated in patients whose immune systems are weakened because of disease or medical treatment and should not be co-administered with other vaccines.
The PRAC’s recommendation will be sent to the EMA’s human medicines committee (the CHMP) which will adopt the Agency’s opinion.
As for all medicines, the safety of Ixchiq is closely monitored and the recommendations for use will be updated if new, relevant information becomes available.
The vaccine Ixchiq is available in Belgium. Recommendations from the Superior Health Council regarding vaccination against chikungunya are available.
More information is available on the EMA website.