European Medicines Agency (EMA) announces that its Pharmacovigilance Risk Assessment Committee (PRAC) is assessing new data from a recent study which used multiple databases in Denmark to investigate the potential risk of neurodevelopmental disorders (NDD) in children born to men treated with valproate, levetiracetam or lamotrigine before conception.
Valproate is a medicine used to treat epilepsy, bipolar disorders and in some countries for migraine.
Neurodevelopmental disorders 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) carried out by companies that market valproate, which used data from multiple registry databases in Denmark, Norway and Sweden, together with other available information, led the PRAC to recommend precautionary measures for the treatment of male patients with valproate medicines. At that time, while the committee acknowledged that the PASS data had limitations, PRAC concluded that NDD are a potential risk in children born to men treated with valproate during the three months before conception, and therefore information to patients and health care professionals were warranted.
The aim of this new study using Danish data sources was to replicate the results from the PASS. However, results from this new study did not suggest an association between valproate use by the father and an increased risk of NDD in the child.
PRAC has initiated a signal procedure to understand the difference in the findings across the studies and requested further information and analysis from the marketing authorisation holders for valproate.
EMA will communicate further when more information becomes available.
Please refer to the following website in EMA for details:
http://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-7-10-july-2025
In Hong Kong, there are 10 registered pharmaceutical products containing valproate. All products are prescription-only medicines. So far, the Department of Health (DH) has received 17 cases of adverse drug reaction with regard to valproate, of which 2 cases were reported as congenital malformations following valproate exposure in utero, and these cases were not related to neurodevelopmental disorders in children after paternal exposure to valproate. Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 2 Jul 2011, with the latest update posted on 11 Jun 2025. Letters to inform local healthcare professionals were issued by the DH on 4 Jul 2011, 7 May 2013, 13 Oct 2014, 12 Feb 2018, 13 Dec 2022, 22 Mar 2023 and 11 Jun 2025.
The Registration Committee of the Pharmacy and Poisons Board discussed the matter related to the risks in pregnancy associated with the use of valproate in Sep 2011, Dec 2014, Dec 2018 and Jun 2019. Currently, the package insert or sales pack label of locally registered valproate-containing products should include safety information on the risk of malformations and impaired cognitive development in children exposed to valproate during pregnancy, and contraindications, e.g. in women of childbearing potential unless pregnancy preventive measures have been implemented, etc. The certificate holders of locally registered valproate-containing products are also required to implement risk minimisation measures, e.g. patient information leaflet should be provided, etc.
As previously reported, the matter will be further discussed by the Registration Committee of the Pharmacy and Poisons Board of Hong Kong.
Ends/Saturday, Jul 12, 2025
Issued at HKT 12:00
|
