Valproate-containing medicines (also known as sodium valproate or valproic acid) are approved in Ireland under the brand name Epilim▼, to treat epilepsy and bipolar disorder. Valproate (Epilim▼) can cause birth defects and problems with the development and learning of the child if their mother takes this medicine during pregnancy. Children exposed in utero to valproate are at a high risk of serious developmental disorders (in up to 30-40% of cases) and congenital malformations (in approximately 10% of cases).
In 2014, an EU-wide review led to the strengthening of restrictions for the use of valproate (Epilim▼) and further characterisation of the risk of birth defects and developmental disorders in the product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)). The impact of the risk minimisation measures was the subject of a further review initiated in 2017 and the recommendations arising from this review were published and endorsed in February and March 2018.
Please see the ‘External and Useful Links’ below to link to the European Medicines Agency’s (EMA) website for more information on the EU reviews.
There are important contraindications, strengthened warnings and risk minimisation measures to prevent valproate (Epilim▼) exposure during pregnancy. Valproate (Epilim▼) must not be used in girls and women who may be able to have children unless the terms of the pregnancy prevention programme, known as ‘prevent’, are followed. This programme includes measures to ensure patients taking valproate (Epilim▼) are fully aware of the risks and the need to avoid becoming pregnant while taking it. Details of the pregnancy prevention programme are included in section 4.4 of the Summary of Product Characteristics (SmPC) which is part of the product information (please see below).
As indicated in the product information, available data show that the risk is dose-dependent. The risk is greatest at higher doses. A threshold dose below which no risk exists cannot be established based on available data. It is important that women and girls who have been prescribed valproate should not stop taking their medicine without consulting their doctor.
Valproate (Epilim) - Product information
The approved product information (Summary of Product Characteristics (SmPC)) and Package Leaflet (PL))* includes detailed warnings and recommendations for healthcare professionals and patients regarding the use of valproate, including the need for treatment to be initiated and supervised by a specialist experienced in the management of epilepsy or bipolar disorder. Copies of the current versions of the product information are available from the HPRA website, by searching for 'Valproate' or 'Epilim' in the 'Find a Medicine' search box.
* The product information is comprised of the Summary of Product Characteristics (SmPC) and Package Leaflet (PL). These documents are issued when a medicine is first licensed for use and are reviewed and updated as necessary throughout the lifetime of a medicine. The SmPC is mainly intended for use by healthcare professionals and includes detailed information on the use, dosing recommendations, precautions for use and the known side-effects of the medicine concerned. SmPCs for all products currently authorised in Ireland are accessible from the HPRA website (www.hpra.ie). The package leaflet (PL) reflects the more comprehensive information described in the SmPC but is required to be presented in an abbreviated and easy-to-read format for patients.
Valproate–containing medicines (Epilim▼) are subject to additional monitoring requirements and healthcare professionals are requested to report any suspected adverse reactions associated with use to the HPRA via the usual methods.