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 strengthening of restrictions for use of valproate 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 link below to the EMA website for more information on the EU reviews.)
There are now important new contraindications, strengthened warnings and 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
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 listed in section 4.4 of the Summary of Product Characteristics (SmPC) which is part of the product information (please see below). It is important that women and girls who have been prescribed valproate should not stop taking their medicine without consulting their doctor.
Educational Materials / Toolkit
The HPRA is working with national stakeholders, including patient representatives and healthcare professionals to implement these new and updated risk minimisation measures in Ireland (external website links below), including materials developed to support safe prescribing and dispensing of valproate (Epilim), and in particular to ensure that patients and/or carers are fully informed of the risks and can discuss options with their doctor.
Measures (which are currently being updated in line with the new recommendations) include;
Changes to the product information (Package Leaflet (PL) for patients and Summary of Product Characteristics (SmPC) for healthcare professionals) to reflect these new conditions.
A visual warning to alert healthcare professionals and patients of the risks to the unborn child if used during pregnancy and advising use of effective contraception will appear on the packaging of Epilim medicines.
Educational Materials (guidance booklets and forms), already available for patients and doctors, are currently being updated to reflect the new measures and provide age-appropriate advice. These will be disseminated to healthcare professionals shortly in hard copy by the Marketing Authorisation Holder (MAH) (i.e. license holder for the medicine) once approved by the HPRA and will also be available to download from the HPRA website (see below). The Educational materials will include the following:
A patient alert card, which will be attached to the packaging so that pharmacists can go through it with the patient when valproate (Epilim) is dispensed (the cards will be provided in hard copy while the Epilim product packaging is being updated).
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 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, under 'Find a Medicine' or see Valproate Product Information page below. These documents will be updated shortly.