Valproate (Epilim) – Use in women of childbearing potential and during pregnancy

Valproate-containing medicines (also known as sodium valproate or valproic acid) are approved in Ireland under the brand name Epilimto 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 (in the womb) to valproate are at a high risk of serious developmental disorders (up to 30-40%) and congenital malformations (approximately 11%).

There are important contraindications, strengthened warnings and risk minimisation measures to prevent valproate (Epilim) exposure during pregnancy.

Treatment with valproate (Epilim) must be initiated and supervised by a suitably experienced specialist. Valproate (Epilim) must not be used in girls and women of childbearing potential (i.e. those that can become pregnant) unless other treatments are ineffective or not tolerated, and the terms of a pregnancy prevention programme, known as ‘prevent’, are followed. The pregnancy prevention programme ‘prevent’ 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 ‘prevent’ are provided in educational materials for patients and healthcare professionals below:

Important information

  • Patients should not stop taking valproate without consulting a doctor

  • It is important that women and girls who have been prescribed valproate should not stop taking their medicine without consulting their doctor. Sudden discontinuation of any treatment for epilepsy should be avoided as this may lead to seizures that could have serious consequences for the woman, and if pregnant, the unborn child.

Reporting suspected side effects (adverse reactions)

Valproate–containing medicines (Epilim) are subject to additional monitoring requirements and healthcare professionals and members of the public are requested to report any suspected adverse reactions associated with use via the HPRA reporting forms. Any medicine subject to additional monitoring in the EU is identifiable by an inverted black triangle after the medicine's name as well as the following explanatory statement in the product information. 

This medicinal product is subject to additional monitoring

The sections below provide information and resources for patients and healthcare professionals. Please click on the title to expand the section and view the information. 

Product information

The approved product information*, which contains the Summary of Product Characteristics (SmPC) and the 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.

* What is contained in the product information? 

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 products currently authorised in Ireland are accessible from the HPRA's Find a Medicine function. 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. The PL should be included in your box of medicine received from your pharmacist.

Educational materials/toolkit

The current valproate pregnancy prevention programme, called prevent, was introduced in 2018 on the recommendation of the European Medicines Agency’s (EMA’s) safety committee (PRAC) following a EU-wide review (further information is available on the EMA's valproate webpage. The HPRA worked with national stakeholders, including patient representatives and healthcare professionals to implement the updated risk-minimisation measures introduced following this review. This work included developing materials 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. These materials include the following guides and forms:

  • guide for healthcare professionals potentially involved in the care of girls and women of childbearing potential treated with valproate (Epilim).
  • A patient guide for women and girls, which the prescriber should provide to all girls and women of childbearing potential who start treatment with valproate (Epilim) or who are already on treatment.
  • An annual risk acknowledgement form, which should be used at time of treatment initiation and during each annual review of valproate (Epilim)treatment by the specialist with their patient.
  • patient card is attached to the packaging of valproate (Epilim)to facilitate discussions between the pharmacist and the patient each time valproate (Epilim) is dispensed. In situations where broken bulk dispensing cannot be avoided, then a copy of the package leaflet should always be provided with a warning sticker added.
  • 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, appears on the inner blister and outer packaging of (Epilim) medicines.
  • Pharmacy materials (A4 poster and shelf barker) to assist pharmacists in dispensing and advising patients taking Epilim
  • Reduced pack size: a pack size of 30 units is now the only available presentation to mitigate against the need for broken bulk dispensing at pharmacy level and to ensure that all patients receive a package leaflet and the outer carton with the patient card at each dispensing.

HPRA-approved communications for healthcare professionals

The HPRA has issued communications to healthcare professionals, advising of the recommendations for use of in girls and women of childbearing potential following two EU-wide reviews of Valproate (Epilim) in 2014 and 2017/2018.

The HPRA communications, listed below, include Direct Healthcare Professional Communications (DHPCs) and articles in the HPRA Drug Safety Newsletter. These were distributed to healthcare professionals such as general practitioners, general hospital doctors, medical specialists including neurologists, gynaecologists/obstetricians, psychiatrists, pharmacists (both community and hospital), specialist epilepsy nurses and family planning clinics), healthcare professional regulatory bodies, and patient organisations.

In addition, the HPRA provided reminder articles which were published in MIMS (Ireland) and the Irish Medicines Formulary (IMF). All of these communications were published on the HPRA website and are linked below.

Further information on the EU-wide reviews of valproate is available from the EMA's valproate webpage.

2022  Drug Safety Newsletter Edition 106 – February 2022

2020

Direct Healthcare Professional Communication for Pharmacists - March 2020 

Drug Safety Newsletter Edition 97 – May 2020

Update of Educational Materials – July 2020

2019

Monthly Index of Medical Specialities (MIMS) Ireland – April 2019

2018

Drug Safety Newsletter Edition 87 – April 2018

Direct Healthcare Professional Communication for Prescribers - April 2018

Direct Healthcare Professional Communication for Pharmacists - April 2018 

Monthly Index of Medical Specialities (MIMS) Ireland – May 2018

Irish Medicines Formulary (IMF) – August 2018

Monthly Index of Medical Specialities (MIMS) Ireland – October 2018

2017 

Drug Safety Newsletter Edition 80 – April 2017

Monthly Index of Medical Specialities (MIMS) Ireland – May 2017

Drug Safety Newsletter Edition 81 – July 2017

2016 

Drug Safety Newsletter Edition 76 – August 2016

Irish Medicines Formulary (IMF) – August 2016

Monthly Index of Medical Specialities (MIMS) Ireland– September 2016

2015  Monthly Index of Medical Specialities (MIMS) Ireland – January 2015

2014 

Direct Healthcare Professional Communication (DHPC) – December 2014

Drug Safety Newsletter Edition 65 – December 2014