Use in women of childbearing potential and during pregnancy

Updated 10 June 2024

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 can cause birth defects and problems with the development and learning of the child if their mother takes this medicine during pregnancy. Children exposed to valproate in the womb 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 exposure during pregnancy.

Treatment with valproate must be initiated and supervised by a specialist experienced in the management of epilepsy or bipolar disorder. Valproate 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 are fully aware of the risks and the need to avoid becoming pregnant while taking it.

Information on the pregnancy prevention programme is available in the approved Epilim product information, accessible here. Additional educational materials which support the pregnancy prevention programme are also available (see below in the educational materials section).

Important information

Patients should not stop taking valproate without consulting a doctor.

Women and girls who have been prescribed valproate must 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.

Educational materials

To support the 'prevent' pregnancy prevention programme, the following educational materials are available in Ireland. These materials aim to support the safe prescribing and dispensing of valproate, help ensure patients are fully informed of the risks of use during pregnancy and can discuss options with their doctors.

  • A patient guide for women and girls, which the prescriber should give to all girls and women of childbearing potential who begin treatment with valproate or are already undergoing treatment [*new version].
  • guide for healthcare professionals potentially involved in the care of girls and women of childbearing potential treated with valproate [*new version].
  • An annual risk acknowledgement form, to be used by the specialist with their patient at the start of valproate treatment and during each annual review.
  • patient card is attached to the packaging of valproate to facilitate discussions between the pharmacist and the patient each time valproate is dispensed [*new version]. When broken bulk dispensing cannot be avoided, a copy of the package leaflet should always be provided with a warning sticker added. The package leaflets for all valproate-containing medicines can be found here.
  • A visual warning to inform healthcare professionals and patients about the risks to an unborn child if used during pregnancy, along with advice to use effective contraception, is displayed on both the inner blister and outer packaging of valproate medicines. See a sample of the outer packaging. [*new version] 
  • Pharmacy materials (A4 poster  and shelf barker) to assist pharmacists in dispensing and advising patients taking Epilim. [*new version]
  • Reduced pack size: a pack size of 30 units is now the only available authorised presentation (excluding injections and oral solutions) to mitigate against the need for broken bulk dispensing at the pharmacy level and to ensure that all patients receive a package leaflet and the outer carton with the patient card at each dispensing.

*New versions of these materials were approved by the HPRA in June 2024. The new versions have been introduced following a review by the EMA of a study by the companies that market the medicines in the EU of healthcare professionals and patients. The recommended changes have been made to improve the understanding and usability of the materials. The conditions of the pregnancy prevention programme remain the same.

Reporting suspected side effects (adverse reactions)

Valproate–containing medicines are subject to additional monitoring requirements, and healthcare professionals and members of the public are requested to report any suspected adverse reactions associated with their 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.

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.

2024

Direct Healthcare Professional Communication - June 2024

Monthly Index of Medical Specialties (MIMS) Ireland – April 2024

2023

Educational material redistribution letter – April 2023

Educational material redistribution for pharmacists – April 2023

Monthly Index of Medical Specialties (MIMS) Ireland – April 2023

2022 

Drug Safety Newsletter Edition 106 – February 2022

Educational material redistribution letter – February 2022

Educational material redistribution letter for pharmacists – February 2022

2021

Educational material redistribution letter - February 2021

Educational materials redistribution letter for pharmacists – February 2021

2020

Educational material redistribution letter – February 2020

Educational material redistribution letter for pharmacists – February 2020

Direct Healthcare Professional Communication for Pharmacists - March 2020 

Drug Safety Newsletter Edition 97 – May 2020

Update of Educational Materials – July 2020

Irish Medicines Formulary (IMF) Ireland - September 2020

Monthly Index of Medical Specialties (MIMS) Ireland - December 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

Direct Healthcare Professional Communication for pharmacists – May 2018

Direct Healthcare Professional Communication for prescribers - May 2018

Irish Medicines Formulary (IMF) – August 2018

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

Monthly Index of Medical Specialties (MIMS) Ireland - December 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 

Direct Healthcare Professional Communication for prescribers - May 2016

Direct Healthcare Professional Communication for pharmacists – May 2016

Drug Safety Newsletter Edition 76 – August 2016

Irish Medicines Formulary (IMF) – August 2016

Irish Medicines Formulary (IMF) Ireland - August 2016

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

Monthly Index of Medical Specialties (MIMS) Ireland - December 2016

2015 

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

Direct Healthcare Professional Communication for prescribers – April 2015

Direct Healthcare Professional Communication for pharmacists - April 2015

2014 

Direct Healthcare Professional Communication (DHPC) – December 2014

Drug Safety Newsletter Edition 65 – December 2014