Use of valproate-containing medicines by girls and women who can become pregnant

Risks of taking valproate during pregnancy

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%).

Preventing pregnancy while using valproate

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.

Learn more about the pregnancy prevention programme in the approved product information for Epilim. Additional educational materials which support the pregnancy prevention programme are also available (see educational materials section below).

Do not stop taking your medicine before speaking to your doctor

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 material for healthcare professionals and patients

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.

New versions of some of these materials were approved by the HPRA in June 2024. The new versions, indicated below, 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.

• 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.

• A guide for healthcare professionals potentially involved in the care of girls and women of childbearing potential treated with valproate.

• 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.

• A 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. Download the package leaflets for all valproate-containing medicines from our website for more information.

• 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.

• 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 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.

Reporting suspected side effects to the HPRA

Valproate-containing medicines are subject to additional monitoring requirements. Any medicine subject to additional monitoring in the EU is identifiable by an inverted black triangle after the medicine's name▼. Healthcare professionals and members of the public are requested to report any suspected adverse reactions associated with their use via the HPRA reporting forms.

Product information for valproate-containing medicines

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 a shortened and easy-to-read format for patients. The PL should be included in your box of medicine received from your pharmacist.

The approved product information for valproate includes detailed warnings and recommendations for healthcare professionals and patients regarding the use of this medicine. This includes the need for treatment to be started 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.

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

2023

2022

2021

2020

2019

2018

2017

2016

2015

2014

Additional resources

• European Medicines Agency (EMA): Information on reviews of valproate 
• RCSI study: Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019
• RCSI study: Awareness, knowledge and practice of healthcare professionals following implementation of a Pregnancy Prevention Program for sodium valproate in Ireland
• HSE: Valproate information page 
• HSE: Specialist perinatal mental health services 
• Irish Epilepsy and Pregnancy Register
• Epilepsy Ireland
• Organisation for Anti-Convulsant Syndrome (OACS)