Post-publication note - January 2024
New measures have been implemented to reduce the harms of valproate treatment, including new safety and educational materials. See Drug Safety Update January 2024 for more information and the valproate guidance page for safety and educational materials.
Advice for healthcare professionals:
valproate is contraindicated in girls and women of childbearing potential, unless the conditions of the valproate pregnancy prevention programme are met
changes have been made to the educational materials to support healthcare professionals and female patients; the updates clarify the existing regulatory situation and are not due to new advice
- use the updated educational materials to support the valproate Pregnancy Prevention Programme:
- Patient card
- Patient booklet
- Booklet for healthcare professionals
- Annual Risk Acknowledgement Form
review all girls and women of childbearing potential using valproate medicines to ensure that the conditions of the valproate pregnancy prevention programme, described in the documents, are met
- consult the latest clinical guidance for use of valproate, including recent amendments by NICE on four clinical guidelines to support the regulatory position that valproate should not be used in women and girls of childbearing unless other options are unsuitable and the pregnancy prevention programme is in place
Reminder of requirements
Valproate should not be used in girls and women of childbearing potential unless other treatments are ineffective or not tolerated, as judged by an experienced specialist. Valproate is contraindicated in girls and women of childbearing potential, unless the conditions of the valproate pregnancy prevention programme (‘prevent’) are met.
Children exposed to valproate in-utero are at high risk of serious developmental disorders (in 30–40% of cases) and of congenital malformations (in approximately 10% of cases). There is no safe dose of valproate that can be used in pregnancy (see Key facts about the risks of valproate in pregnancy).
Evidence from patient surveys suggest that there are still gaps in the implementation of the pregnancy prevention programme, for example women of childbearing potential on valproate medicines who have not been asked to sign the Annual Risk Acknowledgement Form. All girls and women of childbearing potential using valproate medicines should be reviewed at least annually to ensure that the conditions are met.
Changes made to the materials
In January 2020, relevant healthcare professionals were sent by post or Alliance Tote boxes (for pharmacies) a letter and updated educational materials.
The most recent materials are all dated as November 2019 for consistency. To order new or further materials, please contact Sanofi medical information department on 0845 372 7101 or email UK-Medicalinformation@sanofi.com.
Booklet for healthcare professionals
Following comments from the MHRA and stakeholders, including healthcare professionals and patient groups, updates were made to the content of the Booklet for healthcare professionals
The main changes made from the previous version (dated May 2018) are as follows:
New section: Definition of specialist prescribers (page 6)
New section “Contraception” (page 7)
New section “Does ‘prevent’, the pregnancy prevention programme apply to my patient?” (page 8)
Clarification that the provisions apply when a patient is being switched from valproate to another treatment (page 12)
The changes were made to clarify the existing regulatory situation and not due to
new regulatory measures or advice.
Annual Risk Assessment form
The Annual Risk Assessment form was updated in March 2019 to improve the layout and to clarify when a patient was exempt from the pregnancy prevention plan. Specialists should comply with guidance given on the form if they consider the patient is not at risk of pregnancy, including the need for regular review in case her risk status changes. If the absence of pregnancy risk may change (for example, the patient is pre-menarchal), the date for the next annual discussion of the risks must be documented and the patient or the patient’s family or caregivers asked to contact the prescriber rapidly if the situation changes.
More information on how to use the Annual Risk Assessment form can be found in the April 2019, Drug Safety Update. The only change made to the form since March 2019 is to update the date for consistency with the other materials.
The advice in the patient booklet has not changed. Provide the booklet to any female patient who is using valproate for any indication (or their caregiver) and no longer has a copy.
Patient card, pharmacy warning stickers, and dispensary poster
The advice in the pharmacy materials to support the Pregnancy Prevention Programme has not changed. Pharmacy materials are:
Patient Card: provide a card to all female patients when dispensing valproate medicines. Note: If there is a Patient Card already attached to the box, please detach that copy and give to the patient; Do not stick the dispensing label on top of this card or over the warning on the front of the pack
Warning Stickers: for use if valproate is dispensed out of its original packaging
Dispensary A4 poster: for display in the dispensary area to remind pharmacy staff of these requirements
A statutory patient information leaflet should always be provided with a medicine containing valproate, even if dispensed in a pharmacy box.
NICE: updated clinical guidelines
To support the regulatory position that valproate should not be used in women and girls of childbearing potential (including young girls who are likely to need treatment into their childbearing years) unless other options are unsuitable and the pregnancy prevention programme is in place, in January 2020 the National Institute for Health and Care Excellence (NICE) amended their clinical guidelines for:
The Drug Safety Update, April 2019 links to additional clinical guidance to support healthcare professionals in understanding their clinical responsibilities for valproate.
The MHRA continues to monitor trends in the prescribing of sodium valproate to assess the impact of regulatory recommendations and introduction of the pregnancy prevention programme using primary care data from the Clinical Practice Research Datalink GOLD database. For reports, see the MHRA’s Valproate in women and girls guidance page.
We will continue to monitor these and other data sources, including clinical audits and patient surveys, and will take action as necessary to protect public health.
Article citation: Drug Safety Update volume 13, issue 7: February 2020: 3.