Regulatory Requirements for Valproates
A Valproate National Patient Safety Alert was issued by the Medicines and Healthcare products Regulatory Agency (MHRA) with new regulatory measures from January 2024.
The new regulatory measures are:
- Valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply.
- At their next annual specialist review, women of childbearing potential and girls should be reviewed using a revised valproate Risk Acknowledgement Form, which will include the need for a second specialist signature if the patient is to continue with valproate and subsequent annual reviews with one specialist unless the patient’s situation changes.
All female patients treated with valproates must be supported by the Pregnancy Prevention Programme (PPP). Patients who are not sexually active should be included in the PPP unless the prescriber considers there are compelling reasons to indicate there is no risk of pregnancy. See below for more details on PPPs.
It is important that ALL valproate prescriptions presented to a pharmacy for women and girls of childbearing potential are identified, so that steps can be taken to manage the risks in pregnancy.
The associated educational materials to support patients and healthcare professionals have been updated in June 2025 and can be found in the links below.
Pregnancy Prevention Programme (PPP) for Valproates
The PPP ensures all female patients taking valproate:
- Have been told and understand the risks of taking valproate in pregnancy and have signed a risk acknowledgement form
- Have been prescribed, and are using, highly effective contraception if necessary
- Have their medication reviewed by a specialist at least once every year
It is important that ALL valproate prescriptions presented to a pharmacy for women and girls of childbearing potential are identified, so that steps can be taken to manage the risks in pregnancy.
The valproate PPP is supported by the following documents:
- A Patient Guide
- A Guide for Healthcare Professionals
- A Risk Acknowledgement form for female patients
- A Patient Card
- Valproate Dispensary Poster
Advice for Pharmacy Teams when dispensing Valproates
- Pharmacy teams should continue to dispense valproate and valproic acid
- Remind patients on valproates that they must not stop taking their treatment without advice from their specialist highlighting the risks for both mother and baby of stopping the medication abruptly
- Pharmacy teams should be prepared to discuss the current warnings and upcoming measures with their patients including-
- The risks of taking valproates in pregnancy and the need for effective contraception
- Providing a patient card and patient booklet if they have not already received one
- Refer patients not complying with the PPP, planning a family, who may be pregnant, or who report not taking their medicine as prescribed to their prescriber
- Dispense medication in original packs if there is no risk assessment for non-OPD dispensing. See Valproate and Valproic Acid Dispensing for more details
- Ask patients if they are experiencing any suspected adverse reactions, including adverse pregnancy outcomes and report via Yellow Card scheme - valproate is subject to additional monitoring
- Make a record on the Patient Medication Record (PMR) of conversations and advice offered
Valproate Safety in Males
A study on outcomes in children whose fathers took valproate at the time of conception, commissioned by the European Medicines Agency, reviewed by the MHRA suggests there may be an increased risk of neurodevelopmental disorders in children fathered by men on valproate in the three months prior to conception compared with men on other antiseizure medicines.
As a precaution, male patients should be advised to use effective contraception (condoms, plus contraception used by the female sexual partner) throughout the valproate treatment period and for 3 months after stopping valproate, to allow for one completed sperm cycle not exposed to valproate.
The following documents are available to support males:
No patient should stop taking valproate without advice from their healthcare professional and any patients who have concerns should talk to their healthcare professional.