Regulatory Changes for Valproates

A Valproate National Patient Safety Alert has been issued by the Medicines and Healthcare products Regulatory Agency (MHRA) with new regulatory measures being introduced from January 2024. The alert calls on Integrated Care Boards (in England) and Health Boards (in Scotland and Wales) to designate a new or existing group to prepare for and co-ordinate the implementation of the new regulatory measures for oversight of prescribing valproate to new patients and existing female patients.

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 regulatory change and associated educational materials to support patients and healthcare professionals will be published on the MHRA website when available.

Read the NPSA here

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:

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 new study on outcomes in children whose fathers took valproate at the time of conception, commissioned by the European Medicines Agency, has been reviewed by the MHRA. This study 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.

The MHRA has now produced a Risk Acknowledgement form for males starting valproate therapy. As a precaution, male patients already on valproate who are planning a family in the next year should talk to their healthcare professional about their treatment.

In the meantime, no one should stop taking valproate without advice from their healthcare professional and any patients who have concerns should talk to their healthcare professional.