Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures

Babies born to mothers who take valproate medicines (Epilim▼, Depakote▼) during pregnancy have a 30–40% risk of developmental disability and a 10% risk of birth defects. Despite communications to prescribers in January 2015 and February 2016 on the magnitude of this risk and the actions to take, there is evidence that women are still not aware of the risk. Patient Safety Alerts have now been issued asking all organisations to undertake systematic identification of women and girls taking valproate. A new European review is considering whether further regulatory action is necessary and there will be a public hearing at the European Medicines Agency later in 2017.

Advice for healthcare professionals

  • do not prescribe valproate medicines for epilepsy or bipolar disorder in women and girls unless other treatments are ineffective or not tolerated; migraine is not a licensed indication
  • ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental disorders and 10% risk of birth defects and are using effective contraception
  • valproate use in women and girls of childbearing potential must be initiated and supervised by specialists in the treatment of epilepsy or bipolar disorder

Risks of exposure in pregnancy and previous communications

Babies exposed to valproate-containing medicines (Epilim▼, Depakote▼) in utero are at very high risk of developmental disorders and congenital malformations. After warnings were strengthened at the European level, in 2015 we advised you against prescribing valproate-containing medicines in girls and women of or nearing childbearing potential unless other treatments are ineffective or not tolerated.

In 2016 we released further communication materials and resources to support discussion of these risks with women and girls of childbearing potential who take valproate.

The MHRA’s toolkit resources have been disseminated widely. However, evidence suggests as many as 1 in 5 women taking valproate are not aware of any of its risks in pregnancy. Evidence from the Clinical Practice Research Datalink also suggests that, although prescription rates for valproate have been declining gradually in recent years, the measures put in place have not had a significant effect.

New Patient Safety Alerts

On 6 April 2017, NHS Improvement and MHRA sent a Patient Safety Alert through the NHS Central Alerting System to further highlight risks to the unborn child and support the safety of girls and women taking valproate. Consistent action is being taken in Scotland, Wales, and Northern Ireland.

These alerts direct organisations to undertake systematic identification of women and girls taking valproate and to use the MHRA resources to support them to make informed choices.

Further European review

In March 2017, the European Pharmacovigilance Risk Assessment Committee (PRAC) initiated a further review to look at the use of valproate-containing medicines in women and girls of childbearing potential. The committee will consider whether these medicines require further restrictions of use due to their very high risk of causing developmental disorders and congenital malformations to unborn babies and evidence of continued use in pregnancy. The review will also examine the effectiveness of regulatory measures put in place to increase awareness and reduce valproate use in patients at risk.

The European Medicines Agency has decided to organise a public hearing later this year as part of their review of valproate. The hearing will be announced prominently on the European Medicines Agency’s website together with a list of specific questions on which information from the public is sought and information on the date, time, location, and how to register.

We will tell you about the results of the review of the use of valproate-containing medicines when they are announced.

Further information

Patient Safety Alert—Resources to support the safety of girls and women who are being treated with valproate (issued 6 April 2017)

MHRA valproate toolkit

Template letter for GPs to invite in patients

Booklet for Healthcare Professionals

Guidance for those prescribing and dispensing valproate

Consultation checklist for patients and prescribers

Guide to give to patients in English and in Welsh

Card to give to patients in English and in Welsh

Summaries of product characteristics for valproate medicines available in the UK

Drug Safety Update articles on valproate medicines from November 2013, January 2015, and February 2016

NICE Guidance for bipolar disorder (July 2015)

NICE Guidance for epilepsy (February 2016)

A video for GPs, and other healthcare professionals, on our advice about the valproate toolkit and discussing risk of valproate medicine during pregnancy with their patients:

Discussing Valproate

Article citation: Drug Safety Update volume 10 issue 9, April 2017: 1.

Published 24 April 2017