Last reviewed: June 2018
Last updated: June  2018

European Medicines Agency (EMA) strengthens measures to avoid use of valproate medicines in pregnancy

In 2018 the EMA announced stronger measures aimed at avoiding the exposure of babies to valproate medicines in the womb. Under the new restrictions, valproate medicines are contraindicated in epilepsy during pregnancy due to the high risk of congenital malformations and developmental problems in the child. However, the EMA recognises that for some women with epilepsy it may not be possible to stop valproate and they may have to continue treatment during pregnancy with appropriate specialist care.

In addition, valproate medicines must not be used in female patients of childbearing potential unless there is a pregnancy prevention programme in place that includes:

  • An assessment of the patient’s potential for becoming pregnant

  • Pregnancy tests before starting and during treatment as needed

  • Counselling about the risks of valproate treatment and the need for effective contraception throughout treatment

  • A review of ongoing treatment by a specialist at least annually

  • A risk acknowledgement form that patients and prescribers will go through at each such annual review to confirm that appropriate advice has been given and understood.

The EMA said the new measures were put in place because of evidence suggesting that information on the risks of valproate use in pregnancy was still not getting through to women despite earlier steps aimed at ensuring this.

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Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • FHx of childhood seizures
  • staring episode, lasting 5 to 10 seconds; several times per day with no aura/postictal state
  • childhood onset
  • normal physical examination
  • hyperventilation-induced seizure

Other diagnostic factors

  • simple automatisms
  • recent decline in school performance
  • complex automatisms
  • early onset (before age 4 years)

Risk factors

  • family/genetic history of childhood absence epilepsy (CAE) or juvenile myoclonic epilepsy (JME)
  • acquired brain injury: for example, hypoxia-ischaemia, trauma, infection
  • other congenital inborn errors of metabolism, structural defects, chromosomal abnormalities
  • developmental delay or mental retardation
  • female sex

Diagnostic investigations

Investigations to consider

  • MRI brain
  • testing for metabolic disorders (e.g., serum amino acids, urine organic acids, lactate pyruvate or specific enzymatic tests)
  • CSF and serum glucose
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Assistant Professor of Neurology

Washington University Medical School

St. Louis

MO

Disclosures

JLZW declares that she has no competing interests.

Dr Judith L. Z. Weisenberg would like to gratefully acknowledge Dr Michael Wong, a previous contributor to this monograph. MW declares that he has no competing interests.

Peer reviewers VIEW ALL

Consultant Paediatric Neurologist

Royal Victoria Infirmary

NHS Foundation Trust

Newcastle-upon-Tyne

UK

Disclosures

AD and two epilepsy nurses from her department have been reimbursed by UCB Pharma, the manufacturer of levetiracetum, for attending several conferences. One of the epilepsy nurses received a one-off sponsorship payment from UCB Pharma to cover the initial set-up costs of the adolescent epilepsy support group. One epilepsy nurse has been reimbursed by Cyberonics, the manufacturer of vagal nerve stimulators, for attending one or more conferences.

Division of Pediatric Neurology

Columbia University College of Physicians and Surgeons

New York

NY

Disclosures

CA declares that he has no competing interests.

Associate Professor

Pediatrics and Neurology

Baylor College of Medicine

Medical Director

Comprehensive Epilepsy Program

Texas Children's Hospital

Houston

TX

Disclosures

AAW declares that he has no competing interests.

Head of Neurosciences Unit

The Prince of Wales’s Chair of Childhood Epilepsy

National Centre for Young People with Epilepsy

London

UK

Disclosures

HC has received research funds from HAS, Epilepsy Research UK, SHS, and the Milk Development Council. She has received funding for an epilepsy training fellowship from UCB and Eisai. She has also received travel funding from Eisai, UCB, and GlaxoSmithKline.

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