Last reviewed: September 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.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • movement of one side of the body or one specific body part
  • premonitory sensation or experience (fear, epigastric sensation, déjà vu, jamais vu)
  • automatisms (picking at clothes, smacking of the lips)
  • temporary aphasia
  • staring and loss of contact with the environment

Other diagnostic factors

  • postictal focal neurological deficit (Todd's paralysis, aphasia)
  • persistent focal neurological deficit
  • poor memory
  • stigmata of neurocutaneous syndromes

Risk factors

  • febrile seizure
  • head trauma
  • CNS infection
  • stroke
  • brain tumour
  • mental retardation (MR) and/or cerebral palsy
  • dementia
  • FHx of seizures
  • vascular malformations
  • male

Diagnostic investigations

1st investigations to order

  • blood glucose
  • FBC
  • electrolyte panel
  • toxicology screen
  • lumbar puncture and cerebrospinal fluid analysis
  • CT head
  • MRI brain
  • EEG
Full details

Investigations to consider

  • serum prolactin
  • video/EEG long-term monitoring (LTM)
  • PET scan
  • single photon emission computed tomography (SPECT) scan
  • functional MRI scan
  • magnetoencephalography (MEG scan)
  • neuropsychological testing
  • Wada test
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Assistant Professor

Clinical Neurology

University of California, San Francisco

San Francisco

CA

Disclosures

VRR is an author of a number of references cited in this monograph. He served as a paid consultant for NeuroPace, Inc., manufacturer of the Responsive Neurostimulation (RNS) System.

Associate Professor

Clinical Neurology

University of California, San Francisco

San Francisco

CA

Disclosures

JDH has received research funding and consultancy funds from UCB Inc.

Dr Vikram R. Rao and Dr John D. Hixson would like to gratefully acknowledge Dr Jeffrey Cohen, a previous contributor to this monograph. JC declares that he has no competing interests.

Peer reviewers VIEW ALL

Chief

Epilepsy Division

Brigham and Women's Hospital

Associate Professor of Neurology

Harvard Medical School

Boston

MA

Disclosures

At the time of review, EB declared that between 2004 and 2009, he received speaking honoraria from UCB Pharma, Novartis, Abbott Laboratories, GlaxoSmithKline, and Pfizer. He received consulting fees from UCB Pharma, Genzyme, and Spherics, and research funding from UCB Pharma. Unfortunately, we have since been made aware that EB is deceased.

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.

Assistant Professor

Division of Pediatric Neurology

Columbia University College of Physicians and Surgeons

New York

NY

Disclosures

Not disclosed.

Consultant Neurologist

Muscular and Neurodegenerative Diseases Unit

"G Gaslini" Institute

Genova

Epilepsy Centre

Federico II University

Napoli

Italy

Disclosures

PS declares that he has no competing interests.

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