a pregnant lady taking medicationFebruary 13 2018

The European Medicines Agency has issued new recommendations regarding use of valproates by women who are pregnant or of child-bearing potential.

Following a review of evidence over of drug safety, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has made recommendations about its use in epilepsy and, where licensed, for migraine or bipolar disorder.

For women with epilepsy, it says:

  • in pregnancy – valproate must not be used; however it is recognised that for some women with epilepsy it may not be possible to stop valproate and they may have to continue treatment (with appropriate specialist care) in pregnancy;
  • in female patients from the time they become able to have children – valproate must not be used unless the conditions of the new pregnancy prevention programme are met.

For women taking valproate for migraine or bipolar disorder it says:

  • in pregnancy – valproate must not be used;
  • in female patients from the time they become able to have children – valproate must not be used unless the conditions of a new pregnancy prevention programme are met.

The new valproate pregnancy prevention programme comprises:

  • assessing patients for the potential of becoming pregnant, and involving the patient in evaluating her individual circumstances and supporting informed decision making;
  • pregnancy tests before starting and during treatment as needed;
  • counselling patients about the risks of valproate treatment;
  • explaining the need for effective contraception throughout treatment;
  • carrying out reviews of treatment by a specialist at least annually;
  • introduction of a new risk acknowledgement form that patients and prescribers will go through at each such review to confirm that appropriate advice has been given and understood.

In addition, PRAC has recommended that:

  • the outer packaging of all valproate medicines must include a visual warning about the risks in pregnancy;
  • a patient reminder card will also be attached to the outer package for pharmacists to discuss with the patient each time the medicine is dispensed;
  • companies that market valproate should also provide updated educational materials in the form of guides for healthcare professionals and patients.

“Because valproate medicines are all licensed at national level, the PRAC recommendations will now be sent to Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position,” said the EMA.

PRAC has also called on companies marketing the products to carry out additional studies to further characterise the nature and extent of the risks posed by valproate and to monitor ongoing valproate use and the long-term effects from affected pregnancies.

Commenting on the announcement, Dr Jim Morrow, founder of the UK Epilepsy and Pregnancy Register and member of Epilepsy Action’s Women’s Advisory Panel, said: “We are pleased the European Medicines Agency committee has listened to people’s concerns about sodium valproate and that their recommendations reflect the seriousness of the risks involved for women with epilepsy in pregnancy.

“We know sodium valproate is an effective, easy-to-use and generally well-tolerated drug for women with epilepsy. Unfortunately, this means non-neurology specialists are more likely to prescribe it, which can mean women can take the drug without being fully aware of the risks involved or having regular reviews.

“For many women with epilepsy, sodium valproate is the only drug that works. However, we know for most others, there are equally effective and well-tolerated epilepsy medicines which are safe to use in pregnancy. We would have liked to see the guidelines state that valproate should not be prescribed as a first-line treatment without a full discussion with a specialist.

“It remains to be seen how and when these recommendations will be implemented and we would like the opportunity to meet UK decision makers to see how they will work in practice. Until things change, women and children will continue to be affected by something that can be potentially prevented.”

EMA announcement