In October 2023, following the results of studies conducted in Europe, the European Medicines Agency endorsed new measures to avoid exposure of children to topiramate-containing medicines because of the increased risk of neurodevelopmental problems after exposure in the womb.
It is already known that topiramate increases birth defects in pregnancy, with the risk increasing from 1-3 in 100 children in unexposed pregnancies, to 4-9 in 100 children born to women taking topiramate during pregnancy. In addition to this already known risk, recent research identified a two- to three-fold higher risk of neurodevelopmental disorders, in particular autism spectrum disorders, intellectual disability or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy who were not taking antiepileptic medication.
The Commission on Human Medicines (CHM) reviewed the studies and, following their recommendations, the MHRA is now advising healthcare professionals that topiramate should not be prescribed to treat epilepsy during pregnancy, unless there is no suitable alternative treatment.
Lamotrigine and levetiracetam remain safer options for the management of epilepsy in pregnancy as highlighted by the report published in January 2021 following the CHM review.
The MHRA is now advising healthcare professionals that topiramate should not be prescribed to treat epilepsy during pregnancy
The other licensed use of topiramate is for migraine prophylaxis but because of the known increased risk of birth defects, topiramate should not be used for this indication in pregnancy.
As with sodium valproate, all women and girls of child-bearing potential started on topiramate should be registered with the Pregnancy Prevention Programme. Women should be advised to use highly effective birth control throughout treatment and take a pregnancy test prior to starting topiramate; recommended contraceptives include user independent forms such as copper intrauterine device (Cu-IUD) or levonorgestrel intrauterine system (LNG-IUS).
Healthcare professionals should make patients aware of the risks of this medication during pregnancy and should complete a risk awareness form as part of the requisites of this programme. This should be followed up by regular medication reviews, at least annually. Product information leaflets are available to support patient counselling for both indications – epilepsy and migraine prophylaxis – and patient cards should be given out by pharmacists every time topiramate is dispensed. The new materials are available in electronic form and for printing. A visual symbol (a pregnant woman in a red circle with line through it) will also appear on all boxes of topiramate, and whole original boxes should be dispensed where possible.
It is hoped that the introduction of the Pregnancy Prevention Programme will strengthen safety measures around the use of topiramate and reduce the number of topiramate-exposed pregnancies.
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Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
