Further restrictions on use; pregnancy prevention programme to be put in place

EMA’s safety committee (PRAC) recommends new measures to avoid exposure of children to topiramate-containing medicines in the womb, because the medicine may increase the risk of neurodevelopmental problems after exposure during pregnancy. Topiramate is already known to cause serious birth defects when used during pregnancy.

Topiramate containing medicines are used in the EU for the treatment of epilepsy and prevention of migraine. In some EU countries, the medicine is also used in combination with phentermine for weight reduction. At present, topiramate must not be used to prevent migraine or manage body weight during pregnancy and patients who can become pregnant must use effective birth control when using topiramate.

For patients using topiramate for the treatment of epilepsy, the PRAC is now recommending that the medicine should not be used during pregnancy unless there is no other suitable treatment available.

The PRAC also recommends additional measures, in the form of a pregnancy prevention programme, to avoid exposure of children to topiramate in the womb. These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate.

Healthcare professionals should ensure that all patients who can become pregnant are fully aware of the risks of taking topiramate during pregnancy. Alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.

The product information for topiramate-containing medicines will be updated to further highlight the risks and the measures to be taken. Patients and healthcare professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.

The recommendations follow the PRAC’s review of available data, including three recent observational studies.

Two of these studies, which used largely the same datasets, suggest that children born to mothers with epilepsy and who were exposed to topiramate in the womb may have 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 not taking antiepileptic medication. The third study did not show an increased risk of these outcomes in children born to mothers exposed to topiramate in pregnancy, compared with children born to women with epilepsy not taking antiepileptic medication.

In its review, the PRAC confirmed the known increased risk of birth defects and reduced growth of the unborn child when mothers receive topiramate during pregnancy. Birth defects will occur in 4 to 9 out of every 100 children born to women who take topiramate during pregnancy, compared with 1 to 3 out of every 100 children born to women who do not take such treatment. Further, around 18 in every 100 children were smaller and weighed less than expected at birth when mothers had taken topiramate during pregnancy, compared with 5 in every 100 children born to mothers without epilepsy and not taking antiepileptic medication.

During the review PRAC also consulted a group of experts, patient representatives and specialists. 
The companies that market topiramate must carry out a drug utilisation study and surveys of healthcare professionals and patients to assess the effectiveness of the new measures.

The PRAC recommendations will now be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human  (CMDh), which will adopt a position.

Published on: 01 September 2023