European Medicines Agency recommends new restrictions on Topiramate in pregnancy

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) in a recent press release, has recommended new measures designed to avoid topiramate use for pregnant women.

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 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.

Information for patients:

Exposure to topiramate in the womb can cause birth defects in children, and exposed newborns may be smaller and weigh less than expected at birth. Exposure to topiramate in the womb may also increase the risk of problems with the development of brain function, such as autism spectrum disorders, intellectual disability or attention deficit hyperactivity disorder (ADHD).

If you are pregnant or able to become pregnant, there are important restrictions on the use of topiramate:

you must not use topiramate to prevent migraine or manage your body weight if you are pregnant. If you can become pregnant, you must not use topiramate for these conditions unless you are using highly effective birth control.

if you have epilepsy, you must not use topiramate if you are pregnant unless there are no other treatments that give you sufficient control of seizures.

if you have epilepsy and can become pregnant, you must not use topiramate unless you are using highly effective birth control. If you are planning to become pregnant and topiramate is the only treatment giving you sufficient seizure control, you should speak to your doctor, who will give you information about the risks of taking topiramate during pregnancy and about the risks of seizures during pregnancy.

If you are a patient who can become pregnant, your doctor will provide you with information so you will understand the risks of taking topiramate during pregnancy. This will be done before you start taking topiramate and at least once every year during treatment.

If you can become pregnant, you should always use an effective method of birth control while taking topiramate. Talk to your doctor about which contraceptive method is right for you while you are taking topiramate.

Talk to your doctor if you are planning to become pregnant. Do not stop using effective birth control until you have discussed an alternative treatment with your doctor. If you are taking topiramate for epilepsy, do not stop taking the medicine without consulting your doctor as this could cause harm to you or your unborn child.

Tell your doctor immediately if you become pregnant or think you may be pregnant. If you have any questions or concerns, you should discuss them with your doctor.

Information for healthcare professionals:

It is already well known that topiramate can cause major congenital malformations and foetal growth restriction when used during pregnancy. Recent data also suggest a possibly increased risk of neurodevelopmental disorders following topiramate use during pregnancy.

In the prevention of migraine and as treatment for weight management, topiramate is contraindicated during pregnancy. Topiramate must be discontinued if the patient becomes pregnant or is planning for a baby. Patients of childbearing potential should use highly effective contraception during treatment and for at least 4 weeks after stopping topiramate treatment.

In the treatment of epilepsy, topiramate is contraindicated during pregnancy unless there is no suitable treatment alternative. Topiramate is also contraindicated in women of childbearing potential with epilepsy not using highly effective contraception. The only exception is a woman for whom there is no suitable alternative but who is planning a pregnancy and who has been fully informed about the risks of taking topiramate during pregnancy.

Irrespective of indication, topiramate should be used in women of childbearing potential only when the following conditions of the pregnancy prevention programme are met: a pregnancy test before starting treatment; counselling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment; a review of ongoing treatment at least annually by completion of a risk awareness form.

To confirm that appropriate measures have been taken, patients and prescribers will go through this form at the beginning of treatment and at each annual review and if the patient is planning a pregnancy or has become pregnant. It should be ensured that the patient is fully informed and has understood the risks and measures to be taken.

Topiramate treatment of patients of childbearing potential should be initiated and supervised by a physician experienced in the management of epilepsy or migraine. Treatment with topiramate/phentermine should be handled by a physician experienced in weight management.

Alternative therapeutic options should be considered and the need for treatment should be reassessed together with the patient at least annually. Ongoing treatment should be re‑evaluated to confirm that the measures outlined above have been

Reference: Bjørk M, Zoega H, Leinonen MK, et al. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA Neurol. 2022 Jul 1;79(7):672-681. doi: 10.1001/jamaneurol.2022.1269.

Dreier JW, Bjørk M, Alvestad S, et al. Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders. JAMA Neurol. 2023 Jun 1;80(6):568-577. doi: 10.1001/jamaneurol.2023.0674.

Hernandez-Diaz S, Straub L, Bateman B, et al. Topiramate During Pregnancy and the Risk of Neurodevelopmental Disorders in Children. In: ABSTRACTS of ICPE 2022, the 38th International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE), Copenhagen, Denmark, 26–28 August, 2022. Pharmacoepidemiol Drug Saf, 2022; 31 Suppl 2:3-678, abstract 47.

The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.