Topiramate is available in ireland as Topamax tablets, and Topamax sprinkle capsules.

Topiramate is indicated as:

• Monotherapy in adults, adolescents and children over six years of age with partial seizures with or without secondary generalised seizures, and primary generalised tonic-clonic seizures;
• Adjunctive therapy in children aged two years and above, adolescents and adults with partial onset seizures with or without secondary generalisation or primary generalised tonic-clonic seizures and for the treatment of seizures associated with Lennox-Gastaut syndrome; and
• Prophylaxis of migraine headache in adults after careful evaluation of possible alternative treatment options. Topiramate is not intended for acute treatment.

It is already well known that topiramate can cause major congenital malformations and foetal growth restriction when used during pregnancy. Women with epilepsy who were being treated with Topiramate for their seizures were advised to avoid becoming pregnant, and to consult their doctor for advice if they wished to become pregnant.

Topiramate was already contraindicated in migraine prophylaxis in pregnant women and in women of childbearing potential who are not using highly effective birth control methods.

Last year an EMA review was initiated following the publication of a study that showed that prenatal exposure to topiramate was associated with increased risk of neurodevelopmental disorders including autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder (ADHD) following topiramate use during pregnancy. Additional measures in the form of a pregnancy prevention programme have been agreed, to avoid exposure 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.

Information for healthcare professionals

• Healthcare professionals should ensure that all patients who can become pregnant are fully aware of the risks of taking topiramate during pregnancy. This includes the need for a specialist consultation if the woman is planning pregnancy and for prompt contact with a specialist doctor if she becomes pregnant or thinks she may be pregnant;
• 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;
• In the prevention of migraine, topiramate continues to be contraindicated during pregnancy and in women of childbearing potential not using highly effective contraception;
• In the treatment of epilepsy, topiramate is now 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; and
  • 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.

• At least one highly effective method of contraception (such as an intrauterine device) or two complementary forms of contraception including a barrier method should be used during treatment and for at least four weeks after stopping treatment. Due to a potential interaction, women using systemic hormonal contraceptives should be advised to also use a barrier method;
• Treatment of patients of childbearing potential should be initiated and supervised by a physician experienced in the management of epilepsy or migraine;
• If a woman being treated with topiramate for epilepsy becomes pregnant, she should promptly be referred to specialists to reassess topiramate treatment and consider alternative treatment options, as well as for careful antenatal monitoring and counselling. The woman must also be informed about the risks of uncontrolled epilepsy to the pregnancy;
• If a woman being treated with topiramate as migraine prophylaxis becomes pregnant, treatment should be stopped immediately. The woman should be referred to a specialist for careful antenatal monitoring and counselling; and
• In female children (for epilepsy only), prescribers must ensure that parents/caregivers of female children using topiramate understand the need to contact a specialist once the child experiences menarche. At that time, the patient and parents/caregivers should be provided with comprehensive information about the risks due to topiramate exposure in utero, and the need for using highly effective contraception.

References and further reading:

• EMA referral, ema.europa.eu > Medicines > Search for Topiramate.
• Janssen Safety Update, hpra.ie/docs/default-source/default-document-library/important-safety-information-topamax-(topiramate).pdf, accessed 1 November 2023; and
• HPRA Drug Safety Newsletter November 2023, 113^th