Following a review of three recent studies, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that a Pregnancy Prevention Programme (PPP) be introduced around the use of the Anti-Seizure Medication Topiramate (Topamax).
Two of these studies 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 to children born to mothers without epilepsy. This risk was more significant than previously thought and triggered the regulatory process which has been undertaken by the PRAC over the past year.
It had previously been established that Topiramate was associated with an increased risk of serious birth defects when used during pregnancy.
The review process has now concluded, with the key recommendation being that Topiramate should not be used during pregnancy for the treatment of epilepsy unless there is no other suitable treatment available.
A further recommendation is that a Pregnancy Prevention Programme (PPP) should be introduced in EU member states for women of childbearing potential. A similar programme is in currently in place with the Anti-Seizure Medication, Sodium Valproate (Epilim).
The following is a summary of the PPP which has now been recommended by the PRAC. Note that Topiramate is also used in the treatment of migraine and epilepsy.
Contraindications for use:
Topiramate for epilepsy is contraindicated:
- in pregnancy, unless there is no suitable alternative treatment.
- in women of childbearing potential not using highly effective contraception. The only exception is a woman for whom there is no suitable alternative but who plans a pregnancy and who is fully informed about the risks of taking topiramate during pregnancy.
Use of Topiramate In female children and women of childbearing potential
- Treatment with topiramate should be initiated and supervised by a physician experienced in the management of epilepsy. Alternative therapeutic options should be considered.
- The need for topiramate treatment should be reassessed at least annually.
Use of Topiramate in women of childbearing potential:
- Patients must be fully informed and understand the potential risks related to the use of topiramate during pregnancy. This includes the need for a specialist consultation if the woman is planning a pregnancy and for prompt contact with a specialist if she becomes pregnant or thinks she may be pregnant.
- Pregnancy testing should be performed before initiating treatment.
- At least one highly effective method of contraception or two complementary forms of contraception including a barrier method should be used during treatment and for at least 4 weeks after stopping treatment. Women using systemic hormonal contraceptives should be advised to also use a barrier method due to interactions.
- If a woman is planning to become pregnant, efforts should be made to switch to an appropriate alternative epilepsy treatment before contraception is discontinued. The woman must also be informed about the risks of uncontrolled epilepsy to the pregnancy.
- 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.
Use of Topiramate in female children:
- Prescribers must ensure that parent(s)/caregiver(s) of female children using topiramate understand the need to contact a specialist once the child experiences menarche.
- At that time, the patient and parent(s)/caregiver(s) should be provided with comprehensive information about the risks due to topiramate exposure in utero, and the need for using highly effective contraception.
It is expected that the recommendations will be formally adopted by the EMA in the coming months. The Irish Medicines regulator, the Health Products Regulatory Authority (HPRA) will be responsible for introducing the new PPP in Ireland. Measures are likely to include a new guide for healthcare professionals, a patient guide, a risk awareness form to be signed annually, as well as a patient card to be provided when the medicine is dispensed. A text warning and a pictogram on the risks will be introduced on new product packaging and product information will be updated to include details of the PPP.
We will continue to liaise with the HPRA on this issue, and as soon as there are any further details regarding the new PPP in Ireland, we will update our website and social media channels.
In the meantime, we are fully aware of how this new development will be worrying for many women with epilepsy on Topiramate, particularly those who are planning to start a family.
PLEASE DO NOT STOP taking your medication without first speaking to your medical team. If you have any concerns, seek advice from your epilepsy specialist team. Tell your doctor immediately if you become pregnant or think you may be pregnant.
It is important to note that there is a risk with all medications when taken during pregnancy, and pre-conceptual planning with your medical team is highly recommended in order to take tailored decisions that are best suited for you and your child. You can read more about this by visiting other sections of the OACS Ireland website.
- Read the initial advice resulting from this study the News Section of our website.
- Further information and advice managing epilepsy as a woman can be found by visiting the ‘Women’ section of our website of the Epilepsy Ireland’s website.
- If you need information or support regarding your epilepsy, please contact your local Community Resource Officer. You can find their details by visiting the ‘Our Local Service’ section of our website.