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After concerns around topiramate’s potential to cause teratogenic effects in pregnant women, the United Kingdom’s Medicines and Healthcare Products Agency (MHRA) asked the Commission on Human Medicines to look at findings from studies examining the risks associated with the use of topiramate during pregnancy. This showed that children born to mothers on topiramate during their pregnancy had a 2-3 times higher risk of intellectual disability, autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). There is also increased risk of congenital malformations and low birth weight. Prior to the review, topiramate was already known to be associated with significant harm during pregnancy, including a higher risk of birth defects and low birth weight (Medicines and Healthcare products Regulatory Agency, 2024).

To minimise risk for affected patients, the MHRA has introduced a Pregnancy Prevention Programme. It has released guidance for healthcare practitioners with patients suffering from migraine or epilepsy for both clinicians and patients. Topiramate is now contraindicated in pregnancy and in women of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. When initiated for epilepsy, the specialist prescriber team should counsel the patient accordingly based on the conditions of the MHRA’s healthcare professional guide, with primary care to

• Ensure continuous use of highly effective contraception in all women of childbearing potential.
• Check that all patients on the topiramate Pregnancy Prevention Programme have an up to date, signed, Annual Risk Awareness Form when a repeat prescription is issued.
• Remind all female patients that they will need to see their specialist at least once every year while taking topiramate.
• Refer to the specialist urgently (within days) in case of unplanned pregnancy and inform the patient not to stop taking topiramate until told to do so by her specialist.
• Refer any female patient planning to become pregnant to the specialist. Inform her not to stop using contraception or topiramate until told to do so by her specialist.

If topiramate would be initiated for migraine prophylaxis in primary care, the MHRA suggest that prescribers should:

• Assess potential for pregnancy and, if necessary, discuss the need for the patient to be on the Pregnancy Prevention Programme if she is to take topiramate.
• Discuss the risks with the patient and ensure they understand the:
  • other therapeutic options available
  • risks to the unborn child if topiramate is taken during pregnancy
  • the need to take highly effective contraception throughout treatment and undergo pregnancy testing when required – e.g. if there is any reason to suggest lack of compliance or effectiveness of contraception
  • the need to contact her primary care team urgently if they suspect they might be pregnant or wish to plan a pregnancy.
• Before the first prescription is issued in women of childbearing potential:
  • exclude pregnancy (by serum pregnancy test)
  • arrange for highly effective contraception.
• Complete the Annual Risk Awareness Form with the patient and give them a copy.
• Provide a copy of the Patient Guide to the patient.
• See the patient promptly in case of unplanned pregnancy or if she wants to plan a pregnancy.

All patients on the Pregnancy Prevention Programme should be invited for an annual review and only continue if its conditions are fulfilled. Patients should have an up to date and signed annual risk awareness form. Women should be using at least one highly effective method of contraception, preferably a LARC method. For those on migraine prophylaxis, women planning a pregnancy should stop topiramate at least a month before trying to conceive. For patients with epilepsy planning to become pregnant should be referred to their specialist and told not to stop using contraception or topiramate until told to do so by her specialist. Patients with unplanned pregnancies on topiramate should be referred urgently (Medicines and Healthcare products Regulatory Agency, 2024) (Medicines and Healthcare products Regulatory Agency, 2024).

To implement this into day to day primary care, a member of the team can: 

• do a search on female patients on topiramate
• invite patients to discuss the pregnancy prevention programme
• for those on topiramate for epilepsy, write to the local neurologists to notify them of the patient and request a review by the specialist prescribing team
• discuss alternatives for those on topiramate for migraine
• counsel re the benefits of LARC solutions
• initiate or check current contraceptive solution
• audit female patients on topiramate six months after the implementation of the primary prevention programme to check whether there are gaps in the provision.

Resources

Topiramate Pregnancy Prevention

Healthcare Professional Guide: 

For Epilepsy
For Migraine
Topiramate patient card

MHRA documents:

Topiramate: review of safety in pregnancy; Public Assessment Report
Announcement of new safety measures for topiramate
Direct Healthcare Professional Communication by Janssen-Cilag

References

Fariba KA, Saadabadi A. Topiramate. 2024 Jun 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.

Medicines and Healthcare products Regulatory Agency. Topiramate Healthcare Professional Guide - Epilepsy. Jul 2024. [accessed 11 July 2024]. 

Medicines and Healthcare products Regulatory Agency. Healthcare Professional Guide Prophylaxis of Migraine. Jul 2024. [accessed 11 July 2024].

Medicines and Healthcare products Regulatory Agency. Topiramate: review of safety in pregnancy. Public Assessment Report. Jun 2024. [accessed 11 July 2024]. 

NICE. Topiramate. [accessed 11 July 2024]. 

Spritzer SD, Bravo TP, Drazkowski JF. Topiramate for Treatment in Patients With Migraine and Epilepsy. Headache. 2016 Jun;56(6):1081-5.