New measures to prevent pregnancy for topiramate

Following a major safety review triggered by a new study conducted in Europe, the MHRA is introducing new safety measures for topiramate, also known under the brand name Topamax.

The CHM reviewed the results of studies examining the risks associated with topiramate use during pregnancy, which showed that babies born to mothers who take topiramate during pregnancy face an approximately 2- to 3-fold increased risk of mental retardation. , autism spectrum disorders and attention deficit hyperactivity disorder.

Following advice from the CHM, the MHRA now advises healthcare professionals that topiramate should not be prescribed to treat epilepsy in pregnancy unless there is no suitable alternative treatment. Topiramate should not already be used during pregnancy for migraine due to its known association with an increased risk of birth defects.

To meet the requirements of a birth control plan, women of childbearing potential must use effective contraception during treatment and take a pregnancy test before starting topiramate. Healthcare professionals should make patients aware of the risks of using this drug during pregnancy, so completion of a risk awareness form is another requirement of this programme.

Patients are also advised that some methods of contraception are less effective than others when using topiramate, and their GP or sexologist will be able to help advise which method of contraception is suitable for them. A regular medication review is also recommended, at least once a year. New safety and educational materials have been introduced for patients and healthcare professionals to support the implementation of these procedures.

Topiramate is taken to prevent migraines or to treat epilepsy and is thought to be prescribed to more than 30,000 female patients under the age of 55 in England a month, according to the latest figures from NHS England.

Before the review, topiramate was known to have risks associated with significant harm to pregnancy, including a higher risk of birth defects and low birth weight. For this reason, patients were previously advised to use it during pregnancy and to use highly effective contraception during treatment. Implementation of the pregnancy prevention program will further strengthen safety measures and aim to reduce the number of pregnancies exposed to topiramate.

Pregnant women or those planning to become pregnant who are currently taking topiramate for epilepsy should not stop taking the drug without consulting a specialist, as this may cause seizures to start again, happen more often or last longer. If women are planning to become pregnant, they should make an appointment with their GP to discuss their treatment options.

In 2021, the CHM concluded that of the antiepileptic drugs reviewed for use in pregnancy, lamotrigine and levetiracetam were considered safer, as they were not associated with birth defects when used during pregnancy.

Other recommendations from CHM include updates to the topiramate leaflet to fully reflect the available data on the risks of use in pregnancy.

A visual warning symbol will be added to the carton for all topiramate medications. This “no” symbol will show a pregnant woman in a red circle with a line through it. This will be accompanied by a warning text about the risk.

Suspected side effects related to topiramate should continue to be reported to the Yellow Card.

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Notes to the editor

1. More information can be found in the drug safety update

2. Medicines and Pregnancy Register – updated figures to September 2023. Use of anti-epileptic drugs in women aged 0 to 54 in England: April 2018 to September 2023

3. Topiramate is indicated for preventive treatment against migraine and for the treatment of epilepsy. It is available as tablets, oral liquid, solution, and as capsules that can be swallowed whole or sprinkled on soft food. The brand name of topiramate is Topamax, so this may also appear on the box.

4. Following a comprehensive review of the safety of antiepileptic drugs during pregnancy, including topiramate, new safety advice was published in January 2021. Since then, new research data has become available indicating a possible increased risk of autism spectrum disorder and effects on learning development in children exposed to topiramate during pregnancy. Data from about 4.5 million mother-child pairs were examined, and there were 24,825 children (0.6%) who were exposed to antiepileptic drugs before birth. Of these, 16,170 were born to mothers who had epilepsy. This new information, along with data suggesting increased use of topiramate in women of childbearing age, prompted a new safety review. This review examined the available data on the risk of congenital malformations, the effects on the growth and development of the baby and the risk of neurodevelopmental disorders when topiramate is used during pregnancy.

5. The conclusion of the review was that the use of topiramate during pregnancy is associated with significant harm to the unborn child (both due to the established risk of congenital malformations and low birth weight, and an approximately 2- to 3-fold increased risk of mental retardation, autism spectrum disorders, and attention deficit hyperactivity disorder).

6. Before the new safety review, due to the serious known harms associated with the use of topiramate during pregnancy (higher risk of congenital malformations and low birth weight), it was already recommended that topiramate should not be used for the prevention of migraine in patients who are pregnant.

7. The previous drug safety update for topiramate was issued in July 2022 and announced the new safety review.

8. The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for monitoring medicines and medical devices in the UK by making sure they work and are reasonably safe. All of our work is based on sound and fact-based judgment to ensure that the benefits justify any risks.

9. The MHRA is the executive body of the Ministry of Health and Social Affairs.

10. For media enquiries, please contact newscentre@mhra.gov.uk or 020 3080 7651.