Medicines Healthcare Products Regulatory Agency
General advice for healthcare professionals:
- topiramate should not be used:
- in pregnancy for prophylaxis of migraine
- in pregnancy for epilepsy unless there is no other suitable treatment
- topiramate should not be used in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme are fulfilled. This aims to ensure that all women of childbearing potential:
- are using highly effective contraception
- have a pregnancy test to exclude pregnancy before starting topiramate
- are aware of the risks from use of topiramate
- please see specific advice for prescribers and advice for dispensers
- ensure women of childbearing potential sign the Risk Awareness Form, you will receive materials including the Risk Awareness Form by post in the coming weeks to use in the implementation of the Pregnancy Prevention Programme
- report suspected adverse drug reactions associated with topiramate to the Yellow Card scheme
Advice for healthcare professionals to provide to patients:
- new measures are being introduced because there is evidence that taking topiramate during pregnancy can increase the risk to the baby of congenital malformation, low birth weight, intellectual disability, autistic spectrum disorder and attention deficit hyperactivity disorder
- use effective birth control (contraception) at all times during your treatment with topiramate and for at least 4 weeks after the last dose
- topiramate may interact with some hormonal contraceptives. Your General Practitioner (GP), specialist, sexual health and contraception clinic or contraception service in community pharmacy will discuss which method of birth control is best for you
- if you are thinking about having a baby, make an appointment with your GP. Do not stop using topiramate and contraception before you have talked to your doctor
- if you think you are pregnant and are taking topiramate for epilepsy, do not stop using topiramate. This may cause your seizures to start again or happen more often and last longer. Make an urgent appointment with your GP or epilepsy team (within a few days)
- if you think you are pregnant and are taking topiramate for migraine prevention, stop taking topiramate straight away and contact your GP
- it is important to visit your doctor to review your treatment at least once each year
- always read the safety leaflet that comes with your medicine and consult the new Patient Guide for information about the risk of topiramate use during pregnancy
Review of harms of topiramate use during pregnancy
Topiramate is indicated for the prophylaxis of migraine and for the treatment of epilepsy. It is available as tablets, a liquid oral solution and as capsules that can be swallowed whole or sprinkled on soft food. The brand name of topiramate is Topamax, and so this may also appear on the box. Topiramate has been contraindicated in pregnancy for the prophylaxis of migraine since 2010.
Following a comprehensive review of the safety of antiseizure medications in pregnancy, including topiramate, new safety advice was published in January 2021. Since then, new study data has become available reporting a potential increased risk of autism spectrum disorder and effects on learning development in children exposed to topiramate during pregnancy[footnote 1]. These new data, and data suggesting increasing use of topiramate in women of childbearing age, triggered a new safety review. This review examined the available data on the risk of congenital malformations, effects on growth and development of the baby, and the risk of neurodevelopmental disorders when topiramate is used during pregnancy.
The review concluded that the use of topiramate during pregnancy is associated with significant harm to the unborn child (both from the confirmed risks of congenital malformations and low birth weight and the potential risk of neurodevelopmental disorders). The accumulating data suggest that:
- topiramate is amongst the antiseizure medications associated with a higher risk of congenital malformations (approximately 4 to 9 per 100 babies compared to around 1 to 3 babies in every 100 in the general population)[footnote 2]
- the risk of congenital malformations with topiramate appears to be dose-dependent, however, a threshold dose below which no risk exists cannot be established
- topiramate is associated with a high prevalence of babies being born small for gestational age and weighing less at birth (approximately 18 per 100 babies affected); this is higher than the risk in babies born to women with epilepsy not taking antiseizure medication (approximately 5 in 100 babies affected) and may be higher than the risk with some other antiseizure medications[footnote 3]
- topiramate may be associated with an approximately 2 to 3 times increased risk of intellectual disability, autistic spectrum disorders and attention deficit hyperactivity disorder compared with children born to mothers with epilepsy not taking antiseizure medication.[footnote 1][footnote 4][footnote 5][footnote 6][footnote 7][footnote 8]
Full information on the studies considered and their findings, can be found in the Public Assessment Report. This report also includes a plain language summary of the review and findings.
New safety measures
Due to the accumulating data on these harms, further restrictions are being introduced with regards to the use of topiramate in women of childbearing potential and in pregnancy.
The use of topiramate is now contraindicated:
- in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme are fulfilled (for all indications)
- in pregnancy for prophylaxis of migraine
- in pregnancy for epilepsy unless there is no other suitable treatment
Materials to support the Pregnancy Prevention Programme:
Healthcare professionals will receive materials by post in the coming weeks to support discussions with patients and implementation of the Pregnancy Prevention Programme. These materials are also available online and consist of :
Patient Guide for and - to be provided to all girls and women of childbearing potential who are started on, or continue to use, topiramate-containing medicines
Guide for Healthcare Professionals for and
Risk Awareness Form for and - for the healthcare professional and the patient (or responsible person) to sign at initiation of treatment with