USE OF TOPIRAMATE IN PREGNANCY

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(Date of issue: September 2019, Version: 3)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on topiramate use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Topiramate is an anticonvulsant used in monotherapy or as adjunctive therapy in the treatment of generalised tonic-clonic seizures, focal seizures with or without secondary generalisation, and seizures associated with Lennox-Gastaut syndrome. Topiramate is also licensed for the prophylaxis of migraine, and in the United States for weight loss in combination with phentermine.

The majority of the available epidemiological data relate to topiramate use in pregnancy for the treatment of maternal epilepsy. Gestational topiramate exposure has been associated with orofacial clefts in the offspring, with 5- to 6-fold increased risks having been described. Although evidence has been provided from a single study suggesting that the risk may be highest following doses of >100mg/day, due to data limitations it is not currently possible to rule out any increased risk where mothers have used doses of ≤100mg/day.

There are also conflicting data which have suggested that the overall risk of fetal malformation may be greater with use of topiramate, particularly when used in polytherapy regimens. However, it is not known whether this observation is explained by factors such as use of higher doses of topiramate in polytherapy, a synergistic effect between topiramate and other AEDs or concomitant use of proven teratogenic AEDs. Further research is required to clarify these findings.

Weight loss is a recognised side effect of topiramate use and there is evidence that exposure in pregnancy is associated with reduced infant birth weight. Data relating to rates of miscarriage, stillbirth, premature delivery and neurodevelopmental outcomes in exposed offspring are too limited to facilitate an accurate assessment of any potential risks posed by topiramate use in pregnancy. However, the available evidence concerning these outcomes does not currently provide reliable evidence suggestive of increased risks. Where gestational use of topiramate is being considered, women should be made aware of the lack of data for these outcomes.

Two studies have separately analysed pregnancies exposed to topiramate for other indications, with no observed increase in overall congenital malformation risk or risk of orofacial clefts specifically.

Use of any centrally-acting drug throughout pregnancy or near delivery may be associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug. Delivery should be planned in a unit with adequate facilities.

Topiramate is not known to impact maternal folate status. However, UK guidelines state that women who take any anti-epileptic medication should be prescribed high dose folic acid (5mg).

Where topiramate exposure has occurred during the first trimester, detailed ultrasound scans may be considered to screen for orofacial clefts. Monitoring of maternal weight and fetal growth are also recommended. Plasma concentrations of topiramate have been shown to decline as pregnancy progresses and regular clinical review of women in whom continued treatment with topiramate is indicated is therefore recommended. Topiramate dose may need to be adjusted to maintain seizure control, particularly in the third trimester of pregnancy. Topiramate should only be used during pregnancy where benefits of treatment are considered to outweigh any potential risks. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.