Levetiracetam is an anticonvulsant used either in monotherapy, or as adjunctive therapy for focal or partial onset seizures with or without secondary generalisation, myoclonic seizures in juvenile myoclonic epilepsy, and primary generalised tonic-clonic seizures.
Overall, congenital malformation rates have been studied in approximately 2,000 infants prenatally exposed during the first trimester to levetiracetam monotherapy, with no evidence of any increased risk, although in some cases study methodologies limit conclusions. There are also currently no identified associations between levetiracetam exposure and a small number of specific malformations. Although some studies have shown that use of levetiracetam in polytherapy may be linked to an increased risk of malformations compared to levetiracetam monotherapy, data are conflicting and, in some cases, potentially confounded by co-exposure to sodium valproate, an established teratogen. There is currently no evidence of a dose-effect.
Although generally reassuring, the data relating to miscarriage, stillbirth, premature delivery and infant birth weight are too limited to facilitate an accurate assessment of any potential risks posed by levetiracetam use in pregnancy and women should be made aware of the lack of data for these outcomes. Data regarding adverse neurodevelopmental outcomes following prenatal exposure to levetiracetam are reassuring, however, due to the small number of exposed children analysed, more research is required.
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 neonatal facilities.
Levetiracetam is not known to impact maternal folate status. However, UK guidelines state that women who take any antiepileptic medication should be prescribed high dose folic acid (5mg).
Plasma concentrations of levetiracetam have been shown to decline as pregnancy progresses and regular clinical review of women taking levetiracetam is therefore recommended. Levetiracetam dose may need to be increased to maintain seizure control, particularly in the third trimester of pregnancy. Levetiracetam should only be used during pregnancy where the benefits of treatment are considered to outweigh any potential risks. Other risk factors may be also 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 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 NHS health care professionals who are logged in.
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.