PHARMACOLOGICAL SAFETY OF ANTIEPILEPTIC DRUGS IN PREGNANT AND LACTATING WOMEN

The number of people of reproductive age with epilepsy is increasing worldwide, leading to an increase in the prevalence of epilepsy during pregnancy [1]. Pregnant women with epilepsy are at increased risk of adverse obstetric and fetal outcomes, including increased risk of birth defects and delayed neurocognitive development, compared with women without epilepsy [2, 3]. Seizures during pregnancy can be harmful to both the mother and fetus, increasing the risk of physical injury and metabolic stress, slowed fetal heart rate, hypoxia, preterm birth, and low birth weight [4]. The aim of this study was to analyze the safety profile of commonly used antiepileptic drugs in terms of efficacy and safety and to summarize possible changes in their pharmacokinetics during pregnancy. Materials and methods. The analysis of efficacy, safety, and pharmacokinetic characteristics of antiepileptic drugs was performed on the PubMed platform. The literature search included the following keywords: antiepileptic drugs, anticonvulsants, pregnancy, lactation. The chronological characteristics of the search included information sources from 2003 to 2024, including 88% (37 of 42 literature references) dated in the last 5 years, i.e. from 2019 to 2024. Information sources in English, German, French, Spanish and Japanese were used for the analysis. Results and discussion. The analysis showed that valproate is the most potent teratogenic drug, with a dose-dependent risk of major congenital malformations (up to 10%) in the population. Lamotrigine and levetiracetam are considered relatively safe for use during pregnancy and lactation, but recent studies suggest that levetiracetam is associated with an increased risk of attention deficit hyperactivity disorder and anxiety, whereas lamotrigine is considered safer with respect to postnatal neurodevelopment. Lacosamide and oxcarbazepine are characterized by relative safety during pregnancy, although data are inconclusive in assessing the risk of perinatal mortality with oxcarbazepine monotherapy. Pregabalin is not teratogenic; however, abnormalities of the central nervous system, eyes, genitourinary system, and facial clefts have been observed in newborns exposed to pregabalin. With gabapentin, atypical and/or difficult-to-control signs and symptoms of withdrawal have been observed in newborns, suggesting in utero exposure. Zonisamide administration was associated with a risk of teratogenesis that was directly related to the dose of the drug used by the pregnant woman, at least during the first half of pregnancy.