Association of Levetiracetam Concentration With Seizure Frequency in Pregnant Women With Epilepsy

Background and Objectives Pharmacologic treatment of epilepsy in pregnant women is balancing between risks for the mother and fetus. Levetiracetam (LEV) is considered to be safe during pregnancy because of its low teratogenic potential and lack of drug-drug interaction with other antiseizure medications (ASMs). Recent studies have shown decline of ASM concentrations during pregnancy because of physiologically based pharmacokinetic changes. In this study, we established this decrease in LEV concentration during pregnancy. In addition, we aimed at investigating the effect of the low LEV levels during pregnancy and developing a target value for the level during pregnancy.

Methods Pregnant patients using levetiracetam were studied in this retrospective cohort study. Blood samples were monthly collected through venous puncture or the dried blood spot method. ASM serum concentrations were determined at least 6 months before conception and for each month of pregnancy. Seizure frequency and ASM dosages during pregnancy were obtained from patient records. Patients were divided into 2 groups: a seizure-free group and a non–seizure-free group, which contained pregnancies in which the mother had experienced an epileptic seizure more than 12 months and less than 12 months before pregnancy, respectively.

Results We found decreased concentration/dose ratios in 29 pregnancies throughout all months of pregnancy. In the non–seizure-free group, it was found that low LEV concentrations were associated with seizure increase frequency (p = 0.022). For this group, the cutoff value with the highest sum of sensitivity and specificity was 0.466.

Discussion All in all, we recommend therapeutic drug monitoring for all pregnant patients on LEV as the concentrations of LEV significantly decrease throughout most months of pregnancy. However, this decrease in LEV concentration was only significantly correlated with seizure deterioration in patients who had a seizure in the year preceding the pregnancy. Therefore, we suggest more careful monitoring of non–seizure-free patients as they are at higher risk for experiencing an increase of seizure frequency. For this group, we advise physicians to keep LEV concentration above 65% of the preconceptional concentration. For seizure-free patients, we recommend an LEV threshold value of approximately 46% of the preconceptional concentration.