Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation

Abstract

We present pharmacokinetic data during pregnancy and lactation for brivaracetam, lacosamide and perampanel based on two case studies. Patient 1 used brivaracetam as monotherapy and gave birth to twins. Patient 2 used a combination of brivaracetam, lacosamide and perampanel. In both patients, serum drug concentrations were monitored throughout the pregnancies. Drug concentrations were also analysed in umbilical cord blood at birth, in serum from the offspring and in breastmilk after five days and 3-11 weeks. There were minor changes in concentration/dose-ratios for brivaracetam and lacosamide. The mean milk/serum ratios for brivaracetam and lacosamide were 0.71 and 0.83, respectively, five days and 3-5 weeks after delivery. The perampanel serum concentration increased by up to 80% in Patient 2 during the last part of gestation. The mean milk/serum-ratio for perampanel was 0.13, unchanged from five days to five weeks after delivery. Whereas serum concentrations of brivaracetam and lacosamide remained fairly stable throughout pregnancy, perampanel concentrations seemed to steadily increase towards the end. The distribution to milk was considerable for brivaracetam and lacosamide and low for perampanel. More studies on mother-infant pairs are warranted to confirm these results in larger groups.

Lacosamide effects on placental carriers of essential compounds in comparison with valproate: Studies in perfused human placentas

“…These findings stress the need in therapeutic drug monitoring of lacosamide levels in pregnant women, particularly because dose modifications may be required along pregnancy. A recent study demonstrated that the dose‐normalized concentrations of lacosamide were 40% lower during pregnancy as compared with postpartum levels, 27 similar to earlier observations 28,29 . In this context, our findings support therapeutic monitoring while adjusting lacosamide doses during pregnancy.…”

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

“… 105 Serum concentrations of lacosamide in pregnancy remained fairly stable in a small study. 52 Whereas a decrease was reported in seven pregnancies (lacosamide 200–600 mg/day), through each trimester compared with the baseline without effect on seizure frequency; none of the neonates had MCMs. 106 However, more consistent data come from the recently published MONEAD (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs) study, reporting a decrease of dose-normalized concentrations during pregnancy of 39.9% for lacosamide (26.14–15.71 μg/L/mg; p < 0.001).…”

“…A woman under brivaracetam in monotherapy and another under polytherapy with brivaracetam, lacosamide, and perampanel had only minor changes in concentration/dose ratios of brivaracetam. 52 The few data available are not sufficient to give clinical advice.…”

“… 105 , 264 M/P ratios of brivaracetam, lacosamide, and perampanel are 0.71, 0.83, and 0.13, respectively. 52 …”

Safety and Tolerability of Lacosamide in Patients With Epilepsy: A Systematic Review and Meta-Analysis

“…In our study, the incidence of AEs in children groups is lower than that in patients of all age groups. This was probably because that the number of included study of children was limited, eventhough previous studies have suggested a good level of efficacy and safety for LCM throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities (Lattanzi et al, 2017;Maria et al, 2019); however, since LCM appears to cross the near-term placenta freely and could accumulate in a breastfed infant due to lower renal excretion, more studies are needed to identify the safety of LCM in pregnancy and newborn (Svendsen et al, 2017;Kohn et al, 2020;Landmark et al, 2021).…”