Plasma lacosamide monitoring in children with epilepsy: Focus on reference therapeutic range and influencing factors.

Background: Lacosamide (LCM) is a newer anti-seizure medication (ASM) that was approved in China in 2018, but its real-world clinical data and plasma concentrations in Chinese children with epilepsy are very limited. Of note, the reference range for routine LCM therapeutic drug monitoring is still unknown. The purpose of this study was to investigate the efficacy and safety of LCM as a monotherapy or an adjunctive treatment with other ASMs and to evaluate the potential factors affecting its efficacy and variable LCM plasma concentrations in Chinese children with epilepsy. Methods: Children with epilepsy (<18 years) with routine plasma LCM monitoring from March 2019 to December 2021 at the Department of Pharmacy, Children's Hospital of Nanjing Medical University were retrospectively collected. Clinical data were obtained from the hospital information system. Results: 76 pediatric patients (52 males) were finally enrolled. Mean age was 7.9 years (1.3-17.3 years) with a mean dose of LCM 6.3 mg/kg/day (2.0-11.3 mg/kg/day). The TDM data as a whole showed that the median plasma trough concentration (C 0) was 3.42 µg/mL (1.25-8.31 µg/mL). A 6-month LCM add-on therapy produced 70% of patients achieving ≥50% seizure frequency reductions, and the number was 81% for the one-year follow-up findings. Interestingly, more patients who took LCM monotherapy achieved seizure freedom over the same periods of follow-up observations. Under maintenance dosages, approximately 92.1% of the C 0 values were 2.0-7.0 µg/mL. The plasma-C 0-to-daily dose (C 0/Dose) ratio was significantly associated with age and body weight (BW). The C 0/Dose ratio in patients aged 1- ≤ 6 and 6- ≤ 12 years was significantly higher by 81% and 29% than those aged 12- ≤ 18 years, respectively. The C 0/Dose ratio in patients with a BW of ≥40 kg was 1.7-fold lower than in patients with a BW of ≤ 20 kg. In addition, complex LCM-ASMs interactions were observed. Oxcarbazepine significantly decreased the C 0/Dose ratio of LCM by 28%. Conclusion: This retrospective study confirmed the effectiveness and tolerability of the LCM treatment used alone or with other ASMs in children with focal epilepsy. Children with higher BW and older age have lower C 0/Dose ratio. Complex drug interactions between LCM and other concomitant ASMs were revealed. Notably, based on the data in our hands, the reference range, i.e., 2.0-7.0 µg/mL, for routine LCM monitoring may be feasible. The real-world evidence of this study supports LCM as a promising option in children with focal epilepsy.