Therapeutic Drug Monitoring for Lacosamide in Chinese Pediatric Patients with Epilepsy: Focus on Clinical Effectiveness, Tolerability and Drug Interactions

拉考沙胺在中国儿童癫痫患者中的治疗药物监测:重点关注临床疗效、耐受性和药物相互作用

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Abstract

Objective: To investigate the effectiveness and tolerability of lacosamide (LCM) and to select a better reference range for its concentration in plasma for Chinese pediatric patients with epilepsy. In addition, it is necessary to evaluate the potential determinates of LCM concentration. Methods: Pediatric epilepsy patients using LCM were retrospective included. The clinical data of these patients were retrospectively reviewed, and the effectiveness at 3, 6, and 12 months after treatment was assessed. Drug concentrations from routine therapeutic drug monitoring (TDM) were also obtained. The trough concentration-to-dose ratio (C(0)/dose ratio) of LCM was compared among patients with various potential influencing factors. In addition, a new reference range was established based on the range in which the majority of patients were located and the proportion of responders within this range. Results: A total of 153 pediatric epilepsy patients were finally included. The frequency of seizures decreased by ≥50% was 74.7%, 73.0%, and 71.2% at 3, 6, and 12 months, respectively. Adverse events (AEs) occurred in 53 patients, and most AEs were mild and moderate. The TDM data showed that it is reasonable to recommend using 2.5 to 6.5 µg/mL as the reference range. The C(0)/dose ratio was significantly associated with weight, but those aged 4 to 12 were significantly lower than those aged >12 years. In addition, LCM-antiepileptic drug (AED) interactions were observed. Oxcarbazepine and perampanel significantly decreased the C(0)/dose ratio of LCM. Conclusions: LCM was efficacious in reducing seizure frequency and well tolerated in pediatric patients with epilepsy. The reference range 2.5-6.5 µg/mL, for routine LCM monitoring may be more applicable. As complex LCM-AED interactions were observed, it is necessary to monitor the plasma concentration.

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