左乙拉西坦仿制药与原研药临床疗效及安全性的真实世界研究

Real-World Study of Clinical Efficacy and Safety of Generic and Original Levetiracetam

目的:评价真实世界左乙拉西坦(LEV)仿制药与原研药的安全性和有效性。方法:回顾分析2019年4月至2020年5月西安交通大学第二附属医院使用LEV治疗的600例癫痫患儿临床资料,采用高效液相色谱检测LEV仿制药和原研药血药浓度,并分析两种药物剂量与血药浓度关系以及治疗效果和不良反应发生率。结果:600例癫痫患儿中,使用LEV仿制药125例,单药治疗71例,联合用药54例;使用LEV原研药475例,单药治疗266例,联合用药209例。LEV仿制药单药治疗血药浓度为(9.31±3.34)μg/mL,与肝酶诱导剂(奥卡西平、苯巴比妥)联用时血药浓度分别为(10.26±4.72)μg/mL和(11.05±2.41)μg/mL,与肝酶抑制剂(丙戊酸、托吡酯)联用时血药浓度分别为(10.69±5.78)μg/mL和(8.16±4.37)μg/mL,与肝酶诱导剂、抑制剂(奥卡西平+丙戊酸)联用时血药浓度为(8.74±5.56)μg/mL,与LEV原研药比较差异均无统计学意义。LEV仿制药单药治疗有效率为78.9%,原研药为74.1%;联用肝酶诱导剂,LEV仿制药有效率为64.3%,原研药为62.7%;联用肝酶抑制剂,LEV仿制药有效率为59.3%,原研药为78.2%;联用肝酶诱导剂、抑制剂,LEV仿制药有效率为69.2%,原研药为71.4%。LEV仿制药与原研药临床疗效比较差异均无统计学意义。LEV仿制药不良反应发生率与原研药相似,常见不良反应均为异常行为及入睡困难。结论:LEV仿制药和原研药在真实世界临床疗效及不良反应比较差异无统计学意义,LEV仿制药替换原研药是安全且有效的。

Objective:To evaluate the safety and efficacy of real-world generic and original levetiracetam levetiracetam(LEV).Methods:Clinical data of 600 children with epilepsy received LEV in the Second Affiliated Hospital of Xi’an Jiaotong University from Apr.2019 to May 2020 were retrospectively analyzed.Blood concentration of generic and original LEV was determined by high performance liquid chromatography.Correlation between the dose of two drugs and blood concentration,therapeutic effect and incidence of adverse drug reactions were analyzed.Results:Among the 600 patients with epilepsy,125 cases received generic LEV,including 71 cases of monotherapy and 54 cases of additive therapy.Totally 475 patients received original LEV,including 266 cases of monotherapy and 209 cases of additive therapy.Blood concentrations were(9.31±3.34)μg/mL for LEV generic monotherapy,(10.26±4.72)μg/mL and(11.05±2.41)μg/mL when combined with liver enzyme inducers(oxcarbazepine and phenobarbital),(10.69±5.78)μg/mL and(8.16±4.37)μg/mL when combined with liver enzyme inhibitors(valproic acid and topiramate),and(8.74±5.56)μg/mL in combination with liver enzyme inducers and liver enzyme inhibitors(oxcarbazepine+valproic acid),with no statistically significant differences compared with the original LEV.The effective rate of LEV generic drug was 78.9%,and that of the original drug was 74.1%.The effective rate of the generic LEV combined with liver enzyme inducers was 64.3%,and that of the original drug was 62.7%.The effective rate of generic LEV combined with liver enzyme inhibitors was 59.3%,and that of the original drug was 78.2%.The effective rate of generic LEV combined with liver enzyme inducers and liver enzyme inhibitors was 69.2%,and that of the original drug was 71.4%.There was no significant difference in clinical efficacy between generic and original LEV.The incidence of adverse drug reactions of generic LEV was similar to that of the original LEV,and the most common adverse drug reactions were abnormal behavior and sleep difficulty.Conclusion:There is no significant difference between the generic and original LEV in clinical efficacy and adverse drug reactions.Generic LEV are safe and effective to replace the original LEV.