Characterisation of Agomelatine-Induced Increase in Liver Enzymes: Frequency and Risk Factors Determined from a Pooled Analysis of 7605 Treated Patients
Characterisation of Agomelatine-Induced Increase in Liver Enzymes: Frequency and Risk Factors Determined from a Pooled Analysis of 7605 Treated Patients
复制标题
DOI：
10.1007/s40263-016-0351-6
复制
发表时间：
2016-09-01
期刊：
影响因子：
6
通讯作者：
Moore, Kevin
中科院分区：
文献类型：
--
作者：
Perlemuter, Gabriel;Cacoub, Patrice;Moore, Kevin
背景抗氧化剂-目的探讨阿戈美拉汀对肝脏的安全性，并对服用阿戈美拉汀引起转氨酶升高的患者进行临床分析。方法回顾性分析9234例服用阿戈美拉汀的患者的转氨酶水平变化，并与对照组比较。阿戈美拉汀（25或50 mg/天; n = 7605）或安慰剂（n = 1629）来自49项II期和III期研究。转氨酶水平显著升高定义为升高至> 3倍正常上限（ULN）（> 3 x ULN）。最终的因果关系由五位学术专家在逐案审查中确定。结果阿戈美拉汀25 mg和50 mg治疗的患者中，血清转氨酶升高至> 3 x ULN的患者分别为1.3%和2.5%，而安慰剂组为0.5%。64%的患者在12周前出现转氨酶升高。中位恢复时间（至
Background Antidepressant-induced liver injury is a major concern and a liver monitoring scheme has been recommended by the European Medicines Agency for agomelatine.Objective The objective of this study was to assess the liver safety and identify the characteristics of patients who developed a significant increase in transaminases whilst taking agomelatine.Method A retrospective pooled analysis of changes in transaminase levels in 9234 patients treated with agomelatine (25 or 50 mg/day; n = 7605) or placebo (n = 1629) from 49 phase II and III studies was undertaken. A significant increase in transaminase levels was defined as an increase to > 3 times the upper limit of normal (ULN) (> 3 x ULN). Final causality was determined in a case-by-case review by five academic experts.Results Serum transaminases increased to > 3 x ULN in 1.3 and 2.5 % of patients treated with 25 and 50 mg of agomelatine, respectively, compared with 0.5 % for placebo. The onset of increased transaminases occurred before 12 weeks in 64 % of patients. The median time to recovery (to