摘要
该文对日本"小柴胡汤事件"和我国涉及柴胡制剂的安全性案例进行了回顾性对比分析与评价,认为日本"小柴胡汤事件"所涉及的间质性肺炎、药物肝炎等严重及死亡病例,与当时日本医师合并使用干扰素、汉方药西用、辨病不辨证等因素可能有关;我国柴胡口服制剂涉及不良事件文献报道较少,表现为皮肤过敏反应和汗出过多;柴胡注射液涉及的不良事件主要表现为过敏样反应,2例违背说明书的肌内注射用法,误用为静脉滴注者分别引起低钾血症和肾衰竭,1例死于过敏性休克,在我国柴胡制剂相关的文献病例中虽尚未见日本"小柴胡汤事件"涉及的2种严重不良事件,目前尚缺乏主动监测和大样本临床研究数据等高级别证据。笔者解析了药品再评价分类并提出对药品安全性或者有效性的质疑的回应均属于"有因再评价"的范畴。鉴于柴胡制剂的临床研究现状,提出围绕"有因再评价"开展中药上市后临床研究,不仅是进一步考察临床安全性、有效性的需要,而且是为国内外药品监管机构风险效益评估提供共同认可而客观临床研究依据的需求,也是提升企业风险控制能力、消除中药负面影响、促进中药知名品牌优秀品种走向国际的必经之路。笔者以该制剂中使用较广、不良事件个案报道相对较多的柴胡注射液为例解析上市后临床研究的思路和内容。
We revisited the ″Xiao Chaihu Decoction event（XCHDE） ″ occurred in late 1980 s in Japan and the Bupleuri Radix related adverse drug reaction（ADR） reports in China.After careful review,comparison,analysis and evaluation,we think the interstitial pneumonitis,drug induced Liver injury（DILI） and other severe adverse drug envents（ADEs） including death happened in Japan is probably results from multiple factors,including combinatory use of XCHDE with interferon,Kampo usage under modern medicine theory guidance,and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation.There are less ADE case reports related to XCHD preparation in China compared to Japan,mostly manifest with hypersensitivity responses of skin and perfuse perspiration.The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivitylike response,2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure.One case died from severe hypersensitivity shock.In Chinese literatures,there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan.So far,there is no voluntary monitoring data and large sample clinical research data available.The author elaborated the classification of ″reevaluation″ and clarified ″re-evaluation upon events″ included the reaction to the suspected safety and efficacy events.Based on the current status of the clinical research on the Radix Bupleuri preparations,the author points out that post-marketing ″re-evaluation upon suspected event″ is not only a necessity of continuous evaluation of the safety,efficacy of drugs,it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation.It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market,in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine.With the widely used and ADR report concentrated Radix Bupleuri injection as an example,the author provide a new approach to post-marketing clinical research.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2014年第15期2983-2988,共6页
China Journal of Chinese Materia Medica
关键词
小柴胡汤事件
柴胡
间质性肺炎
药物性肝损伤
不良反应
上市后临床研究
有因再评价
中药国际化
Xiao Chaihu Decoction event（XCHDE）
Bupleuri Radix
interstitial pneumonia
drug-induced liver injury（DILI）
adverse drug reaction（ADR）
post-marketing clinical study
re-evaluation upon suspected event
internationalization of Chinese medicine
