中药注射剂说明书修订公告及备案现状分析

目的 分析中药注射剂说明书修订公告及其具体要求，以及据此开展的说明书修订备案情况，为中药注射剂说明书监管工作提供依据。方法 将中药注射剂说明书修订公告和现有中药注射剂数据、说明书修订备案情况对比。统计分析中药注射剂说明书修订范本/要求中警示语、禁忌、不良反应、注意事项各方面具体内容。结果 中药注射剂说明书修订公告数近年增加明显，但批文数量少的中药注射剂品种被公告的比例偏低。公告品种批准文号的整体未修订备案率为23.7%，未备案批准文号约82.8%在2020年面临再注册。30份说明书修订范本/要求中，警示语多数列出过敏性休克，所列不良反应累及的系统-器官数在4~10，肝肾系统损害少有被提及，只有2份的禁忌项涉及中医证候，注意事项中特殊人群和药物相互作用的信息较多，警示语、不良反应、禁忌、注意事项之间的关联度偏低。结论 需持续对中药注射剂特别是批文数量较少的品种进行说明书修订，并通过明确法律责任、说明书社会公开和药品再注册落实企业说明书修订和通知使用的责任。需根据系统的循证研究完善不良反应、警示语、禁忌的修订，可考虑将特殊人群用药和药物相互作用单列，并增强说明书各项目之间的联系。

Analysis of Revision Notifications of Traditional Chinese Medicine Injection Leaflets and Relevant Filed Information

OBJECTIVE To analyze the revision notifications of traditional Chinese medicine(TCM) injection leaflets and the relevant filed information of revision, so as to produce evidence to support TCM injection leaflets supervision. METHODS The revision notifications of TCM injection leaflets were compared with the existing data of TCM injection and filed information of revision. A quantitative analysis was conducted on WARNINGS, CONTRAINDICATIONS, ADVERSE REACTIONS and PRECAUTIONS in the TCM injection leaflets revision models/requirements. RESULTS Revision notifications of TCM injection leaflet had risen obviously in recent years, while the notified proportion of the varieties with few licences was low. Approximately 23.7% of the licences of notified varieties was without a filed revision, of which 82.8% needed to be renewed in 2020. Among the 30 leaflets revision models/requirements, WARNINGS almost related to anaphylactic shock. The number of system-organ classes influenced by ADVERSE REACTIONS listed was between 4 to 10, with renal toxicity and liver toxicity less mentioned. TCM syndromes appeared only in 2 revision models/requirements in CONTRAINDICATIONS. PRECAUTIONS were focused on USE IN SPECIFIC POPULATIONS and DRUG INTERACTIONS. The correlation between WARNINGS, CONTRAINDICATIONS, ADVERSE REACTIONS was low. CONCLUSION Constant revision of TCM injection leaflets needs to be made, especially aiming at those varieties with limited approvals. The enterprises should be impelled to shoulder the responsibility of leaflets revision and renewed leaflets use through legal duty specification, entire leaflets disclosure and license renew review by regulators. It is also recommended to improve the revision of ADVERSE REACTIONS, WARNINGS and CONTRAINDICATIONS according to systematic evidence-based researches, to list USE IN SPECIFIC POPULATIONS and DRUG INTERACTIONS as individual items, and to strengthen the connection between the items in the leaflets.