耐药结核病化疗过程中药品不良反应处理的专家共识

doi:10.3969/j.issn.1000-6621.2019.06.003

摘要/Abstract

摘要：

耐药结核病具有疗程长、用药种类多、不良反应发生率高的临床特征,如何正确处理药品不良反应是提高耐药结核病治疗转归的重要因素之一。本专家共识从不同药品发生不良反应的处理、各类系统不良反应的处理、药品不良反应的监测等方面进行阐述,提出了较为规范的处理方法及原则。

关键词: 结核, 抗多种药物性, 抗结核药, 药物毒性, 超敏反应, 人群监测, 处理方法

Abstract:

Drug-resistant tuberculosis (TB) has the characteristics of long treatment course, regimens with variety of drugs,high incidence rate of drug side-effect, how to treat drug side-effect correctly is one of essential factors of improving the outcome of drug-resistant tuberculosis. This expert consensus will elaborate in the treatment of side-effects from each drug and each system,treatment monitoring for drug side-effect and will provide the normative methods and principles for side-effects of drugs.

Key words: Tuberculosis, multidrug-resistant, Antitubercular agents, Drug toxicity, Hypersensitivity, Population surveillance, Treatment methods

《中国防痨杂志》编委会. 耐药结核病化疗过程中药品不良反应处理的专家共识[J]. 中国防痨杂志, 2019, 41(6): 591-603. doi: 10.3969/j.issn.1000-6621.2019.06.003

Board of Chinese Journal of Antituberculosis Editorial. Expert consensus on the solutions of drug side effects during the treatment of drug resistance tuberculosis[J]. Chinese Journal of Antituberculosis, 2019, 41(6): 591-603. doi: 10.3969/j.issn.1000-6621.2019.06.003

图/表 4

表1

表2

表3

药品不良反应监测表

监测项目	监测频率
血常规(血红蛋白、血小板、白细胞)^a	一般每月检测1次。使用利奈唑胺者开始时每周检测1次,以后每月检测1次,或根据症状调整检测频率
肝功能(天冬氨酸氨基转移酶、丙氨酸氨基转移酶)^a	长期接受吡嗪酰胺治疗或有肝损伤高危因素和(或)有肝炎症状者,每2~4周检测1次;并发HIV感染者,建议每2周1次;接受贝达喹啉治疗者每2~4周检测1次;并发病毒性肝炎者,第1个月每1~2周检测1次,以后每1~4周检测1次
血肌酐与血清钾^a	接受注射类抗结核药物治疗时,每月检测1~2次;并发HIV感染、糖尿病及其他高危患者每1~3周检测1次
血清镁和钙离子	出现低钾血症时,应注意同时检测血清镁和钙离子水平;如果使用贝达喹啉建议每2~4周检测1次;如果出现心电图异常(Q-T间期延长)者,应及时进行复查
血糖^a	使用加替沙星治疗者,治疗前快速检测血糖,以后每月检测1~2次
促甲状腺激素(TSH)	乙硫异烟胺、丙硫异烟胺和对氨基水杨酸同时使用时,每3个月检测1次;单独使用时,每6个月检测1次;对于临床上有甲状腺功能减退症状和(或)体征者每月检测1次
脂肪酶	使用利奈唑胺、贝达喹啉而出现腹痛者,为排除胰腺炎时应该进行检测;使用贝达喹啉者建议治疗前进行检测
乳酸	使用利奈唑胺或抗逆转录病毒药物治疗(ART)者出现乳酸性酸中毒症状时应该进行检测
听力测定^a	接受注射类抗结核药物者,治疗前及开始治疗后每月检测1次;每次访视注意询问患者有无听力改变,判断他们是否能够完成正常对话
视力测定^a	需长时间使用乙胺丁醇或利奈唑胺的患者,建议治疗前进行视力测定;视力或辨色能力发生可疑变化时,要进行重复检测
心电图^a	使用贝达喹啉者于治疗开始前即进行检查,以后在治疗第2、4、8、12周分别进行1次复查;并发心脏功能、甲状腺功能减退或发生电解质紊乱者,应增加检测频率
心理咨询^a	治疗前即可进行,治疗中需要按照患者病情随时进行;必要时可向心理医师咨询

表3

表4

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组别	药物名称(缩略词)
1.一线口服类抗结核药物	异烟肼(H);利福平(R);乙胺丁醇(E);吡嗪酰胺(Z);利福布汀(Rfb);利福喷丁(Rpt)
2.注射类抗结核药物	链霉素(S);卡那霉素(Km);阿米卡星(Am);卷曲霉素(Cm)
3.氟喹诺酮类药物	左氧氟沙星(Lfx);莫西沙星(Mfx);加替沙星(Gfx)
4.二线口服类抗结核药物	乙硫异烟胺(Eto);丙硫异烟胺(Pto);环丝氨酸(Cs); 特立齐酮(Trd);对氨基水杨酸(PAS);对氨基水杨酸-异烟肼(Pa)
5.其他类抗结核药物	贝达喹啉(Bdq);德拉马尼(Dlm);利奈唑胺(Lzd); 氯法齐明(Cfz);阿莫西林-克拉维酸(Amx-Clv);亚胺培南-西司他丁(Ipm-Cln);美罗培南(Mpm); 氨硫脲(Thz);克拉霉素(Clr)

组别	药物名称(缩略词)
A组:氟喹诺酮类药物	左氧氟沙星(Lfx);莫西沙星(Mfx);加替沙星(Gfx)
B组:二线注射类药物	阿米卡星(Am);卷曲霉素(Cm);卡那霉素(Km);链霉素(S)
C组:其他核心二线药物	乙硫异烟胺或丙硫异烟胺(Eto或Pto);环丝氨酸-特立齐酮(Cs-Trd);利奈唑胺(Lzd);氯法齐明(Cfz)
D组:其他药物(非MDR核心药物)
D1	吡嗪酰胺(Z);乙胺丁醇(E);高剂量异烟肼(Hh)
D2	贝达喹啉(Bdq);德拉马尼(Dlm)
D3	对氨基水杨酸(PAS);亚胺培南-西司他丁(Ipm-Cln);美罗培南(Mpm);阿莫西林-克拉维酸钾(Amx-Clv);氨硫脲^a(Thz)

不良反应类别	常用辅助治疗药物
恶心、呕吐、胃部不适	胃复安、多潘立酮、苯海拉明、奋乃静、异丙嗪、恩丹西酮,以及其他5-羟色胺3(5-HT3)受体拮抗剂
胸口灼热、反酸和消化不良	组胺2受体(H2受体)阻滞剂(雷尼替丁、西米替丁、法莫替丁等),质子泵抑制剂(奥美拉唑、兰索拉唑等)。抑酸剂可降低氟喹诺酮类药物的吸收,若化疗方案中含氟喹诺酮类药物应避免使用
腹泻	洛派丁胺、益生菌
口腔念珠菌病	制霉菌素混悬液局部涂抹,或口服氟康唑、伊曲康唑、泊沙康唑等抗真菌药物
抑郁症	选择性5-HT重摄取抑制剂(氟西汀、舍曲林),三环类抗抑郁药(阿米替林)
严重焦虑	氯羟安定、安定
失眠症	茶苯海明
精神错乱	氟哌啶醇、氯丙嗪、利培酮(也包括苯托品或比哌立登阻止椎体外束反应)
癫痫	苯妥英钠、卡马西平、丙戊酸钠、苯巴比妥
预防环丝氨酸和异烟肼所致的精神和神经性并发症	吡哆醇(维生素B6)
周围神经病变	阿米替林、加巴喷丁
前庭症状	氯苯甲嗪、晕海宁、奋乃静、盐酸异丙嗪
肌肉、骨骼痛,关节疼痛,头痛	布洛芬、对乙酰氨基酚、可待因
皮肤不良反应,瘙痒	氢化可的松乳膏、炉甘石洗剂
系统性超敏反应	抗组胺药(苯海拉明、氯苯吡胺、晕海宁)及皮质类固醇(强的松、泼尼松龙、地塞米松)
支气管痉挛	吸入性β受体阻滞剂(沙丁胺醇等),吸入皮质类固醇(倍氯米松等),口服糖皮质激素(强的松、泼尼松龙),注射类固醇药物(地塞米松、甲强龙)
甲状腺功能减退	口服左旋甲状腺素
电解质降低	根据检测结果补充钾、镁、钙(以口服或静脉用药形式)