结核病共病治疗中利福霉素类药物合理应用专家共识

doi:10.19982/j.issn.1000-6621.20250254

摘要/Abstract

摘要：

结核病常与多种慢性疾病共存,需联合用药。利福霉素类抗结核药物与多种共病治疗药物存在显著相互作用,可能导致后者减效、失效或毒性增加,但目前缺乏相关临床指导意见。为提升临床医生对利福霉素类药物与共病治疗药物相互作用的认识并指导其合理应用,本共识基于国内外文献、药品说明书及循证证据评价,经3次集中研讨及修订达成一致意见。本共识涵盖利福霉素类药物概述、相互作用机制、临床应用指导原则,以及对常见共病治疗药物相互作用的证据总结及调整建议,旨在为结核病共病患者提供安全有效的利福霉素类药物治疗方案,并为临床应用提供实践依据。

关键词: 利福霉素类, 结核, 共病现象, 治疗应用, 指南

Abstract:

Tuberculosis frequently coexists with multiple chronic diseases, necessitating combination pharmacotherapy. Rifamycin-class anti-tuberculosis agents exhibit clinically significant interactions with many drugs used to treat comorbidities, potentially reducing their efficacy, causing treatment failure, or increasing toxicity. However, evidence-based clinical guidance on these interactions is currently lacking. To improve clinicians’ understanding of the interactions between rifamycins and medications for comorbid conditions and to support their rational use, this consensus statement was developed. It was based on a systematic review of domestic and international literature, drug-label information, and appraisal of the best available evidence, and was finalized after three rounds of focused discussion and revision. The document covers an overview of rifamycins agents, their mechanisms of drug-drug interaction, guiding principles for clinical application, and a comprehensive summary of evidence on interactions with commonly prescribed comorbidity medications, together with practical dose-adjustment recommendations. The aim is to provide safe and effective rifamycin-based therapeutic regimens for tuberculosis patients with comorbidities and to offer an actionable reference for clinical practice.

Key words: Rifamycins, Tuberculosis, Comorbidity, Therapeutic uses, Guidebooks

中图分类号:

深圳市第三人民医院(国家感染性疾病临床医学研究中心), 中国防痨协会结核病与糖尿病专业分会, 中国防痨协会多学科诊疗专业分会. 结核病共病治疗中利福霉素类药物合理应用专家共识[J]. 中国防痨杂志, 2025, 47(11): 1391-1415. doi: 10.19982/j.issn.1000-6621.20250254

National Clinical Research Center for Infectious Disease/Shenzhen Third People's Hospital , Tuberculosis and Diabetes Branch of Chinese Antituberculosis Association , Multidisciplinary Diagnosis and Treatment Branch of Chinese Antituberculosis Association . Expert consensus on the rational use of rifamycins in the treatment of tuberculosis with comorbidities[J]. Chinese Journal of Antituberculosis, 2025, 47(11): 1391-1415. doi: 10.19982/j.issn.1000-6621.20250254

图/表 17

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糖尿病常用药物与利福霉素类药物的相互作用证据及合用推荐

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
二甲双胍	降糖作用增强	-	-	监测血糖,必要时减少二甲双胍剂量	1B
沙格列汀	沙格列汀AUC降低73%,峰浓度降低53%,作用不受影响	-	-	监测血糖,与利福平、利福喷丁、利福布汀谨慎合用	1B
利格列汀	利格列汀AUC降低约40%	-	-	监测血糖,必要时增加利格列汀剂量,或将利福平更换为利福喷丁、利福布汀	2B
维格列汀	无报道	-	-	与利福平、利福喷丁、利福布汀谨慎合用	2C
卡格列净	卡格列净AUC降低51%	-	-	监测血糖,必要时增加卡格列净剂量,或将利福平更换为利福喷丁、利福布汀	1B
达格列净	达格列净AUC降低22%,峰浓度降低7%	-	-	与利福平、利福喷丁、利福布汀谨慎合用,不调整剂量	1B
格列齐特	格列齐特AUC降低70%	-	-	监测血糖,必要时增加格列齐特剂量,或将利福平更换为利福喷丁、利福布汀	1B
格列美脲	格列美脲AUC降低34%	-	-	监测血糖,必要时增加格列美脲剂量,或将利福平更换为利福喷丁、利福布汀	1B
那格列奈	那格列奈AUC降低24%	-	-	监测血糖,必要时增加那格列奈剂量,或将利福平更换为利福喷丁、利福布汀	1B
瑞格列奈	瑞格列奈AUC降低57%	-	-	监测血糖,增加瑞格列奈的给药剂量,或将利福平更换为利福喷丁、利福布汀	1B
吡格列酮	吡格列酮AUC降低54%	-	-	监测血糖,增加吡格列酮剂量,最大剂量不超过45mg;当使用45mg吡格列酮,血糖仍控制不理想时,建议考虑将利福平更换为利福喷丁、利福布汀继续监测,或更换其他降糖方案	2B 1B
罗格列酮	罗格列酮AUC降低54%~65%			监测血糖;必要时更换降糖药物;或将利福平更换为利福喷丁、利福布汀	2B
多格列艾汀	多格列艾汀预计AUC降低51%以上			监测血糖;必要时更换降糖药物;或将利福平更换为利福喷丁、利福布汀	2C
利拉鲁肽	相互作用可能性极低	-	-	与利福平、利福喷丁、利福布汀谨慎合用,监测胃肠道不良反应	1C
司美格鲁肽	相互作用可能性极低	-	-	与利福平、利福喷丁、利福布汀谨慎合用,监测胃肠道不良反应	1C

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表5

常用降血压药物与利福霉素类药物的相互作用及合用推荐

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
螺内酯	可能存在潜在的相互作用	-	-	与利福平、利福喷丁、利福布汀谨慎合用,监测治疗反应	1D
硝苯地平	硝苯地平AUC降低60%,高血压恶化增加	-	-	与利福平、利福喷丁、利福布汀避免合用	1C
氨氯地平	氨氯地平血药浓度降低,肾功能损伤者降低81.7%±20.6%	-	-	密切监测血压;与利福平避免合用,尤其是肾功能损伤者。与利福喷丁、利福布汀谨慎合用。确需使用利福平时更换降压药物,或增加氨氯地平剂量	1A
二氢吡啶类钙通道阻滞剂 (尼卡地平、尼莫地平、非洛地平等)	二氢吡啶类血药浓度剧烈降低	-	-	密切监测血压;与利福平避免合用,与利福喷丁、利福布汀谨慎合用。更换降压药物,确需使用利福平时增加本类药物剂量,或将利福平更换为利福喷丁、利福布汀	1A
厄贝沙坦	对厄贝沙坦的影响可能较小	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
氯沙坦	氯沙坦AUC降低35%,活性代谢物AUC降低40%	-	-	监测血压;与利福平、利福喷丁、利福布汀谨慎合用,在出现血压升高时,考虑增加氯沙坦的剂量,或将利福平更换为利福喷丁、利福布汀	1B
沙库巴曲缬沙坦	影响较小	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
美托洛尔	肾功能不全者美托洛尔药物浓度降低91.9%±16.2%	-	-	监测血压;肾功能不全者,美托洛尔与利福平避免合用。确需与利福平合用时,增加美托洛尔剂量,或将利福平更换为利福喷丁、利福布汀	2B
比索洛尔	比索洛尔AUC降低34%	-	-	监测血压;仅在治疗反应不佳时,考虑增加比索洛尔的剂量,或将利福平更换为利福喷丁、利福布汀	2B
普萘洛尔	普萘洛尔血药浓度降低20%~40%,预计会发生临床疗效减弱	-	-	建议更换为同类药物,或将利福平更换为利福喷丁、利福布汀,并监测治疗反应	2C
特拉唑嗪	可能不存在有意义的药物相互作用	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
福辛普利	可能不存在有意义的药物相互作用	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
卡托普利	可能不存在有意义的药物相互作用	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
贝那普利	可能不存在有意义的药物相互作用	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C

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常见抗肿瘤药物与利福霉素类药物的相互作用及合用推荐

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
奥希替尼	奥希替尼AUC降低约78%	-	-	与利福平、利福喷丁、利福布汀避免合用,或按说明书增加奥希替尼剂量	1B
伏美替尼	伏美替尼AUC降低86%,总活性物质AUC降低62%	-	-	与利福平、利福喷丁、利福布汀避免合用,或按说明书增加伏美替尼剂量	1B
吉非替尼	吉非替尼AUC降低83%	-	-	与利福平、利福喷丁、利福布汀避免合用,或按说明书增加吉非替尼剂量	1B
厄洛替尼	厄洛替尼AUC降低约67%	-	-	与利福平、利福喷丁、利福布汀避免合用,或按说明书增加厄洛替尼剂量	1B
克唑替尼	克唑替尼AUC降低82%,活性代谢物AUC降低94%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
伊马替尼	伊马替尼峰浓度降低54%,AUC降低74%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
尼洛替尼	尼洛替尼AUC降低80%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
瑞戈非尼	瑞戈非尼AUC降低50%,代谢物AUC升高264%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
阿帕替尼	阿帕替尼AUC降低83%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
多纳非尼	预计药物相互作用较小	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
仑伐替尼	预计仅有轻微影响			与利福平、利福喷丁、利福布汀谨慎合用	1C
培美曲塞	预计影响较小	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
铂类	预计影响较小			与利福平、利福喷丁、利福布汀谨慎合用	1C
紫杉醇	紫杉醇的药物暴露可能降低	-	-	与利福平、利福喷丁、利福布汀谨慎合用,关注其疗效下降	1C
多西他赛	多西他赛的药物暴露可能降低	-	-	与利福平、利福喷丁、利福布汀谨慎合用,关注其疗效下降	1C
吉西他滨	-	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
氟尿嘧啶	-	-	-	与利福平、利福喷丁、利福布汀谨慎合用	1C
他莫昔芬	他莫昔芬AUC降低86%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
托瑞米芬	托瑞米芬AUC降低87%	-	-	与利福平、利福喷丁、利福布汀避免合用	1B
伊立替康	伊立替康活性代谢物SN-38的AUC降低20%,SN-38G的AUC降低58.8%	-	-	与利福平、利福喷丁、利福布汀谨慎合用	2C

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表16

抗HIV病毒药物与利福霉素类药物的相互作用及合用推荐

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
多替拉韦	多替拉韦AUC下降54%	多替拉韦谷浓度下降53%	多替拉韦AUC下降5%	与利福平合用时,多替拉韦剂量增加到2次/d。与利福喷丁合用时,如利福喷丁给药频次为1次/d,需增加多替拉韦剂量;如利福喷丁给药频次为1次/周,则无需调整剂量;如利福喷丁给药频次为2次/周,需加强疗效监测。多替拉韦与利福布汀合用无需调整剂量	1B
拉替拉韦	拉替拉韦AUC下降40%	拉替拉韦AUC无明显变化	-	与利福平合用时,拉替拉韦剂量增加到2次/d,与利福喷丁、利福布汀合用无需调整剂量	1B
比克替拉韦	比克替拉韦AUC下降75%	-	比克替拉韦AUC下降38%	与利福平、利福喷丁、利福布汀避免合用	1B
拉米夫定	预计不存在有临床意义的相互作用	预计不存在有临床意义的相互作用	预计不存在有临床意义的相互作用	与利福平、利福喷丁、利福布汀谨慎合用	1B
阿巴卡韦	预计不存在有临床意义的相互作用	预计不存在有临床意义的相互作用	预计不存在有临床意义的相互作用	与利福平、利福喷丁、利福布汀谨慎合用	1B
多拉韦林	多拉韦林AUC下降88%	-	多拉韦林AUC降低50%	与利福平、利福喷丁避免合用,与利福布汀合用,多拉韦林给药增加到2次/d	1B
利匹韦林	利匹韦林AUC下降80%	-	利匹韦林AUC下降43%	与利福平、利福喷丁避免合用,与利福布汀合用,利匹韦林给药量增加到50mg(1次/d)	1B
依非韦伦	依非韦伦AUC降低26%	依非韦伦表观清除率增加4%	利福布汀AUC下降38%	与利福平合用,体质量50kg以上者增加依非韦伦的剂量到800mg(1次/d);与利福布汀合用,利福布汀剂量增加50%;与利福喷丁合用,无需调整剂量	1B
达芦那韦/ 考比司他	预计达芦那韦、考比司他的血药浓度降低	达芦那韦AUC下降71%	预计达芦那韦、考比司他的血药浓度降低,利福布汀的暴露增加	达芦那韦/考比司他与利福平、利福喷丁避免合用,与利福布汀合用时,减少利福布汀的剂量到150mg(1次/2d)	1B

表16

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证据级别	具体描述	研究类型	表达字母
高级证据	非常有信心;真实效应接近评估的结果	随机对照试验;质量升高二级的观察性研究	A
中级证据	对效应估计有中等信心;真实效应可能接近评估的结果,但也可能存在差异	质量降低一级的随机对照试验;质量升高一级的观察性研究	B
低级证据	对效应的评估确信度较低;真实效应可能与评估的结果不同,进一步研究可能对现有评估产生重要影响	质量降低二级的随机对照试验;观察性研究	C
极低证据	对效应的估计几乎没有信心;真实效应可能与评估结果大不相同	病例系列和病例报告;基于机制的药理作用推测	D

推荐强度	具体描述	表达数字
支持使用某项干预措施的强推荐	评价者确信干预措施利大于弊	1
支持使用某项干预措施的弱推荐	利弊不确定或无论高低质量的证据均显示利弊相当	2

代谢特征	利福平	利福喷丁	利福布汀
成人常用量	10~20mg/kg,1次/d, 不超过600mg	600mg,一周1~2次, 体质量<55kg者酌情减量	0.15~0.3g,1次/d
口服生物利用度(%)	68	未知	20
达峰时间(h)	1.5~2.0	5~6	2.5~4.0
峰浓度(mg/L)	8~20	8~30	0.2~0.6
食物的影响	AUC降低6%, 峰浓度降低36%	AUC升高40%~50%, 峰浓度升高44%	AUC、峰浓度不变, 达峰时间增加
抑酸剂的影响	无影响	未知	无影响
主要代谢途径	去乙酰化、水解	去乙酰化、水解	羟基化、去乙酰化
血清半衰期(h)	2~5	14~18	32~67
对细胞色素P450酶的诱导作用	显著	中等	弱
自身诱导作用	有	有	有
给予细胞色素P450酶抑制剂时AUC的变化	无影响	无影响	升高293%

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
华法林	华法林AUC降低15%~74%	-	-	与利福平避免合用,与利福喷丁、利福布汀合用时监测国际标准化比值,增加华法林的剂量	1A
利伐沙班	利伐沙班AUC降低49%	-	-	与利福平避免合用。在有条件进行利伐沙班血药浓度检测时,考虑增加利伐沙班的剂量。与利福喷丁、利福布汀谨慎合用	1B
艾多沙班	艾多沙班AUC降低34%	-	-	与利福平避免合用。在有条件进行艾多沙班血药浓度检测时,建议考虑增加艾多沙班的剂量。与利福喷丁、利福布汀谨慎合用	2C
达比加群酯	达比加群AUC降低67%;C_max降低65%~70%	-	达比加群 AUC降低 20%	与利福平避免合用,与利福布汀谨慎合用。在可以选择利福布汀时,避免使用利福喷丁	1C

药物	利福平	利福喷丁	利福布汀	推荐意见	证据等级
泼尼松龙	泼尼松龙AUC降低50%~66%	-	泼尼松龙 AUC降低 33%	增加糖皮质激素的剂量。合用利福平时,糖皮质激素剂量增加50%;合用利福布汀时,糖皮质激素剂量增加33%	2B
环孢素	环孢素血药浓度降低	环孢素暴露降低	-	与利福平、利福喷丁避免合用,与利福布汀谨慎合用,无论使用何种利福霉素,都需监测环孢素的血药浓度,调整剂量	1B
他克莫司	他克莫司血药浓度降低约80%	-	他克莫司血药浓度降低	与利福平避免合用,与利福喷丁、利福布汀谨慎合用,无论使用何种利福霉素,都需密切监测他克莫司谷浓度,根据血药浓度增加他克莫司剂量,都需密切监测移植物功能	1B
西罗莫司	西罗莫司AUC降低82%	-	-	与利福平、利福喷丁避免合用,与利福布汀谨慎合用	1B
依维莫司	谷浓度/剂量比例降低87%~97%	-	-	与利福平、利福喷丁、利福布汀避免合用。确有必要合用时,根据血药浓度增加依维莫司的剂量	1C
吗替麦考酚酯、麦考酚钠	吗替麦考酚酯活性代谢产物霉酚酸AUC降低70%	-	-	与利福平避免合用,与利福喷丁、利福布汀谨慎合用,无论使用何种利福霉素,都需监测暴露水平,调整剂量	1B