Expert consensus of clinical application of fixed-dose combination formulations

doi:10.3969/j.issn.1000-6621.2020.09.001

Abstract

Abstract:

The global modern tuberculosis control strategy puts forward that the anti-tuberculosis drugs should be continuously supplied to the patients with pulmonary tuberculosis, and the standardized short-term chemotherapy regimen and the whole-course management should be implemented to the patients with new pulmonary tuberculosis. The purpose is to improve the regular treatment rate and cure rate of the patients with pulmonary tuberculosis. In order to further improve the treatment compliance of patients with tuberculosis, reduce the number of drugs taken by patients each time, simplify the prescription of medicine prescribed by doctors, and prevent the occurrence of drug-resistant tuberculosis caused by unreasonable prescription and dosage. In 1994, WHO and IUATLD recommended the use of fixed dose combination (FDC) of anti-tuberculotic drugs in patients with tuberculosis. Since the beginning of this century, China had carried out a number of implementation studies on the application of FDC consecutively in different provinces. The results show the feasibility and effectiveness of FDC in the treatment of tuberculosis, and provide an important scientific basis for FDC to be included in the national tuberculosis control program. This consensus has been repeatedly discussed by experts in the fields of tuberculosis prevention and control, clinicians and researchers. Based on the significance of use, pharmacodynamics and pharmacokinetics, a number of application research results of FDC, preparation types and specifications of FDC, and suggestions for clinical use of FDC in China, the experts formed ‘the consensus on clinical use of fixed dose combinations of anti-tuberculosis drugs’ which provides reference for formulating the use strategy of anti-tuberculosis drugs and the treatment of tuberculosis patients in China.

Key words: Antibiotics, antituberculosis, Fixed dose combination, Therapeutic uses, Expert consensus

Academic Working Committee of Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis . Expert consensus of clinical application of fixed-dose combination formulations[J]. Chinese Journal of Antituberculosis, 2020, 42(9): 885-893. doi: 10.3969/j.issn.1000-6621.2020.09.001

Figures/Tables 6

References 30

[1]	World Health Organization. Global tuberculosis report 2019. Geneva: World Health Organization, 2019.
[2]	The promise and reality of fixed-dose combinations with rifampicin. A joint statement of the International Union Against Tuberculosis and Lung Disease and the Tuberculosis Programme of the World Health Organization.Tubercule Lung Dis, 1994,75(3):180-181. doi: 10.1016/0962-8479(94)90004-3.
[3]	Blomberg B, Spinaci S, Fourie B, et al. The rational for recom-mending fixed-dose combination tablets for treatment of tuberculosis. Bull World Health Organ, 2001,79(1):61-68. URL pmid: 11217670
[4]	李运葵, 何金戈, 李婷, 等. 抗结核固定剂量复合制剂治疗初治肺结核患者的不良反应监测结果分析. 中国防痨杂志, 2016,38(6):465-470. doi: 10.3969/j.issn.1000-6621.2016.06.009. doi: 10.3969/j.issn.1000-6621.2016.06.009 URL
[5]	李运葵, 何金戈, 李婷, 等. 四川省抗结核固定剂量复合制剂与板式组合药治疗效果分析. 预防医学情报杂志, 2016,32(4):359-364.
[6]	孔雯, 刘巧. 我省抗结核固定剂量复合制剂使用情况分析. 临床肺科杂志, 2014,19(7):1275-1277. doi: 10.3969/j.issn.1009-6663.2014.07.039.
[7]	张国钦, 商健, 张玉华, 等. 天津市试点推行抗结核固定剂量复合制剂(FDC)应用效果分析. 现代预防医学, 2014,41(14):2661-2664,2666.
[8]	中华人民共和国国务院办公厅. 全国结核病防治规划(2011—2015). 国办发〔2011〕53号. 2011-11-17.
[9]	刘勇, 张智洁, 王群, 等. 抗结核药复方制剂的体外药效学研究. 中华医院感染学杂志, 2001,11(6):460-461,477. doi: 10.3321/j. issn:1005-4529.2001.06.031.
[10]	赵伟杰, 李惠文, 梁桂芳, 等. 国产含利福平复方制剂药效学及药动学研究. 中国药师, 2007,10(7):637-640. doi: 10.3969/j.issn.1008-049x.2007.07.006.
[11]	朱莉贞, 严碧涯, 马伟路. 固定剂量复合剂卫非特/卫非宁治疗结核病的临床对照研究. 中华结核和呼吸杂志, 1998,21(11):645-647.
[12]	成诗明, 王黎霞, 陈明亭, 等. 固定剂量复合制剂在国家结核病防治规划中的应用研究报告. 北京: 中国协和医科大学出版社, 2010.
[13]	谭卫国, 杨应周, 吴清芳, 等. 抗结核固定剂量复合制剂与板式组合药物治疗肺结核效果分析对比. 中国防痨杂志, 2007,29(2):117-121.
[14]	钟球, 高翠南, 方兰君, 等. 四联抗结核固定剂量复合制剂的临床疗效研究. 中国防痨杂志, 2010,32(3):162-167.
[15]	Becker C, Dressman JB, Junginger HE, et al. Biowaiver mono-graphs for immediate release solid oral dosage forms: rifam-picin. J Pharm Sci, 2009,98(7):2252-2267. doi: 10.1002/jps.21624. URL pmid: 19160441
[16]	兰静, 胡昌勤. 制剂中利福平晶型的确定. 中国抗生素杂志, 2003,28(6):347-350.
[17]	Singh S, Mariappan TT, Sharda N, et al. The reason for an increase in decomposition of rifampicin in the presence of isonia-zid under acid conditions[J/OL]. Pharmacy Pharmacol Commun, 2000,6(9): 405-410. https://onlinelibrary.wiley.com/doi/abs/10.1211/146080800128736277.
[18]	Bhutani H, Singh S, Jindal KC, et al. Mechanistic explanation to the catalysis by pyrazinamide and ethambutol of reaction between rifampicin and isoniazid in anti-TB FDCs. J Pharm Biomed Anal, 2005,39(5):892-899. doi: 10.1016/j.jpba.2005.05.015. doi: 10.1016/j.jpba.2005.05.015 URL pmid: 15978767
[19]	郭善斌, 肇丽梅, 邱枫, 等. 异福酰胺片人体生物利用度和药代动力学研究. 中国药房, 2003,14(2):95-97.
[20]	Xu J, Jin H, Zhu H, et al. Oral bioavailability of rifampicin, isoniazid, ethambutol, and pyrazinamide in a 4-drug fixed-dose combination compared with the separate formulations in healthy Chinese male volunteers. Clin Ther, 2013,35(2):161-168. doi: 10.1016/j.clinthera.2013.01.003. doi: 10.1016/j.clinthera.2013.01.003 URL pmid: 23410999
[21]	Zhu H, Guo SC, Hao LH, et al. Relative bioavailability of rifampicin in four Chinese fixed-dose combinations compared with rifampicin in free combinations. Chin Med J (Engl), 2015,128(4):433-437. doi: 10.4103/0366-6999.151061.
[22]	郭少晨, 朱慧, 徐建, 等. 两种国产抗结核固定剂量复合剂中利福平的药代动力学和生物等效性研究. 中国防痨杂志, 2014,36(12):1075-1079. doi: 10.3969/j.issn.1000-6621.2014.12.015. doi: 10.3969/j.issn.1000-6621.2014.12.015 URL
[23]	张斯钰, 白丽琼, 谭红专, 等. Morisky 服药依从性量表在肺结核患者中的应用. 中国防痨杂志, 2010,32(9):527-530.
[24]	张斯钰, 白丽琼, 谭红专, 等. 初治涂阳肺结核患者服用固定剂量复合制剂与板式组合药的疗效比较. 中国防痨杂志, 2011,33(10):655-658.
[25]	王宇. 全球基金结核病控制项目在中国——成就与经验. 北京: 人民卫生出版社, 2015.
[26]	周宇辉, 刘剑君. 创新结核病控制——中盖结核病项目三期典型实践. 北京: 人民卫生出版社, 2019.
[27]	王倪, 周林, 池俊英, 等. 不同服药方式抗结核固定剂量复合剂的疗效与不良反应分析. 现代预防医学, 2012,39(23):6275-6277.
[28]	周林, 王倪, 刘二勇, 等. 5981例肺结核患者服用抗结核固定剂量复合制剂所致肝损伤分析. 中国防痨杂志, 2014,36(4):256-259. doi: 10.3969/j.issn.1000-6621.2014.04.007. doi: 10.3969/j.issn.1000-6621.2014.04.007 URL
[29]	周林, 王倪. 抗结核药品管理手册. 2版. 北京: 人民军医出版社, 2011.
[30]	中华人民共和国国家卫生健康委员会办公厅. 中国结核病预防控制工作技术规范(2020年版). 国卫办疾控函〔2020〕279号. 2020-04-02.

化疗方案	强化期(连续治疗2个月)		继续期(连续治疗4个月)
化疗方案	规格	用法	规格	用法
方案1	H 75mg,R 150mg,Z 400mg,E 275mg	每日	H 100mg, R 150mg	每日
方案2	H 120mg,R 120mg,Z 400mg,E 250mg	隔日	H 200mg, R 200mg	隔日
方案3	H 75mg,R 150mg,Z 400mg,E 275mg	每日	H 75mg, R 150mg	每日
方案4	H 75mg,R 150mg,Z 400mg,E 275mg	每日	H 150mg, R 300mg	每日
方案5	H 80mg,R 120mg,Z 250mg	每日	H 100mg, R 150mg	每日
方案6	H 80mg,R 120mg,Z 250mg	每日	H 150mg, R 300mg	每日
方案7	H 80mg,R 120mg,Z 250mg	每日	H 75mg, R 150mg	每日

化疗方案	强化期(连续治疗2个月)		继续期(连续治疗4个月)
化疗方案	规格	用法	规格	用法
方案1	H 75mg,R 150mg, Z 400mg,E 275mg	每日	H 150mg, R 300mg	每日
方案2	H 120mg,R 120mg, Z 400mg,E 250mg	隔日	H 200mg, R 200mg	隔日
方案3	H 75mg, R 150mg,Z 400mg,E 275mg	每日	H 75mg, R 150mg	每日
方案4	H 75mg, R 150mg,Z 400mg,E 275mg	每日	H 100mg, R 150mg	每日
方案5	H 75mg, R 150mg,Z 400mg,E 275mg	每日	H 200mg, R 200mg	隔日

种类	剂型	规格	用法
H-R	片剂/胶囊	R 150mg,H 75mg	每日服药
		R 150mg,H 100mg
		R 300mg,H 150mg
H-R-Z	片剂/胶囊	R 120mg,H 80mg,Z 250mg	每日服药
		R 75mg,H 50mg,Z 250mg
		R 60mg,H 40mg,Z 125mg
H-R-Z-E	片剂	H 75mg,R 150mg,Z 400mg,E 275mg	每日服药
		H 37.5mg,R 75mg,Z 200mg,E 137.5mg
H-R-Z-E	片剂	H 120mg,R 120mg,Z 400mg,E 250mg	隔日服药
H-R-E	片剂	H 120mg,R 120mg,E 250mg
H-R	片剂	H 200mg,R 200mg

规格	患者体质量(kg)
规格	30~	38~	55~	≥71
H 75mg,R 150mg,Z 400mg,E 275mg	2片/d	3片/d	4片/d	5片/d
H 37.5mg,R 75mg,Z 200mg,E 137.5mg	4片/d	6片/d	8片/d	10片/d

规格	患者体质量(kg)
规格	<50	≥50
H 150mg,R 300mg	不选择	2片/d
H 100mg,R 150mg	3片/d	不选择
H 75mg,R 150mg	不选择	4片/d