Rui Zheng1, Liyuan Tao2, Joey S W Kwong3, Changming Zhong4, Chengyu Li5, Shiqi Chen6, Yang Sun7, Xiaoyu Zhang8, Hongcai Shang9. 1. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: zhengrui0904@163.com. 2. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China; Research Center of Clinical Epidemiology, Peking University Third Hospital, China. Electronic address: tendytly@163.com. 3. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: jswkwong@hotmail.com. 4. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: 20180931212@bucm.edu.cn. 5. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: lichengyu@bucm.edu.cn. 6. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: cheesechen@foxmail.com. 7. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: ivory10@163.com. 8. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: zbzhangxiaoyu@aliyun.com. 9. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China. Electronic address: shanghongcai@bucm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Xiyanping injection (XYP), extraction of Andrographis paniculate (Andrographis paniculata (Burm. f.) Nees, chuan xin lian), is a Chinese patent medicine approved to treat bronchitis in China. In 2017, safety incidents associated with treatment of XYP began to emerge throughout China. However, the risk factors of severity of adverse reactions by XYP remain uncertain. AIM OF THE STUDY: To determine risk factors for the severity of XYP-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: We analyzed a total of 26,317 cases of ADRs linked to the use of XYP injection in the China National Adverse Drug Reaction Monitoring Information System from 2004 to 2017. Data were analyzed with respect to age, gender, ethnicity, previous ADRs, family history of ADRs, dosage specification, medication frequency specification, body weight, route of administration, herb-drug interactions (ribavirin, cefatriaxone, penicillin sodium, ambroxol hydrochloride, clindamycin, cefoxitin sodium, azithromycin, ceftazidime, amoxicillin sodium and clavulanate potassium, levofloxacin, cefazolin sodium pentahydrate, acyclovir) by univariate analysis and multivariate analysis. Propensity score matching was used to compare severity of (general or serious) ADRs. RESULTS: We included 24,911 cases of general ADRs and 1406 cases of serious ADRs. Univariate analysis identified age (p < 0.001), body weight (p < 0.001), route of administration (p = 0.008), co-administration of XYP with ribavirin (p = 0.031) as risk factors of severity of ADRs. Multivariate analysis identified XYP + ribavirin combination (p = 0.048) and age (p < 0.001) as the independent risk factors. Upon propensity score matching, the variables were relatively balanced amongst the two groups of patients with general or severe ADRs, and the level of severity in patients who received treatment of XYP + ribavirin increased (p = 0.020). CONCLUSIONS: Age and co-administration of ribavirin may be potential risk factors for the severity of XYP-associated ADRs. This reminds us to pay more attention to the safety of elderly medication. Minimizing the herb-drug-interaction effects of XYP and ribavirin is a viable treatment target for healthcare professionals in managing serious ADRs amongst patients receiving XYP injection.
ETHNOPHARMACOLOGICAL RELEVANCE: Xiyanping injection (XYP), extraction of Andrographis paniculate (Andrographis paniculata (Burm. f.) Nees, chuan xin lian), is a Chinese patent medicine approved to treat bronchitis in China. In 2017, safety incidents associated with treatment of XYP began to emerge throughout China. However, the risk factors of severity of adverse reactions by XYP remain uncertain. AIM OF THE STUDY: To determine risk factors for the severity of XYP-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: We analyzed a total of 26,317 cases of ADRs linked to the use of XYP injection in the China National Adverse Drug Reaction Monitoring Information System from 2004 to 2017. Data were analyzed with respect to age, gender, ethnicity, previous ADRs, family history of ADRs, dosage specification, medication frequency specification, body weight, route of administration, herb-drug interactions (ribavirin, cefatriaxone, penicillin sodium, ambroxol hydrochloride, clindamycin, cefoxitin sodium, azithromycin, ceftazidime, amoxicillin sodium and clavulanate potassium, levofloxacin, cefazolin sodium pentahydrate, acyclovir) by univariate analysis and multivariate analysis. Propensity score matching was used to compare severity of (general or serious) ADRs. RESULTS: We included 24,911 cases of general ADRs and 1406 cases of serious ADRs. Univariate analysis identified age (p < 0.001), body weight (p < 0.001), route of administration (p = 0.008), co-administration of XYP with ribavirin (p = 0.031) as risk factors of severity of ADRs. Multivariate analysis identified XYP + ribavirin combination (p = 0.048) and age (p < 0.001) as the independent risk factors. Upon propensity score matching, the variables were relatively balanced amongst the two groups of patients with general or severe ADRs, and the level of severity in patients who received treatment of XYP + ribavirin increased (p = 0.020). CONCLUSIONS: Age and co-administration of ribavirin may be potential risk factors for the severity of XYP-associated ADRs. This reminds us to pay more attention to the safety of elderly medication. Minimizing the herb-drug-interaction effects of XYP and ribavirin is a viable treatment target for healthcare professionals in managing serious ADRs amongst patients receiving XYP injection.
Keywords:
Adverse drug reaction; Herb-drug interaction; Propensity score matching; Ribavirin; Risk factor; Traditional Chinese medicine injection; Xiyanping injection