PMID- 35153776 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220216 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Adverse Effects of Andrographolide Derivative Medications Compared to the Safe use of Herbal Preparations of Andrographis paniculata: Results of a Systematic Review and Meta-Analysis of Clinical Studies. PG - 773282 LID - 10.3389/fphar.2022.773282 [doi] LID - 773282 AB - Background and objective: Andrographis paniculata (AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP are often used to treat respiratory tract infections. This study aims to systematically evaluate the safety of andrographolide derivative medications and herbal preparations of AP based on clinical studies. Methods: English and Chinese databases were searched for all types of clinical studies that reported adverse drug reactions (ADRs) and adverse events (AEs) of andrographolide derivative medications and herbal preparations of AP. The ADRs and AEs were classified according to manifestations, and graded according to severity. Single-rate meta-analysis was performed for ADR incidence using R software. Results: A total of 262 studies were included, including 125 randomized controlled trials, 23 non-randomized controlled trials, 6 case series, and 108 case reports. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs. Meta-analysis showed that the ADR incidence of three most frequently used injections of andrographolide derivatives (andrographolide sulfonate, potassium sodium dehydroandrographolide succinate, and potassium dehydroandrographolide succinate) were 5.48% [95% CI (4.47%, 6.72%)], 3.69% [95% CI (2.59%, 4.94%)] and 5.33% [95% CI (3.68%, 7.72%)], respectively, which may be slightly higher than the actual ADR incidence, because only studies that reported the occurrence of ADRs or AEs were included, but studies without ADR and AE were not included. The ADRs of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Fifty-five patients experienced life-threatening anaphylactic shock, three patients died, and the causation attributed to the andrographolide derivative injection. Other ADRs were mild, moderate or medically significant. Nine herbal preparations of AP were tested in 10 studies, and the reported ADRs were mainly mild to moderate gastrointestinal, skin and subcutaneous tissue disorders. Except for five patients using andrographolide derivative injections eventually died, most of the ADRs were alleviated after drug withdrawal and symptomatic treatment. Conclusions: The ADRs of andrographolide derivative medications are few, but can be life-threatening, mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Injections of andrographolide derivatives should be used with caution. Herbal preparations of AP are essentially safe. Systematic Review Registration: [website], identifier [registration number]. CI - Copyright (c) 2022 Shang, Shen, Stub, Zhu, Qiao, Li, Wang, Li and Liu. FAU - Shang, Ya-Xi AU - Shang YX AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Shen, Chen AU - Shen C AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Stub, Trine AU - Stub T AD - The National Research Center in Complementary and Alternative Medicine (NAFKAM), Department of Community Medicine, Faculty of Health Science, UiT, The Arctic University of Norway, Tromso, Norway. FAU - Zhu, Si-Jia AU - Zhu SJ AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Qiao, Shu-Yu AU - Qiao SY AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Yu-Qi AU - Li YQ AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Wang, Rui-Ting AU - Wang RT AD - Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Jing AU - Li J AD - Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic Disease, China National Research Institute of Food and Fermentation Industries Co, Ltd., Beijing, China. FAU - Liu, Jian-Ping AU - Liu JP AD - Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. LA - eng PT - Journal Article PT - Review DEP - 20220128 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8831758 OTO - NOTNLM OT - Andrographis paniculata OT - adverse drug reaction OT - adverse event OT - andrographolide OT - clinical study OT - drug safety COIS- Author JL was employed by the company China National Research Institute of Food and Fermentation Industries Co, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/15 06:00 MHDA- 2022/02/15 06:01 PMCR- 2022/01/28 CRDT- 2022/02/14 05:29 PHST- 2021/09/09 00:00 [received] PHST- 2022/01/10 00:00 [accepted] PHST- 2022/02/14 05:29 [entrez] PHST- 2022/02/15 06:00 [pubmed] PHST- 2022/02/15 06:01 [medline] PHST- 2022/01/28 00:00 [pmc-release] AID - 773282 [pii] AID - 10.3389/fphar.2022.773282 [doi] PST - epublish SO - Front Pharmacol. 2022 Jan 28;13:773282. doi: 10.3389/fphar.2022.773282. eCollection 2022.