Objective To improve the knowledge of lung injury induced by rituximab. Methods Clinical data of 5 lymphoma patients with lung injury caused by rituximab chemotherapy were analyzed. Results Five patients received chemotherapy including rituximab, and had fever, cough and dyspnea after 3 to 5 chemotherapy cycles. Chest CT showed bilateral diffuse interstitial infiltrates. All 5 cases experienced hypoxemia or respiratory failure. Clinical symptoms were improved 3 to 5 days after the treatment of glucocorticoids, and pulmonary lesions were significantly alleviated 1 to 2 weeks after the treatment. According to the literature, the incidence rate of lung injury caused by rituximab was 0. 03% to 4. 9%, which has increased recently. Conclusions With the comprehensive application of rituximab, lung injury caused by this drug is not rare. The good prognosis depends on early diagnosis and treatment by further recognition of the side effect of rituximab.
Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned—the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Medicine Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI.
A total of 109 varieties of Chinese medicine injections have been approved by the State Food and Drug Administration of China, all of which have the potential to induce adverse drug reactions (ADRs). Major ADRs include systemic anaphylaxis, anaphylactic shock, acute intravascular hemolysis, hepatorenal damage, skin lesion, cardiac damage, respiratory system injury, and gastrointestinal disorders. Contributing factors of ADRs include healthcare workers’ inadequate attention to ADRs of Chinese medicine injections, complex ingredients, allergic uncertainties, and inappropriate drug use in children and the aged. To decrease ADRs resulting from Chinese medicine injections, it is essential to improve the selection of drug indications, delivery of proper dosage regimens, compliance with drug instructions, and selection of solvents for the drugs.
Objectives To systematically evaluate the clinical characteristics of adverse drug reactions (ADRs) caused by Shuanghuanglian Injection (SHLI) and to provide reference for post-market evaluation and clinical application of SHLI. Methods We searched electronic databases such as the Chinese National Knowledge Infrastructure (CNKI, 1979.1-2009.9), the Chinese Science and Technology Journal Full-text Database (VIP, 1989.1-2009.9), and the Chinese Biomedical Disc (CBMdisc, 1978.1-2009.9). ADR cases were analyzed according to occurrences categorized. Available data was assessed using the Chi-square test including relative ratios (RR) with 95% confidence intervals (95%CI). Different medicine combinations and comparisons between SHL powder injection and SHL injection were calculated using the statistical software Stata 9.1. Results (1) A total of 452 articles were included with a total of 2 799 ADR cases reported. Case reports were the main design type of included literature, which accounted for 84.51%. According to 31165 cases of SHLI treatment and 1 013 corresponding ADRs, the incidence of SHLI ADR was calculated as 3.25%. (2) The ratio of male to female in the reported ADR cases was 1.13׃1. (3) Allergy to Penicillin, which accounted for 13.38% of the total cases, was at the top for past allergic history, followed by sulfonamides and asthma (2.68%). (4) In terms of disease treated respiratory disease accounted for 91.75% of all cases of SHLI ADRs, followed by digestive diseases (5.17%), and urinary diseases (1.11%). (5) Penicillins were the most common combination choice with SHLI, and such combination showed higher ADR risk than SHLI used alone [RR=3.14, 95%CI (2.58, 3.81)]. (6) Multiple systems/organs were involved in SHLI ADRs, and were ranked downwards according to proportion as: skin, digestive system, general reactions, respiratory system, nervous system, cardiovascular system, local reactions, urinary system, hematologic system and others. (7) According to the WHO ADR Classification Criteria, ADR cases were divided into four grades. There were 6.36%, 5.48%, 45.62%, and 2.12% cases of Grade Ⅰ, Ⅱ, Ⅲ and Ⅳ , respectively. And the prognoses of the rest 52.42% cases were reported unclearly. (8) All cases of death were caused by allergic shock, except for one, which was caused by myocardial infarction induced by pain at the injection site. The fastest ADR case occurred 1 minute after being injected. (9) There was a remarkable difference (Plt;0.05) in the rate of ADR caused by SHLI in power form (2.25%) and as a solution (4.14%). Conclusion The clinical manifestations of ADRs caused by SHLI mainly include skin allergic reactions and gastrointestinal reactions. There is an increased risk of ADR induced by combined uses of SHLI and other drugs, especially antibiotics. Compared to the solution, the powder has lower ADR occurrence and higher safety with statistical significance. We propose strengthening management and surveillance on SHLI from manufacturing to application, and improving the level of the risk management for post-market drugs.
Objectives We conducted a literature review of 33 kinds of Traditional Chinese medicine injections (CMIs) on the national essential medicine list (2004 edition) of China in ADR articles to retrieve basic ADR information and research trends related to CMIs and to provide evidence for the research and development as well as the rational use of CMIs, particularly pharmacovigilance and risk management of CMIs. Methods We electronically searched Chinese Biomedical Literature Database (CBM, Jan. 1978-April 2009), the China National Knowledge Infrastructure Database (CNKI, Jan. 1979-April 2009), Chinese Science and Technology Periodical Database (VIP, Jan. 1989-April 2009) and the Traditional Chinese Medicine Database (Jan. 1984 April 2009). We also retrieved the websites of Ministry of Health and State Food and Drug Administration, to collect data about CMIs ADRs reports and regulations from “Newsletter of Adverse Drug Reactions” (Issue 1 to 22). Then we descriptively analyzed all the results on the year published, periodicals and types of study design of included ADR literatures, the major CMIs as well as the regulations about their ADRs. Results (1) There were 5 405 citations found in total and 2160 were removed because of duplication. After screening the title, abstract and full text of the selected papers, 1 010 studies finally met the eligible criteria. (2) The total and cumulative amount of research articles published about CMIs ADRs significantly increases over time. (3) The included 1,010 articles were scattered among 297 periodicals. A total of 55 journals on pharmaceutical medicine, containing 399 articles, accounted for 39.50% of total; 64 journals on traditional Chinese medicine and pharmaceutical medicine, containing only 197 articles, amounted for 19.50% of total. Only 22 periodicals were included on the core journals of the Beijing University List (2008 edition) (8.94% of the total journals in the list), which published 129 articles (12.77% of the total articles published). (4) We categorized the articles included into eight categories based on their content and study methodology. There were: 348 case reports and 254 case series which accounted for 34.46% and 25.15% of the total articles, 119 overviews (11.78%), 116 randomized controlled trials (11.49%), 78 cross-sectional studies (7.72%), 61 ADR literature analyses (6.04%), and 28 non-randomized controlled clinical studies (2.77%). (5) In the three of top ten journals, "Adverse Drug Reactions Journal", "China Medical Herald", and "Chinese Pharmaceuticals" published literature accounted for 5.84%, 3.76% and 2.67% of the total respectively. (6) The reports of ADRs to Shuanghuanglian, Qingkailing and Yuxingcao injections were the most in all reports for CMIs (All the three injections had more than 200 articles, accounting for 41.95% of the total). The Ministry of Health and the State Food and Drug Administration took measures to supervise them. (7) The four kinds of CMIs (Shuanghuanglian, Ciwujia, Yuxingcao, and Yinzhihuang injections) among the top 5 reported ADR literatures were removed from the market or were suspended for sale. The varieties and numbers of reports for CMIs ADRs have relationship with the supervision to them. Conclusions (1) Articles published on CMIs ADRs increased year by year, but overall the research is of low quality and is scattered in a large number of sources. (2) It is very urgent to create a clear standard to grade ADRs of CMIs for the risk management. (3) It is necessary to enforce safety re-evaluation work for CMIs and to promote the clinical rational use.
Objective While reporting of adverse drug reactions (ADR) and adverse drug events (AE) following Chinese medicine injection (CMI) is becoming more common, the reporting quality is of concern. Methods A checklist about the reporting quality of ADR/AE was set up, and the ADR/AE reporting of Herba Houttuyniae injection was chosen as an example. Electronic databases Chinese Journal Net (CJN) (1994-2009) and Chinese Science and Technological Journal Net (VIP) (1989-2009) were searched for target literature. Results Based on our search strategy, 210 articles were included, with 175 articles reporting single or several cases of ADR/AE following Herba Houttuyniae injection (type I report). There were 7 reports from regional or national ADR monitoring centers (type II report), and 28 summary reports from a single hospital or medical center (type III report). All 210 papers mentioned ‘adverse effect,’ ‘safety’ or related meaning words in their titles, but 199 articles did not have abstract. Patient demographic characteristics were not fully reported in these articles. In type I articles, only 97 cases (43.11%) mentioned whether patients had or did not have a history of allergies, while 128 cases (56.89%) in Type II papers and Fourteen (50%) type III papers, did not mention allergic history of patients. Only three articles (3/210, 1.43%), all of them type I, mentioned the syndrome type in Chinese medicine. None of the papers gave clear indications of the type and grade of ADR/AE of patients. Most papers did not report details of the CMI procedure, such as the drug company, product serial number, or the drug’s validity period. Data about the occurrence time and management of ADR/AE was also inadequately reported. Conclusion and recommendations The current reporting format of ADR/AE in clinical CMIs is not standardized. Much fundamental information of ADR/AE following CMI is therefore missing. A standard reporting format for ADR should be developed, and should include the following: 1) a title mentioning adverse effects and safety; 2) a structured abstract including adequate information about the patient and the disease treated, the drug used, the specific ADR/AE, physician response to the ADR/AE, and result of management; 3) demographic characteristic of the patients (gender, age, etc.); 4) clinical characteristics of patients (disease, syndrome, etc); 5) allergic history of patients; 6) diagnosis and syndrome based on Chinese medicine theory; 7) detailed information about the Chinese materia medica intervention (the manufacturer of the drug, series number, valid dates, dosage, route of administration, menstruum, dripping speed, etc.); 8) concomitant drug use; 9) time and symptoms of ADR/AE; 10) type and grading of ADR/AE; 11) physiological systems affected by ADR/AE; 12) specific treatment and prognosis for ADR/AE; 13) evidence of the cause and effect of ADR/AE; 14) any other possibility of ADR/AE. Also, a ADR/AE registration system should be established.
Objective Qin Kai Ling injection (QKL) is made upon traditional Chinese medicine formulation “An Gong Niu Huang Wan”, is widely used to treatment a lot of diseases. This review aims to assess the safety of QKL. Methods We searched Chinese databases CNKI, VIP from 1987 to April 2009. Two authors extracted the data. Results Totally 1 486 cases were included in this review. We unable to answer the question about the incidence of adverse drug reaction/adverse event (ADR/AE) induced by QKL due to absence of total numbers of producing and market information. It was estimated based on the limited data that the possibility of ADR/AE by using QKL should be low. We found some ADR/AE may induced by incorrect use of QKL, such as used in infants, and some incompatibility drugs were used together with QKL, four patients died in private clinics or patient’s home. We unable to distinguish the ADR or AE based on the poor reported data. Conclusion Current weak evidence shows that QKL has a low risk of ADR/AE. The use of QKL in some ADR/AE cases may be questionable. The reporting of ADR/AE needs to be much improved based on “Recommendation for reporting traditional Chinese medicine adverse drug reaction”.
Objective To analyze the adverse drug reactions (ADR) of Ciwujia injection and the relative influence factors. Methods We searched all clinical studies and ADR reports of Ciwujia injection from the China National Knowledge Infrastructure (CNKI) database. The relevant information such as the diseases for treatment; menstruum, dosage and compatibility of Ciwujia injection; the age, gender and allergic history of patients; and the category, treatment and prognosis of ADR were collected and analyzed. Results In the 800 clinical studies, only 97 (12.1%) reported 285 ADR cases, 144 ADR reports including 236 ADR cases. Of the ADR cases, the male to female ratio was 1׃1.34, mainly in 40 to 69 years group; The ADR cases mainly including anaphylactic shock and local pain in ADR reports and clinical studies, respectively; 72.3 percent ADR cases were Ⅲ to Ⅳ class, 4 anaphylactic shock cases died; the diseases for treatment of ADR cases mainly were coronary artery heart disease and cerebral infarction; 27 (11.4%) ADR cases had allergic history; The menstruum of Ciwujia injection mainly were 5% glucose, 0.9% NaCl and 10% glucose, drug incompatibility in 36 ADR cases; The usual dosage of Ciwujia injection was 20-60 ml; 196 (83.0%) ADR cases occurred in first time medication, mainly in the early 30 minutes of medication used. Conclusion (1) In both ADR reports and clinical studies of Ciwujia injection, there are some problems of ADR and adverse drug events (AE) were not easily distinguishable, key information of total prescriptions divided by drug persons were lacking, so we can’t calculate the ADR rate, the reporting quality remained to be improved. (2) To support the rational drug use, the basic researches of Ciwujia injection remains to be further studied, especially the dose-finding studies. (3) As one of the most frequently reported ADR of traditional Chinese medicine (TCM) injection, high quality ADR monitoring, normative ADR reporting and timely analyzing the ADR reason of Ciwujia injection is extremely urgent.
Objective To assess the efficacy and safety of glimepiride for type 2 diabetes mellitus (T2DM). Methods We searched the literature from PubMed, Ovid (All EBM Reviews), CNKI, Wanfang, VIP, CBM and other databases. Evaluating the quality of the study according to Cochrane systematic reviews, Meta-analysis was performed for the results of homogeneous studies by The Cochrane Collaboration’s software RevMan 5.0, and the heterogeneous data conducted a descriptive qualitative analysis. Results Six RCTs included in the analysis and Meta-analysis was not performed due to the insufficient data (for the median or standard deviation). Six RCTs are multi-center, randomized, double-blind, placebo-controlled trials. The results showed that glimepiride groups to reduce glycosylated hemoglobin, lower fasting and postprandial blood glucose, postprandial plasma insulin enhance the efficacy were statistically significant differences (Plt;0.05) compared to placebo groups. Four studies informed the impact of fasting plasma insulin (FI) and 3 studies showed that the glimepiride groups improving the fasting plasma insulin (FI) were statistically significant differences (Plt;0.05), but 1 study showed the two groups had no significant difference (Pgt;0.05). All studies showed minor adverse reactions of glimepiride. Conclusion Glimepiride can reduce the glycosylated hemoglobin, lower the fasting and postprandial blood glucose, improve fasting and postprandial plasma insulin for type 2 diabetes patients, and have minor adverse reactions. In a word, glimepiride is an effective and security sulfonylureas drug.
Objective To assess reduction of adverse drug reaction incidence in patients with colorectal cancer receiving Jianpi herbs combined with chemotherapy. Methods The randomized controlled trials (RCTs) comparing Jianpi herbs combined with chemotherapy were searched through CBMdisc, CJFD, Wangfang Data and PubMed. The search was updated to September 2007. Software RevMan5, provided by Cochrane Library, was used to perform meta-analysis. Results Six RCTs were identified in this systematic review. All the methodology quality of the enrolled RCTs was gaded C. The pooled analysis showed that Jianpi herbs combined chemotherapy significantly reduced the incidences of grade I and grade II leucopenia [grade I with RR= 0.50 and 95%CI (0.31 to 0.80); grade II with RR= 0.37 and 95%CI (0.21 to 0.66)], grade II nausea and vomiting [RR= 0.51, 95%CI (0.31 to 0.84)] compared with routine chemotherapy. There was no statistical difference in reduction of neurotoxicity between the two groups. Conclusion The methodological quality of the RCTs using Jianpi herbs combined with chemotherapy on treating colorectal cancer should be improved. Based on this systematic review, Jianpi herbs combined with chemotherapy may reduce the incidence of mild to moderate adverse drug reaction, such as leucopenia and nausea and vomiting, in patients with colorectal cancer. Well-designed RCTs are needed in the future.