康莱特注射液上市后安全性再评价研究

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目的 了解康莱特注射液的不良反应及其发生率,并探讨影响该药临床使用安全性的因素. 方法 研究设计为非干预前瞻性医院集中监测和巢式病例对照研究.观察对象为2013年9月17日至2014年8月26日在我国东北、华北、华中、华东、华南、西南、西北地区14个省级行政区域28家医院接受康莱特注射液治疗的住院肿瘤患者.主要监测内容为患者一般情况、用药情况(包括适应证、合并用药)、用药安全性相关情况.以发生康莱特注射液相关不良反应患者为病例组,按1∶ 3配对原则随机抽取各方面情况相近的未发生不良反应患者作为对照组,分析影响康莱特注射液临床使用安全性的因素. 结果 纳入监测的患者5 022例,男性2 926例,女性2 096例;年龄9~95岁,平均(60±12)岁;位列前五的肿瘤依次为肺癌(1 456例,28.99%)、肠癌(867例,17.26%)、乳腺癌(372例,7.41%)、胃癌(346例,6.89%)和肝癌(335例,6.67%);肿瘤分期为Ⅲ、Ⅳ期者3 863例(76.92%);有过敏史者348例(6.93%);合并其他疾病者2 524例(50.26%);合并使用其他药物者4 687例(93.33%).监测期间5 022例患者中发生不良事件者751例(14.95%),其中18例(静脉炎7例,恶心呕吐3例,寒战3例,皮疹2例,心慌1例,转氨酶升高1例,发热1例)符合ADR因果关系判断标准,不良反应发生率为0.36%.单因素分析结果显示,不良反应发生率有合并疾病者高于无合并疾病者(χ2=5.4723, P=0.019),合并西药者高于西药加中药者(p=0.002).Logistic回归分析结果显示,影响不良反应发生的因素为有合并疾病(OR=1.636, 95%CI:1.100~2.433, P=0.013)和合并用药(OR=1.475,95%CI:1.108~1.965, P=0.027).巢式病例对照研究结果显示,康莱特注射液不良反应的影响因素为放射治疗(OR=1.864, 95%CI: 0.930 ~3.736, P<0.01)和合并用药(OR=1.622, 95%CI: 1.102~2.389, P<0.01). 结论 康莱特注射液临床应用不良反应发生率较低,安全性较好.合并其他疾病、合并用药和正在接受放疗为影响该药临床应用安全性的主要因素.“,”To understand the adverse reactions of Kan,glaite injection and its incidencernand explore the factors affecting the safety of Kan,glaite Injection in clinical use.Methods A noninterventional and prospective hospital based monitoring study and nested case-control study were conducted.All hospitalized cancer patients receiving Kan.glaite injections from 28 hospitals in northeast, north, central,east, south, southwest, northwest regions of China from September 2013 to September 2014 were enrolled in this study. The main monitoring contents included the general status of patients, the drug administration (including indications and combined use), medication safety, and so on. Patients developing adverse reactions related to Kan,glaite injection distributed in the case group and patients who did not develop adverse reactions were randomly selected and distributed into the control group with a ratio of l : 3 , and the factors that affect the safe use of Kan,glaite injection were analyzed.Results A total of 5 022 cancer patients were entered into the study, including 2 926 males and 2 096 females with age from 9 t0 95 years and their average age was (60 + 12) years. The top five tumors were lung cancer (1 456 patients,28.99%) ,intestinal cancer (867 patients,17.26% ) , marmuary cancer ( 372 patients, 7.41% ) , gastric cancer ( 346 patients, 6.89%) , and liver cancer (335 cases,6.67%). There were 3 863 patients (76.92% ) with tumor stage III and IV, 348 patients with allergic history (6.93%) ; 2 524 patients were complicated with other diseases (50.26% ) ; 4 687 patients (93.33%) had combined drug therapy.During the monitoring period,751(14.95%) of 5 022 patients developed adverse events and of them, 18 cases met the criteria of causality of adverse reactions, including 7 cases of phlebitis, 3 cases of nausea and vomiting, 3 cases of chills, 2 cases of rash, 1 case of palpitation, 1 case of transammase increase, and l case of fever. The incidence of adverse reactions was 0.36%. Univariate analysis showed that the incidence of adverse reactions in patients with combined diseases was higher than that in patients without combined diseases (X2=5.4723,P=0.019),the incidence of adverse reactions in patients with combined western medication was higher than that in patients with combined westem and Chinese medication (P=0.002).Logistic regression analysis showed that the influencing factors of adverse reactions were coexisting diseases (OR=1. 636, 95%C/:1.100-2.433,P= 0.013)and combined medication (OR=1.475,95%C/:1.108-1.965,P=0.027).Nested case-control study showed that the influencing factors of adverse reactions induced by Kan.glaite injection were radiotherapy (OR= 1.864,95% C/:0.930-3.736,P<0.01)and corubined medication (OR=1.622,95% C/:1.102-2.389,P<0.01) .Conclusions The incidence of adverse reactions of Kan,glaite injection in clinical application is lower and the safety is good. Coexisting diseases, combined medication and radiotherapy are main factors affecting its clinical safety.
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