2015 National Adverse Drug Reaction Monitoring Annual Report (Full Text)
为全面反映2015年我国药品不良反应监测情况，促进临床合理用药，保障公众用药安全，依据《药品不良反应报告和监测管理办法》，国家食品药品监管总局组织国家药品不良反应监测中心编撰《国家药品不良反应监测年度报告(2015年)》。
一、药品不良反应监测工作进展
2015年，根据《药品不良反应报告和监测管理办法》有关要求，为督促药品生产企业建立健全药品不良反应报告和监测体系，切实履行报告和监测责任，国家食品药品监管总局发布了《药品不良反应报告和监测检查指南(试行)》，明确开展药品不良反应报告和监测工作检查的相关程序，促进药品不良反应报告和监测工作深入开展。
2015年，国家药品不良反应监测网络建设进一步深入，基层网络用户数量快速增长，全国已有28万余个医疗机构、药品生产经营企业注册为药品不良反应监测网络用户，并通过该网络报送药品不良反应报告。全国县级报告比例达到96.6%，每百万人口平均报告数量达到1044份，较2014年均有所增长，表明我国发现和收集药品不良反应信息的能力进一步增强。2015年，继续加强与世界卫生组织的合作及数据共享，得到世界卫生组织的高度赞扬和肯定。
2015年，药品不良反应报告和监测工作有序开展。通过日监测、周汇总、季度分析等方法加强对国家药品不良反应监测数据的分析评价，深入挖掘药品风险信号，对醒脑静注射液、酒石酸唑吡坦口服制剂、地塞米松注射剂等45个(类)品种进行了安全性评价，并采取了风险管理和沟通措施。编发《药物警戒快讯》12期，共计62条信息，涉及76个品种。继续推进药品不良事件聚集性信号处置工作，加强预警平台建设，提高预警工作效能，对重点关注的150多条药品不良事件聚集性信号及时进行处置，进一步保障公众用药安全。
II. Reporting of adverse drug reactions/incidents
(I) Overall report
1. Annual and monthly reports of adverse drug reactions/incidents in 2015
In 2015, the national adverse drug reaction monitoring network received 1.398 million copies of the "Adverse Drug Reaction/Event Report Form", an increase of 5.3% over 2014. From 1999 to 2015, the national adverse drug reaction monitoring network received nearly 9.30 million copies of the "Adverse Drug Reaction/Event Report Form".
2. Reporting of new and serious adverse drug reactions/incidents
In 2015, the national adverse drug reaction monitoring network received 393,734 new and serious adverse drug reaction/incident reports, an increase of 15.3% compared with 2014; the number of new and serious reports accounted for 28.2% of the total number of reports in the same period, an increase of 2.5% compared with 2014. The proportion of new and serious adverse drug reaction/event reports continued to increase, indicating that the overall quality and availability of adverse drug reaction reports in our country continued to improve.
3. Average case reporting per million population
The average number of cases reported per million population is one of the important indicators to measure the level of adverse drug reaction monitoring in a country. In 2015, the average number of cases reported per million population in our country was 1044, an increase of 5.4% compared with 2014.
4. County-level reporting of adverse drug reactions/incidents
The proportion of county-level reports of adverse drug reactions/events is one of the important indicators to measure the balanced development and coverage of adverse drug reaction monitoring in our country. In 2015, the proportion of county-level reports of adverse drug reactions/events nationwide was 96.6%, an increase of 2.2% compared with 2014.
5. Sources of adverse drug reactions/incident reports
According to the source of the report, 82.2% of the reports were from medical institutions, 16% from pharmaceutical distributors, 1.4% from pharmaceutical manufacturers, and 0.4% from individuals and other sources. In 2015, medical institutions were still the main source of reports; the number of reports from manufacturing enterprises was still low, but among the top 30 production enterprises with the number of reports, the number of domestic enterprises increased significantly.
6. Reporter occupation
According to the occupational statistics of reporters, doctors accounted for 53.0%, pharmacists accounted for 27.6%, nurses accounted for 14.6%, and other reports accounted for 4.8%. The occupational composition of reporters in 2014 was basically the same.
7. Reports of adverse drug reactions/incidents involving patients
According to the statistics of the age of the patients involved in the report, the reports of children under the age of 14 accounted for 9.9%, a slight decrease compared with 2014. The reports of the elderly over the age of 65 accounted for 21.5%, an increase of 1.6% compared with 2014. According to the statistics of the gender of the patients involved in the report, the ratio of male and female patients was close to 0.92:1, and there were slightly more females than males. The gender distribution trend was basically the same as in 2014.
8. Adverse drug reaction/incident reports involve the drug
According to the category of suspected drugs, chemical drugs accounted for 81.2%, traditional Chinese medicine accounted for 17.3%, and biological products (excluding vaccines) accounted for 1.5%. The number of reports of anti-infective drugs still ranked first, accounting for 44.9% of chemical drugs, a decrease of 1.3% from 2014, and the proportion of reports has been declining for 6 consecutive years. Cardiovascular system drugs accounted for 10.3% of the total number of chemical drugs reported, an increase of 0.1% from 2014, and an upward trend for 6 consecutive years. Electrolytes, acid-base balance and nutritional drugs all showed an upward trend for 6 consecutive years, and the proportion increased slightly compared with 2014.
According to the statistics of drug dosage forms, among the distribution of drug dosage forms involved in adverse drug reaction/incident reports in 2015, injections accounted for 61.3%, oral formulations accounted for 34.7%, and other formulations accounted for 4.0%. The proportion of injections increased by 3.5% compared with 2014, and the proportion of oral formulations decreased by 1.5%.
按照药品给药途径统计，2015年药品不良反应/事件报告涉及的药品给药途径分布中，静脉注射给药占57.9%、其他注射给药占3.2%、口服给药占35.8%、其他给药途径占3.1%，与2014年相比，总体给药途径分布无明显变化。
9.不良反应累及系统情况
2015年报告的药品不良反应/事件中，累及系统排名前三位的为皮肤及其附件损害(占27.3%)、胃肠系统损害(占26.2%)和全身性损害(占10.8%)，前三位之和占64.3%。化学药、中成药累及系统前三位排序与总体一致，但生物制品累及系统前三位与总体有所不同，依次是皮肤及其附件损害、全身性损害、免疫功能紊乱。
注射剂报告中累及系统排名前三位与总体报告一致，分别是皮肤及其附件损害(占32.5%)、胃肠系统损害(占19.1%)、全身性损害(占13.5%)，与2014年相比，全身性损害下降1.1%。口服制剂累及系统前三位为胃肠系统损害(占41.6%)、皮肤及其附件损害(占16.7%)、神经系统损害(12.9%)，与2014年基本持平。
10.药品不良反应/事件报告总体情况分析
2015年药品不良反应/事件报告总体情况与2014年相比未出现显著差异。在患者年龄分布中，老年患者不良反应报告比例依然出现增高态势，提示应继续关注老年人群用药安全。在剂型和给药途径分布中，化学药品注射制剂比例仍有小幅增加，提示应建立注射剂风险管理的长效机制，并应加强相关宣传、教育和研究工作。在化学药总体排名中，心血管系统用药所占比例有所增加，提示应继续加强心血管系统用药不良反应监测，及时发现风险并采取有效控制措施，保证患者的用药安全。
小贴士：
What is Adverse Drug Reaction Reporting and Monitoring? Why should the state establish a reporting system for adverse drug reactions?
Adverse drug reaction reporting and monitoring refers to the process of discovery, reporting, evaluation and control of adverse drug reactions. The main purpose of establishing an adverse drug reaction reporting system is to understand the occurrence of adverse drug reactions and detect new and serious adverse drug reactions in a timely manner. Due to the particularity of drugs, pre-market research is very limited, and its inherent risks need to be discovered through a wide range of clinical applications. Therefore, by strengthening the reporting and monitoring of adverse drug reactions, the potential inherent risks of drugs can be discovered in a timely manner, the risk-benefit ratio can be evaluated, and the safety information of drugs can be continuously improved to protect the public’s drug safety.
(Ii) Monitoring of essential drugs
1. Overall situation of national essential drug monitoring
In 2015, the overall situation of national essential drug monitoring remained basically stable. In 2015, the national adverse drug reaction monitoring network received a total of 575,000 reports of adverse reactions/events of national essential drugs (accounting for 41.1% of the overall reports in 2015), an increase of 1.9% over 2014. Among them, 37,000 cases were seriously reported, accounting for 6.4%, an increase of 0.8% over 2014. 83.1% of cases reported involving chemical drugs and biological products, and 16.9% of cases reported involving proprietary Chinese medicines.
2. Analysis of the situation of national essential medicines, chemicals and biological products
The "National Essential Drugs List (Primary Medical Institutions Equipped and Used Part) " (2012 Edition) includes chemical drugs (including biological products), divided into 25 categories and 317 varieties. In 2015, the National Adverse Drug Reaction Monitoring Network received 482,740 reports of adverse reactions/events of 359 specific varieties, of which 35,358 were serious reports, accounting for 7.3%.
2015年国家基本药物化学药品和生物制品报告按类别统计，报告数量排名前5位的分别是抗微生物药、心血管系统用药、抗肿瘤药、消化系统用药、镇痛/解热/抗炎/抗风湿/抗痛风药，占基本药物化学报告的73.1%。抗微生物的报告比例最高。化学药品(含生物制品)报告数量排名前五位的品种均为抗微生物药，分别是左氧氟沙星、头孢曲松、头孢呋辛、头孢他啶和青霉素。
2015年国家基本药物化学药品和生物制品不良反应/事件报告中，药品不良反应/事件累及系统排名前5位的是胃肠系统损害(占27.9%)、皮肤及其附件损害(占26.9%)、全身性损害(占9.5%)、中枢及外周神经系统损害(占9.1%)以及免疫功能紊乱和感染(占4.5%)；前5位不良反应例次之和占77.9%。
3.国家基本药物中成药情况分析
《国家基本药物目录(基层医疗卫生机构配备使用部分)》(2012版)中成药部分涉及内科用药、外科用药、妇科用药、眼科用药、耳鼻喉科用药、骨伤科用药6大类共203个品种。2015年全国药品不良反应监测网络收到该部分共203个相关品种的报告98,176例次，其中严重报告5,480例次，占5.6%。
2015年国家基本药物中成药部分六大类中，药品不良反应/事件报告总数由多到少依次为内科用药、骨伤科用药、妇科用药、耳鼻喉科用药、外科用药、眼科用药。其中内科用药报告总数占到总体报告数量的84.9%，内科用药构成比较大可能与内科用药临床使用量大，且基本药物目录中中药注射剂都属于内科用药有关。内科用药中排名前五位的分别是祛瘀剂、温理剂、开窍剂、清热剂、扶正剂，此五类药品报告占到内科用药报告数的88.9%。
2015年国家基本药物目录中成药部分药品不良反应/事件报告中，累及系统排名前三位的是皮肤及其附件损害(占29.0%)、胃肠系统损害(占23.8%)和全身性损害(占14.4%)。不同剂型报告累及系统中，注射剂不良反应/事件累及系统排名前三位的是皮肤及其附件损害(占21.1%)、全身性损害(占12.8%)、胃肠系统损害(占6.2%)，口服制剂累及系统排名前三位的是胃肠系统损害(占16.9%)、皮肤及其附件损害(占5.5%)、中枢及外周神经系统损害(占2.7%)。
2015年，根据药品不良反应监测风险信号，组织对可待因单方制剂、血栓通、血塞通注射制剂、缩宫素注射剂等基本药物品种开展了安全性评价，并采取了相应风险控制措施。
(三)抗感染药监测情况
1.抗感染药不良反应/事件报告总体情况
2015年全国药品不良反应监测网络共收到抗感染药的药品不良反应/事件报告51.3万例，其中严重报告2.84万例，占5.5%。抗感染药的药品不良反应/事件报告占2015年总体报告的36.7%。与2014年相比，2015年抗感染药报告数量同期增长1.2%，严重报告同期增加16.6%。严重报告构成比与2014年(4.8%)相比增加0.7%。
2.报告涉及患者情况及不良反应情况
2015年抗感染药药品不良反应/事件的总报告与总体报告年龄分布相比，1-4岁年龄段上升4.8%，45-64岁年龄段下降6%，65岁以上年龄段下降4.2%，其余各年龄段患者的比例浮动范围在4个百分点以内；与2014年抗感染药物的年龄分布相比基本一致。按报告涉及患者年龄统计，14岁以下儿童患者的报告占16.4%，高于整体数据儿童患者所占比例；65岁以上老年人的报告占17.3%。
In the 2015 report of adverse drug reactions/events of anti-infective drugs, the top three systems involved in adverse drug reactions/events were skin and its appendages (39.5%), gastrointestinal system damage (25.5%), and systemic damage (7.4%). The top three systems involved in oral anti-infective drugs were gastrointestinal system damage (44.6%), skin and its appendages damage (26.6%), and central and peripheral nervous system damage (6.9%); the top three systems involved in injection preparations were skin and its appendages damage (43.0%), gastrointestinal system damage (20.7%), and systemic damage (8.5%).
3. The report involves the situation of drugs
The 2015 anti-infective drug adverse reaction/incident reports involved 9 categories and 321 varieties, of which antibiotics accounted for 65.8%. The top five were cephalosporins (31.9%), macrolides (10.1%), penicillins (9.6%), beta-lactamase inhibitors (5.8%) and lincomycin (3.7%); synthetic antimicrobials accounted for 24.7%, mainly quinolones (18.4%) and nitroimidazoles (5.5%). There was no significant difference in the composition ratio of drugs and the composition of anti-infective drug reports in 2014.
In 2015, antibiotics accounted for 65.4% and synthetic antimicrobials 14.5% of serious adverse reactions/incident reports of anti-infective drugs, with no significant difference from the composition of anti-infective drug reports in 2014. The top five serious reports were cephalosporins (32.4%), quinolones (11.5%), penicillins (11.3%), anti-tuberculosis drugs (10.4%), and beta-lactamase inhibitors (7.6%). Compared with 2014, the ranking of quinolones rose to No. 2, and the ranking of penicillins fell to No. 3.
From the analysis of drug dosage forms, in 2015, injections accounted for 76.6%, oral formulations accounted for 16.8%, and other dosage forms accounted for 0.5%. Compared with the overall drug report, the proportion of injections (76.6%) was higher, which was basically the same as the distribution of dosage forms in 2014.
4. Analysis of anti-infective drug safety trends
In 2015, the total number of adverse reactions/events reported by anti-infective drugs increased compared with 2014, and the number of serious reports increased by 16.6%, which was higher than the increase in overall case reports in 2015. Compared with 2014, the proportion of adverse reactions/events reported by anti-infective drugs in 2015 decreased by 1.5%, the proportion of serious reports increased by 0.2%, and the proportion of serious reports increased by 0.7%.
小贴士：
What are the side effects of antibiotics?
Antibiotics are effective drugs for controlling various infections today, and they are one of the most commonly used drug categories. Nearly 100 kinds have been used. Their most common adverse reactions are as follows:
(1) Allergic reaction. Penicillin, streptomycin, pioneer mycin, etc. can cause allergic reactions in people, which can be life-threatening in severe cases. Allergic reactions caused by antibiotics are common for drug rashes, dermatitis and drug fever.
(2) Toxic reactions. Common toxic reactions caused by antibiotics include auditory nerve damage, hematopoietic system disorders, kidney damage, liver damage, and gastrointestinal reactions. The nature and extent of toxic reactions vary depending on the type of drug and individual patients.
(3) Drug resistance. Most bacteria can develop resistance to antibiotics. With the wide application of antibiotics and the overuse of antibiotics caused by irrational use of antibiotics, the number of drug-resistant strains is increasing, which affects the treatment of diseases, and even has serious consequences due to the lack of sensitive antibiotics to control infections.
(4) Local stimulation. Intramuscular injection of antibiotics can mostly cause local pain, and intravenous injection may also cause thrombophlebitis. It can be seen that antibiotics must be used rationally, and must not be used indiscriminately as a "panacea".
(IV) Monitoring of traditional Chinese medicine injections
1. Overall status of adverse reactions/incident reports of traditional Chinese medicine injections
In 2015, the safety status of traditional Chinese medicine injections was basically consistent with the overall situation in the country. In 2015, the national adverse drug reaction monitoring network received a total of 127,000 reports of traditional Chinese medicine injections, of which 9,798 were serious reports (7.7%). In 2015, the proportion of injections in adverse reaction/event reports of traditional Chinese medicine was 51.3%, a decrease of 2.1% compared with 2014.
2015年中药注射剂报告数量排名居前的类别是理血剂、补益剂、开窍剂、清热剂、解表剂、祛痰剂，共占中药注射剂总体报告的97.0%。报告数量排名前五名的药品分别是：清开灵注射剂、参麦注射剂、血塞通注射剂、双黄连注射剂、舒血宁注射剂。
2015年，中药注射剂严重报告主要涉及全身性损害、呼吸系统损害、皮肤及其附件损害等，包括过敏样反应、过敏性休克、寒战、发热、呼吸困难、胸闷、心悸、瘙痒、皮疹、恶心、呕吐等表现，与往年监测情况基本一致。
2.中药注射剂不良反应/事件报告合并用药情况
对2015 年中药注射剂总体报告排名前20 位药品(占全年中药注射剂报告87.6%)合并用药情况进行分析，其总体报告涉及合并用药占43.4%，严重报告涉及合并用药占56.5%，以上数据提示单独或联合其他药品使用中药注射剂均可出现不良事件，合并用药可能加大中药注射剂的安全风险。
三、用药安全提示
(一)关注老年患者用药问题
根据对2015年国家药品不良反应监测数据库收到的药品不良反应报告年龄分布情况分析，2015年65岁以上老年患者药品不良反应报告比例达21.5%，严重报告比例达28.7%。国家药品不良反应监测数据库分析显示，自2009年以来，该两项比例持续7年上升，老年患者用药安全问题需引起特别关注。一般来说，老年人脏器功能退化，新陈代谢减慢，容易发生药品不良反应；老年人往往身患一种以上的疾病，有些老年人还服用一些保健品等，所以老年人用药要特别慎重，选择药品时要多咨询医生，注意给药途径和时间、加强用药前和用药期间监护。
小贴士：
老年人使用抗菌药物应注意的相关问题及用药十忌原则：
老年人因肝肾功能衰退，对药物的耐受性降低，尤其是一些活性较强的药物，极易产生毒副作用和过敏反应。抗菌药物在人体吸收以后，多由肝脏和肾脏解毒、排泄。因此，肝肾功能不全的老人，在用这些药时需慎重，不宜长期或大剂量应用。故长期、大剂量使用这些抗菌药物，对老年人是非常不利。老年用药十忌原则：一忌随意滥用；二忌品种过多；三忌时间太长；四忌不遵医嘱；五忌生搬硬套；六忌乱用偏方、秘方、验方；七忌滥用补药；八忌更换过频；九忌嗜药成瘾；十忌联用毒副作用强的药物。
(二)关注心血管系统用药安全
2015年化学药总体排名中，心血管系统用药占10.3%(排名第二)，仅次于抗感染药，连续5年呈上升趋势。按照化学药剂型排名，口服制剂前20名的品种中心血管系统用药为7个，与2014年相比心血管系统用药所占比例均有所增长。随着我国居民生活水平的逐步提高，高血压、冠心病、高血脂等心血管疾病的发病率亦呈增长的趋势，心血管系统用药尤其是口服制剂使用也随之越来越广泛。相关数据显示，近20年间，我国心血管病死亡率一直呈上升趋势，且35岁-55岁的中青年男性冠心病死亡率增加最快，心血管用药安全应引起格外关注。
小贴士：
如何合理使用心血管药物？
高血压、冠心病、心律失常、心力衰竭是临床最常见的心血管疾病。在治疗心血管疾病时，要注意鉴别疾病类型和分期，恰当的选择最适合病情的药物，以求达到最佳治疗效果和最大程度的降低不良反应的发生。在用药过程中还应注意一些特殊情况，例如：高血压患者应加强血压监测，确定最佳服药时间，在服用降压药时要谨防“首剂反应”，服药过程中忌频繁换药，患者用药前应仔细阅读所服药物的说明书，掌握心血管药物适应症、禁忌症、不良反应，注意合理用药。
(三)关注基层医疗机构注射剂使用安全
2015年化学药不良反应/事件报告中，注射剂所占比例为62.9%；中药不良反应/事件报告中，注射剂所占比例为51.3%；而严重药品不良反应报告的给药途径以静脉注射为主，占70%以上。国家药品不良反应监测数据分析显示，部分中药注射剂的不良反应主要来源于基层医疗卫生机构。注射剂的不良反应主要表现为过敏及类过敏反应，部分病例可出现过敏性休克等严重过敏反应，需要紧急救治。基层医疗卫生机构的救治设备、设施较为有限，医护人员救治经验和能力相对缺乏，影响抢救效果及预后，基层医疗机构的输液风险值得关注。
小贴士：
如何合理使用注射剂？
静脉输液是高风险、高获益的临床用药方法，起效迅速，易于调节给药剂量和速度，可恒定维持治疗所需的药物浓度。如能合理使用，静脉输液的临床获益大于风险；过度使用时，静脉输液的风险则明显增加，甚至可能超过临床获益，给患者带来不必要的风险及经济损失。国内绝大多数医疗机构都有门诊输液，门诊输液几乎成了中国老百姓的就医习惯，长期以来人们形成了“输液好、输液快”的错误认识和就医习惯。用药要遵循能不用就不用、能少用就不多用、能口服不肌注、能肌注不输液的原则。
(四) 关注合理用药问题
据统计，2008年至2015年国家发布的《药品不良反应信息通报》总计66个药品中，27个存在明显不合理用药情况；如：2015年药品不良反应信息通报(第69期)中提醒注射用头孢硫脒，存在比较严重的不合理用药现象，包括单次超剂量、日剂量超量给药，未分次给药等，增加了患者发生严重不良反应的风险。2015年，国家药品不良反应监测中心对国内医学文献中涉及不合理用药情况进行了系统分析，结果显示抗菌药、静脉输液和中药注射剂不合理用药问题突出。
小贴士：
合理用药十大提示？
1.优先使用基本药物；
2.遵循能不用就不用、能少用就不多用，能口服不肌注、能肌注不输液的原则；
3.买药要到合法医疗机构和药店，注意区分处方药和非处方药，处方药必须凭执业医师处方购买；
4.阅读药品说明书，特别要注意药物的禁忌、慎用、注意事项、不良反应和药物间的相互作用等事项；
5.处方药要严格遵医嘱，切勿擅自使用。特别是抗菌药物和激素类药物，不能自行调整用量或停用；
6.任何药物都有不良反应，非处方药长期、大量使用也会导致不良后果；
7.孕期及哺乳期妇女用药要注意禁忌；儿童、老人和有肝脏、肾脏等方面疾病的患者，用药应谨慎，用药后要注意观察；从事驾驶、高空作业等特殊职业者要注意药物对工作的影响；
8. Drugs should be stored scientifically and properly; beware of misuse and misuse by children and mentally ill persons;
9. Vaccination is the most effective and economical measure to prevent some infectious diseases, and the state provides free first-class vaccines.
10. Health foods cannot replace medicines.
IV. Relevant risk control measures
According to the adverse drug reaction monitoring data and evaluation results in 2015, the State Food and Drug Administration has taken corresponding risk control measures in a timely manner for drugs found to have potential safety hazards to ensure the safety of public medication.
(1) Issued the 4th issue of the "Adverse Drug Reaction Information Circular", reporting serious adverse reactions such as metoclopramide, atypical antipsychotics, Chinese and Western medicine compound preparations, and ceftiramide for injection, timely reminding of drug safety risks.
(2) Published 12 issues of "Pharmacovigilance Alert", reporting 62 pieces of foreign drug safety information such as suicide risk of pregabalin and severe skin reactions of ziprasidone.
(3) According to the monitoring and evaluation results, the organization revised the instructions of 40 (categories) of drugs such as Xuesaitong, Naoluotong Capsule, and Trikrutin Injection.
V. Relevant Instructions
(1) The data in this annual report is derived from the data reported by each region from January 1, 2015 to December 31, 2015 in the National Adverse Drug Reaction Monitoring Database.
(2) Like most countries, the data collected by the adverse drug reaction monitoring database in our country has limitations, such as underreporting, irregular filling, lack of detailed information, and inability to calculate the incidence of adverse reactions.
(III) At the time of the completion of this annual report, some of the serious reports and death reports were still under investigation and evaluation. All statistical results were a true reflection of the data collection situation, and some issues did not represent the final evaluation results.
(Iv) The number of adverse drug reactions/events reported is influenced by many factors such as the amount of the drug used and the incidence of adverse drug reactions. Therefore, the ranking of the number of adverse drug reactions/events reported is only a direct reflection of the number of reported data, and does not represent the incidence of adverse reactions.
(V) This annual report does not include surveillance data on vaccine adverse reactions/events.