阿帕替尼上市后的ADR文献分析

Literature analysis of ADR after the listing of apatinib

目的探讨阿帕替尼所致药物不良反应(ADR)的特点及规律,为其临床安全用药提供参考。方法检索自阿帕替尼2014年上市以来,中国知网、万方医学网、维普及PubMed等中英文数据库中关于其ADR及安全性评估的个案和群体报道,经筛选后对文献资料进行提取及分析。结果共纳入病例101例,涉及ADR 221例次。发生ADR的患者中,男女比例为1.24∶1,年龄以51~70岁最多,给药剂量以500 mg及以上者居多,但其中给予小剂量阿帕替尼并联合使用了其他抗肿瘤药物的患者也较易发生ADR。ADR的种类以1~2种居多,而种类最多者可高达6种。该药的ADR多发生在用药后30 d内,累及器官/系统以心血管系统损害、皮肤及其附件损害、胃肠系统损害和泌尿系统损害为主,主要临床表现为高血压/加重、手足综合征、腹痛腹泻和蛋白尿等,其严重ADR以高血压/加重、手足综合征和骨髓抑制多见。多数ADR均可通过停药、减量及对症处理实现好转/痊愈。4例死亡患者均存在基础病,且美国东部肿瘤协作组评分均≥2分。特殊ADR(如可逆性后部脑病综合征、精神异常和认知障碍等)多由阿帕替尼自身引起,亦存在阿帕替尼与原发疾病或基础疾病共同引起的可能。结论高龄、剂量较大、联合用药、存在基础病及体力状态不佳是使用阿帕替尼患者发生ADR的高危因素。建议对所有使用该药患者的血压、尿蛋白及手足皮肤进行日常监测,并注意特殊ADR的发生,以便及时发现并给予有效干预,从而避免ADR加重及继发其他ADR。

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions(ADR)caused by apatinib,and to provide a reference for the safe use of apatinib in clinic.METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI,Wanfang medical network,VIP and PubMed since its listing in 2014,literature data were extracted and statistically analyzed after screening.RESULTS Totally 101 cases were included,involving 221 ADR.In the above cases,the male-to-female ratio was 1.24∶1,with the highest proportion of patients aged 51 to 70 years,most of the patients were given a dose of 500 mg or more,and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR.One to two types of adverse reaction were the most common,while the types could reach up to six.Most ADR occurred within 30 days after medication,and the systems/organs involved were mainly the cardiovascular system damage,skin and its accessories damage,gastrointestinal system damage and urinary system damage;the main clinical manifestations were hypertension/aggravation,hand-foot syndrome,abdominal pain diarrhea and albuminuria,etc.Hypertension/aggravation,hand-foot syndrome and myelosuppression were the most common serious ADR.Most ADR could be improved/cured by suspension of administration,dose downregulation and symptomatic treatment.All 4 patients who died had underlying diseases,and their ECOG scores all≥2 points.Special ADR(such as reversible posterior encephalopathy syndrome,psychiatric disorders,and cognitive impairment)were mostly caused by apatinib itself,or may be caused by apatinib in combination with the primary or underlying disease.CONCLUSIONS Advanced age,large dose,combination medication,underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib.It is recommended to monitor the blood pressure,urine protein and skin of hands and feet of all patients with medication on a daily basis,pay attention to the occurrence of special ADR,and timely detect abnormal states and give effective intervention,so as to avoid the aggravation of ADR and other secondary ADR.