基于美国FDA不良事件报告系统数据库的不同年龄段人群多西环素风险信号分析

Analysis of risk signals of doxycycline in different age groups based on the FDA Adverse Event Reporting System database

目的利用美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)数据库,挖掘和分析不同年龄段患者的多西环素不良事件(AE)信号,为临床安全用药提供参考。方法检索FAERS数据库2004年第1季度至2023年第3季度期间多西环素AE报告数据,使用报告比值比(ROR)法、比例报告比值(PRR)法及英国药品和保健品管理局(MHRA)的综合标准法对多西环素的AE报告进行挖掘,并分析不同年龄段病例的AE风险信号。结果共收集到以多西环素为首要怀疑药物的AE报告13603例,涉及AE 39920例次,其中有效信号数517个,涉及26个系统/器官。≥18岁患者常见的AE有药物性超敏反应、恶心、呕吐、皮疹、光敏性反应等,与药品说明书收载的常见不良反应一致;8~17岁的患者常见的AE有药品说明书收载的呕吐、恶心、食管溃疡、食管炎和溃疡性结肠炎,以及药品说明书未收载的雅里希-赫克斯海默反应、硬化性胆管炎、抑郁和自杀想法;<8岁的患者发现了牙齿变色、颅内压增高等药品说明书特别警示的罕见不良反应,以及药品说明书未收载的高铁血红蛋白血症以及代谢性酸中毒等。结论多西环素在临床使用中除需要关注常见胃肠道、皮肤、免疫系统等AE外,还应警惕罕见的或药品说明书未收载的可疑AE,尤其是对于<8岁的患者,需重点关注用药安全性,保障患者用药安全。

AIM To mine and analyze the adverse event(AE)signals of doxycycline in patients of different age groups based on the FDA Administration Adverse Event Reporting System(FAERS)database,to provide references of the clinical safety information.METHODS AE reports of doxycycline from the FAERS database during the first quarter of 2004 to the third quarter of 2023 were collected.The AE reports of doxycycline were mined by using the reporting odds ratio(ROR),proportional reporting ratio(PRR),and the comprehensive standard method established by the Medicines and Healthcare Products Regulatory Agency(referred to as MHRA method),and key signals of AE in different age groups were deeply analyzed.RESULTS A total of 13603 AE reports of doxycycline were retrieved,involving 39920 AE occurrences,which resulted in 517 positive signals mapped to 26 systems organ classification(SOC).In adults aged 18 and above,common AEs such as drug-induced hypersensitivity,nausea,vomiting,rash,and photosensitivity were consistent with the drug instructions.For the age group of 8 to 17 years,AEs included those documented in the instructions such as vomiting,nausea,esophageal ulcers,esophagitis and ulcerative colitis,as well as undocumented AEs like Jarisch-Herxheimer reaction,sclerosing cholangitis,depression,and suicidal ideation.In children under 8 years old,rare AEs explicitly warned in drug instruction,such as tooth discoloration and increased intracranial pressure,along with undocumented AEs like methemoglobinemia and metabolic acidosis were observed.CONCLUSION During clinical use of doxycycline,attention should be paid not only to common gastrointestinal,dermatological,and immune system AEs but also to rare or undocumented potential AEs in the instructions,especially in children under 8 years old,it is crucial to focus on the safety of of f-label drug use to prevent severe irreversible damage and ensu re patient medication safety.