Kuroda Yasufumi, Hirayama Chie, Hotoda Hitoshi, Nishikawa Yasuhiro, Nishiwaki Akinori
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Vasc Health Risk Manag. 2013;9:593-8. doi: 10.2147/VHRM.S51244. Epub 2013 Oct 7.
Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor approved in Japan for the prevention of venous thromboembolism following major orthopedic surgery. Currently, edoxaban is in Phase III clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation, and for the treatment and prevention of recurrences of venous thromboembolism. This report describes the adverse drug reactions (ADRs) spontaneously reported during early postmarketing phase vigilance from the time of its commercial launch in Japan.
All spontaneously reported ADRs following edoxaban use received by Daiichi Sankyo during early postmarketing phase vigilance from July 19, 2011, to January 18, 2012, were entered into the safety database and included in this review. Approximately 20,000 patients were estimated to have been treated with edoxaban.
The mean age of patients was 74.2 years, their mean weight was 59.4 kg, and approximately 70% were female. A total of 67 ADRs were reported in 56 patients, of which the majority included bleeding events (51 ADRs in 42 patients). Of these, 15 ADRs (in 14 patients) were serious, including cerebral hemorrhage (n = 1), gastric hemorrhage (n = 2; gastric hemorrhage [n = 1] and gastric ulcer hemorrhage [n = 1]), and surgical-site hemorrhage (n = 12; hemorrhage [n = 6], subcutaneous hemorrhage [n = 3], wound hemorrhage [n = 2], and wound hematoma [n = 1]). Most ADRs occurred within the first week of treatment and there were no fatalities. Nonserious ADRs associated with bleeding that occurred in >1 patient included subcutaneous hemorrhage (n = 9), wound hemorrhage (n = 5), postprocedural hematoma (n = 4), anemia (n = 4), and hemarthrosis (n = 3). Other nonserious ADRs not associated with bleeding and occurring in >1 patient included abnormal hepatic function (n = 4) and diarrhea (n = 2).
Safety data from the first 6 months of postmarketing experience with edoxaban did not identify any unforeseen safety signals, consistent with the known safety profile of edoxaban.
依度沙班是一种口服、每日一次的选择性直接因子Xa抑制剂，在日本被批准用于预防大型骨科手术后的静脉血栓栓塞。目前，依度沙班正处于III期临床开发阶段，用于预防心房颤动患者的中风和全身性栓塞事件，以及治疗和预防静脉血栓栓塞的复发。本报告描述了依度沙班在日本上市后早期警戒阶段自发报告的药物不良反应（ADR）。
2011年7月19日至2012年1月18日依度沙班上市后早期警戒阶段期间，第一三共公司收到的所有依度沙班使用后自发报告的ADR均录入安全数据库并纳入本综述。估计约有20000名患者接受了依度沙班治疗。
患者的平均年龄为74.2岁，平均体重为59.4kg，约70%为女性。56名患者共报告了67例ADR，其中大多数为出血事件（42例患者中有51例ADR）。其中，15例ADR（14例患者）为严重事件，包括脑出血（1例）、胃出血（2例；胃出血[1例]和胃溃疡出血[1例]）以及手术部位出血（12例；出血[6例]、皮下出血[3例]、伤口出血[2例]和伤口血肿[1例]）。大多数ADR发生在治疗的第一周内，且无死亡病例。在超过1名患者中发生的与出血相关的非严重ADR包括皮下出血（9例）、伤口出血（5例）、术后血肿（4例）、贫血（4例）和关节积血（3例）。在超过1名患者中发生的与出血无关的其他非严重ADR包括肝功能异常（4例）和腹泻（2例）。
依度沙班上市后前6个月的安全性数据未发现任何不可预见的安全信号，这与依度沙班已知的安全性概况一致。
