title: Postmarketing safety experience with edoxaban in Japan for thromboprophylaxis following major orthopedic surgery.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Chie
authors.initials: C
authors.lastname: Hirayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hotoda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishiwaki
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors; D013844:Thiazoles / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D011725:Pyridines; D013844:Thiazoles; C552171:edoxaban
keywords: early postmarketing phase vigilance; edoxaban; factor Xa; spontaneous reporting; thromboprophylaxis; venous thromboembolism