Post-Marketing Safety Experience with Edoxaban in Japan for Thromboprophylaxis Following Major Orthopedic Surgery

Abstract

AbstractAbstract 4697 BackgroundEdoxaban, an oral, selective, direct factor Xa inhibitor, is approved in Japan as a once-daily dose (15 mg or 30 mg tablets) for the prevention of venous thromboembolism (VTE) following major orthopedic surgery, including total knee arthroplasty, total hip arthroplasty, and hip fracture surgery. Currently, edoxaban is in phase 3 clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation as well as treatment and prevention of recurrence of VTE. This report describes the adverse drug reactions (ADRs) that were spontaneously reported during early post-marketing phase vigilance (EPPV) since the July 2011 commercial launch in Japan. MethodsEPPV was conducted for the initial 6 months from launch: July 19, 2011, to January 18, 2012. All ADRs that were spontaneously reported, were collected and analyzed. ResultsThe estimated exposure was approximately 20,000 patients. A total of 67 ADRs were reported in 56 patients, of which 15 (in 14 patients) were serious. The mean age of the patients was 74.1 years, mean weight was 59.4 kg, and approximately 70% of the patients were female. The majority of ADRs were bleeding events (51 ADRs in 42 patients), and serious ADRs included cerebral hemorrhage (n=1), gastric hemorrhage (n=1), gastric ulcer hemorrhage (n=1), and surgical site hemorrhage (n=12). Most of these ADRs occurred within the first week of treatment and there were no fatalities. The majority of non-serious adverse events associated with bleeding that occurred in more than one patient included subcutaneous hemorrhage (n=9), wound hemorrhage (n=5), post-procedural hematoma (n=4), anemia (n=4), and hemarthrosis (n=3). Other non-serious adverse events occurring in more than one patient included abnormal hepatic function (n=4) and diarrhea (n=2).SystemADRSeriousNon-seriousTotalBloodAnemia44NervousCerebral hemorrhage11VascularVenous embolism11Vascular hemorrhage617GastrointestinalDiarrhea22Feces discolored11Gastric hemorrhage11Gastric ulcer hemorrhage11Gastrointestinal hemorrhage11Gingival bleeding11Hematemesis11Hematochezia11HepatobiliaryAbnormal hepatic function44Hyperbilirubinemia11Jaundice11Liver disorder11SkinSubcutaneous hemorrhage3912Rash11MusculoskeletalHemarthrosis33Joint swelling11RenalHematuria11ReproductiveMetrorrhagia11GeneralEdema11Test resultsAlanine aminotransferase increased11Aspartate aminotransferase increased11Hemoglobin decreased11Liver function abnormal11Platelet count increased11InjurySubcutaneous hematoma11Wound hemorrhage257Post-procedural hematoma44Wound hematoma11Total155267 ConclusionsPreliminary data from EPPV for the first 6 months of commercial use of edoxaban did not identify any unforeseen safety signals. This evidence confirms the known safety profile of edoxaban—that edoxaban has been shown to be well tolerated. Disclosures:Kuroda:Daiichi Sankyo Pharma Development: Employment. Hotoda:Daiichi Sankyo Co., Ltd.: Employment. Nishikawa:Daiichi Sankyo Co., Ltd.: Employment. Nishiwaki:Daiichi Sankyo Co., Ltd.: Employment.