Abstract
Abstract 4697
Edoxaban, 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.
EPPV 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.
The 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).
| System . | ADR . | Serious . | Non-serious . | Total . |
|---|---|---|---|---|
| Blood | Anemia | 4 | 4 | |
| Nervous | Cerebral hemorrhage | 1 | 1 | |
| Vascular | Venous embolism | 1 | 1 | |
| Vascular hemorrhage | 6 | 1 | 7 | |
| Gastrointestinal | Diarrhea | 2 | 2 | |
| Feces discolored | 1 | 1 | ||
| Gastric hemorrhage | 1 | 1 | ||
| Gastric ulcer hemorrhage | 1 | 1 | ||
| Gastrointestinal hemorrhage | 1 | 1 | ||
| Gingival bleeding | 1 | 1 | ||
| Hematemesis | 1 | 1 | ||
| Hematochezia | 1 | 1 | ||
| Hepatobiliary | Abnormal hepatic function | 4 | 4 | |
| Hyperbilirubinemia | 1 | 1 | ||
| Jaundice | 1 | 1 | ||
| Liver disorder | 1 | 1 | ||
| Skin | Subcutaneous hemorrhage | 3 | 9 | 12 |
| Rash | 1 | 1 | ||
| Musculoskeletal | Hemarthrosis | 3 | 3 | |
| Joint swelling | 1 | 1 | ||
| Renal | Hematuria | 1 | 1 | |
| Reproductive | Metrorrhagia | 1 | 1 | |
| General | Edema | 1 | 1 | |
| Test results | Alanine aminotransferase increased | 1 | 1 | |
| Aspartate aminotransferase increased | 1 | 1 | ||
| Hemoglobin decreased | 1 | 1 | ||
| Liver function abnormal | 1 | 1 | ||
| Platelet count increased | 1 | 1 | ||
| Injury | Subcutaneous hematoma | 1 | 1 | |
| Wound hemorrhage | 2 | 5 | 7 | |
| Post-procedural hematoma | 4 | 4 | ||
| Wound hematoma | 1 | 1 | ||
| Total | 15 | 52 | 67 |
| System . | ADR . | Serious . | Non-serious . | Total . |
|---|---|---|---|---|
| Blood | Anemia | 4 | 4 | |
| Nervous | Cerebral hemorrhage | 1 | 1 | |
| Vascular | Venous embolism | 1 | 1 | |
| Vascular hemorrhage | 6 | 1 | 7 | |
| Gastrointestinal | Diarrhea | 2 | 2 | |
| Feces discolored | 1 | 1 | ||
| Gastric hemorrhage | 1 | 1 | ||
| Gastric ulcer hemorrhage | 1 | 1 | ||
| Gastrointestinal hemorrhage | 1 | 1 | ||
| Gingival bleeding | 1 | 1 | ||
| Hematemesis | 1 | 1 | ||
| Hematochezia | 1 | 1 | ||
| Hepatobiliary | Abnormal hepatic function | 4 | 4 | |
| Hyperbilirubinemia | 1 | 1 | ||
| Jaundice | 1 | 1 | ||
| Liver disorder | 1 | 1 | ||
| Skin | Subcutaneous hemorrhage | 3 | 9 | 12 |
| Rash | 1 | 1 | ||
| Musculoskeletal | Hemarthrosis | 3 | 3 | |
| Joint swelling | 1 | 1 | ||
| Renal | Hematuria | 1 | 1 | |
| Reproductive | Metrorrhagia | 1 | 1 | |
| General | Edema | 1 | 1 | |
| Test results | Alanine aminotransferase increased | 1 | 1 | |
| Aspartate aminotransferase increased | 1 | 1 | ||
| Hemoglobin decreased | 1 | 1 | ||
| Liver function abnormal | 1 | 1 | ||
| Platelet count increased | 1 | 1 | ||
| Injury | Subcutaneous hematoma | 1 | 1 | |
| Wound hemorrhage | 2 | 5 | 7 | |
| Post-procedural hematoma | 4 | 4 | ||
| Wound hematoma | 1 | 1 | ||
| Total | 15 | 52 | 67 |
Preliminary 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.
Kuroda:Daiichi Sankyo Pharma Development: Employment. Hotoda:Daiichi Sankyo Co., Ltd.: Employment. Nishikawa:Daiichi Sankyo Co., Ltd.: Employment. Nishiwaki:Daiichi Sankyo Co., Ltd.: Employment.
Author notes
Asterisk with author names denotes non-ASH members.
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