Postmarketing safety experience with edoxaban in Japan for thromboprophylaxis following major orthopedic surgery.

PURPOSE: 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. MATERIALS AND 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). CONCLUSION: 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.

Molecular states of prednisolone dispersed in folded sheet mesoporous silica (FSM-16).

Modes of molecular interaction between prednisolone and mesoporous materials have been investigated by the technique of solid-state NMR. Folded sheet mesoporous material (FSM-16) was used as host material and prednisolone was used as guest molecule. A suspension of FSM-16 in prednisolone dichloromethane solution was evaporated to prepare the evaporated samples. (13)C NMR spectroscopy was used as well as powder X-ray diffractometry and differential scanning calorimetry. Crystalline behavior of prednisolone disappeared in the evaporated samples, indicating the monomolecular dispersion of prednisolone in FSM-16 matrices. NMR peak shifts and broadening could be attributed to the molecular interaction between the A ring of prednisolone and FSM-16. Thermal properties of prednisolone were investigated after heat treatment of the evaporated samples. The results indicated that the thermal stability of the dispersion made from FSM-16 of large pore size was superior to that from FSM-16 of small pore size. Hydrocortisone was used to compare the dispersion state with prednisolone. It was suggested that the double bond at the C-1 and C-2 positions of prednisolone might play an important role in the process of adsorption of prednisolone to FSM-16.