Dabigatran etexilate, the oral direct thrombin inhibitor, has now been successfully introduced into the clinic for the reduction of stroke in patients with atrial fibrillation in many countries around the world. In addition, it has found a role in 83 countries world wide in the prevention of venous thromboembolism after orthopedic hip and knee surgery. Dabigatran is a potent, selective and reversible inhibitor of thrombin that was developed by classical medicinal chemistry techniques in the early-mid 1990s. The resulting pharmacological profiling of the compound demonstrated potent anticoagulant and antithrombotic activity in various venous and arterial thrombosis models. In addition, no effect of vitamin K supplementation on its antithrombotic actions was found, in contrast to warfarin. The bleeding profile of this compound was very favorable when measured as safety margin over antithrombotic activity and as compared to warfarin. Dabigatran has also shown efficacy as an antithrombotic agent in models with mechanical heart valves, both in vitro and in vivo. In addition, the effect of thrombin inhibition by dabigatran on PAR1-mediated pathophysiology is also being elucidated. Chronic treatment of dabigatran etexilate in a mouse model of breast cancer has shown beneficial effects in reducing tumor growth progression and metastases. Fibrosis in the lungs induced by bleomycin was also attenuated in an animal model of pulmonary fibrosis after chronic treatment with dabigatran etexilate. In addition, atherosclerosis progression has been reduced in several models of atherosclerosis in mice after treatment of dabigatran for up to 20 weeks. These studies imply that thrombin may be a mediator between coagulation and inflammation and other proliferative processes and its direct inhibition by dabigatran may provide an added benefit, in addition to its antithrombotic and anticoagulant properties.

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In order to confirm the efficacy and safety of Desmopressin Injection 4 Kyowa, we conducted a post-marketing survey in the patients with mild / moderate hemophilia A or type 1 / type2A von Willebrand disease in Japan. During the ten-year survey, 234 patients from 83 medical institutions were enrolled. Two hundred twelve patients were eligible for the analysis of safety. One hundred thirty nine adverse reactions were reported in 66 patients (31.13%). Frequent adverse reactions were facial flushing (39 events, 18.40%), warm feeling (27 events, 12.74%), hot flushes (18 events, 8.49%), headache (13 events, 6.13%), oliguria (12 events, 5.66%), nausea (7 events, 3.30%) and thirst 7 events, 3.30%). Two cases of convulsive attack were reported and one of the events could have been prevented with a care on fluid balance. Based on these results of the survey, we considered that patients should be carefully controlled in fluid replacement therapy and water intake.
Hemostatic effects were found 65.22%, 62.50%, 93.10% and 94.74% in the patients with mild hemophilia A, moderate hemophilia A, type 1 von Willebrand disease and type2A von Willebrand disease, respectively. The percentage of clotting factors improvement were found 76.47%, 85.71% and 100% in the patients with hemophilla A, type 1 von Willebrand disease and type2A von Willebrand disease, respectively.

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