去纤苷获批适应症是什么？

The approved indication of defibrotide (defiteli) is the treatment of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT), and it is currently recognized as the most promising new drug for the treatment of this disease. The recommended dose for adult and pediatric patients is 6.25 mg/kg given as a 2-hour intravenous infusion every 6 hours. Defibrotide was administered for a minimum of 21 days. If signs and symptoms of hepatic VOD have not resolved after 21 days, continue defibrotide until resolution of VOD or up to a maximum of 60 days. Defibrotide must be diluted prior to infusion.

Defibrotide was first developed by Gentium Pharmaceuticals in Italy and was approved for marketing in the EU in October 2013. After Gentium Pharmaceuticals was acquired by American Jazz Pharmaceuticals, it was approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 30, 2016.

The mechanism of action of defibrotide has not been fully elucidated. Studies evaluating the pharmacological effects of defibrotide on endothelial cells (ECs) have been primarily conducted in human microvascular endothelial cell lines. Defibrinoside increases tissue plasminogen activator (t-PA) and thrombomodulin expression, and decreases von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis. Defibrotide protects ECs from chemotherapy, tumor necrosis factor-α (TNF-α), serum starvation, and perfusion-induced injury.

Hepatic veno-occlusive disease (HVOD) is one of the serious complications after hematopoietic stem cell transplantation (HSCT), and the mortality rate in patients with severe HVOD can be as high as 100%. Defibrotide (defiteli) is a mixture of single-stranded oligonucleotides with anti-thrombotic and fibrinolytic effects. In recent years, multiple clinical research results have shown that defibrotide is a safe and effective drug for preventing and treating HVOD after HSCT.