What conditions can defibrotide treat?

What conditions can defibrotide treat? On March 30, 2016, the FDA approved Defitelio® (defibrotide sodium) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome (SOS), renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT).

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 is a mixture of single-stranded oligonucleotides with anti-thrombotic and fibrinolysis-promoting 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.

The recommended dose of defibrotide for adult and pediatric patients is 6.25 mg/kg given every 6 hours as a 2-hour intravenous infusion. The dose should be based on the patient's baseline weight, which is defined as the patient's weight before the HSCT preparation protocol. 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 may enhance the pharmacodynamic activity of antithrombotic/fibrinolytic agents such as heparin or alteplase. Concomitant use of defibrinoside with antithrombotic or fibrinolytic agents is contraindicated due to increased risk of bleeding.

The mechanism of action of defibrotide has not been fully elucidated. In vitro, defibrinoside enhances the enzymatic activity of plasmin, which hydrolyzes fibrin clots. Studies evaluating the pharmacological effects of defibrotide on endothelial cells (ECs) have been primarily conducted in human microvascular endothelial cell lines. In vitro, 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.