Defibrotide

General information

Defibrotide is a polydeoxyribonucleotide extracted from mammalian organ [ ]. Its antithrombotic activity is partly ascribed to enhancement of eicosanoid metabolism, in particular increased release of prostacyclin, with ensuing vasodilatation and inhibition of platelet aggregation. An additional mechanism is activation of the fibrinolytic system, primarily increased activation of tissue plasminogen in the vessel wall.

The antithrombotic potential of defibrotide has been reported in patients with hepatic veno-occlusive disease after stem cell transplantation. In a randomized, placebo-controlled trial in 310 patients with claudication there was significant improvement in walking distance with defibrotide, but no difference in efficacy between the two doses of the drug tested (800 and 1200 mg/day) [ ]. Twenty patients stopped taking the drug because of cardiovascular events, the preset endpoints of the study. Seven others stopped because of adverse drug reactions, mainly gastrointestinal intolerance and skin reactions. They were equally distributed among the placebo and the two defibrotide groups.