Defibrotide is a
deoxyribonucleic acid derivative extracted from mammalian organs, which has been developed for the treatment of a number of vascular disorders. It appears to increase fibrinolysis and may possess antithrombotic, antiatherosclerotic and anti-ischaemic actions, probably due to its ability to selectively increase
prostaglandin I2 and E2 levels and to increase
tissue plasminogen activator and decrease
plasminogen activator inhibitor function.
Defibrotide is available as an intravenous and intramuscular preparation, and also as an oral formulation for long term use. Trials performed to date have provided initial evidence that
defibrotide is effective in the treatment of peripheral obliterative arterial disease and acute
thrombophlebitis, while preliminary data suggest possible use in preventing
fibrin deposition in the circuitry of renal haemodialysis equipment. Efficacy in preventing
deep vein thrombosis after surgery has been demonstrated but
defibrotide does not appear to offer any therapeutic advantage over
heparin. Further clinical experience is required in other disorders, including acute
myocardial infarction, Raynaud's phenomenon, renal
thrombotic microangiopathy and renal transplant rejection, before adequate assessment of efficacy in these areas can be made.
Defibrotide is well tolerated, as assessed in trials of up to 6 months duration, with a low global incidence of adverse events (< 1 to 9%). Mild
allergic reactions and gastrointestinal disturbances have occasionally been described, and a hypotensive effect has also infrequently been observed. Thus, available data suggest that
defibrotide is a well tolerated agent with little or no
anticoagulant activity, which is conveniently available in both parenteral and oral formulations. Initial data indicate that the
drug may be a useful alternative in the treatment of peripheral obliterative arterial disease and
thrombophlebitis, while its therapeutic potential in other vascular disorders and efficacy relative to established agents remains to be fully determined.