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Clinical data
AHFS/ International Drug Names
  • X
Routes of
oral, i.m., i.v.
Legal status
Legal status
  • Rx only (where available)
Pharmacokinetic data
Bioavailability 58 - 70% orally (i.v. and i.m. = 100%)
Biological half-life t1/2-alpha = minutes; t1/2-beta = a few hours
CAS Number 83712-60-1 YesY
ATC code B01AX01 (WHO)
DrugBank DB04932 YesY
ChemSpider none
KEGG D07423 YesY
 NYesY (what is this?)  (verify)

Defibrotide (Defitelio, Gentium)[1] is a deoxyribonucleic acid derivative (single-stranded) derived from cow lung or porcine mucosa. It is an anticoagulant with a multiple mode of action (see below).

It has been used with antithrombin III.[2]


Defibrotide is available as an oral, intravenous, and intramuscular formulation. Its oral bioavailability is in the range of 58-70% of the parenteral forms. T1/2 alpha is in the range of minutes while T1/2 beta is in the range of hours in studies with oral radiolabelled defibrotide. These data suggest that defibrotide, in spite of its macromolecular nature, is absorbed well after oral administration. Due to the drug's short half-life, it is necessary to give the daily dose divided in 2 to 4 doses (see below).

Mode of action[edit]

The drug appears to prevent the formation of blood clots and to help dissolve blood clots by increasing levels of prostaglandin I2, E2, and prostacyclin, altering platelet activity, increasing tissue plasminogen activator (tPA-)function, and decreasing activity of tissue plasminogen activator inhibitor. Prostaglandin I2 relaxes the smooth muscle of blood vessels and prevents platelets from adhering to each other. Prostaglandin E2 at certain concentrations also inhibits platelet aggregation. Moreover, the drug provides additional beneficial anti-inflammatory and antiischemic activities as recent studies have shown. It is yet unclear, if the latter effects can be utilized clinically (e.g., treatment of ischemic stroke).

Unlike heparin and warfarin, defibrotide appears to have a relatively mild anticoagulant activity, which may be beneficial in the treatment of patients at high risk of bleeding complications. Nevertheless, patients with known bleeding disorders (e.g., hemophilia A) or recent abnormal bleedings should be treated cautiously and under close medical supervision.

The drug was marketed under the brand names Dasovas (FM), Noravid, and Prociclide in a variety of countries. In the USA it is marketed as Defitelio. The manufacturer is Gentium.

Approvals and indications[edit]

Defibrotide is used to treat or prevent a failure of normal blood flow (Veno-occlusive disease, VOD) in the liver of patients having had bone marrow transplants or received certain drugs such as oral estrogens, mercaptopurine, and many others.[citation needed] Without intensive treatment, VOD is often a fatal condition, leading to multiorgan failure. It has repeatedly been reported that defibrotide was able to resolve the condition completely and was well tolerated.[citation needed]

In April 2016 the US FDA approved it for the treatment of hepatic VOD after hematopoietic stem cell transplantation (HSCT).[3]

Other indications are: peripheral obliterative arterial disease, thrombophlebitis, and Raynaud's phenomenon.[citation needed] In very high doses, defibrotide is useful as treatment of acute myocardial infarction.[citation needed] The drug may also be used for the pre- and postoperative prophylaxis of deep venous thrombosis and can replace the heparin use during hemodialytic treatments.[citation needed]


It has been investigated for use in treatment of chronic venous insufficiency.[4]

Potential indications in the future[edit]

Other recent preclinical studies have demonstrated that defibrotide used in conjunction with Granulocyte Colony-Stimulating Factor (rhG-CSF) significantly increases the number of Peripheral Blood Progenitor Cells (Stem cells). The benefit of this increase in stem cells may be crucial for a variety of clinical indications, including graft engineering procedures and gene therapy programs. This would expand the clinical usefulness of defibrotide to a complete distinct area.

Very recently (since early 2006) combination therapy trials (phase I/II) with defibrotide plus melphalan, prednisone, and thalidomide in patients with multiple myeloma have been conducted. The addition of defibrotide is expected to decrease the myelosuppressive toxicity of melphalan. However, is too early for any definitive results at that stage.

Cautions and contraindications[edit]

  • The efficacy of the drug has been reported to be poorer in patients with diabetes mellitus.
  • Pregnancy: The drug should not be used during pregnancy, because adequate and well controlled human studies do not exist.
  • Lactation: No human data is available. In order to avoid damage to the newborn, the nursing mother should discontinue either the drug or breastfeeding, taking into account the importance of treatment to the mother.
  • Known Bleeding Disorders or Bleeding Tendencies having occurred recently: Defibrotide should be used cautiously. Before initiation of treatment, the usual coagulation values should be obtained as baseline and regularly controlled under treatment. The patient should be observed regularly regarding local or systemic bleeding events.


Increased bleeding and bruising tendency, irritation at the injection site, nausea, vomiting, heartburn, low blood pressure. Serious allergic reactions have not been observed so far.

Drug interactions[edit]

Use of heparin with defibrotide may increase the aPTT, reflecting reduced ability of the body to form a clot. Nothing is known about the concomitant application of other anticoagulants than heparin and dextran containing plasma-expanders, but it can be anticipated that the risk of serious bleeding will be increased considerably.


  1. ^ "Jazz Pharma Acquiring Gentium for $1B". Gen. Eng. Biotechnol. News (paper). 34 (2). January 15, 2014. p. 10. 
  2. ^ Haussmann U, Fischer J, Eber S, Scherer F, Seger R, Gungor T (June 2006). "Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy". Haematologica. 91 (6): 795–800. PMID 16769582. 
  3. ^ FDA Approves First Drug for Severe Hepatic VOD After HSCT. April 2016
  4. ^ Coccheri S, Andreozzi GM, D'Addato M, Gensini GF (June 2004). "Effects of defibrotide in patients with chronic deep insufficiency. The PROVEDIS study". Int Angiol. 23 (2): 100–7. PMID 15507885. 

External links[edit]