Defibrotide
Identification
- Summary
Defibrotide is a mixture of single-stranded oligonucleotides used in the treatment of severe hepatic veno-occlusive disease with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation.
- Brand Names
- Defitelio
- Generic Name
- Defibrotide
- DrugBank Accession Number
- DB04932
- Background
Defibrotide is the sodium salt of a mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has been shown to have antithrombotic, anti-inflammatory and anti-ischemic properties (but without associated significant systemic anticoagulant effects). It is marketed under the brand names Dasovas (FM), Noravid, and Prociclide in a variety of countries. In the USA it is was approved in March, 2016 as Defitelio.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Nucleic Acid Based Therapies
Oligonucleotides - Synonyms
- Defibrotide free acid
- Defibrotide free acid (porcine mucosa)
- Defibrotide free acid (porcine)
Pharmacology
- Indication
Indicated for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).Label
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- Contraindications & Blackbox Warnings
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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.
- Mechanism of action
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 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 sudies have shown. It is yet unclear, if the latter effects can be utilized clinically (e.g., treatment of ischemic stroke).
Target Actions Organism UAdenosine receptor A1 Not Available Humans UAdenosine receptor A2a Not Available Humans UAdenosine receptor A2b Not Available Humans - Absorption
Bioavailability is 58-70% following oral administration, compared to parenteral forms (i.v. and i.m. = 100%).
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
t1/2-alpha = minutes (10-20 minutes in rat); t1/2-beta = a few hours
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Defibrotide. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Defibrotide. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Defibrotide is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Defibrotide is combined with Acenocoumarol. Acetylsalicylic acid Acetylsalicylic acid may increase the antiplatelet activities of Defibrotide. Albutrepenonacog alfa The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Defibrotide. Alclofenac The risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Defibrotide. Aldesleukin The risk or severity of bleeding can be increased when Defibrotide is combined with Aldesleukin. Alemtuzumab The risk or severity of bleeding can be increased when Defibrotide is combined with Alemtuzumab. Alteplase The risk or severity of bleeding can be increased when Defibrotide is combined with Alteplase. 
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- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
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Ingredient UNII CAS InChI Key Defibrotide sodium L7CHH2B2J0 Not Available Not applicable - International/Other Brands
- Dasovas / Noravid / Prociclide
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Defitelio Solution 80 mg / mL Intravenous Jazz Pharmaceuticals Ireland Limited 2017-09-06 Not applicable Canada 
Defitelio Injection, solution 80 mg/1mL Intravenous Jazz Pharmaceuticals, Inc. 2016-03-30 Not applicable US 
Categories
- ATC Codes
- B01AX01 — Defibrotide
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 568FY5I1YI
- CAS number
- 83712-60-1
References
- General References
- Noseda G, Fragiacomo C, Ferrari D: Pharmacokinetics of defibrotide in healthy volunteers. Haemostasis. 1986;16 Suppl 1:26-30. [Article]
- Palmer KJ, Goa KL: Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. Drugs. 1993 Feb;45(2):259-94. [Article]
- Fisher J, Johnston AM, Holland TK, McCallum J, Pescador R, Mantovani M, Prino G: Pharmacokinetics, absorption, distribution and disposition of [125I]-defibrotide following intravenous or oral administration in the rat. Thromb Res. 1993 Apr 1;70(1):77-90. [Article]
- Koehl GE, Geissler EK, Iacobelli M, Frei C, Burger V, Haffner S, Holler E, Andreesen R, Schlitt HJ, Eissner G: Defibrotide: an endothelium protecting and stabilizing drug, has an anti-angiogenic potential in vitro and in vivo. Cancer Biol Ther. 2007 May;6(5):686-90. Epub 2007 Feb 3. [Article]
- Kornblum N, Ayyanar K, Benimetskaya L, Richardson P, Iacobelli M, Stein CA: Defibrotide, a polydisperse mixture of single-stranded phosphodiester oligonucleotides with lifesaving activity in severe hepatic veno-occlusive disease: clinical outcomes and potential mechanisms of action. Oligonucleotides. 2006 Spring;16(1):105-14. [Article]
- Pescador R, Porta R, Ferro L: An integrated view of the activities of defibrotide. Semin Thromb Hemost. 1996;22 Suppl 1:71-5. [Article]
- External Links
- PubChem Substance
- 46508192
- 1311089
- ChEMBL
- CHEMBL2108396
- PharmGKB
- PA164749105
- Wikipedia
- Defibrotide
- FDA label
- Download (254 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Endotoxaemia / Healthy Subjects (HS) 1 3 Completed Prevention Veno-Occlusive Disease 1 3 Completed Treatment Severe Hepatic Veno Occlusive Disease 1 3 Completed Treatment Veno Occlusive Disease, Hepatic 1 2 Active Not Recruiting Treatment Acute Chest Syndrome / Sickle Cell Disease (SCD) 1 2 Completed Prevention Thrombotic Microangiopathies 1 2 Completed Treatment Acute Graft-Versus-Host Disease (GVHD) / Graft Versus Host Disease (cGvHD) 1 2 Completed Treatment Veno-Occlusive Disease 1 2 Recruiting Treatment Bone Marrow Transplant Complications / Sinusoidal Obstruction Syndrome (SOS) / Veno-Occlusive Disease 1 2 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 80 mg/1mL Injection, solution, concentrate Intravenous 80 MG/ML Solution Intravenous 80 mg / mL Capsule Injection, solution Intravenous - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US11085043 No 2012-06-22 2032-06-22 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Purine nucleoside binding
- Specific Function
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- ADORA1
- Uniprot ID
- P30542
- Uniprot Name
- Adenosine receptor A1
- Molecular Weight
- 36511.325 Da
References
- Bianchi G, Barone D, Lanzarotti E, Tettamanti R, Porta R, Moltrasio D, Cedro A, Salvetti L, Mantovani M, Prino G: Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist. Eur J Pharmacol. 1993 Jul 20;238(2-3):327-34. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Identical protein binding
- Specific Function
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name
- ADORA2A
- Uniprot ID
- P29274
- Uniprot Name
- Adenosine receptor A2a
- Molecular Weight
- 44706.925 Da
References
- Bianchi G, Barone D, Lanzarotti E, Tettamanti R, Porta R, Moltrasio D, Cedro A, Salvetti L, Mantovani M, Prino G: Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist. Eur J Pharmacol. 1993 Jul 20;238(2-3):327-34. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled adenosine receptor activity
- Specific Function
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name
- ADORA2B
- Uniprot ID
- P29275
- Uniprot Name
- Adenosine receptor A2b
- Molecular Weight
- 36332.655 Da
References
- Bianchi G, Barone D, Lanzarotti E, Tettamanti R, Porta R, Moltrasio D, Cedro A, Salvetti L, Mantovani M, Prino G: Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist. Eur J Pharmacol. 1993 Jul 20;238(2-3):327-34. [Article]
Drug created on October 21, 2007 22:23 / Updated on October 16, 2021 12:31