Defibrotide
Identification
- Name
- Defibrotide
- Accession Number
- DB04932
- Description
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
- Associated Conditions
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
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
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- 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 Unlock Additional DataAbciximab 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 Acemetacin is combined with Defibrotide. 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. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
- Product Ingredients
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 Unlock Additional DataDefitelio Solution 80 mg 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 
Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories
- ATC Codes
- B01AX01 — Defibrotide
- Drug Categories
- Classification
- Not classified
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. [PubMed:3754833]
- 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. [PubMed:7681375]
- 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. [PubMed:8511753]
- 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. [PubMed:17495522]
- 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. [PubMed:16584299]
- Pescador R, Porta R, Ferro L: An integrated view of the activities of defibrotide. Semin Thromb Hemost. 1996;22 Suppl 1:71-5. [PubMed:8807733]
- External Links
- PubChem Substance
- 46508192
- 1311089
- ChEMBL
- CHEMBL2108396
- PharmGKB
- PA164749105
- Wikipedia
- Defibrotide
- AHFS Codes
- 20:12.20 — Thrombolytic Agents
- FDA label
- Download (254 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Endotoxaemia / Healthy Volunteers 1 3 Completed Prevention Veno-Occlusive Disease 1 3 Completed Treatment Hepatic Veno-Occlusive Disease 1 3 Completed Treatment Severe Hepatic Veno-Occlusive Disease 1 2 Completed Prevention Thrombotic Microangiopathies 1 2 Completed Treatment Acute-graft-versus-host Disease / Graft Versus Host Disease (GVHD) / Graft Versus Host Disease, Acute 1 2 Completed Treatment Veno-Occlusive Disease 1 2 Not Yet Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 2 Not Yet Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure 1 2 Recruiting Treatment Acute Chest Syndrome / Sickle Cell Disease (SCD) 1
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 Capsule 400 MG Injection, solution Intravenous 200 MG/2.5ML - Prices
- Not Available
- Patents
- Not Available
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. [PubMed:8405101]
- 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. [PubMed:8405101]
- 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. [PubMed:8405101]
Drug created on October 21, 2007 16:23 / Updated on January 23, 2021 21:03