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

• Sinusoidal Obstruction Syndrome

Contraindications & Blackbox Warnings

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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

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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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Unlock Additional Data
Abciximab	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 Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
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 Data
Defitelio	Solution	80 mg	Intravenous	Jazz Pharmaceuticals Ireland Limited	2017-09-06	Not applicable
Defitelio	Injection, solution	80 mg/1mL	Intravenous	Jazz Pharmaceuticals, Inc.	2016-03-30	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

B01AX01 — Defibrotide

• B01AX — Other antithrombotic agents
• B01A — ANTITHROMBOTIC AGENTS
• B01 — ANTITHROMBOTIC AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Anticoagulants
• Antiplatelet agents
• Aptamers, Nucleotide
• Blood and Blood Forming Organs
• Carbohydrates
• Cardiovascular Agents
• Fibrin Modulating Agents
• Fibrinolytic Agents
• Glycosides
• Hematologic Agents
• Nucleic Acids, Nucleotides, and Nucleosides
• Nucleotides
• Polynucleotides

Classification

Not classified

Chemical Identifiers

UNII

568FY5I1YI

CAS number

83712-60-1

References

General References

1. Noseda G, Fragiacomo C, Ferrari D: Pharmacokinetics of defibrotide in healthy volunteers. Haemostasis. 1986;16 Suppl 1:26-30. [PubMed:3754833]
2. 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]
3. 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]
4. 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]
5. 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]
6. 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

RxNav

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	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	Novel Coronavirus Infectious Disease (COVID-19) / Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure	1
2	Recruiting	Prevention	Thrombotic Microangiopathies	1
2	Recruiting	Treatment	Acute Chest Syndrome / Sickle Cell Disease (SCD)	1
2	Recruiting	Treatment	Bone Marrow Transplant Complications / Sinusoidal Obstruction Syndrome / Veno-Occlusive Disease	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

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

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Drug created on October 21, 2007 16:23 / Updated on October 27, 2020 11:13