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Identification
NameDefibrotide
Accession NumberDB04932
TypeBiotech
GroupsApproved, Investigational
DescriptionDefibrotide 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.
Protein structureNo structure small
Related Articles
Protein chemical formulaNot Available
Protein average weightNot Available
SequencesNot Available
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Defitelioinjection, solution80 mg/mLintravenousJazz Pharmaceuticals, Inc.2016-03-30Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DasovasNot Available
NoravidNot Available
ProciclideNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Defibrotide sodium
ThumbNot applicableDBSALT001719
Categories
UNII438HCF2X0M
CAS number83712-60-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationDefibrotide is used to treat or prevent a failure of normal blood flow (occlusive venous disease, OVD) in the liver of patients who have had bone marrow transplants or received certain drugs such as oral estrogens, mercaptopurine, and many others.
PharmacodynamicsDefibrotide 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 actionThe 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).
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AbsorptionBioavailability is 58-70% following oral administration, compared to parenteral forms (i.v. and i.m. = 100%).
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifet1/2-alpha = minutes (10-20 minutes in rat); t1/2-beta = a few hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionintravenous80 mg/mL
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesB01AX01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabDefibrotide may increase the anticoagulant activities of Abciximab.
AcenocoumarolDefibrotide may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Defibrotide.
AlprostadilAlprostadil may increase the anticoagulant activities of Defibrotide.
AlprostadilDefibrotide may increase the antiplatelet activities of Alprostadil.
AlteplaseDefibrotide may increase the anticoagulant activities of Alteplase.
ALX-0081Defibrotide may increase the anticoagulant activities of ALX-0081.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Defibrotide.
AnagrelideAnagrelide may increase the anticoagulant activities of Defibrotide.
AncrodDefibrotide may increase the anticoagulant activities of Ancrod.
AnistreplaseDefibrotide may increase the anticoagulant activities of Anistreplase.
Antithrombin III humanDefibrotide may increase the anticoagulant activities of Antithrombin III human.
ApixabanDefibrotide may increase the anticoagulant activities of Apixaban.
AprotininThe therapeutic efficacy of Defibrotide can be decreased when used in combination with Aprotinin.
ArdeparinDefibrotide may increase the anticoagulant activities of Ardeparin.
ArgatrobanDefibrotide may increase the anticoagulant activities of Argatroban.
AstaxanthinDefibrotide may increase the anticoagulant activities of Astaxanthin.
AzelastineAzelastine may increase the anticoagulant activities of Defibrotide.
AzelastineDefibrotide may increase the antiplatelet activities of Azelastine.
BatroxobinDefibrotide may increase the anticoagulant activities of Batroxobin.
BecaplerminDefibrotide may increase the anticoagulant activities of Becaplermin.
BemiparinDefibrotide may increase the anticoagulant activities of Bemiparin.
BeraprostDefibrotide may increase the anticoagulant activities of Beraprost.
BivalirudinDefibrotide may increase the anticoagulant activities of Bivalirudin.
CangrelorDefibrotide may increase the anticoagulant activities of Cangrelor.
CertoparinDefibrotide may increase the anticoagulant activities of Certoparin.
CilostazolCilostazol may increase the anticoagulant activities of Defibrotide.
Citric AcidDefibrotide may increase the anticoagulant activities of Citric Acid.
ClopidogrelClopidogrel may increase the anticoagulant activities of Defibrotide.
CollagenaseThe risk or severity of adverse effects can be increased when Defibrotide is combined with Collagenase.
Dabigatran etexilateDefibrotide may increase the anticoagulant activities of Dabigatran etexilate.
DalteparinDefibrotide may increase the anticoagulant activities of Dalteparin.
DanaparoidDefibrotide may increase the anticoagulant activities of Danaparoid.
DasatinibDasatinib may increase the anticoagulant activities of Defibrotide.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Defibrotide is combined with Deoxycholic Acid.
DesirudinDefibrotide may increase the anticoagulant activities of Desirudin.
DesmoteplaseDefibrotide may increase the anticoagulant activities of Desmoteplase.
DextranDefibrotide may increase the anticoagulant activities of Dextran.
Dextran 40Defibrotide may increase the anticoagulant activities of Dextran 40.
Dextran 70Defibrotide may increase the anticoagulant activities of Dextran 70.
Dextran 75Defibrotide may increase the anticoagulant activities of Dextran 75.
DicoumarolDefibrotide may increase the anticoagulant activities of Dicoumarol.
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Defibrotide.
DipyridamoleDipyridamole may increase the anticoagulant activities of Defibrotide.
DitazoleDefibrotide may increase the anticoagulant activities of Ditazole.
Drotrecogin alfaDefibrotide may increase the anticoagulant activities of Drotrecogin alfa.
Edetic AcidDefibrotide may increase the anticoagulant activities of Edetic Acid.
EdoxabanDefibrotide may increase the anticoagulant activities of Edoxaban.
EnoxaparinDefibrotide may increase the anticoagulant activities of Enoxaparin.
EpinastineEpinastine may increase the anticoagulant activities of Defibrotide.
EpinastineDefibrotide may increase the antiplatelet activities of Epinastine.
EpoprostenolEpoprostenol may increase the anticoagulant activities of Defibrotide.
EptifibatideEptifibatide may increase the anticoagulant activities of Defibrotide.
Ethyl biscoumacetateDefibrotide may increase the anticoagulant activities of Ethyl biscoumacetate.
FibrinolysinDefibrotide may increase the anticoagulant activities of Fibrinolysin.
Fondaparinux sodiumDefibrotide may increase the anticoagulant activities of Fondaparinux sodium.
GlucosamineGlucosamine may increase the antiplatelet activities of Defibrotide.
HeparinDefibrotide may increase the anticoagulant activities of Heparin.
HirulogDefibrotide may increase the anticoagulant activities of Hirulog.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Defibrotide is combined with Ibritumomab tiuxetan.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Defibrotide.
IbudilastIbudilast may increase the anticoagulant activities of Defibrotide.
IbudilastDefibrotide may increase the antiplatelet activities of Ibudilast.
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Defibrotide.
Icosapent ethylDefibrotide may increase the antiplatelet activities of Icosapent ethyl.
IfenprodilIfenprodil may increase the anticoagulant activities of Defibrotide.
IfenprodilDefibrotide may increase the antiplatelet activities of Ifenprodil.
IloprostIloprost may increase the anticoagulant activities of Defibrotide.
LepirudinDefibrotide may increase the anticoagulant activities of Lepirudin.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Defibrotide.
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Defibrotide.
MilrinoneMilrinone may increase the anticoagulant activities of Defibrotide.
MilrinoneDefibrotide may increase the antiplatelet activities of Milrinone.
NadroparinDefibrotide may increase the anticoagulant activities of Nadroparin.
NCX 4016Defibrotide may increase the anticoagulant activities of NCX 4016.
NimesulideNimesulide may increase the anticoagulant activities of Defibrotide.
NimesulideDefibrotide may increase the antiplatelet activities of Nimesulide.
ObinutuzumabThe risk or severity of adverse effects can be increased when Defibrotide is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Defibrotide.
OtamixabanDefibrotide may increase the anticoagulant activities of Otamixaban.
ParnaparinDefibrotide may increase the anticoagulant activities of Parnaparin.
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Defibrotide.
Pentosan PolysulfateDefibrotide may increase the anticoagulant activities of Pentosan Polysulfate.
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Defibrotide.
PhenindioneDefibrotide may increase the anticoagulant activities of Phenindione.
PhenprocoumonDefibrotide may increase the anticoagulant activities of Phenprocoumon.
PlasminDefibrotide may increase the anticoagulant activities of Plasmin.
PrasugrelDefibrotide may increase the anticoagulant activities of Prasugrel.
Protein CDefibrotide may increase the anticoagulant activities of Protein C.
ProtocatechualdehydeDefibrotide may increase the anticoagulant activities of Protocatechualdehyde.
ResveratrolResveratrol may increase the anticoagulant activities of Defibrotide.
ResveratrolDefibrotide may increase the antiplatelet activities of Resveratrol.
ReteplaseDefibrotide may increase the anticoagulant activities of Reteplase.
ReviparinDefibrotide may increase the anticoagulant activities of Reviparin.
RidogrelRidogrel may increase the anticoagulant activities of Defibrotide.
RidogrelDefibrotide may increase the antiplatelet activities of Ridogrel.
RivaroxabanDefibrotide may increase the anticoagulant activities of Rivaroxaban.
RosiglitazoneDefibrotide may increase the anticoagulant activities of Rosiglitazone.
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Defibrotide.
SCH-530348SCH-530348 may increase the anticoagulant activities of Defibrotide.
SCH-530348Defibrotide may increase the antiplatelet activities of SCH-530348.
SelexipagDefibrotide may increase the anticoagulant activities of Selexipag.
SevofluraneSevoflurane may increase the anticoagulant activities of Defibrotide.
SevofluraneDefibrotide may increase the antiplatelet activities of Sevoflurane.
SRT501SRT501 may increase the anticoagulant activities of Defibrotide.
SRT501Defibrotide may increase the antiplatelet activities of SRT501.
StreptokinaseDefibrotide may increase the anticoagulant activities of Streptokinase.
SulodexideDefibrotide may increase the anticoagulant activities of Sulodexide.
TenecteplaseDefibrotide may increase the anticoagulant activities of Tenecteplase.
TesmilifeneTesmilifene may increase the anticoagulant activities of Defibrotide.
TesmilifeneDefibrotide may increase the antiplatelet activities of Tesmilifene.
TicagrelorDefibrotide may increase the anticoagulant activities of Ticagrelor.
TiclopidineTiclopidine may increase the anticoagulant activities of Defibrotide.
TinzaparinDefibrotide may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the antiplatelet activities of Defibrotide.
TirofibanTirofiban may increase the anticoagulant activities of Defibrotide.
TositumomabThe risk or severity of adverse effects can be increased when Defibrotide is combined with Tositumomab.
TranilastTranilast may increase the anticoagulant activities of Defibrotide.
TranilastDefibrotide may increase the antiplatelet activities of Tranilast.
TrapidilTrapidil may increase the anticoagulant activities of Defibrotide.
TrapidilDefibrotide may increase the antiplatelet activities of Trapidil.
TreprostinilDefibrotide may increase the anticoagulant activities of Treprostinil.
TreprostinilTreprostinil may increase the antiplatelet activities of Defibrotide.
TriflusalDefibrotide may increase the anticoagulant activities of Triflusal.
UrokinaseDefibrotide may increase the anticoagulant activities of Urokinase.
Vitamin EVitamin E may increase the antiplatelet activities of Defibrotide.
VorapaxarDefibrotide may increase the anticoagulant activities of Vorapaxar.
WarfarinDefibrotide may increase the anticoagulant activities of Warfarin.
XimelagatranDefibrotide may increase the anticoagulant activities of Ximelagatran.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
Molecular Weight:
36511.325 Da
References
  1. 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
Human
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
Molecular Weight:
44706.925 Da
References
  1. 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
Human
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
Molecular Weight:
36332.655 Da
References
  1. 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 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24