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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
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.
Structured Indications
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).
TargetKindPharmacological actionActionsOrganismUniProt ID
Adenosine receptor A1ProteinunknownNot AvailableHumanP30542 details
Adenosine receptor A2aProteinunknownNot AvailableHumanP29274 details
Adenosine receptor A2bProteinunknownNot AvailableHumanP29275 details
Related Articles
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
Interactions
Drug Interactions
DrugInteractionDrug group
AbciximabDefibrotide may increase the anticoagulant activities of Abciximab.Approved
AcenocoumarolDefibrotide may increase the anticoagulant activities of Acenocoumarol.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Defibrotide is combined with Acetylsalicylic acid.Approved, Vet Approved
AlprostadilAlprostadil may increase the anticoagulant activities of Defibrotide.Approved, Investigational
AlteplaseDefibrotide may increase the anticoagulant activities of Alteplase.Approved
ALX-0081Defibrotide may increase the anticoagulant activities of ALX-0081.Investigational
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Defibrotide is combined with Aminosalicylic Acid.Approved
AnagrelideAnagrelide may increase the anticoagulant activities of Defibrotide.Approved
AncrodDefibrotide may increase the anticoagulant activities of Ancrod.Investigational
AnistreplaseDefibrotide may increase the anticoagulant activities of Anistreplase.Approved
Antithrombin III humanDefibrotide may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanThe risk or severity of adverse effects can be increased when Defibrotide is combined with Apixaban.Approved
AprotininThe therapeutic efficacy of Defibrotide can be decreased when used in combination with Aprotinin.Approved, Withdrawn
ArdeparinDefibrotide may increase the anticoagulant activities of Ardeparin.Approved, Withdrawn
ArgatrobanDefibrotide may increase the anticoagulant activities of Argatroban.Approved, Investigational
AstaxanthinDefibrotide may increase the anticoagulant activities of Astaxanthin.Investigational
AzelastineAzelastine may increase the anticoagulant activities of Defibrotide.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Defibrotide is combined with Balsalazide.Approved, Investigational
BatroxobinDefibrotide may increase the anticoagulant activities of Batroxobin.Experimental
BecaplerminDefibrotide may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BemiparinDefibrotide may increase the anticoagulant activities of Bemiparin.Approved
BeraprostDefibrotide may increase the anticoagulant activities of Beraprost.Investigational
BivalirudinDefibrotide may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
ButylphthalideButylphthalide may increase the anticoagulant activities of Defibrotide.Investigational
CangrelorDefibrotide may increase the anticoagulant activities of Cangrelor.Approved
CertoparinDefibrotide may increase the anticoagulant activities of Certoparin.Approved
CilostazolCilostazol may increase the anticoagulant activities of Defibrotide.Approved
Citric AcidDefibrotide may increase the anticoagulant activities of Citric Acid.Nutraceutical, Vet Approved
ClopidogrelClopidogrel may increase the anticoagulant activities of Defibrotide.Approved, Nutraceutical
CollagenaseThe risk or severity of adverse effects can be increased when Defibrotide is combined with Collagenase.Approved
Dabigatran etexilateDefibrotide may increase the anticoagulant activities of Dabigatran etexilate.Approved
DalteparinDefibrotide may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidDefibrotide may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DasatinibDasatinib may increase the anticoagulant activities of Defibrotide.Approved, Investigational
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Defibrotide is combined with Deoxycholic Acid.Approved
dersalazineThe risk or severity of adverse effects can be increased when Defibrotide is combined with dersalazine.Investigational
DesirudinDefibrotide may increase the anticoagulant activities of Desirudin.Approved
DesmoteplaseDefibrotide may increase the anticoagulant activities of Desmoteplase.Investigational
DextranDefibrotide may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Defibrotide may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Defibrotide may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Defibrotide may increase the anticoagulant activities of Dextran 75.Approved
DicoumarolDefibrotide may increase the anticoagulant activities of Dicoumarol.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Defibrotide is combined with Diflunisal.Approved
DipyridamoleDipyridamole may increase the anticoagulant activities of Defibrotide.Approved
DitazoleDefibrotide may increase the anticoagulant activities of Ditazole.Approved, Withdrawn
Drotrecogin alfaDefibrotide may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational, Withdrawn
Edetic AcidDefibrotide may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanDefibrotide may increase the anticoagulant activities of Edoxaban.Approved
EnoxaparinDefibrotide may increase the anticoagulant activities of Enoxaparin.Approved
EpinastineEpinastine may increase the anticoagulant activities of Defibrotide.Approved, Investigational
eplivanserineDefibrotide may increase the anticoagulant activities of eplivanserine.Investigational
EpoprostenolEpoprostenol may increase the antiplatelet activities of Defibrotide.Approved
EptifibatideEptifibatide may increase the anticoagulant activities of Defibrotide.Approved, Investigational
Ethyl biscoumacetateDefibrotide may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FibrinolysinDefibrotide may increase the anticoagulant activities of Fibrinolysin.Approved
FluindioneDefibrotide may increase the anticoagulant activities of Fluindione.Investigational
FondaparinuxDefibrotide may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumDefibrotide may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
GabexateDefibrotide may increase the anticoagulant activities of Gabexate.Investigational
GlucosamineGlucosamine may increase the antiplatelet activities of Defibrotide.Approved
HeparinDefibrotide may increase the anticoagulant activities of Heparin.Approved, Investigational
HigenamineDefibrotide may increase the anticoagulant activities of Higenamine.Investigational
HirulogDefibrotide may increase the anticoagulant activities of Hirulog.Experimental
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Defibrotide is combined with Ibritumomab tiuxetan.Approved
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Defibrotide.Approved
IbudilastIbudilast may increase the anticoagulant activities of Defibrotide.Approved, Investigational
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Defibrotide.Approved, Nutraceutical
idraparinuxDefibrotide may increase the anticoagulant activities of idraparinux.Investigational
IfenprodilIfenprodil may increase the anticoagulant activities of Defibrotide.Approved, Withdrawn
IloprostIloprost may increase the antiplatelet activities of Defibrotide.Approved, Investigational
IndobufenDefibrotide may increase the anticoagulant activities of Indobufen.Investigational
Kct 0809Defibrotide may increase the anticoagulant activities of Kct 0809.Investigational
KetanserinKetanserin may increase the anticoagulant activities of Defibrotide.Investigational
LepirudinDefibrotide may increase the anticoagulant activities of Lepirudin.Approved
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Defibrotide.Approved
MesalazineThe risk or severity of adverse effects can be increased when Defibrotide is combined with Mesalazine.Approved
MilrinoneMilrinone may increase the anticoagulant activities of Defibrotide.Approved
NadroparinDefibrotide may increase the anticoagulant activities of Nadroparin.Approved
NafamostatDefibrotide may increase the anticoagulant activities of Nafamostat.Investigational
NaftopidilNaftopidil may increase the anticoagulant activities of Defibrotide.Investigational
NCX 4016The risk or severity of adverse effects can be increased when Defibrotide is combined with NCX 4016.Investigational
NimesulideNimesulide may increase the anticoagulant activities of Defibrotide.Approved, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Defibrotide is combined with Nitroaspirin.Investigational
ObinutuzumabThe risk or severity of adverse effects can be increased when Defibrotide is combined with Obinutuzumab.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Defibrotide is combined with Olsalazine.Approved
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Defibrotide.Approved
OtamixabanDefibrotide may increase the anticoagulant activities of Otamixaban.Investigational
ParnaparinDefibrotide may increase the anticoagulant activities of Parnaparin.Approved
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Defibrotide.Approved
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Defibrotide.Approved, Investigational
PhenindioneDefibrotide may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonDefibrotide may increase the anticoagulant activities of Phenprocoumon.Approved
PlasminDefibrotide may increase the anticoagulant activities of Plasmin.Investigational
PrasugrelDefibrotide may increase the anticoagulant activities of Prasugrel.Approved
Protein CDefibrotide may increase the anticoagulant activities of Protein C.Approved
Protein S humanDefibrotide may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeDefibrotide may increase the anticoagulant activities of Protocatechualdehyde.Approved
RamatrobanRamatroban may increase the anticoagulant activities of Defibrotide.Investigational
ResveratrolResveratrol may increase the anticoagulant activities of Defibrotide.Experimental, Investigational
ReteplaseDefibrotide may increase the anticoagulant activities of Reteplase.Approved
ReviparinDefibrotide may increase the anticoagulant activities of Reviparin.Approved
RidogrelRidogrel may increase the anticoagulant activities of Defibrotide.Approved
RivaroxabanDefibrotide may increase the anticoagulant activities of Rivaroxaban.Approved
RosiglitazoneDefibrotide may increase the anticoagulant activities of Rosiglitazone.Approved, Investigational
Salicylic acidThe risk or severity of adverse effects can be increased when Defibrotide is combined with Salicylic acid.Approved, Vet Approved
SCH-530348SCH-530348 may increase the anticoagulant activities of Defibrotide.Investigational
SelexipagDefibrotide may increase the anticoagulant activities of Selexipag.Approved
SevofluraneSevoflurane may increase the anticoagulant activities of Defibrotide.Approved, Vet Approved
SRT501SRT501 may increase the anticoagulant activities of Defibrotide.Investigational
StreptokinaseDefibrotide may increase the anticoagulant activities of Streptokinase.Approved
SulodexideDefibrotide may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TenecteplaseDefibrotide may increase the anticoagulant activities of Tenecteplase.Approved
TesmilifeneTesmilifene may increase the anticoagulant activities of Defibrotide.Investigational
TicagrelorDefibrotide may increase the anticoagulant activities of Ticagrelor.Approved
TiclopidineTiclopidine may increase the anticoagulant activities of Defibrotide.Approved
TinzaparinDefibrotide may increase the anticoagulant activities of Tinzaparin.Approved
TipranavirTipranavir may increase the antiplatelet activities of Defibrotide.Approved, Investigational
TirofibanTirofiban may increase the anticoagulant activities of Defibrotide.Approved
TositumomabThe risk or severity of adverse effects can be increased when Defibrotide is combined with Tositumomab.Approved
TranilastTranilast may increase the anticoagulant activities of Defibrotide.Approved, Investigational
TrapidilTrapidil may increase the anticoagulant activities of Defibrotide.Approved
TreprostinilTreprostinil may increase the antiplatelet activities of Defibrotide.Approved, Investigational
TriflusalDefibrotide may increase the anticoagulant activities of Triflusal.Approved
UrokinaseDefibrotide may increase the anticoagulant activities of Urokinase.Approved, Investigational, Withdrawn
Vitamin EVitamin E may increase the antiplatelet activities of Defibrotide.Approved, Nutraceutical, Vet Approved
VorapaxarDefibrotide may increase the anticoagulant activities of Vorapaxar.Approved
WarfarinDefibrotide may increase the anticoagulant activities of Warfarin.Approved
XimelagatranDefibrotide may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
Ym150Defibrotide may increase the anticoagulant activities of Ym150.Investigational
Food InteractionsNot 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous80 mg/mL
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
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

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 ]
Comments
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24