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Identification
NameNadroparin
Accession NumberDB08813
TypeSmall Molecule
GroupsApproved
Description

Nadroparin is a low molecular weight heparin (LMWH) which, when bound to antithrombin III (ATIII), accelerates the inactivation of factor II and factor Xa. Nadroparin halts the coagulation pathway by inhibiting the activation of thrombin (factor IIa) by factor Xa. The amplification of the fibrin clotting cascade is stopped once factors Xa and IIa are inactivated. It is derived from porcine sources and has a mean molecular size of 5000 daltons. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fraxiparinesolution9500 unitintravenous; subcutaneousAspen Pharma Trading Limited1998-02-05Not applicableCanada
Fraxiparinesolution9500 unitintravenous; subcutaneousAspen Pharma Trading Limited1998-02-05Not applicableCanada
Fraxiparinesolution9500 unitintravenous; subcutaneousAspen Pharma Trading Limited1998-02-05Not applicableCanada
Fraxiparinesolution9500 unitintravenous; subcutaneousAspen Pharma Trading Limited1998-02-05Not applicableCanada
Fraxiparinesolution9500 unitintravenous; subcutaneousAspen Pharma Trading Limited1998-02-05Not applicableCanada
Fraxiparine Fortesolution19000 unitintravenous; subcutaneousAspen Pharma Trading Limited1999-06-22Not applicableCanada
Fraxiparine Fortesolution19000 unitintravenous; subcutaneousAspen Pharma Trading Limited1999-06-22Not applicableCanada
Fraxiparine Fortesolution19000 unitintravenous; subcutaneousAspen Pharma Trading Limited1999-06-22Not applicableCanada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Nadroparin calcium
ThumbNot applicableDBSALT001135
Categories
UNIINot Available
CAS number9041-08-1
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
Pharmacology
IndicationNadroparin is used for prophylaxis of thromboembolic disorders and general surgery in orthopedic surgery, treatment of deep vein thrombosis, prevention of clotting during hemodialysis and treatment of unstable angina and non-Q wave myocardial infarction
PharmacodynamicsNadroparin is a low molecular weight heparin that is composed of a heterogeneous mixture of sulfated polysaccaride glycosaminoglycan chains. Th mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.
Mechanism of actionThe mechanism of action for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a pentasaccharide sequence which binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited.
Related Articles
AbsorptionAbsorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%.
Volume of distribution

3.59L

Protein bindingMuch lower compared to heparin, which has over 90% protein bound.
Metabolism

Nadroparin is metabolized in the liver.

Route of eliminationNadroparin is eliminated via the kidneys through non-saturable mechanisms.
Half lifeIn healthy patients, the half life is between 3.5hrs to 11.2hrs following subcutaneous administration.
Clearance

The clearance of nadroparin is 21.4 +/- 7.0mL/min

ToxicityOsteopenia with extended use, skin necrosis, thrombocytosis, severe immunologically-mediated thrombocytopenia, eosinophilia (rare), calcinosis rarely occurs at the injection site, severe bleeding, transient elevation of liver transaminases.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Solutionintravenous; subcutaneous9500 unit
Solutionintravenous; subcutaneous19000 unit
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
References
Synthesis ReferenceNot Available
General References
  1. Collignon F, Frydman A, Caplain H, Ozoux ML, Le Roux Y, Bouthier J, Thebault JJ: Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost. 1995 Apr;73(4):630-40. [PubMed:7495071 ]
  2. Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. [PubMed:8707165 ]
  3. Lai KN, Wang AY, Ho K, Szeto CC, Li M, Wong LK, Yu AW: Use of low-dose low molecular weight heparin in hemodialysis. Am J Kidney Dis. 1996 Nov;28(5):721-6. [PubMed:9158210 ]
  4. Boneu B, Navarro C, Cambus JP, Caplain H, d'Azemar P, Necciari J, Duret JP, Gaud C, Sie P: Pharmacodynamics and tolerance of two nadroparin formulations (10,250 and 20,500 anti Xa IU x ml(-1)) delivered for 10 days at therapeutic dose. Thromb Haemost. 1998 Feb;79(2):338-41. [PubMed:9493587 ]
  5. Laporte S, Mismetti P, Piquet P, Doubine S, Touchot A, Decousus H: Population pharmacokinetic of nadroparin calcium (Fraxiparine) in children hospitalised for open heart surgery. Eur J Pharm Sci. 1999 May;8(2):119-25. [PubMed:10210734 ]
  6. Ng HJ, Lee LH: Heparin-induced thrombocytopenia: acknowledging its presence in low-molecular weight heparin therapy. Int J Hematol. 2003 Feb;77(2):185-7. [PubMed:12627856 ]
  7. Breddin HK: Prophylaxis and treatment of deep-vein thrombosis. Semin Thromb Hemost. 2000;26 Suppl 1:47-52. [PubMed:11011806 ]
  8. Haas SK: Venous thromboembolic risk and its prevention in hospitalized medical patients. Semin Thromb Hemost. 2002 Dec;28(6):577-84. [PubMed:12536351 ]
  9. Davis R, Faulds D: Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. Drugs Aging. 1997 Apr;10(4):299-322. [PubMed:9108990 ]
  10. Iaremchuk AIa, Zotov AS, Cheshuk VE, Anikuc'ko NF, Zakhartseva LM, Diatel MV, Kravchenko AV, Lobanova OE, Sidorchuk OI: [Clinical effectiveness of nadroparin calcium in the surgical treatment of breast cancer]. Vopr Onkol. 2003;49(2):205-8. [PubMed:12785206 ]
  11. Vitale FV, Rotondo S, Sessa E, Antonelli G, Colina P, Parisi A, Giamo V, Ferrau F: Successful administration of a low dose of calcium nadroparin in patients suffering from pulmonary embolism and brain metastases: a report of two cases. J Oncol Pharm Pract. 2011 Jun;17(2):141-4. doi: 10.1177/1078155209353465. Epub 2009 Dec 16. [PubMed:20015933 ]
  12. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M: Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009 Oct;10(10):943-9. doi: 10.1016/S1470-2045(09)70232-3. Epub 2009 Aug 31. [PubMed:19726226 ]
External LinksNot Available
ATC CodesB01AB06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabAbciximab may increase the anticoagulant activities of Nadroparin.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Nadroparin.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Nadroparin.
AliskirenNadroparin may increase the hyperkalemic activities of Aliskiren.
AlteplaseAlteplase may increase the anticoagulant activities of Nadroparin.
AnistreplaseAnistreplase may increase the anticoagulant activities of Nadroparin.
ApixabanApixaban may increase the anticoagulant activities of Nadroparin.
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Nadroparin.
CanagliflozinNadroparin may increase the hyperkalemic activities of Canagliflozin.
ChlorotrianiseneChlorotrianisene may decrease the anticoagulant activities of Nadroparin.
Citric AcidCitric Acid may increase the anticoagulant activities of Nadroparin.
CollagenaseThe risk or severity of adverse effects can be increased when Nadroparin is combined with Collagenase.
Dabigatran etexilateDabigatran etexilate may increase the anticoagulant activities of Nadroparin.
DalteparinDalteparin may increase the anticoagulant activities of Nadroparin.
DasatinibDasatinib may increase the anticoagulant activities of Nadroparin.
DeferasiroxThe risk or severity of adverse effects can be increased when Nadroparin is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Nadroparin is combined with Deoxycholic Acid.
DesogestrelThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Desogestrel.
DicoumarolDicoumarol may increase the anticoagulant activities of Nadroparin.
DydrogesteroneThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Dydrogesterone.
Edetic AcidEdetic Acid may increase the anticoagulant activities of Nadroparin.
EdoxabanEdoxaban may increase the anticoagulant activities of Nadroparin.
EnoxaparinEnoxaparin may increase the anticoagulant activities of Nadroparin.
EplerenoneNadroparin may increase the hyperkalemic activities of Eplerenone.
Ethyl biscoumacetateEthyl biscoumacetate may increase the anticoagulant activities of Nadroparin.
Fondaparinux sodiumFondaparinux sodium may increase the anticoagulant activities of Nadroparin.
GestodeneThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Gestodene.
HeparinHeparin may increase the anticoagulant activities of Nadroparin.
HomoharringtonineThe risk or severity of adverse effects can be increased when Nadroparin is combined with Homoharringtonine.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Nadroparin is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Nadroparin.
InfliximabInfliximab may increase the anticoagulant activities of Nadroparin.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Nadroparin.
NintedanibThe risk or severity of adverse effects can be increased when Nadroparin is combined with Nintedanib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Nadroparin is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Nadroparin.
PaliferminThe serum concentration of Palifermin can be increased when it is combined with Nadroparin.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Nadroparin.
PentoxifyllinePentoxifylline may increase the anticoagulant activities of Nadroparin.
PerindoprilNadroparin may increase the hyperkalemic activities of Perindopril.
PhenindionePhenindione may increase the anticoagulant activities of Nadroparin.
PhenprocoumonPhenprocoumon may increase the anticoagulant activities of Nadroparin.
ProgesteroneThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Progesterone.
ReteplaseReteplase may increase the anticoagulant activities of Nadroparin.
RidogrelRidogrel may increase the anticoagulant activities of Nadroparin.
RivaroxabanNadroparin may increase the anticoagulant activities of Rivaroxaban.
StreptokinaseStreptokinase may increase the anticoagulant activities of Nadroparin.
SugammadexSugammadex may increase the anticoagulant activities of Nadroparin.
SulodexideSulodexide may increase the anticoagulant activities of Nadroparin.
TenecteplaseTenecteplase may increase the anticoagulant activities of Nadroparin.
TiboloneTibolone may increase the anticoagulant activities of Nadroparin.
TipranavirTipranavir may increase the anticoagulant activities of Nadroparin.
TositumomabThe risk or severity of adverse effects can be increased when Nadroparin is combined with Tositumomab.
TreprostinilTreprostinil may increase the anticoagulant activities of Nadroparin.
TriamtereneNadroparin may increase the hyperkalemic activities of Triamterene.
UrokinaseUrokinase may increase the anticoagulant activities of Nadroparin.
ValsartanNadroparin may increase the hyperkalemic activities of Valsartan.
Vitamin EVitamin E may increase the anticoagulant activities of Nadroparin.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Nadroparin.
WarfarinWarfarin may increase the anticoagulant activities of Nadroparin.
Food Interactions
  • Danshen, dong quai, evening primrose oil, gingko, policosanol, willowbark

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Serine-type endopeptidase inhibitor activity
Specific Function:
Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin.
Gene Name:
SERPINC1
Uniprot ID:
P01008
Molecular Weight:
52601.935 Da
References
  1. Davis R, Faulds D: Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. Drugs Aging. 1997 Apr;10(4):299-322. [PubMed:9108990 ]
  2. Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. [PubMed:8707165 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sialic acid binding
Specific Function:
Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.
Gene Name:
SELP
Uniprot ID:
P16109
Molecular Weight:
90833.105 Da
References
  1. Simonis D, Christ K, Alban S, Bendas G: Affinity and kinetics of different heparins binding to P- and L-selectin. Semin Thromb Hemost. 2007 Jul;33(5):534-9. [PubMed:17629851 ]
  2. Ludwig RJ, Alban S, Bistrian R, Boehncke WH, Kaufmann R, Henschler R, Gille J: The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo. Thromb Haemost. 2006 Mar;95(3):535-40. [PubMed:16525583 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regul...
Gene Name:
FOS
Uniprot ID:
P01100
Molecular Weight:
40694.855 Da
References
  1. Nagy Z, Turcsik V, Blasko G: The effect of LMWH (Nadroparin) on tumor progression. Pathol Oncol Res. 2009 Dec;15(4):689-92. doi: 10.1007/s12253-009-9204-7. [PubMed:19757196 ]
  2. Sustar V, Jansa R, Frank M, Hagerstrand H, Krzan M, Iglic A, Kralj-Iglic V: Suppression of membrane microvesiculation--a possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis. 2009 May-Jun;42(3):223-7. doi: 10.1016/j.bcmd.2009.01.012. Epub 2009 Mar 3. [PubMed:19261492 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.
Gene Name:
MYC
Uniprot ID:
P01106
Molecular Weight:
48803.55 Da
References
  1. Nagy Z, Turcsik V, Blasko G: The effect of LMWH (Nadroparin) on tumor progression. Pathol Oncol Res. 2009 Dec;15(4):689-92. doi: 10.1007/s12253-009-9204-7. [PubMed:19757196 ]
  2. Sustar V, Jansa R, Frank M, Hagerstrand H, Krzan M, Iglic A, Kralj-Iglic V: Suppression of membrane microvesiculation--a possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis. 2009 May-Jun;42(3):223-7. doi: 10.1016/j.bcmd.2009.01.012. Epub 2009 Mar 3. [PubMed:19261492 ]
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Drug created on June 14, 2011 23:17 / Updated on June 19, 2011 17:04