Identification

Name
Nadroparin
Accession Number
DB08813
Type
Small Molecule
Groups
Approved, Investigational
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.

Synonyms
  • Nadroparina
  • Nadroparine
Product Ingredients
IngredientUNIICASInChI Key
Nadroparin calciumLIA7Z4002P37270-89-6Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FraxiparineSolution9500 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1998-02-05Not applicableCanada
FraxiparineSolution9500 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1998-02-05Not applicableCanada
FraxiparineSolution9500 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1998-02-05Not applicableCanada
FraxiparineSolution9500 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1998-02-05Not applicableCanada
FraxiparineSolution9500 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1998-02-05Not applicableCanada
Fraxiparine ForteSolution19000 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1999-06-22Not applicableCanada
Fraxiparine ForteSolution19000 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1999-06-22Not applicableCanada
Fraxiparine ForteSolution19000 unitIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1999-06-22Not applicableCanada
Categories
UNII
1K5KDI46KZ
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Nadroparin 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.

Associated Conditions
Pharmacodynamics

Nadroparin 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 action

The 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.

TargetActionsOrganism
AAntithrombin-III
potentiator
Human
UP-selectin
inhibitor
Human
UProto-oncogene c-Fos
inhibitor
Human
UMyc proto-oncogene protein
inhibitor
Human
Absorption

Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%.

Volume of distribution

3.59L

Protein binding

Much lower compared to heparin, which has over 90% protein bound.

Metabolism

Nadroparin is metabolized in the liver.

Route of elimination

Nadroparin is eliminated via the kidneys through non-saturable mechanisms.

Half life

In 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

Toxicity

Osteopenia 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 organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Nadroparin can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Nadroparin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Nadroparin is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Nadroparin can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Nadroparin can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Nadroparin is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Nadroparin can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Nadroparin can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Nadroparin.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Nadroparin.
Food Interactions
  • Danshen, dong quai, evening primrose oil, gingko, policosanol, willowbark

References

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 Links
PubChem Substance
347910374
Wikipedia
Nadroparin
ATC Codes
B01AB06 — Nadroparin
AHFS Codes
  • 20:12.04.16 — Heparins

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedTreatmentHepatocellular,Carcinoma1
2, 3Unknown StatusPreventionDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
3CompletedPreventionCancer, Advanced / Metastatic Cancers1
3CompletedPreventionThrombosis, Venous1
3CompletedPreventionVenous Thromboembolism (VTE)1
3CompletedTreatmentThrombosis, Venous1
3TerminatedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
3Unknown StatusPreventionPregnancy and Thrombophilia1
4CompletedTreatmentAcute Renal Failure (ARF)1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Liver Cirrhosis / Status;Splenectomy / Thrombosis, Venous1
4CompletedTreatmentPulmonary Embolism (PE) / Thromboembolism / Thrombotic events / Vascular Diseases1
4Not Yet RecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
4RecruitingPreventionDeep Venous Thrombosis / Pulmonary Embolism (PE)1
4RecruitingPreventionHigh Blood Pressure (Hypertension) / Liver Cirrhosis / Status;Splenectomy / Thrombosis, Venous1
4RecruitingTreatmentEndstage Renal Disease1
4RecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
4TerminatedNot AvailableMalignancies / Venous Thromboembolism (VTE)1
4Unknown StatusPreventionBypass Complications / Obesity, Morbid / Thromboembolism1
4Unknown StatusTreatmentAcute Ischemic Stroke (AIS)1
4Unknown StatusTreatmentPE - Pulmonary Thromboembolism / Pulmonary Embolism (PE)1
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedPreventionDeep Venous Thrombosis / Pulmonary Embolism (PE)2
Not AvailableCompletedPreventionNeoplasms, Esophageal / Neoplasms, Lung / Venous Thromboembolism (VTE)1
Not AvailableNot Yet RecruitingTreatmentRecurrent Pregnancy Losses / Undifferentiated Connective Tissue Disease1
Not AvailableRecruitingPreventionDeep-Venous Thrombosis1
Not AvailableUnknown StatusBasic ScienceHemodialysis Treatment / Renal Failure1
Not AvailableWithdrawnTreatmentAnticoagulation / Liver Cirrhosis / Portal Vein Thrombosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous; Subcutaneous9500 unit
SolutionIntravenous; Subcutaneous19000 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

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 a...
Gene Name
SERPINC1
Uniprot ID
P01008
Uniprot Name
Antithrombin-III
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 ligan...
Gene Name
SELP
Uniprot ID
P16109
Uniprot Name
P-selectin
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 s...
Gene Name
FOS
Uniprot ID
P01100
Uniprot Name
Proto-oncogene c-Fos
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
Uniprot Name
Myc proto-oncogene protein
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]

Drug created on June 14, 2011 23:17 / Updated on November 14, 2018 12:55