Identification

Name
Tinzaparin
Accession Number
DB06822
Description

Tinzaparin is a low molecular weight heparin (LMWH), produced by enzymatic depolymerization of unfractionated heparin from porcine intestinal mucosa. It is a heterogeneous mixture of with an average molecular weight between 5500 and 7500 daltons. Tinzaparin is composed of molecules with and without a special site for high affinity binding to antithrombin III (ATIII). This complex greatly accelerates the inhibition of factor Xa. It is an anticoagulant and considered an antithrombotic. Tinzaparin must be given either subcutaneously or parenterally. LMWHs are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Type
Small Molecule
Groups
Approved
Synonyms
  • Tinzaparin sodium
  • Tinzaparina

Pharmacology

Indication

Tinzaparin is used for the prevention of postoperative venous thromboembolism in patients undergoing orthopedic surgery and in patients undergoing general surgery who are at high risk of developing postoperative venous thromboembolism. It is also used for the treatment of deep vein thrombosis and/or pulmonary embolism. It is indicated for use in preventing clot formation in indwelling intravenous lines for hemodialysis.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Tinzaparin, like other LMWHs, have a higher anti-Xa activity than anti-IIa activity. The anti-Xa activity of tinzaparin is 2.0 +/- 0.5 times greater than its to anti-IIa activity. Heparin exhibits approximately equal inhibitory activity against Xa and IIa. Tinzaparin is an anticoagulant that blocks the formation of thrombi. Like all LMWHs, tinzaparin only causes activated partial thromboplastin time (aPTT) prolongation at higher doses and routine monitoring is not recommended. However, anti-factor Xa levels may be monitored in some conditions such as pregnancy and renal dysfunction. Its use should be avoided in patients with a creatinine clearance less than 20 mL/min. In these patients, unfractionated heparin should be used. Tinzaparin can be used in patients who have a creatinine clearance between 20-30 mL/min, giving it the highest safety threshold for use in renal failure patients compared to all the LMWHs.

Mechanism of action

Tinzaparin binds to the plasma protein antithrombin III, forming a complex with then accelerates the inhibition of factor Xa. Its affinity for factor Xa is 2-4 times greater than that of unbound ATIII. The inactivation of factor Xa in turn will exponentially generation of thrombin (factor IIa) molecules, which is needed to activate fibrinogen to fibrin. The coagulation cascade is inhibited because fibrin cannot be formed in the presence of tinzaparin. Like all LMWH, it cannot be given intramuscularly due to increased risk of hematoma.

TargetActionsOrganism
AAntithrombin-III
potentiator
Humans
UIntegrin alpha-4
inhibitor
Humans
UStromal cell-derived factor 1
binder
Humans
Absorption

Subcutaneous injection - about 90% when measured as anti-Xa activity versus 67% for anti-IIa activity.

Volume of distribution

Anti-Xa activity is 4 L. Anti-IIa activity is 10.9 L

Protein binding

Low protein binding compared to unfractionated heparin.

Metabolism

Sulfation and polymerization occurs in the liver.

Route of elimination

Linear elimination through kidneys

Half-life

Anti-Xa activity is 82 minutes. Anti-IIa activity is 71 minutes.

Clearance

Clearance is dose-dependant. The clearance of tinzaparin based on anti-Xa activity ranged from 1.14 to 2.04 L/hr

Adverse Effects
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Toxicity

Osteoporosis with increasing duration of use, bleeding, alopecia, heparin induced thrombocytopenia (HIT). All of these adverse drug reactions occur less with LMWH compared to unfractionated heparin. Tinzaparin showed no toxic effects at doses up to 5 mg/kg in mice, rats, or dogs in standard acute, subacute, and chronic toxicity studies.

Affected organisms
Not Available
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.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Tinzaparin.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Tinzaparin.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Tinzaparin.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Tinzaparin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Tinzaparin.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Tinzaparin.
Albutrepenonacog alfaThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Tinzaparin.
AlclofenacThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Tinzaparin.
AldesleukinThe risk or severity of bleeding can be increased when Tinzaparin is combined with Aldesleukin.
AlemtuzumabThe risk or severity of bleeding can be increased when Tinzaparin is combined with Alemtuzumab.
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

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
InnohepInjection, solution20000 [iU]/1mLSubcutaneousLeo Pharma2010-07-012013-08-01US flag
InnohepSolution10000 unitSubcutaneousLeo Pharma2011-09-09Not applicableCanada flag
InnohepSolution12000 unitSubcutaneousLeo Pharma2014-09-30Not applicableCanada flag
InnohepSolution20000 unitSubcutaneousLeo Pharma1997-02-28Not applicableCanada flag
InnohepSolution20000 unitSubcutaneousLeo Pharma2011-09-16Not applicableCanada flag
InnohepInjection20000 [iU]/1mLSubcutaneousCelgene2008-04-14Not applicableUS flag
InnohepSolution20000 unitSubcutaneousLeo Pharma1997-09-23Not applicableCanada flag
InnohepSolution8000 unitSubcutaneousLeo Pharma2014-09-30Not applicableCanada flag
InnohepSolution10000 unitSubcutaneousLeo Pharma1995-12-31Not applicableCanada flag
InnohepSolution10000 unitSubcutaneousLeo Pharma2011-12-10Not applicableCanada flag
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
B01AB10 — Tinzaparin
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
7UQ7X4Y489
CAS number
9041-08-1

References

General References
  1. Friedel HA, Balfour JA: Tinzaparin. A review of its pharmacology and clinical potential in the prevention and treatment of thromboembolic disorders. Drugs. 1994 Oct;48(4):638-60. [PubMed:7528134]
  2. Simonneau G, Sors H, Charbonnier B, Page Y, Laaban JP, Azarian R, Laurent M, Hirsch JL, Ferrari E, Bosson JL, Mottier D, Beau B: A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire. N Engl J Med. 1997 Sep 4;337(10):663-9. [PubMed:9278462]
  3. Planes A, Samama MM, Lensing AW, Buller HR, Barre J, Vochelle N, Beau B: Prevention of deep vein thrombosis after hip replacement--comparison between two low-molecular heparins, tinzaparin and enoxaparin. Thromb Haemost. 1999 Jan;81(1):22-5. [PubMed:10348714]
  4. Cheer SM, Dunn CJ, Foster R: Tinzaparin sodium: a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease. Drugs. 2004;64(13):1479-502. [PubMed:15212562]
  5. Hoy SM, Scott LJ, Plosker GL: Tinzaparin sodium: a review of its use in the prevention and treatment of deep vein thrombosis and pulmonary embolism, and in the prevention of clotting in the extracorporeal circuit during haemodialysis. Drugs. 2010 Jul 9;70(10):1319-47. doi: 10.2165/11203710-000000000-00000. [PubMed:20568836]
  6. Hedner U: Development of tinzaparin: a heparinase-digested low-molecular-weight heparin. Semin Thromb Hemost. 2000;26 Suppl 1:23-9. [PubMed:11011803]
  7. Pautas E, Siguret V, d'Urso M, Laurent M, Gaussem P, Fevrier M, Durand-Gasselin B: [Monitoring of tinzaparin in a ten day treatment dose in elderly patients]. Rev Med Interne. 2001 Feb;22(2):120-6. [PubMed:11234669]
  8. Pineo GF, Hull RD: Tinzaparin in the treatment of venous thromboembolism. Expert Opin Pharmacother. 2003 Dec;4(12):2355-62. [PubMed:14640933]
  9. Fossler MJ, Barrett JS, Hainer JW, Riddle JG, Ostergaard P, van der Elst E, Sprogel P: Pharmacodynamics of intravenous and subcutaneous tinzaparin and heparin in healthy volunteers. Am J Health Syst Pharm. 2001 Sep 1;58(17):1614-21. [PubMed:11556655]
  10. Cambus JP, Saivin S, Heilmann JJ, Caplain H, Boneu B, Houin G: The pharmacodynamics of tinzaparin in healthy volunteers. Br J Haematol. 2002 Mar;116(3):649-52. [PubMed:11849226]
KEGG Drug
D06398
PubChem Substance
347910373
RxNav
104466
Wikipedia
Tinzaparin_sodium
AHFS Codes
  • 20:12.04.16 — Heparins

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableVenous Thromboembolism1
4CompletedPreventionChronic Renal Failure (CRF)1
4CompletedTreatmentAcute Pulmonary Embolism1
4CompletedTreatmentDeep Vein Thrombosis1
4CompletedTreatmentIntrauterine Growth Retardation1
4CompletedTreatmentThromboembolism / Thrombosis, Venous / Thrombotic events2
4CompletedTreatmentVenous Thromboembolism1
4RecruitingPreventionCOVID / COVID - 19 / Deep Vein Thrombosis / Novel Coronavirus Infectious Disease (COVID-19) / Pulmonary Embolism / Thrombotic events1
4RecruitingPreventionDeep Venous Thrombosis / Pulmonary Embolism1
4RecruitingSupportive CareAcute Kidney Injury (AKI) / Anticoagulants / Renal Replacement Therapies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous20000 [iU]/1mL
Injection, solution10000 iu/0.5mL
Injection, solution14000 iu/0.7mL
Injection, solution18000 iu/0.9mL
Injection, solution20000 iu/2mL
Injection, solution2500 iu/0.25mL
Injection, solution3500 iu/0.35mL
Injection, solution40000 iu/2mL
Injection, solution4500 iu/0.45mL
Injection, solutionSubcutaneous20000 [iU]/1mL
SolutionSubcutaneous10000 unit
SolutionSubcutaneous12000 unit
SolutionSubcutaneous16000 unit
SolutionSubcutaneous20000 unit
SolutionSubcutaneous8000 unit
Injection, solutionParenteral0.5 ml
InjectionSubcutaneous10000 iu/0.5ml
Injection, solutionParenteral0.6 ml
Injection, solutionParenteral0.7 ml
InjectionSubcutaneous14000 iu/0.7ml
Injection, solutionParenteral0.8 ml
Injection, solutionParenteral0.9 ml
InjectionSubcutaneous18000 iu/0.9ml
Injection, solutionParenteral0.25 ml
Injection, solutionParenteral20000 IU
Injection, solutionParenteral0.35 ML
Injection, solutionParenteral4500 IU
Injection, solutionParenteral0.45 ml
Injection, solutionParenteral0.4 ml
LiquidSubcutaneous
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

Targets

Kind
Protein
Organism
Humans
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. Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G: Structural features of low-molecular-weight heparins affecting their affinity to antithrombin. Thromb Haemost. 2009 Nov;102(5):865-73. doi: 10.1160/TH09-02-0081. [PubMed:19888521]
  2. Florian-Kujawski M, Hoppensteadt D, Maddineni J, Ziegler H, Fareed J: Differential regulation of thrombin activatable fibrinolytic inhibitor by low molecular weight heparins. Pharmacologic implications. Int Angiol. 2004 Dec;23(4):346-54. [PubMed:15767980]
  3. Morris TA, Jacobson A, Marsh JJ, Lane JR: Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thromb Res. 2005;115(1-2):45-51. [PubMed:15567452]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are...
Gene Name
ITGA4
Uniprot ID
P13612
Uniprot Name
Integrin alpha-4
Molecular Weight
114898.745 Da
References
  1. Schlesinger M, Simonis D, Schmitz P, Fritzsche J, Bendas G: Binding between heparin and the integrin VLA-4. Thromb Haemost. 2009 Nov;102(5):816-22. doi: 10.1160/TH09-01-0061. [PubMed:19888514]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Not Available
Gene Name
CXCL12
Uniprot ID
P48061
Uniprot Name
Stromal cell-derived factor 1
Molecular Weight
10665.75 Da
References
  1. Koo CY, Sen YP, Bay BH, Yip GW: Targeting heparan sulfate proteoglycans in breast cancer treatment. Recent Pat Anticancer Drug Discov. 2008 Nov;3(3):151-8. [PubMed:18991783]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in ...
Gene Name
ADAMTS4
Uniprot ID
O75173
Uniprot Name
A disintegrin and metalloproteinase with thrombospondin motifs 4
Molecular Weight
90196.02 Da
References
  1. Mousa SA: Effect of low molecular weight heparin and different heparin molecular weight fractions on the activity of the matrix-degrading enzyme aggrecanase: structure-function relationship. J Cell Biochem. 2005 May 1;95(1):95-8. [PubMed:15723278]

Drug created on September 14, 2010 10:21 / Updated on October 19, 2020 07:46

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