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Identification
NameTinzaparin
Accession NumberDB06822
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
Synonyms
Tinzaparin sodium
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Innohepinjection, solution20000 [iU]/mLsubcutaneousLEO Pharma Inc.2010-07-01Not applicableUs
Innohepsolution10000 unitsubcutaneousLeo Pharma Inc2011-12-10Not applicableCanada
Innohepsolution10000 unitsubcutaneousLeo Pharma Inc2011-09-09Not applicableCanada
Innohepsolution16000 unitsubcutaneousLeo Pharma Inc2014-09-30Not applicableCanada
Innohepsolution20000 unitsubcutaneousLeo Pharma Inc1997-09-23Not applicableCanada
Innohepsolution12000 unitsubcutaneousLeo Pharma Inc2014-09-30Not applicableCanada
Innohepsolution10000 unitsubcutaneousLeo Pharma Inc1997-07-31Not applicableCanada
Innohepsolution8000 unitsubcutaneousLeo Pharma Inc2014-09-30Not applicableCanada
Innohepsolution20000 unitsubcutaneousLeo Pharma Inc2011-09-13Not applicableCanada
Innohepsolution20000 unitsubcutaneousLeo Pharma Inc2011-09-16Not applicableCanada
Innohep - 20000anti-XA Iu/mlliquid20000 unitsubcutaneousLeo Pharma Inc1997-02-28Not applicableCanada
Innohep Disp.syr.-11700 Anti-XA Iu/mlliquid11700 unitsubcutaneousLeo Pharma Inc1995-12-311998-08-05Canada
Innohep Multi-dose Vial- 10000 Anti-XA Iu/mlliquid10000 unitsubcutaneousLeo Pharma Inc1995-12-31Not applicableCanada
Logiparin Liq Sc 10000 Fxaiu/mlliquid10000 unitsubcutaneousNovo Nordisk Canada Inc1994-12-311997-08-14Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
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
IndicationTinzaparin 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.
PharmacodynamicsTinzaparin, 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 actionTinzaparin 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.
Related Articles
AbsorptionSubcutaneous 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 bindingLow protein binding compared to unfractionated heparin.
Metabolism

Sulfation and polymerization occurs in the liver.

Route of eliminationLinear elimination through kidneys
Half lifeAnti-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

ToxicityOsteoporosis 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 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
Injection, solutionsubcutaneous20000 [iU]/mL
Solutionsubcutaneous10000 unit
Solutionsubcutaneous12000 unit
Solutionsubcutaneous16000 unit
Solutionsubcutaneous20000 unit
Solutionsubcutaneous8000 unit
Liquidsubcutaneous20000 unit
Liquidsubcutaneous11700 unit
Liquidsubcutaneous10000 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. 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 ]
External Links
ATC CodesB01AB10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabAbciximab may increase the anticoagulant activities of Tinzaparin.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Tinzaparin.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Tinzaparin.
AliskirenTinzaparin may increase the hyperkalemic activities of Aliskiren.
AlteplaseAlteplase may increase the anticoagulant activities of Tinzaparin.
AnistreplaseAnistreplase may increase the anticoagulant activities of Tinzaparin.
ApixabanApixaban may increase the anticoagulant activities of Tinzaparin.
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Tinzaparin.
CanagliflozinTinzaparin may increase the hyperkalemic activities of Canagliflozin.
ChlorotrianiseneChlorotrianisene may decrease the anticoagulant activities of Tinzaparin.
Citric AcidCitric Acid may increase the anticoagulant activities of Tinzaparin.
CollagenaseThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Collagenase.
Dabigatran etexilateDabigatran etexilate may increase the anticoagulant activities of Tinzaparin.
DalteparinDalteparin may increase the anticoagulant activities of Tinzaparin.
DasatinibDasatinib may increase the anticoagulant activities of Tinzaparin.
DeferasiroxThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Deoxycholic Acid.
DesogestrelThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Desogestrel.
DicoumarolDicoumarol may increase the anticoagulant activities of Tinzaparin.
DydrogesteroneThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Dydrogesterone.
Edetic AcidEdetic Acid may increase the anticoagulant activities of Tinzaparin.
EdoxabanEdoxaban may increase the anticoagulant activities of Tinzaparin.
EnoxaparinEnoxaparin may increase the anticoagulant activities of Tinzaparin.
EplerenoneTinzaparin may increase the hyperkalemic activities of Eplerenone.
Ethyl biscoumacetateEthyl biscoumacetate may increase the anticoagulant activities of Tinzaparin.
Fondaparinux sodiumFondaparinux sodium may increase the anticoagulant activities of Tinzaparin.
GestodeneThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Gestodene.
HeparinHeparin may increase the anticoagulant activities of Tinzaparin.
HomoharringtonineThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Homoharringtonine.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Tinzaparin.
InfliximabInfliximab may increase the anticoagulant activities of Tinzaparin.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Tinzaparin.
NintedanibThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Nintedanib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Tinzaparin.
PaliferminThe serum concentration of Palifermin can be increased when it is combined with Tinzaparin.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Tinzaparin.
PentoxifyllinePentoxifylline may increase the anticoagulant activities of Tinzaparin.
PerindoprilTinzaparin may increase the hyperkalemic activities of Perindopril.
PhenindionePhenindione may increase the anticoagulant activities of Tinzaparin.
PhenprocoumonPhenprocoumon may increase the anticoagulant activities of Tinzaparin.
ProgesteroneThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Progesterone.
ReteplaseReteplase may increase the anticoagulant activities of Tinzaparin.
RidogrelRidogrel may increase the anticoagulant activities of Tinzaparin.
RivaroxabanTinzaparin may increase the anticoagulant activities of Rivaroxaban.
StreptokinaseStreptokinase may increase the anticoagulant activities of Tinzaparin.
SugammadexSugammadex may increase the anticoagulant activities of Tinzaparin.
SulodexideSulodexide may increase the anticoagulant activities of Tinzaparin.
TenecteplaseTenecteplase may increase the anticoagulant activities of Tinzaparin.
TiboloneTibolone may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the anticoagulant activities of Tinzaparin.
TositumomabThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Tositumomab.
TreprostinilTreprostinil may increase the anticoagulant activities of Tinzaparin.
TriamtereneTinzaparin may increase the hyperkalemic activities of Triamterene.
UrokinaseUrokinase may increase the anticoagulant activities of Tinzaparin.
ValsartanTinzaparin may increase the hyperkalemic activities of Valsartan.
Vitamin EVitamin E may increase the anticoagulant activities of Tinzaparin.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Tinzaparin.
WarfarinWarfarin may increase the anticoagulant activities of Tinzaparin.
Food Interactions
  • Herbs with anticoagulant/antiplatelet properties (ginger, gingko, garlic) may increase the risk of bleeding.

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. 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
Human
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 also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On act...
Gene Name:
ITGA4
Uniprot ID:
P13612
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
Human
Pharmacological action
unknown
Actions
binder
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
CXCL12
Uniprot ID:
P48061
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
Human
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 the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.
Gene Name:
ADAMTS4
Uniprot ID:
O75173
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 ]
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Drug created on September 14, 2010 10:21 / Updated on October 26, 2015 10:58