Identification
- Name
- Dalteparin
- Accession Number
- DB06779
- Type
- Small Molecule
- Groups
- Approved
- Description
Dalteparin, a low molecular weight heparin (LMWH) prepared by nitrous acid degradation of unfractionated heparin of porcine intestinal mucosa origin, is an anticoagulant. It is composed of strongly acidic sulphated polysaccharide chains with an average molecular weight of 5000 and about 90% of the material within the range of 2000-9000. LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin. Dalteparin can also be safely used in most pregnant women. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.
- Synonyms
- alpha-heparin
- Product Ingredients
Ingredient UNII CAS InChI Key Dalteparin sodium 12M44VTJ7B Not Available Not applicable - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Fragmin Injection 5000 [iU]/0.2mL Subcutaneous Eisai Limited 1994-12-22 2016-09-30 US Fragmin Injection 7500 [iU]/0.3mL Subcutaneous Pfizer Laboratories Div Pfizer Inc 2015-04-01 Not applicable US Fragmin Solution 3500 unit Intravenous; Subcutaneous Pfizer 2015-03-25 Not applicable Canada Fragmin Injection 25000 [iU]/1mL Subcutaneous Eisai Limited 1994-12-22 2016-09-30 US Fragmin Solution 10000 unit Intravenous; Subcutaneous Pfizer 2011-02-01 Not applicable Canada Fragmin Injection 10000 [iU]/1mL Subcutaneous Eisai Limited 1994-12-22 2016-09-30 US Fragmin Injection 15000 [iU]/0.6mL Subcutaneous Pfizer Laboratories Div Pfizer Inc 2015-04-01 Not applicable US Fragmin Injection 5000 [iU]/0.2mL Subcutaneous Pfizer Laboratories Div Pfizer Inc 2015-04-01 Not applicable US Fragmin Solution 5000 unit Intravenous; Subcutaneous Pfizer 1995-12-31 Not applicable Canada Fragmin Injection 2500 [iU]/0.2mL Subcutaneous Eisai Limited 1994-12-22 2016-09-30 US - International/Other Brands
- Boxol (Pharmacia) / Eurodal (Gland) / Ligoframin (Pfizer) / Low Liquemine (Roche)
- Categories
- UNII
- S79O08V79F
- CAS number
- 9005-49-6
- Weight
- Not Available
- Chemical Formula
- Not Available
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
Pharmacology
- Indication
Dalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications.
Dalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes).
It is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency.
- Associated Conditions
- Pharmacodynamics
Dalteparin has an antithrombin binding site that is essential for high affinity binding to the plasma protein antithrombin (ATIII). Anti-Xa activity of plasma is used as both as an estimate of clotting activity, and as a basis to determine dosage. Its use should be avoided in patients with a creatinine clearance less than 20mL/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
Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage.
Target Actions Organism AAntithrombin-III potentiatorHumans AVascular endothelial growth factor A inhibitorHumans ATissue factor pathway inhibitor inhibitorHumans UP-selectin inhibitorHumans - Absorption
Almost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%.
- Volume of distribution
3 litres
- Protein binding
Less than unfractionated heparin, which is more than 90%.
- Metabolism
Liver and the reticulo-endothelial system are the sites of biotransformation. They are partially metabolized by desulphatation and depolymerization.
- Route of elimination
After 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal studies).
- Half life
Terminal Half life: Intravenous - 2 hours. Subcutaneous - 3-5hours
- Clearance
Excreted via kidneys. The plasma clearance rate is 33 mL/min.
- Toxicity
Overdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (1,2,6,7-3H)Testosterone The therapeutic efficacy of Dalteparin can be increased when used in combination with (1,2,6,7-3H)Testosterone. (R)-warfarin The risk or severity of bleeding can be increased when Dalteparin is combined with (R)-warfarin. (S)-Warfarin The risk or severity of bleeding can be increased when Dalteparin is combined with (S)-Warfarin. 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The risk or severity of hyperkalemia can be increased when 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid is combined with Dalteparin. 1-Testosterone The therapeutic efficacy of Dalteparin can be increased when used in combination with 1-Testosterone. 18-methyl-19-nortestosterone The therapeutic efficacy of Dalteparin can be increased when used in combination with 18-methyl-19-nortestosterone. 4-hydroxycoumarin The risk or severity of bleeding can be increased when Dalteparin is combined with 4-hydroxycoumarin. 4-Hydroxytestosterone The therapeutic efficacy of Dalteparin can be increased when used in combination with 4-Hydroxytestosterone. 5beta-dihydrotestosterone The therapeutic efficacy of Dalteparin can be increased when used in combination with 5beta-dihydrotestosterone. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Dalteparin. - Food Interactions
- Herbs (anticoagulant/antiplatelet properties such as ginseng, ginkgo, ginger, garlic)
References
- General References
- King DJ, Kelton JG: Heparin-associated thrombocytopenia. Ann Intern Med. 1984 Apr;100(4):535-40. [PubMed:6367579]
- Bell WR, Royall RM: Heparin-associated thrombocytopenia: a comparison of three heparin preparations. N Engl J Med. 1980 Oct 16;303(16):902-7. [PubMed:6997743]
- Ockelford PA, Patterson J, Johns AS: A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thromb Haemost. 1989 Dec 29;62(4):1046-9. [PubMed:2559484]
- Hartl P, Brucke P, Dienstl E, Vinazzer H: Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin. Thromb Res. 1990 Feb 15;57(4):577-84. [PubMed:2158151]
- Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A: Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia. Eur J Clin Pharmacol. 1989;37(4):415-8. [PubMed:2557219]
- Holmer E, Soderberg K, Bergqvist D, Lindahl U: Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties. Haemostasis. 1986;16 Suppl 2:1-7. [PubMed:3744129]
- Malm K, Dahlback B, Arnljots B: Low-molecular-weight heparin (dalteparin) effectively prevents thrombosis in a rat model of deep arterial injury. Plast Reconstr Surg. 2003 Apr 15;111(5):1659-66. [PubMed:12655212]
- Tincani E, Mannucci C, Casolari B, Turrini F, Crowther MA, Prisco D, Cenci AM, Bondi M: Safety of dalteparin for the prophylaxis of venous thromboembolism in elderly medical patients with renal insufficiency: a pilot study. Haematologica. 2006 Jul;91(7):976-9. Epub 2006 Jun 1. [PubMed:16757417]
- Schmid P, Brodmann D, Fischer AG, Wuillemin WA: Study of bioaccumulation of dalteparin at a prophylactic dose in patients with various degrees of impaired renal function. J Thromb Haemost. 2009 Apr;7(4):552-8. doi: 10.1111/j.1538-7836.2009.03292.x. Epub 2009 Jan 19. [PubMed:19175499]
- Abe W, Ikejima K, Lang T, Okumura K, Enomoto N, Kitamura T, Takei Y, Sato N: Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat. J Hepatol. 2007 Feb;46(2):286-94. Epub 2006 Oct 25. [PubMed:17166617]
- 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]
- Samama MM, Gerotziafas GT: Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26 Suppl 1:31-8. [PubMed:11011804]
- Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. [PubMed:11044537]
- External Links
- KEGG Drug
- D03353
- PubChem Substance
- 347910371
- Wikipedia
- Dalteparin_sodium
- ATC Codes
- B01AB04 — Dalteparin
- AHFS Codes
- 20:12.04.16 — Heparins
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection Subcutaneous 10000 [iU]/0.4mL Injection Subcutaneous 10000 [iU]/1mL Injection Subcutaneous 12500 [iU]/0.5mL Injection Subcutaneous 15000 [iU]/0.6mL Injection Subcutaneous 18000 [iU]/0.72mL Injection Subcutaneous 2500 [iU]/0.2mL Injection Subcutaneous 25000 [iU]/1mL Injection Subcutaneous 5000 [iU]/0.2mL Injection Subcutaneous 7500 [iU]/0.3mL Solution Intravenous; Subcutaneous 10000 unit Solution Intravenous; Subcutaneous 12500 unit Solution Intravenous; Subcutaneous 15000 unit Solution Intravenous; Subcutaneous 18000 unit Solution Intravenous; Subcutaneous 2500 unit Solution Intravenous; Subcutaneous 25000 unit Solution Intravenous; Subcutaneous 3500 unit Solution Intravenous; Subcutaneous 5000 unit Solution Intravenous; Subcutaneous 7500 unit Liquid Intravenous; Subcutaneous 2500 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
- 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
- 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]
- Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. [PubMed:11044537]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor receptor binding
- Specific Function
- Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
- Gene Name
- VEGFA
- Uniprot ID
- P15692
- Uniprot Name
- Vascular endothelial growth factor A
- Molecular Weight
- 27042.205 Da
References
- Norrby K, Nordenhem A: Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS. 2010 Dec;118(12):949-57. doi: 10.1111/j.1600-0463.2010.02635.x. Epub 2010 Oct 12. [PubMed:21091776]
- Marchetti M, Vignoli A, Russo L, Balducci D, Pagnoncelli M, Barbui T, Falanga A: Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin. Thromb Res. 2008;121(5):637-45. Epub 2007 Aug 10. [PubMed:17692905]
- Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. [PubMed:16041398]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action...
- Gene Name
- TFPI
- Uniprot ID
- P10646
- Uniprot Name
- Tissue factor pathway inhibitor
- Molecular Weight
- 35014.835 Da
References
- Mousa SA: Low-molecular-weight heparins in thrombosis and cancer: emerging links. Cardiovasc Drug Rev. 2004 Summer;22(2):121-34. [PubMed:15179449]
- Naumnik B, Rydzewska-Rosolowska A, Mysliwiec M: Different effects of enoxaparin, nadroparin, and dalteparin on plasma TFPI during hemodialysis: a prospective crossover randomized study. Clin Appl Thromb Hemost. 2011 Oct;17(5):480-6. doi: 10.1177/1076029610376936. Epub 2010 Aug 3. [PubMed:20682597]
- Bendz B, Andersen TO, Sandset PM: Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins. Blood Coagul Fibrinolysis. 2000 Jun;11(4):343-8. [PubMed:10847421]
- Kind
- Protein
- Organism
- Humans
- 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
- Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. [PubMed:11044537]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Syndecan binding
- Specific Function
- Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Se...
- Gene Name
- HPSE
- Uniprot ID
- Q9Y251
- Uniprot Name
- Heparanase
- Molecular Weight
- 61148.17 Da
References
- Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. [PubMed:16041398]
Drug created on September 14, 2010 10:21 / Updated on February 18, 2019 20:23