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
IngredientUNIICASInChI Key
Dalteparin sodium12M44VTJ7BNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FragminInjection7500 [iU]/0.3mLSubcutaneousPfizer Laboratories Div Pfizer Inc2015-04-01Not applicableUs
FragminInjection15000 [iU]/0.6mLSubcutaneousEisai Limited1994-12-222016-09-30Us
FragminInjection2500 [iU]/0.2mLSubcutaneousEisai Limited1994-12-222016-09-30Us
FragminSolution10000 unitIntravenous; SubcutaneousPfizer1995-12-31Not applicableCanada
FragminSolution12500 unitIntravenous; SubcutaneousPfizer2011-02-01Not applicableCanada
FragminSolution18000 unitIntravenous; SubcutaneousPfizer2011-02-01Not applicableCanada
FragminInjection12500 [iU]/0.5mLSubcutaneousPfizer Laboratories Div Pfizer Inc2015-04-01Not applicableUs
FragminInjection25000 [iU]/1mLSubcutaneousEisai Limited1994-12-222016-09-30Us
FragminInjection7500 [iU]/0.3mLSubcutaneousEisai Limited1994-12-222016-09-30Us
FragminSolution2500 unitIntravenous; SubcutaneousPfizer1995-12-31Not applicableCanada
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.

TargetActionsOrganism
AAntithrombin-III
potentiator
Human
AVascular endothelial growth factor A
inhibitor
Human
ATissue factor pathway inhibitor
inhibitor
Human
UP-selectin
inhibitor
Human
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
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Dalteparin 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 Dalteparin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Dalteparin is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Dalteparin can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Dalteparin can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Dalteparin is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Dalteparin can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Dalteparin can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Dalteparin.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Dalteparin.
Food Interactions
  • Herbs (anticoagulant/antiplatelet properties such as ginseng, ginkgo, ginger, garlic)

References

General References
  1. King DJ, Kelton JG: Heparin-associated thrombocytopenia. Ann Intern Med. 1984 Apr;100(4):535-40. [PubMed:6367579]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. Samama MM, Gerotziafas GT: Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26 Suppl 1:31-8. [PubMed:11011804]
  13. 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
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentAntiphospholipid Syndrome in Pregnancy / Pregnancy Loss1
1CompletedTreatmentClear Cell Sarcoma of the Kidney / Renal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
1, 2CompletedPreventionNeoplasms, Lung / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentEmbolism and Thrombosis1
2CompletedTreatmentMalignant Neoplasm of Pancreas / Thromboembolism1
2CompletedTreatmentShock, Septic1
2CompletedTreatmentSickle Cell Disorders / Vaso-Occlusive Crises1
2CompletedTreatmentVenous Thromboembolism (VTE)1
2Not Yet RecruitingTreatmentBMI >30 kg/m2 / Malignancies / Venous Thromboembolism (VTE)1
2Not Yet RecruitingTreatmentCerebral Venous Thrombosis1
2RecruitingTreatmentCancer-associated Thrombosis / Duodenal Cancer / Esophageal Cancers / Hepatobiliary Cancers / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach1
2TerminatedSupportive CareDeep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Thrombotic events / Venous Thromboembolism (VTE)1
2TerminatedTreatmentDeep Vein Thrombosis (DVT) / Neoplasms1
2TerminatedTreatmentStage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
2, 3CompletedPreventionHemodialysis Treatment / Thromboembolism1
2, 3CompletedScreeningImpaired Renal Function1
2, 3CompletedTreatmentDiabetic Foot Ulcers (DFU)1
3Active Not RecruitingPreventionStrokes1
3Active Not RecruitingSupportive CareCerebral Vein Thrombosis / Deep Vein Thrombosis (DVT) / Gonadal Thrombosis / Hepatic Thrombosis / Mesenteric Thrombosis / Metastatic Malignant Neoplasm / Neoplasms, Malignant / Portal Vein Thrombosis / Pulmonary Embolism (PE) / Renal Vein Thrombosis / Splenic thrombosis / Venous Thromboembolism (VTE)1
3CompletedPreventionCritical Illness / Deep Venous Thrombosis1
3CompletedPreventionNeoplasms, Brain / Venous Thromboembolism (VTE)1
3CompletedPreventionPostpartum / Venous Thromboembolism (VTE)1
3CompletedSupportive CareCervical Cancers / Chronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Precancerous/Nonmalignant Condition / Unspecified Adult Solid Tumor, Protocol Specific / Veno-Occlusive Disease1
3CompletedTreatmentArterial Thromboembolic Events / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentCancer, Breast / Colorectal Cancers / Lung Cancers / Prostate Cancer / Veno-Occlusive Disease1
3CompletedTreatmentChronic Renal Failure (CRF)1
3CompletedTreatmentComplications, Pregnancy / Hypercoagulability / Pregnancy1
3CompletedTreatmentDeep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
3CompletedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
3CompletedTreatmentRecurrent Abortion1
3Not Yet RecruitingPreventionTraumatic Brain Injury (TBI)1
3RecruitingTreatmentVenous Thromboembolism (VTE)1
3TerminatedPreventionPulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
3TerminatedTreatmentMalignant Neoplasm of Pancreas / Thromboembolism1
3TerminatedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
3Unknown StatusSupportive CareLung Cancers / Thromboembolism1
4CompletedPreventionArthritis of the Hip / Infection NOS / Transfusion Related Complications / Wound Discharge1
4CompletedPreventionDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
4CompletedTreatmentDeep Vein Thrombosis (DVT)1
4CompletedTreatmentLower Extremity Superficial Thrombophlebitis / Superficial Thrombophlebitis / Upper Extremity Superficial Thrombophlebitis1
4CompletedTreatmentLung Cancers1
4CompletedTreatmentMalignancies1
4CompletedTreatmentMalignant Neoplasm of Pancreas / Venous Thromboembolism (VTE)1
4CompletedTreatmentSuperficial Thrombophlebitis1
4RecruitingPreventionDeep Venous Thrombosis / Pulmonary Embolism (PE)1
4RecruitingPreventionRenal Failure1
4TerminatedNot AvailablePreeclampsia1
4TerminatedPreventionDalteparin / Deep Vein Thrombosis (DVT) / Thromboembolism1
4TerminatedPreventionVenous Thromboembolism (VTE)2
4TerminatedTreatmentMyocardial Infarction / Unstable Angina (UA)1
Not AvailableActive Not RecruitingPreventionBone Cancer / Femur Fractures / Malignant Lymphomas / Neoplasms, Metastatic / Pathologic fracture / Plasma Cell Myeloma / Sarcoma, Bone / Soft Tissue Sarcoma (STS)1
Not AvailableCompletedNot AvailableAcute Coronary Syndromes (ACS)1
Not AvailableCompletedNot AvailableAcute Deep Vein Thrombosis1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedNot AvailableThrombosis, Venous1
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedNot AvailableVenous Thromboembolism (VTE)1
Not AvailableCompletedPreventionThrombophylaxis in Transurethral Surgery1
Not AvailableCompletedPreventionVenous Thromboembolism (VTE)1
Not AvailableEnrolling by InvitationTreatmentAcute DVT of Lower Extremity1
Not AvailableNot Yet RecruitingTreatmentRecurrent Pregnancy Losses / Undifferentiated Connective Tissue Disease1
Not AvailableRecruitingTreatmentBlood Clots / Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableTerminatedDiagnosticCoagulation, Blood / Compression Devices, Intermittent Pneumatic / Postoperative Complications / Thrombelastography1
Not AvailableTerminatedTreatmentAntiphospholipid Antibody Syndrome / Recurrent Pregnancy Losses1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous10000 [iU]/0.4mL
InjectionSubcutaneous10000 [iU]/1mL
InjectionSubcutaneous12500 [iU]/0.5mL
InjectionSubcutaneous15000 [iU]/0.6mL
InjectionSubcutaneous18000 [iU]/0.72mL
InjectionSubcutaneous2500 [iU]/0.2mL
InjectionSubcutaneous25000 [iU]/1mL
InjectionSubcutaneous5000 [iU]/0.2mL
InjectionSubcutaneous7500 [iU]/0.3mL
SolutionIntravenous; Subcutaneous10000 unit
SolutionIntravenous; Subcutaneous12500 unit
SolutionIntravenous; Subcutaneous15000 unit
SolutionIntravenous; Subcutaneous18000 unit
SolutionIntravenous; Subcutaneous2500 unit
SolutionIntravenous; Subcutaneous25000 unit
SolutionIntravenous; Subcutaneous3500 unit
SolutionIntravenous; Subcutaneous5000 unit
SolutionIntravenous; Subcutaneous7500 unit
LiquidIntravenous; Subcutaneous2500 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. 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]
  2. 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
Human
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
  1. 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]
  2. 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]
  3. 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
Human
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
  1. Mousa SA: Low-molecular-weight heparins in thrombosis and cancer: emerging links. Cardiovasc Drug Rev. 2004 Summer;22(2):121-34. [PubMed:15179449]
  2. 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]
  3. 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
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. 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
Human
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
  1. 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 December 10, 2018 13:38