Dalteparin

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
Fragmin	Injection	7500 [iU]/0.3mL	Subcutaneous	Pfizer Laboratories Div Pfizer Inc	2015-04-01	Not applicable
Fragmin	Solution	3500 unit	Intravenous; Subcutaneous	Pfizer	2015-03-25	Not applicable
Fragmin	Injection	25000 [iU]/1mL	Subcutaneous	Eisai Limited	1994-12-22	2016-09-30
Fragmin	Solution	10000 unit	Intravenous; Subcutaneous	Pfizer	2011-02-01	Not applicable
Fragmin	Injection	10000 [iU]/1mL	Subcutaneous	Eisai Limited	1994-12-22	2016-09-30
Fragmin	Injection	15000 [iU]/0.6mL	Subcutaneous	Pfizer Laboratories Div Pfizer Inc	2015-04-01	Not applicable
Fragmin	Injection	5000 [iU]/0.2mL	Subcutaneous	Pfizer Laboratories Div Pfizer Inc	2015-04-01	Not applicable
Fragmin	Solution	5000 unit	Intravenous; Subcutaneous	Pfizer	1995-12-31	Not applicable
Fragmin	Injection	2500 [iU]/0.2mL	Subcutaneous	Eisai Limited	1994-12-22	2016-09-30

International/Other Brands

Boxol (Pharmacia) / Eurodal (Gland) / Ligoframin (Pfizer) / Low Liquemine (Roche)

Categories

• Agents causing hyperkalemia
• Anticoagulants
• Blood and Blood Forming Organs
• Carbohydrates
• Cardiovascular Agents
• Fibrin Modulating Agents
• Fibrinolytic Agents
• Glycosaminoglycans
• Hematologic Agents
• Heparin (Low Molecular Weight)
• Heparin and similars
• Polysaccharides

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

• Cardiovascular Events
• Clotting
• Deep Vein Thrombosis (DVT)
• Symptomatic Venous Thromboembolism
• Venous Thromboembolism (VTE)

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	potentiator	Humans
AVascular endothelial growth factor A	inhibitor	Humans
ATissue factor pathway inhibitor	inhibitor	Humans
UP-selectin	inhibitor	Humans

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

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

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

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

• B01AB — Heparin group
• B01A — ANTITHROMBOTIC AGENTS
• B01 — ANTITHROMBOTIC AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

AHFS Codes

• 20:12.04.16 — Heparins

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Antiphospholipid Syndrome in Pregnancy / Pregnancy Loss	1
1	Completed	Treatment	Clear Cell Sarcoma of the Kidney / Renal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer	1
1, 2	Completed	Prevention	Neoplasms, Lung / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)	1
2	Completed	Treatment	Brain and Central Nervous System Tumors	1
2	Completed	Treatment	Cancer of the Ovary	1
2	Completed	Treatment	Embolism and Thrombosis	1
2	Completed	Treatment	Malignant Neoplasm of Pancreas / Thromboembolism	1
2	Completed	Treatment	Shock, Septic	1
2	Completed	Treatment	Sickle Cell Disorders / Vaso-Occlusive Crises	1
2	Completed	Treatment	Venous Thromboembolism (VTE)	1
2	Not Yet Recruiting	Treatment	Cerebral Venous Thrombosis	1
2	Recruiting	Treatment	BMI >30 kg/m2 / Malignancies / Venous Thromboembolism (VTE)	1
2	Recruiting	Treatment	Cancer-associated Thrombosis / Duodenal Cancer / Esophageal Cancers / Hepatobiliary Cancers / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach	1
2	Terminated	Supportive Care	Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Thrombotic events / Venous Thromboembolism (VTE)	1
2	Terminated	Treatment	Deep Vein Thrombosis (DVT) / Neoplasms	1
2	Terminated	Treatment	Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma	1
2, 3	Completed	Prevention	Hemodialysis Treatment / Thromboembolism	1
2, 3	Completed	Screening	Impaired Renal Function	1
2, 3	Completed	Treatment	Diabetic Foot Ulcers (DFU)	1
3	Active Not Recruiting	Prevention	Strokes	1
3	Active Not Recruiting	Supportive Care	Cerebral 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
3	Completed	Prevention	Critical Illness / Deep Venous Thrombosis	1
3	Completed	Prevention	Neoplasms, Brain / Venous Thromboembolism (VTE)	1
3	Completed	Prevention	Postpartum / Venous Thromboembolism (VTE)	1
3	Completed	Supportive Care	Cervical 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 Disease	1
3	Completed	Treatment	Arterial Thromboembolic Events / Nonvalvular Atrial Fibrillation	1
3	Completed	Treatment	Cancer, Breast / Colorectal Cancers / Lung Cancers / Prostate Cancer / Veno-Occlusive Disease	1
3	Completed	Treatment	Chronic Renal Failure (CRF)	1
3	Completed	Treatment	Complications, Pregnancy / Hypercoagulability / Pregnancy	1
3	Completed	Treatment	Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)	1
3	Completed	Treatment	Neoplasms / Venous Thromboembolism (VTE)	1
3	Completed	Treatment	Recurrent Abortion	1
3	Not Yet Recruiting	Prevention	Traumatic Brain Injury (TBI)	1
3	Recruiting	Treatment	Venous Thromboembolism (VTE)	1
3	Terminated	Prevention	Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)	1
3	Terminated	Treatment	Malignant Neoplasm of Pancreas / Thromboembolism	1
3	Terminated	Treatment	Neoplasms / Venous Thromboembolism (VTE)	1
3	Unknown Status	Supportive Care	Lung Cancers / Thromboembolism	1
4	Completed	Prevention	Arthritis of the Hip / Infection NOS / Transfusion Related Complications / Wound Discharge	1
4	Completed	Prevention	Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)	1
4	Completed	Treatment	Deep Vein Thrombosis (DVT)	1
4	Completed	Treatment	Lower Extremity Superficial Thrombophlebitis / Superficial Thrombophlebitis / Upper Extremity Superficial Thrombophlebitis	1
4	Completed	Treatment	Lung Cancers	1
4	Completed	Treatment	Malignancies	1
4	Completed	Treatment	Malignant Neoplasm of Pancreas / Venous Thromboembolism (VTE)	1
4	Completed	Treatment	Superficial Thrombophlebitis	1
4	Recruiting	Prevention	Deep Venous Thrombosis / Pulmonary Embolism (PE)	1
4	Recruiting	Prevention	Renal Failure	1
4	Terminated	Not Available	Preeclampsia	1
4	Terminated	Prevention	Dalteparin / Deep Vein Thrombosis (DVT) / Thromboembolism	1
4	Terminated	Prevention	Venous Thromboembolism (VTE)	2
4	Terminated	Treatment	Myocardial Infarction / Unstable Angina Pectoris	1
Not Available	Active Not Recruiting	Prevention	Bone Cancer / Femur Fractures / Malignant Lymphomas / Neoplasms, Metastatic / Pathologic fracture / Plasma Cell Myeloma / Sarcoma, Bone / Soft Tissue Sarcoma (STS)	1
Not Available	Completed	Not Available	Acute Coronary Syndromes (ACS)	1
Not Available	Completed	Not Available	Acute Deep Vein Thrombosis	1
Not Available	Completed	Not Available	BMI >30 kg/m2	1
Not Available	Completed	Not Available	Thrombosis, Venous	1
Not Available	Completed	Not Available	Unsuspected Pulmonary Embolism	1
Not Available	Completed	Not Available	Venous Thromboembolism (VTE)	1
Not Available	Completed	Prevention	Thrombophylaxis in Transurethral Surgery	1
Not Available	Completed	Prevention	Venous Thromboembolism (VTE)	1
Not Available	Enrolling by Invitation	Treatment	Acute DVT of Lower Extremity	1
Not Available	Not Yet Recruiting	Treatment	Recurrent Pregnancy Losses / Undifferentiated Connective Tissue Disease	1
Not Available	Recruiting	Treatment	Blood Clots / Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)	1
Not Available	Terminated	Diagnostic	Coagulation, Blood / Compression Devices, Intermittent Pneumatic / Postoperative Complications / Thrombelastography	1
Not Available	Terminated	Treatment	Antiphospholipid Antibody Syndrome / Recurrent Pregnancy Losses	1

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

Drug created on September 14, 2010 10:21 / Updated on February 18, 2019 20:23