1/11/2019 Bemiparin - DrugBank

Drugs

Bemiparin Targets (3) Enzymes (1) Biointeractions (3)

IDENTIFICATION

Name Bemiparin

Accession Number DB09258

Type Small Molecule

Groups Approved, Investigational

Description Bemiparin is an antithrombotic and belongs to the group of drugs known as the low molecular weight heparins (LMWH). Like semuloparin, bemiparin is classified as an ultra-LMH because of its low mean molecular mass of 3600 daltons, which is a unique property of this class [1]. These heparins have lower anti-thrombin activity than the traditional low molecular weight heparins and act mainly on factor-Xa, reducing the risk of bleeding due to selectivity for this specific clotting factor. Interestingly, current research is underway for the potential benefit of bemiparin in the treatment of tumors and diabetic foot ulcers [12, 1].

Synonyms Not Available

Product Ingredients INGREDIENT UNII CAS INCHI KEY

Bemiparin sodium P59JKU02CE Not Available Not applicable

International/Other Badyket / Heporax / Hibor / Zibor Brands

Categories Agents causing hyperkalemia Carbohydrates Heparin and similars

Anticoagulants Glycosaminoglycans Polysaccharides

Blood and Blood Forming Heparin (Low Molecular Weight) Organs

UNII PUE0TO3XDR

CAS number 91449-79-5

Weight Not Available

Chemical Formula Not Available

InChI Key Not Available

InChI Not Available

IUPAC Name Not Available

SMILES Not Available

PHARMACOLOGY

https://www.drugbank.ca/drugs/DB09258 1/7 1/11/2019 Bemiparin - DrugBank Indication Bemiparin is indicated in the following cases: To prevent blood clots in the veins aer general abdominal surgery in patients with a moderate risk of venous thromboembolism; in the prevention of the thromboembolic disease in non-surgical patients; prevention of clotting in the extracorporeal circuit during hemodialysis; to prevent blood clots inDrugs the veins aer a major orthopedic surgery in patients with high risk of venous thromboembolism; secondary prevention of venous thromboembolism; recurrence in patients with deep vein thrombosis; transient prevention and treatment of deep vein thrombosis (DVT) [8].

Pharmacodynamics Bemiparin is an anticoagulant classified under the broad category of low molecular weight heparins. In humans, bemiparin has been proven to possess antithrombotic activity and, at therapeutic doses, does not significantly prolong global clotting laboratory tests [9].

Mechanism of This drug is a second-generation low molecular weight heparin (LMWH). It has a very low mean action molecular weight (3600 Dalton), a long half-life (5.3 hrs) and a large anti-Xa: anti-IIa ratio (8:1)[8]. The mechanism of action of bemiparin is inhibition of factor Xa, which is a necessary step in the clotting cascade. Factor-Xa is necessary for the propagation of a thrombus. Combined with various co-factors that bind to activated platelets, Factor-Xa increases coagulation by converting prothrombin to thrombin [11]. Activated Factor-X, bound as part of the prothrombinase complex on the external surface of activated platelets, converts significant amounts of prothrombin to thrombin, promoting the so-called ‘thrombin burst’, referring to a burst of thrombin release [11].

A secondary but less potent mechanism of action of this drug is binding to antithrombin III and activated factor II (Factor IIa), which further prevents the propagation of thrombi [14].

Due to its excellent pharmacological profile-the second-generation LMWH with the lowest molecular weight, the longest half-life and the highest anti-Factor Xa/anti-Factor IIa activity ratio- it can be safely used in special categories of patients (children, elderly, patients with renal impairment and congestive heart failure). Several studies demonstrated its safety and efficacy, while cost analyses show the economic benefits of bemiparin treatment as compared to other heparins [1, 2].

TARGET ACTIONS ORGANISM

A Coagulation factor X antagonist Humans

U Antithrombin-III antagonist Humans

U Heparin cofactor 2 antagonist Humans

Absorption Hemiparin sodium is rapidly absorbed following its subcutaneous dose of injection, and the bioavailability is estimated to be 96% [7].

Volume of 5.1 L [4]. distribution

Protein binding There are currently no data available with regards to plasma protein binding, metabolism and excretion of bemiparin in humans [9].

Metabolism In a study of healthy volunteers, bemiparin 3500 IU achieved more anti-Xa activity than enoxaparin 4000 IU, measured by the area under the curve. The peak of anti-Xa activity was reached at 3h post-administration, and there were anti-Xa measurable levels up to 16 h aer subcutaneous injection [6].

Route of This drug is eliminated by the renal and hepatic routes. Elimination is prolonged in those with elimination renal or hepatic impairment [10].

Half life Bemiparin, when administered in the dose range of 2,500 IU to 12,500 (therapeutic dosing), it has an approximate half-life of 5-6 hours [7].

Clearance Elimination occurs in a linear fashion, with a mean clearance time of over 7 h and total clearance of 0.9 L/h [4].

Toxicity Bemiparin, like other drugs in its class, may suppress adrenal secretion of aldosterone, leading to elevated potassium (hyperkalemia) This may occur more frequently in patients with conditions https://www.drugbank.ca/drugs/DB09258 2/7 1/11/2019 Bemiparin - DrugBank elevated potassium (hyperkalemia). This may occur more frequently in patients with conditions such as diabetes mellitus, chronic renal failure, metabolic acidosis, an increased plasma potassium, and those ingesting potassium sparing drugs. There is a linear relationship between duration of therapy and adverse effects, but this is usually reversible with cessation of treatment. Drugs Serum electrolytes should be measured in at-risk patients before starting bemiparin, and these patients should be monitored regularly thereaer particularly if treatment is prolonged beyond 1 week.

In rare cases, mild transient thrombocytopenia (HIT type I) at the beginning of therapy with heparin with platelet counts between 100,000/mm3 and 150,000/mm3 due to temporary platelet activation has been noted in clinical studies.

On rare occasions, antibody-mediated severe thrombocytopenia (HIT type II) with platelet counts clearly below 100,000/mm3 has been observed (see section 4.8). This effect usually occurs within 5-21 days aer the initiation of treatment, although in patients with a history of heparin-induced thrombocytopenia this may occur more rapidly.

Platelet count studies are recommended before the administration of bemiparin, on the first day of therapy and then every 3-4 days, in addition to repeating platelet studies at the end of therapy. Treatment must be discontinued immediately and an alternate therapy initiated if significant reductions in platelet counts are observed ( 30% decrease and above) [7].

As with other heparin products, cases of cutaneous necrosis, oen preceded by purpura or painful erythematous, ecchymose-like lesions have been reported with bemiparin. In these cases, treatment should cease immediately [7].

Overdosage aer subcutaneous or other routes of administration of bemiparin may lead to hemorrhagic complications. Neutralization can be obtained by slow intravenous of a suitable dose of the antidote protamine sulphate [8].

Affected organisms Humans

Pathways Not Available

Pharmacogenomic Not Available Effects/ADRs

INTERACTIONS

Drug Interactions ALL DRUGS APPROVED VET APPROVED NUTRACEUTICAL ILLICIT WITHDRAWN

INVESTIGATIONAL EXPERIMENTAL

Show 10 entries Search

DRUG ↑↓ INTERACTION ↑↓ (1,2,6,7-3H)Testosterone The therapeutic efficacy of Bemiparin 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 Bemiparin is combined with (R)- warfarin.

(S)-Warfarin The risk or severity of bleeding can be increased when Bemiparin is combined with (S)- Warfarin.

1-Testosterone The therapeutic efficacy of Bemiparin can be increased when used in combination with 1- Testosterone.

18-methyl-19- The therapeutic efficacy of Bemiparin can be increased when used in combination with nortestosterone 18-methyl-19-nortestosterone.

4-hydroxycoumarin The risk or severity of bleeding can be increased when Bemiparin is combined with 4- hydroxycoumarin.

https://www.drugbank.ca/drugs/DB09258 3/7 1/11/2019 Bemiparin - DrugBank

DRUG ↑↓ INTERACTION ↑↓ 4-Hydroxytestosterone The therapeutic efficacy of Bemiparin can be increased when used in combination with 4- Hydroxytestosterone. Drugs 5beta- The therapeutic efficacy of Bemiparin can be increased when used in combination with dihydrotestosterone 5beta-dihydrotestosterone.

Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Bemiparin.

Acebutolol The risk or severity of hyperkalemia can be increased when Acebutolol is combined with Bemiparin.

Showing 1 to 10 of 830 entries ‹ 1 2 3 4 5 … 83 ›

Food Interactions Not Available

REFERENCES

General References 1. Chapman TM, Goa KL: Bemiparin: a review of its use in the prevention of venous thromboembolism and treatment of deep vein thrombosis. Drugs. 2003;63(21):2357-77. [PubMed:14524738] 2. Planes A: Review of bemiparin sodium--a new second-generation low molecular weight heparin and its applications in venous thromboembolism. Expert Opin Pharmacother. 2003 Sep;4(9):1551-61. [PubMed:12943485] 3. Jeske WP, Hoppensteadt D, Gray A, Walenga JM, Cunanan J, Myers L, Fareed J, Bayol A, Rigal H, Viskov C: A common standard is inappropriate for determining the potency of ultra low molecular weight heparins such as semuloparin and bemiparin. Thromb Res. 2011 Oct;128(4):361-7. doi: 10.1016/j.thromres.2011.03.001. Epub 2011 Apr 2. [PubMed:21458847] 4. Sanchez-Ferrer CF: Bemiparin: pharmacological profile. Drugs. 2010 Dec 14;70 Suppl 2:19-23. doi: 10.2165/1158581-S0- 000000000-00000. [PubMed:21162606] 5. Hoffman M, Monroe DM: Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin North Am. 2007 Feb;21(1):1-11. doi: 10.1016/j.hoc.2006.11.004. [PubMed:17258114] 6. Antonijoan RM, Rico S, Martinez-Gonzalez J, Borrell M, Valcarcel D, Fontcuberta J, Barbanoj MJ: Comparative pharmacodynamic time-course of bemiparin and enoxaparin in healthy volunteers. Int J Clin Pharmacol Ther. 2009 Dec;47(12):726-32. [PubMed:19954711] 7. Irish Medicines Board: Bemiparin [Link] 8. Hibor-Bemiparin Sodium [Link] 9. Zibor 2,500 IU Solution for Injection [Link] 10. Injectable drugs guide [Link] 11. Thrombosis Advisors- Factor Xa inhibitor [Link] 12. Anti-tumor effects of bemiparin in HepG2 and MIA PaCa-2 cells [Link] 13. Bemiparin, an effective and safe low molecular weight heparin: a review [Link] 14. Bemiparin sodium [Link]

External Links PubChem Substance 347910422

Wikipedia Bemiparin_sodium

ATC Codes B01AB12 — Bemiparin B01AB — Heparin group B01A — ANTITHROMBOTIC AGENTS B01 — ANTITHROMBOTIC AGENTS B — BLOOD AND BLOOD FORMING ORGANS

CLINICAL TRIALS

Clinical Trials Show 10 entries Search

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓ 0 Completed Prevention Unexplained Stillbirth 1

1 Completed Not Available Healthy Volunteers 1

1 Completed Treatment Impaired Renal Function 1

2 Completed Treatment Peritoneal Diseases 1

2 Terminated Treatment Carcinoma, Small Cell 1

2, 3 Terminated Treatment Diabetic Angiopathies / Diabetic Foot Ulcers 1 (DFU) https://www.drugbank.ca/drugs/DB09258 4/7 1/11/2019 Bemiparin - DrugBank

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓ 3 Active Not Prevention Cirrhosis and Coagulation 1 Recruiting Drugs 3 Completed Prevention Malignancies / Venous Thromboembolism (VTE) 1

3 Completed Treatment Deep Vein Thrombosis (DVT) 1

3 Completed Treatment Diabetic Foot Ulcers (DFU) 1

Showing 1 to 10 of 19 entries ‹ 1 2 ›

PHARMACOECONOMICS

Manufacturers Not Available

Packagers Not Available

Dosage forms Not Available

Prices Not Available

Patents Not Available

PROPERTIES

State Solid

Experimental PROPERTY VALUE SOURCE Properties melting point (°C) >228 https://www.trc-canada.com/prod-img/MSDS/H245800MSDS.pdf

Predicted Not Available Properties

Predicted ADMET Not Available features

SPECTRA

Mass Spec (NIST) Not Available

Spectra Not Available

TAXONOMY

Classification Not classified

TARGETS

1. Coagulation factor X Details

Kind Protein

Organism Humans

Pharmacological action Yes

Actions Antagonist General Function Serine-type endopeptidase activity https://www.drugbank.ca/drugs/DB09258 5/7 1/11/2019 Bemiparin - DrugBank Specific Function Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Drugs Gene Name F10

Uniprot ID P00742

Uniprot Name Coagulation factor X

Molecular Weight 54731.255 Da

2. Antithrombin-III Details

Kind Protein

Organism Humans

Pharmacological action Unknown

Actions Antagonist 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

3. Heparin cofactor 2 Details

Kind Protein

Organism Humans

Pharmacological action Unknown

Actions Antagonist General Function Serine-type endopeptidase inhibitor activity

Specific Function Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT...

Gene Name SERPIND1

Uniprot ID P05546

Uniprot Name Heparin cofactor 2

Molecular Weight 57070.16 Da

ENZYMES

1. Plasma serine protease inhibitor Details

https://www.drugbank.ca/drugs/DB09258 6/7 1/11/2019 Bemiparin - DrugBank Kind Protein

Organism Humans

Pharmacological action Unknown Drugs General Function Serine-type endopeptidase inhibitor activity

Specific Function Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of...

Gene Name SERPINA5

Uniprot ID P05154

Uniprot Name Plasma serine protease inhibitor

Molecular Weight 45674.315 Da

References

1. Thrombosis Advisors- Factor Xa inhibitor [Link]

Drug created on October 26, 2015 10:50 / Updated on November 02, 2018 08:49

About Support Commercial Products About DrugBank FAQ API Pricing DrugBank Blog Help This project is supportedAPI by tDocshe Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Wishart Research Group Email Support Data Licenses Metabolomics Innovation Centre (TMIC), a nationally-funded research Terms of Use and core facility that supSupportports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome Privacy Policy British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc.

https://www.drugbank.ca/drugs/DB09258 7/7