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
IngredientUNIICASInChI Key
Bemiparin sodiumP59JKU02CENot AvailableNot applicable
International/Other Brands
Badyket / Heporax / Hibor / Zibor
Categories
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

Indication

Bemiparin is indicated in the following cases: To prevent blood clots in the veins after 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 in the veins after 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 action

This drug is a second-generation low molecular weight heparin (LMWH). It has a very low mean 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].

TargetActionsOrganism
ACoagulation factor X
antagonist
Human
UAntithrombin-III
antagonist
Human
UHeparin cofactor 2
antagonist
Human
Absorption

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

Volume of distribution

5.1 L [4].

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 after subcutaneous injection [6].

Route of elimination

This drug is eliminated by the renal and hepatic routes. Elimination is prolonged in those with 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 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. Serum electrolytes should be measured in at-risk patients before starting bemiparin, and these patients should be monitored regularly thereafter 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 after 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, often preceded by purpura or painful erythematous, ecchymose-like lesions have been reported with bemiparin. In these cases, treatment should cease immediately [7].

Overdosage after 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 Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Bemiparin.
AcebutololThe risk or severity of hyperkalemia can be increased when Bemiparin is combined with Acebutolol.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Bemiparin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Bemiparin.
AliskirenBemiparin may increase the hyperkalemic activities of Aliskiren.
AloxiprinThe risk or severity of adverse effects can be increased when Aloxiprin is combined with Bemiparin.
AlteplaseThe risk or severity of bleeding can be increased when Alteplase is combined with Bemiparin.
AmikacinThe therapeutic efficacy of Amikacin can be decreased when used in combination with Bemiparin.
AmilorideThe risk or severity of hyperkalemia can be increased when Amiloride is combined with Bemiparin.
Aminosalicylic AcidThe risk or severity of bleeding can be increased when Aminosalicylic Acid is combined with Bemiparin.
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

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingPreventionUnexplained Stillbirth1
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentImpaired Renal Function1
2CompletedTreatmentPeritoneal Diseases1
2TerminatedTreatmentCarcinoma, Small Cell1
2, 3TerminatedTreatmentDiabetic Angiopathies / Foot Ulcer, Diabetic1
3Active Not RecruitingPreventionCirrhosis and Coagulation1
3CompletedPreventionCancers / Venous Thromboembolism (VTE)1
3CompletedTreatmentDeep Vein Thrombosis (DVT)1
3CompletedTreatmentFoot Ulcer, Diabetic1
3TerminatedPreventionCancers / Thrombosis1
3TerminatedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
4CompletedTreatmentAcute Gastrointestinal Bleeding1
4RecruitingTreatmentInfertilities1
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedPreventionDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
Not AvailableCompletedPreventionVenous Thromboembolic Diseases1
Not AvailableCompletedTreatmentVenous Thromboembolism (VTE)1
Not AvailableRecruitingNot AvailablePatients Undergoing Microvascular Surgery1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>228https://www.trc-canada.com/prod-img/MSDS/H245800MSDS.pdf
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
Antagonist
General Function
Serine-type endopeptidase activity
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.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 October 01, 2018 16:36