Lepirudin
Identification
- Name
- Lepirudin
- Accession Number
- DB00001
- Description
Lepirudin is identical to natural hirudin except for substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. It is produced via yeast cells. Bayer ceased the production of lepirudin (Refludan) effective May 31, 2012.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Structure
- Protein Chemical Formula
- C287H440N80O110S6
- Protein Average Weight
- 6963.425 Da
- Sequences
>DB00001 sequence LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIP EEYLQ
Download FASTA Format- Synonyms
- Hirudin variant-1
- Lepirudin recombinant
Pharmacology
- Indication
For the treatment of heparin-induced thrombocytopenia
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Lepirudin is used to break up clots and to reduce thrombocytopenia. It binds to thrombin and prevents thrombus or clot formation. It is a highly potent, selective, and essentially irreversible inhibitor of thrombin and clot-bond thrombin. Lepirudin requires no cofactor for its anticoagulant action. Lepirudin is a recombinant form of hirudin, an endogenous anticoagulant found in medicinal leeches.
- Mechanism of action
Lepirudin forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen and initiate the clotting cascade. The inhibition of thrombin prevents the blood clotting cascade.
Target Actions Organism AProthrombin inhibitorHumans - Absorption
Bioavailability is 100% following injection.
- Volume of distribution
- 12.2 L [Healthy young subjects (n = 18, age 18-60 years)]
- 18.7 L [Healthy elderly subjects (n = 10, age 65-80 years)]
- 18 L [Renally impaired patients (n = 16, creatinine clearance below 80 mL/min)]
- 32.1 L [HIT patients (n = 73)]
- Protein binding
- Not Available
- Metabolism
Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, con-clusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.
- Route of elimination
Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.
- Half-life
Approximately 1.3 hours
- Clearance
- 164 ml/min [Healthy 18-60 yrs]
- 139 ml/min [Healthy 65-80 yrs]
- 61 ml/min [renal impaired]
- 114 ml/min [HIT (Heparin-induced thrombocytopenia)]
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Lepirudin Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Lepirudin. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Lepirudin. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Lepirudin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Lepirudin. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Lepirudin. Albutrepenonacog alfa The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Lepirudin. Alclofenac The risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Lepirudin. Aldesleukin The risk or severity of bleeding can be increased when Lepirudin is combined with Aldesleukin. Alemtuzumab The risk or severity of bleeding can be increased when Lepirudin is combined with Alemtuzumab. Alteplase The risk or severity of bleeding can be increased when Lepirudin is combined with Alteplase. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataRefludan Powder 50 mg/1mL Intravenous Bayer 1998-03-06 2013-06-30 US 
Refludan Injection, solution, concentrate 50 mg Intravenous Celgene Europe Limited 1997-03-13 2012-07-27 EU 
Refludan Injection, solution, concentrate 20 mg Intravenous Celgene Europe Limited 1997-03-13 2012-07-27 EU Refludan Injection, solution, concentrate 50 mg Intravenous Celgene Europe Limited 1997-03-13 2012-07-27 EU Refludan Powder, for solution 50 mg Intravenous Bayer 2000-01-31 2013-07-26 Canada 
Refludan Injection, solution, concentrate 20 mg Intravenous Celgene Europe Limited 1997-03-13 2012-07-27 EU Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
Categories
- ATC Codes
- B01AE02 — Lepirudin
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- Y43GF64R34
- CAS number
- 138068-37-8
References
- General References
- Smythe MA, Stephens JL, Koerber JM, Mattson JC: A comparison of lepirudin and argatroban outcomes. Clin Appl Thromb Hemost. 2005 Oct;11(4):371-4. [PubMed:16244762]
- Tardy B, Lecompte T, Boelhen F, Tardy-Poncet B, Elalamy I, Morange P, Gruel Y, Wolf M, Francois D, Racadot E, Camarasa P, Blouch MT, Nguyen F, Doubine S, Dutrillaux F, Alhenc-Gelas M, Martin-Toutain I, Bauters A, Ffrench P, de Maistre E, Grunebaum L, Mouton C, Huisse MG, Gouault-Heilmann M, Lucke V: Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood. 2006 Sep 1;108(5):1492-6. Epub 2006 May 11. [PubMed:16690967]
- Lubenow N, Eichler P, Lietz T, Greinacher A: Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost. 2005 Nov;3(11):2428-36. [PubMed:16241940]
- Google books [Link]
- External Links
- UniProt
- P01050
- KEGG Drug
- D06880
- PubChem Substance
- 46507011
- 237057
- ChEMBL
- CHEMBL1201666
- Therapeutic Targets Database
- DAP000541
- PharmGKB
- PA450195
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lepirudin
- FDA label
- Download (128 KB)
- MSDS
- Download (567 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Terminated Treatment Heparin Induced Thrombocytopenia (HIT) 1 4 Withdrawn Treatment Heparin Induced Thrombocytopenia (HIT) 1 2 Completed Treatment Thrombotic events 1 1, 2 Terminated Treatment Lung Cancers 1 Not Available Completed Not Available Acute HIT II (Heparin-induced Thrombocytopenia Type II) 1
Pharmacoeconomics
- Manufacturers
- Bayer healthcare pharmaceuticals inc
- Packagers
- Bayer Healthcare
- Berlex Labs
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 20 mg Injection, solution, concentrate Intravenous 50 mg Powder Intravenous 50 mg/1mL Powder, for solution Intravenous 50 mg - Prices
Unit description Cost Unit Refludan 50 mg vial 273.19USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region Unlock Additional DataUS5180668 No 1993-01-19 2010-01-19 US Additional Data Available- Filed On
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 65 °C Otto, A. & Seckler, R. Eur. J. Biochem. 202:67-73 (1991) hydrophobicity -0.777 Not Available isoelectric point 4.04 Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Turpie AG: Anticoagulants in acute coronary syndromes. Am J Cardiol. 1999 Sep 2;84(5A):2M-6M. [PubMed:10505536]
- Warkentin TE: Venous thromboembolism in heparin-induced thrombocytopenia. Curr Opin Pulm Med. 2000 Jul;6(4):343-51. [PubMed:10912644]
- Eriksson BI: New therapeutic options in deep vein thrombosis prophylaxis. Semin Hematol. 2000 Jul;37(3 Suppl 5):7-9. [PubMed:11055889]
- Fabrizio MC: Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced thrombocytopenia and cardiopulmonary bypass. J Extra Corpor Technol. 2001 May;33(2):117-25. [PubMed:11467439]
- Szaba FM, Smiley ST: Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood. 2002 Feb 1;99(3):1053-9. [PubMed:11807012]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Drug created on June 13, 2005 07:24 / Updated on July 10, 2020 21:42
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