Identification

Name
Lepirudin
Accession Number
DB00001  (BTD00024, BIOD00024)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
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.

Protein structure
Db00001
Protein chemical formula
C287H440N80O110S6
Protein average weight
6963.425 Da
Sequences
>DB00001 sequence
LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIP
EEYLQ
Download FASTA Format
Synonyms
  • Hirudin variant-1
  • Lepirudin recombinant
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RefludanPowder, for solution50 mgIntravenousBayer2000-01-312013-07-26Canada
RefludanPowder50 mg/1mLIntravenousBayer1998-03-062013-06-30Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RefludanLepirudin (20 mg)Injection, solution, concentrateIntravenousCelgene Europe Limited1997-03-132012-07-27Eu
RefludanLepirudin (50 mg)Injection, solution, concentrateIntravenousCelgene Europe Limited1997-03-132012-07-27Eu
RefludanLepirudin (20 mg)Injection, solution, concentrateIntravenousCelgene Europe Limited1997-03-132012-07-27Eu
RefludanLepirudin (50 mg)Injection, solution, concentrateIntravenousCelgene Europe Limited1997-03-132012-07-27Eu
Categories
UNII
Y43GF64R34
CAS number
138068-37-8

Pharmacology

Indication

For the treatment of heparin-induced thrombocytopenia

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.

TargetActionsOrganism
AProthrombin
inhibitor
Human
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)]
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
PathwayCategory
Lepirudin Action PathwayDrug action
Lepirudin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may increase the anticoagulant activities of Lepirudin.
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Lepirudin.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Lepirudin.
AceclofenacAceclofenac may increase the anticoagulant activities of Lepirudin.
AcemetacinThe risk or severity of bleeding can be increased when Lepirudin is combined with Acemetacin.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Lepirudin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Lepirudin.
AlclofenacAlclofenac may increase the anticoagulant activities of Lepirudin.
AllylestrenolThe therapeutic efficacy of Lepirudin can be decreased when used in combination with Allylestrenol.
AlminoprofenAlminoprofen may increase the anticoagulant activities of Lepirudin.
Food Interactions
Not Available

References

General References
  1. 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]
  2. 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]
  3. 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]
  4. Google books [Link]
External Links
UniProt
P01050
KEGG Drug
D06880
PubChem Substance
46507011
ChEMBL
CHEMBL1201666
Therapeutic Targets Database
DAP000541
PharmGKB
PA450195
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lepirudin
ATC Codes
B01AE02 — Lepirudin
FDA label
Download (128 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentLung Cancers1
2CompletedTreatmentThrombosis1
4TerminatedTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
4WithdrawnTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
Not AvailableCompletedNot AvailableAcute HIT II (Heparin-induced Thrombocytopenia Type II)1

Pharmacoeconomics

Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
  • Bayer Healthcare
  • Berlex Labs
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous20 mg
Injection, solution, concentrateIntravenous50 mg
PowderIntravenous50 mg/1mL
Powder, for solutionIntravenous50 mg
Prices
Unit descriptionCostUnit
Refludan 50 mg vial273.19USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5180668No1993-01-192010-01-19Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)65 °COtto, A. & Seckler, R. Eur. J. Biochem. 202:67-73 (1991)
hydrophobicity-0.777Not Available
isoelectric point4.04Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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
  1. Turpie AG: Anticoagulants in acute coronary syndromes. Am J Cardiol. 1999 Sep 2;84(5A):2M-6M. [PubMed:10505536]
  2. Warkentin TE: Venous thromboembolism in heparin-induced thrombocytopenia. Curr Opin Pulm Med. 2000 Jul;6(4):343-51. [PubMed:10912644]
  3. Eriksson BI: New therapeutic options in deep vein thrombosis prophylaxis. Semin Hematol. 2000 Jul;37(3 Suppl 5):7-9. [PubMed:11055889]
  4. 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]
  5. 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]
  6. 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 August 02, 2018 04:15