Lepirudin

Identification

Summary

Lepirudin is a protein-based direct thrombin inhibitor used to reverse and prevent thrombus formation in heparin-induced thrombocytopenia.

Generic Name

Lepirudin

DrugBank Accession Number

DB00001

Background

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
• Lepirudin recombinant

Pharmacology

Indication

For the treatment of heparin-induced thrombocytopenia

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Contraindications & Blackbox Warnings

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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	inhibitor	Humans

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

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Toxicity

In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.

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.

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• Withdrawn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

Drug	Interaction
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Abciximab	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.

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Food Interactions

• Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Refludan	Injection, solution, concentrate	20 mg	Intravenous	Celgene Europe Limited	2016-09-08	2012-07-27
Refludan	Injection, solution, concentrate	20 mg	Intravenous	Celgene Europe Limited	2016-09-08	2012-07-27
Refludan	Powder	50 mg/1mL	Intravenous	Bayer	1998-03-06	2013-06-30
Refludan	Injection, solution, concentrate	50 mg	Intravenous	Celgene Europe Limited	2016-09-08	2012-07-27
Refludan	Powder, for solution	50 mg / vial	Intravenous	Bayer	2000-01-31	2013-07-26
Refludan	Injection, solution, concentrate	50 mg	Intravenous	Celgene Europe Limited	2016-09-08	2012-07-27

Categories

ATC Codes

B01AE02 — Lepirudin

• B01AE — Direct thrombin inhibitors
• B01A — ANTITHROMBOTIC AGENTS
• B01 — ANTITHROMBOTIC AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Amino Acids, Peptides, and Proteins
• Anticoagulants
• Antithrombin Proteins
• Antithrombins
• Blood and Blood Forming Organs
• Cardiovascular Agents
• Enzyme Inhibitors
• Fibrin Modulating Agents
• Hematologic Agents
• Peptides
• Protease Inhibitors
• Proteins
• Serine Protease Inhibitors
• Serpins
• Thrombin Inhibitors

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

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

Y43GF64R34

CAS number

138068-37-8

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. [Article]
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. [Article]
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. [Article]
4. Google books [Link]

External Links

UniProt

P01050

KEGG Drug

D06880

PubChem Substance

46507011

RxNav

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, powder, for suspension	Intravenous	50 mg
Injection, solution, concentrate	Intravenous	20 mg
Injection, solution, concentrate	Intravenous	50 mg
Powder	Intravenous
Powder	Intravenous	50 mg/1mL
Powder, for solution	Intravenous	50 mg / vial

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
US5180668	No	1993-01-19	2010-01-19

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

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Details1. Prothrombin

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

1. Turpie AG: Anticoagulants in acute coronary syndromes. Am J Cardiol. 1999 Sep 2;84(5A):2M-6M. [Article]
2. Warkentin TE: Venous thromboembolism in heparin-induced thrombocytopenia. Curr Opin Pulm Med. 2000 Jul;6(4):343-51. [Article]
3. Eriksson BI: New therapeutic options in deep vein thrombosis prophylaxis. Semin Hematol. 2000 Jul;37(3 Suppl 5):7-9. [Article]
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. [Article]
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. [Article]
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

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Drug created on June 13, 2005 13:24 / Updated on July 03, 2021 08:54