Identification
- Summary
Bivalirudin is a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia and to prevent thrombosis during percutaneous coronary intervention.
- Brand Names
- Angiomax
- Generic Name
- Bivalirudin
- DrugBank Accession Number
- DB00006
- Background
Bivalirudin is a synthetic 20 residue peptide (thrombin inhibitor) which reversibly inhibits thrombin. Once bound to the active site, thrombin cannot activate fibrinogen into fibrin, the crucial step in the formation of thrombus. It is administered intravenously. Because it can cause blood stagnation, it is important to monitor changes in hematocrit, activated partial thromboplastin time, international normalized ratio and blood pressure.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Bivalirudin (DB00006)
- Weight
- Average: 2180.2853
Monoisotopic: 2178.985813062 - Chemical Formula
- C98H138N24O33
- Synonyms
- Bivalirudin
- Bivalirudina
- Bivalirudinum
- External IDs
- BG-8967
- BG8967
Pharmacology
- Indication
For treatment of heparin-induced thrombocytopenia and for the prevention of thrombosis. Bivalirudin is indicated for use in patients undergoing percutaneous coronary intervention (PCI), in patients at moderate to high risk acute coronary syndromes due to unstable angina or non-ST segment elevation in whom a PCI is planned.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Thrombotic events •••••••••••• •• ••••••• ••••••••• •••••••••• •••••••••• ••••••• ••••••••• Prevention of Thrombotic events •••••••••••• ••••• •••••••• •••••••• ••••• •••••• •• ••• •• ••••••• ••••••••• •••••••••• •••••••••• •••••••• ••••••••• Prevention of Thrombotic events •••••••••••• ••••• •••••••• •••••••• ••••• •••••• •• •••••••• •••••• •••••••• ••••••••• Prevention of Thrombotic events •••••••••••• ••••••••••••••• •••••••••••••••• ••• •••••••••• ••••••••• Prevention of Thrombotic events •••••••••••• ••••••• ••••••• •••••••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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Bivalirudin mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.
- Mechanism of action
Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.
Target Actions Organism AProthrombin inhibitorHumans - Absorption
Following intravenous administration, bivalirudin exhibits linear pharmacokinetics. The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.
- Volume of distribution
0.2L/kg
- Protein binding
Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.
- Metabolism
80% proteolytic cleavage
- Route of elimination
Bivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.
- Half-life
- Normal renal function: 25 min (in normal conditions)
- Creatinine clearance 10-29mL/min: 57min
- Dialysis-dependant patients: 3.5h
- Clearance
- 3.4 mL/min/kg [Normal renal function]
- 3.4 mL/min/kg [mild renal function]
- 2.7 mL/min/kg [moderate renal function]
- 2.8 mL/min/kg [severe renal function]
- 1 mL/min/kg [Dialysis-dependent patients]
- Adverse Effects
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Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.
- Pathways
Pathway Category Bivalirudin 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 Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Bivalirudin. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Bivalirudin. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Bivalirudin is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Bivalirudin is combined with Acenocoumarol. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Bivalirudin. - Food Interactions
- Avoid echinacea.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Angiox / Hirulog
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Angiomax Powder, for solution 250 mg / vial Intravenous Sandoz Canada Incorporated 2003-05-08 Not applicable Canada 
Angiomax Injection, powder, lyophilized, for solution 250 mg/1 Intravenous The Medicines Company 2000-12-15 Not applicable US 
Angiomax Injection, powder, lyophilized, for solution 250 mg/1 Intravenous Cardinal Health 2000-12-15 2014-04-30 US Angiomax Injection 250 mg/1 Intravenous Sandoz Inc 2019-08-01 Not applicable US Angiomax RTU Injection, solution 250 mg/1 Intravenous MAIA Pharmaceuticals, Inc. 2019-08-08 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bivalirudin Injection, powder, lyophilized, for solution 250 mg/1 Intravenous Civica, Inc. 2020-12-21 Not applicable US Bivalirudin Injection 250 mg/1 Intravenous Cipla USA Inc. 2018-07-16 Not applicable US Bivalirudin Injection, powder, lyophilized, for solution 250 mg/1 Intravenous Fresenius Kabi USA, LLC 2017-10-30 Not applicable US Bivalirudin Injection, powder, lyophilized, for solution 250 mg/1 Intravenous Sandoz Inc 2015-10-23 Not applicable US Bivalirudin Injection, powder, lyophilized, for solution 250 mg/1 Intravenous Eugia US LLC 2018-07-27 Not applicable US
Categories
- ATC Codes
- B01AE06 — Bivalirudin
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
- Kingdom
- Organic compounds
- Super Class
- Organic Polymers
- Class
- Polypeptides
- Sub Class
- Not Available
- Direct Parent
- Polypeptides
- Alternative Parents
- Hexacarboxylic acids and derivatives / Peptides / Tyrosine and derivatives / Phenylalanine and derivatives / Glutamic acid and derivatives / Asparagine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives / Leucine and derivatives / Proline and derivatives show 22 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine / Aromatic heteromonocyclic compound show 45 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- polypeptide (CHEBI:59173)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- TN9BEX005G
- CAS number
- 128270-60-0
- InChI Key
- OIRCOABEOLEUMC-GEJPAHFPSA-N
- InChI
- InChI=1S/C98H138N24O33/c1-5-52(4)82(96(153)122-39-15-23-70(122)92(149)114-60(30-34-79(134)135)85(142)111-59(29-33-78(132)133)86(143)116-64(43-55-24-26-56(123)27-25-55)89(146)118-67(97(154)155)40-51(2)3)119-87(144)61(31-35-80(136)137)112-84(141)58(28-32-77(130)131)113-88(145)63(42-54-18-10-7-11-19-54)117-90(147)66(45-81(138)139)110-76(129)50-107-83(140)65(44-71(100)124)109-75(128)49-106-73(126)47-104-72(125)46-105-74(127)48-108-91(148)68-21-13-38-121(68)95(152)62(20-12-36-103-98(101)102)115-93(150)69-22-14-37-120(69)94(151)57(99)41-53-16-8-6-9-17-53/h6-11,16-19,24-27,51-52,57-70,82,123H,5,12-15,20-23,28-50,99H2,1-4H3,(H2,100,124)(H,104,125)(H,105,127)(H,106,126)(H,107,140)(H,108,148)(H,109,128)(H,110,129)(H,111,142)(H,112,141)(H,113,145)(H,114,149)(H,115,150)(H,116,143)(H,117,147)(H,118,146)(H,119,144)(H,130,131)(H,132,133)(H,134,135)(H,136,137)(H,138,139)(H,154,155)(H4,101,102,103)/t52-,57+,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,82-/m0/s1
- IUPAC Name
- (4S)-4-[(2S)-2-[(2S)-2-[(2S)-2-{2-[(2S)-2-(2-{2-[2-(2-{[(2S)-1-[(2S)-2-{[(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]pyrrolidin-2-yl]formamido}-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}acetamido)acetamido]acetamido}acetamido)-3-carbamoylpropanamido]acetamido}-3-carboxypropanamido]-3-phenylpropanamido]-4-carboxybutanamido]-4-{[(2S,3S)-1-[(2S)-2-{[(1S)-3-carboxy-1-{[(1S)-3-carboxy-1-{[(1S)-1-{[(1S)-1-carboxy-3-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}propyl]carbamoyl}propyl]carbamoyl}pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]carbamoyl}butanoic acid
- SMILES
- CC[C@H](C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](N)CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O
References
- Synthesis Reference
Avi Tovi, Chaim Eidelman, Shimon Shushan, Alon Hagi, Alexander Ivchenko, Gabriel-Marcus Butilca, Leah Bar-Oz, Tehila Gadi, Gil Zaovi, "Process for production of Bivalirudin." U.S. Patent US20070093423, issued April 26, 2007.
US20070093423- General References
- Seybert AL, Coons JC, Zerumsky K: Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin? Pharmacotherapy. 2006 Feb;26(2):229-41. [Article]
- Dager WE, Dougherty JA, Nguyen PH, Militello MA, Smythe MA: Heparin-induced thrombocytopenia: treatment options and special considerations. Pharmacotherapy. 2007 Apr;27(4):564-87. [Article]
- Dang CH, Durkalski VL, Nappi JM: Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia. Pharmacotherapy. 2006 Apr;26(4):461-8. [Article]
- Robson R: The use of bivalirudin in patients with renal impairment. J Invasive Cardiol. 2000 Dec;12 Suppl F:33F-6. [Article]
- Van De Car DA, Rao SV, Ohman EM: Bivalirudin: a review of the pharmacology and clinical application. Expert Rev Cardiovasc Ther. 2010 Dec;8(12):1673-81. doi: 10.1586/erc.10.158. [Article]
- Shammas NW: Bivalirudin: pharmacology and clinical applications. Cardiovasc Drug Rev. 2005 Winter;23(4):345-60. [Article]
- Gleason TG, Chengelis CP, Jackson CB, Lindstrom P: A 24-hour continuous infusion study of bivalirudin in the rat. Int J Toxicol. 2003 May-Jun;22(3):195-206. [Article]
- External Links
- KEGG Drug
- D03136
- PubChem Compound
- 16129704
- PubChem Substance
- 46507415
- ChemSpider
- 10482069
- BindingDB
- 50248103
- 60819
- ChEBI
- 59173
- ChEMBL
- CHEMBL2103749
- Therapeutic Targets Database
- DAP000542
- PharmGKB
- PA10032
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Bivalirudin
- FDA label
- Download (60.4 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Prevention Microvascular Coronary Dysfunction (MCD) 1 4 Completed Not Available Coronary Artery Disease (CAD) 1 4 Completed Treatment Acute Coronary Syndrome (ACS) 2 4 Completed Treatment Acute Lymphocytic Leukemia, Pediatric / Anticoagulant Therapy / Extracorporeal Membrane Oxygenation Complication 1 4 Completed Treatment Acute Myocardial Infarction (AMI) / Percutaneous Coronary Intervention (PCI) 1
Pharmacoeconomics
- Manufacturers
- The medicines co
- Packagers
- Ben Venue Laboratories Inc.
- Oryx Pharmaceuticals Inc.
- Sepracor Pharmaceuticals Inc.
- The Medicines Co.
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 250 mg/1 Injection, solution Intravenous 250 mg/1 Injection, powder, lyophilized, for solution Intravenous 250 mg Injection, powder, for solution Intravenous bolus 250 MG Injection Intracavernous 250 mg/1 Injection Intravenous 250 mg/1 Injection, powder, lyophilized, for solution Intravenous 250 mg/5mL Injection, powder, lyophilized, for suspension Intravenous 250 mg/1 Injection, powder, lyophilized, for solution Intravenous Powder, for solution Intravenous 250 mg / vial Injection Intravenous 250 mg/50mL Injection Intravenous 500 mg/100mL Solution Intravenous 5 mg / mL Injection, solution Intravenous 5 mg/1mL Powder Intravenous 250 MG Powder Intravenous - Prices
Unit description Cost Unit Angiomax 250 mg vial 780.0USD 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 US5196404 No 1993-03-23 2010-05-23 US CA2065150 No 1999-12-14 2010-08-17 Canada US7598343 Yes 2009-10-06 2029-01-27 US US7582727 Yes 2009-09-01 2029-01-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source - Predicted Properties
Property Value Source Water Solubility 0.0464 mg/mL ALOGPS logP -0.76 ALOGPS logP -14 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 2.78 Chemaxon pKa (Strongest Basic) 11.88 Chemaxon Physiological Charge -4 Chemaxon Hydrogen Acceptor Count 37 Chemaxon Hydrogen Donor Count 28 Chemaxon Polar Surface Area 901.57 Å2 Chemaxon Rotatable Bond Count 66 Chemaxon Refractivity 543.33 m3·mol-1 Chemaxon Polarizability 218.54 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8811 Blood Brain Barrier - 0.996 Caco-2 permeable - 0.8319 P-glycoprotein substrate Substrate 0.8692 P-glycoprotein inhibitor I Non-inhibitor 0.647 P-glycoprotein inhibitor II Non-inhibitor 0.7858 Renal organic cation transporter Non-inhibitor 0.7959 CYP450 2C9 substrate Non-substrate 0.7558 CYP450 2D6 substrate Non-substrate 0.7957 CYP450 3A4 substrate Substrate 0.5794 CYP450 1A2 substrate Non-inhibitor 0.8977 CYP450 2C9 inhibitor Non-inhibitor 0.8331 CYP450 2D6 inhibitor Non-inhibitor 0.8894 CYP450 2C19 inhibitor Non-inhibitor 0.7784 CYP450 3A4 inhibitor Non-inhibitor 0.744 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9357 Ames test Non AMES toxic 0.7642 Carcinogenicity Non-carcinogens 0.8217 Biodegradation Not ready biodegradable 0.9705 Rat acute toxicity 3.1654 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9307 hERG inhibition (predictor II) Non-inhibitor 0.514
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- 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
- Scatena R: Bivalirudin: a new generation antithrombotic drug. Expert Opin Investig Drugs. 2000 May;9(5):1119-27. [Article]
- Bates ER: Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes. Curr Cardiol Rep. 2001 Sep;3(5):348-54. [Article]
- Gladwell TD: Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002 Jan;24(1):38-58. [Article]
- Kleiman NS, Klem J, Fernandes LS, Rubin H, Challa S, Solomon S, Maresh K, Arora U, Klem E, Buergler J, Mathew S, Browning A, DeLao T: Pharmacodynamic profile of the direct thrombin antagonist bivalirudin given in combination with the glycoprotein IIb/IIIa antagonist eptifibatide. Am Heart J. 2002 Apr;143(4):585-93. [Article]
- Carswell CI, Plosker GL: Bivalirudin: a review of its potential place in the management of acute coronary syndromes. Drugs. 2002;62(5):841-70. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Peroxidase activity
- Specific Function
- Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
- Gene Name
- MPO
- Uniprot ID
- P05164
- Uniprot Name
- Myeloperoxidase
- Molecular Weight
- 83867.71 Da
References
- Rudolph V, Rudolph TK, Schopfer FJ, Bonacci G, Lau D, Szocs K, Klinke A, Meinertz T, Freeman BA, Baldus S: Bivalirudin decreases NO bioavailability by vascular immobilization of myeloperoxidase. J Pharmacol Exp Ther. 2008 Nov;327(2):324-31. doi: 10.1124/jpet.108.142414. Epub 2008 Aug 13. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54