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Identification
NameBivalirudin
Accession NumberDB00006  (BIOD00076, BTD00076)
TypeBiotech
GroupsApproved, Investigational
Description

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.

Protein structureNo structure small 354e4808da70a5bd16896d40d8e7c4c304b2c46d0efa4be7aa608033bb036952
Protein chemical formulaC98H138N24O33
Protein average weight2180.2853
Sequences
>Bivalirudin sequence
FPRPGGGGNGDFEEIPEEYL
Download FASTA Format
SynonymsNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Angiomaxinjection, powder, lyophilized, for solution250 mgintravenousCardinal Health2000-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Angiomaxinjection, powder, lyophilized, for solution250 mg/5mLintravenousThe Medicines Company2000-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Angiomaxpowder for solution250 mgintravenousSunovion Pharmaceuticals Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AngioxNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number128270-60-0
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor 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.
PharmacodynamicsBivalirudin directly and reversibly inhibits thrombin by specifically binding both to the catalytic site and to the 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 actionInhibits 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.
AbsorptionFollowing 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 bindingOther than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.
Metabolism

80% proteolytic cleavage

Route of eliminationBivalirudin 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]
ToxicityBased 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.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Bivalirudin Action PathwayDrug actionSMP00277
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • The medicines co
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous250 mg
Injection, powder, lyophilized, for solutionintravenous250 mg/5mL
Powder for solutionintravenous250 mg
Prices
Unit descriptionCostUnit
Angiomax 250 mg vial780.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada20651501999-12-142010-08-17
United States51964041993-05-232010-05-23
United States75827272009-01-272029-01-27
Properties
StateLiquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.985Not Available
isoelectric point3.91Not Available
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 Reference
  1. Seybert AL, Coons JC, Zerumsky K: Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin? Pharmacotherapy. 2006 Feb;26(2):229-41. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. Robson R: The use of bivalirudin in patients with renal impairment. J Invasive Cardiol. 2000 Dec;12 Suppl F:33F-6. Pubmed
  5. 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. Pubmed
  6. Shammas NW: Bivalirudin: pharmacology and clinical applications. Cardiovasc Drug Rev. 2005 Winter;23(4):345-60. Pubmed
  7. 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. Pubmed
External Links
ATC CodesB01AE06
AHFS Codes
  • 20:12.04.12
PDB Entries
FDA labelDownload (60.4 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabMay enhance the anticoagulant effect of other Anticoagulants.
AcenocoumarolMay enhance the anticoagulant effect of other Anticoagulants.
Acetylsalicylic acidMay enhance the anticoagulant effect of Anticoagulants.
AlteplaseMay enhance the anticoagulant effect of Anticoagulants.
AnistreplaseMay enhance the anticoagulant effect of Anticoagulants.
ApixabanMay enhance the anticoagulant effect of Anticoagulants.
Citric AcidMay enhance the anticoagulant effect of other Anticoagulants.
Dabigatran etexilateMay enhance the anticoagulant effect of Anticoagulants.
DalteparinMay enhance the anticoagulant effect of other Anticoagulants.
DasatinibMay enhance the anticoagulant effect of Anticoagulants.
DeferasiroxAnticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Deoxycholic AcidAnticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
DesogestrelMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
DicoumarolMay enhance the anticoagulant effect of other Anticoagulants.
DydrogesteroneMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Edetic AcidMay enhance the anticoagulant effect of other Anticoagulants.
EnoxaparinMay enhance the anticoagulant effect of other Anticoagulants.
Ethyl biscoumacetateMay enhance the anticoagulant effect of other Anticoagulants.
Fondaparinux sodiumMay enhance the anticoagulant effect of other Anticoagulants.
GestodeneMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
HeparinMay enhance the anticoagulant effect of other Anticoagulants.
IbritumomabAnticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding.
ObinutuzumabAnticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
PhenindioneMay enhance the anticoagulant effect of other Anticoagulants.
PhenprocoumonMay enhance the anticoagulant effect of other Anticoagulants.
ProgesteroneMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
ReteplaseMay enhance the anticoagulant effect of Anticoagulants.
RidogrelMay enhance the anticoagulant effect of Anticoagulants.
RivaroxabanAnticoagulants may enhance the anticoagulant effect of Rivaroxaban.
Salicylate-sodiumMay enhance the anticoagulant effect of Anticoagulants.
StreptokinaseMay enhance the anticoagulant effect of Anticoagulants.
SugammadexMay enhance the anticoagulant effect of Anticoagulants.
SulodexideMay enhance the anticoagulant effect of other Anticoagulants.
TenecteplaseMay enhance the anticoagulant effect of Anticoagulants.
TipranavirMay enhance the anticoagulant effect of Anticoagulants.
TreprostinilMay enhance the anticoagulant effect of other Anticoagulants.
UrokinaseMay enhance the anticoagulant effect of Anticoagulants.
Vitamin EMay enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding.
VorapaxarMay enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding.
WarfarinMay enhance the anticoagulant effect of other Anticoagulants.
Food Interactions
  • Dan shen, dong quai, evening primrose oil, gingko, policosanol, willow bark
  • Echinacea

Targets

1. Prothrombin

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prothrombin P00734 Details

References:

  1. Scatena R: Bivalirudin: a new generation antithrombotic drug. Expert Opin Investig Drugs. 2000 May;9(5):1119-27. Pubmed
  2. Bates ER: Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes. Curr Cardiol Rep. 2001 Sep;3(5):348-54. Pubmed
  3. Gladwell TD: Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002 Jan;24(1):38-58. Pubmed
  4. 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. Pubmed
  5. Carswell CI, Plosker GL: Bivalirudin: a review of its potential place in the management of acute coronary syndromes. Drugs. 2002;62(5):841-70. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. 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. Epub 2008 Aug 13. Pubmed[

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Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:48