Bivalirudin

Bivalirudin
Clinical data
Trade namesAngiomax, Angiox, others
Other namesd-Phenylalanyl-l-prolyl-l-arginyl
-l-prolylglycylglycylglycylglycyl-l-asparaginylglycyl
-l-alpha-aspartyl-l-phenylalanyl
-l-alpha-glutamyl-l-alpha-glutamyl-l-isoleucyl
-l-prolyl-l-alpha-glutamyl-l-alpha-glutamyl
-l-tyrosyl-l-leucine
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous injection/infusion only
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityN/A (IV application only)
MetabolismAngiomax is cleared from plasma by a combination of renal mechanisms and proteolytic cleavage
Elimination half-life~25 minutes in patients with normal renal function
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC98H138N24O33
Molar mass2180.317 g·mol−1
3D model (JSmol)
  • CC[C@H](C)[C@@H](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](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]5CCCN5C(=O)[C@@H](CC6=CC=CC=C6)N
  • 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 checkY
  • Key:OIRCOABEOLEUMC-GEJPAHFPSA-N checkY
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Bivalirudin, sold under the brand names Angiomax and Angiox, among others, is a specific and reversible direct thrombin inhibitor (DTI).[2] Chemically, it is a synthetic congener of the naturally occurring drug hirudin, found in the saliva of the medicinal leech Hirudo medicinalis. It is manufactured by The Medicines Company.[5]

Bivalirudin lacks many of the limitations seen with indirect thrombin inhibitors, such as heparin. A short, synthetic peptide, it is a potent and highly specific inhibitor of thrombin[2][6][7] that inhibits both circulating and clot-bound thrombin,[7] while also inhibiting thrombin-mediated platelet activation and aggregation.[8] Bivalirudin has a quick onset of action and a short half-life.[2] It does not bind to plasma proteins (other than thrombin) or to red blood cells. Therefore, it has a predictable antithrombotic response. There is no risk for heparin-induced thrombocytopenia or heparin-induced thrombosis-thrombocytopenia syndrome.[2] It does not require a binding cofactor such as antithrombin and does not activate platelets.[6][9] These characteristics make bivalirudin an ideal alternative to heparin.

Bivalirudin clinical studies demonstrated consistent positive outcomes in patients with stable angina, unstable angina (UA), non–ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) undergoing PCI in seven major randomized trials.[2][7][8][10][11] Patients receiving bivalirudin had fewer adverse events compared to patients that received heparin.[12][13]

  1. ^ "Regulatory Decision Summary - Bivalirudin Injection". Health Canada. 23 October 2014. Retrieved 5 June 2022.
  2. ^ a b c d e f "Angiomax- bivalirudin injection". DailyMed. 30 June 2019. Retrieved 31 March 2024.
  3. ^ "Angiomax RTU- bivalirudin injection, solution". DailyMed. 5 November 2019. Retrieved 31 March 2024.
  4. ^ "Angiox EPAR". European Medicines Agency (EMA). 2 September 2009. Retrieved 31 March 2024.
  5. ^ "The Medicines Company Reacquires Angiox Rights in Europe from Nycomed". Fierce Biotech (Press release). 2 July 2007. Retrieved 31 March 2024.
  6. ^ a b Anand SX, Kim MC, Kamran M, Sharma SK, Kini AS, Fareed J, et al. (August 2007). "Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin". The American Journal of Cardiology. 100 (3): 417–24. doi:10.1016/j.amjcard.2007.02.106. PMID 17659921.
  7. ^ a b c Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J (August 1990). "Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors". The Journal of Clinical Investigation. 86 (2): 385–91. doi:10.1172/JCI114723. PMC 296739. PMID 2384594.
  8. ^ a b Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, et al. (November 2006). "Bivalirudin for patients with acute coronary syndromes" (PDF). The New England Journal of Medicine. 355 (21): 2203–16. doi:10.1056/NEJMoa062437. hdl:2445/49765. PMID 17124018. S2CID 12034067.
  9. ^ Weitz JI, Bates SM (April 2002). "Acute coronary syndromes: a focus on thrombin". The Journal of Invasive Cardiology. 14 Suppl B: 2B–7B. PMID 11967385.
  10. ^ Bittl JA, Chaitman BR, Feit F, Kimball W, Topol EJ (December 2001). "Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study". American Heart Journal. 142 (6): 952–9. doi:10.1067/mhj.2001.119374. PMID 11717596.
  11. ^ Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, et al. (February 2003). "Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial". JAMA. 289 (7): 853–63. doi:10.1001/jama.289.7.853. PMID 12588269.
  12. ^ Brauser D (13 April 2015). "BRIGHT in Print: Bivalirudin Bests Heparin for Fewer Bleeding Events During PCI, but Dose Matters". Medscape. Retrieved 14 April 2015.
  13. ^ Clinical trial number NCT01696110 for "BivaliRudin in Acute Myocardial Infarction vs Glycoprotein IIb/IIIa and Heparin :a Randomised Controlled Trial. (BRIGHT)" at ClinicalTrials.gov