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| Primary information |
|---|
| ID | 10032 |
| Therapeutic ID | Th1006 |
| Protein Name | Bivalirudin |
| Sequence | >Th1006_Bivalirudin
FPRPGGGGNGDFEEIPEEYL
|
| Molecular Weight | 2180.285 |
| Chemical Formula | C98H138N24O33 |
| Isoelectric Point | 3.91 |
| Hydrophobicity | -0.985 |
| Melting point | NA |
| Half-life | Normal renal function: 0.42 hours (in normal conditions) |
| Description | Bivalirudin is a synthetic 20 residue peptide which acts as a thrombin inhibitor. Once bound to the active site of the inhibitor, thrombin cannot activate fibrinogen into fibrin which is a crucial step in the formation of thrombus. As it can cause blood stagnation, it is important to monitor changes in hematocrit, activated partial thromboplastin time, international normalized ratio and blood pressure. It is administered intravenously. |
| Indication/Disease | 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. |
| Pharmacodynamics | Bivalirudin directly and reversibly inhibits thrombin by specifically binding to both the catalytic site and the anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible as 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 to both its catalytic site and to its anion-binding exosite. Thrombin, a serine proteinase that plays a central role in the thrombotic process, acts to cleave fibrinogen into fibrin monomers and 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. |
| Toxicity | 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. |
| Metabolism | 80% proteolytic cleavage |
| Absorption | 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. |
| 0.2L/kg |
| Clearance | 3.4 mL/min/kg [Normal renal function] |
| Categories | Amino Acids, Peptides, and Proteins, Anticoagulants, Antithrombins, Blood and Blood Forming Organs, Enzyme Inhibitors, Hematologic Agents, Peptides, Protease Inhibitors, Serine Protease Inhibitors, Thrombin Inhibitors |
| Patents Number | US7582727 |
| Date of Issue | 1-Sep-2009 |
| Date of Expiry | 27-Jul-2028 |
| Drug Interaction | Deferasirox, Anticoagulants increase the risk for gastrointestinal ulceration/irritation and/or GI bleeding. If these two agents must be used, patients need to be closely monitored for signs and symptoms of GI toxicity. |
| Target | Prothrombin |
| Brand Name | Angiomax |
| Company | Sandoz Canada Incorporated, The Medicines Company,Cardinal Health, Sandoz Inc |
| Brand Description | Sandoz Canada Incorporated, The Medicines Company,Cardinal Health, Sandoz Inc |
| Prescribed For | It is used for thinning the blood in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA) and in patients undergoing percutaneous coronary intervention (PCI). |
| Chemical Name | D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycylglycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine trifluoroacetate (salt) hydrate |
| Formulation | Each vial contains 250 mg bivalirudin, 125 mg mannitol, and sodium hydroxide to adjust the pH to 5-6 (equivalent of approximately 12.5 mg sodium). When reconstituted with Sterile Water for Injection, the product yields a clear to opalescent, colorless to |
| Physical Appearance | Supplied in single-use vials as a white lyophilized cake |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Intravenous (IV) bolus dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for the duration of the PCI/PTCA procedure. |
| Contraindication | Allergic and have major active bleeding |
| Side Effects | Anxiety; back, stomach, or pelvic pain; headache; nausea; nervousness; pain at the injection site; trouble sleeping; upset stomach; vomiting. And severe side effect may include Severe allergic reactions (rash; hives; itching; difficulty breathing. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |