Bivalirudin: Difference between revisions
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==Mechanism of Action== | ==Mechanism of Action== | ||
Bivalirudin directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine proteinase that plays a central role in the thrombotic process. It cleaves fibrinogen into fibrin monomers, activates Factor V, VIII, and XIII, allowing fibrin to develop a covalently cross-linked framework that stabilizes the thrombus. Thrombin also promotes further thrombin generation, and activates platelets, stimulating aggregation and granule release. The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg<sub>3</sub>-Pro<sub>4</sub> bond, resulting in recovery of thrombin active site functions. | |||
Video describing bivalirudin’s mechanism of action: http://www.angiomax.com/AboutAngiomax/mechanismAction.aspx?launch=true{{dead link|date=May 2012}} | |||
'''Pharmacokinetics'''<ref name=Angiomax /> | |||
*Following an IV bolus of bivalirudin of 1 mg/kg and a 4-hour 2.5 mg/kg/h IV infusion a mean steady state concentration of 12.3 ± 1.7 µg/mL is achieved | |||
*Bivalirudin is cleared from plasma by a combination of renal mechanisms and proteolytic cleavage | |||
*Half-life: | |||
-Normal renal function (≥ 90 mL/min) = 25 minutes | |||
-Mild renal dysfunction (60–89 mL/min) = 22 minutes | |||
-Moderate renal dysfunction (30-59 mL/min) = 34 minutes | |||
-Severe renal dysfunction (≤ 29 mL/min) = 57 minutes | |||
-Dialysis-dependent = 3.5 hours | |||
*Clearance is reduced approximately 20% in patients with moderate and severe renal impairment and by 80% in dialysis-dependent patients | |||
*Bivalirudin is hemodialyzable and approximately 25% is cleared by hemodialysis. | |||
'''Pharmacodynamics'''<ref name=Angiomax /> | |||
Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration. | |||
==References== | ==References== | ||
Revision as of 23:11, 10 March 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]
For patient information about Bivalirudin, click here.
Synonyms / Brand Names: ANGIOMAX®
Overview
Bivalirudin (Angiomax or Angiox, manufactured by The Medicines Company) is a specific and reversible direct thrombin inhibitor (DTI).
Chemically, it is a synthetic congener of the naturally occurring drug hirudin (found in the saliva of the medicinal leech Hirudo medicinalis).
Bivalirudin is a DTI that overcomes many limitations seen with indirect thrombin inhibitors, such as heparin. Bivalirudin is a short, synthetic peptide that is potent, highly specific, and a reversible inhibitor of thrombin. It inhibits both circulating and clot-bound thrombin, while also inhibiting thrombin-mediated platelet activation and aggregation. 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/Heparin Induced Thrombosis-Thrombocytopenia Syndrome (HIT/HITTS). It does not require a binding cofactor such as antithrombin and does not activate platelets. 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 7 major randomized trials.
Category
Direct thrombin inhibitor.
FDA Package Insert
Label Title
Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages
Mechanism of Action
Bivalirudin directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine proteinase that plays a central role in the thrombotic process. It cleaves fibrinogen into fibrin monomers, activates Factor V, VIII, and XIII, allowing fibrin to develop a covalently cross-linked framework that stabilizes the thrombus. Thrombin also promotes further thrombin generation, and activates platelets, stimulating aggregation and granule release. The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions.
Video describing bivalirudin’s mechanism of action: http://www.angiomax.com/AboutAngiomax/mechanismAction.aspx?launch=true[dead link]
Pharmacokinetics[1]
- Following an IV bolus of bivalirudin of 1 mg/kg and a 4-hour 2.5 mg/kg/h IV infusion a mean steady state concentration of 12.3 ± 1.7 µg/mL is achieved
- Bivalirudin is cleared from plasma by a combination of renal mechanisms and proteolytic cleavage
- Half-life:
-Normal renal function (≥ 90 mL/min) = 25 minutes
-Mild renal dysfunction (60–89 mL/min) = 22 minutes
-Moderate renal dysfunction (30-59 mL/min) = 34 minutes
-Severe renal dysfunction (≤ 29 mL/min) = 57 minutes
-Dialysis-dependent = 3.5 hours
- Clearance is reduced approximately 20% in patients with moderate and severe renal impairment and by 80% in dialysis-dependent patients
- Bivalirudin is hemodialyzable and approximately 25% is cleared by hemodialysis.
Pharmacodynamics[1]
Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration.