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__NOTOC__
__NOTOC__
{{Argatroban}}
{{Bivalirudin}}
{{CMG}}; {{AE}} {{JH}}
{{CMG}}; {{AE}} {{JH}}
'''''For patient information about Bivalirudin, click [[Bivalirudin (patient information)|here]].'''''
{{SB}} ANGIOMAX<sup>®</sup>


==Overview==
==Overview==


'''Argatroban''' is an [[anticoagulant]] that is a small molecule [[direct thrombin inhibitor]].  In 2000, argatroban was licensed by the [[Food and Drug Administration]] (FDA) for prophylaxis or treatment of [[thrombosis]] in patients with [[heparin-induced thrombocytopenia|heparin-induced thrombocytopenia (HIT)]].  In 2002, it was approved for use during [[Angioplasty|percutaneous coronary interventions]] in patients who have or at risk for developing [[HIT]].
'''Bivalirudin''' (Angiomax or Angiox, manufactured by The Medicines Company) is a specific and reversible [[direct thrombin inhibitor]] (DTI).


Argatroban is given intravenously.  Argatroban is metabolized in the [[liver]] and has a half life of about 50 minutes.  It is monitored by [[PTT]].  Because of its hepatic metabolism, it may be used in patients with [[renal dysfunction]].  (This is in contrast to [[lepirudin]], a [[direct thrombin inhibitor]] that is primarily renally cleared).
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 [[GlaxoSmithKline]].
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 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==
==Category==


Anticoagulants; Direct Thrombin Inhibitor
Direct thrombin inhibitor.


==FDA Package Insert==
==FDA Package Insert==


====ARGATROBAN injection, solution====
====Label Title====
 
'''  [[Bivalirudin indications and usage|Indications and Usage]]'''
'''| [[Bivalirudin dosage and administration|Dosage and Administration]]'''
'''| [[Bivalirudin dosage forms and strengths|Dosage Forms and Strengths]]'''
'''| [[Bivalirudin contraindications|Contraindications]]'''
'''| [[Bivalirudin warnings and precautions|Warnings and Precautions]]'''
'''| [[Bivalirudin adverse reactions|Adverse Reactions]]'''
'''| [[Bivalirudin drug interactions|Drug Interactions]]'''
'''| [[Bivalirudin use in specific populations|Use in Specific Populations]]'''
'''| [[Bivalirudin overdosage|Overdosage]]'''
'''| [[Bivalirudin description|Description]]'''
'''| [[Bivalirudin clinical pharmacology|Clinical Pharmacology]]'''
'''| [[Bivalirudin nonclinical toxicology|Nonclinical Toxicology]]'''
'''| [[Bivalirudin clinical studies|Clinical Studies]]'''
'''| [[Bivalirudin how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Bivalirudin patient counseling information|Patient Counseling Information]]'''
'''| [[Bivalirudin labels and packages|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-Arg<sub>3</sub>-Pro<sub>4</sub> bond, resulting in recovery of thrombin active site functions.
 
'''Pharmacokinetics'''
 
*Following an IV bolus of bivalirudin of 1&nbsp;mg/kg and a 4-hour 2.5&nbsp;mg/kg/h IV infusion a mean steady state concentration of 12.3 ± 1.7&nbsp;µg/mL is achieved
 
*Bivalirudin is cleared from plasma by a combination of renal mechanisms and proteolytic cleavage
 
*Half-life:
 
: Normal renal function (≥&nbsp;90&nbsp;mL/min) = 25 minutes
 
: Mild renal dysfunction (60–89&nbsp;mL/min) = 22 minutes
 
: Moderate renal dysfunction (30-59&nbsp;mL/min) = 34 minutes
 
: Severe renal dysfunction (≤&nbsp;29&nbsp;mL/min) = 57 minutes
 
: Dialysis-dependent  = 3.5 hours


'''  [[Argatroban indications and usage|Indications and Usage]]'''
*Clearance is reduced approximately 20% in patients with moderate and severe renal impairment and by 80% in [[dialysis]]-dependent patients
'''| [[Argatroban dosage and administration|Dosage and Administration]]'''
'''| [[Argatroban dosage forms and strengths|Dosage Forms and Strengths]]'''
'''| [[Argatroban contraindications|Contraindications]]'''
'''| [[Argatroban warnings and precautions|Warnings and Precautions]]'''
'''| [[Argatroban adverse reactions|Adverse Reactions]]'''
'''| [[Argatroban drug interactions|Drug Interactions]]'''
'''| [[Argatroban use in specific populations|Use in Specific Populations]]'''
'''| [[Argatroban overdosage|Overdosage]]'''
'''| [[Argatroban description|Description]]'''
'''| [[Argatroban clinical pharmacology|Clinical Pharmacology]]'''
'''| [[Argatroban nonclinical toxicology|Nonclinical Toxicology]]'''
'''| [[Argatroban clinical studies|Clinical Studies]]'''
'''| [[Argatroban how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Argatroban patient counseling information|Patient Counseling Information]]'''
'''| [[Argatroban labels and packages|Labels and Packages]]'''


==Reference==
*Bivalirudin is hemodialyzable and approximately 25% is cleared by hemodialysis.


* Di Nisio M, Middeldorp S, Buller HR. Direct thrombin inhibitors. ''[[N Engl J Med]]'' 2005;353:1028-40. PMID 16148288.
'''Pharmacodynamics'''


==External links==
[[Coagulation]] times return to baseline approximately 1 hour following cessation of bivalirudin administration.


*[http://www.argatroban.com GlaxoSmithKline's website on argatroban]
==References==


{{Antithrombotics}}
{{Reflist|2}}


[[Category:Anticoagulants]]
[[Category:Cardiology]]
[[Category:Cardiovascular Drugs]]
[[Category:Cardiovascular Drugs]]
[[Category:Drugs]]
[[Category:Drugs]]
[[Category:Hematology]]

Revision as of 13:52, 9 July 2014

Bivalirudin
ANGIOMAX® FDA Package Insert
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
Clinical Trials on Bivalirudin
ClinicalTrials.gov

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.

Pharmacokinetics

  • 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

Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration.

References

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