|Trade names||Angiomax, Angiox, others|
|Drug class||Direct thrombin inhibitor (DTI)|
|Main uses||Percutaneous coronary intervention (PCI)|
|Bioavailability||N/A (IV application only)|
|Metabolism||cleared from plasma by a combination of kidneys and proteolytic cleavage|
|Elimination half-life||~25 minutes with normal kidney function|
|Chemical and physical data|
|Molar mass||2180.317 g·mol−1|
|3D model (JSmol)|
Bivalirudin, sold under the brand names Angiomax and Angiox, is a medication used during percutaneous coronary intervention (PCI). It can be used in people with heparin-induced thrombocytopenia (HIT). It is given by injection into a vein.
Bivalirudin was approved for medical use in the United States in 2000. While it was approved in Europe in 2004, this approval was subsequently withdrawn. It is available as a generic medication. In the United States 250 mg costs about 115 USD as of 2022.
- Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA).
- Bivalirudin with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI).
- Bivalirudin is indicated for patients with, or at risk of HIT/HITTS undergoing PCI.
- Bivalirudin is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin
It appears to behave in a manner similar to that in adults.
Bivalirudin is intended for IV use and is supplied as a sterile, lyophilized product in single-use, glass vials. After reconstitution, each vial delivers 250 mg of bivalirudin.
- PCI bolus: 0.75 mg/kg
- PCI infusion: 1.75 mg/kg/h
-Bolus: 0.1 mg/kg -Infusion: 0.25 mg/kg/h for up to 72 hours for medical management -If patient proceeds to PCI, an additional bolus of 0.5 mg/kg of bivalirudin should be administered before the procedure and the infusion increased to 1.75 mg/kg/h for the duration of the procedure.
-Bolus: 0.75 mg/kg -Infusion: 1.75 mg/kg/h
- Coronary Artery Bypass Graft (CABG)
-Patients proceeding to CABG surgery off-pump:
The IV infusion of bivalirudin should be continued until the time of surgery. Just prior to surgery, a 0.5 mg/kg bolus dose should be administered followed by a 1.75 mg/kg/h infusion for the duration of the surgery. -Patients proceeding to CABG surgery on-pump:
The IV infusion of bivalirudin should be continued until 1 hour prior to surgery after which the infusion should be discontinued
Five minutes after the bolus dose has been administered, an activating clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed.
Continuation of the bivalirudin infusion following PCI for up to 4 hours post-procedure is optional, at the discretion of the treating physician. After 4 hours, an additional IV infusion of bivalirudin may be initiated at a rate of 0.2 or 0.25 mg/kg/h for up to 20 hours, if needed.
Bivalirudin should be administered with optimal antiplatelet therapy (aspirin plus clopidogrel).
A reduction in the infusion dose of bivalirudin should be considered in patients with moderate or severe renal impairment. If a patient is on hemodialysis, the infusion should be reduced to 0.25 mg/kg/h. No reduction in the bolus dose is needed.
Bivalirudin is contraindicated in people with active major bleeding and hypersensitivity to bivalirudin or its components. (In the EU bivalirudin is also contraindicated in patients with an increased risk of bleeding due to hemostasis disorders and/or irreversible coagulation disorders, severe uncontrolled hypertension, subacute bacterial endocarditis, and severe renal impairment [GFR<30 ml/min] and in dialysis-dependent patients).
Bivalirudin is an anticoagulant. Therefore, bleeding is an expected adverse event. In clinical trials, bivalirudin treated patients exhibited statistically significantly lower rates of bleeding than patients treated with heparin plus a GP IIb/IIIa inhibitor. The most common (≥10%) adverse events of bivalirudin are back pain, pain, nausea, headache, and hypotension.
Bivalirudin is classified as Pregnancy Category B.
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.
A short, synthetic peptide, it is a potent and highly specific inhibitor of thrombin that inhibits both circulating and clot-bound thrombin, while also inhibiting thrombin-mediated platelet activation and aggregation. Bivalirudin has a quick onset of action and a short half-life. 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. It does not require a binding cofactor such as antithrombin and does not activate platelets.
- 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
-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.
Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration.
Bivalirudin is a 20 amino acid long peptide with the sequence D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu (FPRPGGGGNGDFEEIPEEYL), where the first residue is D-phenylalanine instead of the natural L-phenylalanine.
It is also known as d-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
Bivalirudin studies demonstrated 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.
Bivalirudin has Class I recommendations in multiple national guidelines.
|STEMI and primary PCI||ACC/AHA/SCAI 2009 Joint STEMI/PCI Focused Update||Class I-B, IIa-B|
|UA/NSTEMI||ACC/AHA 2007 guidelines for UA/NSTEMI patients||Class I-B, IIa-B|
|NSTE-ACS patients||ACCP 2008 clinical practice guidelines for patients with NSTE-ACS||Grade 1A, 2B|
|PCI||ACCP 2008 clinical practice guidelines for patients with NSTE-ACS||Grade 1B|
|STEMI||European Society of Cardiology 2008||Class IIa – B|
|NSTE-ACS||European Society of Cardiology 2007||Class IIa-B, IB|
|PCI||European Society of Cardiology 2005||Class IIa C, IC|
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