is a direct thrombin inhibitor indicated for use as an anticoagulant in patients: ? With unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA). ? Undergoing percutaneous coronary intervention (PCI) with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) as in the REPLACE-2 study. ? With, or at risk of, heparin-induced thrombocytopenia (HIT) or heparininduced thrombocytopenia and thrombosis syndrome (HITTS), undergoing PCI. ? Angiomax is intended for use with aspirin.
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, acting to cleave fibrinogen into fibrin monomers and to 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. 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.
In in vitro studies, bivalirudin inhibited both soluble (free) and clot-bound thrombin, was not neutralized by products of the platelet release reaction, and prolonged the activated partialthromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) of normal human plasma in a concentration-dependent manner. The clinical relevance of these findings is unknown.
For patients who do not have HIT/HITTS ? PCI/PTCA: 0.75 mg/kg intravenous (IV) bolus dose followed immediately by a 1.75 mg/kg/h IV infusion for the duration of the procedure. See FPI for remainder of monitoring and dosing information. For patients who have HIT/HITTS ? PCI: 0.75 mg/kg IV bolus dose followed immediately by a 1.75 mg/kg/h IV infusion for the duration of the procedure. For patients with STEMI ? Consider extending duration of infusion post-procedure up to 4 hours.
Co-administration of Bivalirudin with heparin, warfarin, thrombolytics, or GPIs was associated with increased risks of major bleeding events.
Active major bleeding ? Hypersensitivity to bivalirudin or any product components
Bleeding (28%). Other adverse reactions (incidence >0.5%) were headache, thrombocytopenia and fever.
Pregnancy Category B. No adequate and well-controlled studies in pregnant women. As animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Bivalirudin is intended for use with aspirin . Because of possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Bivalirudin and aspirin should be used together during pregnancy only if clearly needed.
Nursing Mothers: It is not known whether bivalirudin is excreted in human milk. As many drugs are excreted in human milk, caution should be exercised when Bivalirudin is administered to a nursing woman.
Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of Bivalirudin have been reported in clinical trials and in postmarketing reports. A number of the reported overdoses were due to failure to adjust the infusion dose of bivalirudin in persons with renal dysfunction including persons on hemodialysis . Bleeding, as well as deaths due to hemorrhage, have been observed in some reports of overdose. In cases of suspected overdosage, discontinue Bivalirudin immediately and monitor the patient closely for signs of bleeding. There is no known antidote to Bivalirudin. Bivalirudin is hemodialyzable
Store at temperature not exceeding 30º C in a dry place. Do not freeze. Keep out of reach of children
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