Bivalirudin
Bivalirudin Prescribing Information
Bivalirudin for injection is indicated for use as an anticoagulant for use in patients undergoing percutaneous coronary intervention (PCI) including patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.
- The recommended dosage is a 0.75 mg/kg intravenous bolus dose followed immediately by a 1.75 mg/kg/h intravenous infusion for the duration of the procedure. Five minutes after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus dose of 0.3 mg/kg should be given if needed.
- Extending duration of infusion post-procedure up to 4 hours should be considered in patients with ST segment elevation MI (STEMI). ()
2.1 Recommended DosageBivalirudin for injection has been studied only in patients receiving concomitant aspirin.
The recommended dose of bivalirudin for injection is an intravenous bolus dose of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h for the duration of the procedure. Five minutes after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed.
Extended duration of infusion following PCI at 1.75 mg/kg/h for up to 4 hours post-procedure should be considered in patients with ST segment elevation MI (STEMI).
For injection: 250 mg of bivalirudin as a lyophilized powder in a single-dose vial for reconstitution. Each vial contains 250 mg of bivalirudin equivalent to an average of 275 mg bivalirudin trifluoroacetate*.
In studies of patients undergoing PCI, 44% were ≥65 years of age and 12% of patients were ≥75 years old. Elderly patients experienced more bleeding events than younger patients.
No reduction in the bolus dose is needed for any degree of renal impairment.
In patients with creatinine clearance less than 30mL/min (by Cockcroft Gault equation), reduce the infusion rate to 1 mg/kg/h. Monitor anticoagulant status in patients with renal impairment.
In patients on hemodialysis, reduce the infusion rate to 0.25 mg/kg/h
The disposition of bivalirudin for injection was studied in PTCA patients with mild, moderate and severe renal impairment. The clearance of bivalirudin was reduced approximately 21% in patients with moderate and severe renal impairment and was reduced approximately 70% in dialysis-dependent patients
Bivalirudin for injection is contraindicated in patients with:
- Active major bleeding;
- Hypersensitivity (e.g., anaphylaxis) to bivalirudin for injection or its components[see Adverse Reactions (.)]
6.3 Postmarketing ExperienceBecause postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been identified during post approval use of bivalirudin for injection: fatal bleeding; hypersensitivity and allergic reactions including reports of anaphylaxis; lack of anticoagulant effect; thrombus formation during PCI with and without intracoronary brachytherapy, including reports of fatal outcomes; pulmonary hemorrhage; cardiac tamponade; and INR increased.
- Bleeding Events: Bivalirudin for injection increases the risk of bleeding. (,
5.1 Bleeding EventsBivalirudin for injection increases the risk of bleeding
[see Adverse Reactions ]. An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of bivalirudin for injection administration. Monitor patients receiving Bivalirudin for injection for signs and symptoms of bleeding. Monitor patients with disease states associated with an increased risk of bleeding more frequently for bleeding.,6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the BAT trials, 79 of the 2161 (3.7%) patients undergoing PCI for treatment of unstable angina and randomized to bivalirudin for injection experienced major bleeding events which consisted of: intracranial bleeding, retroperitoneal bleeding, and clinically overt bleeding with a decrease in hemoglobin >3 g/dL or leading to a transfusion of >2 units of blood.
)12.2 PharmacodynamicsIn healthy volunteers and patients (with ≥70% vessel occlusion undergoing routine PTCA), bivalirudin exhibited dose- and concentration-dependent anticoagulant activity as evidenced by prolongation of the ACT, aPTT, PT, and TT. Intravenous administration of bivalirudin produces an immediate anticoagulant effect. Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration. Bivalirudin for injection also increases INR. Therefore INR measurements made in bivalirudin for injection treated patients may not be useful for determining the appropriate dose of warfarin.
In 291 patients with ≥70% vessel occlusion undergoing routine PTCA, a positive correlation was observed between the dose of bivalirudin and the proportion of patients achieving ACT values of 300 sec or 350 sec. At a bivalirudin dose of 1 mg/kg IV bolus plus 2.5 mg/kg/h IV infusion for 4 hours, followed by 0.2 mg/kg/h, all patients reached maximal ACT values >300 sec.
- Acute Stent Thrombosis: Increased incidence of acute stent thrombosis in STEMI patients undergoing primary PCI. (,
2.1 Recommended DosageBivalirudin for injection has been studied only in patients receiving concomitant aspirin.
The recommended dose of bivalirudin for injection is an intravenous bolus dose of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h for the duration of the procedure. Five minutes after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed.
Extended duration of infusion following PCI at 1.75 mg/kg/h for up to 4 hours post-procedure should be considered in patients with ST segment elevation MI (STEMI).
)5.2 Acute Stent Thrombosis in Patients with STEMI Undergoing PCIAcute stent thrombosis (AST) (<4 hours) has been observed at a greater frequency in bivalirudin for injection treated patients (1.2%, 36/2889) compared to heparin treated patients (0.2%, 6/2911) with STEMI undergoing primary PCI. Among patients who experienced an AST, one fatality (0.03%) occurred in a bivalirudin for injection treated patient and one fatality (0.03%) in a heparin treated patient. These patients have been managed by Target Vessel Revascularization (TVR). Patients should remain for at least 24 hours in a facility capable of managing ischemic complications and should be carefully monitored following primary PCI for signs and symptoms consistent with myocardial ischemia.
- Thrombotic Risk with Coronary Artery Brachytherapy: An increased risk of thrombus formation, including fatal outcomes, in gamma brachytherapy. ()
5.3 Thrombotic Risk with Coronary Artery BrachytherapyAn increased risk of thrombus formation, including fatal outcomes, has been associated with the use of bivalirudin for injection in gamma brachytherapy.
If a decision is made to use bivalirudin for injection during brachytherapy procedures, maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels
[see Adverse Reactions ].