Bivalirudin

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. Bivalirudin for injection is a direct thrombin inhibitor indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI) including patients with heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS).( 1 )

• 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)
• Recommended Dosage Bivalirudin has been studied only in patients receiving concomitant aspirin
• The recommended dose of bivalirudin 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)
• Dose Adjustment in Renal Impairment Bolus Dose No reduction in the bolus dose is needed for any degree of renal impairment
• Maintenance Infusion 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 [see Use in Specific Populations , Clinical Pharmacology ] . …

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*. *The range of bivalirudin trifluoroacetate is 270 to 280 mg based on a range of trifluoroacetic acid composition of 1.7 to 2.6 equivalents . …

• The safety and effectiveness of bivalirudin
• In pediatric patients have not been established

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.

• Advise patients to watch carefully for any signs of bleeding or bruising and to report these to their health care provider when they occur
• Distributed by: Civica, Inc., Lehi, Utah 84043 Manufactured by: Patheon Italia, S.p.A. Via G.B
• Stucchi, 110 I-20052 Monza (MB), Italy U.S
• Patents 7,598,343; 7,582,727

Bivalirudin is contraindicated in patients with: • Active major bleeding; • Hypersensitivity (e.g., anaphylaxis) to bivalirudin or its components [see Adverse Reactions (6.1) ] . • Active major bleeding ( 4 ) • Hypersensitivity to bivalirudin or its components ( 4 )

In clinical trials in patients undergoing PCI/ percutaneous transluminal coronary angioplasty (PTCA), coadministration of bivalirudin with heparin, warfarin, thrombolytics, or GPIs was associated with increased risks of major bleeding events compared to patients not receiving these concomitant medications. Heparin, warfarin, thrombolytics, or GPIs: Increased major bleeding risk with concomitant use. ( 7 )

• Bleeding Events: Bivalirudin increases the risk of bleeding. ( 5.1 , 6.1 , 12.2 ) • Acute Stent Thrombosis: Increased incidence of acute stent thrombosis in STEMI patients undergoing primary PCI. ( 2.1 , 5.2 ) • Thrombotic Risk with Coronary Artery Brachytherapy: An increased risk of thrombus formation, including fatal outcomes, in gamma brachytherapy. ( 5.3 ) 5.1 Bleeding Events Bivalirudin increases the risk of bleeding [see Adverse Reactions ( 6.1 )] . An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of bivalirudin administration. Monitor patients receiving bivalirudin for signs and symptoms of bleeding. …

Most common adverse reaction (>2%) was bleeding. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because 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. …

8.1 Pregnancy Risk Summary There are no data available on use of bivalirudin in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Reproduction studies in rats and rabbits administered subcutaneously doses up to 1.6 times and 3.2 times the maximum recommended human dose (MRHD) of 15 mg/kg/day based on body surface area (BSA) during organogenesis, respectively, revealed no evidence of fetal harm. …

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 [see Dosage and Administration (2.2) ] . 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. …

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