Bivalirudin

1 INDICATIONS AND USAGE 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 )

6 ADVERSE REACTIONS Most common adverse reaction (>2%) was bleeding. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact The Dr. Reddy’s Laboratories Inc. at 1-888-375-3784 or the 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 trialsof another drug and may not reflect the rates observed in practice. In the BAT trials, 79 of the 2,161 (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. 6.2 Immunogenicity As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observedincidence of antibody (including neutralizing antibody) positivity in an assay may be influencedby several factors including assay methodology, sample handling, timing of sample collection,concomitant medications, and underlying disease. For these reasons, comparison of the incidenceof antibodies to bivalirudin for injection in the studies described below with the incidence ofantibodies in other studies or to other products may be misleading. In in vitro studies, bivalirudin for injection exhibited no platelet aggregation response against serafrom patients with a history of HIT/HITTS. Among 494 subjects who received bivalirudin for injection in clinical trials and were tested forantibodies, 2 subjects had treatment-emergent positive bivalirudin antibody tests. Neither subjectdemonstrated clinical evidence of allergic or anaphylactic reactions and repeat testing was notperformed. Nine additional patients who had initial positive tests were negative on repeat testing. 6.3 Postmarketing Experience Because postmarketing adverse reactions are reported voluntarily from a population of uncertainsize, it is not always possible to reliably estimate their frequency or establish a causalrelationship to drug exposure. The following adverse reactions have been identified during postapproval use of bivalirudin forinjection: fatal bleeding; hypersensitivity and allergic reactions including reports of anaphylaxis;lack of anticoagulant effect; thrombus formation during PCI with and without intracoronarybrachytherapy, including reports of fatal outcomes; pulmonary hemorrhage; cardiac tamponade;and INR increased.