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. 

For injection: 250 mg of bivalirudinas a lyophilized power 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.

Bivalirudin for injection is contraindicated in patients with:

In clinical trials in patients undergoing PCI/ percutaneous transluminal coronary angioplasty(PTCA), co-administration of bivalirudin for injection with heparin, warfarin, thrombolytics, orGPIs was associated with increased risks of major bleeding events compared to patients notreceiving these concomitant medications.

Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of bivalirudin for injection 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 (

Bivalirudin for injection contains bivalirudin which is a specific and reversible direct thrombin inhibitor. Bivalirudin is a synthetic, 20 amino acid peptide, with the chemical name of D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine.

The active pharmaceutical ingredient is in the form of bivalirudin trifluoroacetate as a white to off-white powder. The chemical name for bivalirudin trifluoroacetate is D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-Lphenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine trifluoroacetate (Figure 1). The molecular weight of bivalirudin is 2180 daltons (anhydrous free base peptide).  

Figure 1: Structure formula for bivalirudin trifluoroacetate

In the BAT studies, patients with unstable angina undergoing PCI were randomized 1:1 to a 1 mg/kg bolus of bivalirudin for injection and then 2.5 mg/kg/h for four hours and then 0.2 mg/kg/h for 14 to 20 hours or to 175 IU/kg bolus of heparin followed by an 18 to 24 hour infusion of 15 IU/kg/h infusion. Additional heparin but not bivalirudin for injection could be administered for ACT <350 seconds. The studies were designed to demonstrate the superiority of bivalirudin for injection to heparin on the occurrence of any of the following during hospitalization up to seven days of death, MI, abrupt closure of dilated vessel, or clinical deterioration requiring revascularization or placement of an aortic balloon pump.

The 4,312 subjects ranged in age from 29 to 90 (median 63) years. 68% were male, and 91% were Caucasian. Median weight was 80 kg (39 to 120 kg). 741 (17%) subjects had post-MI angina. Twenty-three percent of patients were treated with heparin within one hour prior to randomization.  

The studies did not demonstrate that bivalirudin for injection was statistically superior to heparin for reducing the risk of death, MI, abrupt closure of the dilated vessel, or clinical deterioration requiring revascularization or placement of an aortic balloon pump, but the occurrence of these events was similar in both treatment groups. Study outcomes are shown in Table 3.

This was a single-arm open-label study in which 51 patients with heparin-induced thrombocytopenia (HIT) or heparin induced thrombocytopenia and thrombosis syndrome (HITTS) underwent PCI. The majority of patients achieved adequate ACT at the time of device activation and no major bleeding was reported. Evidence for the diagnosis of HIT/HITTS was based on a clinical history of a decrease of platelets in patients after heparin administration [new diagnosis or history of clinically suspected or objectively documented HIT/HITTS defined as either: 1) HIT: positive heparin-induced platelet aggregation (HIPA) or other functional assay where the platelet count has decreased to <100,000/mL (minimum 30% from prior to heparin), or has decreased to <150,000/mL (minimum 40% from prior to heparin), or has decreased as above within hours of receiving heparin in a patient with a recent, previous exposure to heparin; 2) HITTS: thrombocytopenia as above plus arterial or venous thrombosis diagnosed by physician examination/laboratory and/or appropriate imaging studies]. Patients ranged in age from 48 to 89 years (median 70); weight ranged from 42 to 123 kg (median 76); 50% were male and 50% were female. Bivalirudin for injection was administered as either 1 mg/kg bolus followed by 2.5 mg/kg/h (high dose in 28 patients) or 0.75 mg/kg bolus followed by a 1.75 mg/kg/h infusion (lower dose in 25 patients) for up to 4 hours. Ninety-eight percent of patients received aspirin, 86% received clopidogrel and 19% received GPIs.  

The median ACT values at the time of device activation were 379 sec (high dose) and 317 sec (lower dose). Following the procedure, 48 of the 51 patients (94%) had TIMI grade 3 flow and stenosis <50%. One patient died during a bradycardic episode 46 hours after successful PCI, another patient required surgical revascularization, and one patient experienced no flow requiring a temporary intra-aortic balloon.  

Two of the fifty-one patients with the diagnosis of HIT/HITTS developed thrombocytopenia after receiving bivalirudin for injection and GPIs.

Advise patients to watch carefully for any signs of bleeding or bruising and to report these to their health care provider when they occur.

Rx Only

Distributor:

Princeton, NJ 08540

Issued: 0719