Bivalirudin

BIVALIRUDIN- bivalirudin injection, powder, lyophilized, for solution
Athenex Pharmaceutical Division, LLC.

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.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Bivalirudin 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).

2.2 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 30 mL/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 (8.6), Clinical Pharmacology (12.3)].

2.3 Instructions for Preparation and Administration

Bivalirudin for injection is intended for intravenous bolus injection and continuous infusion after reconstitution and dilution.

Preparation Instructions for Bolus Injection and Continuous Infusion

• To each 250 mg vial, add 5 mL of Sterile Water for Injection, USP.
• Gently swirl until all material is dissolved.
• Withdraw and discard 5 mL from a 50 mL infusion bag containing 5% Dextrose in Water or 0.9% Sodium Chloride for Injection.
• Add the contents of the reconstituted vial to the infusion bag containing 5% Dextrose in Water or 0.9% Sodium Chloride for Injection to yield a final concentration of 5 mg/mL (e.g., 1 vial in 50 mL; 2 vials in 100 mL; 5 vials in 250 mL).
• Adjust the dose to be administered according to the patient’s weight (see Table 1).

Table 1: Dosing Table

Weight (kg)	Using 5 mg/mL Concentration
	Bolus 0.75 mg/kg (mL)	Infusion 1.75 mg/kg/h (mL/h)
43-47	7	16
48-52	7.5	17.5
53-57	8	19
58-62	9	21
63-67	10	23
68-72	10.5	24.5
73-77	11	26
78-82	12	28
83-87	13	30
88-92	13.5	31.5
93-97	14	33
98-102	15	35
103-107	16	37
108-112	16.5	38.5
113-117	17	40
118-122	18	42
123-127	19	44
128-132	19.5	45.5
133-137	20	47
138-142	21	49
143-147	22	51
148-152	22.5	52.5

Drug Compatibilities

No incompatibilities have been observed with administration sets.

Do not administer the drugs listed in Table 2 in the same intravenous line with bivalirudin for injection.

Table 2: Drugs Not for Administration in the Same Intravenous Line with Bivalirudin for Injection

Alteplase

Amiodarone HCl

Amphotericin B

Chlorpromazine HCl

Diazepam

Dobutamine

Prochlorperazine Edisylate

Reteplase

Streptokinase

Vancomycin HCl

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Preparations of bivalirudin for injection containing particulate matter should not be used. Reconstituted material will be a clear to slightly opalescent, colorless to slightly yellow solution.