Bivalirudin

Contraindications

4 CONTRAINDICATIONS Bivalirudin for Injection is contraindicated in patients with: • Active major bleeding; • Hypersensitivity (e.g., anaphylaxis) to bivalirudin or its components [see Adverse Reactions ( 6.3 )] . • Active major bleeding ( 4 ) • Hypersensitivity to bivalirudin or its components ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary There are no data available on use of Bivalirudin for Injection 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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Animal Data Reproductive studies have been performed in rats at subcutaneous doses up to 150 mg/kg/day (1.6 times the maximum recommended human dose based on body surface area) and rabbits at subcutaneous doses up to 150 mg/kg/day (3.2 times the maximum recommended human dose based on body surface area). These studies revealed no harm to the fetus attributable to bivalirudin. At 500 mg/kg/day (equivalent to 5.4 times the maximum recommended human dose based on body surface area) subcutaneously, litter sizes and live fetuses in rats were reduced. Fetal skeletal variations were also noted. Some of these changes could be attributed to maternal toxicity observed at high doses. There is no study covering the peri-natal period because of the potential complications of drug-induced hemorrhage during delivery.