Thrombin Inhibitor
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of bivalirudin in human pregnancy have been located. The animal data suggest low risk. The absence of human data prevents an assessment of the embryo–fetal risk. However, the manufacturer recommends that bivalirudin should always be used with aspirin (300–325 mg/day) and aspirin may cause developmental toxicity (see Aspirin). In addition, maternal bleeding secondary to both agents is a potential complication, especially in the 3rd trimester, and in the newborn if exposure has occurred within a week of delivery. If indicated, however, the maternal benefit appears to outweigh the potential, but unknown embryo–fetal risk.
FETAL RISK SUMMARY
The reversible direct thrombin inhibitor bivalirudin is a synthetic 20-amino acid peptide. It is indicated, in combination with aspirin, for use as an IV anticoagulant in patients undergoing percutaneous transluminal coronary angioplasty. In patients with normal renal function, bivalirudin has a very short half-life (25 minutes) but may be as long as 3.5 hours for dialysis-dependent patients. Bivalirudin is not bound to plasma proteins (other than thrombin) or to red blood cells (1).
Reproduction studies have been conducted in rats and rabbits. In rats, SC doses up to 1.6 times the maximum recommended human dose based on BSA (MRHD) revealed no evidence of impaired fertility or fetal harm. Similar findings were observed in rabbits with SC doses up to 3.2 times the MRHD (1).
It is not known if bivalirudin crosses the human placenta. The molecular weight (about 2180 for the anhydrous free base) and the very short elimination half-life in patients with normal renal function suggest that little, if any, of the peptide will cross the placenta.
BREASTFEEDING SUMMARY
No reports describing the use of bivalirudin during human lactation have been located. The molecular weight (about 2180 for the anhydrous free base) and short elimination half-life (25 minutes in patients with normal renal function) suggest that little, if any, drug will be excreted into milk. The indication for the drug suggests that women should not breastfeed while receiving bivalirudin. Waiting 3 hours or longer for patients with impaired renal function after the last dose would assure that the exposure of a nursing infant was minimal or nil. In addition, bivalirudin is a peptide that should be digested in the nursing infant’s gastrointestinal tract.
Reference
1.Product information. Angiomax. The Medicines Company, 2004.