Hematologic Agent (Antiplatelet)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Hold Breastfeeding
PREGNANCY SUMMARY
One report describing the use of eptifibatide in human pregnancy has been located. The animal data are reassuring but more human pregnancy experience is required to assess the risk this agent presents to the embryo–fetus. The primary risk, however, appears to be from maternal hemorrhage during drug administration. If this is adequately controlled, the benefits of the drug to the mother appear to far outweigh the unknown risks to the fetus.
FETAL RISK SUMMARY
The cyclic heptapeptide, eptifibatide, is indicated for the treatment of acute coronary syndrome in patients who will be managed medically or in those undergoing percutaneous coronary intervention. Eptifibatide acts as a reversible inhibitor of platelet aggregation by blocking the GP IIb/IIIa receptor on the platelet surface. It is in the same subclass of antiplatelet agents as abciximab and tirofiban. The drug undergoes some metabolism. Plasma protein binding is about 25% and the plasma elimination half-life is about 2.5 hours (1).
Reproduction studies with eptifibatide have been conducted in rats and rabbits. In pregnant rats and rabbits, continuous daily IV infusions at total daily doses up to about four times the maximum recommended human daily dose based on BSA (MRHDD) revealed no evidence of fetal harm. Although long-term studies in animals for carcinogenicity have not been conducted, no evidence of mutagenicity was found in several tests. Similarly, no evidence of impaired fertility or reproductive performance was observed in rats given daily doses up to about four times the MRHDD (1).
It is not known if eptifibatide crosses the human placenta to the fetus. The molecular weight (about 832), low plasma protein binding, and the elimination half-life suggest that the drug will cross to the embryo–fetus. Moreover, the drug is given as a continuous IV infusion for periods up to 72 hours, thus allowing for prolonged contact at the maternal–fetal interface.
A 44-year-old woman at 8 weeks’ gestation presented with an acute myocardial infarction (2). She was treated with intracoronary stent placement and clopidogrel (600 mg), heparin, and a 24-hour IV infusion of eptifibatide. The next day, she was started on clopidogrel, aspirin, and propranolol and discharged home on these agents. At 36 weeks, she underwent a planned cesarean section for a healthy infant (no further details on the newborn were provided) (2).
BREASTFEEDING SUMMARY
No reports describing the use of eptifibatide during lactation have been located. Because of the indications for eptifibatide, it is doubtful if such reports will be forthcoming. The molecular weight (about 832), low plasma protein binding, and the elimination half-life suggest that the drug will be excreted into breast milk. Moreover, the drug is given as a continuous IV infusion for periods up to 72 hours. The effect of this exposure for a nursing infant is unknown, but most likely the risk is very low or nil because the drug should be digested in the infant’s gastrointestinal tract. Until data are available, however, the safest course is to hold breastfeeding while the drug is being infused.
References
1.Product information. Integrilin. Schering, 2009.
2.Al-Aqeedi RF, Al-Nabti AD. Drug-eluting stent implantation for acute myocardial infarction during pregnancy with use of glycoprotein IIb/IIIa inhibitor. J Invasive Cardiol 2008;20:E146–9.