Drugs in Pregnancy and Lactation: Tenth Edition

TIROFIBAN

Antiplatelet Agent

PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk

BREASTFEEDING RECOMMENDATION: Hold Breastfeeding

PREGNANCY SUMMARY

Only one report describing the use of tirofiban in human pregnancy has been located. The pregnancy was still ongoing at the time of the report. The animal data are reassuring but 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

Tirofiban, a nonpeptide antagonist of the platelet glycoprotein IIb/IIIa receptor, is an inhibitor of platelet aggregation. It is given by continuous IV infusion for up to 108 hours depending on the indication. Tirofiban is in the same subclass of antiplatelet agents as abciximab and eptifibatide. It is indicated, in combination with heparin, for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy. The metabolism of the agent is limited and about 65% is bound to plasma proteins. The half-life is about 2 hours (1).

Reproduction studies have been conducted in rats and rabbits. In these species, IV doses up to 5 and 13 times, respectively, the maximum recommended human dose based on BSA (MRHD) revealed no harm to the fetus (1).

Studies evaluating the carcinogenic potential of tirofiban have not been conducted. Multiple assays for mutagenicity and chromosomal aberration were negative. Fertility and reproductive performance were not affected in male and female rats given IV doses up to about 5 times the MRHD (1).

It is not known if tirofiban crosses the human placenta. The drug does cross the placenta in rats and rabbits. The molecular weight (about 441 for the nonhydrated free base), limited metabolism, and moderate plasma protein binding suggest that the drug will cross to the embryo–fetus. Moreover, the drug is given as a continuous IV infusion for periods up to 108 hours, thus allowing for prolonged contact at the maternal–fetal interface.

A 43-year-old woman, with a history of diabetes and hypertension, was in her sixth pregnancy when she had an acute myocardial infarction at 20 weeks’ gestation (2). She was treated with aspirin, nitroglycerin, and then tirofiban with heparin for PTCA and intracoronary stenting. She was discharged home, 5 days after the procedure, on aspirin, clopidogrel, and metoprolol (doses not specified). The pregnancy was ongoing at the time of the report (2).

BREASTFEEDING SUMMARY

No reports describing the use of tirofiban during human lactation have been located. The molecular weight (about 441 for the nonhydrated free base), limited metabolism, and moderate plasma protein binding (65%) suggest that the drug will be excreted into breast milk. Moreover, the drug is given as a continuous IV infusion for periods up to 108 hours. The drug is commonly combined with heparin and sometimes with aspirin. The effect of this exposure on a nursing infant is unknown, as is its oral bioavailability. However, the safest course is to hold breastfeeding during the infusion.

References

1.Product information. Aggrastat. Medicure International, 2007.

2.Boztosun B, Olcay A, Avci A, Kirma C. Treatment of acute myocardial infarction in pregnancy with coronary artery balloon angioplasty and stenting: use of tirofiban and clopidogrel. Int J Cardiol 2008;127:413–6.