Hematologic Agent (Antiplatelet)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of treprostinil during human pregnancy have been located. The animal data suggest low risk, but the lack of human pregnancy experience prevents an assessment of the embryo–fetal risk. However, maternal hypotension, resulting in decreased placental perfusion and fetal hypoxia, is a potential risk.
FETAL RISK SUMMARY
Treprostinil is an inhibitor of platelet aggregation. Its action includes direct vasodilation of pulmonary and systemic arterial vascular beds. Treprostinil is administered by continuous SC infusion for the treatment of pulmonary arterial hypertension. The terminal elimination half-life is about 2–4 hours. Treprostinil is extensively metabolized in the liver but the biological activity of the metabolites is unknown (1).
Reproduction studies have been conducted in rats and rabbits. In pregnant rats during organogenesis, continuous SC infusions of doses up to about 117 times the recommended starting rate in humans based on BSA (HD) and about 16 times the average rate achieved in clinical trials (AR) revealed no evidence of fetal harm. At doses up to about 8 times the AR, continuous SC infusions administered from implantation to the end of lactation had no effect on growth or development of offspring. In pregnant rabbits during organogenesis, a continuous SC infusion at 41 times the HD and about 5 times the AR produced fetal skeletal variations. However, maternal toxicity (decreased body weight and food consumption) was evident at this dose (1).
It is not known if treprostinil crosses the human placenta. The molecular weight (about 412) is low enough that passage to the fetus should be expected. Moreover, the drug is administered as a continuous SC infusion that should result in relatively constant plasma drug concentrations at the placental maternal–fetal interface.
BREASTFEEDING SUMMARY
No reports describing the use of treprostinil during lactation have been located. The molecular weight (about 412) and method of administration (continuous SC infusion) suggest that the drug will be excreted into breast milk. In adults, treprostinil undergoes extensive hepatic metabolism, but the biological activity of the metabolites has not been characterized. However, even if the metabolites are inactive, the neonatal immature hepatic function could allow systemic levels of the parent drug. Although the effect of this exposure on a nursing infant is unknown, treprostinil has caused clinically significant adverse effects in adults (e.g., headache, nausea/vomiting, restlessness, and anxiety). A nursing infant should be closely observed for these effects if a woman receiving treprostinil elects to breastfeed.
Reference
1.Product information. Remodulin. United Therapeutics, 2002.