Endocrine/Metabolic Agent (Prostaglandin)
PREGNANCY RECOMMENDATION: Contraindicated (Unless for Termination/Evacuation of Pregnancy)
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the outcomes of human pregnancies following the use of carboprost in failed medical abortions have been located. Carboprost exposure in animals has resulted in embryotoxicity, but the doses were based on body weight and not compared to the human dose. However, another prostaglandin analog, misoprostol, when used unsuccessfully in the 1st trimester as an abortifacient, has been associated with cranial nerve defects in the fetus.
FETAL RISK SUMMARY
Carboprost tromethamine is a synthetic prostaglandin F2α analog that is given IM to stimulate myometrial contractions in the gravid uterus, leading to evacuation of the products of conception. Carboprost is approved for induced abortion between 13 and 20 weeks’ gestation. It also is indicated for postpartum uterine bleeding. In pregnant women in the 2nd trimester who were administered carboprost by continuous IV infusion, the elimination half-life of the drug was approximately 30–45 minutes, with similar findings when carboprost was given by IM injection (1).
Reproductive studies have been conducted with carboprost in rats and rabbits. Rabbits were given doses ranging between 0.0025 and 0.5/mg/kg on 3 consecutive days during organogenesis. Doses above 0.025 mg/kg interfered with implantation, were embryolethal, or induced abortion, but no teratogenic effects were seen. In rats, doses ranging from 0.001 to 1.0 mg/kg were given beginning on gestational day 15. Doses larger than 0.025/mg/kg caused abortions. At doses as low as 0.003 mg/kg, abortions or early deliveries occurred and most pups did not survive. There were no effects on structural development of the pups noted (1).
Studies for carcinogenicity have not been conducted with carboprost. No evidence of mutagenicity was observed in various assays. There was no effect on fertility in male and female rats treated with SC injections of 0.25–1.0 mg/kg for 3 or 6 days before breeding (1).
It is not known if carboprost crosses the placenta. The molecular weight (about 489) suggests that the drug will cross the placenta, but the relatively short elimination half-life should limit passage (1).
No reports describing the outcomes of human pregnancies following the use of carboprost in failed medical abortions have been located. Although a failed attempted abortion would typically be followed by completion of the procedure by some other means; in rare cases a woman may wish to maintain the pregnancy. Isolated case reports suggest that the failed procedure(s) themselves may result in damage to the placenta and therefore damage to the fetus (2). First-trimester exposure to another prostaglandin, misoprostol, in failed induced abortion, has been associated with an increased risk for 6th and 7th cranial nerve damage, leading to Möbius syndrome (3). However, in the case of carboprost, if used as indicated, exposure to the product would typically occur after the first trimester.
BREASTFEEDING SUMMARY
No reports describing the use of carboprost during human lactation have been located. The molecular weight of carboprost (about 489) suggests that the agent might cross into breast milk. Based on the elimination half-life, the manufacturer suggests that breastfeeding be avoided for a minimum of 6 hours after the last dose of carboprost (1).
References
1.Product information. Hemabate. Pfizer, 2004, 2006.
2.Arnon J, Ornoy A. Clinical teratology counseling and consultation case report: outcome of pregnancy after failure of early induced abortions. Teratology 1995;52:126–7.
3.Pastuszak AL, Schuler L, Speck-Martins CE, Coehlo KE, Cordello SM, Vargas F, Brunoni D, Schwarz IV, Larrandaburu M, Safattle H, Meloni VF, Koren G. Use of misprostol during pregnancy and Möbius syndrome in infants. N Engl J Med 1998;338:1881–5.