Emergency Contraceptive
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of ulipristal in human pregnancy have been located. As an emergency contraceptive, the main action is delaying or inhibiting ovulation (1–5). Animal studies suggest that pregnancy loss is a risk, but the absence of human pregnancy experience prevents a more complete assessment of this effect. The drug is contraindicated in pregnancy.
FETAL RISK SUMMARY
Ulipristal is an oral selective progesterone receptor modulator with potent antagonist/partial agonist properties that is used as an emergency contraceptive. It is indicated for prevention of pregnancy within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. The pharmacodynamic effects of ulipristal depend on the phase of the menstrual cycle when it is administered. Administration in the mid-follicular phase results in the inhibition of folliculogenesis and a reduction in estradiol concentration. When given at the time of the luteinizing hormone peak, follicular rupture is delayed by 5–9 days. Dosing in the early luteal phase does not significantly delay endometrial maturation but does decrease endometrial thickness, thereby interfering with implantation. Ulipristal is metabolized to its active metabolite, monodemethyl-ulipristal. Ulipristal is highly bound (>94%) to plasma proteins, including lipoproteins, α-1-acid glycoprotein, and albumin. The terminal half-lives of ulipristal and monodemethyl-ulipristal are about 32 and 27 hours, respectively (1).
Reproduction studies have been conducted in rats, rabbits, and monkeys. In rats and rabbits, doses during organogenesis at daily exposures that were 0.33 and 0.5 times, respectively, the human exposure based on BSA (HE-BSA) resulted in embryo–fetal loss in all of the pregnant rats and in half of the pregnant rabbits. No malformations were noted in the surviving fetuses. Adverse effects were not observed in rat offspring when the dose was about 0.04 times the HE based on AUC during organogenesis through lactation. In pregnant monkeys, daily doses for 4 days during the 1st trimester that were about 4 times the HE-BSA caused pregnancy termination in two of five animals (1).
Carcinogenicity studies have not been conducted with ulipristal. The drug was not genotoxic in multiple assays. In rats, single doses at 2 times the HE-BSA prevented ovulation in 50% of the animals. When given on postcoital days 4 or 5, single doses that were 4–12 times the HE-BSA prevented pregnancy in 80%–100% of the rats. Similar doses in rabbits on postcoital days 5 or 6 prevented pregnancy in 50% of the animals. Lower doses for 4 days in rats and rabbits were also effective in preventing ovulation and pregnancy (1).
It is not known if ulipristal or its active metabolite crosses the human placenta. The molecular weights (about 476 for ulipristal acetate; lower for the active metabolite) and the long elimination half-lives of both agents suggest that they will cross to the embryo–fetus, but the high plasma protein binding may limit the exposure.
BREASTFEEDING SUMMARY
No reports describing the use of ulipristal during human lactation have been located. The molecular weights (about 476 for ulipristal acetate; lower for the active metabolite) and the long elimination half-lives (32 and 27 hours) of the parent drug and active metabolite suggest that both will be excreted into breast milk, but the high plasma protein binding may limit the amount excreted. The effect on a nursing infant from short-term exposure to a potent progesterone antagonist/partial agonist is unknown. However, not breastfeeding is the best course.
References
1.Product information. Ella. Watson Pharma, 2010.
2.Benagiano G, Bastianelli, Farris M. Selective progesterone receptor modulators 1: use during pregnancy. Expert Opin Pharmacother 2008;9:2459–72.
3.Gemzell-Danielsson K, Meng CX. Emergency contraception: potential role of ulipristal acetate. Int J Womens Health 2010;2:53–61.
4.Fine PM. Ulipristal acetate: a new emergency contraceptive that is safe and more effective than levonorgestrel. Women’s Health (Long Engl) 2011;7:9–17.
5.Fine PM. Update on emergency contraception. Adv Ther 2011;28:87–90.