Ophthalmic (Prostaglandin Agonist)
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Neither the limited human pregnancy experience nor the animal reproduction data suggest that latanoprost is a clinically significant risk to the embryo–fetus. The amount of drug in the systemic circulation after ophthalmic use of the recommended dose is likely minimal. The limited data suggest that, if indicated, latanoprost should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Latanoprost, a prostaglandin F2α analog, is a topical ophthalmic solution indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is in the same class as bimatoprost, tafluprost, and travoprost. Latanoprost is a prostanoid selective FP receptor agonist, which is believed to reduce the intraocular pressure by increasing the outflow of aqueous humor. Latanoprost is a prodrug that is hydrolyzed by esterases in the cornea to the biologically active acid. Metabolites of the active acid are inactive. The elimination half-life of the active acid form is 17 minutes (1,2).
Reproduction studies have been performed in rats and rabbits. In rabbits, 4 of 16 dams had no viable fetuses at a dose that was about 80 times the maximum human dose (MHD) (assumed to be based on body weight). The no-effect dose for embryo death in rabbits was about 15 times the MHD (1,2). No information on studies conducted in pregnant rats was provided.
Latanoprost was not carcinogenic in mice and rats at doses up to 2800 times the MHD. Mutagenicity studies were also negative in multiple assays, but the drug did cause chromosome aberrations in an in vitro assay with human lymphocytes. The drug had no effect on male or female fertility in animal studies (1,2).
It is not known if latanoprost or its active acid crosses the human placenta. The molecular weight of the prodrug (about 433) is low enough, but plasma concentrations are probably very low and have a very short elimination half-life. These properties suggest that clinically significant exposure of the embryo–fetus is unlikely.
Prostaglandin F2α has been used for pregnancy termination in humans via intrauterine extra-amniotic infusion to treat missed abortion or intrauterine death. However, there is no evidence that at doses given to reduce elevated ophthalmic pressure, an increased risk for uterine contractions would be seen (3,4).
Eleven 1st trimester latanoprost-exposed pregnancies were identified by a teratology information service in Italy (5). Exposure in the 1st trimester occurred for 4–70 days. Three women continued therapy throughout gestation and one discontinued the drug in the 3rd trimester. One pregnancy was lost to follow-up, one ended in a spontaneous abortion 2 weeks after therapy was discontinued (in a 46-year-old woman), and nine women gave birth at term to normal, healthy infants (5).
BREASTFEEDING SUMMARY
No reports describing the use of latanoprost during human lactation have been located. The molecular weight of the prodrug (about 433) is low enough, but plasma concentrations are probably very low and have a very short elimination half-life (17 minutes). These properties suggest that clinically significant amounts will not be excreted into breast milk.
References
1.Product information. Xalatan. Pharmacia & Upjohn, 2009.
2.Product information. Latanoprost. Apotex, 2011.
3.Lipitz S, Grisaru D, Libshiz A, Rotstein Z, Schiff E, Lidor A, Achiron R. Intra-amniotic prostaglandin F2 alpha for pregnancy termination in the second and early third trimesters of pregnancy. J Reprod Med 1997;42:235–8.
4.Salamalekis E, Kassanos D, Hassiakos D, Chrelias C, Ghristodoulakos G. Intra/extra-amniotic administration of prostaglandin F2α in fetal death, missed and therapeutic abortions. Clin Exp Obstet Gynecol 1990;17:17–21.
5.De Santis M, Lucchese A, Carducci B, Cavaliere AF, De Santis L, Merola A, Straface G, Caruso A. Latanoprost exposure in pregnancy. Am J Ophthalmol 2004;138:305–6.