Ophthalmic (Prostaglandin Agonist)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of travoprost in human pregnancy have been located. The animal data suggest moderate risk, but the amount appearing in the systemic circulation is very low. Moreover, the elimination half-life from plasma is very fast. Although the absence of human pregnancy experience prevents a more complete assessment of embryo–fetal risk, the risk of harm appears to be low. Nevertheless, because the drug will be given daily for long periods, it may be best to use other anti-glaucoma agents that have some human data (e.g., Latanoprost).
FETAL RISK SUMMARY
Travoprost is a synthetic prostaglandin F analog that acts as a selective FP prostanoid receptor agonist to reduce intraocular pressure by increasing uveoscleral outflow. It is available as an 0.004% ophthalmic solution that is given as one drop in the affected eye(s) once daily. It is in the same class of prostaglandin agonists as bimatoprost, latanoprost, and tafluprost. Travoprost is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is hydrolyzed in the eye to the active free acid and systemically to inactive metabolites. In most nonpregnant subjects, plasma concentrations were below the quantification limit (0.01 ng/mL) of the assay. In subjects with quantifiable plasma levels, the mean plasma maximum concentration was 0.018 ng/mL and the elimination half-life was estimated to be 45 minutes (range 17–86 minutes) (1).
Reproduction studies have been conducted in mice and rats. In rats, a daily IV dose up to 250 times the maximum recommended human ocular dose (MRHOD) was associated with an increase in the incidence of skeletal malformations and external and visceral defects (fused sternebrae, domed head, and hydrocephaly). Teratogenicity was not observed with daily IV doses up to 75 times the MRHOD in rats or in mice with daily SC doses up to 25 times the MRHOD. Travoprost caused an increase in postimplantation loses and a decrease in fetal viability in rats at daily IV doses up to 75 times the MRHOD or in mice with daily SC doses up to 7.5 times the MRHOD. When rats received a daily SC dose that was 3 times the MRHOD from day 7 of pregnancy to lactation day 21 there was an increased incidence of postnatal mortality and decreased neonatal body weight gain. Neonatal development also was affected as evidenced by delayed eye opening, pinna detachment, preputial separation, and decreased motor activity (1).
No evidence of carcinogenicity was observed in 2-year studies in mice and rats with SC doses. Most assays for mutagenicity were negative but a slight increase in mutant frequency was observed in one assay. No effect on mating or fertility was observed in male or female rats, but at the highest dose (250 times the MRHOD), the mean number of corpora lutea was reduced and postimplantation losses were increased (1).
It is not known if travoprost free acid crosses the human placenta. The molecular weight of the parent drug (about 501) is low enough but the short elimination half-life and very low plasma concentrations suggest that clinically significant amounts of the drug will not cross to the embryo–fetus.
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 (see Latanoprost).
BREASTFEEDING SUMMARY
No reports describing the use of travoprost during human lactation have been located. The molecular weight of the parent drug (about 501) is low enough but the short elimination half-life (45 minutes) and very low plasma concentrations suggest that clinically significant amounts of the drug will not be excreted into breast milk.
Reference
1.Product information. Travatanz. Alcon Laboratories, 2011.