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 tafluprost 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 appears to be 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 antiglaucoma agents that have some human data (e.g., Latanoprost).
FETAL RISK SUMMARY
Tafluprost, a fluorinated analog of prostaglandin F2α, is available as a 0.0015% ophthalmic solution that is given as single drop in the conjunctival sac of the affected eye(s) once daily. It is in the same class of prostaglandin agonists as bimatoprost, latanoprost, and travoprost. Tafluprost is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is hydrolyzed within the eye to an active metabolite, tafluprost acid, that undergoes further metabolism to inactive metabolites. Very small amounts of tafluprost acid are absorbed into the systemic circulation. At a median 10 minutes postinstillation in each eye of healthy adults, mean plasma concentrations were 26–27 pg/mL. At 30 minutes postinstillation, mean plasma concentrations were below the limit of quantification (10 pg/mL) (1). This suggests an elimination half-life of about <17 minutes.
Reproduction studies have been conducted in rats and rabbits. When IV doses of tafluprost were given, increased postimplantation losses were observed in rats and rabbits and reduced fetal body weights in rats. The drug also increased the incidence of vertebral skeletal defects in rats. In rats, the no-effect dose corresponded to maternal plasma levels of tafluprost acid that were 343 times the maximum clinical exposure based on the maximum plasma concentration (Cmax). In a prenatal and postnatal study in rats, increased mortality of newborns, decreased body weights, and delayed pinna unfolding were noted in offspring. The no observed adverse effect level for these effects was at a tafluprost IV dose that was >3 times the maximum recommended clinical dose based on BSA. In rabbits, an increased incidence of skull, brain, and spine malformations was observed at maternal plasma levels of tafluprost acid during organogenesis that were about 5 times higher than the clinical exposure based on Cmax. At the no-effect dose in rabbits, maternal plasma levels of tafluprost acid were below the level of quantification (20 pg/mL) (1).
In long-term studies, tafluprost was not carcinogenic in mice and rats, nor was it mutagenic or clastogenic in multiple assays. No adverse effects on mating performance or fertility were observed in given high IV doses of the drug (1).
It is not known if tafluprost acid crosses the human placenta. The molecular weight (about 453) is low enough, but the very small plasma concentrations of the drug are below the limit of quantification (10 pg/mL) 30 minutes postinstillation.
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 tafluprost during human lactation have been located. The molecular weight (about 453) is low enough for excretion, but the very small plasma concentrations (26–27 pg/mL) of the drug are below the limit of quantification (10 pg/mL) 30 minutes postinstillation. It is unlikely that these brief concentrations would have any effect on a nursing infant.
Reference
1.Product information. Zioptan. Merck, 2013.