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 bimatoprost in human pregnancy have been located. The animal data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. However, clinically significant exposure of the embryo–fetus is unlikely and use of the drug in pregnancy is probably compatible.
FETAL RISK SUMMARY
Bimatoprost is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It is given as one drop in the affected eye(s) once daily. It is in the same class of prostaglandin agonists as latanoprost, tafluprost, and travoprost. Bimatoprost is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. In healthy adults given one drop daily in each eye for 2 weeks, blood concentrations peaked (mean 0.08–0.09 ng/mL) at 10 minutes and were below the limit of detection (0.025 ng/mL) in most subjects at 1.5 hours after dosing. The drug is metabolized to apparently inactive metabolites. Plasma protein binding is about 88% and the elimination half-life, after an IV dose, was about 45 minutes (1). A similar elimination half-life appears to reflect the blood levels after ocular administration.
Reproduction studies have been conducted in mice and rats. In these species, abortion occurred at oral doses that were about 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC (MIHE). At doses at least 41 times the MIHE, the gestation length was reduced, and the incidence of dead fetuses, late resorptions, perinatal and postnatal pup mortality was increased. In addition, pup body weights were decreased (1).
Carcinogenicity studies were negative in mice or rats given oral doses of bimatoprost. The drug was not mutagenic or clastogenic in multiple assays. No impairment of fertility was observed in male and female rats given oral doses up to about 103 times MIHE (1).
It is not known if bimatoprost crosses the human placenta. The molecular weight (about 416) and moderate plasma protein binding suggest that the drug will cross to the embryo–fetus. However, the short elimination half-life and the very low blood concentrations probably indicate that any exposure will not be clinically significant.
Prostaglandin F2a 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 bimatoprost during human lactation have been located. The molecular weight (about 416) and moderate plasma protein binding (about 88%) suggest that the drug will be excreted into breast milk. However, the short elimination half-life (about 45 minutes) and the very low blood concentrations suggest that clinically significant exposure will not occur.
Reference
1.Product information. Lumigan. Allergan, 2012.