Pregnancy: Risk summary: There is a limited amount of data from the use of olopatadine in pregnant women. Studies in rats and rabbits in which olopatadine was orally administered did not show any embryo fetal toxicity up to 2480-times the maximum recommended ocular human dose (MROHD) (one drop of 0.7 % olopatadine ophthalmic solution in each eye, based on body surface area (BSA)). Reduction in the fetal weight was not observed in rats up to 25 times the MROHD, based on BSA.
No effects during pregnancy are anticipated since systemic exposure to olopatadine is negligible by the topical ocular route. However, the possibility of harm to the fetus cannot be ruled out.
Data: Animal data: In an embryo-fetal development (EFD) study in rats, olopatadine (60, 200 and 600 mg/kg/day) was administered orally throughout the period of organogenesis. Mydriasis, hyperaemia and congestion of the ocular fundus, abnormal respiratory sounds were observed in treated dams at high dose levels and the maternal no-effect dose level was 60 mg/kg/day (corresponding to 746-times the MROHD, based on BSA). In offspring, decrease in body weight of live fetuses and decrease in number of ossification were observed at 600 mg/kg/day (corresponding to 7460-times the MROHD, based on BSA). At 60 mg/kg/day, cleft palate was observed in 2 fetuses but not at higher doses. No dose related abnormalities were observed in external, skeletal and visceral examination and hence the no effect dose for offspring was 200 mg/kg/day (corresponding to 2480-times the MROHD, based on BSA).
In a rabbit EFD study, olopatadine (25, 100 and 400 mg/kg/day) was administered orally during the period of organogenesis. Abnormal respiration and lacrimation was seen at the 400 mg/kg/day dose and the maternal no effect dose level was 100 mg/kg/day (corresponding to 2480-times the MROHD, based on BSA). No effects on the fetuses were observed and hence the no effect dose for offspring was 400 mg/kg/day (corresponding to 9950-times the MROHD, based on BSA).
In a peri-/postnatal toxicity study, rats received oral doses of olopatadine up to 600 mg/kg/day during late gestation and throughout lactation. Maternal toxicity was observed at 600 mg/kg/day. Olopatadine produced decreased neonatal survival at 60 mg/kg/day and reduced body weight gain in offspring at 4 mg/kg/day (50-times the MROHD, based on BSA) which is attributed to milk as demonstrated in a cross-fostered study (see Animal Data under Lactation as follows).
Lactation: Risk summary: It is not known if olopatadine is transferred into human milk after administration of Patanol. There are no data on the effects of olopatadine on the breastfed child or on milk production. Based upon the low level of olopatadine present in human plasma following topical ocular administration, the concentration of olopatadine potentially present in breast milk is expected to be negligible. However, as there is no data available on the concentration of olopatadine/metabolites in human milk following topical ocular administration, a risk to the breast-feeding child cannot be excluded.
Olopatadine is transferred into the milk of lactating rats after oral administration and was associated with fetal toxicity (see Animal Data as follows).
Patients should be informed that antihistamines may affect the milk production of a nursing mother. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Patanol and any potential adverse effects on the breast-fed child from Patanol.
Data: Animal Data: In a cross-fostered study in which pups of untreated dams were nursed by olopatadine (60 mg/kg/day) treated dams, the body weight gain of pups was suppressed confirming that the effect of olopatadine was through milk.
Oral administration of 1 mg/kg radiolabelled olopatadine in rats demonstrated that olopatadine and/or its metabolites were significantly transferred into milk with milk:plasma ratio (AUC0-∞) of 1.5. Maximal levels of radioactivity in the milk was determined at around 1 hour post-dose, with an elimination half-life of 28.3 hours.
Females and males of reproductive potential: Studies have not been performed to evaluate the effect of administration of olopatadine on human fertility. Effects in non-clinical fertility studies in male and female animals were observed only at dosages considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
No effects on human fertility are anticipated since systemic exposure to olopatadine is negligible by the topical ocular route.
Olopatadine can be used by women of childbearing potential.