8.1 Pregnancy
Risk Summary
Clinical administration of cyclosporine ophthalmic emulsion 0.05% is not detected systemically following topical ocular administration [see Clinical Pharmacology ( 12.3)], and maternal use is not expected to result in fetal exposure to the drug. Oral administration of cyclosporine to pregnant rats or rabbits did not produce teratogenicity at clinically relevant doses [see Data].
Data
Animal Data
At maternally toxic doses (30 mg/kg/day in rats and 100 mg/kg/day in rabbits), cyclosporine oral solution (USP) was teratogenic as indicated by increased pre- and postnatal mortality, reduced fetal weight and skeletal retardations. These doses (normalized to body surface area) are 5,000 and 32,000 times greater, respectively, than the daily recommended human dose of one drop (approximately 28 mcL) of cyclosporine ophthalmic emulsion 0.05% twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine during organogenesis at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively. These doses in rats and rabbits are approximately 3,000 and 10,000 times greater, respectively, than the daily recommended human dose.
An oral dose of 45 mg/kg/day cyclosporine administered to rats from Day 15 of pregnancy until Day 21 postpartum produced maternal toxicity and an increase in postnatal mortality in offspring. This dose is 7,000 times greater than the daily recommended human dose. No adverse effects in dams or offspring were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the daily recommended human dose).
8.2 Lactation
Risk Summary
Cyclosporine is known to appear in human milk following systemic administration, but its presence in human milk following topical treatment has not been investigated. Although blood concentrations are undetectable following topical administration of RESTASIS ophthalmic emulsion [see Clinical Pharmacology ( 12.3)], caution should be exercised when RESTASIS is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RESTASIS and any potential adverse effects on the breast-fed child from cyclosporine.