Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Patients should also be advised that if they develop an intercurrent ocular condition (e.g., trauma or infection) or have ocular surgery, they should immediately seek their physician's advice concerning the continued use of the multidose container.

Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice.

If more than one topical ophthalmic drug is being used the drugs should be administered at least five minutes apart.

Carcinogenesis, Mutagenesis, Impairment of Fertility

ResculaÒ was not carcinogenic in rats administered oral doses up to 12 mg/kg/day for up to 2 years (approximately 580 and 240 fold the recommended human dose of 0.005 mg/kg/day based on AUC_0-24 in male and female rats, respectively).

Under the conditions tested, unoprostone isopropyl and unoprostone free acid were neither mutagenic in an Ames assay nor clastogenic in a chromosome aberration assay in Chinese hamster lung-derived fibroblast cells. Under the conditions tested, unoprostone isopropyl was not genotoxic in a mouse lymphoma mutation assay or clastogenic in an in vivo chromosomal aberration test in mouse bone marrow.

Unoprostone isopropyl did not impair male or female fertility in rats at subcutaneous doses up to 50 mg/kg (approximately 10,000 fold the recommended human dose of 0.005 mg/kg/day).

Pregnancy: Teratogenic Effects: Pregnancy Category C.

There were no teratogenic effects observed in rats and rabbits up to 5 and 0.3 mg/kg/day (approximately 1000 and 60 fold the recommended human dose of 0.005 mg/kg/day in the rat and rabbit, respectively). There was an increase in the incidence of miscarriages and a decrease in live birth index in rats administered unoprostone isopropyl during organogenesis at subcutaneous doses of 5 mg/kg. There was an increase in incidence of miscarriages and resorptions and a decrease in the number of live fetuses in rabbits administered unoprostone isopropyl during organogenesis at subcutaneous doses of 0.3 mg/kg. The no observable adverse effect level (NOAEL) for embryofetal toxicity in rats and rabbits was 2.0 and 0.1 mg/kg (approximately 400 and 20 fold the recommended human dose of 0.005 mg/kg/day in the rat and rabbit, respectively).

There was an increase in incidence of premature delivery, a decrease in live birth index, and a decrease in weight at birth and through postpartum Day 7 in rats administered unoprostone isopropyl during late gestation through postpartum Day 21 at subcutaneous doses of 1.25 mg/kg. In addition, pups from rats administered 1.25 mg/kg subcutaneously exhibited delayed growth and development characterized by delayed incisor eruption and eye opening. There was an increase in the number of stillborn pups and a decrease in perinatal survival in rats administered unoprostone isopropyl during late gestation through weaning at subcutaneous doses of ≥ 0.5 mg/kg. The NOAEL for pre and postnatal toxicity in rats was 0.2 mg/kg (approximately 40 fold the recommended human dose of 0.005 mg/kg/day).

There are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, RESCULA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Unoprostone isopropyl has been identified in breast milk in rats following intravenous administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in breast milk. Nevertheless, caution should be exercised when RESCULA^Ò is administered to a nursing mother.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Bookmark this page: