RESCULA Ophthalmic solution Ref.[50225] Active ingredients: Unoprostone

Rescula has been reported to cause changes to pigmented tissue. These changes may be permanent.

Rescula may gradually change eye color, increasing the amount of brown pigment in the iris. The long-term effects and the consequences of potential injury to the eye are currently unknown. The change in iris color occurs slowly and may not be noticeable for months to several years. Patients should be informed of the possibility of iris color change.

In clinical studies, the most common ocular adverse events were burning/stinging, burning/stinging upon drug instillation, dry eyes, itching, increased length of eyelashes and injection. These were reported in approximately 10-25% of patients. Approximately 10-14% of patients were observed to have an increase in the length of eyelashes (≥1 mm) at 12 months, while 7% of patients were observed to have a decrease in the length of eyelashes.

Ocular adverse events occurring in approximately 5% to 10% of patients were abnormal vision, eyelid disorder, foreign body sensation, and lacrimation disorder.

Ocular adverse events occurring in approximately 1% to 5% of patients were blepharitis, cataract, conjunctivitis, corneal lesion, discharge from the eye, eye hemorrhage, eye pain, keratitis, irritation, photophobia, and vitreous disorder.

Other ocular adverse events reported in less than 1% of patients were acute elevated intraocular pressure, color blindness, corneal deposits, corneal edema, corneal opacity, diplopia, hyperpigmentation of the eyelid, increased number of eyelashes, iris hyperpigmentation, iritis, optic atrophy, ptosis, retinal hemorrhage, and visual field defect.

The most frequently reported nonocular adverse event associated with the use of Rescula in the clinical trials was flu syndrome that was observed in approximately 6% of patients. Nonocular adverse events reported in the 1% to 5% of patients were accidental injury, allergic reaction, back pain, bronchitis, cough increased, diabetes mellitus, dizziness, headache, hypertension, insomnia, pharyngitis, pain, rhinitis, and sinusitis.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface (see Information for Patients).

RESCULA should be used with caution in patients with active intraocular inflammation (e.g., uveitis).

RESCULA has not been evaluated for the treatment of angle closure, inflammatory or neovascular glaucoma.

RESCULA has not been studied in patients with renal or hepatic impairment and should be used with caution in such patients.

RESCULA should not be administered while wearing contact lenses. Patients should also be advised that RESCULA contains benzalkonium chloride which may be adsorbed by contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of RESCULA.

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.

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.

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 is administered to a nursing mother.

Safety and effectiveness in pediatric patients have not been established.

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