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RESTASIS ® (Cyclosporine Ophthalmic Emulsion) 0.05% and RESTASIS MULTIDOSE ® (Cyclosporine Ophthalmic Emulsion) 0.05% BRIEF SUMMARY—PLEASE SEE THE RESTASIS ® AND RESTASIS MULTIDOSE ® PACKAGE INSERTS FOR FULL PRESCRIBING INFORMATION. INDICATION AND USAGE RESTASIS ® and RESTASIS MULTIDOSE ® ophthalmic emulsion are indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. CONTRAINDICATIONS RESTASIS ® and RESTASIS MULTIDOSE ® are contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation. [see Adverse Reactions] WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination Be careful not to touch the container tip to your eye or other surfaces to avoid potential for eye injury and contamination. Use with Contact Lenses RESTASIS ® and RESTASIS MULTIDOSE ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® and RESTASIS MULTIDOSE ® ophthalmic emulsion. ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Potential for Eye Injury and Contamination [see Warnings and Precautions] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, the most common adverse reaction following the use of cyclosporine ophthalmic emulsion 0.05% was ocular burning (17%). Other reactions reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring). Post-marketing Experience The following adverse reactions have been identified during post approval use of cyclosporine ophthalmic emulsion 0.05%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Reported reactions have included: hypersensitivity (including eye swelling, urticaria, rare cases of severe angioedema, face swelling, tongue swelling, pharyngeal edema, and dyspnea); and superficial injury of the eye (from the container tip touching the eye during administration). USE IN SPECIFIC POPULATIONS 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). 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 cyclosporine ophthalmic emulsion 0.05% [see Clinical Pharmacology (12.3)], caution should be exercised when RESTASIS ® and RESTASIS MULTIDOSE ® are 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 RESTASIS MULTIDOSE ® and any potential adverse effects on the breast-fed child from cyclosporine. Pediatric Use Safety and efficacy have not been established in pediatric patients below the age of 16. Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Systemic carcinogenicity studies were carried out in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males significantly exceeded the control value. In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/ day, pancreatic islet cell adenomas significantly exceeded the control rate in the low-dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 80 times greater (normalized to body surface area) than the daily 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. Mutagenesis: Cyclosporine has not been found to be mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE). Impairment of Fertility: No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/ day (approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating. PATIENT COUNSELING INFORMATION Handling the Container Advise patients to not allow the tip of the container to touch the eye or any surface, as this may contaminate the emulsion. Advise patients to not touch the container to their eye to avoid the potential for injury to the eye. [see Warnings and Precautions] Use with Contact Lenses RESTASIS ® and RESTASIS MULTIDOSE ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. Advise patients that if contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® and RESTASIS MULTIDOSE ® ophthalmic emulsion. [see Warnings and Precautions] Administration Advise patients that the emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration. Advise patients to read the Instructions for Use for detailed first-time use instructions for the multidose bottle. Rx Only Based on package inserts 71876US19 and 72843US12 © 2017 Allergan. All rights reserved. All trademarks are the property of their respective owners. RES103567_v3 09/17 Patented. See www.allergan.com/products/patent_notices Made in the U.S.A.

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