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BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Verkazia ophthalmic emulsion (0.1% (1mg/mL) cyclosporine) is indicated for the treatment of vernal keratoconjunctivitis (VKC) in children and adults. GENERAL DOSING INFORMATION Contact lenses should be removed before applying Verkazia and may be reinserted 15 minutes after administration. If a dose is missed, treatment should be continued as normal, at the next scheduled administration. If more than one topical ophthalmic product is being used, administer the eye drops at least 10 minutes apart to avoid diluting products. Administer Verkazia 10 minutes prior to using any eye ointment, gel or other viscous eye drops. DOSAGE AND ADMINISTRATION Instill one drop of Verkazia, 4 times daily (morning, noon, afternoon, and evening) into each affected eye. Treatment can be discontinued after signs and symptoms are resolved and can be reinitiated if there is a recurrence. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination To avoid the potential for eye injury or contamination, advise patients not to touch the vial tip to the eye or other surfaces. ADVERSE EVENTS Table 1: Adverse Reactions Reported in ≥ 1% of Patients Receiving Verkazia (N=135) Eye Disorders Eye pain a 12% Eye pruritus b 8% Ocular discomfort c 6% Visual acuity reduced 5% Ocular hyperemia 4% Systemic Cough 5% Headache 4% Upper respiratory tract infection 2% a Including eye pain and instillation site pain b Including eye pruritus and instillation site pruritus c Including foreign body sensation and ocular discomfort USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no adequate and well-controlled studies of Verkazia administration in pregnant women to inform a drug-associated risk. Oral administration of cyclosporine to pregnant rats or rabbits did not produce teratogenicity at clinically relevant doses [see Data]. Data Animal Data Oral administration of cyclosporine oral solution (USP) to pregnant rats or rabbits was teratogenic at maternally toxic doses of 30 mg/kg/day in rats and 100 mg/kg/day in rabbits, as indicated by increased pre- and postnatal mortality, reduced fetal weight and skeletal retardations. These doses (normalized to body weight) were approximately 320 and 2150 times higher than the daily maximum recommended human ophthalmic dose (MRHOD) of 0.015 mg/kg/day, respectively. No adverse embryofetal effects were observed in rats or rabbits receiving cyclosporine during organogenesis at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively (approximately 185 and 650 times higher than the MRHOD, respectively). An oral dose of 45 mg/kg/day cyclosporine (approximately 485 times higher than MRHOD) administered to rats from Day 15 of pregnancy until Day 21 postpartum produced maternal toxicity and an increase in postnatal mortality in offspring. No adverse effects in mothers or offspring were observed at oral doses of up to 15 mg/kg/day (160 times greater than MRHOD). Pediatric Use Verkazia's safety and effectiveness has been established in patients from 4 through 18 years of age. 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. The low dose in mice is approximately 5 times greater than MRHOD. 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 dose in rats is approximately 5 times greater than MRHOD. Mutagenesis In genetic toxicity tests, 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. Cyclosporine was positive in an in vitro sister chromatid exchange (SCE) assay using human lymphocytes. Impairment of Fertility Oral administration of cyclosporine to rats for 12 weeks (male) and 2 weeks (female) prior to mating produced no adverse effects on fertility at doses up to 15 mg/kg/day (160 times higher than MRHOD). CLINICAL STUDIES The safety and efficacy of Verkazia for the treatment of VKC was evaluated in two randomized, multi-center, double-masked, vehicle- controlled, clinical trials (VEKTIS Study; NCT01751126 and NOVATIVE Study; NCT00328653). A total of 168 and 118 patients were enrolled in the VEKTIS and NOVATIVE studies for the efficacy analyses, respectively. Patients' age ranged from 4 through 17 years (mean age 9 years) in VEKTIS and 4 through 21 years (mean age 9 years) in NOVATIVE, with most patients being between 4 and 11 years of age (76% in VEKTIS and 80% in NOVATIVE) and male (79% in VEKTIS and 81% in NOVATIVE). Most of the patients had both limbal and tarsal forms of VKC (65% in VEKTIS and 74% in NOVATIVE). In both studies, patients had experienced VKC for a mean of 3 years prior to enrollment and all patients had a history of at least one recurrence of VKC in the year prior to study entry. STORAGE AND HANDLING Do not freeze Verkazia. Store at 20°C to 25°C (68°F to 77°F). After opening the aluminum pouch, the single-dose vial should be kept in the pouch to protect from light and avoid evaporation. Any opened individual single-dose vial with any remaining emulsion should be discarded immediately after use. © 2021 Santen Inc. All rights reserved. PP-VKC-US-0024

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