VERKAZIA

Verkazia (cyclosporine ophthalmic emulsion) 0.1% contains a topical calcineurin inhibitor immunosuppressant. Cyclosporine is a white or almost white powder. Cyclosporine’s chemical name is Cyclo[[( E )-(2 S ,3 R ,4 R )-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl- N -methylglycyl- N -methyl-L-leucyl-L-valyl- N -methyl-L-leucyl-L-alanyl-D-alanyl- N -methyl-L-leucyl- N -methyl-L-leucyl- N -methyl-L-valyl] and it has the following structure: Structural Formula Formula: C 62 H 111 N 11 O 12 Mol. Wt.: 1202.61 Verkazia ophthalmic emulsion is a sterile, unpreserved topical emulsion. It appears as a milky-white homogeneous emulsion. It has an osmolality of approximately 265 mOsmol/kg and a pH of 5-7. Each mL of Verkazia ophthalmic emulsion contains: Active: Cyclosporine 1 mg/mL. Inactives: Cetalkonium chloride, Glycerol, Medium-chain triglycerides, Poloxamer 188, Sodium Hydroxide to adjust pH, Tyloxapol and Water for Injection. Structural Formula

Verkazia ophthalmic emulsion is indicated for the treatment of vernal keratoconjunctivitis (VKC) in children and adults. Verkazia ophthalmic emulsion is a calcineurin inhibitor immunosuppressant indicated for the treatment of vernal keratoconjunctivitis in children and adults ( 1 )

Instill one drop of Verkazia, 4 times daily (morning, noon, afternoon, and evening) in each affected eye ( 2 ) 2.1 General Dosing Information Gently shake the single-dose vial several times to obtain a uniform, white, opaque emulsion before use. 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. Discard the vial immediately after use. 2.2 Recommended Dosage and Dose 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. 2.1 General Dosing Information Gently shake the single-dose vial several times to obtain a uniform, white, opaque emulsion before use. 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. Discard the vial immediately after use. 2.2 Recommended Dosage and Dose 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.

None None ( 4 )

The most common adverse reactions following the use of Verkazia were eye pain (12%) and eye pruritus (8%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Harrow at 1-833-4HARROW(427769) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION and FDA‑approved patient labeling. 6.1 Clinical Trials Experience Since 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 the VEKTIS study, a multicenter, randomized, double-masked, placebo‑controlled trial, a total of 57 patients received Verkazia dosed four times a day (QID) for 4 months. Forty-two (42) patients received Verkazia in an 8 month extension, safety follow-up of the VEKTIS study. In the NOVATIVE study, a multicenter, randomized, double-masked, placebo‑controlled trial, 39 patients received Verkazia 1 mg/mL dosed QID for one month. A total of 53 patients received Verkazia 1 mg/mL QID during a 3-month safety follow‑up. The majority of the treated patients were male (79%). The most common adverse reactions reported in greater than 5% of patients were eye pain (12%) and eye pruritus (8%) which were usually transitory and occurred during instillation (Table 1). 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 6.1 Clinical Trials Experience Since 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 the VEKTIS study, a multicenter, randomized, double-masked, placebo‑controlled trial, a total of 57 patients received Verkazia dosed four times a day (QID) for 4 months. Forty-two (42) patients received Verkazia in an 8 month extension, safety follow-up of the VEKTIS study. In the NOVATIVE study, a multicenter, randomized, double-masked, placebo‑controlled trial, 39 patients received Verkazia 1 mg/mL dosed QID for one month. A total of 53 patients received Verkazia 1 mg/mL QID during a 3-month safety follow‑up. The majority of the treated patients were male (79%). The most common adverse reactions reported in greater than 5% of patients were eye pain (12%) and eye pruritus (8%) which were usually transitory and occurred during instillation (Table 1). 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