Verkazia

5 WARNINGS AND PRECAUTIONS To avoid the potential for eye injury and contamination, advise patient not to touch the vial tip to the eye or other surfaces ( 5.1 ) 5.1 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.

5.1 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.

6 ADVERSE REACTIONS 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 Santen at 1-855-7-SANTEN (855-772-6836) 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

<table border="1" cellpadding="0" cellspacing="0" width="624px"><tbody><tr><td/><td><paragraph>(N=135)</paragraph></td></tr><tr><td colspan="2"><paragraph>Eye Disorders</paragraph></td></tr><tr><td><paragraph>Eye pain ^a</paragraph></td><td><paragraph>12%</paragraph></td></tr><tr><td><paragraph>Eye pruritus ^b</paragraph></td><td><paragraph>8%</paragraph></td></tr><tr><td><paragraph>Ocular discomfort ^c</paragraph></td><td><paragraph>6%</paragraph></td></tr><tr><td><paragraph>Visual acuity reduced</paragraph></td><td><paragraph>5%</paragraph></td></tr><tr><td><paragraph>Ocular hyperemia</paragraph></td><td><paragraph>4%</paragraph></td></tr><tr><td colspan="2"><paragraph>Systemic</paragraph></td></tr><tr><td><paragraph>Cough</paragraph></td><td><paragraph>5%</paragraph></td></tr><tr><td><paragraph>Headache</paragraph></td><td><paragraph>4%</paragraph></td></tr><tr><td><paragraph>Upper respiratory tract infection</paragraph></td><td><paragraph>2%</paragraph></td></tr><tr><td><paragraph/></td><td><paragraph/></td></tr><tr><td colspan="2"><paragraph>^a Including eye pain and instillation site pain </paragraph><paragraph>^b Including eye pruritus and instillation site pruritus </paragraph><paragraph>^c Including foreign body sensation and ocular discomfort </paragraph></td></tr></tbody></table>

<table border="1" cellpadding="0" cellspacing="0" width="624px"><tbody><tr><td/><td><paragraph>(N=135)</paragraph></td></tr><tr><td colspan="2"><paragraph>Eye Disorders</paragraph></td></tr><tr><td><paragraph>Eye pain ^a</paragraph></td><td><paragraph>12%</paragraph></td></tr><tr><td><paragraph>Eye pruritus ^b</paragraph></td><td><paragraph>8%</paragraph></td></tr><tr><td><paragraph>Ocular discomfort ^c</paragraph></td><td><paragraph>6%</paragraph></td></tr><tr><td><paragraph>Visual acuity reduced</paragraph></td><td><paragraph>5%</paragraph></td></tr><tr><td><paragraph>Ocular hyperemia</paragraph></td><td><paragraph>4%</paragraph></td></tr><tr><td colspan="2"><paragraph>Systemic</paragraph></td></tr><tr><td><paragraph>Cough</paragraph></td><td><paragraph>5%</paragraph></td></tr><tr><td><paragraph>Headache</paragraph></td><td><paragraph>4%</paragraph></td></tr><tr><td><paragraph>Upper respiratory tract infection</paragraph></td><td><paragraph>2%</paragraph></td></tr><tr><td><paragraph/></td><td><paragraph/></td></tr><tr><td colspan="2"><paragraph>^a Including eye pain and instillation site pain </paragraph><paragraph>^b Including eye pruritus and instillation site pruritus </paragraph><paragraph>^c Including foreign body sensation and ocular discomfort </paragraph></td></tr></tbody></table>