Omidria

1 INDICATIONS AND USAGE Omidria ® is added to an ocular irrigating solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain. OMIDRIA is an alpha 1-adrenergic receptor agonist and nonselective cyclooxygenase inhibitor indicated for: Maintaining pupil size by preventing intraoperative miosis ( 1 ) Reducing postoperative pain ( 1 ) OMIDRIA is added to an ocular irrigating solution used during cataract surgery or intraocular lens replacement.

2 DOSAGE AND ADMINISTRATION Omidria must be diluted prior to intraocular use. For administration to patients undergoing cataract surgery or intraocular lens replacement, 4 mL of Omidria is diluted in 500 mL of ocular irrigating solution. Irrigation solution is to be used as needed for the surgical procedure for a single patient. The storage period for the diluted product is not more than 4 hours at room temperature or 24 hours under refrigerated conditions. Do not use if the solution is cloudy or if it contains particulate matter. Each vial of OMIDRIA must be diluted prior to use for administration to a single patient undergoing cataract surgery or intraocular lens replacement. Dilute 4 mL of OMIDRIA in 500 mL of ocular irrigating solution. Irrigation solution is to be used as needed for the surgical procedure. ( 2 )

4 CONTRAINDICATIONS Omidria is contraindicated in patients with a known hypersensitivity to any of its ingredients. Hypersensitivity to any component of this product ( 4 )

5 WARNINGS AND PRECAUTIONS Systemic exposure to phenylephrine can cause elevations in blood pressure ( 5.1 ). 5.1 Elevated Blood Pressure Systemic exposure to phenylephrine can cause elevations in blood pressure. 5.2 Cross-Sensitivity or Hypersensitivity There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti- inflammatory drugs (NSAIDs). There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac in patien ts who either have a known hypersensitivity to aspirin/NSAIDs or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these drugs.

6 ADVERSE REACTIONS The most common reported adverse reactions (≥2%) are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rayner Surgical Inc. at 1-877-0MIDRIA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. Table 1 shows frequently reported ocular adverse reactions with an incidence of ≥ 2% of adult patients as seen in the combined clinical trial results from three randomized, placebo-controlled studies [see Clinical Studies ( 14 )] . Table 1: Ocular Adverse Reactions Reported by ≥ 2% of Adult Patients MedDRA Preferred Term Placebo (N=462) Omidria (N=459) n (%) n (%) Ocular Events Anterior Chamber Inflammation 102 (22%) 111 (24%) Intraocular Pressure Increased 15 (3%) 20 (4%) Posterior Capsule Opacification 16 (4%) 18 (4%) Eye Irritation 6 (1%) 9 (2%) Foreign Body Sensation in Eyes 11 (2%) 8 (2%) In a safety study that enrolled 72 pediatric patients up to 3 years old, no overall difference in safety was observed between pediatric and adult patients.

8.1 Pregnancy Risk Summary There are no available data on Omidria use in pregnant women or animals to inform any drug-associated risks. Oral administration of ketorolac to rats during late gestation produced dystocia and increased pup mortality at a dose 740-times the plasma exposure at the recommended human ophthalmic dose (RHOD). Since human systemic exposure to Omidria following a lens replacement procedure is low (see Clinical Pharmacology (12.3)], the applicability of animal findings to the risk of Omidria in humans during pregnancy is unclear. Omidria should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Ketorolac plasma concentrations are detectable following ocular Omidria administration [see Clinical Pharmacology (12.3)]. The use of Omidria during late pregnancy should be avoided. .Q.a1a Animal Data No well-controlled animal reproduction studies have been conducted with Omidria or phenylephrine. Ketorolac, administered during organogenesis, did not cause embryofetal abnormalities or mortalities in rabbits or rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day, respectively. These doses produced systemic exposure that is 1150 times and 4960 times the plasma exposure (based on Cma,c) at the RHOD, respectively. When administered to rats during late gestation (after Day 17 of gestation) at oral doses up to 1.5 mg/kg/day (740 times the plasma exposure at the RHOD), ketorolac produced dystocia and increased pup mortality. Risk Summary There are no available data on Omidria use in pregnant women or animals to inform any drug-associated risks. Oral administration of ketorolac to rats during late gestation produced dystocia and increased pup mortality at a dose 740-times the plasma exposure at the recommended human ophthalmic dose (RHOD). Since human systemic exposure to Omidria following a lens replacement procedure is low [ see Clinical Pharmacology ( 12.3 ) ], the applicability of animal findings to the risk of Omidria in humans during pregnancy is unclear. Omidria should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Ketorolac plasma concentrations are detectable following ocular Omidria administration [see Clinical Pharmacology ( 12.3 )] . The use of Omidria during late pregnancy should be avoided. Data Animal Data No well-controlled animal reproduction studies have been conducted with Omidria or phenylephrine. Ketorolac, administered during organogenesis, did not cause embryofetal abnormalities or mortalities in rabbits or rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day, respectively. These doses produced systemic exposure that is 1150 times and 4960 times the plasma exposure (based on C max ) at the RHOD, respectively. When administered to rats during late gestation (after Day 17 of gestation) at oral doses up to 1.5 mg/kg/day (740 times the plasma exposure at the RHOD) , ketorolac produced dystocia and increased pup mortality.