Ketorolac Tromethamine

1 INDICATIONS AND USAGE Ketorolac tromethamine ophthalmic solution 0.5% is indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. Ketorolac tromethamine ophthalmic solution 0.5% is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction. Ketorolac tromethamine ophthalmic solution 0.5% is a nonsteroidal, anti- inflammatory indicated for: • The treatment of inflammation following cataract surgery. ( ) • The temporary relief of ocular itching due to seasonal allergic conjunctivitis. ( )

2 DOSAGE AND ADMINISTRATION One drop of ketorolac tromethamine ophthalmic solution 0.5% should be applied to the affected eye(s) four times a day for relief of ocular itching due to seasonal allergic conjunctivitis. For the treatment of postoperative inflammation in patients who have undergone cataract extraction, one drop of ketorolac tromethamine ophthalmic solution 0.5% should be applied to the affected eye four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period. ( 2.1 ) 2.1 Recommended Dosing Patient Dosing The recommended dose of ketorolac tromethamine ophthalmic solution 0.5% is one drop four times a day to the affected eye(s) for relief of ocular itching due to seasonal allergic conjunctivitis. For the treatment of postoperative inflammation in patients who have undergone cataract extraction, one drop of ketorolac tromethamine ophthalmic solution 0.5% should be applied to the affected eye four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period. 2.2 Use with Other Topical Ophthalmic Medications Ketorolac tromethamine ophthalmic solution 0.5% has been safely administered in conjunction with other ophthalmic medications such as antibiotics, alpha-agonists, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

5 WARNINGS AND PRECAUTIONS • Delayed healing ( 5.1 ) • Cross-sensitivity or hypersensitivity ( 5.2 ) • Increased bleeding time due to interference with thrombocyte aggregation ( 5.3 ) • Corneal effects including keratitis ( 5.4 ) 5.1 Delayed Healing Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. 5.2 Cross-Sensitivity or Hypersensitivity There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac tromethamine ophthalmic solution in patients who have either a known hypersensitivity to aspirin/non-steroidal anti-inflammatory drugs or a past medical history of asthma. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs. 5.3 Increased Bleeding Time With some NSAIDs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti- inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. It is recommended that ketorolac tromethamine ophthalmic solution 0.5% be used with caution in patients with known bleeding tendencies or who are receiving other medications, which may prolong bleeding time. 5.4 Corneal Effects Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health. Postmarketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Postmarketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events. 5.5 Contact Lens Wear Ketorolac tromethamine ophthalmic solution 0.5% should not be administered while wearing contact lenses.

4 CONTRAINDICATIONS Ketorolac tromethamine ophthalmic solution 0.5% is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation. Hypersensitivity to any component of this product. ( )

8.1 Pregnancy Teratogenic Effects. Pregnancy Category C Pregnancy Category C: Ketorolac tromethamine, administered during organogenesis, was not teratogenic in rabbits and rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day, respectively. These doses are approximately 100 times and 250 times higher respectively than the maximum recommended human topical ophthalmic daily dose of 2 mg (5 mg/mL x 0.05 mL/drop, x4 drops x 2 eyes) to affected eyes on a mg/kg basis. Additionally, when administered to rats after Day 17 of gestation at oral doses up to 1.5 mg/kg/day (approximately 40 times the typical human topical ophthalmic daily dose), ketorolac tromethamine resulted in dystocia and increased pup mortality. There are no adequate and well-controlled studies in pregnant women. Ketorolac tromethamine ophthalmic solution 0.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects: Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ketorolac tromethamine ophthalmic solution 0.5% during late pregnancy should be avoided.

8.3 Nursing Mothers Because many drugs are excreted in human milk, caution should be exercised when ketorolac tromethamine ophthalmic solution 0.5% is administered to a nursing woman.

6 ADVERSE REACTIONS The most frequent adverse reactions reported by up to 40% of patients participating in clinical trials have been transient stinging and burning on instillation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs Limited at 1-855-839-8195 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. The most frequent adverse reactions reported with the use of ketorolac tromethamine ophthalmic solutions have been transient stinging and burning on instillation. These reactions were reported by up to 40% of patients participating in clinical trials. Other adverse reactions occurring approximately 1 to 10% of the time during treatment with ketorolac tromethamine ophthalmic solutions included allergic reactions, corneal edema, iritis, ocular inflammation, ocular irritation, superficial keratitis, and superficial ocular infections. Other adverse reactions reported rarely with the use of ketorolac tromethamine ophthalmic solutions included: corneal infiltrates, corneal ulcer, eye dryness, headaches , and visual disturbance (blurry vision). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-marketing use of ketorolac tromethamine ophthalmic solution 0.5% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to topical ketorolac tromethamine ophthalmic solution 0.5% or a combination of these factors, include bronchospasm or exacerbation of asthma, corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown [see Warnings and Precautions ( 5.2 , 5.4 )] .