ACULAR LS

1 INDICATIONS AND USAGE ACULAR LS ophthalmic solution is indicated for the reduction of ocular pain and burning/stinging following corneal refractive surgery. ACULAR LS ophthalmic solution is a nonsteroidal, anti-inflammatory drug (NSAID) indicated for the reduction of ocular pain and burning/stinging following corneal refractive surgery. ( 1 )

2 DOSAGE AND ADMINISTRATION One drop of ACULAR LS should be applied in the operated eye 4 times per day as needed for pain and burning/stinging for up to 4 days following corneal refractive surgery. ( 2.1 ) 2.1 Recommended Dosing The recommended dose of ACULAR LS ophthalmic solution is one drop four times a day in the operated eye as needed for pain and burning/stinging for up to 4 days following corneal refractive surgery. 2.2 Use With Other Topical Ophthalmic Medications ACULAR LS has been safely administered in conjunction with other topical ophthalmic medications such as alpha-agonists, antibiotics, beta-blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

4 CONTRAINDICATIONS ACULAR LS ophthalmic solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation [see Adverse Reactions ( 6.1 )] . Hypersensitivity to any component of this product. ( 4 )

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 ACULAR LS ophthalmic solution 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 Risk of Contamination Do not allow the tip of the bottle to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. 5.6 Contact Lens Wear ACULAR LS should not be administered while wearing contact lenses.

6 A DVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Delayed Healing [ see Warnings and Precautions (5.1) ] Cross-Sensitivity or Hypersensitivity [ see Warnings and Precautions (5.2) ] Increased Bleeding Time [ see Warnings and Precautions (5.3) ] Corneal Effects [ see Warnings and Precautions (5.4) ] The most common adverse reactions occurring in 1 - 5% of patients included conjunctival hyperemia, corneal infiltrates, headache, ocular edema and ocular pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because 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. The most frequently reported adverse reactions for ACULAR LS ophthalmic solution occurring in approximately 1 to 5% of the overall study population were conjunctival hyperemia, corneal infiltrates, headache, ocular edema, and ocular pain. 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 in 1 to 10% of the time during treatment with other ketorolac tromethamine ophthalmic solutions included allergic reactions (including eye swelling, eyelid edema, and hyperemia), 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 ulcer, eye dryness, and visual disturbance (blurry vision). 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of ketorolac tromethamine ophthalmic solutions 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 solutions or a combination of these factors, include bronchospasm or exacerbation of asthma, corneal erosion, corneal perforation, corneal thinning and corneal melt, and epithelial breakdown [see Warnings and Precautions ( 5.2 , 5.4 )] .

8.1 Pregnancy Risk Summary There are no adequate or well-controlled studies with ACULAR LS in pregnant women. No evidence of teratogenicity has been observed in rats or rabbits with ACULAR LS at clinically relevant doses.