Ketorolac Tromethamine

RECENT MAJOR CHANGES Warnings and Precautions ( 5.5 ) 9/2025

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

2 DOSAGE AND ADMINISTRATION One drop of ketorolac tromethamine ophthalmic solution 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 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 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 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 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.

2.1 Recommended Dosing Patient Dosing The recommended dose of ketorolac tromethamine ophthalmic solution 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 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 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.

3 DOSAGE FORMS AND STRENGTHS Ketorolac tromethamine ophthalmic solution 0.5% is supplied sterile in white opaque LDPE dropper bottles with white opaque plug and sealed with gray pantone opaque pilfer-proof caps as follows: 5 mL size bottle filled with 3 mL of solution 5 mL size bottle filled with 5 mL of solution 10 mL size bottle filled with 10 mL of solution Ophthalmic solution containing 5 mg/mL ketorolac tromethamine. ( 3 ) 5 mL size bottle filled with 3 mL of solution 5 mL size bottle filled with 5 mL of solution 10 mL size bottle filled with 10 mL of solution

4 CONTRAINDICATIONS Ketorolac tromethamine 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 )

6 ADVERSE 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 to 5% of patients included conjunctival hyperemia, corneal infiltrates, headache, ocular edema and ocular pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 ketorolac tromethamine 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 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratogenic Effects. P regnancy Category C Pregnancy Category C: Ketorolac tr o metha min e, ad ministered 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 approxi mately 100 ti mes and 250 ti mes higher respectively than the max i m um recom mended hu man topical op hthal mic daily d ose of 2 mg (5 mg / mL x 0.05 mL/drop, x 4 drops x 2 eyes) to affected eyes on a mg/kg basis. Additionally, when ad ministered to rats after Day 17 of gestation at oral doses up to 1.5 mg/ k g/day (approxi mately 40 ti mes the typical hu man topical ophthal mic daily dose), ketorolac tro me tha mine resulted in dystocia and increased pup mortality. There are no adequate a nd well-controlled studies in pregnant w o men. Keto ro lac t ro met ham ine op htha lm ic so lut i on should be used during pregnancy only if the potential bene fit j usti fies the p otential risk to the fetus. Nonterato genic Effect s: Because of the known effects of prostaglandin-inhibiting drugs on the fetal c ardio vascul ar syst em (closure of the ductus art eriosu s), the use of keto ro lac t ro met ham ine op htha lm ic so lut i on 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 is administered to a nursing woman. 8.4 Pediatric Use Safety and efficacy in pediatric patients bel ow t he age of 2 have not been esta blished. 8.5 Geriatric Use No overall clinical di fferences in sa fety or effectiveness have been observed between elderly and other ad ult patie nts.

12.1 Mechanism of Action Ketorolac tr o metha mine is a nonsteroidal ant i-inflammatory drug which, when a d ministered syste micall y, has de monstrated anal gesic, a nti-inflam matory, and anti-pyretic activity. The mechani sm of its action is thought to be due to i ts ability to inhibit prostaglandin biosynthesis.

11 DESCRIPTION Keto ro lac t ro met ham ine op htha lm ic so lut i on 0.5% is a m ember of the pyrrolo-­pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthal mic use. Its che mical na me is (±)-5-Benzoyl-2, 3-dihydro-1H pyrrolizi ne-1-carboxylic acid co m pound with 2-a mino-2-(hydroxy methyl)-1,3-propanediol ( 1:1) and it has the following structure: Keto ro lac t ro met ham ine op htha lm ic so lut i on is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4. Keto ro lac t ro met ham ine op htha lm ic so lut i on is a race mic m ixture of R-(+) and S-(-)- ketor olac tro metha mine. Ketorol ac tro methamine may exist in t hree cr ystal for ms. All for ms are equally soluble in water. The pKa of ketorolac is 3.5. This white to o ff-white c rystalline su bstance discolors on prolonged exposure to light. The m o lecular weight of ketorolac tro metha mine is 376.41. The os molality of keto ro lac t ro met ham ine op htha lm ic so lut i on is 290 m O s mol/kg. Each mL of ketorolac tromethamine ophthalmic solution contains: Active: ketorolac tromethamine USP 0.5%. Preservative: benzalkonium chloride solution (50%) NF 0.02%. Inactives: edetate disodium USP 0.1%; octoxynol 40; water for injection USP; sodium chloride USP; hydrochloric acid NF and/or sodium hydroxide NF to adjust the pH. ketorolac-structure

16 HOW SUPPLIED/STORAGE AND HANDLING Ketorolac tromethamine ophthalmic solution 0.5% is supplied sterile in white opaque LDPE dropper bottles with white opaque plug and sealed with gray pantone opaque pilfer-proof caps as follows: 3 mL in 5 mL bottle NDC 47335-219-90 5 mL in 5 mL bottle NDC 47335-220-90 10 mL in 10 mL bottle NDC 47335-221-90 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature]. Protect from light.