KETOROLAC TROMETHAMINE ophthalmic solution 0.4% sterile

Mechanism of Action

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory, and anti-pyretic activity. The mechanism of its action is thought to be due to its ability to inhibit prostaglandin biosynthesis. Ketorolac tromethamine given systemically does not cause pupil constriction.

Pharmacokinetics

One drop (0.05 mL) of 0.5% ketorolac tromethamine ophthalmic solution was instilled into one eye and one drop of vehicle into the other eye TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range 10.7 to 22.5 ng/mL) at day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hours, peak plasma levels at steady state are around 960 ng/mL.

Clinical Studies

In two double-masked, multi-centered, parallel-group studies, 313 patients who had undergone photorefractive keratectomy received ketorolac tromethamine 0.4% or its vehicle QID for up to 4 days. Significant differences favored ketorolac tromethamine for the reduction of ocular pain and burning/stinging following photorefractive keratectomy surgery.

Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure.

The safety and effectiveness of ketorolac tromethamine ophthalmic solution in post-cataract surgery patients has not been established.

All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac tromethamine ophthalmic solution, 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.

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 24 hours prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events.

It is recommended that ketorolac tromethamine ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications, which may prolong bleeding time.

Ketorolac tromethamine ophthalmic solution should not be administered while wearing contact lenses.

Ketorolac tromethamine was neither carcinogenic in rats given up to 5 mg/kg/day orally for 24 months (156 times the maximum recommended human topical ophthalmic dose, on a mg/kg basis, assuming 100% absorption in humans and animals) nor in mice given 2 mg/kg/day orally for 18 months (62.5 times the maximum recommended human topical ophthalmic dose, on a mg/kg basis, assuming 100% absorption in humans and animals).

Ketorolac tromethamine was not mutagenic in vitro in the Ames assay or in forward mutation assays. Similarly, it did not result in an in vitro increase in unscheduled DNA synthesis or an in vivo increase in chromosome breakage in mice. However, ketorolac tromethamine did result in an increased incidence in chromosomal aberrations in Chinese hamster ovary cells.

Ketorolac tromethamine did not impair fertility when administered orally to male and female rats at doses up to 280 and 499 times the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg basis, assuming 100% absorption in humans and animals.

Caution should be exercised when ketorolac tromethamine ophthalmic solution is administered to a nursing woman.

Safety and effectiveness of ketorolac tromethamine in pediatric patients below the age of 3 have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

The following events 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 events, 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 corneal erosion, corneal perforation, corneal thinning and epithelial breakdown (see PRECAUTIONS, General).

Storage: Store at 15°-25°C (59°-77°F).

Revised: 10/2013

© 2013 Allergan, Inc., Irvine, CA 92612, U.S.A.
® marks owned by Allergan, Inc.
Patented. See: www.allergan.com/products/patent_notices
Made in the U.S.A.

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71654PY10

NDC 54868-6416-0

KETOROLAC TROMETHAMINE

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