Ketorolac Ophthalmic Solution

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.

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 either have 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.

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 be used with caution in patients with known bleeding tendencies or who are receiving other medications, which may prolong bleeding time.

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.

Contact Lens Wear

Ketorolac Tromethamine Ophthalmic Solution should not be administered while wearing contact lenses.

Ketorolac Tromethamine Ophthalmic Solution 0.45% is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1), and its molecular weight is 376.40. Its molecular formula is C19H24N2O6. Its chemical structure is:

Ketorolac Tromethamine Ophthalmic Solution is supplied as a sterile isotonic aqueous 0.45% preservative-free solution, with a pH of approximately 6.8. Ketorolac Tromethamine Ophthalmic Solution contains a racemic mixture of R-(+) and S-(-)- ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. The pKa of ketorolac is 3.5. This white to off-white crystalline substance discolors on prolonged exposure to light. The osmolality of Ketorolac Tromethamine Ophthalmic Solution is approximately 285 mOsml/kg.

Each mL of Ketorolac Tromethamine Ophthalmic Solution contains: Active: ketorolac tromethamine 0.45%. Inactives: carboxymethylcellulose sodium; sodium chloride; sodium citrate dihydrate; and water for injection with sodium hydroxide and/or hydrochloric acid to adjust pH.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Ketorolac tromethamine was not carcinogenic in either rats given up to 5 mg/kg/day orally for 24 months or in mice given 2 mg/kg/day orally for 18 months. These doses are approximately 900 times and 300 times higher respectively than the typical human topical ophthalmic daily dose given as twice daily to an affected eye on a mg/kg basis.

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 9 mg/kg/day and 16 mg/kg/day, respectively. These doses are respectively 1,500 and 2,700 times higher than the typical human topical ophthalmic daily dose.

Two multicenter, randomized, double-masked, parallel group comparison studies including approximately 500 patients were conducted to evaluate the effects of Ketorolac Tromethamine Ophthalmic Solution on anterior chamber cell and flare, and ocular pain relief following cataract extraction with posterior chamber intraocular lens (IOL) implantation. Results of these studies indicated that patients receiving Ketorolac Tromethamine Ophthalmic Solution had a significantly higher incidence of clearing of anterior chamber inflammation 53% (167/318) vs. patients receiving vehicle 26% (41/155) at day 14.

Ketorolac Tromethamine Ophthalmic Solution was also significantly superior to vehicle in resolving ocular pain. On Day 1 post cataract surgery, 72% (233/322) of patients in the Ketorolac Tromethamine Ophthalmic Solution group were pain free compared to 40% (62/156) of patients in the vehicle group.

Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.

More Common Side Effects

The more common side effects that can occur with use of ketorolac eye drops include:

• burning or stinging when drops are given

• allergic reactions, with symptoms such as rash, itching, or swelling of the face or throat

• corneal edema (swelling of the outer layer of the front of the eye)

• painful inflammation of the iris (the colored part of the eye)

• inflammation or irritation of the middle layer of the eye

• eye infections

Serious Side Effects

Call your doctor right away if you have serious side effects. Call 9-1-1 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Asthma attacks. Symptoms can include:

  • shortness of breath
  • trouble breathing

• Damage on the cornea (outer layer of the front of the eye). Symptoms can include:

  • small, gray areas on the cornea
  • blurry or hazy vision
  • very painful eyes