Ketorolac Tromethamine Ophthalmic Solution, 0.5%

Sterile

Rx only

Ketorolac Tromethamine Ophthalmic Solution 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)-l,3-propanediol(1:1) and it has the following structural formula:

The molecular formula of Ketorolac Tromethamine Ophthalmic Solution is C₁₅H₁₃NO₃•C₄H₁₁NO₃.

Ketorolac Tromethamine Ophthalmic Solution is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4.

Ketorolac Tromethamine Ophthalmic Solution is 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 molecular weight of ketorolac tromethamine is 376.41. The osmolality of Ketorolac Ophthalmic Solution is 290 mOsml/kg.

Each mL of Ketorolac Tromethamine Ophthalmic Solution contains:

Active: ketorolac tromethamine 0.5%

Inactives: edetate disodium 0.1%; octoxynol 40; sodium chloride; hydrochloric acid and/or sodium hydroxide may be added to adjust the pH (6.8 to 7.4) and purified water.

Preservative: benzalkonium chloride 0.01%

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.

Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure. Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms.

Two drops (0.1 mL) of 0.5% Ketorolac Tromethamine Ophthalmic Solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved measurable levels in 8 of 9 patients' eyes (mean ketorolac concentration 95 ng/mL aqueous humor, range 40 to 170 ng/mL). Ocular administration of ketorolac tromethamine reduces prostaglandin E₂ (PGE₂) levels in aqueous humor. The mean concentration of PGE₂ was 80 pg/mL in the aqueous humor of eyes receiving vehicle and 28 pg/mL in the eyes receiving ketorolac ophthalmic solution, 0.5%.

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.

Two controlled clinical studies showed that Ketorolac Tromethamine Ophthalmic Solution was significantly more effective than its vehicle in relieving ocular itching caused by seasonal allergic conjunctivitis.

Two controlled clinical studies showed that patients treated for two weeks with Ketorolac Tromethamine Ophthalmic Solution were less likely to have measurable signs of inflammation (cell and flare) than patients treated with its vehicle.

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.

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 contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation.

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory agents. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

With some nonsteroidal anti-inflammatory drugs, 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.

The most frequent adverse events reported with the use of ketorolac ophthalmic solution have been transient stinging and burning on instillation. These events were reported by up to 40% of patients participating in clinical trials.

Other adverse events occurring approximately 1% - 10% of the time during treatment with ketorolac ophthalmic solution including allergic reactions, corneal edema, iritis, ocular inflammation, ocular irritation, superficial keratitis, and superficial ocular infections.

Other adverse events reported rarely with the use of ketorolac tromethamine ophthalmic solutions included corneal infiltrates, corneal ulcer, eye dryness, headaches, and visual disturbance (blurry vision).

The recommended dose of Ketorolac Tromethamine Ophthalmic Solution is one drop (0.25 mg) 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(s) four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period.

Ketorolac Tromethamine Ophthalmic Solution has been safely administered in conjunction with other ophthalmic medications such as antibiotics, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.

Ketorolac Tromethamine Ophthalmic Solution is supplied sterile in white LDPE plastic bottles with natural droppers and gray short skirt caps as follows:

5 mL in l0 mL bottle - NDC 63187-628-05

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Protect from light. Retain in carton until time of use.

Rx only

Manufactured by: Akorn, Inc.
Lake Forest, IL 60045

KR00N Rev.05/12

Relabeled by: Proficient Rx LP

Thousand Oaks, CA 91320

Principal Display Panel Text for Container Label:

NDC 63187-628-05

Ketorolac

Tromethamine

Ophthalmic Solution

0.5%

Sterile

Rx only 5 mL