ketorolac 0.5% ophth solution generic acular

Uses

Conjunctivitis

In ophthalmology, topical ketorolac tromethamine 0.5% is used for its anti-inflammatory effect in the symptomatic treatment of seasonal allergic (hay fever, pollinosis) conjunctivitis. Results from a limited number of controlled studies indicate that ketorolac tromethamine ophthalmic solution is more effective than vehicle in providing short-term relief of ocular itching associated with such conjunctivitis. Topically applied NSAIAs also may provide some relief of other ocular inflammatory manifestations of this condition but additional study and experience are needed to clarify the role of these agents in the management of seasonal allergic conjunctivitis.

Avoidance of allergen and other triggering factors (e.g., irritants) and application of cold compresses and lubricating eye drops are the initial means of managing allergic conjunctivitis. Drug therapy generally is reserved for use when such avoidance is not possible or is ineffective, and can include both prophylactic (e.g., topical mast-cell stabilizers such as cromolyn sodium, lodoxamide tromethamine) and symptomatic (e.g., topical and/or systemic antihistamines, topical vasoconstrictors, topical steroidal and nonsteroidal anti-inflammatory agents [NSAIAs]) therapy. The specific therapy(ies) employed will depend on the characteristics and severity of the allergic conjunctivitis. For patients with seasonal allergic conjunctivitis, prophylaxis with a mast-cell stabilizer often is initiated before and maintained throughout the pollen season, and symptomatic therapy with other agents (e.g., topical antihistamines, topical NSAIAs) generally is initiated as necessary to provide acute relief. Topical steroids usually are reserved for short-term use in patients with moderate to severe symptoms of allergic conjunctivitis.

While the efficacy of topical NSAIAs versus corticosteroids for the relief of inflammatory manifestations of allergic conjunctivitis remains to be established, NSAIAs generally are considered less toxic (e.g., absence of predisposition to superinfection, absence of adverse effect on IOP and cataract formation) than corticosteroids and therefore may be preferred as initial topical anti-inflammatory therapy in certain patients. An initial trial with topical NSAIA therapy may be particularly suited for mild to moderately severe conjunctivitis and when the risk of topical corticosteroid therapy, particularly prolonged therapy (which rarely is indicated), is of concern. However, because NSAIAs do not share the full range of anti-inflammatory and immunologic effects of corticosteroids, response may be limited. Regardless of the therapy employed (antihistamine, NSAIA, corticosteroid, vasoconstrictors), relief of all of the clinically important manifestations of allergic conjunctivitis may not be possible despite combined topical and/or systemic administration. In general, the least toxic therapy providing adequate relief should be employed.

Results from a limited number of controlled studies indicate short-term administration (up to 1 week) of ketorolac tromethamine 0.5% ophthalmic solution is more effective than vehicle in providing short-term symptomatic relief of seasonal allergic conjunctivitis. In these studies, administration of ketorolac tromethamine ophthalmic solution was associated with decreased conjunctival inflammation and ocular itching. In some patients, improvement in other ocular allergic manifestations (e.g., swollen eye, discharge or tearing, foreign body sensation) also was reported.

Topical NSAIAs also have been used for their anti-inflammatory activity in the symptomatic treatment of vernal or atopic keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. However, management of these ocular allergic conditions often is more complex than that of seasonal allergic conjunctivitis. Because of the severity of manifestations, topical corticosteroids, topical cromolyn sodium, and systemic antihistamines often are necessary for the management of acute episodes in patients with vernal or atopic keratoconjunctivitis. For patients with contact lens-associated giant papillary conjunctivitis, meticulous lens care, frequent replacement of lenses (e.g., switching to disposable lenses), changing the type of lens, and/or temporary or permanent discontinuance of contact lens use are the mainstay of management of this condition. However, despite the current paucity of efficacy data in either condition, a trial with topical NSAIA therapy may be attempted to provide some symptomatic relief since the risk of such therapy, at least in adults, appears minimal.

Postoperative and Posttraumatic Ocular Inflammation

In ophthalmology, topical ketorolac tromethamine 0.5% also has been used prophylactically after ocular surgery (e.g., cataract extraction, with or without implantation of an intraocular lens) to prevent or relieve postoperative ocular inflammation. Because NSAIAs inhibit prostaglandin formation rather than the effects of these autacoids once formed, efficacy of the drugs may be reduced if administration is delayed until inflammation is established. Therefore, some clinicians advocate that topical NSAIA therapy be initiated prior to surgery. However, optimal timing of such therapy remains to be established.

In controlled studies, perioperative topical application to the eye of ketorolac tromethamine 0.5% reduced lid edema, conjunctival vasodilation, ciliary flush, and the number of anterior chamber cells and flare as determined by slit-lamp biomicroscopic or fluorophotometric evaluation. The drug also has reduced postoperative disruption of the blood-aqueous barrier. While topical corticosteroids were used concomitantly in some patients, the need for these drugs was less in ketorolac-treated patients than in those receiving placebo. In addition, there is evidence of ketorolac's efficacy from a placebo-controlled study in which concomitant corticosteroid therapy was not permitted. There also is some evidence that ketorolac tromethamine 0.5% may be at least as effective as dexamethasone sodium phosphate 0.1% (of dexamethasone phosphate) or prednisolone acetate 1% in the management of postoperative ocular inflammation and in restabilization of the blood-aqueous barrier, and evidence from studies with various NSAIAs suggests that the drugs actually may be more effective than corticosteroids in restabilizing the barrier. Additive or synergistic ocular anti-inflammatory activity may occur when a topical NSAIA and a corticosteroid are used concomitantly, and some patients may benefit from such combined therapy to the eye.

Postoperative Ocular Pain

In ophthalmology, topical ketorolac tromethamine 0.5% as a preservative-free solution is used after ocular incisional refractive surgery to reduce ocular pain and photophobia. Results from 2 double-blind, multicenter, placebo-controlled studies in over 300 patients indicate that short-term application (up to 3 days) of ketorolac tromethamine 0.5% (as a preservative-free solution) is more effective than vehicle in reducing ocular pain and photophobia following ocular incisional refractive surgery.

In ophthalmology, topical ketorolac tromethamine 0.4% is used following corneal refractive surgery to reduce ocular pain and burning/stinging. Ketorolac tromethamine 0.5% also provides analgesic and anti-inflammatory effects; however, use of the preparation is associated with ocular irritation, mainly burning and stinging on instillation. Ketorolac tromethamine 0.4% ophthalmic solution (Acular LS) is formulated with a lower concentration of the drug and certain inactive ingredients (i.e., benzalkonium chloride, edetate disodium) to reduce the incidence of adverse effects while maintaining clinical efficacy. Ketorolac tromethamine 0.4% ophthalmic solution has been evaluated for the treatment of ocular pain in patients undergoing photorefractive keratectomy (PRK), a procedure associated with severe postoperative ocular pain. In 2 multicenter, randomized, double-blind studies in over 300 patients undergoing PRK surgery, short-term therapy (up to 4 days) with ketorolac tromethamine 0.4% ophthalmic solution was more effective than placebo (vehicle) in reducing ocular pain and burning/stinging following surgery.

Cystoid Macular Edema

NSAIAs, including ketorolac tromethamine, also have been applied topically to the eye, with or without concomitant topical corticosteroid therapy, to prevent or relieve postoperative cystoid macular edema associated with cataract extraction. The drugs also have been used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema. While prophylactic therapy with the drugs has effectively prevented or reduced angiographic evidence of cystoid macular edema for up to several months after cataract surgery, there is less evidence for improvement in visual acuity. The potential benefit on visual acuity of active treatment of cystoid macular edema also is unclear. There is limited evidence indicating that topical ketorolac therapy (without concomitant corticosteroid therapy) may improve distance acuity in many patients when used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema but such improvement may not be permanent.

The comparative efficacy of topical NSAIAs, topical corticosteroids, topical NSAIAs combined with topical corticosteroids, or other agents for the prevention or active treatment of cystoid macular edema remains to be established. Most experience to date has involved combined therapy with a topical NSAIA and a topical corticosteroid. While there is limited evidence that NSAIAs alone can effectively prevent or relieve cystoid macular edema, there also is limited evidence that combined topical NSAIA and corticosteroid therapy may have an additive or synergistic effect in this condition. In addition, some clinicians state that the need for the development or identification of more effective therapy persists.

Inhibition of Intraoperative Miosis

In ophthalmology, NSAIAs also have been used prophylactically before ocular surgery (e.g., cataract extraction) to prevent or reduce intraoperative miosis, which may occur secondary to surgery-induced trauma despite preoperative induction of mydriasis. However, the clinical value of such therapy remains controversial, in part because of the variability and degree of the effect.

For systemic uses of ketorolac tromethamine,

Dosage and Administration

Administration

Ketorolac tromethamine is applied topically to the eye as an ophthalmic solution. To prevent contamination of the solution, patients should be instructed to avoid allowing the tip of the dispensing container to contact any surface, the eyelids, or surrounding structures. Contact lenses should be removed prior to administration of ketorolac tromethamine ophthalmic solution. The preservative-free solution is for single use only in one or both eyes; the preservative-free solution should be used immediately after opening and any unused portion should be discarded immediately after administration.

Dosage

Conjunctivitis

For relief of ocular itching associated with seasonal allergic conjunctivitis, the usual adult dosage of ketorolac tromethamine is 1 drop of a 0.5% solution (250 mcg) in the affected eye(s) 4 times daily.

Postoperative and Posttraumatic Ocular Inflammation

For the prevention and relief of postoperative ocular inflammation in patients undergoing cataract extraction, the usual dosage of ketorolac tromethamine is 1 drop of a 0.5% solution (250 mcg) in the eye(s) undergoing surgery 4 times daily beginning 24 hours after surgery. Ketorolac tromethamine therapy usually is continued at this dosage for 2 weeks after surgery.

Postoperative Ocular Pain

To reduce ocular pain and photophobia in patients undergoing ocular incisional refractive surgery, the usual dosage of ketorolac tromethamine 0.5% (as a preservative-free solution) is 1 drop (250 mcg) 4 times daily in the operated eye(s) as needed for up to 3 days after surgery.

To reduce pain and burning/stinging in patients undergoing corneal refractive surgery, the usual dosage of ketorolac tromethamine is 1 drop of a 0.4% solution (200 mcg) 4 times daily in the operated eye(s) as needed for up to 4 days.

Cystoid Macular Edema

For the prevention and relief of postoperative cystoid macular edema associated with cataract extraction, 1 or 2 drops of a 0. 5% ketorolac tromethamine solution (250 or 500 mcg) have been applied topically to the eye(s) undergoing surgery every 6-8 hours beginning 24 hours before surgery and continuing for 3-4 weeks after surgery.

For the active treatment of chronic aphakic or pseudophakic cystoid macular edema, 1 or 2 drops of a 0. 5% ketorolac tromethamine solution (250 or 500 mcg) have been applied topically to the affected eye(s) 4 times daily for 2-3 months. Occasionally, such therapy has been continued for longer periods, but the long-term risks versus benefits remain to be established.

Cautions

Ketorolac tromethamine ophthalmic solution generally is well tolerated following topical application to the eye.

Ocular Effects

The most frequent adverse effects of topical ketorolac tromethamine are stinging and burning following instillation of the solution; these effects have occurred in about 20-40% of patients receiving the drug in some clinical studies and usually are transient. Ocular irritation, allergic reactions, superficial ocular infections, superficial keratitis, ocular inflammation, corneal edema, and iritis have occurred in 1-10% of patients receiving ketorolac ophthalmic solutions. Conjunctival hyperemia, corneal infiltrates, ocular edema, or ocular pain has been reported in 1-5% of patients receiving ketorolac tromethamine 0.5% (as a preservative-free solution) or ketorolac tromethamine 0.4% solution in clinical studies. Ocular dryness, corneal ulcer, or visual disturbance (blurred vision) has occurred rarely in patients receiving ketorolac tromethamine ophthalmic solutions. Corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown have been reported during postmarketing surveillance.(See Cautions: Precautions and Contraindications.)

In patients receiving ketorolac tromethamine 0.5% ophthalmic solution for the prevention or relief of postoperative inflammation associated with cataract surgery, most ocular complaints reported in clinical studies could not be distinguished from those associated with the trauma of surgery and/or implantation of an intraocular lens. In such patients, the most common adverse ocular effects were conjunctivitis (erythema, scratchiness, foreign body sensation), ocular pain (pain, ache, burning), and ptosis, occurring in 5-10% of patients. Keratitis was reported in 3% of patients, and iritis, corneal lesion, photophobia, pupillary disorder, blepharitis, and glaucoma were reported in 2% of patients. Postsurgical atonic mydriasis, which is resistant to reversal with parasympathomimetic agents, also has been reported in patients receiving topical NSAIAs prior to cataract surgery; however, this effect also has been reported following such surgery in patients who did not receive NSAIAs. In a controlled study of ketorolac tromethamine ophthalmic solution for the prevention or treatment of cystoid macular edema, the incidence and severity of ocular complaints also were similar in patients receiving the drug or placebo.

There is some evidence that topically applied ketorolac tromethamine to the eye is less likely than topically applied corticosteroids to predispose to various ocular infections. In studies in rabbits, topically applied ketorolac tromethamine did not exacerbate ocular bacterial (e.g., Pseudomonas aeruginosa), fungal (e.g., Candida albicans), or viral (e.g., herpes simplex type 1) infections, while similarly applied corticosteroids did.

Topically applied ketorolac tromethamine does not appear to adversely affect intraocular pressure (IOP). However, changes in IOP may occur following cataract surgery.

The effect of ketorolac tromethamine on ocular wound healing remains to be fully elucidated, although topical application to the eye in rabbits of ketorolac tromethamine 0.5% did not delay healing in corneal wounds. The manufacturers of ketorolac tromethamine ophthalmic solutions and some other ophthalmic NSAIAs (e.g., flurbiprofen, diclofenac) caution that topical application of NSAIAs to the eye may slow or delay wound healing; however, early corneal epithelialization rather than corneal stromal healing appears to be affected. The possibility that a similar effect might occur with ketorolac tromethamine should be considered.

Topical NSAIAs can inhibit platelet aggregation and therefore may increase bleeding (e.g., hyphemas) of ocular tissues in patients undergoing ocular surgery.

Systemic Effects

Since systemic absorption may occur following topical application of ketorolac tromethamine to the eye, the possibility of adverse systemic effects may exist. However, some evidence suggests that the risk of systemic effects following topical application to the eye in usual dosages is low. Headache has been reported rarely following instillation of ketorolac tromethamine ophthalmic solution. For additional information on adverse systemic effects of the drug, .

Precautions and Contraindications

The manufacturer cautions that topical application of NSAIAs may slow wound healing. Because topical application of corticosteroids also may interfere with wound healing, concomitant use of these agents with topical NSAIAs, including ophthalmic ketorolac tromethamine, may increase the potential for healing problems.

Use of topical NSAIAs may result in keratitis. In some susceptible patients, continued use of topical NSAIAs also may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation; these events may be sight-threatening. The manufacturer states that patients presenting with evidence of corneal epithelial breakdown should be advised to discontinue topical NSAIA therapy immediately and should be closely monitored for corneal health.

Postmarketing experience with topical NSAIAs 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 of developing adverse corneal effects that may become sight-threatening. Therefore, the manufacturer states that topical NSAIAs should be used with caution in these patients.

Postmarketing experience suggests that use of topical NSAIAs more than 24 hours prior to surgery or use beyond 14 days postoperatively may precipitate or exacerbate adverse corneal effects.

Ketorolac tromethamine ophthalmic solution should be used with caution in patients who may be affected adversely by a prolongation of bleeding time, including those receiving drugs known to prolong bleeding time or with underlying bleeding tendencies, since the drug inhibits platelet aggregation.

Since there is potential for cross-sensitivity between ketorolac and other NSAIAs (including aspirin), ketorolac tromethamine ophthalmic solution should be used with caution in patients in whom asthma, rhinitis, or urticaria is precipitated by aspirin or other NSAIAs. For further discussion of cross-sensitivity of NSAIAs, .

The manufacturer of one NSAIA ophthalmic solution (suprofen [no longer commercially available]) states that the drug is contraindicated in patients with active epithelial herpes simplex keratitis (dendritic keratitis). This contraindication previously was included in the labeling of another NSAIA (flurbiprofen) based on findings in a study in rabbits in which the drug at a concentration more than 3 times the usual concentration exacerbated the infection (increased severity of corneal ulceration and conjunctivitis) and delayed healing; subsequently, however, all such cautionary information was removed from this labeling following completion by the same investigator of another study in rabbits that failed to demonstrate risk at usual concentrations of the drug. This contraindication also currently is not included in the labeling of ketorolac tromethamine or diclofenac, and studies with these topically applied drugs to the eye in rabbits revealed no evidence of exacerbation of viral or certain other microbial infections at usual concentrations of the drugs. Therefore, appropriate use of ketorolac tromethamine ophthalmic solution in patients with ocular infections currently is not precluded, although caution would be prudent.

Patients who wear contact lenses should remove their lenses prior to receiving a dose of ketorolac tromethamine ophthalmic solution.(See Dosage and Administration: Administration.)

Ketorolac tromethamine ophthalmic solution is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.

Pediatric Precautions

Safety and efficacy of ketorolac tromethamine ophthalmic solution in children younger than 3 years of age have not been established.

Geriatric Precautions

The manufacturer states that no overall differences in safety or efficacy have been observed between geriatric and younger patients.

Mutagenicity and Carcinogenicity

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

No evidence of carcinogenic potential was seen in an 18-month study in mice receiving oral ketorolac tromethamine dosages of 2 mg/kg daily (approximately equivalent to 60 times the maximum recommended human topical ophthalmic dosage of ketorolac tromethamine 0.5% on a mg/kg basis). There also was no evidence of carcinogenic potential in a 24-month study in rats receiving oral ketorolac tromethamine dosages up to 5 mg/kg daily (approximately 151 times the maximum recommended human topical ophthalmic dosage of ketorolac tromethamine 0.5% on a mg/kg basis).

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rabbits and rats receiving oral ketorolac tromethamine dosages up to 109 and 303 times the maximum recommended human topical ophthalmic dosage of ketorolac tromethamine 0.5% (on a mg/kg basis), respectively, have not revealed evidence of harm to the fetus. However, oral dosages exceeding 45 times the maximum recommended human topical ophthalmic dosage of ketorolac tromethamine 0.5% (on a mg/kg basis) in rats produced dystocia and was associated with an increased neonatal death rate. There are no adequate and controlled studies to date using ophthalmic ketorolac tromethamine in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risk to the fetus. Ketorolac tromethamine ophthalmic solution should not be used during late pregnancy, since inhibitors of prostaglandin synthesis may have adverse effects on the fetal cardiovascular system (e.g., premature closure of the ductus arteriosus).

Fertility

Ketorolac tromethamine did not impair fertility when administered orally to male and female rats at dosages up to 272 and 484 times the maximum recommended human topical ophthalmic dose of ketorolac tromethamine 0.5%, respectively, on a mg/kg basis.

Lactation

Because ketorolac is distributed into milk following systemic administration , the ophthalmic solution should be used with caution in nursing women.

Drug Interactions

The manufacturer states that ketorolac tromethamine ophthalmic solution has been used safely in conjunction with other ophthalmic agents, including antibiotics, β-adrenergic blocking agents, carbonic anhydrase inhibitors, cycloplegics, and/or mydriatics. The ophthalmic solution also has been used in conjunction with injectable sedatives (e.g., diazepam, hydroxyzine, lorazepam, promethazine hydrochloride), hyaluronidase, and/or local anesthetics (bupivacaine hydrochloride, lidocaine hydrochloride, tetracaine hydrochloride).

Corticosteroids

Ophthalmic NSAIAs, including ketorolac tromethamine, have been used concomitantly with ophthalmic corticosteroids. While NSAIAs and corticosteroids both can inhibit prostaglandin synthesis, the drugs appear to act principally at different sites in the synthetic pathway and corticosteroids can affect leukotriene synthesis as well as possibly other mediators of inflammation. Additive or synergistic ocular anti-inflammatory activity may result when a topical NSAIA and corticosteroid are used concomitantly. This effect has been used to therapeutic advantage in some patients for the management of postoperative ocular inflammation, including cystoid macular edema. However, because administration of topical NSAIAs and corticosteroids may slow wound healing, the manufacturer states that concomitant use of these agents may increase the potential for healing problems.(See Cautions: Precautions and Contraindications.)

Pharmacokinetics

Absorption

The extent of ocular and systemic absorption of ketorolac tromethamine following topical application to the eye in humans has not been fully elucidated; however, only limited concentrations are achieved systemically following such application relative to usual oral or parenteral doses of the drug. Following topical application to the eyes of 2 drops (100 mcL) of a 0.5% solution (500 mcg) of ketorolac tromethamine 12 hours and 1 hour before surgery in a limited number of patients undergoing cataract extraction, measurable aqueous humor concentrations of the drug were detected in almost all patients, averaging 95 ng/mL (range: 40-170 ng/mL) during surgery. Following topical application to one eye of 1 drop (50 mcL) of a 0.5% solution (250 mcg) of the drug 3 times daily for 10 days in a limited number of healthy adults, plasma concentrations of drug were detectable (range: 10.7-22.5 ng/mL) in about 20% of these individuals. Following topical application to the eye of a 250-mcg dose of ketorolac tromethamine in rabbits, peak plasma concentrations of approximately 200 ng/mL occurred within about 15 minutes. In these rabbits, mean aqueous humor concentrations of the drug exceeded those of plasma 13-fold. In healthy adults, steady-state plasma concentrations of ketorolac average approximately 600-800 or 1300-1500 ng/mL with IM ketorolac tromethamine dosages of 15 or 30 mg, respectively, 4 times daily.

Distribution

Distribution of ketorolac tromethamine into human ocular tissues and fluids has not been fully characterized to date. Following topical application to the eye of a 0.5% solution of ketorolac tromethamine in rabbits, the drug distributes throughout ocular tissues and fluids, including cornea, external tissues (e.g., sclera), intraocular tissues (e.g., aqueous humor, choroid-retina, iris, ciliary body), lens, and vitreous humor; concentrations are highest in scleral and corneal tissues and lowest in the lens. Following topical application of 50 mcL of a 0.5% solution (250 mcg) of ketorolac tromethamine to each eye in anesthetized rabbits, peak anterior chamber ketorolac concentrations of 19 mcg/mL were reached within 3.4 hours; the relative bioavailability in aqueous humor following topical application to the eye was about 4% of that following intracameral injection.

Following oral, IM, or IV administration of ketorolac tromethamine in humans, ketorolac does not appear to be distributed widely. Ketorolac is more than 99% bound to plasma proteins, but does not appear to bind irreversibly to ocular tissues.

Ketorolac crosses the placenta. The drug also is distributed into milk, but in relatively small amounts.

Elimination

Ketorolac tromethamine dissociates into ketorolac (anion) and tromethamine (cation) at physiologic pH. Following topical application to the eye or intracameral injection of a single dose of ketorolac tromethamine in rabbits, aqueous humor concentrations of drug decline with an average half-life of 3.8 or 2.1 hours, respectively. The principal mechanism of elimination from the eye of ocularly absorbed drug in these rabbits is thought to be via distribution into the iris-ciliary body and subsequent elimination via intraocular venous circulation. It is likely that substantial portions of a topically applied dose to the eye also are eliminated via systemic absorption from the conjunctiva.

Following single oral, IM, or IV doses of ketorolac tromethamine in healthy adults, plasma concentrations of the drug appear to decline in a biphasic manner with a terminal elimination half-life of about 4-6 hours (range: 3.8-6.3 hours). Similar plasma half-lives have been reported following ocular administration.

The exact metabolic fate of systemically absorbed ketorolac is not clearly established, but the drug undergoes hydroxylation in the liver to form p-hydroxyketorolac. This hydroxy metabolite exhibits limited pharmacologic activity, having less than 20% of the anti-inflammatory potency of the parent drug. Systemically absorbed ketorolac also undergoes conjugation with glucuronic acid and is metabolized to unidentified polar metabolites. Ketorolac reportedly does not undergo metabolism in the eye of rabbits and is present in plasma mainly as unchanged drug following ocular administration.

Following oral, IM, or IV administration, ketorolac and its metabolites are excreted mainly in the urine; only small amounts of the drug and its metabolites are excreted in feces, probably via biliary elimination.