Medication Guide App

Ketorolac (Ophthalmic)


VA CLASSIFICATION
Primary: OP302
Secondary: OP900

Commonly used brand name(s): Acular.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anti-inflammatory, nonsteroidal (ophthalmic)—

antipruritic (ophthalmic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Conjunctivitis, allergic (treatment)1—Ketorolac ophthalmic is indicated for the treatment of ocular itching caused by seasonal allergic conjunctivitis. {01} {09} {10} {11}

Inflammation, ocular (treatment)—Ketorolac is indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction. {15} {16}

[Inflammation, ocular (prophylaxis)]—Ketorolac ophthalmic is indicated for the prophylaxis of postoperative ocular inflammation in patients undergoing cataract extraction with or without implantation of an intraocular lens. {03} {05} {06} {07} {08} {13}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Ketorolac tromethamine: 376.41 {01} {02}


Osmolality
    290 mOsmol per kg. {01}

pKa—
    3.5 {01}


pH
    7.4 {01}.

Mechanism of action/Effect:

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that is chemically related to indomethacin and tolmetin. Ocular administration of ketorolac reduces prostaglandin E 2 levels in aqueous humor, secondary to inhibition of prostaglandin biosynthesis. {01} {03} {09}


Other actions/effects:

Ketorolac ophthalmic has no significant effect on intraocular pressure. {01} {03} {08}

Absorption:

Negligible. {01} {09}

Distribution:

Plasma—In a study where 26 subjects were administered 1 drop of 0.5% ketorolac ophthalmic solution in 1 eye 3 times a day for 21 days, 5 of 26 subjects had detectable (greater than 10 nanograms per mL) plasma levels of 11 to 22 nanograms per mL of ketorolac when they were tested 15 minutes after the first dose on day 10. When the subjects were tested on day 24, none had detectable plasma levels. In comparison, 10 mg of systemic ketorolac administered every 6 hours results in a steady state plasma level of approximately 960 nanograms per mL. {01} {03}

Aqueous humor—Eight of 9 patients administered 2 drops of 0.5% ketorolac ophthalmic solution in each eye 12 hours and 1 hour prior to cataract extraction had detectable (greater than or equal to 40 nanograms per mL) levels of 40 to 170 nanograms per mL (mean concentration 95 nanograms per mL) of ketorolac in the aqueous humor. {01} {03}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to aspirin; phenylacetic acid derivatives, such as diclofenac; or other systemic or ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) may be sensitive to ketorolac also. {01} {03}

Tumorigenicity

No evidence of tumorigenicity was found in an 18-month study in mice given oral doses of ketorolac equivalent to the parenteral maximum recommended human dose (MRHD) and a 24-month study in rats given oral doses of ketorolac equivalent to 2.5 times the parenteral MRHD. {01}

Mutagenicity

Ketorolac was not mutagenic in the Ames test, the unscheduled DNA synthesis and repair test, and in forward mutation assays. In addition, ketorolac did not cause chromosome breakage in the in vivo mouse micronucleus assay. However, at 1590 mcg per mL and higher concentrations of ketorolac, there was an increased incidence of chromosomal aberrations in Chinese hamster ovarian cells. {01}

Pregnancy/Reproduction
Fertility—
Male and female rats given ketorolac at oral doses of 9 mg per kg of body weight (mg/kg) and 16 mg/kg, respectively, did not show impairment of fertility. {01}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. {01}

Studies in rabbits and rats given ketorolac at oral doses of 3.6 mg/kg a day and 10 mg/kg a day, respectively, during organogenesis did not show evidence of teratogenicity. However, rats given oral doses of 1.5 mg/kg after gestation day 17 had a higher pup mortality rate. {01}

FDA Pregnancy Category C. {01}

Labor—

Rats given oral doses of 1.5 mg/kg of ketorolac after gestation day 17 developed dystocia. {01}

Breast-feeding

Problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of ophthalmic ketorolac have not been performed in the pediatric population. Safety and efficacy have not been established. {01} {03}


Geriatrics


Appropriate studies on the relationship of age to the effects of ophthalmic ketorolac have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Any medication that may interfere with blood clotting or prolong bleeding time, such as:
Anticoagulants, coumarin- or indandione-derivative, or
Heparin or
Platelet aggregation inhibitors    (ophthalmic NSAIDs, such as ketorolac, may also increase the tendency to bleed; concurrent use may increase the risk of postoperative ocular bleeding {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Hemophilia or other bleeding problems or coagulation defects or
Prolonged bleeding time    (increased risk of bleeding following ocular surgery {01} {03})


Sensitivity to ophthalmic ketorolac{03}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
{14}    
Hypersensitivity{01} (itching, rash, redness, swelling, or other sign of irritation not present before therapy)
    
keratitis, superficial{01} (redness of the clear part of the eye)
    
ocular irritation{01} (itching, redness, tearing, or other sign of eye irritation not present before use of this medicine or becoming worse during use)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Stinging or burning upon instillation of medication{01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ketorolac (Ophthalmic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ophthalmic or systemic ketorolac; aspirin; phenylacetic acid derivatives, such as diclofenac; or other systemic or ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs)

Proper use of this medication
Proper administration; using a second drop if necessary; not touching applicator tip to any surface; keeping container tightly closed

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose; using next dose at regularly scheduled time; not doubling doses

» Proper storage

Precautions while using this medication
Checking with doctor if symptoms do not improve or if they become worse

Expecting stinging or burning of eye upon administration of medication


Side/adverse effects
Signs of potential side effects, especially hypersensitivity; keratitis, superficial; or ocular irritation


General Dosing Information
The manufacturer recommends that patients not wear soft contact lenses during treatment with ketorolac ophthalmic solution. {01} However, medical experts do not believe this precaution is necessary unless the patient has corneal epithelial problems and the medication is to be used more often than once every 1 to 2 hours. No significant problems have been documented with ophthalmic solutions that contain 0.03% or less of benzalkonium chloride as a preservative and are used as eye drops in patients with no significant corneal surface problems. {04} {13}

Ketorolac ophthalmic may be administered in conjunction with other ophthalmic medications, such as antibiotics, beta-adrenergic blocking agents, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. {01}


Ophthalmic Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

KETOROLAC TROMETHAMINE OPHTHALMIC SOLUTION

Usual adult and adolescent dose
Conjunctivitis, allergic (treatment)1
Topical, to the conjunctiva, 1 drop in each eye four times a day. {01}

Inflammation, ocular (treatment)
In the U.S.: Topical, to the conjunctiva, 1 drop in the affected eye(s) four times a day beginning twenty-four hours after cataract surgery and continuing for two weeks. {15}

[Inflammation, ocular (prophylaxis and treatment)]
In Canada: Topical, to the conjunctiva, 1 drop in each eye every six to eight hours beginning twenty-four hours before surgery and continuing for three to four weeks. {03}


Usual pediatric dose
Safety and efficacy have not been established. {01} {03}

Strength(s) usually available
U.S.—


0.5% (Rx) [Acular{01} (benzalkonium chloride 0.01%)]

Canada—


0.5% (Rx) [Acular{03} (benzalkonium chloride)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {01} {03} unless otherwise specified by manufacturer. Protect from light. {01} {03}

Auxiliary labeling:
   • For the eye. {01}



Developed: 08/11/1994
Revised: 11/20/1998



References
  1. Acular package insert (Allergan—US), Rev 11/92, Rec 2/93.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 365.
  1. Acular package insert (Allergan—Canada), Rev 8/92, Rec 1/94.
  1. Reviewers' consensus on the use of benzalkonium chloride-containing ophthalmic solutions and soft contact lenses in the Lodoxamide ophthalmic monograph revision of 11/11/93.
  1. Flach AJ, Jaffe NS, Akers WA. The effect of ketorolac tromethamine in reducing postoperative inflammation: double-mask parallel comparison with dexamethasone. Ann Ophthalmol 1989 Nov; 21(11): 407-11.
  1. Flach AJ, Levelle CJ, Olander KW, et al. The effect of ketorolac tromethamine solution 0.5% in reducing postoperative inflammation after cataract extraction and intraocular lens implantation. Ophthalmology 1988 Sep; 95(9): 1279-84.
  1. Flach AJ, Kraff MC, Sanders DR, et al. The quantitative effect of 0.5% ketorolac tromethamine solution and 0.1% dexamethasone sodium phosphate solution on postsurgical blood-aqueous barrier. Arch Ophthalmol 1988 Apr; 106(4): 480-3.
  1. Flach AJ, Graham J, Kruger LP, et al. Quantitative assessment of postsurgical breakdown of the blood-aqueous barrier following administration of 0.5% ketorolac tromethamine solution. A double-masked, paired comparison with vehicle-placebo solution study. Arch Ophthalmol 1988 Mar; 106(3): 344-7.
  1. Ketorolac for seasonal allergic conjunctivitis. Med Lett Drugs Ther 1993 Sep 17; 35(905): 88-9.
  1. Tinkelman DG, Rupp G, Kaufman H, et al. Double-masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol 1993 Jul-Aug; 38 Suppl: 133-40.
  1. Ballas Z, Blumenthal M, Tinkelman DG, et al. Clinical evaluation of ketorolac tromethamine 0.5% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol 1993 Jul-Aug; 38 Suppl: 141-8.
  1. Open.
  1. Reviewers" consensus on monograph revision of 5/5/94.
  1. Panel comment, 5/5/94.
  1. Acular (Allergan). In: PDR Physicians" desk reference for ophthalmology. 26th ed. 1998. Montvale, NJ: Medical Economics Company; 1998. p. 221-2.
  1. Acular (Allergan). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 28-9.
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