Skip to main content

Ketorolac (EENT) (Monograph)

Brand name: Acular
Drug class: Nonsteroidal Anti-inflammatory Agents
- Nonsteroidal Anti-inflammatory Agents, Ophthalmic
- NSAIAs, EENT
- NSAIDs, EENT

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Prototypical NSAIA; a pyrrolizine carboxylic acid derivative.1 2 3 4 14 21 22 25 26 27 28

Uses for Ketorolac (EENT)

Conjunctivitis

Temporary relief of ocular itching due to seasonal allergic (hay fever, pollinosis) conjunctivitis.1 141 142 143

Postoperative Ocular Inflammation

Management of postoperative inflammation associated with cataract extraction.1 11 17 18 19 61 85 110 147

Postoperative Ocular Pain

Reduction of ocular pain and burning/stinging following corneal refractive surgery and photorefractive keratectomy (PRK).155 156

Ketorolac tromethamine 0.5% preservative-free ophthalmic solution is used for the reduction of ocular pain and photophobia following incisional refractive surgery.154

Cystoid Macular Edema

Treatment, with or without concomitant topical corticosteroid therapy, to prevent or relieve postoperative cystoid macular edema associated with cataract extraction [off-label].61

Has been used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema [off-label].14 20 23

Inhibition of Intraoperative Miosis

Has been used prophylactically before ocular surgery to prevent or reduce intraoperative miosis [off-label].53 81 106 107 108 110 137 139

Ketorolac (EENT) Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the eye as an ophthalmic solution.1 154 155

Avoid contamination of the solution container.154

Do not administer while wearing contact lenses.1 154 155

Preservative-free solution is for single use only in one or both eyes; use immediately after opening and discard any unused portion immediately after administration.154

Has been safely administered with other ophthalmic medications (e.g., antibiotics, β-blockers, carbonic anhydrase inhibitors, cycloplegics, mydriatics).1

Dosage

Available as ketorolac tromethamine; dosage expressed in terms of the salt.154 155

Pediatric Patients

Conjunctivitis
Ophthalmic

Children ≥3 years of age: 1 drop (250 mg) of a 0.5% solution in the affected eye(s) 4 times daily.1 141 142

Postoperative Ocular Inflammation
Ophthalmic

Children ≥3 years of age: 1 drop (250 mcg) of a 0.5% solution in the eye(s) undergoing surgery 4 times daily beginning 24 hours after surgery and typically continuing for 2 weeks after surgery.1

Postoperative Ocular Pain
Ophthalmic

Children ≥3 years of age undergoing ocular incisional refractive surgery: 1 drop (250 mcg) of a 0.5% preservative-free solution 4 times daily in the eye(s) that underwent surgery as needed for up to 3 days after surgery.154

Children ≥3 years of age undergoing corneal refractive surgery: 1 drop (200 mcg) of a 0.4% solution 4 times daily in the eye(s) that underwent surgery as needed for up to 4 days after surgery.155

Adults

Conjunctivitis
Ophthalmic

1 drop (250 mg) of a 0.5% solution in the affected eye(s) 4 times daily.1 141 142

Postoperative Ocular Inflammation
Ophthalmic

1 drop (250 mcg) of a 0.5% solution in the eye(s) undergoing surgery 4 times daily beginning 24 hours after surgery and typically continuing for 2 weeks after surgery.1

Postoperative Ocular Pain
Ophthalmic

Patients undergoing ocular incisional refractive surgery: 1 drop (250 mcg) of a 0.5% preservative-free solution 4 times daily in the eye(s) that underwent surgery as needed for up to 3 days after surgery.154

Patients undergoing corneal refractive surgery: 1 drop (200 mcg) of a 0.4% solution 4 times daily in the eye(s) that underwent surgery as needed for up to 4 days after surgery.155

Cystoid Macular Edema
Postoperative Cystoid Macular Edema† [off-label]
Ophthalmic

1–2 drops (250–500 mcg) of a 0.5% solution in the eye(s) undergoing surgery every 6–8 hours beginning 24 hours prior to surgery and continuing for 3–4 weeks after surgery.11 17 18 19 61 85

Chronic Aphakic or Pseudophakic Cystoid Macular Edema† [off-label]
Ophthalmic

1–2 drops (250–500 mcg) of a 0.5% solution in the affected eye(s) 4 times daily for 2–3 months.20 23

Cautions for Ketorolac (EENT)

Contraindications

Known hypersensitivity to ketorolac tromethamine or any ingredient in the formulation.1 154 155

Warnings/Precautions

Warnings

Hematologic Effects

May inhibit platelet aggregation and prolong bleeding time.1 137 154 155

May increase bleeding (e.g., hyphemas) of ocular tissues in patients undergoing ocular surgery.1 24 53 106 154 155

Use with caution in patients with underlying bleeding tendencies or in those receiving drugs known to prolong bleeding time.1 154 155

Sensitivity Reactions

Cross-sensitivity

Possible cross-sensitivity with aspirin, phenylacetic acid derivatives, and other NSAIAs.1 154 155 Use with caution in patients with history of hypersensitivity to these drugs.1 54 55 56 57 58 59 85 117 118 154 155

General Precautions

Wound Healing Complications

Possible slow or delayed wound healing; may be potentiated with concomitant adminsitration of topical NSAIAs or topical corticosteroids.1 154 155 (See Specific Drugs under Interactions.)

Ocular Effects

Use may result in keratitis.1 85 139 154 155 In susceptible patients, continued use may result in epithelial breakdown, corneal thinning, erosion, ulceration, or perforation, which may be sight-threatening.1 154 155

If manifestations of corneal epithelial breakdown occur, discontinue immediately and closely monitor corneal health.1 154 155

Increased risk of sight-threatening, adverse corneal effects in 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; use with caution in such patients.1 154 155

Use >24 hours prior to surgery or >14 days postoperatively may precipitate or exacerbate adverse corneal effects.1 154 155

Specific Populations

Pregnancy

Category C.1 154 155 Avoid use in the third trimester because of possible premature closure of the ductus arteriosus.1 154 155

Lactation

Distributed into milk after systemic administration.2 14 21 22 48 85 Caution if used in nursing women.1 154 155

Pediatric Use

Safety and efficacy not established in children <3 years of age.1 154 155

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 154 155

Common Adverse Effects

Ocular stinging and burning.1 154 155

Drug Interactions

No formal drug interaction studies to date.1 154 155

Specific Drugs

Drug

Interaction

Comments

Corticosteroids, ophthalmic

Possible additive effects on delaying wound healing1 154 155

Additive ocular anti-inflammatory activity1 154 155

Concomitant use may increase the potential for wound healing complications1 154 155

Potential for additive effects used to therapeutic advantage11 18 81

Ketorolac (EENT) Pharmacokinetics

Absorption

Bioavailability

Extent of ocular and systemic absorption not fully elucidated;1 however, limited concentrations are achieved systemically following topical application to the eye relative to usual oral or parenteral doses.1 14 16 18

Following topical application to the eye, plasma ketorolac concentrations were detectable (range: 10.7–22.5 ng/mL) in about 20% of patients.1 154 155

Distribution

Extent

Distribution into human ocular tissues and fluids not fully characterized to date.1 14 78

Ketorolac crosses the placenta21 28 46 47 78 and is distributed into milk following systemic administration.2 14 21 22 48 78

Plasma Protein Binding

>99%.2 14 28 45 49 78

Stability

Storage

Ophthalmic

0.4% Solution

15–25°C.155

0.5% Solution

Light-resistant containers at 15–30°C.1 154

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Ketorolac Tromethamine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.4%

Acular LS (with benzalkonium chloride)

Allergan

0.5%

Acular (with benzalkonium chloride)

Allergan

Acular PF (preservative-free)

Allergan

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Allergan. Acular (ketorolac tromethamine) ophthalmic solution 0.5% sterile prescribing information. Irvine, CA; 2002 Feb.

2. Syntex Laboratories Inc. Toradol (ketorolac tromethamine) tablets and injection prescribing information. Physicians’ desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2411-5.

3. Muchowski JM, Unger SH, Ackrell J et al. Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole -1-carboxylic acids and related compounds. J Med Chem. 1985; 28: 1037-49. http://www.ncbi.nlm.nih.gov/pubmed/4020827?dopt=AbstractPlus

4. Rooks WH II, Maloney PJ, Shott LD et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res. 1985; 11:479-92. http://www.ncbi.nlm.nih.gov/pubmed/3879752?dopt=AbstractPlus

5. Guzman A, Yuste F, Toscano RA et al. Absolute configuration of (-)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole -1-carboxy lic acid, the active enantiomer of ketorolac. J Med Chem. 1986; 29:589-91. http://www.ncbi.nlm.nih.gov/pubmed/3959034?dopt=AbstractPlus

6. Syntex Laboratories Inc, Palo Alto, CA: Personal communication on ketorolac 28:08.04.

7. Gu L, Strickley RG. Preformulation salt selection: physical property comparisons of the tris(hydroxymethyl)aminomethane (THAM) salts of four analgesic/antiinflammatory agents with the sodium salts and the free acids. Pharm Res. 1987; 4:255-7. http://www.ncbi.nlm.nih.gov/pubmed/3509292?dopt=AbstractPlus

8. Insel PA. Analgesic-antipyretics and antiinflammatory agents: drugs employed in the treatment of rheumatoid arthritis and gout. In: Gilman AG, Rall TW, Nies AS, et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:638-81.

9. Fraser-Smith EB, Matthews TR. Effect of ketorolac on phagocytosis of Candida albicans by peritoneal macrophages. Immunopharmacology. 1988; 16:151-5. http://www.ncbi.nlm.nih.gov/pubmed/3075603?dopt=AbstractPlus

10. Rooks WH II, Tomolonis AJ, Maloney PJ et al. The analgesic and anti-inflammatory profile of (±)-5-benzoyl-1,2-dihydro-3 H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (rS -37619). Agents Actions. 1982; 12:684-90. http://www.ncbi.nlm.nih.gov/pubmed/6984594?dopt=AbstractPlus

11. Flach AJ, Lavelle 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; 95:1279-84. http://www.ncbi.nlm.nih.gov/pubmed/3062540?dopt=AbstractPlus

12. Fraser-Smith EB, Matthews TR. Effect of ketorolac on Pseudomonas aeruginosa ocular infection in rabbits. J Ocul Pharmacol. 1988; 4:101-9. http://www.ncbi.nlm.nih.gov/pubmed/3262701?dopt=AbstractPlus

13. Fraser-Smith EB, Matthews TR. Effect of ketorolac on Candida albicans ocular infection in rabbits. Arch Ophthalmol. 1987; 105:264-7. http://www.ncbi.nlm.nih.gov/pubmed/3492994?dopt=AbstractPlus

14. Buckley MMT, Brogden RN. Ketorolac: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs. 1990; 39:86-109. http://www.ncbi.nlm.nih.gov/pubmed/2178916?dopt=AbstractPlus

15. Fraser-Smith EB, Matthews TR. Effect of ketorolac on herpes simplex virus type one ocular infection in rabbits. J Ocul Pharmacol. 1988; 4:321-6. http://www.ncbi.nlm.nih.gov/pubmed/3246566?dopt=AbstractPlus

16. Ling TL, Combs DL. Ocular bioavailability and tissue distribution of [14C]ketorolac tromethamine in rabbits. J Pharm Sci. 1987; 76:289-94. http://www.ncbi.nlm.nih.gov/pubmed/3598886?dopt=AbstractPlus

17. 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. Arch Ophthalmol. 1988; 106:344-7. http://www.ncbi.nlm.nih.gov/pubmed/3345153?dopt=AbstractPlus

18. 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; 106:480-3. http://www.ncbi.nlm.nih.gov/pubmed/3355415?dopt=AbstractPlus

19. Flach AJ, Jaffe NS, Akers WA. The effect of ketorolac tromethamine in reducing postoperative inflammation: double-mask parallel comparison with dexamethasone. Ann Ophthalmol. 1989; 21:407-11. http://www.ncbi.nlm.nih.gov/pubmed/2619149?dopt=AbstractPlus

20. Flach AJ, Dolan BJ, Irvine AR. Effectiveness of ketorolac tromethamine 0.5% ophthalmic solution for chronic aphakic and pseudophakic cystoid macular edema. Am J Ophthalmol. 1987; 103:479-86. http://www.ncbi.nlm.nih.gov/pubmed/3551617?dopt=AbstractPlus

21. Syntex Laboratories Inc. Toradol product monograph. Palo Alto, CA; 1990 Mar.

22. Syntex Laboratories Inc. Toradol pharmacy information. Palo Alto, CA; 1990 Mar.

23. Flach AJ, Jampol LM, Weinberg D et al. Improvement in visual acuity in chronic aphakic and pseudophakic cystoid macular edema after treatment with topical 0.5% ketorolac tromethamine. Am J Ophthalmol. 1991; 112:514-9. http://www.ncbi.nlm.nih.gov/pubmed/1951587?dopt=AbstractPlus

24. CIBA Vision Ophthalmics. Voltaren Ophthalmic (diclofenac sodium) 0.1% sterile ophthalmic solution prescribing information. Physicians’ desk reference for ophthalmology. 21st ed. Montvale, NJ: Medical Economics Company Inc; 1993:273-4.

25. Budavari S, ed. The Merck index. 11th ed. Rahway, NJ: Merck & Co, Inc; 1989:836.

26. Syntex Laboratories Inc. Toradol formulary facts. Palo Alto, CA; 1990.

27. Anon. Ketorolac tromethamine. Med Lett Drugs Ther. 1990; 32:79- 82. http://www.ncbi.nlm.nih.gov/pubmed/2199809?dopt=AbstractPlus

28. Gannon R. Focus on ketorolac: a nonsteroidal, anti-inflammatory agent for the treatment of moderate to severe pain. Hosp Formul. 1989; 24:695-702.

29. Yee JP, Koshiver JE, Allbon C et al. Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy. 1986; 6:253-61. http://www.ncbi.nlm.nih.gov/pubmed/3540877?dopt=AbstractPlus

30. Bloomfield SS, Mitchell J, Cissell GB et al. Ketorolac versus aspirin for postpartum uterine pain. Pharmacotherapy. 1986; 6:247-52. http://www.ncbi.nlm.nih.gov/pubmed/3540876?dopt=AbstractPlus

31. Reviewers’ comments (personal observations) on ketorolac.

32. Robinson DR. Prostaglandins and the mechanism of action of anti-inflammatory drugs. Am J Med. 1983; 10:26-31.

33. Koch-Weser J. Nonsteroidal antiinflammatory drugs (first of two parts). N Engl J Med. 1980; 302:1179-85. http://www.ncbi.nlm.nih.gov/pubmed/6988717?dopt=AbstractPlus

34. Abramson S, Edelson H, Kaplan H et al. Inhibition of neutrophil activation by nonsteroidal anti-inflammatory drugs. Am J Med. 1984; 10:3-6.

35. Deraedt R, Jouquey S, Benzoni J et al. Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs. Arch Int Pharmacodyn Ther. 1976; 224:30-42. http://www.ncbi.nlm.nih.gov/pubmed/13749?dopt=AbstractPlus

36. Atkinson DC, Collier HOJ. Salicylates: molecular mechanism of therapeutic action. Adv Pharmacol Chemother. 1980; 17:233-88. http://www.ncbi.nlm.nih.gov/pubmed/7004141?dopt=AbstractPlus

37. Hart FD. Rheumatic disorders. In: Avery GS, ed. Drug treatment: principles and practice of clinical pharmacology and therapeutics. 2nd ed. New York: ADIS Press; 1987:846-61.

38. Haynes WL, Proia AD, Klintworth GK. Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat. Invest Ophthalmol Vis Sci. 1989; 30:1588-93. http://www.ncbi.nlm.nih.gov/pubmed/2473047?dopt=AbstractPlus

39. Mahoney JM, Waterbury LD. Drug effects on the neovascularization response to silver nitrate cauterization of the rat cornea. Curr Eye Res. 1985; 4:531-5. http://www.ncbi.nlm.nih.gov/pubmed/2410194?dopt=AbstractPlus

40. Havener WH. Ocular pharmacology. 5th ed. St. Louis: The CV Mosby Company; 1983:18-43,223-35.

41. Conrad KA, Fagan TC, Mackie MJ et al. Effects of ketorolac tromethamine on hemostasis in volunteers. Clin Pharmacol Ther. 1988; 43:542-6. http://www.ncbi.nlm.nih.gov/pubmed/3259170?dopt=AbstractPlus

42. Spowart K, Greer IA, McLaren M et al. Haemostatic effects of ketorolac with and without concomitant heparin in normal volunteers. Thromb Haemost. 1988; 60:382-6. http://www.ncbi.nlm.nih.gov/pubmed/3266379?dopt=AbstractPlus

43. Roe RL, Bruno JJ, Ellis DJ. Effects of a new nonsteroidal anti-inflammatory agent on platelet function in male and female subjects. Clin Pharmacol Ther. 1981; 29:277.

44. Bruno JJ, Yang D, Taylor LA. Differing effects of ticlopidine and two prostaglandin synthetase inhibitors on maximum rate of ADP-induced aggregation. Thromb Haemost. 1981; 46:412.

45. Mroszczak EJ, Lee FW, Combs D et al. Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans. Drug Metab Dispos. 1987; 15:618-26. http://www.ncbi.nlm.nih.gov/pubmed/2891477?dopt=AbstractPlus

46. Walker JJ, Johnstone J, Lloyd J et al. The transfer of ketorolac tromethamine from maternal to foetal blood. Eur J Clin Pharmacol. 1988; 34:509-11. http://www.ncbi.nlm.nih.gov/pubmed/3264528?dopt=AbstractPlus

47. Greer IA, Johnston J, Tulloch I et al. Effect of maternal ketorolac administration on platelet function in the newborn. Eur J Obstet Gynecol Reprod Biol. 1988; 29:257-60. http://www.ncbi.nlm.nih.gov/pubmed/3265921?dopt=AbstractPlus

48. Wischnik A, Manth SM, Lloyd J. The excretion of ketorolac tromethamine into breast milk after multiple oral dosing. Eur J Clin Pharmacol. 1989; 36:521-4. http://www.ncbi.nlm.nih.gov/pubmed/2787750?dopt=AbstractPlus

49. Jung D, Mroszczak E, Bynum L. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur J Clin Pharmacol. 1988; 35:423-5. http://www.ncbi.nlm.nih.gov/pubmed/3264245?dopt=AbstractPlus

50. Jung D, Mroszczak EJ, Wu A et al. Pharmacokinetics of ketorolac and p-hydroxyketorolac following oral and intramuscular administration of ketorolac tromethamine. Pharm Res. 1989; 6:62-5. http://www.ncbi.nlm.nih.gov/pubmed/2717521?dopt=AbstractPlus

51. Jallad NS, Garg DC, Martinez JJ et al. Pharmacokinetics of single-dose oral and intramuscular ketorolac tromethamine in the young and elderly. J Clin Pharmacol. 1990; 30:76-81. http://www.ncbi.nlm.nih.gov/pubmed/2303585?dopt=AbstractPlus

52. Sarnquist FH, Mroszczak EJ, Sevelius H. Absorption and metabolism of a new anti-inflammatory, analgesic agent. Clin Pharmacol Ther. 1981; 29:280.

53. Allergan Medical Optics. Ocufen Liquifilm (flurbiprofen sodium) 0.03% sterile ophthalmic solution prescribing information. Physicians’ desk reference for ophthalmology. Montvale, NJ: Medical Economics Company Inc; 1993:236-7.

54. Weinberger M. Analgesic sensitivity in children with asthma. Pediatrics. 1978; 62(Suppl):910-5. http://www.ncbi.nlm.nih.gov/pubmed/103067?dopt=AbstractPlus

55. Pleskow WW, Stevenson DD, Mathison DA et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982; 69(1 Part 1):11-9. http://www.ncbi.nlm.nih.gov/pubmed/7054250?dopt=AbstractPlus

56. VanArsdel PP Jr. Aspirin idiosyncrasy and tolerance. J Allergy Clin Immunol. 1984; 73:431-3. http://www.ncbi.nlm.nih.gov/pubmed/6423718?dopt=AbstractPlus

57. Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1984; 74(4 Part 2):617-22. http://www.ncbi.nlm.nih.gov/pubmed/6436354?dopt=AbstractPlus

58. Stevenson DD, Mathison DA. Aspirin sensitivity in asthmatics: when may this drug be safe? Postgrad Med. 1985; 78:111-3,116-9.

59. Settipane GA. Aspirin and allergic diseases: a review. Am J Med. 1983; 74(Suppl):102-9. http://www.ncbi.nlm.nih.gov/pubmed/6344621?dopt=AbstractPlus

60. Indocin (indomethacin) capsules, oral suspension, and suppositories prescribing information. In: Barnhart ER, ed. Physicians’ desk reference. 44th ed. Oradell, NJ: Medical Economics Company Inc; 1990:1395-8.

61. Flach AJ, Stegman RC, Graham J et al. Prophylaxis of aphakic cystoid macular edema without corticosteroids. A paired-comparison, placebo-controlled double -masked study. Ophthalmology. 1990; 97:1253-8. http://www.ncbi.nlm.nih.gov/pubmed/2243674?dopt=AbstractPlus

62. Bhattacherjee P. Prostaglandins and inflammatory reactions in the eye. Methods Find Exp Clin Pharmacol. 1980; 2:17-31. http://www.ncbi.nlm.nih.gov/pubmed/6803089?dopt=AbstractPlus

63. Eakins KE. Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier. Exp Eye Res. 1977; 25(Suppl):483-98. http://www.ncbi.nlm.nih.gov/pubmed/338326?dopt=AbstractPlus

64. Podos SM, Becker B. Comparison of ocular prostaglandin synthesis inhibitors. Invest Ophthalmol. 1976; 15:841-4. http://www.ncbi.nlm.nih.gov/pubmed/977253?dopt=AbstractPlus

65. Duffin RM, Camras CB, Gardner SK et al. Inhibitors of surgically induced miosis. Ophthalmology. 1982; 89:966-78. http://www.ncbi.nlm.nih.gov/pubmed/7133642?dopt=AbstractPlus

66. Kulkarni PS, Srinivasan BD. Comparative in vivo inhibitory effects of nonsteroidal anti-inflammatory agents on prostaglandin synthesis in rabbit ocular tissues. Arch Ophthalmol. 1985; 103:103-6. http://www.ncbi.nlm.nih.gov/pubmed/3919694?dopt=AbstractPlus

67. Leopold IH, Murray D. Noncorticosteroidal anti-inflammatory agents in ophthalmology. Ophthalmology. 1979; 86:142-55. http://www.ncbi.nlm.nih.gov/pubmed/394060?dopt=AbstractPlus

68. van Alphen GWHM, Dutilh CE, de Deckere EAM. The high yield of prostacyclin biosynthesis by the iris and its effects on the intraocular muscles. Prostaglandins Med. 1978; 1:151-8. http://www.ncbi.nlm.nih.gov/pubmed/362455?dopt=AbstractPlus

69. Hall DWR, Bonta IL. Prostaglandins and ocular inflammation. Doc Ophthalmol. 1977; 2:421-34.

70. Kass MA, Holmberg NJ. Prostaglandin and thromboxane synthesis by microsomes of rabbit ocular tissues. Invest Ophthalmol Vis Sci. 1979; 18:166-71. http://www.ncbi.nlm.nih.gov/pubmed/761971?dopt=AbstractPlus

71. Sawa M, Masuda K. Topical indomethacin in soft cataract aspiration. Jpn J Ophthalmol. 1976; 20:514-9.

72. Ciprandi G, Buscaglia S, Cerqueti PM et al. Drug treatment of allergic conjunctivitis: a review of the evidence. Drugs. 1992; 43:154-76. http://www.ncbi.nlm.nih.gov/pubmed/1372215?dopt=AbstractPlus

73. Abelson MB, Butrus SI, Kliman GH et al. Topical arachidonic acid: a model for screening anti-inflammatory agents. J Ocul Pharmacol. 1987; 3:63-75. http://www.ncbi.nlm.nih.gov/pubmed/3141537?dopt=AbstractPlus

74. Friedlaender MH. Current concepts in ocular allergy. Ann Allergy. 1991; 67:5-10,13. http://www.ncbi.nlm.nih.gov/pubmed/1859041?dopt=AbstractPlus

75. Helleboid L, Khatami M, Wei ZG et al. Histamine and prostacyclin: primary and secondary release in allergic conjunctivitis. Invest Ophthalmol Vis Sci. 1991; 32:2281-9. http://www.ncbi.nlm.nih.gov/pubmed/1712764?dopt=AbstractPlus

76. Abramson SB, Weissmann G. The mechanisms of action of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1989; 32:1-9. http://www.ncbi.nlm.nih.gov/pubmed/2643434?dopt=AbstractPlus

77. Trocme SD. Medical therapy for ocular allergy. Mayo Clin Proc. 1992; 67:557-65. http://www.ncbi.nlm.nih.gov/pubmed/1359206?dopt=AbstractPlus

78. Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet. 1992; 23:415-27. http://www.ncbi.nlm.nih.gov/pubmed/1458761?dopt=AbstractPlus

79. Sabiston D, Tessler H, Sumers K et al. Reduction of inflammation following cataract surgery by the nonsteroidal anti-inflammatory drug, flurbiprofen. Ophthalmic Surg. 1987; 18:873-7. http://www.ncbi.nlm.nih.gov/pubmed/3502173?dopt=AbstractPlus

80. Bhattacherjee P. The role of arachidonate metabolites in ocular inflammation. Prog Clin Biol Res. 1989; 312:211-27. http://www.ncbi.nlm.nih.gov/pubmed/2508125?dopt=AbstractPlus

81. Flach AJ. Cyclo-oxygenase inhibitors in ophthalmology. Surv Ophthalmol. 1992; 36:259-84. http://www.ncbi.nlm.nih.gov/pubmed/1549810?dopt=AbstractPlus

82. Buckley DC, Caldwell DR, Reaves TA Jr. Treatment of vernal conjunctivitis with suprofen, a topical nonsteroidal anti-inflammatory agent. Invest Ophthalmol Vis Sci. 1986; 27:29. http://www.ncbi.nlm.nih.gov/pubmed/3941035?dopt=AbstractPlus

83. Wood TS, Stewart RH, Bowman RW et al. Suprofen treatment of contact lens-associated giant papillary conjunctivitis. Ophthalmology. 1988; 95:822-6. http://www.ncbi.nlm.nih.gov/pubmed/3211485?dopt=AbstractPlus

84. Gupta S, Khurana AK, Ahluwalia BK et al. Topical indomethacin for vernal keratoconjunctivitis. Acta Opthalmol (Copenh). 1991; 69:95-8.

85. Allergan. Acular (ketorolac tromethamine) prescribing information. In: Krogh CME, ed. Compendium of pharmaceuticals and specialties 1993. 28th ed. Ottawa, Ontario: Canadian Pharmaceutical Association; 1993:23.

86. CIBA Vision. Voltaren Ophthalmic (diclofenac sodium) prescribing information. In: Krogh CME, ed. Compendium of pharmaceuticals and specialties 1993. 28th ed. Ottawa, Ontario: Canadian Pharmaceutical Association; 1993:1333-4.

87. Merck Sharp and Dohme. Indocid (indomethacin) ophthalmic suspension prescribing information. In: Krogh CME, ed. Compendium of pharmaceuticals and specialties 1993. 28th ed. Ottawa, Ontario: Canadian Pharmaceutical Association; 1993:583.

88. Asbell PA, Torres MA. Therapeutic dilemmas in external ocular diseases. Drugs. 1991; 42:606-15. http://www.ncbi.nlm.nih.gov/pubmed/1723363?dopt=AbstractPlus

89. Leibowitz HM, Ryan WJ, Kupferman A et al. Bioavailability of corneal anti-inflammatory effect of topical suprofen. Invest Ophthalmol Vis Sci. 1986; 27:628-31. http://www.ncbi.nlm.nih.gov/pubmed/3957583?dopt=AbstractPlus

90. Leibowitz HM, Ryan WJ, Kupferman A et al. Effect of concurrent topical corticosteroid and NSAID therapy of experimental keratitis. Invest Ophthalmol Vis Sci. 1986; 27:1226-9. http://www.ncbi.nlm.nih.gov/pubmed/3733368?dopt=AbstractPlus

91. Kraff MC, Sanders DR, McGuigan L et al. Inhibition of blood-aqueous humor barrier breakdown with diclofenac: a fluorophotometric study. Arch Ophthalmol. 1990; 108:380-3. http://www.ncbi.nlm.nih.gov/pubmed/2178597?dopt=AbstractPlus

92. Bito LZ. Surgical miosis: have we been misled by a bunch of rabbits? Ophthalmology. 1990; 97:1-2. Letter.

93. Kraff MC, Sanders DR, Jampol LM et al. Factors affecting pseudophakic cystoid macular edema: five randomized trials. J Am Intraocul Implant Soc. 1985; 11:380-5. http://www.ncbi.nlm.nih.gov/pubmed/4030486?dopt=AbstractPlus

94. Gnad HD, Paroussis P, Skorpik C. Treatment of cystoid macular edema after intracapsular cataract extraction and implantation of the Binkhorst 4-loop lens. (German; with English abstract.) Wien Klin Wochenschr. 1985; 97:625-7.

95. Alpar JJ. Posterior capsulotomy in sulcus-fixated versus bag-fixated intraocular lenses in diabetic patients. J Am Intraocul Implant Soc. 1985; 11:577-80. http://www.ncbi.nlm.nih.gov/pubmed/4077672?dopt=AbstractPlus

96. Jampol LL. Pharmacologic therapy of aphakic and pseudophakic cystoid macular edema. 1985 update. Ophthalmology. 1985; 92:807-10. http://www.ncbi.nlm.nih.gov/pubmed/3897936?dopt=AbstractPlus

97. Lambrix K. Cystoid macular edema: a postoperative complication. J Ophthalmic Nurs Technol. 1990; 9:152-4. http://www.ncbi.nlm.nih.gov/pubmed/2374166?dopt=AbstractPlus

98. Peterson M, Yoshizumi MO, Hepler R et al. Topical indomethacin in the treatment of chronic cystoid macular edema. Graefes Arch Clin Exp Ophthalmol. 1992; 230:401-5. http://www.ncbi.nlm.nih.gov/pubmed/1521802?dopt=AbstractPlus

99. Sears ML. Aphakic cystoid macular edema. The pharmacology of ocular trauma. Surv Ophthalmol. 1984; 28(Suppl):525-34. http://www.ncbi.nlm.nih.gov/pubmed/6379950?dopt=AbstractPlus

100. Yannuzzi LA. A perspective on the treatment of aphakic cystoid macular edema. Surv Ophthalmol. 1984; 28(Suppl):540-53. http://www.ncbi.nlm.nih.gov/pubmed/6379952?dopt=AbstractPlus

101. Yannuzzi LA, Landau AN, Turtz AL. Incidence of aphakic cystoid macular edema with the use of topical indomethacin. Ophthalmolgy. 1981; 88:947-54.

102. Kraff MC, Sanders DR, Jampol LM et al. Prophylaxis of pseudophakic cystoid macular edema with topical indomethacin. Ophthalmology. 1982; 89:885-90. http://www.ncbi.nlm.nih.gov/pubmed/6752799?dopt=AbstractPlus

103. Miyake K, Sakamura S, Miura H. Long-term follow-up study on the prevention of aphakic cystoid macular edema by topical indomethacin. Br J Ophthalmol. 1980; 64:324-8. http://www.ncbi.nlm.nih.gov/pubmed/7437393?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1043688&blobtype=pdf

104. Foster CS, Calonge M. Atopic keratoconjunctivitis. Ophthalmology. 1990; 97:992-100. http://www.ncbi.nlm.nih.gov/pubmed/1976238?dopt=AbstractPlus

105. Foster CS, Rice BA, Dutt JE. Immunopathology of atopic keratocomjunctivitis. Ophthalmology. 1991; 98:1190-6. http://www.ncbi.nlm.nih.gov/pubmed/1923355?dopt=AbstractPlus

106. Alcon Laboratories. Profenal (suprofen) 1% sterile ophthalmic solution prescribing information. In: Physicians’ desk reference for ophthalmology. 21st ed. Montvale, NJ: Medical Economics Company; 1993;233-5.

107. Stark WJ, Fagadau WR, Stewart RH et al. Reduction of pupillary constriction during cataract surgery using suprofen. Arch Ophthalmol. 1986; 104:364-6. http://www.ncbi.nlm.nih.gov/pubmed/3513744?dopt=AbstractPlus

108. Keates RH, McGowan KA. Clinical trial of flurbiprofen to maintain pupillary dilation during cataract surgery. Ann Ophthalmol. 1984; 16:919-21. http://www.ncbi.nlm.nih.gov/pubmed/6391333?dopt=AbstractPlus

109. Camras CR, Miranda OC. The putative role of prostaglandins in surgical miosis. Prog Clin Biol Res. 1989; 312:197-210. http://www.ncbi.nlm.nih.gov/pubmed/2508124?dopt=AbstractPlus

110. Goa KL, Chrisp P. Ocular diclofenac: a review of its pharmacology and clinical use in cataract surgery, and potential in other inflammatory ocular conditions. Drugs Aging. 1992; 2:473-86. http://www.ncbi.nlm.nih.gov/pubmed/1493352?dopt=AbstractPlus

111. Green K, Cheeks L, Luxenberg MN. Topical indomethacin and prostaglandins in normal and aphakic rabbit eyes. Curr Eye Res. 1988; 7:1105-11. http://www.ncbi.nlm.nih.gov/pubmed/3243084?dopt=AbstractPlus

112. Hersh PS, Rice BA, Baer JC et al. Topical nonsteroidal agents and corneal wound healing. Arch Ophthalmol. 1990; 108:577-83. http://www.ncbi.nlm.nih.gov/pubmed/2322160?dopt=AbstractPlus

113. Trousdale MD, Dunkel EC, Nesburn AB. Effect of flurbiprofen on herpes simplex keratitis in rabbits. Invest Ophthalmol Vis Sci. 1980; 19:267-70. http://www.ncbi.nlm.nih.gov/pubmed/7358477?dopt=AbstractPlus

114. Trousdale MD, Barlow WE, McGuigan LJB. Assessment of diclofenac on herpes keratitis in rabbit eyes. Arch Ophthalmol. 1989; 107: 1664-6.

115. Allergan Medical Optics. Ocufen Liquifilm (flurbiprofen sodium) 0.03% sterile ophthalmic solution prescribing information. Physicians’ desk reference for ophthalmology. 20th ed. Montvale, NJ: Medical Economics Company Inc; 1992:236-7.

116. Haynes RC Jr. Adrenocorticotropic hormone: adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Rall TW, Nies AS, et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:1431-62.

117. Haddow GR, Riley E, Isaacs R et al. Ketorolac, nasal polyposis, and bronchial asthma: a cause for concern. Anesth Analg. 1993; 76:420-2. http://www.ncbi.nlm.nih.gov/pubmed/8424525?dopt=AbstractPlus

118. Zikowski D, Hord AH, Haddox JD et al. Ketorolac-induced bronchospasm. Anesth Analg. 1993; 76:417-9. http://www.ncbi.nlm.nih.gov/pubmed/8424524?dopt=AbstractPlus

119. Campbell WB. Lipid-derived autacoids: eicosanoids and platelet -activating factor. In: Gilman AG, Rall TW, Nies AS, et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:600 -605.

120. Flower RJ, Blackwell GJ. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents PG production. Nature. 1979; 278:456 -9. http://www.ncbi.nlm.nih.gov/pubmed/450050?dopt=AbstractPlus

121. Kremer M, Baikoff G, Charbonnel B. The release of prostaglandins in human aqueous humour following intraocular surgery: effect of indomethacin. Prostaglandins. 1982; 23:695-702. http://www.ncbi.nlm.nih.gov/pubmed/6956947?dopt=AbstractPlus

122. Kremer M, Baikoff G, Charbonnel B. Prostaglandin E2 in side effects of ocular surgery in man: preventive action of indomethacin. Adv Prostaglandin Thromboxane Leukot Res. 1983; 12:121-6. http://www.ncbi.nlm.nih.gov/pubmed/6221587?dopt=AbstractPlus

123. Miyake K, Sugiyama S, Norimatsu I et al. Prevention of cystoid macular edema after lens extraction by topical indomethacin (III) radioimmunoassay measurement of prostaglandins in the aqueous during and after lens extraction procedures. Graefes Arch Klin Exp Ophthalmol. 1978; 209:83-8.

124. Miyake K. Prevention of cystoid macular edema after lens extraction by topical indomethacin (I): a preliminary report. Graefes Arch Klin Exp Ophthalmol. 1977; 203:81-8.

125. Miyake K. Prophylaxis of aphakic cystoid macular edema using topical indomethacin. J Am Intraocul Implant Soc. 1978; 4:174-9. http://www.ncbi.nlm.nih.gov/pubmed/748308?dopt=AbstractPlus

126. Paterson CA, Eakins KE, Paterson E et al. The ocular hypertensive response following experimental acid burns in the rabbit eye. Invest Ophthalmol Vis Sci. 1979; 18:67-74. http://www.ncbi.nlm.nih.gov/pubmed/32151?dopt=AbstractPlus

127. Rowland JM, Ford CJ, Della Puca RA et al. Effects of topical diclofenac sodium in a rabbit model of ocular inflammation and leukotaxis. J Ocul Pharmacol. 1986; 2:23-9. http://www.ncbi.nlm.nih.gov/pubmed/3509726?dopt=AbstractPlus

128. Bhattercherjee P, Eakins KE. Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds. Prostaglandins. 1975; 9:175-82. http://www.ncbi.nlm.nih.gov/pubmed/1135434?dopt=AbstractPlus

129. Neufeld AH, Sears ML. Prostaglandin and the eye. Prostaglandins. 1973; 4:157-75. http://www.ncbi.nlm.nih.gov/pubmed/4199679?dopt=AbstractPlus

130. Waitzman MB. Possible new concepts relating prostaglandins to various ocular functions. Surv Ophthalmol. 1970; 14:301-26. http://www.ncbi.nlm.nih.gov/pubmed/4984791?dopt=AbstractPlus

131. van Haeringen NJ, Glasium E, Oosterhuis JA et al. Drug prevention of blood -aqueous barrier disruption. Ophthalmic Res. 1983; 15:180-4. http://www.ncbi.nlm.nih.gov/pubmed/6634053?dopt=AbstractPlus

132. van Haeringen NJ, Osterhuis JA, van Delft JL et al. A comparison of the effects of non-steroidal compounds on the disruption of the blood -aqueous barrier. Exp Eye Res. 1982; 35:271-7. http://www.ncbi.nlm.nih.gov/pubmed/7117419?dopt=AbstractPlus

133. Eakins KE. Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier. Exp Eye Res. 1977; 25(Suppl):483-98. http://www.ncbi.nlm.nih.gov/pubmed/338326?dopt=AbstractPlus

134. Neufeld AH, Sears ML. The site of action of prostaglandin E2 on the disruption of the blood-aqueous barrier in the rabbit eye. Exp Eye Res. 1973; 17:445-8. http://www.ncbi.nlm.nih.gov/pubmed/4783182?dopt=AbstractPlus

135. Oosterhuis JA, van Haeringen NJ, Glasius E et al. The effect of indomethacin on the anterior segment of the eye after paracentesis. Doc Ophthalmol. 1981; 50:303-13. http://www.ncbi.nlm.nih.gov/pubmed/7227171?dopt=AbstractPlus

136. Eakins KE, Bhattacherjee P. Histamine, prostaglandins and ocular inflammation. Exp Eye Res. 1977; 24:299-305. http://www.ncbi.nlm.nih.gov/pubmed/852527?dopt=AbstractPlus

137. Reviewers’ comments (personal observations).

138. Mahoney JM, Waterbury LD. (+)-5 Benzoyl-1,2-dihydro-3H -pyrrolo(1,2a)pyrrole-1-carboxlic acid (rS-37619)—a non-irritating ophthalmic anti -inflammatory agent. Invest Ophthalmol Vis Sci. 1983; 24(Suppl):151.

139. Allergan, Irvine, CA: Personal communication.

140. Waterbury L, Kunysz EA, Beuerman R. Effects of steroidal and non -steroidal anti-inflammatory agents on corneal wound healing. J Ocul Pharmacol. 1987; 3:43-54. http://www.ncbi.nlm.nih.gov/pubmed/3503908?dopt=AbstractPlus

141. 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; 38(Suppl): 133-140. http://www.ncbi.nlm.nih.gov/pubmed/8236004?dopt=AbstractPlus

142. Ballas Z, Blumenthal M, Tinkeman DG et al. Clinical evaluation of ketorolac tromethamine 0.5% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol. 1993; 38(Suppl): 141-8.

143. Anonymous. Ketorolac for seasonal allergic conjunctivitis. Med Lett Drugs Ther. 1993; 35: 88-9.

144. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician. 1998; 57:735-46. http://www.ncbi.nlm.nih.gov/pubmed/9490996?dopt=AbstractPlus

145. Titi MJ. A critical look at ocular allergy drugs. Am Fam Physician. 1996; 53:2637-42. http://www.ncbi.nlm.nih.gov/pubmed/8644576?dopt=AbstractPlus

146. Galindez OA, Kaufman HE. Coping with the itchy-burnies: the management of allergic conjunctivitis. Ophthalmology. 1996; 103:1335-6. http://www.ncbi.nlm.nih.gov/pubmed/8841290?dopt=AbstractPlus

147. Ostrov CS, Sirkin SR, Deutsch WE et al. Ketorolac, prednisolone, and dexamethasone for postoperative inflammation. Clin Ther. 1997; 19:259-72. http://www.ncbi.nlm.nih.gov/pubmed/9152565?dopt=AbstractPlus

148. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. http://www.ncbi.nlm.nih.gov/pubmed/9929039?dopt=AbstractPlus

149. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. http://www.ncbi.nlm.nih.gov/pubmed/8967954?dopt=AbstractPlus

150. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95. http://www.ncbi.nlm.nih.gov/pubmed/9365818?dopt=AbstractPlus

151. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.

152. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. http://www.ncbi.nlm.nih.gov/pubmed/9990677?dopt=AbstractPlus

153. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.

154. Allergan. Acular PF (ketorolac tromethamine) ophthalmic solution 0.5% preservative free sterile prescribing information. Irvine, CA; 2002 Feb.

155. Allergan. Acular LS (ketorolac tromethamine) ophthalmic solution 0.4% prescribing information. Irvine, CA; 2003 May.

156. Solomon KD, Donnenfeld ED, Raizman M et al. Safety and efficacy of ketorolac tromethamine 0.4% ophthalmic solution in post-photorefractive keratectomy patients. J Cataract Refract Surg. 2004; 30:1653-60. http://www.ncbi.nlm.nih.gov/pubmed/15313287?dopt=AbstractPlus