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Acular eent

Generic Name: Ketorolac Tromethamine eent
Class: Nonsteroidal Anti-inflammatory Agents
ATC Class: S01BC05
VA Class: OP300
CAS Number: 74103-07-4

Medically reviewed on January 1, 2018

Introduction

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

Uses for Acular

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.61

Has been used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema.14 20 23

Inhibition of Intraoperative Miosis

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

Acular 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
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
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 Acular

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

Interactions for Acular

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

Acular 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

  • Inhibits synthesis of certain ocular prostaglandins (e.g., PGE2) in iris, ciliary body, and conjunctiva by inhibiting cyclooxygenase-1 (COX-1) and -2 (COX-2).1 2 4 6 10 21 28 40 62 66 68 69 70 71 72 73 77 80 81 110 154 155

  • Substantially reduces aqueous humor concentrations of these prostaglandins.1 80 81 110 121 122 123 126 128

  • Does not appear to inhibit lipoxygenase;21 81 does not inhibit aspects of inflammation mediated by leukotrienes.81 119 137

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the product.1 154 155

  • Importance of removing contact lenses before administration.1 154 155

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 154 155

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1 154 155

  • Importance of informing patients of other important precautionary information.1 154 155 (See Cautions.)

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 2018, Selected Revisions January 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

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