2.1       Recommended Dosage

Temporary Relief of Ocular Itching Due to Seasonal Allergic Conjunctivitis

The recommended dosage of ACULAR is one drop four times a day to the affected eye(s) for the temporary relief of ocular itching due to seasonal allergic conjunctivitis.

Treatment of Postoperative Inflammation in Patients Who Have Undergone Cataract Extraction

Apply one drop of ACULAR to the affected eye four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period for the treatment of postoperative inflammation in patients who have undergone cataract extraction.

2.2       Use with Other Topical Ophthalmic Medications

ACULAR has been safely administered in conjunction with other ophthalmic medications such as antibiotics, alpha-agonists, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

5.1       Delayed Healing

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.

5.2       Cross-Sensitivity or Hypersensitivity

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac tromethamine ophthalmic solution in patients who have either a known hypersensitivity to aspirin/non-steroidal anti-inflammatory drugs or a past medical history of asthma. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

5.3       Increased Bleeding Time

With some NSAIDs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

It is recommended that ACULAR be used with caution in patients with known bleeding tendencies or who are receiving other medications, which may prolong bleeding time.

5.4       Corneal Effects

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Postmarketing experience with topical NSAIDs 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 for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.

Postmarketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events.

5.5       Risk of Contamination

Avoid allowing the tip of the bottle to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

5.6       Contact Lens Wear

ACULAR should not be administered while wearing contact lenses.

6.1       Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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

Other adverse reactions occurring approximately 1% to 10% of the time during treatment with ketorolac tromethamine ophthalmic solutions included allergic reactions (including eye swelling, hyperemia, and pruritus), corneal edema, iritis, ocular inflammation, ocular irritation, ocular pain, superficial keratitis, and superficial ocular infections.

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

6.2       Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ketorolac tromethamine ophthalmic solution 0.5% in clinical practice. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug.

Eye Disorders: corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown.

Respiratory, Thoracic and Mediastinal Disorders: bronchospasm or exacerbation of asthma.

8.1       Pregnancy

Risk Summary

There are no adequate and well-controlled studies with ACULAR in pregnant women. No evidence of teratogenicity has been observed in rats or rabbits with ACULAR at clinically relevant doses. 

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ACULAR during late pregnancy should be avoided.

8.2       Lactation

Risk Summary

It is not known whether ketorolac when given topically is present in human milk. Because many drugs are excreted in human milk, caution should be exercised when ACULAR is administered to a nursing woman.

8.4       Pediatric Use

The safety and effectiveness of ACULAR have not been established in pediatric patients younger than 2 years old.

8.5       Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

12.1       Mechanism of Action

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory, and anti-pyretic activity. The mechanism of its action is thought to be due to its ability to inhibit prostaglandin biosynthesis.

12.3       Pharmacokinetics

Two drops of 0.5% ketorolac tromethamine ophthalmic solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved a mean ketorolac concentration of 95 ng/mL in the aqueous humor of 8 of 9 eyes tested (range 40 to 170 ng/mL).

One drop of 0.5% ketorolac tromethamine ophthalmic solution was instilled into 1 eye and 1 drop of vehicle into the other eye TID in 26 healthy subjects. Five (5) of 26 subjects had detectable concentrations of ketorolac in their plasma (range 11 to 23 ng/mL) at Day 10 during topical ocular treatment. The range of concentrations following TID dosing of 0.5% ketorolac tromethamine ophthalmic solution are approximately 4 to 8% of the steady state mean minimum plasma concentration observed following four times daily oral administration of 10 mg ketorolac in humans (290 ± 70 ng/mL).