Ketorolac Tromethamine

Akorn

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Ketorolac Tromethamine Ophthalmic Solution safely and effectively. See full prescribing information for Ketorolac Tromethamine Ophthalmic Solution.Ketorolac Tromethamine Ophthalmic Solution 0.45%Initial U.S. Approval: 1991 RECENT MAJOR CHANGESWarnings and Precautions, Cross-Sensitivity or Hypersensitivity (5.2)                11/2012 INDICATIONS AND USAGEKetorolac Tromethamine Ophthalmic Solution is a nonsteroidal, anti-inflammatory indicated for the treatment of pain and inflammation following cataract surgery. (1) DOSAGE AND ADMINISTRATIONOne drop of Ketorolac Tromethamine Ophthalmic Solution should be applied by the patient to the affected eye twice daily beginning 1 day prior to cataract surgery, and continued through the first 2 weeks of the postoperative period. (2.1) DOSAGE FORMS AND STRENGTHS Ketorolac Tromethamine Solution 4.5 mg/mL in a single-use vial. (3) CONTRAINDICATIONSHypersensitivity to any component of this product (4) WARNINGS AND PRECAUTIONS Delayed healing (5.1) Cross-sensitivity or hypersensitivity (5.2) Increased bleeding time due to interference with thrombocyte aggregation (5.3) Corneal effects including keratitis (5.4) Side EffectsMost common adverse reactions occurring in 1 to 6% of patients were increased intraocular pressure, conjunctival hemorrhage, and vision blurred. (6.1) To report SUSPECTED ADVERSE REACTIONS, Contact Akorn at 1-800-932-5676 or FDA at 1-800-FDA-1088 or www.fda.Gov/Medwatch.

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 KETOROLAC TROMETHAMINE INDICATIONS AND USAGE
• 2 KETOROLAC TROMETHAMINE DOSAGE AND ADMINISTRATION
  • 2.1 Recommended Dosing
  • 2.2 Use with Other Topical Ophthalmic Medications
• 3 DOSAGE FORMS AND STRENGTHS
• 4 KETOROLAC TROMETHAMINE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Delayed Healing
  • 5.2 Cross-Sensitivity or Hypersensitivity
  • 5.3 Increased Bleeding Time
  • 5.4 Corneal Effects
  • 5.5 Contact Lens Wear
• 6 KETOROLAC TROMETHAMINE ADVERSE REACTIONS
  • 6.1 Clinical Studies Experience
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 11 KETOROLAC TROMETHAMINE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Slow or Delayed Healing
  • 17.2 Avoiding Contamination of the Product
  • 17.3 Contact Lens Wear
  • 17.4 Intercurrent Ocular Conditions
  • 17.5 Concomitant Topical Ocular Therapy

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Ketorolac Tromethamine Ophthalmic Solution is indicated for the treatment of pain and inflammation following cataract surgery.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing

Patient Dosing

One drop of Ketorolac Tromethamine Ophthalmic Solution should be applied to the affected eye twice daily beginning 1 day prior to cataract surgery, continued on the day of surgery, and through the first 2 weeks of the postoperative period.

2.2 Use with Other Topical Ophthalmic Medications

Ketorolac Tromethamine Ophthalmic Solution may be administered in conjunction with other topical ophthalmic medications such as alpha-agonists, beta-blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

3 DOSAGE FORMS AND STRENGTHS

4.5 mg/mL ketorolac tromethamine solution (0.45%) in a single-use vial.

4 CONTRAINDICATIONS

Ketorolac Tromethamine Ophthalmic Solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation.

5 WARNINGS AND PRECAUTIONS

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 either have 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 Ketorolac Tromethamine Ophthalmic Solution 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 Contact Lens Wear

Ketorolac Tromethamine Ophthalmic Solution should not be administered while wearing contact lenses.

6 ADVERSE REACTIONS

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

6.1 Clinical Studies Experience

The most common adverse reaction were reported in 1 to 6% of patients and included increased intraocular pressure, conjunctival hyperemia and/or hemorrhage, corneal edema, ocular pain, headache, tearing and vision blurred. Some of these events may be the consequence of the cataract surgical procedure.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects.

Pregnancy Category C: Ketorolac tromethamine, administered during organogenesis, was not teratogenic in rabbits and rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day, respectively. These doses are approximately 600 times and 1700 times higher respectively than the typical human topical ophthalmic daily dose of 0.35 mg (4.5 mg/mL x 0.04 mL/drop, twice daily) to an affected eye on a mg/kg basis. Additionally, when administered to rats after Day 17 of gestation at oral doses up to 1.5 mg/kg/day (approximately 300 times the typical human topical ophthalmic daily dose), ketorolac tromethamine resulted in dystocia and increased pup mortality. There are no adequate and well-controlled studies in pregnant women. Ketorolac Tromethamine Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects: Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of Ketorolac Tromethamine Ophthalmic Solution during late pregnancy should be avoided.

8.3 Nursing Mothers

Because many drugs are excreted in human milk, caution should be exercised when Ketorolac Tromethamine Ophthalmic Solution is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

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

11 DESCRIPTION

Ketorolac Tromethamine Ophthalmic Solution 0.45% is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1), and its molecular weight is 376.40. Its molecular formula is C₁₉H₂₄N₂O₆. Its chemical structure is: