DOSAGE & ADMINISTRATION SECTION.

Dosage and Administration. For the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract extraction, one drop of bromfenac ophthalmic solution should be applied to the affected eye(s) two times daily beginning 24 hours after cataract surgery and continuing through the first weeks of the postoperative period.

ADVERSE REACTIONS SECTION.

Adverse Reactions. The most commonly reported adverse experiences reported following use of bromfenac ophthalmic solution after cataract surgery include: abnormal sensation in eye, conjunctival hyperemia, eye irritation (including burning/stinging), eye pain, eye pruritus, eye redness, headache, and iritis. These events were reported in 2-7% of patients.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up to 0.6 mg/kg/day (360 times the recommended human ophthalmic dose [RHOD] of 1.67 ug/kg in 60 kg person on mg/kg/basis, assuming 100% absorbed) and 5.0 mg/kg/day (3000 times RHOD), respectively revealed no significant increases in tumor incidence.Bromfenac did not show mutagenic potential in various mutagenicity studies, including the reverse mutation, chromosomal aberration, and micronucleus tests.Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (540 and 180 times RHOD, respectively).

CLINICAL PHARMACOLOGY SECTION.

Clinical Pharmacology. Mechanism of Action. Bromfenac is nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory activity.The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase and 2. Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure.. Pharmacokinetics. The plasma concentration of bromfenac following ocular administration of bromfenac ophthalmic solution 0.09% in humans is unknown. Based on the maximum proposed dose of one drop to each eye (0.09mg) and PK information from other routes of administration, the systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans.

CLINICAL STUDIES SECTION.

Clinical Trials. Clinical efficacy was evaluated in two randomized, double-masked, vehicle-controlled U.S. trials in which subjects with summed ocular inflammation score >=3 after cataract surgery were assigned to bromfenac ophthalmic solution or vehicle in 2:1 ratio following surgery. One drop of bromfenac ophthalmic solution or vehicle was self-instilled in the study eye twice day for 14 days, beginning the day after surgery. The primary endpoint was reduction of ocular inflammation (to trace inflammation or clearing) assessed 14 days post-surgery using slit lamp binocular microscope. In the intent-to-treat analyses of both studies, significant effect of bromfenac ophthalmic solution on ocular inflammation after cataract surgery was demonstrated (62 to 66% vs. 40 to 48%). An additional efficacy end point was the time required for resolution of ocular pain in subjects who reported pain. Overall, only 20% of the patients undergoing cataract surgery in these trials had pain on the first day after surgery. In these patients, the bromfenac ophthalmic solution group demonstrated statistically significant difference in median time to resolution of ocular pain of days compared to days for patients receiving vehicle.

CONTRAINDICATIONS SECTION.

Contraindications. Bromfenac ophthalmic solution is contraindicated in patients with known hypersensitivity to any ingredient in the formulation.

DESCRIPTION SECTION.

DESCRIPTION. Bromfenac ophthalmic solution 0.09% is sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. Each mL of bromfenac ophthalmic solution contains 1.035 mg bromfenac sodium (equivalent to 0.9 mg bromfenac free acid). Bromfenac sodium is designated chemically as sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate, with an empirical formula of C15H11BrNNaO3 1 1/2 H2O. The structural formula of bromfenac sodium is:Bromfenac sodium is yellow to orange crystalline powder. The molecular weight of bromfenac sodium is 383.17. Bromfenac ophthalmic solution is supplied as sterile aqueous 0.09% solution, with pH of 8.3. The osmolality of bromfenac ophthalmic solution is approximately 300 mOsmol/kg. Each mL of bromfenac ophthalmic solution contains: Active: bromfenac sodium hydrate 0.1035%. Inactives: benzalkonium chloride (0.05 mg/mL), boric acid, disodium edetate (0.2 mg/mL), polysorbate 80 (1.5 mg/mL), povidone (20 mg/mL), sodium borate, sodium sulfite anhydrous (2 mg/mL), sodium hydroxide to adjust the pH, and water for injection, USP.. Chemical Structure.

GENERAL PRECAUTIONS SECTION.

General. All 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.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 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 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.It is recommended that bromfenac ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

GERIATRIC USE SECTION.

Geriatric Use. There is no evidence that the efficacy or safety profiles for bromfenac ophthalmic solution differ in patients 65 years of age and older compared to younger adult patients.

HOW SUPPLIED SECTION.

How Supplied. Bromfenac ophthalmic solution 0.09% is supplied in white LDPE plastic squeeze bottle with 15 mm LDPE white dropper-tip and 15 mm polypropylene gray cap. Tamper evidence is provided with shrink band around the closure and neck area of the package. NDC 54868-6343-02.5 mL in mL container. Storage. Store at 20oC to 25C (68oF to 77F). [See USP Controlled Room Temperature.].

INDICATIONS & USAGE SECTION.

Indications and Usage. Bromfenac ophthalmic solution is indicated for the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract extraction.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. Bromfenac ophthalmic solution should not be administered while wearing contact lenses.

MECHANISM OF ACTION SECTION.

Mechanism of Action. Bromfenac is nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory activity.The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase and 2. Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure.

NONTERATOGENIC EFFECTS SECTION.

Non-Teratogenic Effects. Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), the use of bromfenac ophthalmic solution during late pregnancy should be avoided.

NURSING MOTHERS SECTION.

Nursing Mothers. Caution should be exercised when bromfenac ophthalmic solution is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 2.5 mL Bottle Carton. NDC 54868-6343-0BROMFENAC OPHTHALMIC SOLUTION 0.09%SterileRx only2.5 mL For topical application in the eye. PRINCIPAL DISPLAY PANEL 2.5 mL Bottle Carton.

PEDIATRIC USE SECTION.

Pediatric Use. Safety and efficacy in pediatric patients below the age of 18 have not been established.

PHARMACOKINETICS SECTION.

Pharmacokinetics. The plasma concentration of bromfenac following ocular administration of bromfenac ophthalmic solution 0.09% in humans is unknown. Based on the maximum proposed dose of one drop to each eye (0.09mg) and PK information from other routes of administration, the systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans.

PRECAUTIONS SECTION.

Precautions. General. All 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.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 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 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.It is recommended that bromfenac ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.. Information for Patients. Bromfenac ophthalmic solution should not be administered while wearing contact lenses.. Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up to 0.6 mg/kg/day (360 times the recommended human ophthalmic dose [RHOD] of 1.67 ug/kg in 60 kg person on mg/kg/basis, assuming 100% absorbed) and 5.0 mg/kg/day (3000 times RHOD), respectively revealed no significant increases in tumor incidence.Bromfenac did not show mutagenic potential in various mutagenicity studies, including the reverse mutation, chromosomal aberration, and micronucleus tests.Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (540 and 180 times RHOD, respectively).. Pregnancy. Teratogenic Effects. Pregnancy Category C. Reproduction studies performed in rats at oral doses up to 0.9 mg/kg/day (540 times RHOD) and in rabbits at oral doses up to 7.5 mg/kg/day (4500 times RHOD) revealed no evidence of teratogenicity due to bromfenac. However, 0.9mg/kg/day in rats caused embryo-fetal lethality, increased neonatal mortality, and reduced postnatal growth. Pregnant rabbits treated with 7.5 mg/kg/day caused increased post-implantation loss.There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.. Non-Teratogenic Effects. Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), the use of bromfenac ophthalmic solution during late pregnancy should be avoided.. Nursing Mothers. Caution should be exercised when bromfenac ophthalmic solution is administered to nursing woman.. Pediatric Use. Safety and efficacy in pediatric patients below the age of 18 have not been established.. Geriatric Use. There is no evidence that the efficacy or safety profiles for bromfenac ophthalmic solution differ in patients 65 years of age and older compared to younger adult patients.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects. Pregnancy Category C. Reproduction studies performed in rats at oral doses up to 0.9 mg/kg/day (540 times RHOD) and in rabbits at oral doses up to 7.5 mg/kg/day (4500 times RHOD) revealed no evidence of teratogenicity due to bromfenac. However, 0.9mg/kg/day in rats caused embryo-fetal lethality, increased neonatal mortality, and reduced postnatal growth. Pregnant rabbits treated with 7.5 mg/kg/day caused increased post-implantation loss.There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.. Non-Teratogenic Effects. Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), the use of bromfenac ophthalmic solution during late pregnancy should be avoided.

STORAGE AND HANDLING SECTION.

Storage. Store at 20oC to 25C (68oF to 77F). [See USP Controlled Room Temperature.].

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Pregnancy Category C. Reproduction studies performed in rats at oral doses up to 0.9 mg/kg/day (540 times RHOD) and in rabbits at oral doses up to 7.5 mg/kg/day (4500 times RHOD) revealed no evidence of teratogenicity due to bromfenac. However, 0.9mg/kg/day in rats caused embryo-fetal lethality, increased neonatal mortality, and reduced postnatal growth. Pregnant rabbits treated with 7.5 mg/kg/day caused increased post-implantation loss.There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

WARNINGS SECTION.

Warnings. Contains sodium sulfite, sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.With some NSAIDs, there exists the potential for increased bleeding time due to interference with platelet aggregation. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.