BROMFENAC SODIUM

1 INDICATIONS AND USAGE Bromfenac ophthalmic solution is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. ( 1 ) Bromfenac ophthalmic solution, 0.07% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery.

2 DOSAGE AND ADMINISTRATION Instill one drop into the affected eye once daily beginning 1 day prior to surgery, continued on the day of surgery, and through the first 14 days post-surgery. ( 2.1 ). 2.1 Recommended Dosing One drop of Bromfenac ophthalmic solution should be applied to the affected eye once daily beginning 1 day prior to cataract surgery, continued on the day of surgery, and through the first 14 days of the postoperative period. 2.2 Use with Other Topical Ophthalmic Medications Bromfenac 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 Topical ophthalmic solution: bromfenac 0.07%. Topical ophthalmic solution: bromfenac 0.07%

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The most commonly reported adverse reactions in 3 to 8% of patients were anterior chamber inflammation, foreign body sensation, eye pain, photophobia, and vision blurred. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial 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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most commonly reported adverse reactions following use of bromfenac ophthalmic solution following cataract surgery include: anterior chamber inflammation, foreign body sensation, eye pain, photophobia, and vision blurred. These reactions were reported in 3 to 8% of patients.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on bromfenac ophthalmic solution use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. The systemic exposure to bromfenac following topical ocular administration is low [see Clinical Pharmacology ( 12.3 )]. Consequently, the systemic exposure of a pregnant woman to bromfenac is expected to be minimal following topical ocular administration. However, 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Measurable maternal and fetal plasma drug levels are available with oral and injectable routes of NSAID administration. The maternal plasma level of Bromfenac ophthalmic solution following ocular administration is unknown [see Clinical Pharmacology ( 12.3 )]. Data Animal Data Embryo-fetal lethality and maternal toxicity were produced in rats and rabbits treated with bromfenac during the period of organogenesis at oral doses up to 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. These doses corresponded to a Cmax 90- and 150- times the predicted Cmax at the recommended human ophthalmic dose (RHOD), respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human Cmax at the RHOD), and caused dystocia, increased neonatal mortality, and reduced postnatal growth at 0.9 mg/kg/day (90 times the predicted human Cmax at the RHOD). 8.2 Lactation There are no data on the presence of bromfenac in human milk, the effects on the breastfed infant, or the effects on milk production. The systemic exposure of a breastfeeding woman to bromfenac is expected to be minimalfollowing topical ocular administration, however, the possibility of harm to the breastfed infantcannot be ruled out. The developmental and health benefits of breastfeeding should be considered, along with themother's clinical need for bromfenac ophthalmic solution, and any potential adverse effects on the breastfed infant from bromfenac ophthalmic solution or from the underlying maternal conditions. 8.4 Pediatric Use The safety and effectiveness of bromfenac ophthalmic solution have not been established in pediatric patients. 8.5 Geriatric Use No overall differences in safety or effectiveness of bromfenac ophthalmic solution have been observed between patients 70 years of age and older and younger adult patients.

12.1 Mechanism of Action Bromfenac is a 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 (COX) 1 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.

11 DESCRIPTION Bromfenac ophthalmic solution 0.07 % is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for topical ophthalmic use. Each mL of bromfenac ophthalmic solution contains 0.805 mg bromfenac sodium sesquihydrate (equivalent to 0.7 mg bromfenac free acid). The USAN name for bromfenac sodium sesquihydrate is bromfenac sodium. Bromfenac sodium is designated chemically as sodium [2-amino-3-(4-bromobenzoyl) phenyl] acetate sesquihydrate, with an molecular formula of C 15 H 11 BrNNaO 3 • 1 1⁄2 H 2 O. The chemical structure for bromfenac sodium sesquihydrate is: Bromfenac sodium is a yellow to orange crystalline powder. The molecular weight of bromfenac sodium is 383.17. Bromfenac ophthalmic solution, 0.07 % is supplied as a sterile aqueous 0.07 % solution, with a pH of 7.55 to 8.15. The osmolality of bromfenac ophthalmic solution, 0.07 % is approximately 280 to 340 mOsmol/kg. Each mL of bromfenac ophthalmic solution, 0.07 % contains: Active : Each mL contains bromfenac sodium sesquihydrate 0.0805 %, which is equivalent to bromfenac free acid 0.07 %. Preservative : benzalkonium chloride 0.005 % Inactives : boric acid, edetate disodium (dihydrate), povidone, sodium borate, sodium sulfite, sodium hydroxide to adjust pH, tyloxapol and water for injection USP. Fig-1

16 HOW SUPPLIED/STORAGE AND HANDLING Bromfenac Ophthalmic Solution, 0.07% is supplied in a white low density polyethylene bottle fitted with a white low density polyethylene nozzle and sealed with grey colored high density polyethylene cap with tamper-evident ring as follows: 3 mL in a 5 mL bottle (NDC 68180-433-02) Storage Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [See USP Controlled Room Temperature]. After opening, bromfenac ophthalmic solution 0.07% can be used until the expiration date of the bottle.