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Bromfenac Ophthlamic Solution

Generic Name: bromfenac sodium
Dosage Form: ophthlamic solution

Indications and Usage for Bromfenac Ophthlamic Solution

Bromfenac Ophthalmic Solution, 0.09% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery.

Bromfenac Ophthlamic Solution Dosage and Administration

2.1 Recommended Dosing

For the treatment of postoperative inflammation in patients who have undergone cataract extraction, 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.

Dosage Forms and Strengths

Topical ophthalmic solution: bromfenac 0.09%.

Contraindications

None.

Warnings and Precautions

5.1 Sulfite Allergic Reactions

Contains sodium sulfite, a 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 non asthmatic people.

5.2 Slow or Delayed Healing

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.

5.3 Potential for Cross-Sensitivity

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.

5.4 Increased Bleeding Time

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.

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.

5.5 Keratitis and Corneal Reactions

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.

Post-marketing 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.

Post-marketing 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.

5.6 Contact Lens Wear

Bromfenac ophthalmic solution should not be administered while wearing contact lenses. Remove contact lenses prior to instillation of bromfenac ophthalmic solution. The preservative in bromfenac ophthalmic solution, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of bromfenac ophthalmic solution.

Adverse Reactions

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 reported following use of bromfenac 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 to 7% of patients.

6.2 Post-Marketing Experience

The following reactions have been identified during post-marketing use of bromfenac ophthalmic solution 0.09% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to topical bromfenac ophthalmic solution 0.09% or a combination of these factors, include corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown. [see Warnings and Precautions(5.5)]

USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

Risk Summary

There are no adequate and well-controlled studies with bromfenac ophthalmic solution in pregnant women. No malformations were observed in reproduction studies in rats and rabbits with oral doses of bromfenac at exposures up to 150 times (rats) and 90 times (rabbits) the predicted human systemic exposure; however, both embryolethality and maternal toxicity were observed at the highest dose exposures. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration [see Clinical Pharmacology (12.3)]. 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.

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 following ocular administration is unknown [see Clinical Pharmacology (12.3)].

Animal Data

Reproduction studies performed in rats at oral doses of bromfenac up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and rabbits at oral doses up to 7.5 mg/kg/day (150 times the predicted human systemic exposure) produced no drug-related malformations in reproduction studies. However, embryo-fetal lethality and maternal toxicity were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human exposure), and caused dystocia, increased neonatal mortality and reduced postnatal growth at 0.9 mg/kg/day.

8.3 Nursing Mothers

It is not known if bromfenac is present in human milk. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration [see Clinical Pharmacology (12.3)]. Based on the low level of systemic exposure, it is unlikely that bromfenac would be detected in human milk using available assays. Caution should be exercised when bromfenac ophthalmic solution is administered to a nursing woman.

8.4 Pediatric Use

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

8.5 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.

Bromfenac Ophthlamic Solution Description

Bromfenac Ophthalmic Solution, 0.09% is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. Each mL of Bromfenac Ophthalmic Solution, 0.09% contains 1.035 mg bromfenac sodium sesquihydrate (equivalent to 0.9 mg bromfenac free acid). Bromfenac sodium sesquihydrate is designated chemically as sodium 2-amino-3-(4-bromobenzoyl) phenyl acetate sesquihydrate, with an empirical formula of C15H11BrNNaO33/2 H2O. The structural structure for bromfenac sodium sesquihydrate is:

Bromfenac sodium sesquihydrate is a yellow or orange yellow crystalline powder. The molecular weight of bromfenac sodium sesquihydrate is 383.17. Bromfenac Ophthalmic Solution is supplied as a sterile aqueous 0.09% solution, with a 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 sesquihydrate 0.1035%

Preservative: benzalkonium chloride (0.05 mg/mL)

Inactives: boric acid, edetate disodium dihydrate, polysorbate 80, povidone, sodium borate, sodium sulfite anhydrous, sodium hydroxide to adjust pH and water for injection.

Bromfenac Ophthlamic Solution - Clinical Pharmacology

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 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.

12.3 Pharmacokinetics

The plasma concentration of bromfenac following ocular administration of 0.09% bromfenac ophthalmic solution in humans is unknown. Based on the maximum proposed dose of one drop to the eye (0.045 mg) 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.

Nonclinical Toxicology

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 (systemic exposure 30 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and 5 mg/kg/day (340 times the predicted human systemic exposure), respectively revealed no significant increases in tumor incidence. Bromfenac did not show mutagenic potential invarious 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 (systemic exposure 90 and 30 times the predicted human exposure, respectively).

Clinical Studies

14.1 Ocular Inflammation and Pain following cataract surgery

Clinical efficacy was evaluated in three randomized, double-masked, placebo controlled trials in which subjects requiring cataract surgery were assigned to bromfenac ophthalmic solution or placebo. Patients were dosed with one drop per eye starting the day before surgery and continuing for 14 days. The primary endpoint was clearing of ocular inflammation by day 15. An additional efficacy endpoint was the number of patients who were pain free on day 1 after cataract surgery.

In 2 of the 3 studies, bromfenac ophthalmic solution had statistically significant higher incidence of completely clearing inflammation (46-47% vs. 25-29%) and also had a statistically significant higher incidence of subjects that were pain free at day 1 post cataract surgery (83-89% vs. 51-71%).

How Supplied/Storage and Handling

Bromfenac Ophthalmic Solution, 0.09% is supplied in a white opaque LDPE ophthalmic bottle with white translucent LDPE ophthalmic dropper and grey opaque HDPE ophthalmic cap with sealing tape as follows:

1.7 mL in 5 mL bottle as a Single pack (1 bottle / carton) – NDC 60505-0595-5

1.7 mL in 5 mL bottle as a Twin pack (2 bottles / carton) – NDC 60505-0595-6

STORAGE

Store at 20° - 25°C (68° - 77°F) [See USP Controlled Room Temperature].   

Patient Counseling Information

17.1 Slowed or Delayed Healing

Advise patients of the possibility that slow or delayed healing may occur while using NSAIDs.

17.2 Sterility of Dropper Tip

Advise patients to not touch dropper tip to any surface, as this may contaminate the contents.

Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery.

17.3 Concomitant Use of Contact Lenses

Advise patients that contact lenses should not be worn during the use of this product. The preservative in bromfenac ophthalmic solution, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of bromfenac ophthalmic solution.

17.4 Concomitant Topical Ocular Therapy

Advise patients that if more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart.

Manufactured by: Manufactured for:
Apotex Inc. Apotex Corp.
Toronto, Ontario Weston, Florida
Canada, M9L 1T9 33326
321809 February 2014

Bromfenac Ophthalmic Solution, 0.09%

Bottle

1.7 mL

Once Daily

Rx Only

Bromfenac Ophthalmic Solution, 0.09%

Carton

1.7 mL

Once Daily

Rx Only

BROMFENAC OPHTHALMIC SOLUTION, 0.09% 
bromfenac ophthalmic solution, 0.09% solution/ drops
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:60505-0595
Route of Administration OPHTHALMIC DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Bromfenac Sodium (Bromfenac) Bromfenac 1.035 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
Benzalkonium Chloride  
Boric Acid  
Edetate Disodium  
Polysorbate 80  
Povidone  
Sodium Borate  
Sodium Sulfite  
Sodium Hydroxide  
Water  
Packaging
# Item Code Package Description
1 NDC:60505-0595-5 1 BOTTLE, DROPPER in 1 CARTON
1 1.7 mL in 1 BOTTLE, DROPPER
2 NDC:60505-0595-6 2 BOTTLE, DROPPER in 1 CARTON
2 1.7 mL in 1 BOTTLE, DROPPER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA202620 06/23/2014
Labeler - Apotex Corp. (845263701)
Registrant - Apotex Inc. (209429182)
Establishment
Name Address ID/FEI Operations
Apotex Inc. 255092496 analysis(60505-0595), manufacture(60505-0595)
Revised: 05/2017
 
Apotex Corp.
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