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Bromfenac Ophthalmic Solution, 0.07%, 0.09%

TABLE OF CONTENTS

 

1. DESCRIPTION 6. ADVERSE REACTIONS
2. INDICATIONS AND USAGE 8. USE IN SPECIFIC POPULATIONS
3. DOSAGE AND ADMINISTRATION 10. MECHANISM OF ACTION
4. CONTRAINDICATIONS 12. PHARMACOKINETICS
5. WARNINGS AND PRECAUTIONS 13. HOW SUPPLIED/STORAGE AND HANDLING

 

1. DESCRIPTION

Bromfenac ophthalmic solution 0.09% is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. Bromfenac sodium is designated chemically as sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate, with the structural formula for bromfenac sodium is:

Molecular formula: C15H11BrNNaO3 • 1½H2O - Molecular weight: 383.17

Bromfenac sodium is a yellow to orange crystalline powder.

Bromfenac ophthalmic solution is supplied in two strengths, 0.07% (PROLENSA®) and 0.09% (BROMDAY®).

Bromfenac ophthalmic solution, 0.07% (PROLENSA®):

Bromfenac ophthalmic solution is supplied as a sterile aqueous 0.07% solution, with a pH of 7.8. The osmolality of bromfenac ophthalmic solution is approximately 300 mOsmol/kg.

Each mL of bromfenac ophthalmic solution 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, povidone, sodium borate, sodium sulfite, tyloxapol, sodium hydroxide to adjust pH and water for injection, USP.

Bromfenac ophthalmic solution, 0.09% (BROMDAY®):

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: 1.035 mg bromfenac sodium (0.1035%, equivalent to 0.9 mg bromfenac free acid).

Preservative: benzalkonium chloride (0.05 mg/mL)

Inactives: 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 pH and water for injection, USP.

Bromfenac ophthalmic solution, 0.075% (BROMSITE®):

BromSite is a greenish-yellow to dark yellow viscous liquid with an osmolality of approximately 290 mOsmol/kg.

Active: Each mL contains bromfenac sodium sesquihydrate 0.81 mg, which is equivalent to bromfenac free acid 0.76 mg.

Preservative: benzalkonium chloride 0.005%.

Inactives: boric acid, sodium borate, citric acid anhydrous, sodium citrate dihydrate, poloxamer 407, polycarbophil, sodium chloride, edetate disodium dihydrate, sodium hydroxide (to adjust pH to 8.3), and water for injection (USP).

2. INDICATIONS AND USAGE

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

3. DOSAGE AND ADMINISTRATION

3.1 Recommended Dosing

One drop of bromfenac ophthalmic solution should be applied to the affected eye two times daily (morning and evening) 1 day prior to surgery, the day of surgery, and 14 days postsurgery.

3.2 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.

4. CONTRAINDICATIONS

None.

5. WARNINGS AND PRECAUTIONS

5.1 Slow or Delayed Healing

All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including BromSite (bromfenac ophthalmic solution) 0.075%, 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 Potential for Cross-Sensitivity

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs, including BromSite (bromfenac ophthalmic solution) 0.075%. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

5.3 Increased Bleeding Time of Ocular Tissue

With some NSAIDs, including BromSite (bromfenac ophthalmic solution) 0.075%, 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 BromSite be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

5.4 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, including BromSite (bromfenac ophthalmic solution) 0.075%, 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 postsurgery may increase patient risk for the occurrence and severity of corneal adverse events.

5.5 Contact Lens Wear

BromSite should not be administered while wearing contact lenses. The preservative in BromSite, benzalkonium chloride, may be absorbed by soft contact lenses.

6. ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:

• Slow or Delayed Healing [see Warnings and Precautions (5.1)]

• Potential for Cross-Sensitivity [see Warnings and Precautions (5.2)]

• Increased Bleeding Time of Ocular Tissue [see Warnings and Precautions (5.3)]

• Keratitis and Corneal Reactions[see Warnings and Precautions (5.4)]

• Contact Lens Wear [see Warnings and Precautions (5.5)]

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 in 1-8% of patients were: anterior chamber inflammation, headache, vitreous floaters, iritis, eye pain and ocular hypertension.

8. USE IN SPECIFIC POPULATIONS

8.1 Usage in Pregnancy

Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies with bromfenac 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. 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.

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. 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 differ in patients 65 years of age and older compared to younger adult patients.

10. 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. 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 steadystate in humans.

13. HOW SUPPLIED/STORAGE AND HANDLING

1) How Available:

a) Brand names:

BROMDAY, by ISTA Pharmaceuticals.

BROMSITE, by Sun Pharmaceutical Industries.

PROLENSA, by Bausch & Lomb.

XIBROM, by Bausch & Lomb.

b) Generic drugs: None.

2) How Supplied:

BROMDAY (bromfenac ophthalmic solution) 0.09% is supplied in a white LDPE plastic squeeze bottle with a 15 mm LDPE white dropper-tip and 15 mm polypropylene gray cap as follows:

1.7 mL in 7.5 mL container (NDC 67425-999-17)

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BROMSITE (bromfenac ophthalmic solution) 0.075% is supplied in white opaque low density polyethylene (LDPE) plastic bottles and translucent dropper tips, and gray high density polyethylene (HDPE) eyedropper caps. A white tamper evident overcap is provided. Each bottle is provided in a sealed foil laminated pouch.

5 mL in a 7.5 mL bottle (NDC No. 57664-754-41)

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PROLENSA (bromfenac ophthalmic solution) 0.07% is supplied in a white LDPE plastic squeeze bottle with a 15 mm LDPE white dropper-tip and 15 mm polypropylene gray cap as follows:

• 1.6 mL in a 7.5 mL container (NDC 24208-602-01)

• 3 mL in a 7.5 mL container (NDC 24208-602-03)

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Xibrom (bromfenac ophthalmic solution) 0.09% is supplied in a white LDPE plastic squeeze bottle with a 15 mm LDPE white dropper-tip and 15 mm polypropylene gray cap as follows:

2.5mL in 7.5mL container (NDC 67425-004-12)

5mL in 10mL container (NDC 67425-004-50)

3) Storage and Handling:

Store at 15° to 25°C (59° to 77°F). [see USP Controlled Room Temperature].

Rx only

Rev 04/16