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`Xibrom FDA prescribing information, side effects and uses
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`Xibrom
`
`Generic Name: bromfenac sodium
`Dosage Form: ophthalmic solution
`Visit the Official Site
`
`PAZEO™ (olopatadine hydrochloride ophthalmic solution) 0.7%
`
`Overview
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`Side Effects
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`Dosage
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`Interactions
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`SENJU EXHIBIT 2190
`LUPIN v. SENJU
`IPR2015-01099
`
`
`
`10/22/2015
`Professional
`
`More
`
`Xibrom FDA prescribing information, side effects and uses
`
`Xibrom™ (bromfenac ophthalmic solution) 0.09%
`Sterile
`
`A D V E R TI S E M E N T
`
`Visit the Official Site
`PAZEO™ (olopatadine
`hydrochloride ophthalmic
`solution) 0.7%
`
`Xibrom Description
`Xibrom (bromfenac ophthalmic solution) 0.09% is
`a sterile, topical, nonsteroidal antiinflammatory
`drug (NSAID) for ophthalmic use. Each mL of
`Xibrom contains 1.035 mg bromfenac sodium
`(equivalent to 0.9 mg bromfenac free acid).
`Bromfenac sodium is designated chemically as
`sodium 2amino3(4bromobenzoyl)
`phenylacetate sesquihydrate, with an empirical
`formula of C H BrNNaO • 1½H O. The
`15 11
`3
`2
`structural formula of bromfenac sodium is:
`
`Bromfenac sodium is a yellow to orange
`crystalline powder. The molecular weight of
`bromfenac sodium is 383.17. Xibrom ophthalmic
`solution is supplied as a sterile aqueous 0.09%
`solution, with a pH of 8.3. The osmolality of
`Xibrom ophthalmic solution is approximately 300
`mOsmol/kg. Each mL of Xibrom 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.
`
`Slideshow: Easy On The Eye 8
`Tips for Maintaining Good Eyesight
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`CLINICAL PHARMACOLOGY
`
`Xibrom FDA prescribing information, side effects and uses
`
`Mechanism of Action:
`Bromfenac is a nonsteroidal antiinflammatory
`drug (NSAID) that has antiinflammatory 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 bloodaqueous humor barrier, vasodilation, increased
`vascular permeability, leukocytosis, and increased intraocular pressure.
`
`Pharmacokinetics:
`The plasma concentration of bromfenac following ocular administration of 0.09% Xibrom
`(bromfenac ophthalmic solution) 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 steadystate in humans.
`
`Clinical Trials:
`Clinical efficacy was evaluated in two randomized, doublemasked, vehiclecontrolled U.S.
`trials in which subjects with a summed ocular inflammation score ≥3 after cataract surgery
`were assigned to Xibrom or vehicle in a 2:1 ratio following surgery. One drop of Xibrom or
`vehicle was selfinstilled in the study eye twice a 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 postsurgery using a slit lamp binocular microscope. In the intent
`totreat analyses of both studies, a significant effect of Xibrom on ocular inflammation after
`cataract surgery was demonstrated (6266% vs. 4048%). An additional efficacy endpoint was
`the time required for resolution of ocular pain in subjects who reported pain. Overall, only 20%
`of patients undergoing cataract surgery in these trials had pain on the first day after surgery. In
`these patients, the Xibrom group demonstrated a statistically significant difference in median
`time to resolution of ocular pain of 2 days compared to 4 days for patients receiving vehicle.
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`Xibrom FDA prescribing information, side effects and uses
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`INDICATIONS AND USAGE
`Xibrom ophthalmic solution is indicated for the treatment of postoperative inflammation and
`reduction of ocular pain in patients who have undergone cataract extraction.
`
`CONTRAINDICATIONS
`Xibrom ophthalmic solution is contraindicated in patients with known hypersensitivity to any
`ingredient in the formulation.
`
`Warnings
`Contains sodium sulfite, a sulfite that may cause allergictype reactions including anaphylactic
`symptoms and lifethreatening 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 crosssensitivity 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.
`
`Precautions
`
`General:
`All topical nonsteroidal antiinflammatory drugs (NSAIDs) may slow or delay healing. Topical
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`Xibrom FDA prescribing information, side effects and uses
`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 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 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 Xibrom 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:
`Xibrom ophthalmic solution should not be administered while wearing contact lenses.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`Longterm 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
`µg/kg in 60 kg person on a 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 embryofetal lethality,
`
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`Xibrom FDA prescribing information, side effects and uses
`increased neonatal mortality, and reduced postnatal growth. Pregnant rabbits treated with 7.5
`mg/kg/day caused increased postimplantation loss.
`
`There are no adequate and wellcontrolled 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.
`
`NonTeratogenic Effects:
`Because of the known effects of prostaglandin biosynthesisinhibiting drugs on the fetal
`cardiovascular system (closure of ductus arteriosus), the use of Xibrom ophthalmic solution
`during late pregnancy should be avoided.
`
`Nursing Mothers:
`Caution should be exercised when Xibrom ophthalmic solution is administered to a 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 Xibrom differ in patients 65 years of
`age and older compared to younger adult patients.
`
`Adverse Reactions
`The most commonly reported adverse experiences reported following use of Xibrom 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 27% of patients.
`
`Clinical Practice:
`The following events have been identified during postmarketing 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 events, 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
`PRECAUTIONS, General: ).
`
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`Xibrom FDA prescribing information, side effects and uses
`
`Xibrom Dosage and Administration
`For the treatment of postoperative inflammation in patients who have undergone cataract
`extraction, one drop of Xibrom ophthalmic solution should be applied to the affected eye(s) two
`times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks
`of the postoperative period.
`
`How is Xibrom Supplied
`Xibrom™ (bromfenac ophthalmic solution) 0.09% is supplied in a white LDPE plastic squeeze
`bottle with a 15 mm LDPE white droppertip and 15 mm polypropylene gray cap as follows:
`
`NDC 6742500450
`
`5 mL in 10 cc container
`
`NDC 6742500412
`
`2.5 mL in 7.5 cc container
`
`Storage
`Store at 1525°C (5977°F)
`
`Rx Only
`
`U.S. Patent No. 4,910,225
`
`Manufactured for: ISTA Pharmaceuticals, Inc.
`Irvine, CA 92618
`
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`
`
`10/22/2015
`by: Bausch & Lomb Incorporated
`Tampa, FL 33637
`
`Xibrom FDA prescribing information, side effects and uses
`
`Under license from: Senju Pharmaceutical Co., Ltd.
`Osaka, Japan 5410046
`
`Revised November 2008
`Printed in USA
`©
`COPYRIGHT ISTA Pharmaceuticals, Inc. All rights reserved.
`
`PRINCIPAL DISPLAY PANEL
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`Xibrom FDA prescribing information, side effects and uses
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`NDC 6742500412
`
`Xibrom (bromfenac ophthalmic solution) 0.09%
`™
`
`Sterile 2.5 mL
`Rx only
`Twice Daily
`
`Each mL of Xibrom ophthalmic solution contains:
`
`Active: bromfenac sodium hydrate 0.1035% equivalent to 0.09% bromfenac free acid.
`
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`Xibrom FDA prescribing information, side effects and uses
`Inactives: benzalkonium chloride (0.05 mg/mL), boric acid, disodium edetate (0.2 mg/mL),
`polysorbate 80 (1.5mg/mL), povidone (20mg/mL), sodium borate, sodium sulfite anhydrous
`(2mg/mL), sodium hydroxide to adjust the pH, and water for injection, USP.
`
`This product is sterile when manufactured and should be dispensed in the original unopened
`container. Instruct patient on precautions to avoid contamination.
`
`For topical application in the eye.
`Usual adult dosage:
`One drop in the affected eye(s) two times daily. See accompanying prescribing information.
`
`Store at 1525°C (5977°F).
`
`Xibrom
`bromfenac sodium solution
`Product Information
`Product Type
`
`Item Code (Source)
`
`DEA Schedule
`
`NDC:67425
`004
`
`
`Basis of Strength
`BROMFENAC SODIUM
`
`Strength
`1.035 mg in 1 mL
`
`Strength
`0.05 mg in 1 mL
`11 mg in 1 mL
`0.2 mg in 1 mL
`1.5 mg in 1 mL
`20 mg in 1 mL
`11 mg in 1 mL
`
`2 mg in 1 mL
`
`
`HUMAN PRESCRIPTION DRUG
`LABEL
`Route of Administration
`OPHTHALMIC
`Active Ingredient/Active Moiety
`Ingredient Name
`BROMFENAC SODIUM (BROMFENAC)
`Inactive Ingredients
`Ingredient Name
`BENZALKONIUM CHLORIDE
`BORIC ACID
`EDETATE DISODIUM
`POLYSORBATE 80
`POVIDONE
`SODIUM BORATE
`SODIUM HYDROXIDE
`SODIUM SULFITE
`WATER
`Packaging
`#Item Code
`1 NDC:6742500450
`1
`2 NDC:6742500412
`2
`Marketing Information
`Marketing Category Application Number or Monograph Citation
`NDA
`NDA021664
`Labeler Ista Pharmaceuticals, Inc (957212350)
`Establishment
`Name
`Ista Pharmaceuticals, Inc
`Establishment
`Name
`Bausch & Lomb Incorporated
`
`Package Description
`1 BOTTLE, DROPPER (BOTTLE) in 1 CARTON
`5 mL in 1 BOTTLE, DROPPER
`1 BOTTLE, DROPPER (BOTTLE) in 1 CARTON
`2.5 mL in 1 BOTTLE, DROPPER
`
`Marketing Start Date Marketing End Date
`01/05/2005
`
`ID/FEI
`957212350
`
`Operations
`ANALYSIS
`
`Operations
`ANALYSIS, MANUFACTURE
`
`Address
`
`Address
`
`ID/FEI
`222207751
`
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`
`10/16
`
`Page 10 of 16
`
`
`
`10/22/2015
`Revised: 06/2009
`
`
`Xibrom FDA prescribing information, side effects and uses
`
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`Side Effects
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`Xibrom (AHFS Monograph)
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`Other brands: Prolensa, Bromday
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`10/22/2015
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`Xibrom FDA prescribing information, side effects and uses
`
` Related treatment guides
`Postoperative Ocular Inflammation
`
`DRUG STATUS
`
`Availability
`Prescription only
`
`Pregnancy Category
`Risk cannot be ruled out
`
`CSA Schedule
`Not a controlled drug
`
`Approval History
`Drug history at FDA
`
`
`
`
`
`
`
`Drug Class
`Ophthalmic antiinflammatory agents
`
`A D V E R TI S E M E N T
`
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`Xibrom FDA prescribing information, side effects and uses
`
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`flurbiprofen ophthalmic, Ilevro, Prolensa, Acular, Alrex, Nevanac, bromfenac ophthalmic,
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`CONSUMER UPDATES
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`10/22/2015
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`Xibrom FDA prescribing information, side effects and uses
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