OCUFEN®
`(flurbiprofen sodium ophthalmic solution, USP) 0.03°/o
`sterile
`
`DESCRIPTION
`OCUFEN® (flurbiprofen sodium ophthalmic solution, USP) 0.03% is a sterile topical nonsteroidal
`anti-inflammatory product for ophthalmic use.
`Chemical Name: Sodium (±)-2-(2-fluoro-4-biphenylyl) propionate dihydrate.
`Structural Formula:
`
`OH
`
`flurbiprofen sodium
`
`Contains:
`Active: flurbiprofen sodium 0.03% (0.3 mg/ml).
`Preservative: thimerosal 0.005%.
`Inactives: polyvinyl alcohol 1.4%; edetate disodium; potassium chloride; sodium chloride; sodium citrate;
`citric acid; and purified water. May also contain hydrochloric acid and/or sodium hydroxide to adjust the pH.
`The pH of OCUFEN® ophthalmic solution is 6.0 to 7.0.
`
`CLINICAL PHARMACOLOGY
`Flurbiprofen sodium is one of a series of phenylalkaRoic acids that have shown analgesic, antipyretic, and
`anti-inflammatory activity in animal inflammatory diseases. Its mechanism of action is believed to be through
`inhibition of the cyclo-oxygenase enzyme that is essential in the biosynthesis of prostaglandins.
`Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular
`inflammation. In studies performed on animal eyes, prostaglandins have been shown to produce disruption of
`the blood-aqueous humor barrier, vasodilatation, increased vascular permeability, leukocytosis, and increased
`intraocular pressure.
`Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting
`the iris sphincter indepencfently of cholinergic mechanisms. In clinical studies, OCUFEN® has been shown to
`inhibit the miosis induced during the course of cataract surgery.
`Results from clinical studies indicate that flurbiprofen sodium has no significant effect upon intraocular
`pressure.
`
`INDICATIONS AND USAGE
`OCUFEN® ophthalmic solution is indicated for the inhibition of intraoperative miosis.
`
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`SENJU EXHIBIT 2053
`LUPIN v. SENJU
`IPR2015-01099
`
`

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`CONTRAINDICATIONS
`
`OCUFEN® ophthalmic solution is contraindicated in individuals who are hypersensitive to any components of
`the medication.
`
`WARNINGS
`With nonsteroidal anti-inflammatory drugs, there exists the potential for increased bleeding due to interference
`with thrombocyte aggregation. There have been reports that OCUFEN® ophthalmic solution may cause
`increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
`There exists the potential for cross-sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory
`drugs. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities
`to these drugs.
`
`PRECAUTIONS
`General: Wound healing may be delayed with the use of OCUFEN® (flurbiprofen sodium ophthalmic solution,
`USP) 0.03%.
`It is recommended that OCUFEN® be used with caution in surgical patients with known bleeding tendencies or
`who are receiving other medications which may prolong bleeding time.
`Drug interactions: Interaction of OCUFEN® ophthalmic solution with other topical ophthalmic medicatiOOs
`has not been fully investigated.
`Although clinical studies with acetylcholine chloride and animal studies with acetylcholine chloride or carbachol
`revealed no interference, and there is no known pharmacological basis for an interaction, there have been
`reports that acetylcholine chloride and carbachol have been ineffective when used in patients treated with
`OCUFEN®.
`Carcinogenesis, Mutagenesis, Impairment of fertility: Long-term studies in mice and/or rats have shown
`no evidence of carcinogenicity with flurbiprofen.
`Long-term mutagenicity studies in animals have not been performed.
`Pregnancy:
`Pregnancy category C: Flurbiprofen has been shown to be embryocidal, delay parturition, prolong gestation,
`reduce weight, and/or slightly retard growth of fetuses when given to rats in daily oral doses of 0.4 mg/kg
`(approximately 190 times the human daily topical dose) and above. There are no adequate and well(cid:173)
`controlled studies in pregnant women.
`OCUFEN® ophthalmic solution should be used during pregnancy only if the potential benefit justifies the
`potential risk to the fetus. --
`Nursing mothers: It is not known whether this drug is excreted in human milk. Because many drugs are
`excreted in human milk and because of the potential for serious adverse reactions in nursing infants from
`flurbiprofen sodium, a decision should be made whether to discontinue nursing or to discontinue the drug,
`taking into account the importance of the drug to the mother.
`Pediatric use: Safety and effectiveness in pediatric patients have not been established.
`Geriatric use: No overall differences in safety or effectiveness have been observed between elderly and
`younger patients.
`
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`

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`ADVERSE REACTIONS
`
`Transient burning and stinging upon instillation and other minor symptoms of ocular irritation have been
`reported with the use of OCUFEN® ophthalmic solution. Other adverse reactions reported with the use of
`OCUFEN® include: fibrosis, miosis, and mydriasis.
`Increased bleeding tendency of ocular tissues in conjunction with ocular surgery has also been reported.
`
`OVERDOSAGE
`Overdosage will not ordinarily cause acute problems. If accidentally ingested, drink fluids to dilute.
`
`DOSAGE AND ADMINISTRATION
`A total of four (4) drops of OCUFEN® ophthalmic solution should be administered by instilling one (1) drop
`approximately every 1/2 hour beginning 2 hours before surgery.
`
`HOW SUPPLIED
`OCUFEN® (flurbiprofen sodium ophthalmic solution, USP) is available for topical ophthalmic administration as
`a 0.03% sterile solution, and is supplied in a white opaque low density polyethylene bottle with a controlled
`dropper tip and a white high impact polystyrene cap in the following size:
`2.5 ml - NDC 11980-801-03
`
`Note: Store at room temperature.
`Rx only
`Revised May 2001
`® Registered trademarks of Allergan, Inc
`Allergan, Inc. Irvine, California 92612, U.S.A.
`© 2001 Allergan, Inc.
`
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`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`--------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Linda Ng
`8/17/01 06:39:46 PM
`
`
`
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