Borrower: JNF
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`00ill:3
`
`Patron:
`Journal Title: Physicians‘ desk reference ' PDR.
`
`Volume:
`Issue:
`Month/Year: 2008Pages: 532—533, plus
`title/verso
`
`llillliillllillillllllliiliilllllilllill
`VofIllinoisChica
`
`
`ILLiadTN:658798
`Universit
`
`a
`
`Article Author:
`Article Title: Entries for Patanol and Pataday
`
`Imprint: Oradell, NJ : Medical Economics Co.
`Montvale, NJ 1 Thomson PDR Montvale, NJ : PDR
`Network
`
`mber
`
`iliiliiiilllillilililiillliilllllllmull
`
`59124
`
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`|PR20
`
`-18 01020 and |PR2018—01021, Exhibit 1011 Page 1
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 1
`
`

`

`7i
`
`Clprodex—Cont.
`
`Esr rmlims
`
`Ear ungvslzcn
`
`Adverse Event
`
`Incidence IX=537I
`
`
`
`Superizpusid ear infection
`
`
`
`.
`3
`
`
`
`The {LL—0‘15: Inaunt-st-«elated adu-ne cunts were each
`npcrzrdIn :1 5:31.11e patient; ear dad:1’n; deer!med Inzu-
`mg, and r3! di‘wflll'f ltmglmgv.
`DOSAGE AND ADSIINISTILATION
`_
`ClPflODEXS OTIC SHOULD BE SNAKEN WELL IMP-IEO]:
`_?
`Arm arson: USE
`CII’IIOIIEXE
`in winning 3 mg'mL (3000 1:3}le l
`cfn 9.3.3511 and I czg'ml. dexnmellinscne
`Acute Otiiis Media in pediatric p-Iicnrs wiIh rympanos-
`torny tubes: The nmmrncndtd dosage regimen for the
`
`"rat” ot a! mute 011m media in pdmtric palienls Iago 6
`
`1::
`its and 0313““ through I) mpnnustumy tubes is:
`I'm-r drops '0.” 1111.. 0.42 mg ciprofloxarin. 0.14 In}:
`d!~X.1:::cll:Ai(-:ev installed Into 1l:e 35!}de our twine daily
`for sown days The suspvnsion should be warmed by held.
`in: the bottle in the hand for one or Wm minutes to amid .,
`‘
`d:::::c‘s. “Izivh may woult from the imtillaiion ofn cold '
`suspension The patient should lu- With the affrctcd car up
`ward. and tlzrn the drops should be instilled. The tragus
`should then bc pumpr'd 5 times by pushing inward to {anl‘
`irate penetration oftlif’ drops into the middle car. This pr)
`sition should It maintained {or 60 mods. llrnuit. if no
`essary. for the opposite ear. Discard unust‘d portion afirr
`thrrapy is mmrlt trd
`Acute 01in; Enema: Tho recommended dosage- wmmm
`fur thc trrauzzcnl ofacutc nmis ”tr-ma is: For pancake: logo
`6 months and olden: Four drops '0.“ ml.. 0.42 nix
`nrmflomc‘in. 0.1-! mg dcxnmethnsnnol Instillcd into the III-
`fffinl cor twice dflll)‘ for seven days. The suspension should
`he warmed by holding the bottle in the hand for one or hm
`minutes to amid dizzincss. which may result from the in-
`stillation of a cold suspension. The patimt should lie with
`the aft-dud par upward. and thcn the drops should be in~
`slillrd This position should he maintainn‘l for 60 seconds to
`facilitate penetration of the drops into the ear canal. Rc-
`pent. if necrssan‘. for the opposite ear. Discard unusul por-
`tion nflc! therapy Is completed.
`HOW SUPPLIED
`CII’RODEXT'J lcipmflnxarin 0.3"; and dexamethasone 0.1””
`Sterile Utic Suspension is supplied as follows: 7.5 mL fill in
`a DROP-TAINER’E system. The DROP-TAINERE system
`consists of a natural polyethylene brittle and natural plug.
`with a white polypmpylene closure. Tamper evidence is pm
`vidcd with a shrink band around the closure and neck area
`ofthe package.
`XDC 0065553302. 7.5 mL fill
`Storage:
`Store at controlled room temperature, 15°C to 30‘C (59’F to
`86:5. Avoid freezing. Protect from light.
`CLINICAL STUDIES
`In a randomized, multicenter. controlled clinical trial,
`CIPRODEXE Otic dosed 2 times per day for 7 days demon-
`strated clinical cures in the per protocol analysis in 86% of
`AOMT patients compared to 79’} for ofloxacin solution.
`0.3%. dosed 2 times per day for 10 days. Among culture pos-
`itive patients. clinical cures were 90’»? for CIPRODEX® Otic
`compared to 79’7: for ofloxacin solution, 0,3’71. Microbiologi-
`cal eradication rates for these patients in the same clinical
`trial were 9l’z? for CIPRODEX® Otic compared to 82% for
`ofioxacin solution, 0.3%. In 2 randomized multicenter. con-
`trolled clinical trials. CIPRODEX® Otic dosed 2 times per
`day {or 7 days demonstrated clinical cures in 87% and 94%
`of per protocol evaluable AOE patients, respectively, com-
`pared to 84% and 89"1c, respectively, for otic suspension con-
`taining neomycin 0.35%, polymyxin B 10,000 IU/mL and
`hydrocortisone 1.0% (neolpolnyC). Among culture positive
`patients clinical cures were 86% and 92% for CIPRODEX®
`Otic compared to 84% and 89%, respectively, for nee/poly}
`HC. Microbiological eradication rates for these patients in
`the same clinical trials were 86% and 92% for CIPRODEX®
`Otic
`compared to 85% and 85%,
`respectively,
`for
`neolpoly/HC.
`REFERENCES
`1. CampoliRichards DM, Monk JP, Price A, Benfield P
`Todd PA, Ward A. Ciprofloxacin: A review of its antibac-
`terial activity, ph armamkinetic properties and therapeu-
`tic use. Drugs 19883523737447.
`
`PHYSICIANS' DESK REFERENCE®
`532/ALCON
`Il
`l How should ctPRODEXG Oil: bu given?
`1. Wash lands
`The person giving CIPRODEX®
`Otic should wash his/her hands
`with soap and water.
`
`Hold the bottle of CII’IIODEX®
`Otic in the hand for one or two min-
`utcs to warm the xuspcnsion. than
`shake well.
`
`The person receiving CII’ROI)BX®
`Otic should lie on Iris/her side with
`the infmcd car up.
`
`Patients should have 4 drops of
`CII’RODEXG) Otic put into the in-
`fected car. The tip of the bottle
`should not touch the fingers or the
`car or any other surfaces.
`
`
`
`2. Warm BI Ihakl bottle
`
`3Il
`
`
`
`BE SURE TO FOLLOW INSTRUCTIONS BELOW FOR THE
`PATIENTS SPECIFIC EAR INFECTION.
`4. For Patients with Middle Ear Inlection with Tubes:
`While
`the
`person
`receiving
`CIPRODEX® Otic lies on his/her
`side. the person giving the drops
`should gently press the tragus (see
`diagram) 5 times in a pumping mo-
`tion. This will allow the drops to
`pass through the tube in the ear-
`
`drum and into the middle ear.
`nal.
`both ears are infected.
`
`While the person receiving the
`drops lies on his/her side. the per-
`son giving the drops should gently
`pull the outer ear lobe upward and
`backward. This will allow the ear
`drops to flow down into the ear ca-
`
`The person who received the ear
`drops should remain on his/her side
`for at least 60 seconds.
`Repeat Steps 2-5 for the other ear if
`
`PA'I'ADAYT"I
`R
`lolopatadine hydrochloride ophthalmic solution) 0.2%
`DESCRIPTION
`ophthalmic
`hydrochloride
`PATADAYT‘“
`(olopatadine
`solution) 0.2% is a sterile ophthalmic solution containing
`olopatadine for
`topical administration to the eyes.
`Olopatadine hydrochloride is a white, crystalline, water-
`soluble powder with a molecular weight of 373.88 and a mo-
`lecular formula of Cle23N03 0 HCl. The chemical struc-
`tureIs presented below:
`propyl-
`Chemical Name:
`111-[(Z)-~34Dimethylamino)
`idenel6-ll—dihydrodibenzlb,el oxepin2-acetic acid, hydro-
`chloride.
`Each mL of PATADAYTM solution contains: Active: 2.22 mg
`
`1 Dlopatadine hydrochloride equivalent to 2 mg olopatadine
`Inactives: povidone; dibasic sodium phOSphaoe; sodium chlo-
`ride; edetate disodium; benzalkonium chloride 0.01%
`(preservative) hydrochloric acid I sodium hydroxide ~(adjust
`pH); and purified water.
`'
`
`
`
`If an allergic reaction to CIPRODEX® Otic occurs, stopus-
`ing the product and contact your doctor.
`DO NOT TAKE BY MOUTH
`If CIYRODEX® Otic is accidentally swallowed or overdose
`occurs. call the doctor immediately. This medicine is avail—
`able only with a doctor's prescription. Use only as directed.
`Do not use this mcdicine if outdated. If you wish to loam
`more about CIPRODEX® Otic, call your doctor or pllal'ma.
`List.
`How SUPPLIED
`CIPRODEX® Otic is supplied as follows: 7.5 mL fill in a
`DROP-TAINER® system. The DROP-TAINER® system
`consists of a natural polyethylene bottle and natural plug,
`with a white polypropylene closure. Tamper evidence is pro-
`vided with a shrink band around the closure and neck area
`of the package.
`NDC 0065-8533-02, 7.5 mL fill
`Storage:
`Store at controlled room temperature, 15°C to 30°C (59°F m
`86°F). Avoid freezing. Protect from light.
`US. Patent Nos. 4,844,902; 6,284,804; 6,359,016
`CIPRODEX® is a registered trademark of Bayer AG.
`Licensed to Alcon, Inc. by Bayer AG.
`Manufactured by Alcott Laboratories, Inc.
`Rx Only, 2004 ©2003 Alcon, Inc.
`
`2. hour D. Schustcr 0. and Graul E. Mewndent phar-
`macckineucs ct deumethasone. Eur J Clm Pharwaml
`19543.30 25230
`US. Patent .\os 4.544.902; 6.284.504: 8.359.016
`CIPRODELYE is a registered trademark of Bayer AG.
`Licensdl Io Alcoa. Inc. by Bayer AG.
`Manufadund byAlcon [Arbor-stories. Inc.
`Rx Only
`C'N‘M Alan. Inc.
`Renaion date 17 July 2003
`PATIENT INFORMATION
`(“m-moms -(‘I-l’liO-I)EXD
`lnpmflomno 0 3-“: and demmethasone tum
`Szcnle ()nc Suirerumfi
`IMFORTANT PATIENT INFORMATION AND INSTRUC-
`TIONS. READ BEFORE USE.
`What it CWROOEXE Oiic?
`C'll‘lltllll:X€
`():;c is an omihotio'e-teruid combination prud-
`ud In a 51th:? «mg-wanes: mud to treat:
`. Middle Eu Intuition with Drainage Through I Tube in
`Children 6 months and olden .\ '21:udlt ear infrction is :1
`bartrnnl ”L’f‘letfl
`_
`d llu- uardmm I’rnplr “itlt :1
`lute m the antenna 12.; 33F:IC1* drainage mm the our ra-
`
`not
`0 Outer Ear Canal Infection in Patients 6 months and older.
`K21 tstt! car (Ah \I'.r'I (lion, also known as ‘Quimnwr's
`Ear'.
`I.» a 1mmrm! ”Kath/2!) of Ibo oour ear canal. The
`ear canal Md 1!
`rl’ {an of the car may swell. turn
`
`ml. and to
`. a timid dmharpv may app-or in
`
`LL4- I‘at (3:3!
`Who should NOT an CIPRODEXO 013:7
`- I); at: on» "“‘ polo-r: tf allrrgic to cipmfloxacin or to
`Ell." qux.
`‘
`tubular.»
`‘ Do not u‘ct
`s product if :Illcr‘jzic In dcxamclhasonc Dr to
` or!” Sllflidi
`’ I)“ ”(‘1 WT tlv‘ product to pcdiatric patients who are less
`133:: 6 run-:13“ old.
`How ottcn should CIPRODEXO Otic be given?
`I Cll‘llllIlEKi Ohc car drops should be given 2 times oath
`day labnut ”hours apart. for example. 8 AM and 5 PM! in
`‘~
`rad: infrctrd cor unless the doctor has instructed other-
`} W110. Tho Irv. wars to use the car drops an: in the morning
`4
`and at night. It I“ vcr)‘ important to use the car drops for as
`long as Um dounr has instructul. even it the: symptoms im-
`prove. If (‘ll‘liUDHXE Otic ear drops are not used for as
`long as tlv~ doctor h.“ instructed. the infection may rctum.
`What it I don I: missed?
`II a dou‘ («I (‘II‘RODEX’fi Otic is missed. it should be given
`as man as pmsihlc. If it is almost time for the next dose.
`skip thr- missed dose and go back to the regular dosing
`schedule. Do not use a double dose unless the doctor has
`instntrtcd you to do so. lI'the infection is not improved afier
`one week, you should consult your doctor. lfyou have two or
`morc cpism‘les of drainage within six months. it is recom~
`mnndcd you see your doctor for further evaluation.
`What activities should be avoided while using CIPRODEX®
`Otic‘l
`It is important that the infected earls) remain clean and
`dry. When bathing. avoid getting the infected earls) wet.
`Avoid swimming: unlcss the doctor has instructed otherwise.
`What we the possible side effects of CIPRODEX® Otic?
`During the testing of CIPRODEX® Otic for middle ear in-
`fections,
`the mOSI.
`common side eITect
`related to
`CIPRODEX® Otic was ear discomfort that occurred in up to
`3 out of 100 patients. Other common side efiects were: ear
`pain; ear precipitate (residue); irritability; and abnormal
`taste. During the testing of CIPRODEX® Otic for ear canal
`infections.
`the most. common side effect
`related to
`monogram) one was itching of the ear that occurred in 1
`to 2 out of 100 patients, Other common side edects were: ear
`debris; ear infection in the treated ear; ear congestion; ear
`pain; and rash.
`If any of these side effects persist, call the doctor.
`
`Information will be superseded by supplements and subsequent editions
`
`
`
`|PR2018—01020 and |PR2018—01021, Exhibit 1011, Page 2
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 2
`
`

`

`PRODUCT INFORMATION
`
`ALCON/533
`
`PRECAUTIONS
`It has a pH of approximately 7 and an osmolality of approx-
`ADVERSE REACTIONS
`‘
`.
`imately 300 mOsm/kg.
`Information for Patients: To prevent contaminating the
`Symptoms similar to cold syndrome and pharyngitis were
`dropper tip and solution, care should be taken not to touch
`CLINICAL PHARMACOLOGY
`reported at an incidence of approximately 10%.
`.
`the eyelids or surrounding areas with the dropper tip of the
`The following adverse experiences have been reported in 5%
`bottle. Keep bottle tightly closed when not in use.
`'
`or less of patients:
`.
`_
`.
`.
`Patients should be advised not to wear a contact lens iftheir
`Ocular:
`blurred vision, burning or stinging, conjunctivitis,
`eye
`is
`red. PATANOL® (olopatadiue hydrochloride
`dry eye, foreign body sensation, byperemia, hypersensrtiv-
`ophthalmic solution) 0.1% should not be used to treat con‘
`ity, keratitis, lid edema, pain and ocular pruntus.
`tact lens related irritation. The preservative in PATANOL,
`Non-ocular:
`asthenia, back pain, flu syndrome, headache,
`increased cough, infection, nausea, rhinitis, sinuSJtis and
`benzalkonium chloride, may be absorbed by soft contact
`lenses. Patients who wear soft contact lenses and whose
`taste perversion.
`.
`.
`eyes‘ are not red should be instructed to wait at least ten
`Some of these events were similar to the underlying disease
`being studied.
`minutes
`after
`instilling
`PATANOL
`(olopatadine
`DOSAGE AND ADMINISTRATION
`hydrochloride ophthalmic solution) 0.1% before they insert
`their contact lenses.
`The recommended dose is one drop in each affected eye once
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`a day.
`Olopatadine administered orally was not carcinogenic in
`HOW SUPPLIED
`mice and rats in doses up to 500 mg/kg/day and 200 mg/kg/
`day, respectively Based on a 40 uL drop size, these doses
`were 78,125 and 31,250 times higher than the maximum
`recommended ocular human dose (MROHD). No mutagenic
`potential was observed when olopatadine was tested in an
`in vitro bacterial reverse mutation (Amen) test, an in vitm
`mammalian chromosome aberration assay or an in viva
`mouse micronucleus test. Olopatadine administered to male
`and female rats at oral doses of 62,500 times MROHD level
`resulted in a slight decrease in the fertility index and re-
`duced implantation rate; no effects on reproductive function
`were observed at doses of 7,800 times the maximum recom-
`mended ocular human use level.
`Pregnancy: Pregnancy Category C. Olopatadine was found
`not to be teratogeriic in rats and rabbits. However, rats
`treated at 600 mykg/day, or 93,750 times the MROHD and
`rabbits treated at 400 mg/kg/day, or 62,500 times the
`MROHD, during organogcnesis showed a decrease in live
`fetuses. There are, however, no adequate and well con-
`trolled studies in pregnant women. Because animal studies
`are not always predictive of human responses, this drug
`should be used in pregnant women only if the potential ben-
`efit to the mother justifies the potential risk to the embryo
`or fetus.
`Nursing Mothers: Olopatadine has been identified in the
`milk of nursing rats following oral administration. It is not
`known whether topical ocular administration could result in
`sufficient systemic absorption to produce detectable quanti-
`ties in the human breast milk. Nevertheless, caution should
`be exercised when PATANOIJ® (olopatadine hydrochloride
`mother.
`ophthalmic solution) 0.1% is administered to a nursing
`
`ophthalmic
`hydrochloride
`PATADAY‘m (olopatadine
`solution) 0.2% is supplied in a white, oval, low density poly-
`ethylene DROP-TAINER® dispenser with a natural low
`density polyethylene dispensing plug and a white polypro-
`pylene cap. Tamper evidence is provided with a shrink band
`around the closure and neck area of the package.
`NDC 00650272-25
`2.5 mL fill in 4 mL oval bottle
`Storage:
`,
`Store at 2°C to 25°C (36°F to 77°F)
`U.S. Patents Nos.
`4,871,865; 4,923,892; 5,116,863;
`5,641,805; 6,995,186
`Rx Only
`
`ALCON LABORATORIES. lNC.
`Fort Worth, Texas 76134 USA
`© 2005-2006 Alcon, Inc.
`
`
`PATANOL®
`[pd’ta-ndl]
`loiopatadine hydrochloride ophthalmic solution) 0.1%
`DESCRIPTION
`
`Be
`
`
`
`Pediatric Use: Safety and effectiveness in pediatric pa-
`tients below the age of 3 years have not been established.
`Geriatric Use: No overall differences in safety or effective-
`tients.
`ness have been observed between elderly and younger pa—
`ADVERSE REACTIONS
`Headaches have been reported at an incidence of 7%. The
`following adverse experiences have been reported in less
`than 5% of patients: asthenia, blurred vision, burning or
`stinging, cold syndrome, dry eye, foreign body sensation,
`hyperemia, hypersensitivity, keratitis, lid edema, nausea,
`pharyngitis, pruritus, rhinitis, sinusitis, and taste perver-
`sion. Some of these events were similar to the underlying
`disease being studied.
`.
`DOSAGE AND ADMINISTRATION
`The recommended dose is one drop in each afiected eye two
`times per day at an interval off; to 8 hours.
`.
`HOW SUPPLIED
`PATANOL (olopotadine hydrochloride ophthalmic solution)
`0.1% is supplied as follows: 5 mL in plastic DROP-
`TAINER® dispenser.
`5 mL:
`NDC 0065027105
`Storage: Store at 39°F-77°F (4°C—25°C)
`Rx Only
`US. Patents Nos. 5,116,863; 5,641,805.
`_.
`@2000, 2003, 2007 Alum, Inc.
`,
`5“
`
`l x
`
`SYSTANE®
`[sistc‘rn]
`Lubricant Eye Drops
`DESCRIPTION
`
`OTC
`.
`
`'
`
`Olopatadine is a relatively selective histamine Hl antago-
`nist and an inhibitor of the release of histamine from the
`mast cells. Decreased chcmotaxis and inhibition of cosmo-
`phil activation has also been demonstrated. Olopatadme IS
`devoid of efi‘ects on alpha-adrenergic, dopaminergic, and
`muscarinic type 1 and 2 receptors.
`.
`__
`Systemic bioavailability data upon topical ocular adminis—
`tration of PATADAY'" solution are not available. Followmg
`topical ocular administration of olopatadine 0.15%
`ophthalmic solution in man. olopatadine was shown to have
`a low systemic exposure. ”No studies in normal volunteers
`(totaling 24 subjects) dosed bilaterally with olopatadxne
`0.15% ophthalmic solution once every 12 hours for 2 weeks
`demonstrated plasma concentrations to be generally below
`the quantitation limit of the assay (< 0.5 ng/mL). Samples
`in which olopatadine was quantifiable were typically found
`within 2 hours of dosing and ranged from 0.5 to 1.3 nglmL.
`The elimination half-life in plasma following oral dosing
`was 8 to 12 hours. and elimination was predominantly
`through renal excretion. Approximately 60—70% of' the dose
`was recovered in the urine as parent drug. 'I\vo metabolites,
`the mono—desmcthyl and the Noxide, were detected at low
`concentrations in the urine.
`CLINICAL STUDIES
`Results from clinical studies of up to 12 weeks duration
`demonstrate that PATADAY'“l solution when dosed once a
`day is effective in the treatment of ocular itching associated
`with allergic conjunctivitis.
`INDICATIONS AND USAGE
`PATADAW' solution is indicated for the treatment ofocular
`itching associated with allergic conjunctivitis.
`CONTRAINDICATIONS
`
`Hypersensitivity to any components of this product.
`WARNINGS
`
`For topical ocular use only. Not for injection or oral use.
`PRECAUTIONS
`Information for Patients
`As with any eye drop, to prevent contaminating the dropper
`tip and solution, care should be taken not to touch the eye
`lids or surrounding areas with the dropper tip of the bottle.
`Keep bottle tightly closed when not in use. Patients should
`be advised not to wear a contact lens if their eye is red.
`PATADAYT".
`(olopatadine
`hydrochloride
`ophthalmic
`solution) 0.2% should not be used to treat contact lens re-
`lated irritation. The preservative in PATADAYW‘ solution,
`benzalkonium chloride, may be'absorbed by soft contact
`lenses. Patients who wear soft contact lenses and whose
`eyes are not red, should be instructed to wait at least ten
`minutes
`after
`instilling
`PATADAW‘
`(olopatadine
`hydrochloride ophthalmic solution) 0.2% before they insert
`their contact lenses.
`‘
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`Olopatadine administered orally was not carcinogenic in
`mice and rats in doses up to 500 mg/kg/day and 200 mg/kg/
`day, respectively. Based on a 40 pL drop size and a 50 kg
`person, these doses were approximately 150,000 and 50,000
`times higher than the maximum recommended ocular hu-
`man dose (MROHD). No mutagenic potential was observed
`when olopatadine was tested in an in vitro bacterial reverse
`mutation (Amos) test, an in vitro mammalian chromosome
`aberration assay or an in viva mouse micronucleus test.
`Olopatadine administered to male and female rats at oral
`doses of approximately 100,000 times MROHD level re-
`sulted in a slight decrease in the fertilityindex and reduced
`implantation rate; no effects on reproductive function were
`observed at doses of approximately 15,000 times the
`MROHD level.
`Pregnancy:
`,
`Teratogenic effects: Pregnancy Category C
`Olopatadine was found not to bc teratogenic in rats and rab-
`bits. However, rats treated at 600 mg/kg/day, or 150,000
`times the MROHD and rabbits treated at 400 mg/kg/day, or
`approximately 100,000 times the MROHD, during organo—
`genesis showed a decrease in live fetuses. In addition, rats
`treated with 600 mg/kg/day of olopatadine during organo-
`genesis showed a decrease in fetal weight. Further, rats
`treated with 600 mg/kg/day of olopatadine during late ges-
`tation through the lactation period showed a decrease in
`neonatal survival and body weight.
`There are, however, no adequate and well~controlled studies
`in pregnant women. Because animal studies are not always
`predictive of human responses, this drug should be used in
`pregnant women only if the potential benefit to the mother
`justifies the potential risk to the embryo or fetus.
`/
`,
`Nursing Mothers:
`.
`Olopatadine has been identified in the milk of nursing rats
`following oral administration. It is not known whether top-
`ical ocular administration could result in suficicnt systemic
`absorption to produce detectable quantities in the human
`breast milk. Nevertheless, caution should be exercised
`when PATADAYT“ (olopatadine hydrochloride ophthalmic
`solution) 0.2% is administered to a nursing mother.
`Pediatric Use:
`/
`Safety and effectiveness in pediatric patients below the age
`of 3 years have not been established.
`,
`Geriatric Use:
`No overall differences in safety and effectiveness have been
`observed between elderly and younger patients.
`
`ophthalmic
`hydrochloride
`PATANOL® (olopatadine
`solution) 0.1% is a sterile ophthalmic solution containing
`olopatadine, a relatively selective H1- receptor antagonist
`and inhibitor of histamine release from the mast cell for
`topical
`administration
`to
`the
`eyes. Olopatadine
`hydrochloride is a white, crystalline, water-soluble powder
`with a molecular weight of' 373.88.
`Each mL of PATANOL® contains: Active: 1.11 mg
`olopatadine hydrochloride equivalent to 1 mg olopatadine.
`Preservative: benzalkonium chloride 0.01%. lnacfivesz diba—
`sic sodium phosphate; sodium chloride; hydrochloric acid/
`sodium hydroxide (adjust pH); and purified water. It has a
`pH of approximately 7 and an osmolality of approximately
`300 mOSm/kg.
`,
`CLINICAL PHARMACOLOGY
`Olopatadine is an inhibitor of the release of histamine from
`the mast cell and a relatively selective histamine
`Hrantagonist that inhibits the in vivo and in vitro type 1
`immediate hypersensitivity reaction including inhibition of
`histamine induced eiIeCts on human conjunctival epithelial
`cells. Olopatadine is devoid of effects on alpha-adrenergic,
`dopamine and muscarinic type 1 and 2 receptors. Following
`topical ocular administration in man, olopatadine was
`shown to have low systemic exposure. No studies in nor
`mal volunteers (totaling 24 subjects) dosed bilaterally with
`olopatadine 0.15% ophthalmic solution once every 12 hours
`for 2 weeks demonstrated plasma concentrations to be gen-
`erally below the quantitation limit of
`the assay
`(<05 ng/mL). Samples in which olopatadine was quantifi-
`able were typically found within 2 hours of dosing and
`ranged from 0.5 to 1.3 ng/mL. The half-life in plasma was
`approximately 3 hours, and elimination was predominantly
`through renal excretion. Approximately 60—70% of the dose
`was recovered in the urine as parent drug. Two metabolites,
`the mono-desmethyl and the N-oxide, were detected at low
`concentrations in the urine.
`Results from an environmental study demonstrated that
`PATANOL was effective in the treatment of the signs and
`symptoms of allergic conjunctivitis when dosed twice daily
`for up to 6 weeks. Results from conjunctiva] antigen chal-
`lenge studies demonstrated that PATANOL®, when sub-
`jects were challenged with antigen both initially and up to 8
`hours after dosing, was significantly more effective than its
`vehicle in preventing ocular itching associated with allergic
`conjunctivitis.
`.
`.
`.
`INDICATIONS AND USAGE
`PATANOL (olopatadine hydrochloride ophthalmic solution)
`0.1% is indicated for the treatment of the signs and symp-
`toms of allergic conjunctivitis.
`CONTRAINDICATIONS
`PATANOL (olopatadine hydrochloride ophthalmic solution)
`0.1% is contraindicated in persons with a known hypersen-
`sitivity to olopatadine hydrochloride or any components of
`PATANOL.
`’
`WARNINGS ‘
`
`
`
`PATANOL® (olopatadine hydrochloride ophthalmic solu-
`tion) 0.1% is for topical use only and not for injection or oral
`use.
`
`SYSTANE® is scientifically formulated to shield eyes from
`dry eye discomfort so that eyes feel moist and refreshed
`longer. For the temporary relief of burning and irritation '
`due to dryness of the eye.
`'
`Active Ingredients: Polyethylene Glycol 400 0.4% and
`Propylene Glycol 0.3% as lubricants.
`.
`Inactive Ingredients: boric acid, calcium chloride, hydroxy-
`propyl guar, magnesium chloride, polyquaternium-l as a
`preservative, potassium chloride, purified water, sodium
`chloride, zinc chloride. May contain hydrochloric acid and/or
`sodium hydroxide to adjust pH.
`WARNINGS »
`.
`For external use only
`Do not use
`~ if this product changes color or becomes cloudy
`‘ if you are sensitive to any ingredient in this product
`Continued on next page
`
`|PR2018—01020 and |PR2018—01021, Exhibit 1011, Page 3
`
`Consult 2008 FORD supplements and future editions for reviswns
`
`I"i
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 3
`
`

`

`
`
`2008
`
`EDITION
`
`
`
`PHYSICIANS
`DESK
`‘ REFERENCE
`
`Executive Vice President, PDR: Kevin D. Sanborn
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`THOMSON Copyright © 2007 and published by Thomson Healthcare inc. at Montvale, NJ 07645-1725. All rights reserved. None of the content of this
`w- publication may be reproduced, stored in a retrieval system, resold, redistributed, or transmitted in any form or by any means (electronic,
`mechanical, photocopying, recording, or olhenNise) without the prior written permission of the publisher. Physicians’ Desk Reference“ and PDF!‘3 are registered trade—
`marks of Thomson Healthcare inc, FDR0 for Ophthalmic Medicines: FDR” for Nonprescription Drugs, Dietary Supplements, and Herbs; FDR“ Guide to Drug interactions,
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`Pamela M. Bilash; General Counsel: Darren Pocsik
`
`ISBN: 1-56363-660-3
`
`|PR2018—01020 and |PR2018—01021, Exhibit 1011, Page 4
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 4
`
`

`

`
`
`\\_
`
`FOREWORD TO THE 62nd..EDITION
`
`PDR enters its 62nd year offering a wider array of pharma
`ceutical reference options than ever before. Long available
`unabridged—in print, on CDROM, and via the lntemet—
`PDR also provides essential prescribing information in
`other forms as well detailed later'In this foreword.
`About This Book
`Physicians' Desk Reference0 is published by Thomson
`HealthcareIn cooperation with participating manufacturers.
`The PDR contains Food and Drug Administration (FDA)
`approved labeling for drugs as well as prescription infor—
`mation provided by manufacturers for drugs historically
`marketed without FDA approval; Some dietary: supple
`ments andother products are also included. Each full
`length entry provides you with an exact copy of the pro
`duct’s FDA-approved or other manufacturer-supplied label-
`ing. Under the Federal Food, Drug and Cosmetic ‘(FD&C)
`Act a drug approved for marketing may be labeled pro
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`approved labeling for the products. The FDA. regards the
`words same in language and emphasis as requiring VER-
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`capitals, boldface, or italics. must be given the same
`emphasis in PDR.
`,
`-
`The FDA has also recognized that the FD&C Act does not,
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`approved drug. Once a product has been approved for mar-
`keting, a physician may choose to prescribe it for uses or
`in treatment regimens or patient populations thatare not
`included in approved labeling. The FDA also observes that
`accepted medical practice includes. drug use that is not
`reflected in approved drug labeling. in the case of over-the-
`counter dietary supplements,
`it should be remembered
`that this information has not been evaluated by the Food
`and Drug Administration, and that such products arenot
`intended to diagnose, treat,rcure, or prevent any disease.
`
`The function of the publisherIs the compilation, organiza—
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`description has been prepared by the mantifacttIrer, and
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`Desk Reference, the publisher does not warrant or‘guar—
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