Borrower: JNF
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`Patron:
`Journal Title: Physrcians‘ desk reference 1 PDR.
`Issue:
`2008Pages: 532-533, plus
`
`Volume:
`Montleear:
`title/verso
`
`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
`
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`A 1y a Pharma LLC (IPR2020-00295) EX. 1011 p 001
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`Ayla Pharma LLC (IPR2020-00295) Ex. 1011 p. 001
`
`

`

`7i
`
`PHYSICIANS' DESK REFERENCE®
`532/ALCON
`
`Ciprodex—Cont.
`
`Ear rmrims
`
`Adverse Ev on!
`
`Incidence 1X:5371
`
`
`
`
`Superimposed car infection
`
`Car or ngvstmn
`
`
`(3000 11;”le
`
`The (95111.11...1‘ matnrntvrrlatml adn-rse cvcms WEN each
`npctzrd 1:1 :1 11:1;3‘.e thPnT; car d:.~m::1!on;dt-cn-.1~edheap
`mg. and car 159111111 mingling!
`DOSAGE AND ADMlNlSTIIATION
`ClPflODEXE OTIC SHOULD BE SHAKEN WELL IMMEDlv
`ATELY BEFORE USE
`3 111551111.
`Cll’flolll'lh'i
`11c wounds
`arr-1 Enoch and 1 1:31:21. decorum-thusune
`Acute Otitis Mcdil in pediatric puisnts with tymp-nos-
`tomy tubes:
`'11::- rrmmmondul dosogc rut-mien {or the
`
`tnat" '2'. of nmtc 01111.1 2::trim in putattic patients. (ago 6
`
`1::
`:l:s and o' 131'? through hmpancstomt tutuis;
`Fri” drops IO H 2111.. 042 11:; cipmfioxunn. 0.14 mg
`dv‘xamrllmnczw installid into tlzc 5151de car twicr duly
`fer sewn days Tho suspcnsion should Ir wanna! by held-
`in: thc bottle in the hand for one or him minutes to atmid
`d::2:.~.c<s. “hirh may rcsult from the instillation ofn cold
`susprminn The patient should lu- With the affirm! car up
`ward. and tlzrn the drops should bu unfilled. The trogus
`should thou bu pumped 5 times by pushiuc inward to {M11-
`11.111- gravitation ofthc drops into the middlc car. This 90-
`slim". should It maintainrd for 60 mods. Rrrrot. if mu
`essnr); far tho rvrtmsitr‘ car. Discard unuscd portion nfirr
`thrrapy ir- mmplt 1rd
`Acute Otitis Enoma: Tho recommended dosage women
`for thc trratnzi nl ofarutt Ulllll‘ rxtcmn is: For patients Iago
`6 months and olden: Four drops '0.“ mL. 0.42 m:
`nrmflomc‘in. 0.” mg dcxnmcthnsonel instilled into tho of-
`frfinl cor twirr dolly for seven days. The SUFPTH‘I‘WI should
`be warmed by holding: the bottle in the hand for om- or two
`minutcs to avoid dizziness. whirh may rcsult from the in-
`stillation of n cold suspension. The patimt should lie with
`the aft-(tn! ear upward. and than the drops shOuld be in-
`stillid. This position should to mointoincd for 60 smnds lu
`farilitati- ponctration of the drum: into the ear canal. Re-
`pcol. if nccrssan‘. for the opposite ear. Discard unusul por-
`tion utter thcrapy is mmplcttd.
`HOW SUPPLIED
`CII’RODEXT'J lciproflnxarin 0.37} and dexnmethasone 0.1"”
`Sterile Otic Suspension is supplied as follousz"1 5 mL fill in
`3 DROP-TAIRERD system. The DROP-TAISERE srstem
`consists of a natural polyethylene bottle and natural plug.
`with a white polypnwpylene closure. Tamper ovidence is pro-
`vidcd with a shrink band around the closure and neck arca
`ofthe package.
`NDC 0065-3353302. 7.5 mL fill
`Storage:
`Store at controlled room temperature, 15'C to 30‘C (59°F to
`861:1. Avoid freezing. Protect from light.
`CLINICAL STUDIES
`In a randomized, multicenter, controlled clinical trial,
`ClI’RODEXB Otic dosed 2 times per day for 7 days demon-
`strated clinical cures in the per protocol analysis in 86% of
`AOMT patients comparcd to 79’} for olloxacin 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 79’71 for ofloxacin solution, 0,371. Microbiologi-
`cal eradication rates for those patients in the same clinical
`trial were 9l’71 for CIPRODEX® Otic compared to 82% for
`ofioxacin solution, 0.371.. In 2 randomized multicenter, con-
`trolled clinical trials. CIPRODEX® Otic dosed 2 times per
`day for 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% (neolpolylHC). Among culture positive
`patients clinical cures were 86% and 92% for CIPRODEX®
`Otic compared to 84% and 89%, mspectively, for nee/poly]
`HC. Microbiological eradication rates [or 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. Campoli-Richards DM, Monk JP, Price A, Benfield P,
`Todd PA, Ward A. Ciprolloxacin: A review of its antibac-
`terial activity, 111’) annacokinetic properties and therapeu-
`tic use. Drugs 1988;35:373-447.
`
`2. Low D. Schuster 0. and Graul E. Mewndent phar»
`mockice'irs cf deumethasonc. Eur J Chn Pharmacol
`19$«3,30 2‘25230
`US. Patént .\os 45443016284504; 8.359.016
`CH‘RODEYE is a nfisxcrtd trademark of Bayer AG.
`Licensed to Alton. Inc. by Bayer AG.
`Manufamuml by Alton Later-armies. lnc.
`Rx Only
`C2035 Alan. lac.
`Raision (L111: 17 Jul)‘ 2003
`PATIENT INFORMATION
`Cll‘I-lllllliXE u('l»l’ltO-lll-ZXD
`inpmflomnn [1 3‘: 11nd demote-thawin- OJ'H
`Sunli- ()trc Suifernrnn
`IMPORTANT PATIENT INFORMATION AND INSTRUC‘
`TIONS. READ BEFORE USE.
`Whit it CtPRODEXG Otic?
`Cll’lillmiXi Hut 1; an notitiotio’atcmid combination prud-
`uct m a 11111:.- .1;.3-.»::-1us1 uu’d to 1111211:
`- Middl- Eu Infection with Drainage Through I Tube in
`Childim 6 months and older.
`.-\ mzdtllc car inltctiun is a
`
`bacterial 1...'1'('.' 11:1
`*
`d 1111- rnrdmm l’ruplr “itli a
`tut-e m (hr 1.111!
`,1: notice drainage your 1111- our cw
`
`ml
`0 Outer Eu Canal Infection In P-ticnts 6 months and older:
`K21 (-11! my 12131.1r.’ {11011. aim krioun as ‘Suimmc-‘r5
`Ear. u a 1.11.11:er 1r..1vt.:n of the 01111! (or (1111.11. The
`
`«111 ram! an! t.
`rutrr {an of the car may swell. tum
`
`1115.521! to
`I Also, 51 fluid di~rttarpv may opp-or in
`thc rat 121:3!
`I Who would NOT use CIPRODEXO Otis?
`1
`I211.111ac:
`‘
`- lb tic! L‘ic -' ~1 tzralur'. if 11.12pm to cipmlloxocin or to
`I
`
`cl)(1’ qt:
`' Do not 11w 1
`
`11 pruluct if allergic In dosamrlhnsonc or to
`013.1! Mr 11 :di
`‘ Do not arr thas rut-duct to pcdiotric patirnts who arc less
`L‘Jm fr mnfilljs old.
`‘
`How often should CIPRODEXO Otic be given?
`l
`le‘fllllllixi 01;: car drum should be given 2 timcs t‘tltl‘t
`1
`day rat-nut 12 hours apart. for trample, 8 AM and 8 PM! in
`‘-
`cot}: inlrrtrd cor unless the doctor has instructor! other-
`} Wm‘. T710 l‘Nt “me In use the car dmps 11m in the morning
`and :11 ntzht. It 1‘1 "‘1'.“ important to use the cor drops for as
`long 11: the doanr 11:1:- mstructcd. even ll tho symptoms im-
`prove. ll CII‘I'IUDEX? Otic car drops are not used for as
`ion: as tho doctor hat instructed, the infection may rcturn.
`What it a dose is missed?
`If a dmc («I (‘II‘RODEX’fi Otic is missed, it should be given
`as soon as pmnhlc. If it is almost time for the next dose.
`Fltlp thr- misscd doso and go back to the regular dosing
`srhcdulc. Do not use 11 dnuble dose unless the doctor has
`instnirtul you to do so, lI'the infcction is not improved after
`one week, you should consult your doctor. Ifyou have two or
`morr cpimdcs of drainage within six months. it is recom-
`mcndod you soc your doctor for further evaluation.
`What activities should be avoided while using CIPRODEX®
`O‘tic‘l
`It is important that the infected earls) remain clean and
`dry. \thn bathing. avoid getting the infected cans) wet.
`Avoid swimming: unlcss the doctor has instructed otherwise.
`What are the possible side effects of CIPRODEX® Otic?
`During the testing of CIPRODEX® Otic for middle ear in-
`fections,
`the most
`common side eflect
`related to
`CIPRODEX® Otic uas car discomfort that occurred111 up to
`3 out of 100 patients. Other common side effects “ere: ear
`pain; ear precipitate (residuel; irritability; and abnormal
`taste During the testing of CIPRODEX® Otic for ear canal
`infections,
`the most. common side efiect
`related to
`CIPRODEX® Otic was itching of the ear that occurred in 1
`to 2 out of 100 patients. Other common side effects were: a,"
`debris; ear infection in the treated ear; ear congestion; ear
`pain; and rash.
`If any of thEse side effects persist call the doctor.
`
`If an allergic reaction to CIPRODEX® Otic occurs, stopus-
`ing the product and contact your doctor.
`DO NOT TAKE BY MOUTH
`If CIPRODEK® 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 medicine it" outdated. If you wish to loam
`more about CIPRODEX® Otic, call your doctor or pharma-
`cist.
`.
`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 température, 15°C to 30°C (59°F to
`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.
`
`How should ctPRODEXG 011: ha given?
`1. Wash hands
`
`The person giving CIPRODEX®
`Otic should wash his/her hands
`with soap and watt-r.
`
`
`
`2. Warm a. shake bottle
`
`
`
`Hold the bottle of Cll’IlODEX®
`Otic in the hand for 0110 or two min—
`ulcs to warm the nuspcnalm, than
`shake well.
`
`The person receiving Cll’llOl)EX®
`Otic should lie on his/her side with
`tho infected car up.
`
`Poticnts should have 4 drops of
`CIPRODEK® Otic put into the in-
`fected car. The tip of tho bottle
`should not touch the fingers or the
`
`car or any other surfaces.
`
`BE SURE TO FOLLOW INSTRUCTIONS BELOW FOR THE
`PATIENTS SPECIFIC EAR INFECTION.
`‘. For Patients with Middle Ear Infection 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
`
`B
`PATADAYT'“
`Iolopatadine hydrochloride ophthalmic solution) 0.2%
`
`,
`
`,
`DESCRIPTION
`ophthalmic
`hydrochloride
`PATADAYTM (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 37388 and a mo-
`lecular formula of C21H23N03 0 HCl The chemical struc-
`tureis presented below:
`propyl-
`Chemical Name:111-[(Zi-3-(Dimethylaminu)
`idenel-6-ll-dihydrodibenzlb,el oxepin2-acet‘ic acid, hydro-
`chloride.
`Each mL of PATADAYm solution contains: Active: 222 mg
`olopatadine hydrochloride equivalent to 2 mg olopatadine
`lnactives: povidone; dibasic sodium phosphate; sodium chlo-
`ride; edetate disodium; benzalkonium chloride 0.01%
`(preservative) hydrochloric acid I sodium hydroxide ~(adjuSt
`pH); and purified Water.
`
`
`
`I
`
`Information will be superseded by supplements and subsequent editions
`
`
`
`
`
`11
`
`_
`
`_, 111‘”:
`
`Ayla Pharma LLC (11511202000295) EX. 1011 p. 002
`
`Ayla Pharma LLC (IPR2020-00295) Ex. 1011 p. 002
`
`

`

`PRODUCT INFORMATION
`
`ALCON/533
`
`Olopatadine is a relatively selective histamine Hl antago-
`nist and an inhibitor of the release of histamine from the
`mast cells. Decreased chemotaxis and inhibition of cosmo-
`phi) activation has also been demonstrated. Olppatadine is
`devoid of effects 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. Followtng
`topical ocular administration of olopatadine 0.15%
`ophthalmic solution in man. olopatadinc was shown to have
`a low systemic exposure. TWO studies in normal volunteers
`(totaling 24 subjects) dosed bilaterally with olopatadine
`0.15% ophthalmic solution once every 12 hours for 2 weeks
`demonstrated plasma concentrations to be generally below
`the quantitation limit of the assay (< 0.5ng/mL). Samples
`in which olopatndine was quantifiable were typically found
`within 2 hours of dosing and ranged from 0.5 to 1.3 ng/mL.
`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-dcsmcthyl 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‘“ solution when dosed once a
`day is effective in the treatment of ocular itching associated
`with allergic conjunctivitis.
`INDICATIONS AND USAGE
`PATADAYT" solution is indicated for the treatment ofocular
`itching associated with allergic conjunctivitis.
`CONTRAINDICATIONS
`
`Hypersensitivity to any components of this product.
`WARNINGS
`
`ALCON LABORATORIES, INC.
`Fort Worth, Texas 76134 USA
`© 2005-2006 Alcon, lnc.
`
`
`PATANOL®
`[pri'ta-m‘ill
`(olopatadine hydrochloride ophthalmic solution) 0.1%
`DESCRIPTION
`
`I}
`
`PRECAUTIONS
`ADVERSE REACTIONS
`It has a pH ofapproximately 7 and an osmolality of approx-
`imately 300 mOsm/kg.
`Information for Patients: To prevent contaminating the
`Symptoms similar to cold syndrome and pharyngitis were
`CLINICAL PHARMACOLOGY
`dropper tip and solution, care should be taken not to touch
`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.
`PATANOD® (olopatadine hydrochloride
`dry eye, foreign body sensation, hyperemia, hypersenSitiv-
`ophthalmic solution) 0.1% should not be used to treat con-
`ity, keratitis, lid edema, pain and ocular pruritus.
`tact lens related irritation. The preservative in PATANOL,
`Non-ocular:
`asthenia, back pain, flu syndrome, headache,
`increased cough, infection, nausea, rhinitis, sinusrtis and
`benzalkonium chlon'de, 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
`their contact lenses.
`hydrochloride ophthalmic solution) 0.1% before they insert
`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
`ophthalmic
`hydrochloride
`PATADAYm (olopatadine
`were 78,125 and 31,250 times higher than the maximum
`solution) 0.2% is supplied in a white, oval, low density poly-
`recommended ocular human dose (MROHD). No mutagenic
`ethylene DROP—TAINER® dispenser with a natural low
`potential was observed when olopatadine was tested in an
`density polyethylene dispensing plug and a white polypro-
`in vitro bacterial reverse mutation (Amos) test, an in vitro
`pylene cap. Tamper evidence is provided with a shrink band
`mammalian chromosome aberration assay or an in viva
`around the closure and neck area of the package.
`mouse micronucleus test. Olopatadine administered to male
`NDC 0065-0272—25
`2.5 mL fill in 4 mL oval bottle
`Storage:
`-
`-
`and female rats at oral doses of 62,500 times MROHD level
`Store at 2°C to 25°C (36°F to 77°F)
`resulted in a slight decrease in the fertility index and re-
`duced implantation rate; no efl‘ects on reproductive function
`US. Patents Nos.
`4,871,865,- 4,923,892; 5,116,863;
`were observed at doses of 7,800 times the maximum recom-
`5,641,805; 6,995,186
`mended ocular human use level.
`Rx Only
`Pregnancy: Pregnancy Category C. Olopatadine was found
`not to be teratogenic in rats and rabbits. However, rats
`treated at 600 mg/kg/day, or 93,750 times the MROHD and
`rabbits treated at 400 mg/l-ig/day, or 62,500 times the
`MROHD, during organogencsis 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: OIopatadine 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
`PATANOL® (olopatadine
`solution) 0.1% is a sterile ophthalmic solution containing
`olopatadine, a relatively selective Id,- 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 of373.88.
`1.11 mg
`Each mL of PATANOL® contains: Active:
`olopatadine hydrochloride equivalent to 1 mg olopatadine.
`Preservative: benzalkonium chloride 0.01%. Inactivesz 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 most cell and a
`relatively selective histamine
`Hfantagonist that inhibits the in viva and in uitm type 1
`immediate hypersensitivity reaction including inhibition of
`histamine induced effects 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. 'Dvo 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 he 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 eflective 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)
`011% 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.
`
`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
`PATADAYTM (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 vivo mouse micronucleus test.
`Olopntadine 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 be teratogenic in rats and rab-
`bits. However, rats treated at 600 mg/kg/day, or 150,000
`times the MROHD and rabbits treahed at 400 mg/kg/day or
`approximately 100,000 times the MROHD, during organe—
`genesis showed a decrease in live fetuses. In addition, rats
`treated with 600 mg/kg/day of olopatadine during organe—
`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:
`»
`Olopatodiric has been identified in the milk of nursing rats
`following oral administration. It is not known whether top-
`ical ocular administration could result in suficient 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.
`
`
`
`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 elfective-
`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,
`hyperernia, hypersensitivity, keratitis, lid edema, nausea,
`pharyngitis, pruritus, rhinitis, sinusitis, and taste perver-
`sioni Some of these events were similar to the underlying
`disease being studied.
`.
`DOSAGE AND ADMINIS'I RATION
`The recommended dose is one drop in each affected eye two
`times per day at an interval oft} to 8 hours.
`.
`HOW SUPPLIED
`PATANOL (olopntndine hydrochloride ophthalmic solution)
`0.1% is supplied as follows: 5 mL in plastic DROP-
`TAINER® dispenser.
`5 mL:
`NDC 0065-0271-05
`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 Alcon, Inc.
`
`’3 “
`
`SYSTANE®
`[sistc‘m]
`Lubricant Eye Drops
`DESCRIPTION
`
`OTC
`.
`
`'
`
`
`
`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 imitation '
`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, polyquatcrnium—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
`
`Ayla Pharma LLC (IPR2020-00295) EX. 1011 p. 003
`
`Consult 2008 FORD supplements and future editions for revisions
`
`/
`/‘
`
`x
`
`Ayla Pharma LLC (IPR2020-00295) Ex. 1011 p. 003
`
`

`

`2008
`
`EDITION
`
` PHYSICIANS
`DESK
`‘ REFERENCE?
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`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 othenrvise) without the prior written permission of the publisher. Physicians’ Desk Reference” and FDR“ are registered trade
`marks of Thomson Healthcare inc, PDFi0 for Ophthalmic Medicines: F‘DRE for Nonprescription Drugs, Dietary Supplements, and Herbs; FDR“ Guide to Drug interactions,
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`ISBN: 1-56363-660-3
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`Ayla Pharma LLC (IPR2020-00295) EX. 1011 p. 004
`
`Ayla Pharma LLC (IPR2020-00295) Ex. 1011 p. 004
`
`

`

`\MK
`
`FOREWORD TO THE 62nd.EDITION
`
`to obtain and include any information other than that
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`PDR enters its 62nd year offering a wider array of pharma
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`About This Book
`Physicians’ Desk Reference” is published by Thomson
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