`
`
`
`ofHlinoisChicagoILL
`
`ACUMEO
`iLLiadTN:658798
`
`University
`
`JournalTitle: Physicians desk reference - PDR.
`
`Volume:
`Issue:
`Month/Year: 2008Pages: 532-533, plus
`
`title/verso
`
`using Odyssey. ILLiad libraries can enable
`Odyssey for receiving documents
`seamlessly. Non-ILLiad libraries can
`download Odyssey stand alone for FREE.
`Checkit out at:
`rttprliwwrw.atlas-sys.com/odysseyNt
`
`Article Author:
`Article Title: Entries for Patanol and Pataday
`Imprint: Oradell, N.J.: Medical Economics Co.
`Montvale, NJ: Thomson PDR Montvale, NJ: PDR
`
`Network
`ILL Number: 487659124
`AGAULA
`
`Charge
`Maxcost: 35.001FM
`
`Shipping Address.
`Laura Schaeffer
`Katten Muchin Rosenman LLP Library
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`United States
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`
`IPR2018-18-01020 and IPR2018-01021, Exhibit 1011, Page 1
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 1
`
`

`

`LL &&&&°°»&©
`
`PHYSICIANS’ DESK REFERENCE®
`532/ALCON
`'i
`
`1 |i |
`
`Ciprodex—Cont.
`
`Ear ecngeeticn
`
`(3009 pe'mL
`
`i
`
`
`
`
`
`. I
`
`Information will be superseded by supplements and subsequent editions
`
`PR2018-01020 and IPR2018-01021, Exhibit 1011, Page 2
`
`2. Loew D, Schuster O, and Graul E. Dose-dependent phar-
`macckinetics cf dexamethasone. Eur J Clin Pharmacol
`1986,50 225-23.
`, US. Patent Nos 4,644,902; 6,284,804; 6,359,016
`Incidence 1N=537)
` Adverse Event
`CIPRODEXSis a registered trademark of Bayer AG.
`Licensed to Aleon, Inc. by Bayer AG,
`
`Ear pruritus
`Manufactured by Alcon Laboratories, Inc.
`Ear debris
`Rx Only
`
`COOL Alea, Ine.
`
`Superimposed ear infection
`Revision date 17 July 2003
`PATIENT INFORMATION
`CIPRODENS -CLPRO-DEX?
`
`topmfloracin O3% and dexamethasone 0.1%)
`Stenie Ouie Suspension
`Enthema
`
`IMPORTANT PATIENT (INFORMATION ANO INSTRUC.
`TIONS. READ BEFORE USE.
`What is CIPRODEXE Otic?
`The following Urrvatment-related adverse events were each
`CIPRODEXE Ouc ts an anuibiotic'stervid combination prod-
`reperted in a single patient: ear discomfort; decreased hear:
`uetin a sternite stispenacn used to treat!
`ing. andear desonder tueghng:
`© Middle Ear Infection with Drainage Through 8 Tube in
`DOSAGE AND ADMINISTRATION
`Children 6 months and older. Asniddle car infection is a
`bacterial infection
`aand the eardrum People with a
`CIPRODEX® OTIC SHOULD BE SHAKEN WELLIMMEDI.
`
`ATELY BEFORE USE
`tube in the eardrum may netice drainage from the ear ea-
`nal
`3 me’mL
`centains
`CIPRODEXS
`Ouc
`© Outer Ear Cana! Infection in Patients 6 months and older:
`omg tml dexamethasone
`epm fovacn and |
`An cuter eat canal infiction, also known as “Swimmer’s
`Acute Otitis Medis in pediatric patients with tympanos:
`Ear, s a bactersal infection of the outer ear canal. The
`tomy tubes: The recommended dosage regimen for the
`
`ear canal ard tt
`er part of the ear may swell, tum
`
`treatment of acute otitis media in pediatric patients tage 6
`
`red, and be
`wa uid diecharge mayappear in
`months and older: through lympanestomytubes is:
`the ear canal
`Fesr drops (O14 ml, 0.42 mp ciprofloxacin, O14 mg :
`Who should NOT use CIPRODEX® Otic?
`dexamethasone: instilled into the affected ear twice daily
`® Do net use this preduct if allergic to ciprofloxacin or to
`fer seven days. The suspension should be warmed by hold-
`ether quinct
`nhbctics.
`ing the botule in the hand for ere er two minutes to axaid
`:
`swe
`Pe Danct uset
`s preduct if allergic to dexamethasoneor to
`
`duziness, which may result from the instillation of a cold +:
`:
`‘
`osher stemids
`suspension The patient should he with the affected ear up-
`* Donet pve this product to pediatric patients who are less
`Vian G months ald.
`ward, and then the drops should be instilled. The trazus
`should then be pumped 5 times by pushing inward to faal-
`How often should CIPRODEX® Otic be given?
`|
`Nate penctranion of the dreps into the middle ear. This po.
`CIPRODEXS Otc ear drops should be given 2 times each
`sition should be maintained for 60 seconds. Repeat. if neces”
`day tabout 12 bours apart. for example, § AM and & PMvin
`essary, for the opposite ear. Discard unused portion afer >
`cach infected car unless the doctor has instructed other-
`therapyis comp'ted
`i wise. The hest times to use the ear drops are in the morning
`Acute Otitis Externa: The recommended dosage regimen
`and al night. Itas very important to use the car drops for as
`for the urratnent ofacute otitis externa is: For pahents (age
`leng as the docter has instructed. even if the symptoms im-
`6 months and older: Four drops ‘O14 mL. 0.42 me
`prove. If CIPKODEX® Otic ear drops are not used for nas
`oprefiexacin. 0.14 mg dexamethasone! instilled into the af-
`long as the dector has instructed, the infection may return.
`Whatif a dose is missed?
`fected car twice daily for seven days. The suspension should
`be warmed by holding the bottle in the hand for one or two
`Ha doe of CIPRODEX® Otic is missed, it should be given
`Tainutes te avoid dizziness. which mayresult from the in-
`as soon as possible. If it is almost time for the next dose,
`stilation ef a cold suspension. The patient should lie with
`skip the missed dose and go back to the regular dosing
`schedule, Do not use a double dose unless the doctor has
`the affected ear upward, and then the drops should be in-
`siilied. This position should he maintained for 60 seconds to
`instructed you to do so, If the infection is not improved after
`|
`one week, vou should consult your doctor. If you have two or
`facilitate penetration of the drops into the ear canal. Re-
`1 more episodes of drainage within six months, it is recom-
`peat. if necessary. for the opposite ear. Discard unused por-
`mended you see your doctor for further evaluation.
`tion after therapyis completed.
`Whatactivities should be avoided while using CIPRODEX®
`HOWSUPPLIED
`Otic?
`CIPRODEX® (ciprofloxacin 0.3% and dexamethasone 0.1%)
`It is important that the infected earfs) remain clean and
`dry. When bathing. avoid getting the infected earls) wet.
`Sterile Qtuic Suspension is supplied as follows: 7.5 mL fill in
`Avoid swimming unless the doctor has instructed otherwise.
`a DROP-TAINER® system. The DROP-TAINER® system
`Whatare the possible side effects of CIPRODEX® Otic?
`consists of a natural polyethylene bottle and natural plug.
`During the testing of CIPRODEX® Otic for middle ear in-
`with a white polypropylene closure. Tamper evidence is pro-
`vided with a shrink band around the closure and neck area
`fections,
`the most
`common side effect
`related to
`CIPRODEX® Otic was ear discomfort that occurred in up to
`of the package.
`NDC 0065-8533-02. 7.5 mL fill
`3 out of 100 patients. Other common side effects were: ear
`pain: ear precipitate (residue); irritability; and abnormal
`Storage:
`taste. During the testing of CIPRODEX®Oticfor ear canal
`Store at controlled room temperature, 15°C to 30°C (59°F to
`infections,
`the most common side effect
`related to
`86°F). Avoid freezing. Protect from light.
`CIPRODEX® Otic was itching of the earthat occurred in 1
`CLINICAL STUDIES
`to 2 out of 100 patients. Other common side effects were: ear
`debris; ear infection in the treated ear; ear congestion; ear
`In a randomized, multicenter, controlled clinical trial,
`pain; and rash.
`CIPRODEX®Otic dosed 2 times per day for 7 days demon-
`If any of these side effects persist, call the doctor.
`strated clinical cures in the per protocol analysis in 86% of
`If an allergic reaction to CIPRODEX®Otic occurs, stop uus-
`AOMT patients compared to 79% for ofloxacin solution,
`ing the product and contact your doctor.
`0.3%, dosed 2 times per day for 10 days. Amongculture pos-
`DO NOT TAKE BY MOUTH
`itive patients. clinical cures were 90%for CIPRODEX® Otic
`If CIPRODEX® Otic is accidentally swallowed or overdose
`compared to 79% for ofloxacin solution, 0.3%. Microbiologi-
`occurs, call the doctor immediately. This medicine is avail-
`cal eradication rates for these patients in the sameclinical
`able only with a doctor's prescription. Use only as directed.
`trial were 91% for CIPRODEX® Otic compared to 82% for
`Do not use this medicine if outdated. If you wish to learn
`ofloxacin solution, 0.3%. In 2 randomized multicenter, con-
`more about CIPRODEX® Otic, call your doctor or pharma-
`cist.
`:
`trolled clinical trials, CIPRODEX® Otic dosed 2 times per
`HOW SUPPLIED
`day for 7 days demonstrated clinical cures in 87% and 94%
`of per protocol evaluable AOE patients, respectively, com-
`CIPRODEX® Otic is supplied as follows: 7.5 mL fill in a
`pared to 84% and 89%, respectively, for otic suspension con-
`DROP-TAINER® system. The DROP-TAINER® system
`taining neomycin 0.35%, polymyxin B 10,000 [U/mL,and
`consists of a natural polyethylene bottle and naturalplug,
`hydrocortisone 1.0% (neo/poly/HC). Amongculture positive
`with a white polypropylene closure. Tamperevidenceis pro-
`vided with a shrink band around the closure and neck area
`patients clinical cures were 86% and 92% for CIPRODEX®
`of the package.
`Otic compared to 84% and 89%, respectively, for neo/poly/
`NDC 0065-8533-02, 7.5 mL fill
`HC. Microbiological eradication rates for these patients in
`the same clinicaltrials were 86% and 92% for CIPRODEX®
`Storage:
`Otic
`compared to 85% and 85%,
`respectively,
`for
`Store at controlled room temperature, 15°C to 30°C (59°F to
`neo/poly/HC.
`86°F). Avoid freezing. Protect from light.
`US. Patent Nos. 4,844,902; 6,284,804; 6,359,016
`REFERENCES
`CIPRODEX®is a registered trademark of Bayer AG.
`1. Campoli-Richards DM, Monk JP, Price A, Benfield P,
`Licensed to Alcon, Ine. by Bayer AG.
`‘Todd PA, Ward A. Ciprofloxacin: A review of its antibac-
`Manufactured by Alcon Laboratories, Inc.
`terial activity, pharmacokinetic properties and therapeu-
`tic use. Drugs 1988;35:373-447.
`Rx Only, 2004 ©2003 Alcon,Inc.
`
`How should CIPRODEX® Otic be given?
`4. Wash hands
`
`The person giving CIPRODEX®
`Qtic should wash his/her hands
`with soap and water.
`
`
`
`i 2. Warm & shake bottle
`
`Hold the bottle of CIPRODEX®
`Otic in the handfor oneor two min-
`utes to warm the suspension, then
`shake well.
`
`The person receiving CIPRODEX®
`Otic should lie on hisher side with
`theinfected car up.
`
`Patients should have 4 drops of
`CIPRODEX® Otic put into the in-
`fected ear. The tip of the bottle
`should net touch the fingers or the
`ear or any other surfaces.
`
`
`
`
`BE SURE TO FOLLOW INSTRUCTIONS BELOW FOR THE
`PATIENT'S SPECIFIC EAR INFECTION.
`4. 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.
`
`5. For Patients with Outer Ear Infection (7Swimmer's Ear”):
`
`
`nal. The person who received the ear
`
`While the person receiving the
`drops lies on hitvherside, 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-
`
`drops should remain on his/herside
`for at least 60 seconds.
`Repeat Steps 2-5 for the other earif
`both ears are infected.
`
`PATADAY™
`{olopatadine hydrochtoride ophthalmic solution) 0.2%
`DESCRIPTION
`/
`ophthalmic
`hydrochloride
`PATADAY™ (olopatadine
`solution) 0.2% is a sterile ophthalmic solution containing
`olopatadine fer
`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 C2,;H,;NOQ; * HCl. The chemical struc:
`ture is presented below:
`Chemical Name:
`111-[(Z)--3-(Dimethylamino)
`propyl-
`idene]-6-11-dihydrodibenz{b,e} oxepin-2-acetie acid, hydro-
`chloride.
`Each mL of PATADAY™ solution contains: Active: 2.22 mg
`olopatadine hydrochloride equivalent to 2 mg olopatadine.
`tnactives: povidone; dibasic sodium phosphate; sodium chlo-
`ride; edetate disodium; benzalkonium chloride 0.01%
`(preservative) hydrochloric acid / sodium hydroxide (adjust
`pH); and purified water.
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 2
`
`

`

`ophthalmic
`hydrochloride
`PATADAY™ (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. Tamperevidenceis provided with a shrink band
`around the closure and neck area of the package.
`NDC 0065-0272-25
`2.5 mL fill in 4 mL ovalbottle
`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,INC.
`Fort Worth, Texas 76134 USA
`© 2005-2006 Alcon,Inc.
`
`
`aff
`
`PRODUCT INFORMATION
`ALCON/533
`PRECAUTIONS
`ADVERSE REACTIONS
`It has a pHof approximately 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
`droppertip and solution, care should be taken not to touch
`reported at an incidence of approximately 10%.
`;
`the eyelids or surrounding areas with the droppertip of the
`Thefollowing adverse experiences have been reported in 5%
`bottle. Keep bottle tightly closed when not in use.
`;
`or less of patients:
`oo.
`Patients should be advised not to wear a contactlensiftheir
`Ocular:
`blurred vision, burningor stinging, conjunctivitis,
`eye
`is
`red. PATANOL® (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, sinusitis and
`benzalkonium chloride, may be absorbed by soft contact
`lenses. Patients who wear soft contact lenses and whose
`taste perversion.
`,
`eyesare not red should be instructed to wait at least ten
`Someof 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 doseis one drop in each affected eye once
`Carcinogenesis, Mutagenesis,
`tmpairment of Fertility:
`a day.
`Olopatadine administered orally was not carcinogenic in
`HOW SUPPLIED
`mice andrats in doses up to 500 mg/kg/day and 200 mg/ke/
`day, respectively. Based on a 40 pL 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 (Ames)test, an in vitro
`mammalian chromosome aberration assay or an in vivo
`mouse micronucleustest. Olopatadine administered to male
`and female rats at oral doses of 62,500 times MROHDlevel
`resulted in a slight decrease in the fertility index and re-
`duced implantation rate;noeffects on reproductive function
`were observed at doses of 7,800 times the maximum recom-
`mended ocular human uselevel.
`Pregnancy: PregnancyCategory 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/kg/day, or 62,500 times the
`MROHD,during organogenesis showed a decrease in live
`fetuses. There are, however, no adequate and well con-
`trolled studies in pregnant women. Because animalstudies
`are not always predictive of human responses, this drug
`should be used in pregnant women only if the potential ben-
`efit to the motherjustifies 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
`knownwhethertopical ocular administration could result in
`sufficient systemic absorption to produce detectable quanti-
`ties in the human breast milk. Nevertheless, caution should
`be exercised when PATANGL® (olopatadine hydrochloride
`ophthalmic solution) 0.1% is administered to a nursing
`mother.
`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-
`ness have been observed between elderly and younger pa-
`tients,
`ADVERSE REACTIONS
`Headaches have been Teported at an incidence of 7%. The
`following adverse experiences have been reported in less
`than 5% ofpatients: 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 eachaffected eye two
`times per day at an interval of 6 ta 8 hours,
`.
`HOW SUPPLIED
`PATANOL(olopatadine hydrochloride ophthalmic solution)
`TAINER®dispenser.
`NDC 0065-0271-05
`5 mL:
`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.
`eee
`
`Olopatadineis a relatively selective histamine H, antago-
`nist and an inhibitor of the release of histamine from the
`mastcells. Decreased chemotaxis and inhibition of eosino-
`phil activation has also been demonstrated. Olopatadine is
`devoid of effects on alpha-adrenergie, dopaminergic, and
`muscarinic type 1 and 2 receptors.
`.
`Systemic bioavailability data upon topical ocular adminis-
`tration of PATADAY™solution are not available. Following
`topical ocular administration of olopatadine 0.15%
`ophthalmic solution in man,olopatadine was shownto 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 (< 0.5 ng/mL). Samples
`in which olopatadine was quantifiable were typically found
`within 2 hours of dosing and ranged from 0.5 to 1.8 ng/mL.
`Theelimination 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. Two metabolites,
`the mono-desmethy] and the N-oxide, 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 ance a
`dayis effective in the treatmentof ocular itching associated
`with allergic conjunctivitis.
`INDICATIONS AND USAGE
`PATADAY™solutionis indicated for the treatmentofocular
`itching associated with allergic conjunctivitis.
`CONTRAINDICATIONS
`Hypersensitivity to any components ofthis product.
`WARNINGS
`
`Fortopical ocular use only. Notfor injection or oral use.
`PRECAUTIONS
`Information for Patients
`As with anyeye drop, to prevent contaminating the dropper
`tip and solution, care should be taken nat to touch the eye-
`lids or surrounding areas with the droppertip of the bottle.
`Keepbottle tightly closed when not in use. Patients should
`be advised not to wear a contact lens if their eye is red.
`PATADAY™.
`(olopatadine
`hydrochloride
`ophthalmic
`solution} 0.2% should not be used to treat contactlensre-
`lated irritation. The Preservative in PATADAY™ 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
`PATADAY™ (olopatadine
`hydrochloride ophthalmic solution) 0.2% before they insert
`their contact lenses.
`:
`Carcinogenesis, Mutagenesis, !mpairmentof 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
`whenolopatadine wastested in an in vitro bacterial reverse
`mutation (Ames)test, an in vitro mammalian chromosome
`aberration assay or an in vivo mouse micronucleustest.
`Olopatadine administered to male and female rats at oral
`doses of approximately 100,000 times MROHDlevel re-
`sulted in a slight decrease in the fertility index and reduced
`implantation rate; no effects on reproductive function were
`observed at doses of approximately 15,000 times the
`MROHDlevel.
`Pregnancy:
`:
`Teratogenic effects: Pregnancy Category C
`Olopatadine wasfound not to be teratogenic in rats and rab-
`bits. However, rats treated at 600 mg/kg/day, or 150,000
`times the MROHDandrabbits treated at 400 mg/kg/day, or
`approximately 100,000 times the MROHD,during organo-
`Benesis showed a decreasein live fetuses, In addition, rats
`treated with 600 mg/kg/day of olopatadine during organo-
`genesis showed a decreasein 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.
`Thereare, however, no adequate and well-controlled studies
`in pregnant women. Because animalstudies 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 embryoorfetus.
`.
`.
`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 sufficient systemic
`absorption to produce detectable quantities in the human
`breast milk, Nevertheless, caution should be exercised
`when PATADAY™(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 differencesin safety and effectiveness have been
`observed between elderly and youngerpatients.
`
`
` 0.1% is supplied as follows: &mL in plastic DROP.
`
`PATANOL®
`[pa'ta-ndi]
`{olopatadine hydrochloride ophthalmic solution) 0.1%
`DESCRIPTION
`ophthalmic
`hydrochloride
`PATANOL® (olopatadine
`solution) 0.1% is a sterile ophthalmic solution containing
`olopatadine, a relatively selective H,- 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 L mg olopatadine.
`Preservative: benzalkonium chloride 0.61%. tnactives: 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
`Olopatadineis an inhibitorofthe release of histamine from
`the mast cell and a relatively selective histamine
`H,~antagonist that inhibits the in vivo and in vitro 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. Two 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
`(<0.5 ng/mL). Samples in which olopatadine was quantifi-
`able were typically found within 2 hours of dosing and
`ranged from 0.5 te 1.3 ng/mL. The halflife 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
`PATANOLwas effective in the treatment of the signs and
`symptoms of allergic conjunctivitis when dosed twice daily
`for up to 6 weeks. Results from conjunctival 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 ocularitching associated with allergic
`conjunctivitis.
`.
`.
`INDICATIONS AND USAGE
`*
`.
`PATANOL(olopatadine hydrochloride ophthalmicsolution)
`0.1% is indicated for the treatment of the signs and symp-
`toms ofallergic 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 notfor injection or oral
`use,
`
`SYSTANE®
`[sistan]
`Lubricant Eye Drops
`DESCRIPTION
`
`oTc
`.
`
`.
`
`SYSTANEG®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”
`dueto drynessof the eye.
`:
`Active Ingredients: Polyethylene Glycol 400 0.4% and
`Propylene Glycol 0.3% as lubricants.
`.
`Inactive Ingredients: boric acid, calcium chlaride, hydroxy-
`propyl guar, magnesium chloride, polyquaternium-1 as a
`preservative, potassium chloride, purified water, sodium
`chloride, zine 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
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 3
`
`Consult 2608 PDR® supplements and future editions for revisions
`
`Zc
`
`
`IPR2018-01020 and IPR2018-01021, Exhibit 1011, Page 3
`
`

`

`V2
`e578
`L008
`
`
`
`EDITION
`
`2008
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`
`PHYSICIANS
`EOK
`REFERENCE
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`THONISON Copyright © 2007 and published by Thomson Healthcare Inc. at Montvale, NJ 07645-1725. All rights reserved. Noneof the contentofthis
`= publication may be reproduced, storedin a retrieval system, resold, redistributed, or transmitted in any form or by any means(electronic,
`mechanical, photocopying, recording, or otherwise) without the prior written permission of the publisher. Physicians’ Desk Reference® and PDR?®are registered trade-
`marks of Thomson Healthcare Inc. PDR® for Ophthalmic Medicines; PDR® for Nonprescription Drugs, Dietary Supplements, and Herbs; PDR® Guide to Drug Interactions,
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`
`

`

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