`
`
`
`__ ABPI COMPENDIUMOF DATA SHEETS
`:
`AND
`SUMMARIES OF PRODUCT CHARACTERISTICS
`/ 1999-2000
`; With TheCode of Practice for the
`Pharmaceutical Industry
`
`.Aa Datapharm Publications Limited
`
`8... 12.Whitehall; London SW1A 2DY
`
`-
`
`
`
`CIPLA LTD. EXHIBIT 2027 PAGE 1
`
`CIPLA LTD. EXHIBIT 2027 PAGE 1
`
`

`

`ALLEN & HANBURYS
`
`43
`
`FLIXONASE* AQUEOUS NASAL
`SPRAY
`
`
`
`.
`
` |ii |
`
`”
`
`FLIXOTIDE* ACCUHALER*
`Qualitative and quantitative composition Flixotide
`Accuhaler is a moulded plastic device containing a
`foil strip with 60 regularly placed blisters each contain-
`ing a mixture of microfine fluticasone propicnate
`{50 micrograms, 100 micrograms, 250 micrograms or
`500 micrograms) and largerparticle size lactose.
`Pharmaceutical
`form Muiti-dose
`dry
`powder
`inhalation device.
`
`Presentation Flixonase Aqueous Nasal Spray is an
`aqueous suspension of microfine fluticasone propio-
`nate (0.05% ww} for topical administration to the
`nasal mucosa by means of a metering, atomising
`spray pump. Each 100 mg of spraydelivered by the
`nasal adaptor contains 50 microgramsoffluticasone
`propionate.
`cellulose,
`Other
`ingredients: Microcrystalline
`sodium carboxymethylcellulose,dextrose, polysorbate
`80, purified water, benzalkonium chloride and
`phenylethylaleohaol.
`.
`Uses Flixonase Aqueous Nasal Spray is indicated
`for the prophylaxis and treatmentof seasonalallergic
`rhinitis including hayfever, and perennial rhinitis.
`Fluticasone propionatehas potent anti-inflammmatory
`activity but when used topically on the nasal mucosa
`oof.
`has no detectable systemic activity.
`Dosage and administration
`Flixonase Aqueous
`Nasal Spray is for administration by the intranasal -
`route only.
`Adults and children over 12 years of age: For the
`prophylaxis and treatment of seasonalallergic rhinitis
`and perennial rhinitis: two sprays into each nostril
`once a day, preferably in the morning. In some cases
`two sprays into each nostril
`twice daily may be
`required. The maximum daily dose should not excéed
`four sprays into each nostril.
`Elderly:The normal adult dosage fs applicable.
`Chiidren under 12 years of age: For the prophylaxis
`and treatment of seasonal allergic rhinitis and
`perennialrhinitis in children aged 4 to 14 years a dose
`of one spray into sach nostril once daily is
`recommended. In some cases one spray into each
`nostril twice daily may be required. The maximum
`Clinical particulars
`daily dese should not exceed two sprays into each
`nostril.
`\
`Therapeutic indications: Fluticasone propionate given.
`by inhalation offers preventative treatment for
`therapeutic benefit
`fuli
`For
`regular: usage ‘is.
`asthma. At recommended doses it has: a potent
`essential. The absence of an immediate effect should.
`glucocorticoid anti-inflammatory action within the
`be explained to the patient as maximum reliefmay.
`lungs, with a lowerincidence and severity of adverse
`not be obtained until after 3 to 4 days of treatment.
`effects than those cbserved when corticosteroids are
`Contra-indications, warnings,etc .
`.
`administered systemically. {n the majority of patients
`Contra-indications:Flixonase Aqueous Nasal Spray is ~
`it has no effect on adrenal function or reserve at
`contra-indicated in patients with hypersensitivity to
`.. fecommended doses.
`anyofits ingredients.
`.
`~
`‘Adults: Prophylactic managementin:
`intermittent
`Mild
`asthma: Patients
`requiring
`Precautions: Infections of the nasal airways should be
`symptomatic bronchodilator asthma medication ona
`appropriately treated but do not constitute a specific
`regulardaily basis.
`contra-indication
`to
`treatment with Flixonase
`Moderate asthma: Patients with unstable or
`
`Aqueous Nasal Spray.
`‘
`ae
`.
`worsening asthma despite prophylactic therapy or
`The full benefit of Flixonase Aqueous Nasal 5
`bronchodilator alone.
`:
`
`may not be achieved until treatment has been ad
`Severe asthma:Patients with severechronic asthma
`istered for. several days.
`Sa
`and those who are dependent on systemic cortico-
`Care must bé taken while transferring patients from |
`steroids for adequate control of symptoms. On
`systemic steroid treatment to Flixonase Aqueous
`introduction of inhaled fluticasone propionate many
`Nasal Spray if there is any reason to suppose that
`of these patients may. be able to reduce significantly,
`their adrenal functionis impaired.
`or to. eliminate, their requirement for oral cortico-
`Although Flixenase Aqueous Nasal Spray will
`steroids.
`.
`control seasonal allergic rhinitis in most cases, an.
`Children: Any child who requires prophylactic
`abnormally heavy challenge of summerallergens
`medication, including patients not controlled on cur-
`may in certain instances necessitate appropriate
`rentlyavailable prophylactic medication.
`additional
`therapy, particularly to control
`eye
`symptoms.
`Ce ;
`oe
`Posology and method of administration: Flixotide
`Accuhaler is for oral.
`inhalation. use. only. Flixotide
`Pregnancy:There is inadequateevidence. of safety.in
`Accuhaler is suitable for. many patients,. including
`human pregnancy. Administration of corticosteroids.
`those whocannot .use -a metered-dose inhaler
`to pregnant animals can cause abnormalities of fetal
`successfully.
`.
`development, including cleft palate and intra-uterine
`Patients should be made aware of the prophylactic
`growth retardation. There may therefore be a very
`smail risk of such effects In the humanfetus, Itshould
`nature of therapy with Flixotide Accuhaler and that it
`should be taken regularly even when they are
`benoted, however, that the fetal changes in animals
`
`occur after relatively high systemic exposure; direct
`Treatment with inhaled beclomethasone dipropionate
`than weekly intervals. For maintenance doses of
`should be continued at a dose sufficient to contro!
`intranasal application ensures minimal
`systemic
`prednisolone,orits equivalent, of 10 mg daily or less,
`exposure,
`:
`asthma.
`the decrements in dose should not be greater than
`As with other drugs the use of Flixonase Aqueous
`1 mg per day, at not less than weekly intervals. For
`Pharmaceutical precautions To keep the Rotacaps
`
`Nasal Spray during human pregnancy requires that
`_ maintenance doses of prednisolone in excess of
`capsules in good condition it is important that they
`the possible benefits of the.drug-be weighedagainst
`“10mg daily, it may be appropriate to employ cau- ~
`
`are storéd iiia-dry plate below 30°C wherethey will
`the possible hazards.
`.
`....tiously larger decrements in dose at weekly intervals. .
`not be-exposed-to -extremes of temperatura. A
`Lactation: The secretion offluticasone propionate in
`~~ Some patients feel unwell in a non-specific way
`i
`convenient
`supply may be carried in the special
`human breast milk has not been.investigated. Subcu-
`|. during the withdrawal phase despite maintenance or.
`container“for“the ‘Rotahaler device. The Rotacaps
`taneous administration of fluticasone propionate to
`:
`even improvement of the respiratory function. They
`capsules should be inserted into the Rotahaier
`should be encouraged to persevere with the Rotahaler
`lactating laboratory rats produced measurabte plasma
`immediately prior to use to avoid softening. Failure to
`and withdrawal of systemic steroid continued,unless
`levels and evidence of fluticasone propionate in the
`observethis instruction may affect the delivery of the
`there are objective signs of adrenal insufficiency,
`_ milk. However, following intranasal administration to
`drug. The Rotacaps must only be used in the
`Patients weaned off oral steroids whose adreno-
`Rotahaler.
`primates, no drug was detected in the plasma, and it
`cortical function is impaired should carry a stercid
`is therefore unlikely that the drug would be detectable
`Legal category POM.
`warning card indicating that
`they may need
`in milk. Whenfluticasone propionate is used in breast
`feeding mothers the therapeutic benefits must be
`100
`Rotacaps
`Becotide
`Package
`quantities
`supplementary systemic steroid during periods of
`stress, é.g. worsening asthma attacks, chest infec-
`micrograms, 206 micrograms and 400 micrograms
`weighed against the potential hazards to mother and
`tions, major intercurrent ifness, surgery, trauma,etc.
`baby.
`are supplied in packs of 112.
`Replacement of systemic steroid treatment with
`Further information Nil.
`Side-effeste: Extremely rare cases of nasal septal
`inhaled therapy sometimes unmasks allergies such
`Product licence numbers
`perforation have been reported falfowing the use of
`as allergic rhinitis or eczema previously controlled by
`intranasal corticosteroids, usually in patients who
`Becotide Rotacaps 100 micrograms 10949/0061
`the systemic drug. These allergies
`should be
`have had previous nasal surgery.
`Becotide Rotacaps 200 micrograms 10949/0062
`symptomatically treated with antihistamine and/or
`As with othernasal sprays, dryness andirritati.--
`Becotide Rotacaps 400 micrograms 10949/0063
`topical preparations, including topical steraids.
`the nose and throat, unpleasant taste and smel.
`-..
`-
`Treatment with Becotide Rotacaps should not be
`epistaxis have been reported.
`i
`stopped abruptly,
`.
`Hypersensitivity reactions including skin rast}
`As with all inhaled corticosteroids, special care is
`oedemaofthe face or tongue have been reporte.
`necessary in patients with active or quiescent pulmo-
`There have also been rare reports of anaphy,.
`nary tuberculosis.
`anaphylactoid reactions and bronchospasm.
`—
`‘Pregnancy: There is inadequate evidenceof safety in
`Overdosage:There are no data available on the e
`human pregnancy. Administration of corticosteroids
`of acute or chronic overdosage with Flixd
`to pregnant animals can causa abnormalities of fetal
`Aqueous Nasal Spray. Intranasal administrati¢
`developmentincluding cleft palate and intra-uterine
`~
`2mqg fluticasone propionate twice daily for s:
`growth retardation. There may therefore be a very
`days to healthy human volunteers had no effe,*:.
`gmail risk of such effects in the humanfetus. it should
`hypothalamic-pituitery-adrenal (HPA) axis fun -
`be noted, however,that the fetal changes in animals
`Inhalation or oral administration of high dost:
`
`occur after relatively high systemic exposure. Because
`corticosteroids over a long period may teq::
`beclomethasone dipropionateis delivered directly to
`suppression of HPA function.
`‘
`:
`the lungs by the inhaled route it avoids the high level
`of exposure that occurs when corticosteroids are
`Pharmaceutical precautions Shake gently before
`
`-
`-
`Flixonase Aqueous Nasal Spray should be s
`given by systemic routes.
`
`below 30°C.
`Mess
`The use of beclomethasone dipropionate in preg-
`
`naney requires that the possible benefits of the drug
`Legal category POM.
`be weighed against the possible hazards.It should be
`
`Package quantities Flixonase Aqueous Nasal Sprayis
`noted that the drug has been in widespread use for
`
`supplied in an amber glass bottle fitted with a
`many years without apparentill consequence.
`
`metering, atomising pump, nasal adaptor and a dust
`Lactation: No
`specific
`studies
`examining the
`
`cover. Each bottle provides approximately 120
`transference of beclomethasone dipropionate into the
`metered sprays, when used as recommended.
`
`milk of lactating animals have been performed.It is
`
`reasonable to assume that beclomethasone dipro-
`Further information Nil.
`—
`pionate is secreted in milk, but at the dosages used
`Product licence number 19949/0036
`
`for direct inhalation there is low potential for signifi-
`cant levels in breast milk.
`
`Theuse of beclomethasone dipropionatein mothers
`
`breast feeding their babies requires that the therapeu-
`tic benefits of the drug be weighed against the
`
`potential hazards to the mother and baby.
`
`Side-effects: Systemic effects of inhaled corticoste-
`
`roids may oceur, particularly at high doses prescribed
`
`for prolonged periods. These may include adrenal
`
`suppression, growth retardation in children and ado-
`
`lescents, decrease in bone mineral density, cataract
`
`and glaucoma,
`,
`Candidiasis of the mouth and throat (thrush) occurs
`
`n some patients, the incidence increases with doses
`
`greater than 400 micrograms beclomethasonedipro-
`Pionate per day. Patients with high blood levels of
`
`Candida precipitins, indicating a previous infection,
`
`are more likely to develop this complication, Some-
`
`patients may find it helpful to rinse their mouth
`
`thoroughly with water after using the Rotahaler.
`
`Symptomatic candidiasis can. be-treated with topical
`
`anti-fungal therapy whilst still continuing with the
`
`treatment.
`eed
`/
`In some patients inhaled beclomethasone dipro-
`
`pionate may causé hoarsenessor throatirritation:It
`may be helpfu! to rinse the mouth out with water
`
`immediately after inhalation...‘
`
`As with other inhalationthérapy, paradoxical bron:
`
`chospasm mayoccur with:animmediate increase‘in,
`wheezing after dosing. This respondsto a fast-acting
`
`inhaled bronchodilator. The preparation should be-
`
`discontinued immediately, the patient assessed and,
`
`If necessary,alternative therapy instituted.
`.
`
`Hypersensitivity
`reactions
`including
` rasties,
`
`urticaria, pruritus and erythema, and oedema of the
`ayés, face, lips and throat, have been reported.
`
`Overdosage: Acute. Inhalation of the drug in doses in
`
`excess of those recommended may tead to temporary
`
`Guppression of adrenal function. This does not neces- -
`
`aitate amargency action being taken.In these patients
`
`draktmant with beclomethasone dipropionate by .
`
`inhalation should be continued at a dose sufficient to
`
`control asthina; adrenal function recovers in a few
`
`: days and can be verified by measuring plasmacortisol.
`
`hronle, Use of inhaled beclomethasone dipropion-
`ate in dally doses in excess of 1,500 micrograms over
`prolange perlods may fead to adrenal suppression.
`-
`onitering of adrenal. reserve may be indicated.
`
`CIPLA LTD. EXHIBIT 2027 PAGE 2
`
`
`
`!
`:
`
`:
`|
`
`/
`i
`*
`
`
`
`
`CIPLA LTD. EXHIBIT 2027 PAGE 2
`
`

`

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`
`~CIPLA LTD. EXHIBIT2027PAGE3
`
`CIPLA LTD. EXHIBIT 2027 PAGE 3
`
`

`

`aw
`
`CorporateIntellectual Property
`
`SSSS &
`
`
`Sy es
`QS Ma
`
`
`
`By EPOline ONLY
`
`European Patent Office
`D-80298 Munchen
`Germany
`
`14!" January 2010
`
`Our ref: JLM/OPP10171
`
`Dear Sirs,
`
`European Patent No: 1 519 731B1
`Proprietor: CIPLA Ltd.
`
`
`
`Direct tel
`Direct fax
`
` +44(0) 1438 76 4024
`+44 (0)20 8047 6894
`
`This is an opposition to European Patent No. EP 1 519 731 B1, in the name of CIPLA Ltd. The
`Opponent is Glaxo Group Limited. We attach the following Documents:
`
`(i)
`(ii)
`
`Statement of Grounds of Opposition; and
`Documents D1-D3aslisted in the Statement of Grounds of Opposition.
`
`Instructions for the deduction of the Opposition Fee from Account No. 28050015 in the name of
`GlaxoSmithKline are included with the online submission via Epoline. Please deduct the correct
`amount if the indicated amount is incorrect.
`
`In the event that the Opposition is deemed inadmissible, or that the EPO considers that the
`Patent should be maintained, Oral Proceedings under A116 are hereby requested.
`
`Yoursfaithfully,
`
`ae
`
`A ‘
`cs
`
`Lea”ULiitd
`ft a
`
`Dr Jen L Le Miére
`Patent Counsel
`
`Enc:
`
`Statement of Grounds of Opposition
`D1, EP 0 780 127 A1
`D2, Dykewicz journal article
`D3, ABPI datasheet, Flixonase
`
`
`
`CIPLA LTD. EXHIBIT 2027 PAGE 4
`
`CIPLA LTD. EXHIBIT 2027 PAGE 4
`
`

`

`
`
`Diagnosis and Management of Rhinitis:
`Complete Guidelines of the Joint Task Force
`on Practice Parameters in Allergy, Asthma
`and Immunology
`Mark S Dykewicz, MD,t Stanley Fineman, MD, MBA,§ Editors
`David P Skoner, MD,§9 Chair, Workgroup on Rhinitis
`Richard Nicklas, MD||; Rufus Lee, MD; Joann Blessing-Moore, MD; James T Li, MD, PhD**;
`I Leonard Bernstein, MD*+*t; William Berger, MD, MBAt#; Sheldon Spector, MDS§§; and
`Diane Schuller, MD,]|||| Associate Editors
`
`This document contains complete guidelines for diagnosis and managementof
`thinitis developed by the Joint Task Force on Practice Parameters in Allergy,
`Asthma and Immunology, representing the American Academy ofAllergy, Asthma
`and Immunology, the American College of Allergy, Asthma and Immunology and
`the Joint Council on Allergy, Asthma and Immunology. The guidelines are com-
`prehensive and begin with statements on clinical characteristics and diagnosis of
`different forms ofrhinitis (allergic, non-allergic, occupational rhinitis, hormonal
`rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food
`ingestion), and other conditions that may be confused with rhinitis. Recommenda-
`tions on patient evaluation discuss appropriate use of history, physical examination,
`and diagnostic testing, as well as unproven or inappropriate techniques that should
`not be used. Parameters on management include use of environmental control
`measures, pharmacologic therapy including recently introduced therapies and aller-
`gen immunotherapy. Because of the risks to patients and society from sedation and
`performance impairment caused by first generation antihistamines, second genera-
`tion antihistamines that reduce or eliminate these side effects should usually be
`considered before first generation antihistamines for the treatment of allergic rhi-
`nitis. The document emphasizes the importance of rhinitis management for co-
`morbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on
`special considerations in patients subsets (children, the elderly, pregnancy, athletes
`and patients with rhinitis medicamentosa); and when consultation with an allergist-
`immunologist should be considered.
`
`Ann Allergy Asthma Immunol 1998;81:478-518.
`
`CONTRIBUTORS: Donald W Aaronson, MD;
`Allen D Adinoff, MD; James N Baraniuk, MD;
`Robert
`J Dockhorn, MD; William Dolen,
`MD; Howard M Druce, MD; Marianne Frieri,
`MD,PhD; Morton P Galina, MD; Leon Greos, MD;
`Alfredo A Jalowayski, PhD; Craig F La Force,
`MD; Eli O Meltzer, MD; Robert M Naclerio,
`MD; Keith M Phillips, MD; Gordon Raphael, MD;
`Michael Schatz, MD; Michael J Schumacher,
`MBBS; Howard J Schwartz, MD; Tommy C
`Sim, MD; Chester T Stafford, MD; William W
`Storms, MD; Michael J Tronolone, MD; Mi-
`chael J Welch, MD: Chester C Wood, MD; and
`Robert S Zeiger, MD, PhD
`
`PRINCIPAL REVIEWERS: Jean A Chap-
`mun, MD; Robert A Nathan, MD; John Sanulli,
`Jr, MD; Michael Schatz, MD; and Betty B Wray,
`MD
`This document was developed by the Joint
`Task Force on Practice Parameters in Allergy,
`Asthma and Immunology,
`representing the
`American Academy of Allergy, Asthma and Im-
`munology (AAAAIT), the American College of
`Allergy, Asthma and Immunology (ACAAT) and
`the Joint Council on Allergy, Asthma and lm-
`munology. The AAAAI and the AACAAThave
`jointly accepted responsibility for establishing
`these practice parameters. Because this docu-
`
`ment incorporated the efforts of many partici-
`pants, no single individual, including those who
`served on the Joint Task Force, is authorized to
`provide an official interpretation of this docu-
`ment by the AAAAT or ACAAT. Any request for
`information about or an interpretation of this
`document by the AAAAT or ACAATshould be
`directed to the Executive Offices of the AAAAT,
`ACAAI and the Joint Council on Allergy,
`Asthma and Immunology.
`* This parameter was developed with Dr.
`Nicklas in his private capacity and not in his
`capacity as a medical officer with the Food and
`Drug Administration. No official support or en-
`dorsement by the Food and Drug Administration
`is intended or should be inferred.
`t Division of Allergy and Immunology, De-
`partment of Internal Medicine, Saint Louis
`University School of Medicine, St. Louis, Mis-
`souri; § Department of Pediatrics, Emory Uni-
`versity School of Medicine, Atlanta, Georgia;
`{{ Departments of Pediatrics & Otolaryngology,
`Children’s Hospital of Pittsburgh, University
`of Pittsburgh School of Medicine, Pittsburgh,
`Pennsylvania;
`|| Department
`of Medicine,
`George Washington Medical Center, Washing-
`ton, DC; § Departments of Medicine & Pediat-
`rics, Stanford University Medical Center, Palo
`Alto, California; ** Department of Medicine,
`Mayo Clinic & Medical School, Rochester, Min-
`nesota; +t} Departments of Medicine & Environ-
`mental Health, University of Cincinnati College
`of Medicine, Cincinnati, Ohio; tt Department of
`Pediatrics, Division of Allergy and Immunology,
`University of California College of Medicine,
`Irvine, California; §§ Department of Medicine,
`University of California-Los Angeles, Los An-
`geles, California;
`||| Department of Pediatrics,
`Pennsylvania State University, Milton S. Her-
`shey Medical College, Hershey, Pennsylvania.
`The Joint Task Force has made an intense
`effort to appropriately acknowledge all contrib-
`utors to this parameter. If any contributors are
`inadvertently excluded, the Task Force will in-
`sure that appropriate recognition of such contri-
`butions is subsequently made.
`
`
`478
`ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY
`
`CIPLA LTD. EXHIBIT 2027 PAGE 5
`
`CIPLA LTD. EXHIBIT 2027 PAGE 5
`
`

`

`
`
`Summary
`
`
` Contents and Organization of this Document Statement Page
`INTRODUCTION .1.ee 480
`
`DEFINITION OF RHINITIS «0...0.ee 1
`DIFFERENTIAL DIAGNOSIS OF RHINITIS .......0.0.0.. 0000000 ee eee 2
`
`Allergic Rhinitis 2.0... 0...ceee 3-12
`
`Non-Allergic rhinitis... 0...00eee 13
`Infectious rhinitis2...ee ee
`14
`
`Non-Allergic rhinitis without eosinophilia ...........00.00.0 00000 ce ee eee
`
`15
`
`Non-Allergic rhinitis with eosinophilia syndrome... 2...0. ee 16
`
`Occupational rhinitis ©...2...eee 17
`
`Hormonalrhinitis (@regnancy and hypothyroidism) ........... 00000 eee 18
`Drug-induced rhinitiS 2.0...ee ee eee eee eens
`19
`
`Rhinitis from food ingestion .. 6...ke 20
`
`Other conditions that may be confused with rhinitis ... 1... 0.0.0. 0c ee 21
`
`480
`480
`
`480
`
`484
`485
`
`485
`
`486
`
`486
`
`487
`487
`
`487
`
`488
`
`489
`22
`Nasal polypS. 6...6...ee ee
`EVALUATION OF RHINITIS «2...ne 489
`
`History2.2ee 23-24
`
`Physical examination .. 0.0... 0.eeee 25
`
`Testing for specific IGE... 2.keee 26
`
`Special diagnostic techniqueS 1... 0.0.0.0 ce ee ee ee eee eee eee
`
`27
`
`Nasal cytology .. 0...eeee 28
`
`Total serum IgE, blood eosinophil counts .. 2.2... 2.0ee 29
`
`Unproven or inappropriate testing .......0 0.000 eee 30
`MANAGEMENT OF RHINITIS 2.0.0...ee ee
`Environmental control measures ..1...ee 31
`
`Pharmacologic therapy .. 2.2... ceeee 32
`Antihistamines2...ee 33-35
`
`Issues with sedation/performance impairment ........... 0000 cee ee 34
`Cardiac effects of some antihistamines .............. 00000 eee 35
`
`Intranasal antihistamines
`
`.. 1... 0.0.0.0.ee 36
`
`Oral and nasal decongestants ... 1...00.ee 37
`Nasal corticosteroids 2.0...ee 38
`
`Oral and parenteral corticosteroids .. 2... ..0. 0000 ee ee eee
`
`39
`
`Intranasal cromolyn 2.6...ee 40
`
`Intranasal anti-cholinergics .. 0... 0...ee 41
`
`Oral anti-leukotriene agentS .... 0... 00ce eee 42
`
`Allergen immunotherapy .....0..0. 00 cc ee ee ee ee ee eee eee eens
`
`43
`
`Surgical approaches for co-morbid conditions .. 1.1... 0. eee ee 44
`
`Important considerations in management ....... 2.000cee 45
`
`Education of patient and caregivers .... 0.0.0...ecee 46
`Importance of rhinitis management for concomitant asthma, sinusitis, and otitis media ................
`47
`
`Special considerations in children, the elderly, pregnancy, athletes, and rhinitis medicamentosa .........
`
`48
`
`Consultation with an allergist-immunologist ..........0. 00 eee ee 49
`
`489
`
`491
`
`492
`
`493
`
`494
`
`495
`
`495
`497
`497
`
`500
`501
`
`501
`501
`
`505
`
`505
`506
`
`506
`
`507
`
`508
`
`510
`
`510
`
`511
`
`511
`
`511
`512
`
`513
`
`518
`
`
`VOLUME 81, NOVEMBER(PARTID, 1998
`479
`
`CIPLA LTD. EXHIBIT 2027 PAGE 6
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`CIPLA LTD. EXHIBIT 2027 PAGE 6
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`

`

`
`
`INTRODUCTION
`
`Rhinitis may be caused by allergic,
`non-allergic, infectious, hormonal, oc-
`cupational and other factors. All too
`often, important causcs of rhinitis go
`unrecognized by both physicians and
`patients. This leads to suboptimal con-
`trol of the disease.
`Rhinitis is a significant cause of
`widespread
`morbidity.
`Although
`sometimes mistakenly viewed as a
`trivial disease, symptoms of rhinitis
`may significantly impact the patient’s
`quality of life, by causing fatigue,
`headache, cognitive impairment and
`other systemic symptoms. Appropriate
`management of rhinitis may be an im-
`portant component in effective man-
`agementof co-existing or complicating
`respiratory conditions, such as asthma,
`sinusitis, or chronic otitis media. The
`cost of treating rhinitis and indirect
`costs related to loss of workplace pro-
`ductivity resulting from the disease are
`substantial. The estimated cost of al-
`lergic rhinitis based on direct and in-
`direct costs is 2.7 billion dollars for the
`year 1995, exclusive of costs for asso-
`ciated medical problems such as sinus-
`itis and asthma. Allergic rhinitis, the
`most common form of rhinitis, affects
`20 to 40 million people in the United
`States annually, including 10% to 30%
`of adults and up to 40% of children.
`This document
`reviews clinically
`relevant information about pathogene-
`sis and provides guidelines about diag-
`nosis and managementof rhinitis syn-
`dromes. Throughout
`the document,
`summary statements that articulate key
`points precede supporting text and rel-
`evant citations of evidence-based pub-
`lications.
`
`accompanied by symptoms involving
`the cyes, cars, and throat. Post-nasal
`drainage may also be present
`fre-
`quently.
`
`Reference
`
`1. Druce HM. Allergic and nonallergic
`rhinitis. In: Middleton EJ, Reed CE,
`Ellis EF, et al, eds. Allergy principles
`and practice, 5th edition. St. Louis:
`Mosby-Year Book
`Inc,
`1998:
`1005-1016.
`
`DIFFERENTIAL DIAGNOSIS OF
`RHINITIS
`2. Rhinitis should be classified by
`etiology as allergic or nona