~ ! l
`
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`
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`I
`
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`
`PDR®
`54
`2000
`
`EDITION
`
`PHYS CANS'
`DESK
`REFERENC
`
`rn ® rn ~ w rn
`l!EC 6 1999
`
`FOLEY & tARDNER
`WASHINGTON D.C.
`
`Senior Vice President, Directory Services: Paul Walsh
`
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`Mana~er, Drug Information Se_rvices: Thomas Fleming, RPh
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`Editor, Directory Services: David W. Sifton
`Senior Associate Editor: Lori Murray
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`- - . Copyright© 2000 and published by Medical Economics Company, Inc. at Montvale, NJ 07645-1742. All rights reserved. Nolie: oi the content of this 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
`otherwise) without the prior written permission of the publisher. PHYSICIANS' DESK REFERENCE•, PDR", PDR For Ophthalmology", Pocket PDR", and The PDR° Family
`Guide to Prescription Drugs0 are registered trademarks used herein under license. PDR For Nonprescription Drugs and Dietary Supplements™, PDR Companion Guide™,
`PDR" for Herbal Medicines™, PDR0 Medical Dictionary™, PDR" Nurse's Drug Handbook™, PDR" Nurse's Dictionary™, The PDR" Family Guide Encyclopedia of Medical
`Carer"', The PDR• Family Guide to Natural Medicines and Healing Therapies™, The PDR" Family Guide to Common Ailmentsr"', The PDR" Family Guide to Over-the(cid:173)
`Counter Drugs™, and PDR• Electronic Library TM are trademarks used herein under license.
`
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`Officers of Medical Economics Company: President and Chief Executive Officer: Curtis B. Allen; Vice President, New Media: L. Suz~nne BeDell; Vice President, Corporate Human
`Resources: Pamela M. Bilash; Vice President and Chief Information Officer: Steven M. Bressler; Chief Rnancial Officer: Christopher Caridi; Vice President and Controller: Barry
`Gray; Vice President, New Business Planning: Linda G. Hope; Vice President, Business Integration: David A. Pitier; Vice President, Rnance: Donna Santarpia; Senior Vice President,
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`
`Exhibit 1008
`IPR2017-00807
`ARGENTUM
`
`ISBN: 1-56363-330-2
`
`® Printed on recycled paper
`
`000001
`
`

`

`PRODUCT INFORMATION
`
`MUCO-FEN® 800 DM TABLETS
`(mu-co-fin]
`Guaifenesin/Dextromehorphan HBr
`
`~ Children 6-12 years of age: ~ t?blet every 12 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-104-10)
`
`AST ELIN®
`(azelastine hydrochloride)
`Nasal Spray, 137 mcg
`For Intranasal Use Only
`
`WALLACE/3147
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Guaifenesin ............... , .................... : .................. 800 mg
`Dextromethorphan Hydrobromide ......................... 60 mg
`DOSAGE
`Adults and children over 12 years of age: l tablet every 12
`hours not to exceed 2 tablets in 24 hours
`Children S-12 years of age: 1h tablet every 12 hours not to
`exceed 1 tablet in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-114-10)
`
`MUCO-FEN® 800 Tablets
`(mu-co-fin]
`Guaifenesin
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Guaifenesin ....... ..................... .....••... .....•..•. ... .•. 800 mg
`DOSAGE
`Adults and children over 12 years of age: 1-1 Yi tablets every
`12 hours not to exceed 3 tablets (2400 mg) in 24 hours
`Children 6-12 years of age: Yi tablet every 12 hours not to
`exceed 1200 mg in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-109-10)
`
`MUCO·FEN® 1200 TABLETS
`[mu-co-fin]
`Guaifenesin
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Guaifenesin ...................................................... 1200 mg
`DOSAGE
`Adults and children over 12 years of age: 1 tablet every 12
`hours not to exceed 2 tablets (2400 mg) in 24 hours
`Children 6-12 years of age: Yi tablet every 12 hours not to
`exceed 1 tablet (1200 mg) in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-120-10)
`
`MUCO·FEN® DM TABLETS
`[mu-co-fin]
`Guaifenesin/Dextromethorphan HBr
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Guaifenesin ................ : ....................................... 600 mg
`Dextromethorphan Hydrobromide ...... : ................... 30 mg
`DOSAGE
`Adults and children over 12 years of age: 1-2 tablets every
`12 hours not to exceed 4 tablets in 24 hours
`Children 6-12 years of age: 1 tablet every 12 hours not to
`exceed 2 tablets in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-108-10)
`
`MUCO·FEN® LA Tablets
`(mu-co-fin]
`Guaifenesin ·
`
`PROFEN II® TABLETS
`fpro'-finJ
`Phenylpropanolamine HCl/Guaifenesin
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Phenylpropanolamine Hydrochloride .... ........... ... 37 .5 mg
`Guaifenesin •. ................ .......................... ........... 600 mg
`DOSAGE
`Adults and children over 12 years of age: 1-2 tablets every
`12 hours not to exceed 4 tablets in 24 hours
`Children 6-12 years of age: l tablet every 12 hours not to
`exceed 2 tablets in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-107-10)
`
`PROFEN II OM® Liquid
`fpro'-finJ
`Dextromethorphan HBr/Phenylpropanolamine
`HCl/Guaifenesin
`
`~
`
`DESCRIPTION
`Each 5 mL (one teaspoonful) of PROFEN IT DM® LIQUID
`contains:
`Dextromethorphan HBr ........................................ 10 mg
`Phenylpropanolamine HC! ................................. 12.5 mg
`Guaifenesin •.•... .................................. ............... 200 mg
`In a sugar free, dye free and alcohol free base.
`DOSAGE
`Adults and children 12 years or older: 1-2 teaspoonfuls ev(cid:173)
`ery 4 hours not to exceed 12 teaspoonfuls in 24 hours. Chil(cid:173)
`dren 6-12 years of age: 1/,,-l teaspoonful every 4 hours not
`to exceed 6 teaspoonfuls in 24 hours. Children 2-6 years of
`age: 1/4- 1/ 2 teaspoonful not to. exceed 3 teaspoonfuls in 24
`hours. Children under 2 year5: As directed by physfoian.
`HOW SUPPLIED
`PROFEN II DM® LIQUID is available as a sugar, alcohol
`and dye-free clear liquid having a cherry odor and flavor.
`Pint Bottles: NDC 59310-201-16.
`
`PROFEN II DM® TABLETS
`[pro '-fin]
`Dextromethorphan HBr/Phenylpropanolamine
`HCl/Guaifenesin
`
`~
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Dextromethorphan Hydrobromide ........................ 30 mg
`Phenylpropanolamine Hydrochloride .................. 37 .5 mg
`Guaifenesin
`..... ....... ...... ............. ...•. .. ... .......... .•. 600 mg
`DOSAGE
`Adults and children over 12 years of age: 1-2 tablets every
`12 hours not to exceed 4 tablets in 24 hours
`Children 6-12 years of age: 1 tablet every 12 hours not to
`exceed 2 tablets in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310-110-10)
`
`DESCRIPrlON
`Astelin® (azelastine hydrochloride) Nasal Spray, 137 micro(cid:173)
`grams (mcg), is an antihistamine formulated as a metered(cid:173)
`spray solution for intranasal administration. Azelastine hy(cid:173)
`drochloride occurs as a white, almost odorless, crystalline
`powder with a bitter taste. It has a molecular weight of
`418.37. It is sparingly soluble in water, methanol, and pro(cid:173)
`pylene glycol and slightly soluble in ethanol, octanol, and
`glycerine. It has a melting point of about 225°C and the pH
`of a saturated solution is between 5.0 and 5.4. Its chemical
`name is (:!:)-l-(2Hl-phthalazinone,4-[(4-chloropheny!) meth(cid:173)
`yll-2-(hexahydro-1-methyl-lH-azepin-4-yl)-, monohydro(cid:173)
`chloride. Its molecular formula is C22H,.,.CIN30·HCl with
`the following chemical structure:
`·
`
`Astelin® Nasal Spray contains 0.1% azelastine hydrochlo(cid:173)
`ride in an aqueous solution at pH 6.8 :!: 0.3. It also contains
`benzalkonium chloride (125 mcg/mL), edetate disodium, hy(cid:173)
`droxypropyl methyl cellulose, citric acid, dibasic sodium
`phosphate, sodium chloride, and purified water.
`After priming, each metered spray delivers a 0.137 mL
`mean volume containing 137 mcg of azelastine hydrochlo(cid:173)
`ride (equivalent to 125 mcg of azelastine base). Each bottle
`can deliver 100 metered sprays.
`CLINICAL PHARMACOLOGY
`Azelastin'e hydrochloride, a phthalazinone derivative, ex(cid:173)
`hibits hiatamine H1-receptor antagonist activity ii:> isolated
`tiasues, animal models, and humans. Astelin® Nasal Spray
`is administered as a racemic mixture with no difference in
`pharmacologic activity noted between the enantiomers in in
`vitro studies. The major metabolite, desmethylazelastine,
`also possesses H1-receptor antagonist activity.
`Pharinacokinetics and Metabolism
`After intranasal admimstration, the systemic bioavailabil(cid:173)
`ity of azelnstine hydrochloride is approximately 40%. Max(cid:173)
`imum plasma concentrations (Cmax) are achieved in 2-3
`hours. Based on intravenous and oral administration, the
`elimination half-life, steady-state volume of distribution,
`and plasma clearance are 22 hours, 14.5 IJkg, and 0.5 I.Jhl
`kg, respectively. Approximately 75% of an oral dose of radio(cid:173)
`labeled azelastine hydrochloride was excreted in the feces
`with less than 10% as unchanged azelastine. A.zelastine is
`oxidatively metabolized to the principal active metabolite,
`desmethylazelastine, by the cytochrome P450 enzyme sys(cid:173)
`tem. The specific P450 isoforms responsible for the biotrans(cid:173)
`formation of azelastine have not been identified; however,
`clinical interaction studies with the known CYP3A4 inhibi(cid:173)
`tor erythromycin failed to demonstrate a pharmacoltinetic
`interaction. In a multiple-dose, steady-state drug interac(cid:173)
`tion study in normal volunteers, cimetidine (400 mg twice
`daily), a nosnpecific P450 inhibitor, raised orally adminis(cid:173)
`tered mean azelastine (4 mg twice daily) concentrations by
`approximately 65%.
`The major active metabolite, desmethylazelastine, was not
`measurable (below assay limits) after single-dose intranasal
`administration of azelastine hydrochloride. After intranasal
`dosing of azelastine hydrochloride to steady-state, plasma
`concentrations of desmethylazelastine range from 2()..50%
`of azelastine concentrations. When azelastine hydrochloride
`is admimstered orally, desmethylazelastine has an elimina(cid:173)
`tion half-life of 54 hours. Limited data indicate that the me(cid:173)
`tabolite profile is similar when azelastine hydrochloride is
`administered via the intranasal or oral route.
`In vitro studies with human plasma indicate that the
`plasma protein binding of azelastine and desmethylazelas(cid:173)
`tine are approximately 88% and 97%, respectively.
`Azelastine hydrochloride administered intranasally at
`doses above two sprays per nostril twice daily for 29 days
`resulted in greater than proportional increases in Cmax and
`area under the curve (AUC) for azelastine.
`Studies in healthy subjects admimstered oral doses of
`82elastine hydrochloride demonstrated linear responses in
`Cmax and AUC.
`·
`Special Populations
`Following oral administration, pharmacoltinetic parameters
`were not influenced by age, gender, or hepatic impairment.
`Based on oral, single~dose studies, renal insufficiency (creaw
`tine clearance <50 mUmin) resulted in a 7()..75% higher
`Cmax and AUC compared to normal subjects. Time to max(cid:173)
`imum concentration was unchanged.
`Oral azelastine has been· safely administered to over 1400
`asthmatic subjects, supporting the safety of administering
`Astelin® Nasal Spray to allergic rhinitis patients with
`asl:hnta.
`Pharmacodynamics
`In a placebo-controlled study (95 subjects with allergic rhi(cid:173)
`nitis), there was no evidence of an effect of Aste1in® Nasal
`Spray (2 sprays per nostril twice daily for 56 days) on car~
`
`Continued on next page
`
`l !· l I'
`
`DESCRIPTION
`Each time-released, dye free, scored tablet contains:
`Guaifenesin ...................................................... 600 mg
`DOSAGE
`Adults and children over 12 years of age: 1-2 tablets every
`12 hours not to exceed 4 tablets (2400 mg) in 24 hours
`Children 6-12 years of age: 1 tablet every 12 hours not to
`exceed 2 tablets (1200 mg) in 24 hours
`HOW SUPPLIED
`Bottles of 100 tablets (NDC 59310·102-10)
`
`~
`>·
`
`fpro' -fin]
`Phenylpropanolamine HCl/Guaifenesin
`
`t
`!
`1
`l r t
`! PROFEN LA® TABLETS
`ll·.. DESCRIPTION
`I·.· DOSAGE
`
`Each time-released, dye free, scored tablet contains:
`75 mg
`Phenylpropanolamine Hydrochloride ..................
`Guaifenesin ............... .... .• ... .................... .......... 600 mg
`
`Adults and children over 12 years of age: 1 tablet every 12
`hours
`
`Wallace Laboratories
`P.O. BOX 1001
`CRANBURY, NJ 08512
`
`For Medical Information, Contact:
`Generally:
`Professional Services
`800·526-3840
`After Hours and Weekend Emergencies:
`(609) 655-6474
`Wallace laboratories
`Sales and Ordering:
`Div. of Carter-Wallace, Inc
`P.O. Box 1001
`Cranbury, NJ 08512
`
`AQUATENSEN®
`(methyclothiazide tablets, USP, 5 mg)
`Tablets
`
`000002
`
`

`

`3·148/WALLACE
`
`Astelin-Cont.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`Carcinogenicity studies in rats and mice with oral azelas(cid:173)
`tine hydrochloride for 24 months at doses up to 30 mg/kg/
`day and 25 mg/kg/day, respectively (240 and 100 times the
`maximum recommended human daily intranasal dose on a
`mg/m2 basis), revealed no evidence of carcinogenicity.
`Azelastine hydrochloride showed no genotoxfo effects in the
`Ames test, DNA repair test, mouse lymphoma forward mu(cid:173)
`tation assay, mouse mieronucleus test, or chromosomal ab~
`erration test in rat bone marrow.
`.
`Reproduction and fertility studies in rats showed no effects
`on male or female fertility at oral doses of up to 30.mg/kg/
`day (240 times the maximum recommended human daily in(cid:173)
`tranasal dose on a mg/m2 basis). At 68.6 mg/kg/day (550
`times the maximum recommended human daily intranasal
`dose on a mg/m2 basis), the duration of estrous cycles was
`prolonged and copulatory activity and the number of preg(cid:173)
`nancies were decreased. The numbers of corpora lutea and
`implantations were decreased; however, the implantation
`ratio was not affected.
`Pregnancy Category C: Azelastine hydrochloride has been
`shown to be embryotoxic, fetotoxic, and teratogenic (exter(cid:173)
`nal and skeletal abnormalities) in mice at an oral dose of
`68.6 mg/kg/day (280 times the maximum recommended hu(cid:173)
`man daily intranasal dose on a mg/m2 basis).
`At an oral dose of 30 mg/kg/day (240 times the maximum
`recommended human daily intranasal dose on a mgim2 ba(cid:173)
`sis), delayed ossification (undeveloped metacarpus), and the
`incidence of 14th rib were increased in rats. At 68.6 mglkg/
`day (550 times the maximum recommended human daily in(cid:173)
`tranasal dose on. a mg/m2 basis) azelastine hydrochloride
`caused abortion and fetotoxic effects in rats.
`The relevance to humans of these skeletal findings noted at
`only high drug exposure levels is unknown.
`There are no adequate and well-controlled clinical studies
`in pregnant women. Astelin® Nasal Spray should be used
`during pregnancy only if the potential benefit justifies the
`potential risk to the fetus.
`Nursing Mothers: It is not known whether azelastine hy(cid:173)
`drochloride is excreted in human milk. Because many drugs
`are excreted in human milk, caution should be exercised
`when Astelin® Nasal Spray is administered to a nursing
`woman.
`Pediatric Use: Safety and efficacy of:A.stelin® Nasal Spray
`in pediatric patients below the age of 12 years have not been
`established.
`ADV,ERSE REACTIONS
`Adverse experience information for Astelin!® Nasal Spray is
`derived from six well-controlled, 2-day to 8-week clinical
`studies which included 391 patients who received Astelin®
`Nasal Spray at a dose of 2 sprays per nostril twice daily. In
`placebo-controlled efficacy trials, the incidence of discon(cid:173)
`tinuation due to adverse reactions in patients receiving As(cid:173)
`telin® Nasal Spray was not significantly different from ve(cid:173)
`hicle placebo (2.2% vs 2.8%, respectively).
`In these clinical studies, adverse events that occurred sta(cid:173)
`tistically significantly .more often in patients treated with
`Astelin® Nasal Spray versus vehicle placebo included bitter
`taste (19. 7% vs 0.6%), somnolence (11.5% vs 5.4%), weight
`increase (2.0% vs 0%), and myalgia (1.5% vs 0%).
`The following adverse events were reported with frequen(cid:173)
`cies ;,,,2% in the Astelin® Nasal Spray treatment group and
`more frequently than placebo in short-term (:S2 days) and
`long-term (2-8 weeks) clinical trials.
`
`ADVERSE EVENT
`
`diac repolarization as represented by the ~orrected QT in(cid:173)
`terval (QTc) of the electrocardiogram. At higher oral expo(cid:173)
`sures (;;,,4 mg twice daily), a nonclinically significant mean
`change in the QTc (3-7 millisecond increase) was observed.
`Interaction studies investigating the cardiac repolarization
`effects of concomitantly administered oral azelastine hydro(cid:173)
`chloride and erytbromycin or ketoconazole were conducted.
`Oral erytbromycin bad no·effect on azelastine pharmacoki(cid:173)
`netics or QTc based on analysis of serial electrocardiograms.
`Ketoconazole interfered with the measurement of azelastine
`plasma levels; however, no effect_s on QTc were observed (see
`PRECAUTIONS, Drug Interactions).
`Clinical Trials
`U.S. placebo-controlled clinical trials of Astelin® Nasal
`Spray included 322 patients w:ith seasonal allergic rhinitis
`who received two sprays per nostril twice a day for up to 4
`weeks. These trials included 55 pediatric patients ages 12 to
`16 years. Astelin® Nasal Spray significantly improved a
`complex of symptoms, which included rhinorrhea, sneezing,
`and nasal pruritis.
`In dose-ranging trials, Astelin® Nasal Spray administration
`resulted in a decrease in symptoms, which reached statisti(cid:173)
`cal significance from saline placebo within 8 hours aft.er in(cid:173)
`itial dosing and persisted over the 12-hour dosing interval.
`There were no findings on nasal examination in an 8-week
`study that suggested any adverse effect of azelastine on the
`nasal mucosa.
`INDICATIONS AND USAGE
`Astelin® Nasal Spray is indicated for the treatment of the
`symptoms of seasonal allergic rhinitis such as rhinorrhea,
`sneezing, and nasal pruritus in adults and children 12 years
`and older.
`CONTRAINDICATIONS
`Astelin® Nasal Spray is contraindicated in patients w:ith a
`known hypersensitivity to azelastine hy~oc:bloride or any
`of its components.
`PRECAUTIONS
`In clinical trials,
`Activities Requiring Mental Alertness:
`the occurrence of somnolence has been reported in some pa(cid:173)
`tients taking Astelin® Nasal Spray; due caution should
`therefore be exercised when driving a car or operating po(cid:173)
`tentially dangerous machineii ConcU?Tent use of Astelin®
`Nasal Spray with alcobol or other CNS depressants should
`be avoided because additional reductions in alertness and
`additional impairment of CNS performance may occur.
`Information for Patients: Patients should be instructed to
`useAstelin® Nasal Spray only as prescribed. For the proper
`use of the nasal spray and to attain maximum ilnprove(cid:173)
`ment, the patient should read and follow carefully the ac(cid:173)
`companying patient instructions. Patients should be in(cid:173)
`structed to prime the delivery system before initial use and
`after storage for 3 or more days (see PATIENT INSTRUC(cid:173)
`TIONS FOR USE). Patients should also be instructed to
`store the bottle upright at room temperature with the pump
`tightly closed and out of the reach of children. In cas~ of
`accidental ingestion by a young child, seek professional as(cid:173)
`sistance or contact a poison confJ'o] center immediately.
`Patients should be advised against the concurrent use of
`Astelin® Nasal Spray with other antihistamines without
`consulting a physician. Patients who are, or may become,
`pregnant should be told that this product .should be used in
`pregnancy or during lactation only if the potential benefit
`justifies the potential risks to the fetus or nursing infant.
`Patients should be advised to assess their individual re(cid:173)
`sponses to Astelin® Nasal SpraY before engaging in any ac(cid:173)
`tivity requiring mental alertness, such as driving a car or
`operating machinery. Patients should be advised that the
`concurrent use of Astelin® Nasal Spray with alcohol or
`other CNS depressants may lead to additional reductions in
`alertness and impairment of CNS performance and should
`be avoided (see Drug Interactions).
`Drug Interactions: Concurrent use of Astelin® Nasal
`Spray with alcohol or other CNS depressants should be
`avoided because additional reductions in alertness and ad(cid:173)
`ditional impairment of CNS performance may occur.
`Cimetidine (400 mg tw:ice daily) increased the mean Cmax
`and AUC of orally administered azelastine hydrochloride
`(4 mg twice daily) by approximately 65%. Ranitidine hydro(cid:173)
`chloride (150 mg tw:ice daily) had no effect on azelastine
`pharmacokinetics.
`Interaction studies investigating the cardiac effects, as mea(cid:173)
`sured by the corrected QT interval (Q'Ib), of concomitantly
`administered oral azelastine hydrochloride and erythromy(cid:173)
`cin or ketoconazole were conducted. Oral erythromycin (500
`mg three times daily for seven days) had no effect on azelas(cid:173)
`tine pbarmacokinetics or Q'Ib based on analy~es of. serial
`electrocardiograms. Ketoconazole (200 mg. twice druly for
`seven days) interfered with the measurement of azelastine
`plasma concentrations; however, no effects on QTc were ob~
`served.
`No significant pharmacokinetic interaction was observed
`w:ith the coadministration of an oral 4 mg dose of azelastine
`hydrochloride twice daily and theophylline 300 mg or 400
`mg twice daily.
`Geriatric Use: U.S. placebo-controlled clinical trials in(cid:173)
`cluded 11 patients above the age of 60 years who were
`treated with Astelin® Nasal Spray. While this number is
`very small and no substantial conclusions can be drawn, the
`adverse events in this group were simi1ar to patients under
`age 60 years.
`Information will be superseded by supplements and subsequent editions
`
`Bitter Taste*
`
`Headache
`
`Somnolence*
`
`Nasal Burning
`
`Pharyngitis
`
`Dry Mouth
`
`Paroxysmal
`Sneezing
`
`Nausea
`
`Rhinitis
`
`Fatigue
`
`Dizziness
`
`Epistaxis
`
`Weight Increase*
`
`Astelin®
`Nasal Spray
`n=391
`
`Vehicle
`Placebo
`n=353
`
`19.7
`
`14.8
`
`11.5
`
`4.1
`
`3.8
`
`2.8
`
`3.1
`
`2.8
`
`2.3
`
`2.8
`
`2.0
`
`2.0
`
`2.0
`
`0.6
`
`12.7
`
`5.4
`
`1.7
`
`2.8
`
`1.7
`
`1.1
`
`1.1
`
`1.4
`
`1.4
`
`1.4
`
`1.4
`
`0.0
`
`• P<0.05, Fisher's Exact Tust (two-tailed)
`
`The following events were observed infrequently (<2% and
`exceeding placebo incidence) in patients who received
`Astelin® Nasal Spray (2 sprays/nostril twice daily) in U.S.
`clinical trials.
`Cardiovascular: flushing, hypertension, tachycardia.
`Dermatological: contact dermatitis, eczema, hair and follicle
`infection, furunculosis.
`
`PHYSICIANS' DESK REFERENCE®
`
`Digestive: constipation, gastroenteritis, glossitis, ulcerative
`stomatitis, vomiting, increased SGPT, aphthous stomatitis
`Metabolic and Nutritional: increased appetite.
`·
`Musculoskeletal: myalgia, temporomandibular dislocation
`·
`Neurological: hyperkinesia, hypoesthesia, vertigo.
`Psychological: anxiety, dep~rsonalization, depression, ner(cid:173)
`vousness, sleep disorder, thinking abnormal.
`Respiratory: bronchospasm, coughing, throat burning
`laryngitis.
`'
`Special Senses: conjunctivitisJ eye abnormality, eye pain,
`watery eyes, taste loss.
`'
`Urogenital: albuminuria, amenorrhea, breast pain, hematu(cid:173)
`ria, increased urinary frequency.
`Whole Body: allergic reaction, back pain, herpes simplex, v;.
`ral infection, malaise, pain in extremities, abdominal pain.
`In controlled trials involving nasal and oral azelastine hy(cid:173)
`drochloride formulations, there were infrequent occurrences
`of hepatic transaminase elevations. The clinical relevance of
`these reports has not been established.
`In addition, the following spontaneous adverse events have
`been reported during the marketing of Astelin® Nasal
`Spray and causal relationship with the drug is unknown:
`anaphylactoid reaction, application site irritation, chest
`pain, nasal congestion, confusion) diarrhea, dyspne~ facial
`edema, involuntary muscle contractions, paresthesia, paros.
`mia, pruritus, rash, tolerance, urinary retention, vision ab.
`normal, and xerophthalmia.
`OVERDOSAGE
`There have been no reported overdosages with Astelin®
`Nasal Spray. Acute overdosage by adults with this dosage
`form is unlikely to result in clinically significant adverse
`events, other than increased somnolence, since one bottle of
`Astelin® Nasal Spray contains 17 mg of azelastine hydro(cid:173)
`chloride. Clinical studies in adults with single doses of the
`oral formulation of azelastine hydrochloride (up to 16 mg)
`have not resulted in increased incidence of serious adverse
`events. General supportive measures should be employed if
`overdosage occurs. There is no known antidote to Astelin®
`Nasal Spray. Oral ingestion of antihistamines has the po·
`tential to cause serious adverse effects in young children.
`Accordingly, Astelin® Nasal Spray should be kept out of the
`reach of children. Oral doses greater than 120 mg/kg (480
`times the maximum recommended human daily intranasal
`dose on a mg/m2 basis) produced significant mortality in
`mice. Responses seen prior to mortality were treinor, con·
`vulsions, decreased muscle tone, and salivation. Single
`doses as high as 10 mg/kg (270 times the maximum' recom(cid:173)
`mended human daily intranasal dose on a mg/m2 basis)
`were well tolerated in dogs, but single doses of 20 mg/kg
`were lethal.
`DOSAGE AND ADMINISTRATION
`The recommended dose of Astelin® Nasal Spray in adults
`and children 12 years and older is two sprays per nostnl
`twice daily. Before initial use, the screw cap on the bottle
`should be replaced with the pump unit and the delive.ry S.)'S·
`tern should be primed w:itli 4 sprays or until a fine mist ap·
`pe;irs. When 3 or more days have elapsed since the last U:se,
`the pump should be reprimed w:ith 2 sprays or until a fine
`mist appears.
`CAUTION: Avoid spraying in the eyes.
`Directions for Use:
`Illustrated patient instructions for
`proper use accompany each package of Astelin® Nasal
`Spray.
`HOW SUPPLIED
`Astelin® (azelastine hydl·ochloride) Nasal Spray, 137 mcg,
`(NDC 0037-0241-10) is supplied as a package containing a
`total of 200 metered sprays in two high-density polyethy·
`Jene (HDPE) bottles fitted with screw caps. A separate me(cid:173)
`tered-dose spray pump unit and a leaflet. of patient instruc(cid:173)
`tions are also provided. The spray pump unit is packaged in
`a polyethylene wrapper and consists of a nasal spray pump
`fitted with a blue safety clip and a blue plastic dust cover.
`Each Astelin® (azelastine hydrochloride) Nasal Spray, 137
`mcg, bottle contains 17 mg (1 mg/mL) of azelastine hydro·
`chloride to be used with the supplied metered-dose spray
`pump unit. Each bottle can deliver 100 metered sprays.
`Each spray delivers a mean of 0.137 mL solution contairung
`137 mcg of azelastine hydrochloride.
`ATTENTION: The imprinted expiration date applies to the
`product in the bottles with screw caps. After the spray pump
`is inserted into the first bottle of the dispensing package,
`both bottles of product should be discarded after 3 months,
`not to exceed the expiration date imprinted on the label.
`Storage: Store at controlled room temperature 20•-25•C
`(68•-77'F). Protect from freezing.
`Manufactured by
`Wallace Laboratories
`Division of Carter-Wallace, Inc.
`Cranliury, NJ 08512-0181 for
`Wallace Laboratories/ASTA Medica LLC
`©1999 Wallace Laboratories.I.ASTA Medica LLC
`Rev.
`IN-02SS3-08A
`Show11 in Product Identification Guide, page 341
`
`1199
`
`DEPEN®
`(penicillamine tablets, USP)
`litratable Tablets
`
`I Physicians planning to use penicillamine should th?~l
`
`oughly familiarize themselves with its toxicity, speCJ "
`
`;.
`
`000003
`
`