?"I.ti
`
`Morgan .& Finnegan L.L.P. Library
`3 VItFFC 20TH FL
`New York, NY 10281-2101
`
`PPDR®59EDITION
`
`2005
`
`P YSCA\S'
`DESK
`lenommeme RI\C Amanimmos
`
`11111111111.... ....
`
`EXHIBIT 6
`WIT:DATE: Jae
`
`RPR, CRR
`
`DEBRA STEVENS,
`
`f
`
`Executive Vice President, PDR: David Duplay
`
`Vice President, Sales and Marketing: Dikran N. Barsamian
`Senior Director, Pharmaceutical Sales: Anthony Sorce
`National Account Manager. Marion Reid, RPh
`Senior Account Managers: Frank Karkowsky, Suzanne E. Yarrow, RN
`Account Managers: Marjorie A. Jaxel, Kevin McGlynn. Elaine Musco,
`Lois Smith, Eileen Sullivan, Richard Zwickel
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`Associate Director of Marketing: Jennifer M. Fronzaglia
`Senior Marketing Manager: Kim Marich
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`Manager of Marketing Analysis: Dina A. Maeder
`Promotion Manager: Linda Levine
`Vice President, Regulatory Affairs: Mukesh Mehta, RPh
`Vice President, PDR Services: Brian Holland
`Director of POR Operations: Jeffrey D. Schaefer
`Director of Operations: Robert Klein
`Clinical Content Operations Manager: Thomas Fleming, PharmD
`
`Manager, Editorial Services: Bette LaGow
`Drug Information Specialists: Min Ko, PharmD; Greg Talfis, RPh
`Project Editors: Neil Chesanow, Harris Fleming
`Senior Editor: Lori Murray
`Production Editor: Gwynned L. Kelly
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`
`THOMSON Copyright B 2005 and published by Thomson POR at Montvale, NJ 07645 -1742. All rights reserved, None of 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, record+ng, or otherwise) without the prior written permission of the publisher. Physicians' Desk Reference °, PDR., Pocket
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`PDR ", PDR Family Guide to Prescription Drugs", PDR Family Guide to Women's Health and Prescription Drugs", and PDR Family Guide to
`Nutrition and Health" are registered trademarks used herein under license. PDR. for Ophthalmic Medicines, PDR' for Nonprescription Drugs and Dietary Supplements, PDR'
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`Officers of Thomson lieafthcare, Inc.: President and Chief Executive Officer: Robert Cullen; Chief Financial Officer: Paul Hilger; Chief Technology Officer: Fred Lauber; Executive
`Vice President. Medical Education: Jeff MacDonald; Executive Vice President, Micromedex: Jeff Reiht; Executive Vice President, PDR: David Duplay; Senior Vice President,
`Business Development: Robert Christopher; Senior Vice President, Marketing: Timothy Murray; Vice President, Human Resources: Pamela M. Bilash
`
`ISBN: 1.55363 -497 -X
`
`KVK -TECH EXHIBIT 1059
`
`Page 1
`
`SHIRE EX. 2084
`KVK v. SHIRE
`IPR2018-00290
`
`

`

`OLAXOSMITNKUNE
`
`P 1447
`
`RX
`
`OLAKO5M1fNKLiNE
`
`P. 1407 , 00
`
`gtAko5M1TNKLIKE
`
`P. 1400
`
`01
`
`OLAXOSMITNKLINE
`
`,1477 RX
`
`atAXOSMITNKUlE
`
`P. 1454
`
`PRODUCT IDENTIFICATION GUIDE /315
`
`4111 .
`
`25 mg/37,5 mg
`
`100 mg
`
`Dyazide
`
`( hydroch l o ro t h i a zi d e/t7 i am te rene)
`P 1470.
`
`OLAXOSMITNKUNE
`
`Rk
`
`EpivlrNSlfe
`(lamtvudine)
`OI.AX05MRHKLINE
`
`0,.1477':...
`
`..:
`
`110 rt rg¡inh
`lag canister
`120 metered Inhalations
`Also available in 7.9-g canister.
`
`Floveate 110 mcg
`Inhalation Aerosol
`(fluticasone propionate. 110 mcg)
`P. 1404
`
`CLAKOSMIINMLINE
`
`RX
`
`esa
`
`Coreg®
`(carvedilol)
`CLA7100MITINIUNE
`
`P. 1411
`
`RX
`
`20 mcg /mt sings -dose vial
`Adult Dose
`
`i
`ammo r
`
`itlt
`
`2%
`22 g
`
`3.125
`mg
`b'
`Tiha
`
`6,25 mg
`Tiftab'
`
`12.5 nlg
`Tiltab'
`
`25 mg
`Tittab°
`
`Bactroban Ointment.
`(mupirocin ointment, 2 %)
`While every effort has been
`made to reproduce products
`faithfully, this section is to be
`considered a quick reference
`identification aid. In cases of
`suspected overdosage, etc.,
`chemical analysis of the
`product should be done.
`t. 1445
`N4 town NK101t
`
`# ..:...,....'..;..
`
`.
`
`MOSS
`1.5g
`
`I?"..r»:.w....
`.....+.........
`--
`
`0.05%
`60g
`Also avaaable in 30 g
`
`20 mcg /ml single -dose. prerilled.
`disposable Tip -Lok' syringe
`Anu!t Case
`
`Epivlr 418Y® Oral Solution
`(larnivudine)
`
`RX
`
`GLASOSMITNKLINE
`
`0 -14111
`
`5 mg/mL
`240 ml
`
`7.41171114.
`
`300 mg
`Eskaliths
`(lithium carbonate)
`
`RX
`
`Gux0111MrTIrKLINE
`
`P. 1405
`
`RK
`
`220 mcg /inh
`13g canister
`120 metered inhalations
`Also available in 7.9 g canister
`
`Fbveat® 220 sing
`inhalation Aerosol
`(tiuticasone propionate. 220 mcg)
`P. 1300
`
`CLAXOSMITNKUNE
`
`450 mg
`Eskalith CRe
`Controlled-Release Tablets
`(lithium carbonate)
`
`OLAXOSMITHKUNE
`
`P. 1407
`
`sttw:
`
`42 mcg/sprav
`
`Cutivatee Cream
`(fluticasone propionate cream)
`
`RX
`
`OLAXOSMITNKUNE
`
`P. 1411
`
`io mcg /0.5 mL single -dose vial
`Pediatric Dose /Adolescent Dose
`
`_.._ r
`
`u , 401j
`
`0.005%
`15 g
`
`,
`
`004,431111"-414
`
`10 mcg/05 mL single -dose, prefifled,
`disposable TipLok' syringe
`Pediatric /Adolescent Dose
`
`180 metered ways
`Beconase AQ0
`Nasal
`y4eéolsibt,ësolN!ta óttaSte ñ)
`P. 1410
`
`OLAXOSM1T111fL1NE
`
`RX
`
`.....°°
`
`0.005%
`60 g
`Also available In 30 g
`
`Cutivatee Ointment
`(fluticasone propionate ointment)
`P.1404
`
`OLAKOSMITNKLINE
`
`Ml
`
`i!3 rvtt8 nd
`100 inF,
`
`25 mg
`
`Daraprlwte
`(pyrimethamine)
`
`CLAXOSMITNKLINE
`
`' C:if
`
`250 mg/5 mL
`50 mL
`
`290 tR[(rnt5 ntL
`lea
`
`RK
`
`Also available in Pediatric /Adolescent Dose
`10 mcg /0.5 mL single-dose, prettied,
`disposable Tiptoe' syringes with 5 /8-inch
`25-gauge SatetyGlidem needles.
`
`Engerlxile
`(Hepatitis S Vaccine (Recombinant))
`
`Because tablets and capsules
`are shown in this section,
`do not infer that these are
`the only dosage forms
`name
`available. Where a
`the
`is preceded
`symbol t. refer to the description
`in the Product infortuatiori
`(White Section) for other forms.
`
`i 1440 03
`
`OUXOSMITNMUNO
`
`P. 1470
`
`RR
`
`Catlin° for Oral Suspension
`(cefurozime azetil powder for oral suspension)
`P. 1410
`
`GLAXOSMITNKLINE
`
`Its
`
`15-mg Spansule
`Also imitable as 5-mg Spansule
`and 10-mg Spansule° capsules.
`
`150 mg
`
`ii
`
`1.5 mg
`
`Flotane for Injection
`(epoprostenol sodium)
`
`GLAXOSMITNKLINE
`
`P. 1401
`
`--en+...,s srP
`
`50 mcg/blister
`
`Flovente Rotedlsk° SO meg
`(fluticasone propionate
`inhalation powder. 50 mcg)
`
`RX
`
`CLAXOSMITNKLINE
`
`P.1500
`
`r.
`
`/,.,a
`
`+ <.+v..,.
`..r N`
`*rim
`'` ^..,..... a.y
`
`100 mcg/biister
`
`Flouent® Rotadisk ®100 stcg
`(fluticasone propionate
`inhalation powder. 100 mcg)
`
`ax
`
`41.03108313111111.1111E
`
`P. 1.500
`
`250 mg
`
`5 mg
`
`Dexedrine®
`Idextroamphetamine sulfate)
`CL4X05MRNKUNE
`
`RX
`
`10, 1405
`
`RX
`
`Epivirm
`(lamivudine tablets)
`GUXOSMITocuoe
`
`50 mcg/spray
`16 g
`120 metered sprays
`Flonasee Nasal Spray, 50 mcg
`(fluticasone propionate)
`
`P.1473
`
`RC
`
`OLAXOSMITHSLINE
`
`0,1444
`
`500 mg
`
`Canin°
`Icefuroxime anetli tablets)
`
`OLAXOSMITNKUNE
`
`1414
`
`r
`
`4
`
`150 rng/300 mg
`
`Combivire
`(tamivudine/zidovudine)
`
`38 mg
`
`Digibinde
`Digoxin Immune Fab
`(ovine)
`
`mg/rit
`240 mL
`Epivire Oral Solution
`(lemlvudine oral solution)
`
`250 mcg/blister
`
`Floventa Rotadiske 250 mcg
`(fluticasone propionate
`inhalation powder. 250 mcg)
`
`Designed to help you identify
`drugs, this section contains
`actual size pills and full color
`reproduction of products
`selected for inclusion by
`participating manufacturers_
`
`44 mcg /Inh
`13-g canister
`120 metered inhalations
`Also available it 7.9.5 canister.
`
`Rovente 44 mcg
`Inhalation Aerosol
`(ffut)casone propionate, 44 mcg)
`
`Page 2
`
`

`

`Nb utat1/4. ntrtttt
`
`INFOKMAI IUN
`
`rE
`RN DARAPRIM is
`sis when used
`m exists with this
`DARAPRIM is also
`malaria. It should not
`Fast - acting sciai
`re indicated and
`(aria. However,
`roide (reg suif
`and suppression of
`
`iris: DARAPRIM is
`of malaria due 'to-
`er, resistance to
`s not suitable as "á
`areas.
`
`ttraindicated in pa
`ryrimethamine or to
`e of the drug is also
`nmented megaloblastie
`
`ne required for the
`¡mes the recommended
`s the toxic level. If alga
`ERSE REACTIONS),
`rug according tu the
`scovorin) should be
`aily (orally, IV, or IM)
`'ed.
`that pyrimothatníne
`sale who developed
`Ling pyrimethamine foe
`i- year -old patient who
`ar 14 months of
`
`eported to produce a
`!ung tumors in mice
`if 25 mg/kg.s
`t out of the reach of.
`ely susceptible to
`in pediatric patients
`gestion.
`
`led dosage for
`xceeded. A small
`mended in patients
`potential nervous system
`RIM should be used
`ewe or hepatic timeline.
`deficiency, such ate
`new, alcoholism, as
`py, such as phettytetp,
`y subsection).
`Patients should be
`skin rash they should
`Heal attention
`red that the 3p
`;lossitis may be early
`hich require treat
`d and medical tres
`
`potential who are
`rued against becomi
`I to keep DAIìAPIi
`. should be advised net*
`eta should be warned'
`they may be minimized
`
`of folinic acid is s
`treatment of tmrap
`
`enti receiving high
`molds, aerlitweekiy
`should be gam.
`iethamine may be used
`tarttnthnalatiala, end
`uáerimithnt'tise of
`d with noyeloso
`thoprinr-sul
`idine, or, cytoetátic
`patient is receiving
`sk of bone marrow
`evelop, pyrimethamine,
`(leucovorin) should l
`ppoiesìs is restored (se
`y has been reported tre.
`and
`pyrlme
`a
`ly.
`psis, Impairment of
`formation on
`mine has been shown
`g in vitro assays: the
`say, and the E. Loth
`Y/TK +/- mouse I
`our metabolic activaiiobe
`el in vitro had etructuralar.
`by pyrimethamine.
`
`chromosomes analyzed from the bone marrow of
`with pyrimetltamirte showed an increased num-
`pectesl and numerical aberrations.
`Tarstogen/c Effects: Pregnancy Category C.
`has been shown to be teratogenic in rats
`m oral doses 7 times the human dose for che-
`or malaria or 2.6 times the human úO5e foi
`of toxoplasmosis. At these doses in rats, there
`increase in abnormalities such as cleft pal -
`oligodactyly, and microphthalmia- Pyri-
`has also been shown to produce tarata such as
`in hamsters and cleft palate in miniature pigs
`in oral doses 170 and 5 times the human dose,
`for chemoprophylaxis of malaria or for treat -
`latmosie
`ae Piquet. mid well -controlled studies in preg-
`DARAPRIM should be used during pregnancy
`iíamteatisl benefitjustiHes the potential risk to the
`
`administration of folinic acid is strongly recom-
`aben used for the treatment of toxoplasmosis dur-
`
`MMkes: Pyrimethamine is excreted in human
`/wtstof the potential for serious adverse reactions
`infanta from pyrimethamine and from concur -
`swlfonamide with DARAPRIM for treatment of
`to with toxoplasmosis, a decision should be
`listber to discontinue nursing or to discontinue the
`into account the importenee,of the drug to the
`WARNINGS rind PRECAUTIONS: Pregnancy).
`Ws: See DOSAGE AND ADMINISTRATION
`
`Use: Clinical studies of DARAPRIM did not in-
`West autbere of subjects aged 65 and over to de-
`' whether thee respond differentlyfrom younger sub-
`/sported diniteai expetieneu has not identified
`in responses between the elderly and younger
`'b general, dose selection for an elderly patient
`entices, usually starting at the low end of the
`ndlecting the greater frequency of decreased
`or candiec function, and of concomitant dis-
`drng therapy.
`
`REACTIONS
`-ty reactions, occasionally severe (such as
`syndrome, Ureic epidorsnid neerolyais, ery-
`, and anaphylaxis), and by ierpbenylala
`occur particularly when pyrimethamine is ad-
`cattetitantly with-a sulfonamide. Consult the
`prescribing information far the relevant smiler'.
`!t telfanamdde -associated adverse event*. With
`pyt methazoine used for the treatment of toxoplas-
`and vomiting may occur. Vomiting. may be
`by giving the medication with meals; it usually
`promptly upon reduction of dosage. Doses used
`may produce megaloblastic anemia, leuko-
`nia, pancytopenia, atrophic glossitis,
`end disorders of cardiac rhythm. Hematologic
`However, may also occur at low doses in certain in-
`ere PRECAUTIONS: General).
`earinophilia has been reported rarely.
`
`the ingestion of 300 mg or more of pyrimeth-
`t¡tazi and/or central nervous system signs
`present, including convulsions. The initial symp-
`ueually gastrointestinal and may include abdomi-
`'tl nsosea, severe and repeated vomiting, posaiblyin-
`Central nervous systorn toxicity may
`by initial excitability, generalized and pro-
`'ant which may be followed by respiratory
`*initiatory collapse, and death within a .few
`'cal symptoms appear rapidly (30 minutes
`after drug ingestion), suggesting that in gross
`pyrimethamine has a direct toxic effect on the
`nlN0119 system.
`dote is variable, with the smallest reported fatal
`(being 375 mg. There are, however, reporta of pe-
`ts who have recovered after taking 375 to
`
`specific antidote to acute pyrimethamine poison-
`mist of oveniosage, symptomatic and supportive
`should be employed. Gastric lavage is recom-
`äd is effective if carried out very soon after drug
`)mil diazepam may be used to control con -
`acid should also be administered within 2
`lapstion to be most effective in counteracting
`Pauhematapaietic system (See WARNDICS).
`keg WAX* of pyrirnetlutmine, daily monitoring
`Need counts lie recommended for up to several
`the overdose until normal hematologic values
`
`ADMINISTRATION
`The dosage of
`eut of Toxoplaamosis:
`for the treatment of toxoplaamosis must be
`adjusted so as to provide maximum therapeutic ef.
`*minimum of side effects. At the dosage required,
`a marked variation in the tolerance to the drug.
`may tolerate higher doses than older indi-
`.Ccecurrent administration of folinic acid is
`in all patients.
`dose is 50 to 75 mg of the drug daily, to-
`t to 4 g daily of a sulfonamide of the sulfapyri-
`raigippke.g, sulfadox¡ne. This dosage is ordinarily con-
`
`tinued for 1 to 3 weeks, depending on the responae of the
`patient and tolerance to therapy. The dosage may then be
`reduced to about one -half that previously given for each
`drug and continued for an additional 4 to 5 weeks.
`The pediatric dosage of DARAPRIM is 1 mg/kg/day divided
`into 2 equal daily doses: after 2 to 4 days this dose may be
`reduced to one half and centimwi for approximately 1
`month. The usual pediatric sulfonamide dosage its used in
`conjunction with DARAPRIM.
`For Treatment of Acute Maeda:: DARAPRIM is NOT rec-
`ommended alone in the treatment of acute malaria. Fast -
`acting schizonticidee, such as chloroquine or quinine, are in-
`treatment of acute malaria. However,
`dicated for
`DARAPRIM at a dosage of 25 mg daily for 2 days with a
`sulfonamide will initiate transmission control and suppres-
`sion of non -falciparum malaria. DARAPRIM is only recom-
`mended for patients infected in areas where susceptible
`plasmodia exist. Should circumstances arise wherein
`DARAPRIM must be used alone in semi -immune persons,
`the adult dosage for acute malaria is 50 mg for 2 days; chil-
`dren 4 through 10 years old may be given 25 mg daily for 2
`days. In any event, clinical cure should be followed by the
`once - weekly regimen described below for chemoprophylaxia.
`Regimens which include suppression should be extended
`through any characteristic periods of early recrudescence
`and late relapse, i.e., for at least 10 weeks in each case.
`For Chemoprophylaxis of Malaria:
`Adults and pediatric patients over 10 years - 25 mg (1 tab-
`let) once weekly
`Children 4 through 10 years - 12.5 mg (le tablet) once
`weekly
`Infants and children under 4 years- 6.25 mg (V. tablet)
`once weekly
`HOW SUPPLIED
`White, scored tablets containing 25 mg pyrimethamine, im-
`printed with " DARAPRIM" and "A3A" in bottles of 100
`(NDC 0173- 0201 -55).
`Store at 15° to 25 °C (59° to 77 °F) in a dry place and protect
`from light.
`REFERENCES
`1. Eyles DE, Coleman N. Synergistic effect of sulfadiazine
`and Daraprim against experimental toxoplasmosis in the
`mouse. Antibiot Chernother. 1953;3:483 -490.
`2. Jacobs L, Melton ML, Kaufman HE. Treatment of exper-
`imental ocular toxoplasmosis. Arch Ophthalmol. 1964;71:
`111 -118.
`3. Jim RTS, Elizaga FV. Development of chronic granulo-
`cytic leukemia in a patient treated with pyrimethamine.
`Hawaii Med J. 1977;36:173 -176.
`4. Sadoff L. Antimalarial drugs and Burkitt's lymphoma.
`Lancet. 1973;2:1262 -1263.
`5. Balms. L. Pyrimethamine. LARC Monogr Eval C areinog
`Risk Chem. 1977;13:233 -242.
`6. Clive D, Johnson KO, Spector JKS, et al. Validation and
`of the L5178Y/T'K +/- mouse. lymphoma
`mutagen assay system. Mut Res, 1979;59:61 -108.
`Manufactured by DSM Pharmaceuticals, Inc.
`Greenville, NC 27834 for
`GlaxoSmíthKline, Research Triangle Park, NC 27709
`02003, GlaxaSmithKline. AU rights reserved.
`March 2003/RL -1179
`Shown in Product Identification Guide, page 315
`
`DEXEDRINE®
`Idex 's -drénj
`(dextroamphetamine sulfate)
`SPANSULE®
`sustained release capsules and Tablets
`
`WARNING
`
`AMPHETAMINES HAVE A HIGH POTENTIAL FOR
`ABUSE. ADMINISTRATION OF AMPHETAMINES
`FOR PROLONGED PERIODS OF TIME MAY LEAD
`TO DRUG DEPENDENCE AND MUST BE AVOIDED.
`PARTICULAR ATTENTION SHOULD BE PAID TO
`THE POSSIBILITY OF SUBJECTS OBTAINING AM-
`PHETAMINES FOR NON -THERAPEUTIC USE OR
`DISTRIBUTION TO OTHERS, AND THE DRUGS
`SHOULD BE PRESCRIBED OR DISPENSED
`SPARINGLY
`
`DESCRIPTION
`DEXEDRINE (dextroamphetamine sulfate) is the dextro
`isomer of the compound d,l- amphetamine sulfate, a eym-
`pathomimetic amine of the amphetamine group. Chemi-
`cally, dextroamphetamine is d- alpha - methylphenethyl -
`amine, and is present in all forms of DEXEDRINE as the
`neutral sulfate -
`SPANSULE capsules: Each SPANSULE sustained -release
`capsule is so prepared that an initial dose is released
`promptly and the remaining medication is released gradu-
`ally over a prolonged period.
`Each capsule, with brown cap and clear body, contains dex-
`troamphetamine sulfate. The 5 -mg capsule is imprinted
`5 mg and 3512 on the brown cap and is imprinted 5 mg and
`SB on the clear body. The 10 -mg capsule is imprinted 10 mg
`- 3513 - on the brown cap and is imprinted 10 mg - SB
`-on the clear body. The 15 -mg capsule is imprinted 15 mg
`and 3514 on the brown cap and is imprinted 15 mg and SE
`
`on the clear body. A narrow bar appears above and below
`15 mg and 3514. Product reformulation in 1996 has caused
`a minor change in the color of the time - released pellets
`within each capsule. Inactive ingredients now consist of ce-
`tyl alcohol, D &C Yellow No. 10, dibutyl sebacate, ethylcel-
`lulose, FD&C Blue No. 1, FD &C Blue No. 1 aluminum lake,
`FD &C Red No. 40, FD&C Yellow No. 6, gelatin, hypromel-
`lose, propylene glycol, povidone, silicon dioxide, sodium
`lauryl sulfate, sugar spheres, and trace amounts of other
`inactive ingredients.
`Tablets: Each triangular, orange, scored tablet is debossed
`SKF and E19 and contains dextroamphetamine sulfate,
`5 mg. Inactive ingredients consist of calcium sulfate, FD &C
`Yellow No 5 ( tartrazine), FD&C Yellow No. 6, gelatin, lac-
`tose, mineral oil, starch, stearic acid, sucrose, talc, and trace
`amounts of other inactive ingredients.
`CLINICAL PHARMACOLOGY
`Amphetamines are noncatecholamine, sympathomimetic
`amines with CNS stimulant activity. Peripheral actions in-
`clude elevations of systolic and diastolic blood pressures and
`weak bronchodilator and respiratory stimulant action.
`There is neither specific evidence that clearly establishes
`the mechanism whereby amphetamines produce mental
`and behavioral effects in children, nor conclusive evidence
`regarding how these effects relate to the condition of the
`central nervous system.
`DEXEDRINE SPANSULE capsules are formulated to re-
`lease the active drug substance in vivo in a more gradual
`fashion than the standard formulation, as demonstrated by
`blood levels. The formulation has not been shown superior
`in effectiveness over the same dosage of the standard,
`noncontrolled- release formulations given in divided doses.
`Phanmacokinetics: The pharmacokinetics of the tablet and
`sustained -release capsule were compared in 12 healthy sub-
`jects. The extent of bioavailability of the sustained- release
`capsule was similar compared to the immediate -release tab-
`let. Following administration of three 5 -mg tablets, average
`maximal dextroamphetamine plasma concentrations (CIDe )
`of 36.6 ng/mL were achieved at approximately 3 hours. Fol-
`lowing administration of one 15-mg sustained- release cap-
`sule, maximal dextroamphetamine plasma concentrations
`were obtained approximately 8 hours after dosing. The av-
`erage C " was 23.6 ng/mL. The average plasma TK was
`similar for both the tablet and sustained -release capsule
`and was approximately 12 hours.
`In 12 healthy subjects, the rate and extent of dextroamphet-
`amine absorption were similar following administration of
`the sustained -release capsule formulation in the fed (58 to
`75 gm fat) and fasted state.
`INDICATIONS AND USAGE
`DEXEDRINE is indicated:
`1. In Narcolepsy.
`2. in Attention Deficit Disorder with Hyperactivity, as an in-
`tegral part of a total treatment program that typically in-
`cludes other remedial measures (psychological, educational,
`social) for a stabilizing effect in pediatric patients (ages 3
`years to 16 years) with a behavioral syndrome characterised
`by the following group of developmentally inappropriate
`symptoms: Moderate to severe distractibility, short atten-
`tion span, hyperactivity, emotional lability, and impulsivity.
`The diagnosis of this syndrome should not be made with fi-
`nality when these symptoms ant only of comparatively re-
`cent origin. Nonlocalizing (soft) neurological signs, learning
`disability, and abnormal EEG may or may not be present,
`and a diagnosis of central nervous system dysfunction may
`or may not be warranted.
`CONTRAINDICATIONS
`Advanced arteriosclerosis, symptomatic cardiovascular dis-
`ease, moderate to severe hypertension, hyperthyroidism,
`known hypersensitivity or idiosyncrasy to the sympathomi-
`metic amines, glaucoma.
`Agitated states.
`Patients with a history of drug abuse.
`During or within 14 days following the administration of
`monoamine oxidase inhibitors (hypertensive crises may
`result).
`PRECAUTIONS
`General: Caution is to be exercised in prescribing amphet-
`amines for patients with even mild hypertension.
`The least amount feasible should be prescribed or dis-
`pensed at 1 time in order to minimize the possibility of
`overdosage.
`The tablets contain FD &C Yellow No. 5 (tartrazine), which
`may cause allergic -type reactions (including bronchial
`asthma) in certain susceptible individuals. Although the
`overall incidence of FD &C Yellow No. 5 ( tartrazine) sensi-
`tivity in the general population is low, it is frequently seen
`in patients who also have aspirin hypersensitivity.
`Information for Patients: Amphetamines may impair the
`ability of the patient to engage in potentially hazardous ac-
`tivities such as operating machinery or vehicles; the patient
`should therefore be cautioned accordingly.
`
`Continued on next page
`
`Product information on these pages is effective es of August
`2004. Further information is available at: GlaxoSmithKens, PO
`Roe 13398, Research Triangle Park, NC 27709. 1.888. 825.5249.
`Corporate Web Site: www.gsk.com
`
`Consult 2005 POW supplements and future editions for revisions
`
`Page 3
`
`

`

`1486/GLAXOSM ITHKLINE
`
`Dexedrine -Cont.
`
`Drug !^tCre.t c
`Aadifying agents-- Gastrointestinal
`a
`fy +ng agehhsa iguarneshiciinek, reeerpine, gtutersiic acid
`flEls ascorbic acid, Inuit juice, etc.) lower absorption ofam-
`phetamines. Urinary acidífeing agents tammonìnnt chlo-
`ride, sodium acid phosphate, etc.) increase Use concentra-
`tion of the ionized specks of the ,amphetamine molecule.
`thereby increasing urinary excretion. Both groups of agents
`lower blood kevela sad efficacy of amphetamines.
`Adnnergic blockers-- Adrenergic blockers are inhibited by
`amphetamines.
`AittasYafiirhy aparte-Gastrointestinal alkalinching agents
`(sodium bicarbonate. etc,) Inman absorption of ampheta-
`mines. thirtary alkalinising *tenet (acetaielamide. some
`thiazidest increase the concentration of the son- ionized spe-
`cies of the amphetamine molecule, thereby decreasing uri-
`miry seer stioa. Both grouped agent* increase blood levels
`and amine potentiate the action* of iunphetamines.
`Ana`úspnrssafts, tdcyefie- Amphetamines may enhatete
`the activity of bicyclic or syuspathemimetic agents;
`deunpbetansine with daaipramine of prbtriptyline and pos-
`y other bicyclic* coarse stniting and sastaíned increase*
`in the concentration of d- ampbetamine in the brain; cardio-
`vascular effects can be potentiated.
`MAO inhibitors -MAO! antidepressants, as eel as a ins-
`tabolito of furazofdone, slow amphetamine metabolism.
`Tide siaaring potentiates Aesphebmines, increasing theiref-
`fiect on the release of norepinephrine and other motto*mities
`from adrenergic nerve endings; this can cause headaches
`and other signs of hypertensive crisis. A variety of neurolog-
`leal toxic effecta and malignant hyperpyrecia can occur,
`sometimes with fatal results.
`Antihistamines- Amphetamines may counteract the seda-
`tive effect of antihistamines.
`Anfihyperrensi es- Amphetamines may antagonize the
`hypotensive effects of antrhypertensivel.
`tfoJwpremezine- Chlorpromazine blocks dopamine and
`norepinephrine renptake. thus inhibiting the central
`stimulant etecte of amphetamines, and can be used to treat
`amphetamine poisoning.
`Ethosuxlm /de- Amphetamines may delay intestinal ab-
`sorption of ethosuximide.
`Haloperidof- Haloperidol blocks dopamine and norepineph-
`rine reuptake, thus inhibiting the central stimulant effects
`of amphetamines.
`Lithium carbonate -The stimulatory effects of ampheta-
`mines may be inhibited by lithium carbonate.
`Mepersidns- Amphetamines potentiate the analgesic effect
`of meperidine.
`.Methenamine therapy- Urinary excretion of ampheta-
`mines is increased, and efficacy is reduced, by acidifying
`agents used in methenamine therapy
`Norepinephrine -- Amphetamines enhance the adrenergic
`effect of norepinephrine.
`Phenobarbitals- Amphetamines may delay intestinal ab-
`sorption of pheaobarbitsE co-administration of phenobarbi-
`tal may produce a.sysierginic anticonvulsant action.
`Pheeptoke s- Ampìrtetantines may delay intestinal absorption
`of phenytoin: nu- athtdniMration ofphenytein may produce a
`synergistic anticonvuisant action.
`Propoxyphene -in cases of prnpoxyphene overdosage, am-
`phetamine CNS'stimulation is potentiated and fatal convul-
`sions can occur.
`Veratrum alkaloids- Amphetamines inhibit the hypoten:
`live effect of veratrum alkaloids.
`Drug /Laboratory Teat Interactions: Amphetamines can
`cause a significant elevation in plasma corticosteroid levels.
`TN* increase is greatest in the evening.
`Amphetamines may interfere with urinary steroid
`determinatioat.
`Carcinogenasis/Mutagenesis: Mutagenicity studies and
`long -term studies in animals to determine the carcinogenic
`potential of DEXEDRINE have not been performed.
`Pregnancy- Tsratogenic Effects: Pregnancy Category C.
`DEXEDRINE has been shown to have embryotoxic and ter -
`atogenic effects when administered to A/Jax mice and
`C57BL mice in doses approximately 41 times the maximum
`human dose. Embryotoxic effects were not seen in New
`Zealand white rabbits given the drug in doses 7 times the
`human dose nor in rats given 12.5 times the maximum hu-
`man dose. While there are no adequate and well-controlled
`studies in pregnant women, there has been 1 report of se-
`vere congenital bony deformity, tsncheoeaophageal fistula,
`and anal atresia WATER association) in a baby born to a
`woman who took dextrnempbetamine sulfate with lovasta-
`tin during the first trimester Of pregnancy. DEXEDRINE
`should be used during pregnancy only if the potential
`benefit justifies the potential risk to the fetus.
`Nonteretoycnde Effects:
`Infanta born to mothers depen-
`dent on amphetamine* have an increased risk of piemature
`delivery and low birth weight. Ateo, these infants may
`experience symptoms of withdrawal as demonstrated by
`danphorïa, including agitation, and significant lassitude.
`Nursing Mothers: Amphetamines are excreted in human
`milk. Mothers taking amphetamines should be advised to
`refrain from nursing.
`Pediatric Use:, Long -term effects of amphetamines in pedi-
`atric patiepta have not been well established.
`Amphetamines are aòi recommended for use in pediatric
`patients under P years of isgi ytith Attention Deficit Disor-
`der with Hypensetivltg described under INDICATIONS
`AND USAGE.
`
`-
`
`Information will be superseded by supplements and subsequent editions
`
`distribution in the extracellular space, unlike
`Windy which distributes in a space only about
`- ú, iatprmrement is signs end symptoms of
`f'- ylas avolume. t Ordinarily, followi ng administra-
`
`I toxication begins within one -half hour or
`
`of DIGIBIND for digoxin is in the range of 109
`which is greater than the affinity of digoxin for
`lum) ATPase, the presumed receptor for its
`paF
`The amity of DIGIBIND for digitoxin is about
`
`binds molecules of digoxin, making them un-
`to' binding at their site of action on cells in the
`Fah fragment- digoxin complex accumulates in the
`which it is excreted by the kidney. The net effect
`the equilibrium aim from binding of digoxin to
`lathe body, thereby reversing its effects.
`AND USAGE
`Digtrtin Immune Feb (Ovine), is indicated for
`dpotentislty life - threatening digitxe inertia,
`designed specifically to treat life-threaten-
`Overdose, it has olio been used sucoesittïly to
`taring digitoxin overdoses Since human
`is limited and the consequences of repeated ex-
`Unknown, DIGIBIND is not indicated ibr milder
`toxicity.
`of life- threatening toxicity include severe
`arrhythmias such as ventricular tachycardia or
`fibrillation, or progressive bradyarrhythmias
`severe sinus bradycardie or second or third degree
`Nock not responsive to atropine.
`of more than 10 mg of digoxin in previously
`adults or 4 mg of digoxin in previously healthy chil-
`ft ingestion causing steady -state serum concentra-
`than 10 ng/mL, often results in cardiac arrest.
`progressive elevation of the serum potaa-
`éóoa*tratiou also summits imminent cardiac arrest.
`pótassiwn concentration exceeds 5 miq/L in the aet-
`therapy with
`et severe digitalis
`intoxication,
`is indicated.
`ICATIONS
`0o known contraindications to the use of
`
`'on often involves more than one drug; thus,
`from other drugs should not be overlooked.
`consider the possibility of anaphylactic, hyper -
`or febrile reactions. If an anaphylactoid reaction
`the drug infusion should be discontinued and appro-
`therapy initiated using aminophylline, omen, vol-
`spaneíon, dipbenhydrnmine, conies erada, sod air -
`linesamant as indicated. The need for epinephrine
`bé balanced against its potential risk in the setting
`toxicity.
`ibt Fab fragment of the antibody lacks the antigenic
`of the Fc fragment, it should pose less of an
`threat to patients than does an intact imam-
`molecule. Patients with known allergies would
`at risk, as would individuals who have pre-
`received antibodies or Fab fragments raised in
`is used to cleave the whole antibody into Fab
`ätúgrnetts. and traces of papain or inactivated pa-
`pe;idnes may be present in DIGIBIND. Patients with
`its papain, chymopapain, nr other papaya extracts
`be particularly at risk.
`'testing for allergy was performed during the clinical
`n of DIGTBIND. Only one patient developed er-
`at the sito of skin testing, with no accompanying
`reaction: this individual had no adverse reaction to
`' treatment with DIGIBIND. Since energy testing
`f+ay urgently needed therapy, it is not routinely re-
`before treatment of life -threatening digitalis toxicity
`DIGIBIND.
`testing may be appropriate for high risk individuals,
`patients with known allergies er those previously
`with Digoxán bornons Fab (Ovine). The intradermal
`-seat can be performed by:
`0.1 mT, of reconstituted DIGIBIND (9.5 mg/mL)
`mL sterile isotonic saline (1:100 dilution, 95 mcg/
`
`0.1. mL of the 1:100 dilution (9.5 nail intrader-
`.raally and observing for an urticaria/ when surrounded
`a zone of erythema. The test should be read at 20 min-
`
`= tch test procedure is performed by placing one drop
`1100 dilution of DIGIBIND on the skin and then mak-
`'4 -anch scratch through the drop with a sterile needle.
`Scratch site is inspected at20 minutes for an urticaria1
`surrounded by erythema.
`Waling causes a systemic reaction, a tourniquet
`be applied above the