`.
`W -_
`”—
`._..
`
`REVIEW ARTICLE
`
`Parenteral Formulations of Small Molecules Therapeutics Marketed
`in the United States (1999) Part ll
`
`ROBERT G. STRICKLEY
`
`Axys Pharmaceuticals, Inc., South San Francisco, Califomr'a
`
`{Editor‘s Note: This review anicle on Injccmbie Products is
`being published in three pans. The introduction and mm
`rainy appeared in the November/December 1999 issue. The
`final Part will new in the MarchlApfil 2000 issue of the
`Joanna“
`inlectame Products
`
`39“":‘5 ofI'Efon’m’i‘m’
`l. Physician’s Desk Reference, 53rd cd., Medical Eco.
`nomics Company, Inc., Momvale, NJ. I999.
`
`Correspondence address: 180 Kimball Way. Somh San Francisco, CA
`94080
`
`2. Lawrence A. Trissel, Handbook on Injectable Drugs,
`mm ed., American Socier of Health-System Pharma‘
`cists,1ne., Bethesda, MD, 1998.
`3. Lynn D. Phillips and Merrily A. Kuhn, Manual of iv
`Medications, 2nd ed., Lippincott-Raven Publishes,
`Philadelphia, PA, 1999.
`-
`4. D. A. Hussar, “New drugs of 199&” Journal of the
`American Piiamiacemical Association, 39, 151 (1999).
`5. D. A. Hussar. “New drugs of 1997,” Jonmal of the
`American Pimmzaceim‘ca! Association, 38, 155 (1998).
`6. Food and Drug Administration intemet website. http:/I
`www.fda.govl, See human dmgs’ What’s new’ new and
`generics approvals.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Vel.54.No.1 i January-February 2000
`
`Supplied by The British Library - “The world‘s knowledge"
`
`
`
`i
`
`AstraZeneca Exhibit 2158 p. 1
`InnoPharma Licensing LLC V. AstraZeneca AB IPR2017-00900
`Fresenius-Kabi USA LLC V. AstraZeneca AB IPR2017-01913
`
`

`

`
`
`
`Fonnulation
`
`Solution
`500 mg
`pH 9.2
`
`Prcadministmtion
`preparation
`
`Route of
`Administration
`
`Company and
`Indication
`
`Constitute with 5 ml.
`WFI to-< 100 mgme.
`
`IV bolus!
`IV infusion:
`M but may be
`painful due to
`alkaline pH
`
`Lederle,
`Antiglaueonw;
`diuretic in
`ueatmcnt of
`mountain
`sickness
`
`Drug Name!
`Magriteted
`Name
`
`Accmzol-
`amide
`sodium!
`Diamox
`
`Acyclovir
`sodium!
`Zovirax
`
`Adenosine!
`Adenocard
`V (bolus).
`Adenoscan
`(EV infusion)
`
`Structure
`
`u
`
`”‘3
`
`,9
`\m
`
`pKa = 7.2
`
`,9.
`k
`“8"
`
`ti)
`0
`"N’ Won
`pKa ~ 10
`
`"3
`
`,,
`Ly
`,.
`
`W
`
`Lyoggilizedmwder
`pH 10.5 - 11.6
`
`Solution
`3 mg/mL.
`Sodium chloride 9 mg/mL,
`pH 4.5-7.5
`
`Reconstimte with
`WFI to 50 mglmL;
`Dilute with dextrose
`5% orsaline to < 7
`mglmh
`
`None
`
`
`
`W infusioa
`over l hour
`
`Glaxo Wellcomo,
`Antiviral
`
`IV bolus!
`IV infusion at
`0.14
`mg/kglmin for
`6 minutes
`
`‘ Fujisawa.
`Conversion to
`sinus rhythm of
`PSVT (bolus).
`Adjunct for
`thallium-201
`
`myocardial
`perfusion
`scintigmphy
`(infusion)
`
`Pfizer,
`Antibiotic
`
`IV infusion
`over 60
`minutes
`
`IV bolus!
`IV infusion at
`0.5-3.0
`ug/kymin
`
`Taylor,
`Analgesic
`
`Intros
`cavemosal
`
`Pharmacia &
`Upjohn,
`Erectile
`dysfunction
`
`l
`
`f
`l
`i
`‘
`
` l ll
`
`Alamofloxacin
`mcsylatd
`Trovan
`
`>051
`.
`:5
`.JT'M
`Amide prodrug for
`trovafloxacin
`
`Solution
`5 mgimL
`pH 3.4-4.3
`
`Allentanil
`HCV
`Alfenta
`
`4:
`“/14
`
`"
`
`Solution
`0.5 mglmL,
`\0 Sodium chloride (isotonic)
`pH 4~6
`
`Alprostadil
`Lyophilized powder
`(prostaglan~ W 646 ug
`dinEIl
`:
`=
`lactose 172 mg,
`Caverject
`“0
`°"
`Sodium citrate 47 mg,
`Benzyl alcohol 8.4 mg
`
`Dilutewith dextrose
`5% to l-2 mgImL.
`(potentially
`incompatible with
`331"” ”‘1‘?“3‘“!
`Ringer 3)
`
`None for bolus.
`For IV infusion dilute
`with saline, dextrose
`5%. or lactated
`Ringer‘s to 0.025-
`0.080 mglmL.
`
`Reconstitute with L2
`mLwaterpreserved
`with bone I alcohol
`0.950 wlv
`(~ 0.51 1 ug is lost due
`to adsorption to the vial
`and syringe.)
`
`Al rostadil
`°
`L ophillzed wder
`a fadex m 6-50a);eomplexgiiowith 200-
`(prosta-
`_.
`,
`,
`glandinEll
`m
`m
`1610 aficioczccgficlzgextrln
`Eden;
`complexed with (Xe
`H 4-8
`’
`P
`cyclodextrin
`
`Anfifostine/
`Ethyol "*sz 0..
`Prodm that is
`dephosphoxylated by
`Mggfigfig‘mm
`
`Lyophilized powder
`500mg
`
`Reconstitute with 1.2
`mL saline.
`
`Intta—
`cavemosal
`
`Schwm tha,
`Eipctile
`dys unction
`
`IV infusion
`ovet‘ 15-30
`minutes
`
`Reconstimtc with
`salgne1:? so tog/ml.
`sta e at room
`tempgrjéusn):for5
`Maybefunher diluted
`with saline to 5
`mg/mL.
`
`Alza,
`Angeoptasoc
`3ovant_
`[cytolirnoéecuve
`“0me
`(reduces tom
`effect of
`clspiatinn
`
`Elkins-Sinn.
`Antibiotic
`
`Amikacin
`sulfate
`
`Solution
`I'*-
`250 mg/mL,
`K;%W Sodium metabtsulfite0.66%
`.v.
`Sodium citrate 28 %
`pH 3.5 - 5.5
`
`For IV infusion dilute
`with salineor
`dextrose 5% to 2.5-5
`mg/mL
`
`{Ml
`IV Infusion
`over 30 - 60
`minutes
`
`70
`
`PDAJournal of Pharmaceutical Science a Technology
`WW
`
`
`
`Supplied by The British Library- "The world's knowledge“
`
`
`
`
`
`AstraZeneca Exhibit 2158 p. 2
`
`

`

`
`
`
`
`W.
`
`Drug Name!
`Marketed
`Name
`
`ic
`
`Aminoca
`
`ac:
`
`Sanctum:
`
`Formulation
`
`
`Preadministralion
`Route of
`Company and
`Administration
`mm...mm.~u-mu—-M_M”W-WWWWUW-M
`ication
`preparation
`
`.
`
`”IRE/BEN
`
`Solution
`
`ZSOmymL,
`
`Benzyl alcohol 0.9%
`pH 6.8
`
`Dilute with saline or
`dextrose 5% to ~ 15-
`20 mg/mL.
`
`IV infusion at 4
`gramsihour
`
`lmmuncx.
`Enhancing
`hemosmsis when
`fibrinolysis
`contributes to
`bleeding
`
`Merck.
`Measures
`effective renal
`plasma flow
`
`Amino~
`hippurate
`sodium
`H AH“
`
`K
`
`Solulion
`200 mymL
`
`None
`
`IV infusion at
`640 mgflcg and
`10~24 mglmin
`
`Amiodarone
`HClJ
`Cordamne
`
`Amitriptyline
`HCll
`Elavil
`
`Amphoter-
`low E!
`Abeloct
`
`"'
`
`2:38
`
`.k
`
`,0.
`
`W‘
`complexed lzl (drug-to»
`lipid molar ratio) with [L-
`wdimyristoylphosphatl
`dylcholine (DMPC) and If
`avdimyfistoylphosphati—
`dylglyccrol (DMPG) in a
`7:3 mole ratio]
`
`Amghoter-
`icin B
`clnlestetyl
`sulfate!
`Amphotec
`
`.
`
`
`complexed 1:1 molar
`with cholesteryl sulfate
`
`Ainphoter-
`icin BI
`Ambisome
`
`
`
`Solution
`50 mgme,
`TWEEN 80 at 10%,
`Benzyl alcohol 2%
`pH 4.1
`
`Solution
`10 mg/mL.
`Dextrose 44 mg/mL,
`Methylparaben 1.5 mglmL,
`Propylparaben 0.2 mglmL
`pH 4-6
`
`Llposome opaque
`suspension
`5 mglmL
`DMPC 3.4 mg/mL.
`DM‘PG 1.5 mglmL,
`Sodium chloride 9 mglml.
`PH = 5’7
`
`Lyophilized powder
`50 400 mg
`Alter reconstitution will: WFI
`to a S mglmL colloidal
`liposomal dispersion,
`SodiumcholestgLyl sulfate 2.6
`EDTA le037 m mL,
`Lactose 95 m
`TRIS 0.56 mg/rnL
`
`Lyophilized powder
`50 mg
`After reconstitution with WFI
`to a 4 mglmL translucent
`Iiposomal suSpension,
`Hydrogenated soy
`phosphaddylfholine 18 mg]mL,
`Distemoylphosphatidylglycetol
`7mglmL,
`Cholesterol 4 mglmL
`Alpha tocophero! 0.05 mglmL.
`Sucrose 75 mglmL,
`Disodium suecinate 2 mglmL
`pH 5M.0
`
`Dilute with dextrose
`5% to < 2 mglmL.
`
`WyexhoAyerst.
`[V infusion
`at 5-15 mglmin Amianhythmic,
`dextrose
`Amianginal
`
`None
`
`1M
`
`Zeneca,
`Antidepressant
`
`Dilute with dextrose
`5% to 1.2 mglmL
`
`IV infusion at
`2.5 mglkglhr
`
`The Liposome
`Company.
`Amifimgal
`
`Reconstituic wilh
`WFI to 5 mglmL.
`Dilute with dextrose
`5% to 0.16 - 0.83
`mglmL.
`
`[V infusion at
`3-4 mg/kg/hr
`
`Sequus
`(Purchased by
`Ale).
`Amil’ungal
`
`Reconstimle with
`WFI to 4 mg/mL
`Dilute with dextrose
`5% to 1-2 mymL.
`
`IV infusion at
`$5 mglkglhr
`
`Fugisawa
`(developed by
`NeXstar, now
`Gilead).
`Antifungal
`
`3
`l
`g
`
`g
`3
`
`E
`
`
`
`g
`i
`:
`
`Tl
`Vol. 54. No. ‘l I January-Febmaryzooo
`
`
`Supplied by The British Library “The world‘s knowledge"
`
`AstraZeneca Exhibit 2158 p. 3
`
`

`

`
`
`-.........-—.._w..m
`
`Ow
`
`2
`
`Ampicoigin
`G
`*0
`Sulbactam
`
`Formulation
`Powder
`1—2 grams
`(ampicillin),
`0.5-1.0 grams (sulbactam)
`pH:840
`
`Preadministralion
`preparation
`
`Route of
`Administration
`
`Company and
`
`Indication
`
`Rwonstituto with
`WEI to 250 mglmL
`ampicillin and 125
`mymL snlbactam
`For IV dilute with
`saline or dexuose 5%
`to 3-45 mg/mL
`
`1M!
`IV infusion
`over 1080
`minutes
`
`Pfizer.
`Antibacterial
`(ampicillin)
`
`Amrinone
`lemme!
`Inocor
`(not in 1999
`FDR)
`
`Axcnolol!
`Tenormin
`
`Amndum
`bcsylatel
`Tracrium
`
`Atro hine
`sul ate
`
`Aurothio-
`glucose!
`Solganal
`
`Azitiuomy»
`cinl
`Zithromax
`
`cegowwcoon
`
`l /N
`
`Solution
`5 mglrnL,
`Sodium metabisulfite 0.25
`mgImL.
`pH = 3-4
`
`None or
`dilute with saline or
`halfosalino to 1-3
`mgmL.
`
`Slow IV bolus
`over 2~3
`minutes
`IV infusion at
`540 ug/kglmin
`
`Sanofi Winthrop,
`Inotropic and
`vasodilator (short
`term management
`of CHF)
`
`YukOW
`
`Solution
`0.5 mglmL.
`Sodium chloride (to isotonic),
`Citric acid to
`pH = 5.5 - 6.2
`
`None. or dilution with IV infusion at 1
`saline or dextrose 5%.
`rug/min
`
`Solution
`10 mg’mL
`wlwo Benzyl alcohol 0.9%
`pH : 3.2—3.6
`(benzene sulfonic acid)
`Solution
`0.1-1.0 mgme.
`Sodium chloride 9 mglmL.
`w/wo Benzyl alcohol 1.5%
`pH 36
`
`Suspension
`50mg/mL
`in sesame oil
`Aluminum monostearate 2%,
`Propylparaben 0.1%
`
`None for IV bolus
`For IV infusion dilute
`with saline or
`dexirose 5% to 0.2-
`0.5 mglmL.
`None
`
`None
`
`L o hilized power
`y p100 mg
`pH = 9.841
`
`Roconstitute with 10
`mL WFL
`ForIV infusion dilute
`with saline or
`dextrose 5%.
`
`IV bolus!
`IV infusion at
`543 uglkglmin
`
`SCI
`1M:l
`IV bolus
`IM (oil)
`
`Prolonged
`release due to
`slow
`absorption
`
`iv bolus!
`IV Infusion
`
`Lyopliilizcd powder,
`‘
`500 mg,
`Citric acid 414 mg
`
`IV infusion of
`Reconstitute with 5
`500 mg at I
`m1. WFI. and dilute to
`ins/ml. over 3
`1-2 rug/ml. with
`hours. or 2
`saline. dextrose 5%,
`our
`or loomed Ringer‘s. my? over l
`
`
`in
`
`I
`
`3
`;
`§
`
`9
`
`‘
`
`"
`'
`A
`’
`:
`
`1
`‘
`
`I
`l
`
`g
`F
`’
`‘
`i
`
`‘
`i
`{5
`
`Row,
`Antihypertensivc
`and treatment of
`acute myocardial
`infarction
`
`Glaxo Wellcomo,
`General
`anesthesia
`(Skeletal muscle
`relaxant)
`Elkins-Sinn.
`Astra. and
`Baxter,
`Anticholinergic,
`Antispasrnodic
`Schering Corp"
`
`Antirhcumaoc
`
`.
`
`Glaxo Wellcome,
`Immuno-
`suppressive ami-
`unmbolite:
`management of
`severe
`rheumatoid
`arthritis
`
`Pfizer,
`Antibiotic
`
`72
`
`FDA Journal of Pharmaceutical Science & Technology
`
`
`Supplied by The British Library - "The world‘s knowledge"
`
`W
`
`AstraZeneca Exhibit 2158 p. 4
`
`€
`

`

`Dmg Name!
`Marketed
`Name
`Formulation
`mm..«—.u-mu.m«—.~.m”-~«-m.“a“....W.“.m-_“»-u-
`Amoonaml
`8
`Azactam
`“#413591 a 9"
`
`1) Lyophilized powder
`0.5~2 g,
`L—arginine 780mglgram
`moonmn
`138 = 4.54.5
`2) Frozen Solution
`2040 mg/mL
`Lactose ”~34 mglmL.
`Arginine 16-32 mg/mL
`pH 4.5.7.5
`
`Preadministration
`
`preparation
`
`For 1M reconstitute
`with at least 3 mL
`WFI or saline to ~
`100600 mgImL. For
`IV bolus reconstitute
`with WFI to 50—200
`mglmL. For IV
`infusion reconstitute
`with 3 mL WFI, then
`dilute with saline.
`dextrose 5%, lactazcd
`Ringer's to s 20
`mglmL.
`
`Routo of
`Administration
`
`Com y and
`In ication
`
`1M!
`IV bolus]
`IV Infusion!
`
`BMS.
`Antibiotic
`
`Pfizer,
`Pnevent nausea
`with surgery
`mesmesia
`
`Merck,
`Anticholinergic
`used in psychotic
`patients with
`acute dystonic
`reactions, and in
`Paddnson's
`disease
`
`Schering,
`Ami-
`inflammatory and
`for aliergies
`
`"a
`
`~"°"'
`km.
`
`Powder
`50 mg
`pH = 3-4
`
`Recoostituto with
`WFI to 25 mg/mL.
`
`1M]
`iv infusion
`
`Solution
`1 mglmL.
`Sodium chloride 9 mglmL
`pH = 58
`
`None
`
`1M!
`(IV bolus is
`alright. but has
`no advantage
`over 1M)
`
`None
`
`1M
`
`Suspension
`Betamethasone sodium
`phosphate 3 mglmL,
`Betamethasone acetate 3
`
`.
`. mama
`Sodntm phosphate dibasxc
`7.1 m mL,
`Sodium p osphate
`monobasic 3.4 mglmL
`EDTA 0.1 mglmL.
`Benzalkonium chloride 0.2
`mglmL,
`pH 6.8-7.2
`
`
`
`Water soluble
`phosphate ester
`prodrug
`
`D
`
`a Water insoluble
`acetate ester prodrug
`
`Benzguin—mode
`(Not in 1999
`FDR)
`
`Benztmpine
`mesyIate!
`Cogentin
`
`Betametha-
`son:
`Phosphate
`sodium and
`Betametha-
`sone Acetate}
`Celestone
`soluspan
`
`Bethanechol
`chloride!
`Urecholine
`
`["Yfiéfi
`
`Solution
`5.1 mg/mL,
`pH neutxa!
`
`None
`
`SC
`
`Merck‘
`Cholinergic
`
`Vol.54.No.1 I January-vFebruaty 2000
`
`
`73
`
`
`
`Supplied by The British Library — "The worid's knowledge"
`
`W A
`
`straZeneca Exhibit 2158 p. 5
`
`

`

`DmgNamel
`Magritcted
`Name
`
`Structure
`
`
`"fiiffiiifi’wm‘w'
`Lactato'
`Akineton
`
`Formulation
`.........--.......--......~._....
`Solution
`5 mgme
`Sodium lactate 1.4%
`
`Pmadministration
`
`--.«m.--~..—m
`preparation
`None
`
`Route of
`Company and
`
`Administration
`Indication
`NI
`Knoll,
`1M
`Parkinson’s
`Disease
`
`None for IV bolus or
`1M. For IV infusion
`dilute with saline,
`dextrose 5%. or
`lactated Ringer's to 10
`mgiml...
`
`M
`IV bolus!
`IV infirsion at
`1-2 mg/min
`
`Astra.
`Antidysrhythmic
`
`None for IM/SCIN
`bolus. For IV
`infusion dilute with
`saline to l mglmL.
`
`SCI
`le
`IV bolus!
`1V infusion!
`
`Moro.
`Antlhistamlne
`
`None for [M or IV
`bolus. For N
`infusion dilute with
`saline. dextrose 5% or
`taunted Ringer’s.
`
`1M!
`IV bolus over
`1-2 minutes!
`IV infusion at l
`rag/hr
`
`Baxter.
`Diuretic
`
`None
`
`None
`or dilute with saline,
`dextrose 5 96. lactated
`Ringer’s
`
`E idumll
`pinall
`Sympathetic
`nerve!
`Cadmtcr into
`the area bcing
`anesthetized,~
`”5—225 mg/
`(not IV)
`Deep IMI
`IV bolus ovcr 2
`minutes.
`
`Astra,
`Loco] anesthesia
`
`Reckiti-Colcman,
`Analguic
`
`E
`E
`
`Dilute with saline or
`dextrose 5% to 0.6
`mg/mL.
`
`iv infusion
`
`Orphan Medical
`Neoplastic
`
`None
`
`BMS.
`Analgesic
`
`Naal Spray
`(1 spray is
`~ 1 $31: 0.1
`)1
`M
`IV bolus
`(14 mg)
`
`FDA Journal of Pharmaceutical Science & Technology
`
`i
`
`Bretylium
`tosylatef
`fire 10
`‘5’
`
`Br
`
`(
`
`I
`
`on,
`'7
`cu.
`
`"to
`
`Solution
`50m mL
`pH 5—?
`
`B‘oln‘
`pheniramine
`maleate
`(Li uid
`fomtu ation
`not in 1999
`FDR)
`
`' \
`N /
`
`,
`3:”:
`H000
`..WW:
`
`Bumtnnidei
`
`°o,NH,
`
`Bumcx Wax}:
`WW“ OG
`
`Bu ivacainc
`pncu
`Sensorcainc
`
`“-0
`
`”F
`q I;
`‘3
`cu,
`
`pKa - 8 l
`
`HO
`
`a,
`._
`
`Buprenor—
`phim: HCI
`(SO-times
`more potent
`than
`morphine)/ H,”
`Buprenex
`
`,
`‘
`$153333“:
`
`"\V
`
`Solution
`10 mglmL.
`Methylpmbcn 0 18%
`Propylpamben 002%
`pH: 6.7—7 1
`
`Solution
`0.25 mglmL.
`Sodium chloride 8.5 mglmL.
`Benzyl alcohol 10 m mL.
`EDTA 0.! rug/m ,
`Ammonium acetate 4 tog/ml...
`pH 6.8-7.8
`Solution
`2.5-7.5 mgme
`Sodium chloride to isotonic.
`w/wo Epinephrine 9 uglmL,
`Sodium metabisulfitc 0.5
`mL.
`n 1 mg/mL,
`Methyl
`Citric acid 0.2 mg/mL.
`pH 4—6.5
`Solution
`0.3 mg/rrtl.,
`Dextrose SO mgImL
`pH 3.5-5.5
`
`Busulfnn/
`
`Busulfex
`
`""1
`
`"0
`
`Butorphanol
`Stadol
`(In;octable not
`in 1999 FDR
`the only
`productIS a
`nasal
`fonnulatlon.)
`
`o
`
`.4“
`
`Solution
`6 mg/mL
`PEG 400 at 67%
`N, N-dimethylacetamide
`(DMA) 33%,
`
`0:00:50...
`
`Injectahle solution:
`[-2 mglmL
`Sodium chloride 6.4 mglmL
`Citrate buffer 0.045M
`pH 3.5.5.
`Nasal spray solution:
`10 mgij,
`Sodium chloride, Citric acid.
`Benzethonium chloride.
`pH 5.0.
`
`'
`
`74
`
`I
`
`_.W___. ,
`
`Supplied by The British Library "The world's knowledge"
`
`,, AWW
`
`Lu—un—M
`
`AstraZeneca Exhibit 2158 p. 6
`
`

`

`
`
`Drug Name!
`Marketed
`Name
`
`Structure
`
`Route of
`Proadnfinistrafion
`Company and
`Indication
`Formulation
`«0
`.....—-~...mm.....—..._-.-.-.mu...-.m--~—._......._...._m.__._.,.............,
`preparation
`Administration
`Non:
`IMI
`Solution
`Novartis,
`"$53.31”:'“Rifi'fifiéfifiififiimwm
`SCI
`Treatment of
`Salmon,
`amino-acids
`Pi‘200 LUJmL,
`posunonopausal
`Miacnicin
`(H£ys-Scr»Asn~L¢u-
`cool 5 rug/ml”
`osteoporosis;
`Scr—‘I‘hr-Qs-Val-lgm
`Sodium chloride 7.5 mglmL,
`Acctato buffer
`Paget‘s disease,
`GIy—Lys-lsu‘Ser—Gin.
`and
`pH ~ 4
`GIu~ko~His~LysLeu~
`hypetcalcemia
`Gln-Thr-Tyr-ProoArg-
`Thr—Asn-Thr—GIy-Ser—
`GlyoThrvPrmNHQ
`"
`
`Calcitrioll
`Calcijcx
`
`“-
`
`as
`C“
`
`N
`
`Szolution
`l- uglmL,
`TWEEN 20 at 4 ng'mL.
`Sodium ascorbate Io
`mglmL.
`Sodium chloride LS mglmL.
`EDTA 1.1 mg/mL,
`Sodium phosphates 9.2
`mgImL,
`pH ss-so
`
`also $823380
`5
`y o
`IfiJmL, and
`one spray
`contains 0.!
`mL or 200 LU.
`
`None
`
`IV bolus
`
`Abbott,
`Management of
`hypocalccmia in
`patients
`undergoing
`chronic renal
`dialysis
`
`Caproo-
`midi;
`sul 3
`Capastat
`
`~81
`‘
`“
`\AJU}
`mm?“ in
`
`.
`
`Powder
`1000 mg
`
`Carboplagin/
`Paraplann
`
`NH“ ’0Pl
`”Ha/l ‘0
`
`0
`
`O
`
`Carmustinel
`BiCNU
`
`/o
`
`NI
`WNYMCI
`o
`
`Powder
`50450 mg.
`Mannitol equal mass as
`carbopiatin.
`pH 5-7
`
`Lyophilized solid
`[00 mg
`98 5-6
`
`Ccfamandolc
`[glandol
`( ormate
`ester
`prodrug -
`h “Pi“
`ydro ysis
`after
`dissolution)
`
`o
`
`R "
`‘ ’
`:
`o
`‘10 m coon
`
`o
`
`9'.
`if}.
`
`Solid
`1-10 g
`Sodium carbonate 63 tog/gram
`cefamandolc,
`pH 6-8.5
`
`’r‘
`
`’r‘
`
`in
`“.12..
`pKa 2.6 - 3.0
`
`9"
`.J‘
`
`Reconstitute with 2
`mL WFI or saline to
`500 mglrnl. (~ 3
`minutes lo dissolve).
`For M no dilution,
`but may reconstitute
`with less water to
`200350 mg/mL
`For N infusion dilute
`into 100 mL saline.
`
`Roconstitutc with
`WFI, saline or
`dextrose 5% to 10
`mg/mL. May be
`funhcr diluted to 0.5
`mglmL wilh saline or
`demos: 5%.
`
`1M!
`IV infusion
`over 60
`minutes
`
`Dom,
`Antibiotic
`
`[V infusion of
`at least 15
`minutes using
`05-10 mg/mL.
`
`BMS.
`Antineoplastic
`
`Reconstitute with
`
`IV infusion
`
`supplied 3 mL of
`ethanol, than further
`dilute with 27 mL
`WFI. to a final 10%
`ethanol.
`
`Reconstimte with
`WFI, saline or
`dextrose 5% to 100-
`285 mgr’mL.
`
`over i—Z hoursi
`150200 mglm
`
`M
`IV bolus
`over 3-5
`minutes!
`IV infusion
`over 15-30
`minutes
`
`BMS.
`Antineoplastic
`
`Lilly.
`Antibacterial
`
`75
`Voi.54.No.1 I January-Febmaryzooo
`
`
`
`
`
`Supplied by The Briiish Library - "The wodd's knowledge"
`
`AstraZeneca Exhibit 2158 p. 7
`
`

`

`DmgNamel
`Marketed
`Name
`
`Structure
`
`Formulation
`
`Pmadnnnistmtion
`preparation
`
`Route of
`
`Administration
`
`Company and
`Indication
`
`Cet‘azolin 6w 2!
`sodium!
`Ancef,
`°
`ch201
`
`'3 .
`
`,
`
`,
`13’“
`
`2)
`
`1) Lyophiiizcd powder
`0.540 g
`H 4.5 - 6.
`rozen solution
`10.20 mglmL,
`Dextrose ~ 4048 mglmL
`pH 4.5-?.
`
`Cefepime
`_
`Solid mixture
`HCII
`0.5-2 g.
`"i "
`Maxipime W L—Arginine725 mglg cefepime
`pH 4.0-6.0
`
`Ccfonicid
`sodium!
`Monocid
`
`Ova“ “ "
`°"
`
`r”
`“(‘3
`H
`
`Lyo hilized powder
`P 05t g
`pH 35— 65
`
`Reconstimte with
`WFI. or saline to 225-
`330 rug/ml. for 1M,
`and dilute with WFI.
`to ~ 100 mgme for
`IV boius, and dilute
`with saline. dextrose
`or inflated Ringer‘s to
`10 mm for IV
`infusion
`
`Reconstitnte with
`saline. dextrose 5% or
`lactated Ringer’s to
`280 m mL for M,
`100-1 mglmL for
`IV bolus, 2040
`rug/ml. for IV
`infusion
`
`Reconstimte with
`WFI to 225-325
`m
`for IM and IV
`be us, and dilute with
`saline, dextrose 5% or
`lactated Ringer’s to 10
`mglmL for IV
`infusion.
`
`Cefopera-
`zone
`sodium!
`Cefobid
`
`a
`
`g.
`
`..
`'
`
`°
`
`t:
`“$4
`
`Cefotaxime
`sodium!
`Claforan
`
`"
`a at
`“AN'UT'
`at:
`
`Y"
`
`Cefotetan
`disodium/
`Ccfotan
`
`«-
`
`° ‘5”:
`'
`"
`0
`
`‘
`
`i"
`‘Q'
`
`I) Czystallinc powder
`0.5-! g,
`pH 45 6
`2) Frozen solution
`20-40 mg/mL.
`Dextrose ~ 3646 mg/mL
`pH 4.53].
`
`1) Powder
`0.5-2g
`pH 4sg'6.
`2) Frozen solution
`20-40 mglmL.
`Dextrose ~ 14—34 mgme,
`Sodium citrate
`pI-I 5-7.5
`
`1) Powder
`I103
`pH 4.5-6.5.
`2) Frozen solution
`20-40 mg/mL,
`Dextrose - 22—38 mgme.
`Sodium bicarbonate
`pH 4-6.5
`
`1M]
`Roconstitute with
`saline or dextrose 5% IV in us over
`m 230 at
`1:11. for IV
`3.5 minutes/
`bolus.
`iiute with
`IV infusion
`lidocaine 2% to ~ 200
`over 15.30
`mglml. for M. Dilute
`minutes
`with saline. dextrose
`5% or lactated
`Ringer’s to 2.25
`mglmL for IV
`infusion.
`
`Hoechst Marion
`Roussel,
`Antibiotic
`
`Zeneca,
`Antibiotic
`
`Deep IM/
`IV bolus aver
`3-5 minutes!
`IV infusion
`over 15-30
`minutes
`
`DecpIMl
`IV bolus over
`3-5 minutes]
`IV infusion
`over 20450
`minutes
`
`Reconstitute with
`WFI to 230630
`mg/mL for IM. 50-
`180 mglmL for IV
`bolus, and dilute with
`saline or dextrose to
`10 rug/m1. for IV
`infusion.
`
`For IM, reconstitute
`with WFI, saline,
`0.5% or 1% Iidocaine
`to 400.500 mglmL.
`For IV, reconstitute
`with WFI to 95-180
`mglmL, and dilute
`with saline or
`dextrose 5% to 10
`mymL for IV
`infusion.
`
`1M!
`IV bolus
`over 36
`minutes!
`IV infusion
`
`Smith-Kline
`Beecham and,
`Liiiy,
`Antibiotic
`
`1M!
`IV bolus over
`3—5 minutes!
`IV infusion
`over 30
`minutes
`
`1M]
`IV bolus
`over 3.5
`minutes]
`IV infusion
`
`BMS,
`Antibiotic
`
`Smith-Kline
`Beecham,
`Antibiotic
`
`Pfizer.
`Antibiotic
`
`K
`*
`‘
`
`,
`;
`:
`‘
`i;
`.
`
`.
`
`,
`"
`
`s
`
`;
`t
`
`I
`
`75
`
`PDA Joumat of Pharmaceutical Science & Technology
`
`Supplied by The Bntish Library "Theworld's knowledge"
`
`AstraZeneca Exhibit 2158 p. 8
`
`

`

`Drug Name!
`Marketed
`Name
`Structure
`Cefoxitin w ‘3“;-
`sodium!
`“:1"
`Mefoxin
`a
`
`Ceftazidime/ W a;
`(Ceptaz,
`""
`..
`Fortaz,
`‘a o
`'l‘azidime,
`we",
`Tazicei)
`
`.3
`'
`
`o
`
`«a
`
`Formulation
`1) Powder
`1-10 g
`pH 4.2-7.0.
`2) Frozen solution
`20-40 mghnL,
`Dextrose ~ 2240 mglmL,
`Sodium bicarbonate
`[3}! 6.5
`
`1) Powder
`wlwo Sodium carbonate at l 18
`mg/g eeftazidime.
`wlwo L-Arginine at 349
`mg/grarn ceftazidime
`pH 5-7.
`2) Frozen solution
`20-40 InglmL.
`Dextrose ~ 50 mg/mL.
`Sodium bicarbonate
`pH 465
`
`8
`Celtizoxime
`it
`sodium! M I
`Cefrzox
`u‘
`OGHP
`
`°
`
`.5 R
`t
`= 3
`;:Nl
`coon
`
`Crystalline powder
`0.5—2 3
`pH = 6-8
`
`Ceftriaxone ”1% t: a .
`"(22“
`sodium!
`"
`Rocephin
`‘wt"
`cm .
`a
`u
`
`I) Crystalline powder
`(125-10 g,
`pH = 6.8.
`2) Frozen solution
`20-40 mg/mL,
`Dextrose - 24.38 mg/mL,
`pH 6.7
`
`Route of
`Administration
`IV bolusover
`36 minutes/
`1V infusion
`over ~ 30
`minutes
`
`Company and
`Indication
`Merck,
`Antibiotic
`
`Deep 1M!
`IV bolus over
`3-5 minutes/
`IV infusion
`over ~ 30450
`minutes
`
`Glaxo Wellcome,
`Lilly and,
`SmithKline
`Beecham,
`Antibiotic
`
`DeepM
`1v over 3-5
`minutes!
`IV Infusion
`
`Deep IM/
`IV Infusion
`over 30
`minutes
`
`Fujisawa.
`Antibiotic
`
`Roche,
`Antibiotic
`
`Preadministmtion
`preparation
`Reconstitute with
`WFI to 100-200
`mgImL for IV bolus.
`For XV infusion
`reconstitute with
`saline or dextrose 5%
`to lOO mg/mL. then
`dilute to 10 mglmL
`
`For 1M, reconstitute
`with WFI, saline,
`0.5% or 1% lidocainc
`to 250 mg/mL.
`For N, reconstitute
`with WFI to 90470
`mg]ml., and dilute
`with saline or
`dextrose 5%.
`to 1040 mglmL for
`IV infusion.
`
`Reconstitute with ‘
`WFI to270 mglmL
`for M, 95 mglmL for
`IV bolus, and dilute
`with IV fluids to ID-
`40 mg/mL for IV
`infusion.
`
`For [N], reconstitute
`with WFI. saline,
`dextrose 5% or
`lidocaine 1% to 250
`m mL.
`infusion,
`For
`reconstitute with WFI
`to 100 mg/mL. then
`dilute with saline or
`dextrose 5% to 10-40
`mglmL.
`
`Cefuroxime, W gt
`sodium!
`‘
`Zinaccf
`“mo
`'
`
`.5
`'
`
`Ccphalothin
`sodium!
`Keflin
`Neutral
`(Not in 1999
`PDR)
`
`,, n
`‘
`’
`
`.
`
`,,
`
`y“:
`0
`
`1) Crystalline powder
`0.75-7.5 g,
`98 = 68.5.
`2) Frozen solution
`15-30 mg/mL,
`Dextrose ~ 28 rug/ml.“
`Sodium citrate 60-120 mg/mL
`pH 5-7.5
`
`Reconstitute with
`WFI to 220 mglmL
`for M, and 90
`mglmL for IV bolus.
`For IV infusion,
`reconstitute with
`saline or dextrose 5%
`to 75-15 mg/mL.
`
`Reeonstitute with
`1) Powder
`saline or dextrose 5%
`l-20 g.
`Sodium carbonate 30 rug/gram to 250 rug/ml. for 1M.
`cephalothin
`100 mglmL for IV,
`pH = 6-8.5
`and 20-40 rug/ml. for
`2) Frozen solution
`IV infuston.
`20-40 mg/mL.
`Dextrose ~ 50 rug/um, Sodium
`bicarbonate
`pH = 63.5
`
`Deep 1M!
`IV over 3-5
`minutes!
`IV Infusion
`over 15-60
`minutes
`
`Deep IM/
`1V over 3-5
`minutes/
`IV infusion
`
`Glaxo Wellcome,
`Antibiotic
`
`Lilly,
`Antibiotic
`
`Vol.54, No. 1 l January-February 2000
`
`
`77
`
`Supplied by The British Library - “The world's knowledge“
`
`AstraZeneca Exhibit 2158 p. 9
`
`

`

`
`Sanctum
`
`b} .3
`'
`'
`
`o
`
`0
`f“
`
`H‘
`
`c:
`
`’N\
`o
`
`Dm Name!
`Mfrkeied
`Nam:
`
`Cephapinn
`sodium!
`Ccfadyl
`(No: in 1999
`FDR)
`
`Chlordiaz~
`c
`xide
`CU
`Libtium
`
`Chime.
`procaine
`HCll
`Nesacaine
`
`Chloroquine
`HCL’ am
`Amlen
`WWW”
`m.
`ken.
`
`Chloro-
`ihiazide
`sodium]
`Diuril
`
`0 1°
`“5’
`HzN’
`
`c:
`
`0 lo
`“5’
`‘NH
`,J
`N
`
`0'
`
`Cbloxphenir-
`amine
`maleaze/
`Chlor-
`{rimctun
`mo: in 1999
`PDR as
`injectable)
`‘
`
`Chlorproma—
`zine HCi/
`Thorazinc
`
`Prcadministration
`
`Formulation
`preparation
`
`Route of
`Administration
`
`Company and
`Indicafion
`
`Powder
`05—20 g,
`pH = 68.
`
`Deep 1M!
`Rocomfimtc with
`saline or dextrose 5% W over 3-5
`to 500 mglmL for M,
`. minutes]
`£1403 :zgmléggi
`IV infusion
`, an
`m
`for IV infusion.
`
`Apothecon,
`Amibiotic
`
`Reconsfimte with
`supplied diluent to 50
`mg/mL for M.
`Reconstimte with
`saline orWFIto 20
`nag/ml. for IV bolus.
`
`None
`
`Powder
`100 mg.
`Supplied diluent:
`PG 20 %
`TWEEN so at 4%,
`Benzyi aicohoi 1.5%,
`Maieic acid 1.6%
`p}! = 3
`
`Soiution
`[0-30 mglmL
`Sodium chloride 3.3-6.7
`mg/mL.
`wlwo EDil‘A 01;; mglmL,
`wiwo Methy para
`a i mglmL,
`pH 2.7-4.0
`
`1M!
`Slow IV bolus
`over I minute
`
`ICN.
`Tranquiiizer
`
`Astra,
`Local anesthetic
`‘
`
`Single injection
`or continuously
`through an
`indwelling
`cathacr.
`
`Soiution.
`50nag/ml.
`pH 5.5-6.5
`
`None
`
`1M
`
`Sanofi Winthro .
`Antimalaxiaan
`anfiamcbic
`
`Lyophiiized powder
`500 mg,
`Mannito! 250 mg.
`Thimerasol 0.4 mg,
`pH 9.2-“)
`
`Soiminn,
`10400 mgimL
`pH 4-5.2
`
`Rcconstimte with 13
`mi. WFI to 28
`mglmL.
`
`{W
`IV Infusion
`
`Merck,
`Diumtic and
`hypertensive
`
`None
`
`N (not the 100
`mg/nmy
`SCI
`1M
`
`Schcring,
`Aniihistamine
`
`
`
`,
`5
`z
`{
`I
`I
`
`9H,
`,N
`HH’ccooH
`i
`
`H
`
`coca
`
`N’ !
`\
`
`9H,
`N\
`{V CH;
`cg
`
`s
`
`Solution
`25 mg/mL,
`Sodium chloride 6 mg/mL,
`Sodium bisulfile l mglmL.
`Sodium sulfite I mglmL,
`wlwo benzyl alcohol 2%.
`Ascorbic acid 2 mg/mL.
`pH 3-5
`
`None for M.
`Dilute with saline to 1
`mglmL for N.
`
`Deep [M in
`buttock!
`IV bolus at 0.5-
`l rug/minute
`
`Smith-Kline
`Bcccham,
`Antipsychotic,
`anticmctic
`(nausea).
`aanquilizer
`
`73
`
`PDA Joumai of Pharmaceutical Science &Tachnoiogy
`
`
`Supplied by The British Library — “The worid‘s knowledge"
`
`iW A
`
`straZeneca Exhibit 2158 p. 10
`
`

`

`
`
`N
`
`ML
`
`o
`
`cytomegalovims
`in AIDS patients
`
`Drug Namel
`Route of
`Preadministtation
`Marketed
`Company and
`Indication
`Administration
`Structure
`Formulation
`Name
`preparation
`mam”.-.-»-"-m.m.-wu..«mm--«-a...an"....mwmm.--.~---.-m-...mu.mu~-......”m.u-....---.......u......,,,...-....
`IV infusion
`Dilute into 100 mL
`Solution
`Gilead.
`Cidofovirl
`Antiviral
`saline to ~ 3-5
`Vistide
`at 5 rug/kg over
`75 mg/mL,
`1 hour
`treatment of
`mg/mL
`pH 7.4
`Required
`predose of 2
`grams
`probenecid
`orally (reduces
`renal clearance
`by blocking
`active renal
`tubular
`secretion).
`
`“ii—ECO“
`
`I
`
`a
`
`H
`
`
`
`Cilastatin
`(inhibitor of
`
`renal
`dipcptidase.
`dchydro-
`peptidase I)
`and
`Imipenam!
`Primaxin
`
`Gmtidinc
`HCll
`
`Tagamet
`
`Powder
`500-750 mg each,
`Sodium carbonate 1020 mg
`(1V).
`pH 6.5-7.5
`
`E m
`
`.l
`0
`
`[minute-
`
`s
`
`“3&2
`:a’"
`
`if\
`
`use“
`
`gOSolution
`mglmL
`Phenol 5 mgimL
`, pH 46
`2) Infusion solution
`6 mglmL
`Sodium chloride 9 mglmL.
`
`Ciprofloxacim’
`Cipro
`
`"“0
`
`COOH
`
`Cisplatinl
`Platinol
`
`”sz
`
`HN Cl
`
`Cladn’bind
`Leustatin
`
`1) Solution
`10 mg/mL,
`Lactic acid
`pH 3.3-3.9.
`2) Infusion solution
`2 mgImL
`Dextrose 5%,
`Lactic acid.
`pH 3.5~4.6.
`
`I) Lyophilized powder.
`after reconstitution contains
`l mglmL.
`Mannitol 10 mglmL,
`Sodium chlon‘de 9 mglmL,
`pH = 3.56.5.
`2) Solution
`1 mglmL
`Sodium chloride 9 mgImL
`
`Solution
`1 mg/mL,
`Sodium chloridc 9 mg/mL,
`Sodium he hates,
`pH .5- .0
`
`1M: Reconstitute with
`lidocaine l% to 250
`rug/ml. suspension.
`lV: Reconstitute with
`[00 ml. saline or
`dextrose then diluted
`with 100 ml. saline or
`dextrose to 2.54
`tog/ml. solution
`
`None for IM.
`Dilute with saline,
`dextrose 5% or
`lactated Ringer's to 15
`rug/ml. for IV bolus
`and 6 mglmL for IV
`infusion.
`
`Dilute with saline,
`dextrose 5% or
`lactated Ringer’s to l-
`2 mglmL.
`
`M
`W infusion
`
`Merck,
`Antibiotic
`treatment of
`serious infections
`
`Smith-Kline
`Beecham,
`Amiulcemtive
`(histamine H2-
`receptor
`antagonist
`
`Bayer.
`Antibacterial
`
`IMI
`Slow IV bolus
`at least 5
`minutes!
`1‘! Infusion
`over 15-29
`minutes
`
`IV infusion
`over 60
`minutes, 200-
`400 mg every
`12 hours
`
`Reconstitute with
`WFI to 1 mg/mL
`
`IV infusion
`
`BristoloMcyers
`Oncology.
`Antineoplastic
`
`IV infusion
`over 24 hours
`after
`
`Ortho.
`Antineoplastic
`
`Dilute with 500 mL
`saline to 0.09
`to
`da (not
`fungi/mid to use
`dextrose 5% due to
`increased drug
`degradation)
`
`Vol.54, No.1 i January—February 2000
`
`
`
`79
`
`
`Supplied by TheBritishlibrary-”The worlds knowledge"
`
`
`
`AstraZeneca Exhibit 2158 p. 11
`
`

`

`Structure
`
`Formulation
`
`Preadministration
`preparation
`
`Route of
`Administration
`
`y and
`from
`
`
`
`1) Powder
`Clavulanate 0. lg.
`tharclllin 3 g.
`w W 2) Frozen solution
`Clawlanatel mghnL,
`'l‘icarcillin 30 mglmL
`
`'1"ka
`
`' Reconstitute with
`WFI or saline to 8
`mglmL clawlanate
`and 200 tug/ml.
`tlcareillin, further
`dilute with saline or
`lactated Ringer‘s to
`[0—100 mg/mL
`
`Dilute concentrated
`solution with saline or
`lactatcd Ringer’s to S
`18 mglmL.
`
`IV infusion
`over 30
`minutes
`
`SmithKline
`Beecham,
`Antibiotic
`
`IV infusion at
`30 mgfhour
`
`Phamtacia &
`Upjohn,
`Antibiotic
`
`u,
`
`95%.
`M
`“
`
`9S
`‘°'
`
`on
`
`99‘:
`3,0
`a a.
`Water soluble
`phosphate ester
`prodrug
`
`1) Solution
`150 mgme.
`EDTA 0.5 mgimL,
`Benzyl alcohol 9.4 mglmL
`p=H 5-6
`2) Ready to use solution
`05-18 mglmL
`Dextrose 5%.
`EDTA 0.04 mglmL.
`
`Solution
`0.! mglmL.
`Sodium chloride 9 mglmL
`pH 5-7
`
`”
`
`
`
`n
`
`’
`
`Solution,
`15-60 mglmL.
`wlwo Chlorobutanol 5 mglmL,
`EDTA l mglmL,
`Sodium metabisult'tte 1-2 mgme,
`Acetate buffer
`pH 3-6.
`
`‘
`
`1M
`“mm
`“31??
`Tyloxapol. oxyethylated
`tertiary oct lpltenol
`formaldehy e polymer
`
`”Tm
`-0"
`
`0
`
`Water insoluble
`ester prodrug
`
`Lyophilized powder
`DPPC 108 mg
`Cetyl alcohol )2 mg
`Tyloxa
`18 mg,
`Sodium ch oride 47 mg
`PH 57
`(A synthetic lung surfactant)
`
`Sns ension
`50 fitglmL,
`Sodium earhoxy-
`methylcellulose 5 mg/mL.
`TWEEN 80 at 4 mgknL,
`Sodium chloride 9 mglmL
`Benzyl alcohol 9 ”Wm”
`
`None
`
`N infusion
`
`Roxane,
`Analgesic
`
`None
`
`SCI
`1M!
`IV occasionally
`
`Elkinssinn and
`Wyeth,
`Analgesic,
`anticough
`
`Reconstitute with 8
`mL WFI.
`
`Intratmcheal
`Suspension
`
`None
`
`1M on!
`
`y
`
`Glaxo Wellcome,
`Prevention and
`treatment of
`Respiratory
`Dtseasc
`Syndrometn low
`ybirth weight
`infants
`Merck,
`Endocrine
`disorders.
`rheumatoid
`arthritis,
`allergies
`
`Drug Name!
`Marketed
`Name
`
`Clavulanate
`potassium
`and
`ticaxcillin
`disodium/
`Trmentin
`
`Clindamycin
`Phosphate!
`Cleocin
`phosphate
`
`Clonidinel
`Duraclon
`
`Codeine
`phosphate
`(Not in 1999
`FDR as an
`injeetable)
`
`Colfosceril
`palmitmte
`(DPPC),
`Cctyl alcohol
`and
`Tyloxapol/
`Exosurf
`neonatal
`Cortisone
`Acetate!
`Cortone
`
`
`
`i
`I
`'
`’
`
`Cyanocobal- MW - 1355, poxphoryn
`amin
`like with Co (+) at the
`(Vitamin
`center, synthesized by
`812)
`bacteria
`
`Solution
`0025-1 in mi.
`Sodium ch oxide
`Benzyl alcohol.
`pH 4.5-7
`
`None
`
`SCI
`N
`
`Blkins-Sinn,
`Nutrient
`
`Cyclophos-
`phamidd
`Cytoxan
`
`O
`
`(\0'
`N
`‘9’ \/\Cl
`1\
`NH 0
`
`Lyophilized powder
`100.2000 mg
`Mannitol 75 mglloo mg
`cycloph
`harnide
`pH -9
`
`Reconstitute with
`WFlto20 mg/mL.
`For IV infusion dilute
`with saline. dextrose
`5% or lactated
`Ringer‘s.
`
`M
`IV bolus]
`IV infusion]
`IP/
`intrapieural
`
`Bristol-Myers
`Squibb,
`Antineoplastic
`
`so
`
`PDAJoumal of Pharmaceutical Science & Technology
`WM,W~WW .. A.
`
`
`Supplied by The British Library "The world's knowledge"
`
`
`
`AstraZeneca Exhibit 2158 p. 12
`
`

`

`Drug Name!
`Marketed
`Name
`
`Cyctospodnl
`Sandimmunc
`
`Qtambine
`(Am-C)!
`Cymsaw
`
`CyIarabine
`(Ara-C)!
`DepoCyte
`
`Dacarbazinel
`DTIC—Domc
`
`Dactino‘
`mycinl
`Cosmcgcn
`
`Dalteparinl
`Fragmin
`
`_
`
`Danaparoid!
`Orgaran
`
`Structure
`
`Formulation
`
`Preadministration
`
`pneparation
`
`Route of
`Adnfinisuation
`
`Company and
`Indication
`
`
`Cyclicpe idc (II
`ammo aoi
`, MW -
`1200
`
`NH-
`Nv/Jj
`Ho ov'xN
`\l o l
`H
`
`N":
`N2)
`H0 odk-N
`0
`
`H
`
`{CH3
`N=N~N
`
`CH3
`
`"‘6
`“.0
`
`o
`
`°
`
`°
`
`VoWlo
`”mm,
`
`a
`v
`mvuSu
`“f” ”i
`
`Sqution,
`50 mglmL
`Cremophnr EL 65%,
`Ethnnol 35%,
`bianketod with niu‘ogcn
`
`Lyophilized powdcr
`500~2000 mg
`pH 5
`
`Dilute with saiine or
`dextrose 5% to 1-25
`mg/mL(I ml. into 20-
`100 mi.)
`
`IV infusion
`over 26 hours
`
`Reconstitutc with
`saline or WFI with
`benzyl axcohot 0.9%
`to 20-100 mgme.
`
`Intramecall
`SCI
`IV bolus!
`IV Infusion]
`
`None
`
`Immhocal
`
`Suspension Multivesicular
`Lipid Particle
`5 mg/mL
`Cholesterol 4 mgimL
`Dioleoylphos hatidylcholinc
`(POPC)
`.7 mghnL.
`palmiEoyPI hosphatadylgiyccrol
`)I mg!glmL
`Sodiumchlonde 9 mg/mL
`pH 5.5-8.5
`
`Solid
`100-200 mg
`Mannitoi and Citric acid.
`pH 3—4
`
`Reconstimte with
`WP] to ID ngmL.
`For IV infusion may
`be further diluted with
`saline or doxlrosc 5%
`to 0.4 mg/mL
`
`IV over 1
`minute!
`IV Infusion
`over 15450
`minutes
`
`Novanis,
`Immunrr
`supprcsent
`
`Pharmacia &
`Upjohn,
`Amineoplastic.
`Antiviral
`
`Chimn
`(DcveIoped by
`Depochh)
`Antimoplaslic,
`Antiviral
`
`Bayer,
`Antincoplastic
`
`Lyophilizcd powder
`05 mgg.
`Mannitol 20 mg,
`pH 5.5-?
`
`Reconstimlc with 1.!
`mL WFI. For IV
`infusion further dilute
`with saline or
`dextrose 5%.
`
`IV bolus!
`IV Infusion!
`
`Merck.
`Antflyiotic
`
`Low MW heparin
`W "‘ m
`{1}“
`
`3'11.»-
`E’xs‘fi“
`"’"
`
`Solution
`V!
`(prefillod syringacifnd mum-use
`64160 mglmL
`Sodium chloride.
`wlwo Benzyl alcohol 0 15%
`pH 5.0-75
`
`84% heparin sulfate,
`12% dot-mam sulfate.
`4% chondmitin suifatc
`(isoiazed from porcine
`intestinal mucosa)
`
`Solution
`(prefilled syringe or nmpuie)
`1250 anti-Xa units/mL,
`Sodium chloride
`Sodium sulfite 0.15%
`pH 7
`
`None
`
`SC
`
`Pharmacia 84
`Upjohn,
`Antithrombotic
`
`Nonc
`
`SC
`
`Organon.
`Antithromboiic
`
`Dantrolcnc
`sodium!
`Dantrium
`
`°«~O~Q¢i
`
`Lyophiiized powder
`20 mg.
`Mannitol 3000 mg.
`pH 9.5
`
`Roconsiitute with 60
`mL WM :0 0.3
`mglmL. For IV
`infusion further dilute
`with IV fluids.
`
`IV bolus]
`1v infusion
`over 1 hour.
`
`V01.54.No.1 I Januaty-Februaryzooo
`
`
`Supplied by The British Library- "The world‘s knowledge"
`
`
`Promo: &
`Gamble Pharm.
`(Muscle relaxant)
`Treatment of
`hypennetaholism
`and hypenhezmia
`
`81
`
`
`
`AstraZeneca Exhibit 2158 p. 13
`
`

`

`Drug Name!
`Route of
`Pmadmlnistration
`Marketed
`Administration
`Name
`Structure
`Formulation
`preparation
`um-“o-Mm‘.-«.¢--.-mu.M...“.m.......-.W.mwnu-nmn.-mu-Wwom...»_-mmmm..
`'IV infusion
`Dannorublein
`o
`0
`Hell
`Cerubidine
`
`=
`
`“on
`
`cargo
`up
`
`on 5
`
`““2
`
`Lyophilized powder
`2L4 mg.
`Mannitol [00 mg
`pH 4.562
`
`Reconstimte with 4
`mL WFI to 5 InglmL.
`then fnnher dilute
`with 10.15 mL saline
`and then inject into
`rapidly flowing [V
`infusion of saline or
`dextrose 5%.
`
`Company and
`Indication
`
`Redford.
`Antibiotic
`
`Daunombicin
`Citrate!
`DaunoXomc
`
`o
`
`0
`
`"on
`
`cargo
`3,0
`
`cm :
`
`m
`
`Solution Iiposome
`2 mgme.
`Distcmyiphosphmidylcholine:
`Cholestcml in 2:1 molar ratio.
`lipid to drug ratio of l8.7:l
`diameter of 45 nm
`
`Dilute [:1 with
`dextrose 5% to I
`mglml...
`
`IV infusion
`over 60
`minutes
`
`NeXstar (now
`Gilead),
`Antibiotic
`
`Desmo— m
`H
`pressin
`‘7
`066mm
`Synthetic analog of
`DDAVP
`natural hormone 8-
`arginine vasopressin
`(ADH)
`
`Solution
`4 uglmL,
`Sodium chloride 9 mglmL,
`w/wo Chlorobutanol
`pH 4
`
`None for SC or IV
`bolus. For IV
`infusion dilute with
`saline to (0.3 uglkg)
`in 50 mL.
`
`SC!
`IV bolus]
`[V infusion
`over 15-30
`minutes
`
`Rhone‘Poulenc,
`Rotor,
`Hemophilia
`(maintain
`homeostasis)
`
`Dexametha—
`sone
`
`Acetate!
`Decadron-
`[A
`
`Dexametha»
`sone
`Acetate!
`Dalalonc
`DP.
`
`Dexametha-
`son:
`Phosphate
`50le
`Decadmn
`
`Dexrazoxanl
`Zinecard
`
`«n I
`
`u.
`
`l
`
`0 Water insoluble
`acetate ester
`prodrog
`
`
`
`0 Water insoluble
`acetate ester
`prodrug
`
`°"
`‘5‘“
`on
`
`
`
`‘3
`Water soluble
`phosphate ester
`prodrug
`
`Gentle swirl contents
`to resuspcnd settled
`paniclcs.
`
`IM/
`Intralesionall
`Inna-articular!
`Soft tissue
`
`Merck,
`Anti-
`inflammatory
`
`Gentle swirl contents
`to resuspend settled
`particles.
`
`lM/
`lnun-anicularl
`Soft tissue
`(Not
`intralesional)
`
`Forest.
`Anti-
`inflammatory
`
`For IV infusion dilute
`with saline or
`dextrose 5%.
`
`Merck.
`Ami-
`inflammatory
`
`IV bolus!
`1V infusion!
`IMI
`lntralaionall
`Inna-articular]
`Soft tissue
`
`Suspension
`8 mg/mL
`Sodium chloride 6.7 mglmL,
`Creatinine 5 mg/mL,
`TWEEN 80 at 0.75 mglmL,
`ED