`
`III
`
`I __........
`
`.—
`
`REVIEW ARTICLE
`
`Parenteral Formulations of Small Molecules Therapeutics Marketed
`in the United States (1999) Part ll
`
`
`
`
`
`2. Lawrence A. Ttlssel, Handbook on lnjectable Drugs,
`lOlh ed., American Society of Health»System Pharma‘
`cists, Ina, Bethesda, MD, 1998.
`3. Lynn D. Phillips and Merrily A. Kuhn, Manual of 1V
`Medications, 2nd ed., Lippincott-Raven Publishers,
`Philadelphia, PA, 1999.
`-
`4. D. A. Hussar, “New drugs of 199&” Journal of the
`American Piramracemical Association, 39, 151 (1999).
`5. D. A. Hussar. “New drugs of 1997.” Journal of the
`American Pimmzaceruical Association, 38, 155 (1998).
`6. Food and Drug Administration inlemet website. http:/I
`www.fda.govl, See human drugs, what’s new, new and
`generics approvals.
`
`ROBERT G. STRIC KLEY
`
`Axys Pharmaceuticals, Inc., South San Francisco, Califomr'a
`
`{Editor‘s Note: This review article on Injccmble Products is
`being published in three pans. The introduction and sum—
`mary appeared in the NovemberlDecember 1999 issue. The
`final Pan will appear in the MarchlApril 2000 issue of the
`Joumat]
`
`lnleclable Products
`
`Saumcs ofllgfommtion:
`
`l. Physician’s Desk Reference, 53rd ed., Medical Eco.
`nomics Company, Inc., Momvale, NI. I999.
`
`Correspondence address:
`94080
`
`l80 Kimball Way. Somh San Francisco. CA
`
`Vel.54.No.1 i January-February 2000
`
`
`
`Supplied by The British Library - “The world‘s knowledge"
`
`
`AstraZeneca Exhibit 2158 p. 1
`InnoPharma Licensing LLC V. AstraZeneca AB IPR2017-00905
`
`

`

`
`
`Drug Name!
`Marketed
`Name
`
`“Xcemzol-
`amide
`sodium/
`Diamox
`
`Acyclovir
`sodium!
`Zovrrax
`
`Adenosine!
`Adenocard
`IV (bolus).
`Adenoscan
`(EV infusion)
`
`Structure
`
`t.
`
`M
`
`2
`\NHQ
`
`pKa = 7.2
`
`ti)
`,9.
`Hack New“
`pKa ~ It)
`
`"i
`
`,,
`Ly
`,.
`
`DH
`
`
`Formulation
`
`Solution
`500 mg
`pH 9.2
`
`Preadministration
`preparation
`
`Constitute with 5 ml.
`WFI to S 100 mgme;
`
`Lyoggilized wder
`S
`< 1
`mg
`[13 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% or saline to < 7
`mglmh
`
`None
`
`Route of
`Administration
`
`IV bolus!
`IV infusion:
`M but my be
`painful due to
`alkaline pH
`
`IV infusion
`over i hour
`
`IV bolus!
`IV infusion at
`0.14
`mg/kglmin for
`6 minutes
`
`Alatmfloxacin
`mesylatel
`Trovan
`
`“
`“
`.
`205*
`.
`ts
`uJT'M q
`Amide prodrug for
`trovat‘loxacin
`
`Solution
`5 mgimL
`pH 3.4-4.3
`
`Alfegtanil
`H ll
`Alfenta
`
`o
`“Al-4
`
`"
`
`\O
`
`Solution
`0.5 mglmL,
`Sodium chloride (isotonic)
`pH 4~6
`
`Alprostadil Wm
`(prostaglam
`'
`dinEll
`:
`.
`Caverject
`
`Lyophilized powder
`646 ug
`Lactose 172 mg,
`Sodium citrate 47 mg,
`Benzyl alcohol 8.4 mg
`
`Al rostadil
`
`° (Wow
`
`it fadex M(prosta-
`.
`glandinEll
`"°'
`W
`Eden;
`complexed with no
`cyclodextrin
`
`m’
`
`Amitbstine/
`Ethyol
`
`“WW/E9.
`Prong that is
`dephosphorylated by
`alkaline phosphatase to
`active free thiol
`
`Lyophilized powder
`6-50 ug complexed with 200-
`1610 ug of avcyclodextrin
`Lactose 56 mg ,
`pH 4-8
`
`Lyophilized powder
`500 mg
`
`IV infusion
`over 60
`minutes
`
`IV bolus!
`IV infusion at
`0.5-3.0
`ug/kymin
`
`Intra‘
`cavemosal
`
`Dilute with dextrose
`5% to l-2 mglmL
`(potentially
`incompatible with
`saline and lactated
`Ringer’s)
`
`None for bolus.
`For IV infusion dilute
`with saline, dextrose
`5%. or lactated
`Ringer‘s to 0.025-
`0.080 mglmL.
`
`Reconstitute with 1.2
`mL water preserved
`with bone 1 alcohol
`0.95 a wlv.
`(-- 0.5-1.1 ug is lost due
`to adsorption to the vial
`and syringe.)
`
`Reconstitute with 1.2
`mL saline.
`
`Intra—
`cavemosal
`
`{V infusion
`over 15-30
`minutes
`
`Reconstimte with
`saline to 50 mglmL
`(stable at room
`temperature for 5
`hours).
`May be further diluted
`with saline to 5
`mg/mL.
`
`Amikacin
`sulfate
`
`I“-
`
`IV!
`
`Solution
`250 Ins/“1].,
`Sodium metabtsulfite 0.66%
`Sodium citrate 2.8 %
`pH 3.5 - 5.5
`
`For IV infusion dilute
`with saline or
`dextrose 5% to 2.5-5
`rug/nth
`
`aw
`IV Infusion
`over 30 - 60
`minutes
`
`Company and
`Indication
`
`Lederle,
`Antiglaueoma;
`diuretic in
`treatment of
`mountain
`sickness
`
`Glaxo Wellcome.
`Antiviral
`
`‘ Fujisawa.
`Conversion to
`sinus rhythm of
`PSVT (bolus).
`Adjunct for
`thallium-201
`myocardial
`perfusion
`scintigmplty
`(infusion)
`
`Pfizer,
`Antibiotic
`
`dysfunction Schwm thna,
`
`Taylor,
`Analgesic
`
`Phatmacia &
`Upjohn.
`Erectile
`
`Emctile
`dysfunction
`
`.Alza,
`Anuneoplastic
`adjuvant
`[cytoprotective
`and
`radioprotective
`(reduces toxic
`effect of
`clsplatinn
`
`EIkins-Sinn.
`Antibiotic
`
`70
`
`PDAJoumal of Pharmaceutical Science & Technology
`WW
`
`l ll
`
`
`
`Supplied by The British Library - "The world's knowledge"
`
`AstraZeneca Exhibit 2158 p. 2
`
`

`

`
`
`
`
`W.
`
`Drug Name!
`Marketed
`Name
`
`to
`
`Aminoga
`ac:
`Amioar
`
`Structure
`
`
`Formulation
`
`Preadministration
`preparation
`
`Route of
`Administration
`
`Com any and
`I
`ication
`
`v
`
`H2
`“2
`Ham/3mm
`a
`“"2
`
`Solution
`250 mghnL,
`Benzyl alcohol 0.9%
`pH 6.8
`
`Dilute with saline or
`dextrose5% to ~ 15-
`20 mg/mL.
`
`IV infusion at 4
`gramsihour
`
`g
`g
`
`g
`
`3
`
`E
`
`
`
`x
`l
`
`Amino‘
`hippurate
`sodium
`“ AH“
`
`“
`
`Amiodarotte
`HCLI
`
`Cordamne
`
`Amitriptyline
`HQ!
`Elavil
`
`"'
`
`Amphoter-
`icm Bl
`Abeloct
`
`21’s
`
`.5
`
`,0.
`
`W‘
`complexed lzl (drug-to»
`lipid molar ratio) with [L-
`wdimyristoylphosphatt
`dylcholine (DMPC) and L‘
`avdimyfistoylphosphati—
`dylglyccrol (DMPG) in a
`7:3 mole ratio]
`
`icin B
`
`Amphoter-
`
`clnlestetyl
`Sulfath
`Amphomc
`
`.
`
`‘
`
`complexed 1:1 molar
`with cholestctyl sulfate
`
`Amphoter-'
`icin BI
`Ambisome
`
`
`
`Immunex,
`Enhancing
`hemostasis when
`fibrinolysis
`contributes to
`bleeding
`
`Merck,
`Measures
`effective renal
`plasma flow
`
`Solution
`200 mymL
`
`None
`
`IV infusion at
`640 mgflcg and
`10~24 mglmin
`
`Sointion
`50 mgme,
`
`v{ TWEEN 80 at 10%,
`
`Benzyl alcohol 2%
`pH 4.1
`
`Dilute with dextrose
`5% to < 2 mglmL.
`
`WyethoAyerst .
`[V infusion
`at 5-15 mgy’min Antianhythmic,
`
`dextrose
`
`Anfianginal
`
`None
`
`1M
`
`Zeneca,
`‘
`Antidepressant
`
`Dilute with dextrose
`5% to 1-2 ngmL.
`
`IV infusion at
`2.5 mglkglhr
`
`The Liposomc
`Company.
`Antifimgal
`
`Reconstitutc with
`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).
`Antifungal
`
`Recomtimtc with
`WFI to 4 mg/mL
`Dilute with dextrose
`5% to 1-2 mglmL.
`
`IV infusion at
`3.5 mglkglhr
`
`Fugisawa
`(developed by
`NeXstar, now
`Gilead),
`Antifungal *
`
`Solution
`10 mg/mL,
`Dextrose 44 mg/mL,
`Memylparaben 1.5 mglmL,
`Propylparaben 0.2 mglmL
`pH 4-6
`
`Liposome opaque
`suspension
`SmymL
`DMPC 3.4 mg/mL.
`DM‘PG 1.5 mglmL,
`Sodium chloride 9 mgImL
`PH = 5’7
`
`Lyophtlized powder
`50 400 mg
`Afier reconstitution with WFI
`to a S mgImL colloidal
`liposomal dispersion,
`Sodium cholestg-Lyl sulfate 2.6
`mg!
`.
`EDTA 0.037 m 1111.,
`Lactose 95 m mL,
`TRIS 0.56 mg/mL
`
`Lyophilized powder
`50 mg
`After reconstitution with WFI
`to a 4 mglmL translucent
`Iiposomal suSpension,
`Hydrogenated soy
`phosphatldylclmline 18 mg]mL,
`Distemoylphosphatidylglycetol
`7 mgImL.
`Cholesterol 4 mglmL,
`Alpha tocophoro! 0.05 mglmL.
`Sucrose 75 mglmL,
`Disodium suecinate 2 mglmL
`pH 5.06.0
`
`71
`Vol. 54, No. 1 I January-Febmaryzooo
`
`
`,,,
`
`Supplied by The British Library - “The world‘s knowtedge“
`
`AstraZeneca Exhibit 2158 p. 3
`
`

`

`
`Structure
`Fonnulalion
`
`Preadministralion
`prepamlion
`
`Route of
`Adnfinistralion
`
`Company and
`
`Indication
`
`,
`
`0‘
`
`Amman“
`con
`
`0
`~o
`Sulbactam
`
`,
`
`Powder
`1'2 grams (ampicillin),
`0.5-1.0 grams (sulbaciam)
`pH = & l0
`
`Reoonstitute with
`WEI to 250 mg/rnL
`ampicillin and 125
`mymL snibaciam.
`For IV dilute with
`saline or demos: 5%
`to 3-45 mg/mL
`
`1M!
`IV infusion
`over 1080
`minutes
`
`Pfizer.
`Antibacterial
`(ampicillin)
`
`I
`
`“
`
`\
`
`mm
`
`l A,
`
`Solution
`S mglmL,
`Sodium metabisulfito 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
`vusodilator (short
`term management
`of CHF)
`
`Marketed
`Name
`
`Ampicillin
`and
`Sulbactam
`sodium!
`Unasyn
`
`Amrinonc
`lemme!
`lnocor
`(not in 1999
`FDR)
`
`Axcnololl
`Tenormin
`
`A
`
`INA”
`0“
`
`0
`
`NH:
`
`Solution
`0.5 mglmL.
`Sodium chloride (to isotonic),
`Citric acid to
`1)}! = 5.5 - 6.2
`
`None, ordilution with IV infusion at 1
`saline or dextrose 5%.
`rug/min
`
`Alracmium I“
`bcsylatel
`Tracrium
`“'"
`
`(VAL?
`" '03:"
`
`"‘
`
`Soluxion
`10 mg’mL
`wlwo Benzyl alcohol 0.9%
`pH =: 3.2—3.6
`(benzene sulfonic acid)
`
`None for IV bolus
`For IV infusion dilute
`with saline or
`dcxirose 5% to 0.2-
`0.5 mglmL.
`
`IV bolus!
`IV infusion at
`543 uglkglmin
`
`Atro him:
`so] are
`
`‘
`
`Aurothio-
`glucose!
`Solganal
`
`H
`
`on
`
`a
`
`0
`
`Azathiopnnc
`sodium!
`Imuran
`
`
`
`Azilhromy»
`sin!
`Zithromax
`
`[0;
`,,
`m
`u
`
`"
`
`“a
`
`\g‘g
`
`Solution
`0.1-1.0 mgImL.
`Sodium chloride 9 mglmL.
`wlwo Benzyl alcohol 1.5%
`pH 36
`Suspension
`50 mg/mL
`in sesame oil
`Aluminum monostearatc 2%,
`Propylparaben 0.l%
`
`None
`
`None
`
`Lyophilizod power
`100 mg
`pH = 9.841
`
`Reconstitute with 10
`mL WFl.
`For IV infusion dilule
`with saline or
`dextrose 5%.
`
`Lyopliilizcd powder,
`‘
`500 mg.
`Citric acid 414 mg
`
`Reconstituto with 5
`mL WFL and dilute to
`1-2 mymL with
`saline. dextrose 5%,
`or loomed Ringer‘s.
`
`SCI
`[Ml
`IV bolus
`IM (oil)
`Prolonged
`release. due to
`slow
`absorption
`
`IV bolus!
`lV Infusion
`
`IV infusion of
`500 mg at I
`myml. over 3
`hours. or 2
`mymL over l
`
`hour
`
`3
`;
`E
`I
`g
`
`i
`
`‘
`
`"
`
`1
`‘
`I
`;
`
`g
`F
`i
`i
`l
`{‘
`
`Row,
`Antihypenensivc
`and neuronal. of
`acute myocardial
`infarction
`
`Glaxo Wellcomo,
`General
`anesthesia
`(Skeletal muscle
`relaxant)
`
`Blkins-Sinn.
`Astra. and
`Baxter,
`Anzicholinergic.
`Antispasmodic
`Schering Corp"
`
`Antirhcumauc
`
`.
`
`Glaxo Wellcomc,
`Immuno-
`suppressive anti-
`Mabolite:
`management of
`severe
`ziteumamid
`arthritis
`
`Pfizer,
`Antibiotic
`
`72
`
`PDA Journal of Pharmaceutical Science & Technology
`
`Supplied by The British Library - "The world‘s knowledge"
`
`W
`
`AstraZeneca Exhibit 2158 p. 4
`
`€
`

`

`Dmg Name!
`Mmketed
`Name
`
`Stmcmre
`
`Formulation
`
`Preadministrafion
`preparation
`
`
`Routc of
`Administration
`
`Com y and
`
`Indgxgtion
`
`Azueonaml
`8
`Azactam WAM “ ‘5“:
`«y
`u ‘
`“i
`o
`‘50,)!
`a,
`
`Have
`
`1M!
`IV bolus]
`IV Infusion!
`
`BMS.
`Anubiosic
`
`l) Lyophiliud powder
`0.52 g,
`L—arginine 780mglgram
`mannam
`pH = 4.54.5
`2) Frozcn Solution
`2040 mg/mL
`Lactose 1484 mglmL.
`Arginine 16-32 mg/mL
`pH 4.5.7.5
`
`For N reconstitute
`with at least 3 mL
`WFI or saline to ~
`100600 rug/ml... For
`IV bolus reconstitute
`with WFI to 50—200
`mglmL. For IV
`infusion reconstituu:
`with 3 mL WFI, then
`dilute with saline.
`dextrose 5%, Iaclazcd
`Ringer's to s 20
`mglmL.
`
`
`
`Water soluble
`phosphate ester
`prodrug
`
`°
`
`Benzguin—
`amxdc
`(Not in 1999
`FDR)
`
`Bempine
`meswa
`Cogentin
`
`Betamctha-
`son:
`Phosphate
`sodium and
`Betamcflxa-
`sane Acetate}
`Celestone
`soluspan
`
`a
`
`V
`‘
`Water insoluble
`acetate ester prodrug
`
`Bethanechol
`chloride! “W” cm
`Urecholine
`in.
`
`Solution
`5.] mg/mL,
`pH neutxa!
`
`None
`
`SC
`
`Merck.
`Cholincrgic
`
`Vol. 54. No. 1 I Januaryvflbruary 2000
`
`
`73
`
`Supplied by The British Library — "The worid‘s knowledge"
`
`W A
`
`straZeneca Exhibit 2158 p. 5
`
`"a
`
`K
`
`“M
`km»
`
`’
`
`Powder
`50 mg
`pH = 3-4
`
`Reconstith with
`WFI to 25 mg/mL.
`
`1M]
`iv infusion
`
`Solution
`1 mglmL.
`Sodium chloddc 9 mg/mL
`pH = 5.8
`
`None
`
`1M!
`(IV bolus is
`alright. but has
`no advantagc
`over 1M)
`
`:
`6
`
`Pfizer,
`Pneva nausea
`with surgery
`mesmesia
`
`Merck,
`Anticholincrgic
`used in psychotic
`patients with
`acme dystonic
`reactions, and in
`Parkinson's
`disease
`
`Schering,
`Ami-
`inflammatory and
`for aliergies
`
`None
`
`1M
`
`Suspension
`Betamcthasone sodium
`phosphate 3 mglmL,
`chmethasone acetate 3
`mglmL,
`Sodium phosphalc dibasic
`7.1 m mL,
`Sodium p osphate
`monobasic 3.4 rug/um,
`EDTA 0.1 mglmL.
`Benzalkonium chloride 0.2
`mglmL,
`pH 6.8-7.2
`
`

`

`Drug Name!
`Marketed
`Name
`
`Biperidan
`Lactate'
`Akinetou
`
`i
`
`Bretylium
`tosylatel
`Bretylol
`
`Brook
`pheniramlne
`maleate
`(Li uid
`fomtu zlttglgg
`not in
`FDR
`’
`
`
`Structure
`
`
`Formulation
`
`Pmadministration
`
`preparation
`
`Route of
`Company and
`
`Administration
`Indication
`
`Solution
`5 mgme
`Sodium lactate 1.4%
`
`None
`
`NI
`1M
`
`Knoll,
`Parkinson’s
`Disease
`
`Br
`
`m
`0“:
`9":
`
`I
`
`"=0
`
`WOO—‘50;H
`
`\
`N‘ /
`
`,CH:
`EH:
`“we
`..
`WW:
`
`Solution
`50 m mL
`pH .5—7
`
`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 infiJsion at
`1—2 mg/miu
`
`Astra.
`Antidysrhythmlo
`
`Solution
`10 mglmL,
`Methylpmben 0.18%,
`Propylpamben 0.02%,
`9!! = 6.7—7.1
`
`None for IM/SCIN
`bolus. For IV
`infusion dilute with
`saline to l mglmL.
`
`SCI
`le
`IV bolus!
`1V infusion!
`
`Moro.
`Antlhlsmmlne
`
`Bummnlde}
`
`0“ (ml
`
`Solution
`0.25 mglmL.
`Bum” W5?)
`Sodium chloride 8.5 mglmL.
`°’© Benzyl alcohol 10 m ml...
`EDTA 0.! mg/m ,
`Ammonium acetate 4 mg/mL.
`pH 6.8-7.8
`
`“aw”
`
`None for [M or IV
`bolus. For IV
`infusion dilute with
`saline. dextrose 5% or
`lactated Ringer’s.
`
`1M!
`IV bolusover
`l-2 minutes!
`IV infusion at l
`rag/hr
`
`Baxter.
`
`Diuretic
`
`Solution
`2.5-7.5 mgme
`Sodium chloride to isotonic.
`w/wo Epinephrine 9 uglmL,
`Sodium metabisulfite 0.5
`mL.
`Methyl
`n 1 mg/mL.
`Cilnc acid 0.2 mg/mL.
`pH 4—6.5
`Solution
`0.3 mg/mL,
`Dextrose SO mgImL
`pH 3.56.5
`
`None
`
`None
`or dilute with saline,
`dextrose 5%. lactated
`Ringer’s
`
`E idumll
`pinall
`Sympathetic
`new
`Catheter into
`the area being
`anesthetized,~
`l7S—225 mg!
`(not IV)
`DeepIMI
`IV bolus over 2
`minutes.
`
`Astra,
`Loom anesthesia
`
`Reckitt-Colcman,
`Analgesic
`
`Bupivaeaine
`ECU
`Sensorcaiuc
`
`up
`
`“F
`
`3
`
`c...
`
`K3 _ 8 I
`" ’
`
`1”
`
`Buprenor—
`phiue HCl
`(SO-times
`more potent
`than
`morphiney
`Bupreuex
`
`H0
`
`“a
`moo
`
`,
`‘
`akfieg‘m’
`
`Busulfnn/
`Busulfex
`
`“*3
`
`"\V
`
`a
`—.csq.
`
`Solution
`6 mg/mL
`PEG 400 at 67%
`N, N -dlmethylacetamide
`(DMA) 33%,
`
`Dilute with saline or
`dextrose 5% to 0.6
`mg/mL.
`
`lV infusion
`
`Orphan Medical,
`Neoplastic
`
`HO
`
`Bulorphanol
`tartmte/
`Slade!
`(Injectable not
`in 1999 FDR,
`the only
`product is a
`nasal
`fonnulatlon.)
`
`Ho
`
`cow
`0“
`ca ’\0
`
`Injectahle solution:
`[-2 mglmL
`Sodium chloride 6.4 mglmL
`Citrate buffer 0.045M
`pH 35.5.
`Nasal spray solution:
`[0 mglmL,
`Sodium chloride, Citric acid.
`Benzethonium chloride.
`pH 5.0.
`
`'
`
`None
`
`<
`‘
`
`Naal Spray
`(l spray is
`~ I filo OJ
`)/
`M
`IV bolus
`(l4 mg)
`
`BMS,
`Analgesic
`
`74
`
`PDA Journal of Pharmaceutical Science & Technology
`_.W___. ,
`
`
`
`E
`
`A
`
`r
`
`Supplied by The British Library - "The world‘s knowledge"
`
`IM A
`
`straZeneca Exhibit 2158 p. 6
`
`

`

`
`
`Drug Name!
`Marketed
`Name
`
`Suucturc
`
`Calcitrioll
`Calcijcx
`
`“-
`
`Formulation
`Solution
`‘EéiEiio’Elixfimfiifi'fifié’ERSEESimw"m
`Salmon,
`amino-acids
`Pi‘200 LUJmL,
`Miacnlcin
`(H£ys-Scr»Asn~L¢u-
`cool 5 rug/ml”
`Scr—‘I‘hr-Qrs-Val-lgm
`Sodium chloride 7.5 mglmL,
`Acctan buffer
`GIy—Lys-lsu‘Ser—Gln.
`pH ~ 4
`GIu~ku~His~LysLeu~
`Gln-Thr-Tyr-ProoArg-
`Thr—Asn-Thr—Gly-Ser—
`GlyoThrvProaNHQ
`"
`
`Szolution
`I- uglmL,
`TWEEN 20 at 4 ng'mL.
`Sodium ascorbate Io
`mglmL.
`Sodium chloride LS mgImLI
`EDTA 1.1 mg/mL,
`Sodium phosphates 9.2
`mgImL,
`pH as-m
`
`as
`C“
`
`N
`
`Capreo-
`midi;
`~81
`sul 3
`‘
`“
`Capastal Vvv'cj}
`mitts“ in
`
`.
`
`Powder
`1000 mg
`
`Carboplalin/
`Paraplann
`
`NH3\ ’0Pl
`NHs/ ‘0
`
`0
`
`O
`
`Carmustinel
`BiCNU
`
`/o
`
`NI
`WNYMC'
`o
`
`Powder
`50450 mg.
`Mannitol equal mass as
`carboplatiu.
`pH 5-7
`
`Lyophilized solid
`[00 mg
`98 5-6
`
`Ccfamandolc
`[gando‘
`( ormate
`55m!
`prodrug -
`h “*l"
`ydro ysis
`after
`dissolution)
`
`o
`
`R "
`:
`x 3
`{
`o
`‘10 m coon
`
`o
`
`'a,‘
`
`Solid
`1-10 g
`Sodium carbonate 63 mglgram
`cefamandolc,
`pH 6-8.5
`
`’f 5‘
`
`in
`m3,“
`pKa 2.6 - 3.0
`
`'m'
`.4?
`
`3
`7
`
`l
`
`E
`l
`2
`
`I
`I
`.
`
`Pmadnfinistrafion
`preparation
`Non:
`
`None
`
`Reconstituce with 2
`mL WFI or saline to
`500 mglml. (~ 3
`minutes lo dissolve).
`For M no dilution,
`but may rcconstitulc
`with less water to
`200350 mglmL
`For N infusion dilute
`into 100 mL saline.
`
`Reconstith with
`WFI, saline or
`demos: 5% to 10
`mg/mL. May be
`funhcr diluted to 0.5
`mglmL wilh saline or
`dcxtrosc 5%.
`
`Reconstitute with
`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 mgImL.
`
`Route of
`Administration
`1M!
`SCI
`also Nasal
`spray of 2000
`LUJmL, and
`one spray
`contains 0.!
`mL or 200 LU.
`IV bolus
`
`Company and
`Indication
`Novanis,
`Treatment of
`postmenopausal
`osteoporosis;
`Paga‘s disease,
`and
`hypetcalcemia
`
`Abbott,
`Management of
`hypocalccmia in
`patients
`undergoing
`chronic xenal
`dialysis
`
`1M!
`IV infusion
`over 60
`minutes
`
`Dom.
`Antibiolic
`
`[V infusion of
`at least 15
`minutes using
`05-10 mg/mL.
`
`EMS.
`Amineoplastic
`
`IV infusion
`over l—Z hoursi
`150200 mglm
`
`BMS,
`Amineoplastic
`
`Lilly.
`Aniibaclerial
`
`M
`IV bolus
`over 3-5
`minutes!
`IV infusion
`over 15-30
`minutes
`
`Vol.54.No.1 I January-Febmaryzooo
`
`75
`
`
`
`
` Supplied by The Brilish Library - "The world's knowledge"
`
`AstraZeneca Exhibit 2158 p. 7
`
`

`

`Dmg Name!
`Route of
`Pmadministmtion
`Marketed
`
`Administration
`Structure
`Name
`Formulation
`preparation
`-.-....-...---..-...~---_..-.--~.----_..—...-——..--.----.-......-..-..--_........---—~—-«-m_...-».—.-...mn..-....-
`1M!
`Cei'azolin
`IV bolus
`sodium!
`over 36
`Ancef,
`minutes!
`Kefzol
`N infusion
`
`aw t: '3 .
`111$?”
`
`I) Lyophiiizcd powder
`0.540 g
`H 4.5 - 6.
`rozen solution
`10.20 mglmL,
`Dextrose ~ 4048 mglmL
`pH 4.5-?.
`
`2)
`
`Reconstimte with
`WFI. or saline to 225-
`330 tug/ml. for 1M,
`and diiote with WFI.
`to ~ 100 mgfml. for
`IV betas, and dilute
`with saline. dextrose
`or inflated Ringer‘s to
`10 mm for IV
`infusion
`
`Company and
`Indication
`w-”uwmnm
`Smith-Kline
`Beecham and,
`Liiiy.
`Antibiotic
`
`BMS,
`Antibiotic
`
`Smith-Kline
`Beecham ,
`Antibiotic
`
`Pfizer.
`Antibiotic
`
`Hoechst Marion
`Roussei,
`Antibiotic
`
`Zeneca,
`Antibiotic
`
`,
`"
`
`Cefepime
`HCII
`Maxipime
`
`Ccfonicid
`sodium!
`Monocid
`
`Cefopera-
`zone
`sodium!
`Cefobid
`
`Cefotaximo
`sodium]
`Claforan
`
`“A “Hnay a?
`
`Ccfotetan
`disodium/
`Ccfotan
`
`Solid mixture
`0.5-2 g.
`L-Argininc 725 mgr'g ccfepime
`pH 4.0-6.0
`
`Lyophilized powder
`0.5-! g,
`pH 3.5 — 6.5
`
`I) Czystaliinc powder
`0.5-! g.
`pH 4.5 - 6.
`2) Frozen solution
`2040 mg/mL.
`Dextrose ~ 3646 mg/mL
`pH 4.53].
`
`1) Powder
`0.5-2 g.
`pH 4.5 - 6.
`2) Frozen solution
`20-40 mglmL.
`Dextrose ~ 14—34 mg/mL,
`Sodium citrate
`pI-I 5-7.5
`
`1) Powder
`HO g
`pH 4.5-6.5.
`2) Frozen solution
`20-40 mg/mL,
`Dextrose ~ 22—38 mg/mL,
`Sodium bicarbonate
`pH 4-6.5
`
`1M!
`IV boius over
`3—5 minutes!
`IV infusion
`over 30
`minutes
`
`IM/
`IV bolus
`over 3.5
`minutes]
`IV infusion
`
`1M!
`IV bo us over
`3-5 minutes/
`IV infusion
`over 1580
`minutes
`
`Deep IM/
`IV bolus over
`3-5 minutes!
`IV infusion
`over 15-30
`minutes
`
`Deep IMI
`IV bolus over
`3—5 minutes]
`IV infusion
`over 2060
`minutes
`
`Reconstitute with
`saline. dextroso 5% or
`lactated Ringer’s to
`280 m (:11. for M,
`100-! mglmL for
`IV bolus, 20-40
`lug/mi. for IV
`infusion.
`
`Reconstitute with
`WFI to 225-325
`for IM and IV
`m
`ho us, and dilute with
`saline, dextrose 5% or
`lactated Ringer’s to 10
`mglmL for IV
`infusion.
`
`Reconstitute with
`saline or dextrose 5%
`to 280 m mL for IV
`bolus.
`iiute with
`lidocaine 2% to ~ 200
`mglml. for M. Dilute
`with saline. dextrose
`5% or Iactated
`Ringer’s to 2.25
`mglmL for IV
`infusion.
`
`Roconstitute with
`WFI to 230.330
`mg/mL for IM. 50-
`180 mglmL for IV
`bolus, and dilute with
`saline or dextrose to
`10 mg/mL 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-i80
`mglmL, and dilute
`with saline or
`dextrose 5% to 10
`mymL for IV
`infusion.
`
`76
`
`FDA Joumai of Pharmaceutical Science & Technology
`
`Supplied by The British Library ~ "The world's knowledge"
`
`
`
`AstraZeneca Exhibit 2158 p. 8
`
`

`

`
`
`Drug Name!
`Marketed
`Name
`Structure
`Cefoxitin w ‘3“;-
`sodium!
`Mefoxin
`a
`
`Ceftazidime/ W a;
`(Ceptaz,
`""
`n
`Fortaz,
`‘a o
`'l‘azidime,
`we",
`Tazicei)
`
`.3
`'
`
`o
`
`H
`
`Formulation
`1) Powder
`1-10 g
`pH 4.2-7.0.
`2) Frozen solution
`20-40 mglmL,
`Dextrose ~ 2240 mglmL,
`Sodium bicarbonate
`[3}! 6.5
`
`1) Powder
`wlwo Sodium carbonate at 1 18
`mg/g ceftazidime.
`\vlwo L-Arginine at 349
`mg/gram ceftazidinte
`pH 5-7.
`2) Frozen solution
`20-40 InglmL.
`Dextrose ~ 50 mg/mL.
`Sodium bicarbonate
`pH 465
`
`.5 R
`8
`Ceftizoxime
`a t
`= 3
`sodium! M I
`;:Nl
`Cetizox
`u‘
`OGHP
`coo“
`
`°
`
`Crystalline powder
`0.5—2 3
`pH = 6-8
`
`Ccftriaxone “1% t: a .
`.Yi’;
`sodium!
`"
`Rocephin
`\W’ m .
`0
`u
`
`l) 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}
`IV 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
`Boecham,
`Antibiotic
`
`DeepM
`1v over 3-5
`minutes!
`IV Infusion
`
`Deep IMI
`IV Infusion
`over 30
`minutes
`
`Fujisawa.
`Antibiotic
`
`Roche,
`Antibiotic
`
`Preadministmtion
`preparation
`Reconstitute with
`WFI to 100-200
`mgImL for IV bolus.
`For N infusion
`reconstitute with
`saline or dextrose 5%
`to lOO mg/mL. then
`dilute to 10 mglmL
`
`For M, reconstitute
`with WFI, saline,
`0.5% or 1% lidocainc
`to 250 mg/mL.
`For N, reconstitute
`with WFI to 90470
`mglmL, and dilute
`with saline or
`dextrose 5%.
`to 1040 mglmL for
`IV infusion.
`
`Reconstitute with ‘
`WFI to 270 mglmL
`for M, 95 mglmL for
`IV bolus, and dilute
`with IV fluids to 10-
`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 {I
`sodium!
`‘
`Zinaccf
`“mo
`'
`
`t,
`'
`
`Ccphalothin
`sodium!
`Keflin
`Neutral
`(Not in l999
`FDR)
`
`,, 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
`trig/ml. for IV bolus.
`For N infusion,
`reconstitute with
`saline or dextrose 5%
`to 75-15 mg/mL.
`
`Reconstitute with
`1) Powder
`saline or dextrose 5%
`1-20 g.
`Sodium carbonate 30 tug/gram to 250 rug/ml. for 1M.
`cephalothin
`100 mg/mL for IV,
`pH = 6-8.5
`and 20-40 rug/ml. for
`2) Frozen solution
`IV infusron.
`20-40 mg/mL,
`Dextrose ~ 50 rug/mil, Sodium
`bicarbonate
`pH = 63.5
`
`Deep IM!
`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
`
`Prcadministrazion
`
`Formulation
`preparation
`Powder
`Recomfimte with
`“““*“”‘“““5e:5m”m'"xmeesaf“
`W over 3-5
`Amibiotic
`V 0.5—20 g,
`saline or dextrose 5%
`. minutes}
`pH = 68.
`to 500 mglmL for M,
`IV infusion
`50400 mglml. for
`IV, and 100 mgme
`for IV infusion.
`
`Route of
`Administration
`
`Company and
`Indication
`
`Powder
`100 mg.
`Supplied diluent:
`PG 20 %
`TWEEN 80 at 4%,
`Benzyi aicohoi 1.5%,
`Maleic acid 1.6%
`p}! = 3
`
`IM/
`Slow IV bolus
`over I minute
`
`Reconsfimte with
`supplied diluent to 50
`mg/mL for M.
`Reconstimte with
`saline or WFI to 20
`mg/mL for IV bolus.
`
`Solution
`
`None
`
`ICN.
`Tranquiiizer
`
`Single injection
`or continuously
`through an
`indwelling
`cathacr.
`
`Astra,
`Local anesthetic
`‘
`
`(zanquilizer
`
`[0—30 mymL
`Sodium chloride 3.3-6.7
`mg/mL.
`wlwo EDil‘A 01.x!3 {mg/r1381};nL
`wiwo Methy para
`a i m
`pH 2.7-4.0
`
`.
`
`Soiution.
`50 rug/ml.
`pH 5.5-6.5
`
`None
`
`1M
`
`Sanofi Winthro .
`Antimalaxia an
`anfiamcbic
`
`1 EIiI E
`
`0 o
`
`o o
`
`CI
`
`,N
`
`Lyophiiized powder
`500 mg,
`Mannitol 250 mg.
`Thimerasol 0.4 mg,
`pH 9240
`
`Solution,
`[0400 mgimL
`pH 4.5.2
`
`Reconstimte with 13
`mL WFI to 28
`mglmL.
`
`1W
`IV Infusion
`
`None
`
`IV (not the 100
`mgfinL)!
`SCI
`1M
`
`Solution
`
`None for 1M.
`
`Dilute with saline to 1
`mglmL for IV.
`
`25 mg/mL,
`Sodium chlonde 6 log/mi...
`Sodium bisulfile l mglmL.
`Sodium sulflte 1 mg/mL,
`wlwo benzyl alcohol 2%.
`Ascorbic acid 2 mg/mL.
`pH 3—5
`
`Deep [M in
`buttock!
`IV bolus at 0.5-
`l rug/minute
`
`Merck,
`Diuretic and
`hypertensive
`
`Schcring,
`Aniihistamine
`
`Smith-Kline
`Bcccham,
`Antipsychotic,
`anaemic
`(nausea),
`
`Ccfadyl
`(Not in 1999
`FDR)
`
`Chlordiar
`c
`xide
`CU
`Libtium
`
`Chloroo
`procaine
`HClI
`Nesacaine
`
`Chloroquine
`HCL’
`Amien
`
`Chloro-
`thiazide
`sodium]
`Dim-i1
`
`Cbloxphenir—
`amine
`maleazel
`Chlor-
`{rimcton
`(No: in 1999
`PDR as
`injectable)
`
`Chlorproma—
`zine HCV
`Thorazinc
`
`78
`
`FDA Joumai of Pharmaceutical Science & Technoiogy
`
`
`Supplied by The British Library — “The worid's knowledge"
`
`W A
`
`straZeneca Exhibit 2158 p. 10
`
`

`

`
`
`n
`
`ML
`
`Drug Namel
`Route of
`Preadministration
`Marketed
`Company and
`indication
`Administration
`Formulation
`Name
`Structure
`preparation
`mam”.-.-.-"-m.m.-wu..«mm--«-a...an"....mwmm.--.~---.-m-...mmm.~-......“m.u-....---.......u......,,,...-....
`IV infusion
`Dilute into 100 mL
`Solution
`Gilcad.
`Cidofovirl
`a
`Antiviral
`saline to ~ 3-5
`Vistide
`at 5 rug/kg over
`75 mg/mL,
`1 hour.
`treatment of
`mg/mL
`pH 7.4
`cytomegalovims
`Required
`in AIDS patients
`predose of 2
`grams
`probenecid
`orally (reduces
`renal clearance
`by blocking
`active renal
`tubular
`secretion).
`
`0
`
`“1575-0”a
`
`H
`
`
`
`renal mM
`
`K:
`
`°
`
`Cilastatin
`(inhibitor of
`
`dipcptidasc.
`dchydro-
`peptidase I)
`
`and Wimipenam!
`
`Primaxin
`
`0
`
`[minute-
`
`Cimetidine
`HCil
`Tagatnct
`
`:6
`9”
`":c‘figl‘w-ds
`
`N
`
`Ciprofloxacim’
`Cipro
`
`"‘0
`
`COOP!
`
`Cisplatinl
`Platinol
`
`Hark
`Hzn’
`
`Cladn’bind
`Leustatin
`
`Powder
`500-750 mg each,
`Sodium carbonate 1020 mg
`(1V).
`pH 6.5-7.5
`
`m
`l§§°‘§}l?£i
`Phenol 5 mgimL
`. pH 46.
`2) Infusion solution
`6 rug/ml.
`Sodium chloride 9 mglmL.
`
`1) Solution
`to 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 mg/mL,
`pH = 3.56.5.
`2) Solution
`1 mglmL
`Sodium chloride 9 mgImL
`
`Solution
`1 mg/mL,
`Sodium chloridc 9 mg/mL,
`Sodium ho hates,
`pH .5- .0
`
`lM: Reconstitute with
`lidocaine l% to 250
`mg/mL suspension.
`xv: Roconsu'mte with
`[00 ml. saline or
`dextrose then diluted
`with 100 ml. saline or
`dextrose to 2.54
`tug/ml. solution
`
`None for IM.
`Dilute with saline,
`dextrose 5% or
`lactated Ringer's to 15
`rug/ml. for IV bolus
`and 6 mgImL for IV
`infusion.
`
`Dilute with saline,
`dextrose 5% or
`lactatcd Ringer’s to l-
`2 mglmL.
`
`M
`iv infusion
`
`Merck,
`Antibiotic
`treatment of
`serious infections
`
`Smith-Kline
`Beecham,
`Amittlcemtive
`(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
`
`Rcconstitute with
`WFI to 1 mg/mL
`
`IV infusion
`
`BristoloMcyers
`Oncology.
`Antineoplastic
`
`IV infusion
`over 24 hours
`after
`
`Onho.
`Antinooplastic
`
`Dilute with 500 mL
`saline to 0.09
`mg/kg/day (not
`recommended to use
`dextrose 5% due to
`increased drug
`degradation)
`
`Vol.54, No.1 i January—February 2000
`
`
`
`79
`
`
`Supplied by The British Library - "The world‘s knowledge"
`
`
`
`AstraZeneca Exhibit 2158 p. 11
`
`

`

`
`
`Prcadnfinistration
`preparation
`
`Route of
`Administration
`
`Com y and
`In ication
`
`' Reconstitute with
`WFI or saline to 8
`mglmL ctavulanate
`and 200 tug/ml.
`ttcareillin, 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
`
`Phaxmacia &
`Upjohn,
`Anhbiotic
`
`None
`
`N infusion
`
`Roxane,
`Analgesic
`
`None
`
`SCI
`1M!
`IV occasionally
`
`Elkinsvsinn and
`Wyeth,
`Analgesic,
`anticough
`
`Reconstitute with 8
`mL WFI.
`
`Inuatmcheal
`Suspension
`
`None
`
`1M onl
`
`y
`
`Glaxo Wellcome,
`Prevention and
`(moment of
`Respiratory
`Disease
`Syndrome in ’0‘”
`birth weight
`infants
`Merck,
`Endocrine
`disorders.
`rheumatoid
`arthritis,
`allergies
`
`i
`I
`'
`’
`
`1) Solution
`150 mgme.
`EDTA 0.5 mgimL,
`Benzyi alcohol 9.4 mglmL
`pH = 5-6.
`2) Ready to use solution
`0.5-18 mglmL
`Dextrose 5%.
`EDTA 0.04 mgme
`
`Solution
`0.! mglmL.
`Sodium chloride 9 mglmL
`pH 5-7
`
`Solution,
`15-60 mglmL.
`wlwo Chlotobutanol 5 mglmL,
`EDTA 1 mglmL,
`Sodium metabisuifite 1-2 mgme,
`Acetate buffer
`pH 3-6.
`
`Lyophilized powder
`DPPC 108 mg
`Cetyl alcohol )2 mg
`Tyloxa
`18 mg,
`Sodium ch oxide 47 mg
`PH 5'7
`(A synthetic lung surfactant)
`
`Sus ension
`50 fitglmL,
`Sodium carboxy-
`methylcellulose 5 mg/mL.
`TWEEN 80 at 4 mg/mL,
`Sodium chloride 9 mglmL
`Ben“ 31mm! 9 “Wm”
`
`
`
`Drug Name!
`Marketed
`Name
`
`Ciavulanate
`potassium
`and
`ticaxcillin
`disodium/
`'fimentin
`
`Structure
`
`Fomulation
`
`1) Powder
`Clamlanate 0. lg.
`Ticarcillin 3 g.
`w W 2) Frozen solution
`Clavulanatel mg/mL,
`Txcarcillln 30 mglmL
`
`'1"ka
`
`Clindamycin
`Phosphath
`Cicocin
`phosphate
`
`Clonidincl
`Duraclon
`
`Codeine
`phosphate
`(No: in 1999
`FDR as an
`injectablc)
`
`u,
`
`950k
`M
`“
`
`9S
`‘°
`
`on
`
`99‘:
`3,0
`a 5..
`Water soluble
`phosphate ester
`prodrug
`
`”
`
`“10°
`
`
`
`”
`
`’
`
`,
`
`“°‘
`I.
`“mm
`“$123”
`Tyloxapol: oxyethylaled
`tertiary 0c; {phenol
`formaldchy e polymer
`
`Colfosceril
`palmitmte
`(DPPC), M ‘
`Cctyl alcohol
`and
`TYIOXBPOV
`Exosurf
`“comm
`Cortisone
`Acetate!
`Cartoon
`
`ATM
`-0"
`
`0
`
`Water insoluble
`ester prodrug
`
`Cyanocobal- MW - 1355, poxphoryn
`amin
`like with Co (+) at the
`(Vitamin
`center, synthesized by
`812)
`bacteria
`
`Solution
`003-! in mi.
`Sodium ch oxide
`Benzyl alcohol.
`pH 4.5-?
`
`None
`
`SCI
`IM
`
`Blkins-Sinn,
`Nutrient
`
`Cyclophos-
`phamidel
`Cytoxan
`
`o
`
`(\0'
`N
`‘9’ \/\c3
`1\
`NH 0
`
`Lyophilized powder
`100.2000 mg
`Mannitol 75 mglloo mg
`cycloph
`hamide
`pH -9
`
`Reconstitute with
`wnmzo mg/mL.
`For IV infusion dilute
`with saline. dextrose
`5% or lactated
`Ringer‘s.
`
`M
`IV bolus]
`IV infusion]
`IP/
`intrapieural
`
`Bristol-Myers
`Squibb,
`Amineoplastic
`
`so
`
`PDAJoumal of Phannaceutical Science & Technology
`WM,WWW .. A.
`
` Supplied by The British Library - "The world's knowledge"
`
`AstraZeneca Exhibit 2158 p. 12
`
`

`

`Structure
`
`Formulation
`
`Preadministmtion
`
`pmparation
`
`Route of
`Administration
`
`Company and
`Indication
`
`
`SOIution,
`50 mglmL
`Cremophor EL 65%,
`Ethnnol 35%,
`bianketod with nittogcn
`
`Lyophilized powdcr
`500~2000 mg
`pH 5
`
`Dilute with saiine or
`dextrose 5% to 1-25
`mg/mL(1 mL into 20-
`100 mL}.
`
`Reconstitutc with
`saline or WFI with
`benzyl aicohot 0.9%
`to 20-100 mgme.
`
`IV infusion
`over 26 hours
`
`Novanis,
`Immunrr
`supprcsent
`
`Intrathccall
`SCI
`IV bolus]
`IV Infusion]
`
`Pharmacia &
`Upjohn,
`Antineoplastic,
`Antiviral
`
`Cyclic pc idc (II
`ammo aci
`, MW -
`1200
`
`NH-
`Nv/Jj
`Ho 04‘...
`\l o l
`H
`
`N":
`mfi
`Ho Odk-N
`0
`
`H
`
`\
`
`N
`/
`
`[j
`
`"‘6
`
`“.0
`
`o
`
`H
`2
`[CH
`N=N~N\
`
`CH3
`
`°
`
`°
`
`v
`“mm,
`
`a
`v
`MOVu-Su
`“f” “’i
`
`Dacarbazinel
`DTIC—Domc
`
`0
`
`Drug Name!
`Marketed
`Nam:
`
`Cyctospodnl
`Sandimmunc
`
`Qtambine
`(Am-C)!
`Cytosar‘U
`
`CytarabIne
`(Ara-C)!
`DepoCyte
`
`Dactint»
`mycinl
`Cosmcgcn
`
`Dalteparinl
`Fragmin
`
`Suspension Multlvesicular
`Lipid Particle
`5 mg/mL
`Cholesterol 4 mgimL
`DioIeoylphos hatidylcholinc
`(DOPC)
`.7 mghnL,
`Dipalmitoyl hosphattdylglyccrol
`(DP
`) t mglmL
`Sodium chloride 9 mg/mL
`pH 5.5-8.5
`
`Solid
`100-200 mg
`Mannito} and Citric acid.
`pH 3—4
`
`Lyophilizcd powder
`0.5 mg.
`Mannitol 20 mg,
`pH 5.5-?
`
`None
`
`Intrmhecal
`
`Chimn
`(DcveIoped by
`Dcpochh)
`Antimoplastic,
`Antiviral
`
`IV over 1
`minute!
`IV Infusion
`over 15450
`minutes
`
`Bayer,
`Antincoplastic
`
`IV bolus!
`IV Infusion]
`
`Merck.
`Antibiotic
`
`Reconstitute with
`WP] to ID 1113ij
`For IV infusion may
`be further diluted with
`saline or dcxlrosc 5%
`to 0.4 mg/mL
`
`Reconstitute with 1.1
`mL WFI. For IV
`infusion further dilute
`with saline or
`dextrose 5%.
`
`None
`
`Nonc
`
`SC
`
`SC
`
`Pharmacia 84
`Upjohn,
`Antithrombotic
`
`Organon,
`Antithrombotic
`
`Low MW heparin
`' W "‘ m _’
`'
`.
`{if
`mmm
`
`"’"
`
`Solution
`V!
`(prefilled swing; and mum-use
`64—160 mglmL
`Sodium chloride,
`wlwo Benzyl alcohol 0.15%
`pH 5.0-7.5
`
`Danaparoid!
`Otgaran
`
`84% heparin sulfate,
`12% dcnnzdan sulfate.
`4% chondmitin suifatc
`(isoIated from porcine
`intestinal mucosa)
`
`Solution
`(prefilled syringe or ampule)
`1250 anti-Xa units/mL,
`Sodium chloride,
`Sodium sulfite 0.15%
`pH 7
`
`Dantmlcnc
`sodium]
`Danttium
`
`°"*O‘Q'fi
`
`Lyophilized powder
`20 mg.
`Mannitol 3000 mg.
`pH 9.5
`
`Reconstitute with 60
`mL WFI to 0.3
`mglmL. For [V
`infusion further dilute
`with IV fluids.
`
`IV bolus]
`IV infusion
`over 1 hour.
`
`Promo: &
`Gamble Pharm.
`(Muscle relaxant)
`Treatment of
`hypennetaholism
`and hypenhetmia
`
`
`
`V01.54.No.1 I Januaty-Februaryzooo
`
`
`81
`
`Supplied by The British Library - "The world‘s knowledge"
`
`
`AstraZeneca Exhibit 2158 p. 13
`
`

`

`,
`i
`
`I
`3
`
`‘ l
`
`
`
`l
`E
`
`;
`
`5
`g
`
`i
`E
`
`E
`;I
`
`;
`1
`
`Drug Name!
`Marketed
`Name
`
`Dannorubicin
`not;
`Cerubidinc
`
`Daunorobicin
`Citrate!
`DaunoXomo
`
`Structure
`
`o
`
`0
`
`“on
`
`a
`
`:
`0“ 0
`
`N“:
`
`063:0
`“9
`
`o
`
`cargo
`3,0
`
`:
`
`cm
`
`mt
`
`Formulation
`
`Lyophilized powder
`21.4 mg.
`Mannitol [00 mg
`pH 4.562
`
`Pmadministtation
`preparation
`
`Route of
`Administration
`
`Company and
`Indication
`
`IV infusion
`
`Redford.
`Antibiotic
`
`Reconstitutc with 4
`mL WFI to 5 mymL.
`then further diluto
`with 10.15 mL saline
`and than inject into
`rapidly flowing [V
`infusion of saline or
`demos: 5%.
`
`0
`
`"on
`
`Solution liposome
`2 mgme.
`Distemyiphospltatidylcholine:
`Cholesterol in 2:1 molar ratio.
`lipid to drug ratio of l8.7:l
`diameter of 45 um
`
`Dilute [:1 with
`dextrose 5% to I
`mglml...
`
`IV infusion
`over 60
`minutes
`
`NeXstar (now
`Gilead),
`Antibiotic
`
`Desmo— mm Solution
`pressin
`‘7
`4 uglmL,
`cosmic!
`synthetic analog of
`Sodium chloridc 9 mglmL,
`DDAVP
`natural hormone 3.
`wlwo Chlorobutanol
`argininc vasopressiu
`pH 4
`(ADH)
`
`None for SC or IV
`bolus. For W
`infusion dilute. with
`saline to (0.3 uS/kg)
`in 50 mL
`
`SC!
`IV bolus]
`[V infusion
`over 15-30
`minutes
`
`Rhone‘Poulenc,
`Rotor,
`Hemophilia
`(maintain
`homeostasis)
`
`Gentle swirl contents
`to resuspend settled
`particles.
`
`IMI
`Intralesionall
`Inna-articular!
`Soft tissue
`
`Merck,
`Anti~
`inflammatory
`
`Gentle swirl contents
`to resuspend settled
`paniclcs.
`
`lM/
`Intro-articular]
`Soft tissue
`(Not
`intralesional)
`
`Forest.
`Anti-
`inflammatory
`
`For iv infusion dilute
`with saline or
`dextrose 5%.
`
`Merck.
`Anti-
`inflammatory
`
`IV bolus!
`IV infusion!
`1M!
`lntralcsionall
`lntra-articular/
`Soft tissue
`
`Suspension
`8 mg/mL
`Sodium chloride 6.7 mg/mL,
`Craatinioc 5 mglmL,
`TWEEN 80 at 0.75 mglmL.
`EDTA 0.5 mg/mL,
`Benzyl alcohol 9 mg‘mL,
`Sodium bisulfite I mg/mL
`pH 5.0-7.5
`
`Suspension
`16 mglmL
`Sodium carboxy-
`methylcellulose 5 mglmL,
`TWEEN 80 at 0.75 mgImL.
`Sodicurm chloridg: 6.7 mglmL.
`“minim mymh
`EDTA 0'5 mE’mL-
`Benzyl alcohol 9 mglmL,
`Sodium bisulfitc