Free Response in Opposition to Motion - District Court of Arizona - Arizona

PEGM"l'S• [pegimemarun alfa-Za) I
lntenwls may ¤¤ ¤¤S¤¤l¤t¤¤ with evletlt enenle lt i= ¤¤tlS¤¤ the ¤¤¤n>l¤t¤ ¤l¤¤¤ ¤¤¤¤l¤ l¤¤<>l eels emnaulat ‘rrfo me me ltlg-llét tml ifltwe with seems alone or in wmelnalun with
hemmmed pm`t"°mm°"t and munmm muhndy mmg malawklw mmumms: uhmmw T“°)· COP’glGU§ will prsvent transmission of HCV infection trgpgthers or prevent clrrhosas, liver tallure or liver
PEGASYS and GGPEGUS Snpuid ¤¤ ¤>=¤¤ wllli ¤¤¤¤¤¤ ·¤ pawns wen baseline ¤¤¤tr=;l>n¤l ¤¤¤¤tS ami me magna it-snr trom nov seems who develop dizziness, eenluslnn, sumneleme.
§é50G c¤i§1/mm“.l?1llt¤|d¤§$¤i;i¤¤ n|la_$meLe;@¤=;¤r}gsast<§#U¤¤0 cellstmgnaipvrwbwrellng nem¤oi¤¤·¤ E10 u/dh r will fatigue should be cautioned to me driving oroperatinu machinery: e
· GASYS ezapysou e sen empolan ,ln len wo eveepsevere ecreases l - - . -‘ - - In; -
in neutrophil amen: platelet UOLIITIS (see IJUSAGE anu mmgsrnmou; om llmutneannml. . l 2ng3FQ°b§S§u§§§s§"3?p§u%1§mpE,i§SgS?l,"Dn°§"§"@rn$rn§2§ §,'s§,E §Q°°J,Y'§,,T,`&dD?”§,%°p%s,
n“"di°V“F“'“" m*’·‘“'”"$ . . , , _ disposal and cautioned against any reuse of any needlesand syringe. The full container should he
l;lly§te%,l%·;;aél:jp$;;l?1nmcuIar arrhythmias, chest pain, and myocardial infarction have been observed ~ drspnsng qnmnnjhn my-in nyqmnns grrmdgd bythe physrmn (gee (1|tl]§)_
' B PEGAS'$ Lal: l T ts K
PEGASYS $il¤¤i¤ ¤¤ ¤¤nl¤lSl¤r¤¤ with ¤v¤¤¤¤ tv Mem win on-MSM www dense B¤¤¤¢e¤ ¤¤¤l¤¤ el emT€{gl¤;$g eeensvs or eecltsws and copesos eemelnalan new standard nmelngleal _
disease may be worsened DY rllsavtin-induced anemia patients www a hisgg of slnrlrflnant ur u·‘lS¤¤|e me biuchernical laearamry lasts are reeummenued mr all patients Pregnanw seeenirn lor women of
cardiac dsease should not use COPEGUS {see 'IMRMGS: Anemn and Pedmge Insert). V- j nnnnnnnnnn nmnnnl nm; nn pnmymggd · -
Hlrl¤¤r=¤¤=i¤lvilv _ _ _ _ , _ _ e n n After initiation or new lemamlogleal tests smulu be pemrmeu at 2 weeks anu 4 weeks and biochemical .
Severe acute hypersensitivity reactions (eg, urtrcara, angroedema, nroncnoconstrlctlon, anaphylaxis) n msgs nhnnkj bg nam-nm at 4 uyggkg Apjdiiignaj tggljng gmuiq be performed periodically during therapy
have been rarelg observed duringE aloha interferon and ribavirln therapy. if such reaction occurs, ` gn g-n nnninnj mum, un geo (inglugjng llemoglgnm level and write bkjgd wil engl platelet owl-its) and
therapy with P GASYS and GDP GUS should be discontinued and appropriate medical therapy = ghgmigmgg nndnnhg tiger mnmpn mt; and gm; aci;2 were measured a;1_2_4_5, and 3, gpg men eww
immediately institulned. ` 4 weeks or more lrequendy ti abnormalities were toon Thryroltt stimulating hormone (TSH) was memuled
Endocrine Disorders _ _ _ _ _ .- n ·
PEGASYS causes or aggravates hypothyroidism and hyperthymldlsm. Hypergltyéemla, hypoglyoemga, , .
and ueumgit mB||l`g.|tSg|3V:I been toosawergnmbdevtzlnop in patéamietéegtee wgli t_ ASISL lzerlantlshwrat ; . -
li ese CDH lOI1S as lI'I0 W D Gallll B E Clive y l'Ba y lTlB ICE IDl'| S Dil l1D Bgllt I pmhgysm lnwlmnmmn a"a.ga}
PEGASYS therapy: Patients who develop mesa contttions during lrealznent and cannot be controlled { . . . .
with medication may require discontinuation ot Peensvs therapy; glrI§nn¤¢n§Snl§§S|;¤Dc:_[1n%illIl{ngpmgnanw testing should be pertevmed dunno comlmeiren titerqyy and mr
E:\|;{%Ti;.|l|:E}'s:Xr`1Hg;?bB`l£lD|'l uf autoimmune disorders including m?r¤elns_ nepannn mq nsnriasrn The ¤;latL=?¤l@:nteria ilsed1for_tt;eatqlinlcz%ltslug_;‘les lol PEGASYS may he considered as a guideline tu . V .
iiiimli mls- lntielilal time- **~en*gg,g¤¤ etiimlc ¤¤~¤.=¤fm¤n¤*e¤S tm itil ?h§i¤latEm°i%i»`铤3°€e&illL1·'§i‘n'§§e“B¤¤sllemm$lapalnnnleemen =
` Eiggirumepgtibgpdsmméelvlm alpha mtel-fm"` shuum be umd Wm] mmm In pmms wm ··Caution shculttlgelengercised in initgating treatment in any patient with baseline risk of severe anemia i
P¤*¤··=¤=·~ ¤*==·~*¤·= - ~ -lF»?iéiET€'€§3.’¥?.?'%ll“é??SRl’ ElE駰°§iSiiS%ar»amm= l
Dyspnea, pulmonary inllltrates, pneumonia, hronchiolitis ohliterans, interstitial pneumonitis and , _ Serum crmmingcunnnntmtinn d 5 X upper umimfmrmd l
sa"°°b°sJS· 5°m° mumng in mspimmw site www mmm dgam? mw b° i"d"'°Eid °r aggm"m°d i ·TSH and T, within normal limits otadequately controlled thyroid function `
QQIPEGASYS or alpha tntecrgemn therapy Faillentg soho dt$\r'BlD{.) I5;BlttEmD1’ Pggetglalned pulmonary PEGASYS ms imc with dwmasss in wm Am I m md Plmm Owns mn
Eluzxms Or pu Emmy un tm Impammn S Du mm me en wl j starting within me tirst 2 lgaeeks of treatrnent [sea AmlEH‘¥nlEAEllt;lg)r·0:y¤5wr|a’duch'o`nu`? reconmended
Ulcerative anal hemormeglcnsche-nie colitis, senenmee fatal, new mn gbsgyvgd Wren-. 12-went; np i with h€|Tli=!0i?Ql¤ ao ¤¤tAGEGm UT gtémnfgry ilstlcalhrlsb [ga
starting dom interferon treatment. Abdominal pain, bloody diarrhea, and fever are the typical manifestations 'F i rl !$ mmm? Yaiauset W . mw Dem mu E "U OUT- _
of colitis. PEGASYS should be discontinued immediately if these symptoms devetop. The colitis usually I PMD}! *1 Y"' Wien _ W "W 'UPEWB (5* _ °'¤)· V _ _ _
IESGIVBS witrin 1 m e weeks or dsconlinualion or alpha interferon. _ l[E¤¤=•¤¤t elevellms in ALT l2-Feld l¤ mid ¤l¤¤v§ bvuglmgjew wwmdigsgvrgghcavgm mvelvno
sornetimesiatal, has occurred during alphainterferon and rihavirtn treatment. PEGASYS and Ai? 1*5;% ?gdp'2E‘r%s[I§t"'°a%é;%?t§d°*:g° ragga:} Spas “°°mL:{j°d by innmséd bi?;"biE·ln§EmG$`§§`;g ,
G{:LpE(g[éFé5l5gu|g h?¤SUb2‘§ndBd gf Sygnpmnlrkgi-ssggns Of p§?mis are Observed Sl'lDUig¤:: GISCDITKIITUBI! (SBB DDSAGE NID RDMIHISTHUIDN1 DOSE MDUHIGIHIIIIS). g
-- · · · · · » - ;_ anda 5%increaseln een e nesertlm ss mom
Eqmoflltaoceskgsd i lil; H¤¤mEri_tht•6 IgéJEB_|_gd]US‘l1'Y1BHtS cfwigllerteg folhyoetlem? gtlggnopoéh ago PEGl¤T'?zYBa} ‘
· wrlh &ASYS clrolher aloha lnwrfercns. All patients should receive en eye examination at ment-. veneers g ls CYP 2 CYP Zéa éfepvéegsm gm, 3M li il P 9
with pre-existing ophthalmologlc disorders (eg. dlatledc or hypertensive retinopathy) should receive penodc DV C9- il Di _ · , , ,
gphmgfmgjggb exams dujng fnggrfggn ajpha |]g3{mgm_ Any pgtigm whg dgggiggg Dculgr qrmptgmg n In 3 PK Study of HCV DQTBFITS QDIICONITBITUY TBCBNIHQ i’T|€W`BUD|'|E, T|'B3U'|'lB|'|T Vflm DHDQ WEHKIY
should remive a rompt and complete eye examination. PEGASYS ueatmemsheulu be discontinued in l lor 4 weeks was 8S$0<2l&T8fJ‘W¢U'| methadone levels that were lQ°/»_to 15% higher than at tgaeelrne (see I
patients wl·ode.leEip neworworsening cphlhalmologic dieordes. 1 . CLINICAL PljlARMAEULUGt‘. Drtlg Interaction;). The clinical slgngflcanoheagf thlaugndlng is unknown, E
Preqllamy: Llsc with Fliltavlrln (ated, eee CDPEGLIS Pauragc tiger;) l wt flatlltfgls slnculd be furthe S1? Pig! Asgvrgptomsmrggu onem cSlPt§GUS PEGASYS _;
ninavirm my mm umn cereus andior mm ur me mma tems. Extreme care moe ne mlm 5 il li ;’n"t‘—;mmt°r'°"p R gwbuum Ofc '” °° ' °“ “" · I
tnavnld pregnancytn Inmate patient: andintermte rlnersotmale patients taltirlgPEEA$YSanl1 , , " ' _
GOPEGUS mmlllnauul tlmpy. coeeous mam sntitito not ee sninreu UNLESS A Eleven': or A ; Ni·¤l¤¤¤;E-jg A¤¤l¤¤¤¤¤
woman nt Ehlllilubeanng n 8lE:1 must us?lvL:11lorn1: ur mmm ¤¤Trl·?uL¤pu¤n ¤;»l:gTnmmi · Co-adrpimsvaxlogsésgj C0PE<;la1§1yand d;d;2to§;=e£.d¤mnT}¤mg1T§r2%mh;%eIn:g1;leem?;1 .
I `I'|'lG‘I“I$3M’I'B3"l'I|'ItPI$|§0l‘IlL’[IItIBII.FIlIIIIB omni lasts stue’ HSWBHSDGHQ neuron . ll . l l
gn1e§sae amteo MGARIING, GD?|'I’HAI|DI2§I'l0;1|1S. nvmmlilnn nw E gimpmwggghwws lm EZNN l’HNWiI¤i-¤G"¤ Ut"! i¤i¤¤*=**¤l¤i· l _
me , = me an ov e
nn,nntn' E D ]_ Ribevlrin can antagonize the ln_vitro antiviral activity of stavudlne and zldovudlne against HIV. Therefore
The primary llnxidlly of riiiavirin is hemolytic anemie. Hemoglulgin 410 gmt uva; obsqved in appruxirnaldy concomitant use of nbavlnn wrth enher ot these drugs should be avoided .
13% of CQPEGLIS and PEGASYS treated patients in clmlcal lrels (me_l{ttEl;ltLl'l'lCItS; Lebqmry 'lssls). , Carcinogenesis, Mutagenesis, Impairment crfferlilrty n l
The awernta assoqated with GOPQGUS occurs llvrlhln 1 to 2 weeks of lnlhahon of lhelalpy with maximum I Carcinogenesis _ ` _ r
drop ln observed dtméllg the first eight weeks. BECAUSE l'I-IE lM'l`lAL DRD IN HEl‘vlt]GLUBlN l PEGASYS has not been tested for ns carcinogenic potential.
MAY BE SIGN I lT|SAD'v'lS Tl-lAT H IN OH lEiWÂ¥|'UCFl|T BE DBTNNED PHE-TRE.FG'MENT ~ Mute enesls l
AND M WEEK 2 AND wEEl<_=l DF 'I'l·|ERAl’Y DH MORE FHEQUENTIX lF CLlNlCAl.lX |l‘~lDlCFil'El1 Patients l PEGAQSYS did not cause DNA damage when lasted ln the Ames bacterial mutaqentclty assay and ln the
should then lClBTOil0VlEd as clinlcalty approprote ` ln vitro phmrnoeomal aberration assay in human lymphocytes, either in the presence or absence of
Fatal and nonfatal myocardial intarctiuns have beerrrepurted in vntltanerhla caused ty_ ntlawln. metabolic activation. l 4
Pahmts should he messed lor undertymg cardiac disease lactose lngtiatm uf nbalnnn thereon Patients with ~ Use l·yrp‘i .l?ll;•avlrln _ _ _ _ _ -
pre-exlstlnq cardiac dlseese should rove electrocanllograms admnlstered before treatment, and should be Rlbavirin is oenutoxio and mutagenic. The carcinogenic potential nl nhmnnn has mt been fully
appropriately monitored during therapy lf there is any detelioration of cardiovascular status, ttermy should determined. I1 a p53 (el-) ITIEIISB carcinogenicity study el doses up tu the maximum talented dose T
be suspended or discontinued (see DUSAGE AND ADMINISTHMIUN: GDPEGUS ·-`— ge Modllioation ot 111l] mg/kglday rilminn was nut nncogsnlc. However, un a body surface area basis. this dose 5
Gulttelines). Because cardiac disease may be worsened by drug-induced anemia, patients with a history 01 . was l1.5 tunes maximum recommended human 24-hour dine ul rllmirin. A study in rats tu assess ‘
siqnincarlt or unstable cardiac disease should not um COFEGUS (see t:t'|’EBtlS Paokago Insert). l the carcinogenic potential of rihavirin ts nngnlng (eee HDPEGUS Package Insert).
Renal Impairment of Fertll
it is recommended that renal function tie evaluated in ali patients started on GOPEGUS COPEGUS should ; PEGASYS may inltlslgertiilty in women. Prolonged menstrual les andlor ernenurrhea were observed in
gotml:;a';l¤rr`;in|is:1ered)m patients with creatinine ciearanoe <5U mlJmin [see GLIIIEAL Pl-IMMPEDLDGY: g female cynormlgrrrs monkeys given sc iniecttons of 600 oggg:/dose (72§gdugl'rmdt'lse) ¤fdEGAT§rYS
p ' u a `ons. ' every other day one month, at approximately 1BU times the reoclmmen _ wee urren use a n
PRECAUTIONS - 50 lcg person (based on body surface area]. llllenstrual cycle lnegulaiities were aocompaniedhy both n
General ` _ _ _ l a decrease and delay in the peak UB-estradiol and progesterone levels follmrlng administration r
The safetz and efficacy of PEGASY5 alone or ln combination with CDPEGUS for the treatment oi e of PEGASYS to female monlews. A retum to nomtal menstrual rhythm followed oessatgon of lreatrnent. n
hepatitis have not been established in: - Every 0i1ll¤fd¤s'd¤Sl¤l;l with 100 me STZUU to/mil PEBW5 l¤¤¤~¤i¤rrl t¤ ¤¤¤r¤¤¤¤¤1¤n 30 times r
· Patients who have failed other alpha interferon treatments - , the recommended tr.ln‘la.l‘l dose) had no on cycle duration or renmductne homlone status _ I
. · Liver or other organ transmant recipients · V · The effects of PEGASYS on male fertility have not been studied. However; no adverse eftects on fertility l
• Patients co-infected with men immunodeficiency virus [HIV) cr hepatitis B virus (HBV] l iévere otiservgcg in rgaalzllzlxius monkeys treated with non-pegylated interferon alfa-2a for 5 months at g
Renal Impairment ¤5¤$ UD U3 X all ` i
A 25% to 45% hghar exposure to PEGASYS is seen in subjects undergoing mmndlalysis. ln patients ~ Use lll·7t‘f‘r Flfbavirlh i
with impaired ren function, signs and symptnrns of interferon toxicity should be closely monitored. p Fllhavirin has shown reversible toxicity in anknal studies of male fertility (see DOPEGUS Pauley HSM}. _
Doses of PEGASYS should be adiugsted PEGASYS shouid he used with caution in patients pmnnanny
with creatinine clearance <5D mL/mln (see D AND ADMltltSTHltmN: Dose Nlodtticatlons). ; pnagnanny; gnnnnry rg - · ‘
i¤f¤¤¤¤ti¤¤l¤rP¤ii¤fli=· · PEI3A$‘vSh notbeenstiritlediorts ncetlect.Non- l8IBjll'|`IBl”Bi’0113}Y3.·23,TIN]l'llEfli0f nant _
Patients receiving PEGASYS atone or in combination with DOPEGUS should be directed in its appropriate Flhesus mh at approximley so tre nwrenpiwjeeley dose resulted in a statlstlcalg
use, informed the benefits and risks associated with treatment, and referred to the PEGASYS and. increase in ami-een; lnpemlugersc effecls me seen ln the offspring deiverad at term should be .
if applicable CDPEGUS {ribavinn] MEDIDATEDN GUIDES. ` assumed lc have aborlilaoient pdmlial. Tl·em are no adequate and well-controlled studies oi PEGASYS _in
PEGASYS ard CUPEGUS combination tltlex must not be used by women who are pregnant or by men pregnarrlwomm. PEGASPS is to be used dunno pregnancy onlyifthe potential bellenlglylzshhesllie potential :
whosefemaIeparmersarepregnant.GG Slheraoyshouldnotbeinitiamdundlampodotanogathe ~ fBk'DUHlBtUS.PEGRSY$l5i'%mtlH1dBdYNU5€HWDWBHMdIHbBBJ’|DQMiB cnlywhentheyare
pregnancy test has been ohtatned immediately before starting therapy. Female patients of childbearing ‘ using effective contraception duringitteram ‘
potential Igloo {rnale gtienlg with fegag pgwegdogg childbearing potenliel mlaslt beiadvlsggptgs |=n;gr1;ney;c;|ng¤ry x; ug; wnn nluevlrin (eee cn|lTFtA||·|ulcA11n||s) -
¥¤¤¤¤¤¤¤` Gm fwd its an mv ¤ t>¤¤¤¤¤` ¤T‘iB¤¤`V¤-¤¤¤.®¤ `¤¤ ¤li¤¤ ‘ meant ‘ a|·d[mu|11I:q¤:1'd Ittffacl.: lnavalaen demnnsti-deal I ll nlnul ems d
. therapy and for 6 months Patients snotdd be advised b notify the physician immediately in §g,?nn,nnn_ ;:mnmw is nmnnnhtnn in mn;. wnn nn, nan'; gndaln mn my pngggg
lie Milt ¤f a nrvonanw (SBB GUN ¤l¤·*Tl¤N$ i1¤¤V•i¤R¥|N6$l- mm wnn am pregnant (ma conrrwnmcnrlonsr WARIINGS, anliietiloeeoss Package mnt.
Wornm ot childbearing potential and men must usetwo forms of effective oonnaoeption durirg treatmerrl H pregnancy nnnlnn in n paiknt gl pgymg nt n pmknt dur-l mmm; Df during ug 5 months after
and during the B months after treatment has concluded; mutine menltlly pregnancy tests must be nnnnnn,-n nnnnnjnn_ Snnnnnsnnsnnnln bg mn,-nn; mmnggpggls prngnnnny Rnnsnya; 1.ggg.5g5-535; .
V performed during this time (see EGNTHAINDIIRTIIJNS and CDPEGUS Package Insert). Nursing Mmm `
if DFEGUEUQY (NBS 000-ll lii¤l’iFlQ it'¤3Ui’l€m ¤F¤Ll¥‘i¤Q 5 i'fi¤iii¤S l¤¤Si·Ul¤l3Dll.ii‘¤ DRUM i”¤¤$tT?·€ advised It is not known whether peginterfemn or rihavirln or its components are excreted ln human milk.
of the slgnsticant temtogenic risk of CDPEGUS there to the fetus. T0 monitor maternalmetal outcomes The effect ot orally it ested peglnlerlerun or rloavlrin trom breast milk on the nursing Imam has not been
gi1§S*?Q"am lgumifi EWGSEU W CUPEGUs» ii}? wpgteus PWQEBNW H¤Lll$gg heal" Esiahiished- evaluated. Because 0% the potential for adverse reactions from the thugs in nursing infants, a decision
¤¤¤$ ¤¤ P6 Bil W6 SUOND lil · · st be . r ‘ ‘ ` dlscon ` e PEG and GUS treatment
Patients should be 3.lZ®@ ' l thele§9@¤Glel6Hi`d®I'lt 1 07-71 OCIOE
thereafter (see Laboratory Tests). Patients should be instnlcted to remain well hPgd)rate , especially during n .
the initial stages of treatment Patients should be advised to take GUPEGUS wrlh cl. -

Pediatric Use . `
§1*i§1Wy1?g f1t1gil1111¤1¤11¤1§§n¤;SlE1$A§1Y§. aione or in combination with conscus in pgtienm salon the PEGASYS°(pcg1¤terf¤r¤l1 site-Ze]
is e . . . . .
1¤E1;ASyS m111a1115 11111.1Z1,1111m11111_ 1111112111 111001.101 has 11111111 1 11 111 11 · . 11111 .111 . 11 _ liable 4 itclvegse Reactions Dccur in 25% of Patients
1';11f1i€11"1§f1.1'1‘11111i‘1i1'11'1’112,!1_1*13i111;1i[j mt ¤¤tt‘l¤li¤ati¤ns in neortagepuanii inmniséstzmiy . '¤ HBPNWF G Clint ~= Tt‘1¤|= {Pooled Stlmes 1. 2, 3, and Slutty 4)
G111.1111111 um 1 ‘ U I ’ V I Body System ~ Piggitgs HUFEHDN-lt*t 1l1111.;.1i1tn»;;1
timber patients have hig11e11;t11mlogc response rates than older patients. cir-ical studies or PEQASYS atcne g 48 weekt . t000 m or 1200 mg
ot in oombinahon with C_ S did not include sufficient numbers of subjects aged 55 or overto detcrtttilte · 1znu m |t(EBE't'|]t_¤
Wh€ih¤l’ they FBSDQHG differently from younger subjects. Adverse reactions related to alpha interierons, = _ cgpsgug 43 wegiw
Stttth as CNS cardiac, and systemic ,1lp-likeleftects may be more elmo in me elderly and caution 45 warm-
Si““““ “° “°“""°'i“° '" 0 Uri °i - '" iii tipim FEMS eil CUPEGUS at mimi lr bi = 7 ( @@¤msn¤mm
lodnqt and the risk oftoxrc reectionsto this therapy maybe greater in patients with impaired renal function. 1 ‘
Because efderiv pevem are more ivory to have decreased renar ronenan, care should be taken rr rinse °f· “ °/·· m ·
rt may he ussegil to monitor renal function. PEGASYS shoutdbe used with caution in 1111111111,11¤,1 $111, mwmm _
C1 <5r11e11c151»11r:ce rrtL·`mrn and COPEGUS should not be administered to patients with creatrnne 1 111111111011 S1111 18811101.1 22
ADVERSE sanctions . · V . 1;,,11,,,;,1,1a ummm . n r
, PEGASYS alone or rn combination with GOPEGUS causes a broad variety of serious advese reactions HY9¤*hY'¤'d'5*'i" 3 4 5 1
· (see BOXED 'qV§RNlNG_a[td WARNINGS). In all stitches, one or more serious adverse reactions occurred p|11.||;m gympigm; and sign; . Q
in i¤% of patients receiving PEGASYS alone or in combhation with GDPEGU5. 1;111111UB1.11S11111111a 55 5-; 55 GB :
- Tre most common hfedhreatening or fatal events induced or aggravated by PEGASYS and CUPEGUS ‘ p1.m1a 37 41 41 55
w?re depress1on1$.1rt:rde, relapse of dnrg abuseroverdose, and bacterial infections; each occurred at , 1;11gO1S 35 44 ESV 3-1r
B |'E!qUBf1C§,' D < a. . · 1 .
Nearly all patients in clinical trials eirperienoed one or more adverse events. The most commonly reported -1 Pam _ _ H 12 $0 9
adverse reactions were psychnatrac reactions. including depression, irritability anxiety, and flu-like G¤¥if¤l¤t°$“¤FI
Svmhtvms welt as fattoue pyretia, rnyatptat headache and rigors. Nauseailviomrtrng 24 33 _ 25 29
Oyetall 11% ufératients receiving 48 weeks of tnera11y with PEGASYS either alone (ry,11 or in aumuinauan Diarrhea 15 16 11 10 i
with COPEGU (10%) discontinued therapy. T e most common reasons for iscontinuation of Abdominal pain 15 15 S 9 i
U'l¤l6tQ!r' were itsvvhtatttv. liu-like Syndrome (eo. letltarott fatigue headache]. dermatologic, and gastm= ` Dry mouth 5 3 4 7 r _
intestinal disorders. J Dyspepsqa me mtgst ggrnmorgfeason for dose modification in patients receiving combination therapy was for l -1111m111D111g111a I
122% 13 cUr1;•1Erc1t11Srtres, neutropenia (20%) and thrombocytopenia (4 rt) tor PEGASYS and anemia 1 11111111111111§pe1.11a 3 1 11 i
· PEGASYS dose was reduced in12°! of patients receiving 1000 rn to 1200 m DOPEGUST 48 lcs E V - -
- and in 7%1of patients receiving apo mg CUPEGU5 for 24 wegks; CDPEGSS dose wascreduggdein T Nemmpgma i 2; 8 2; $ 2
21% of patients recent? tooo-mg to taco mg covscus mr is weeks and r2·r.. in patients receiving i T“'°'“”°“V‘“l’°""* 2 _ ‘
.Eai"3t“iiii'ri“i*i.§tLi.t“’§.i“i·...i...t. in W. .1. ..1 ( **°‘“"°"°““‘*“"‘""““°* rr i
· < nu rwreyva a G MD diti , dve r An ` V 17 24
glee o1igenred1J:¤t:I:1n'12:11bleIs ot a drug et11rnot he dlretgty compatednto caros igrntiteacttnm Wetigeltctilectease 4 3 10 1 _
1m1Emput1i1t1t:1s11un1n 1111111 1;: rates sterl rrny not predict the rates observed tn e breeder i N111'?11g11:E1,1111_ c1,1111,1,,111,, nssua .
Patients treated for 24 weeks with PEGASYS and B00 mg CGPEGUS were observed to have lower Myalgia I 37 38 . 40 49 `
incidence of serious adverse events 131% vs 10%), Hgb <10¤g}dl. (3% vs 15%}, dose modrticatron of » Arthralgra 28 29 22 23
PEGASYS [30% vs 36 A) and CDPEG S [19% vs 38% and withdrawal trom lTEHIll'lBI11°g5°r"¤ vs 15%] Back pam 9 _ 10 5 5
compared to patients treated for 48 weeks with and 1000 mg or 1200 mg D0 GUS Un the j 11111111111111111a1
other hand the overail incidence ot adverse events appeared to be similar in the two treatment groups. 1 H181111111111. 511 511 43 19 1
The most common serious adverse event 11?1%g11rtB·as bacterial infection (eg, sepsis, osteomyelitis, ; 1:11¤11.111sS1_,11111:11111111g1,11111111111 16 12 14 . 111
endocarditis, pyetonephritis, pneumonia]. 0_ r _ occurred at a frequency ot <1% and included: 1 111111111_11111,111111111111111111 5 1 11 5 -
suicide, suicidal ideation, psychosis, aggression, anxiety drup_abuse and drug overdose angina, hepatic 1 _ _
dysfunction, fatty liver cholangitis, arrhythmia, diabetes l'ne|ltus,au10lmmune phenorrena (eg, hyper- Psyctrretrre _
tiryroidia-,m1 hypothyroidism, sarcoidosis, systemic iupos erythematosus. rheumatoid arthritis), perrpheral irritability/Anxrettr(Nen·ousness 19 22 33 38 .
neuropathy; aplastic anemia, peptic uloen gastrointestinal bleeding. pancreatitis. colitis. corneal UIGHE insomnia 19 23 30 37 1
pulmonary embolism, coma. myositis, and oerdxat hemorrhage Depression tg 23 1
Lab rate T st Val 1 Concentration impairment 1 r
"°° ...1 ae ri t . 12 at - 1 dl .. r, 1 22 rr., 1 l iiiii
ern in oncen ion crease eow rn menang rop=.g . - · ,
monome§p?r and: 52% (median Hgh drop = 3.7 g.·'dL) of combination therapy patients. Severe ~ Rgzgsrnu Muhamsm ummm 12 n ‘ 1
anemia (Hgh <10 grdL) was encountered in 13% ot patients receiving combination therapy and 2% of · _ . i
monotherapy recipients. Dose modification tor anemia was required rn 22% of rrbavrrrn_ recipients r Respiratory, Thnmsltt and Medlestlnel ~ 1 _
treated for 48 weeks. Hemoglobin decreases in PEGASYS monotherapy weregenerally mild and did Dyspnea 4 2 13 14
. not require dose modification [see DDSAGE AND ADI\‘llNl$TFtA‘1'I'|II: Dose Modrficationsl. Cough 1 H1 4 :1. 12 _ 1 1
111e1111.¤111111s Dyspnee exertion <1 < - 1 _ ~
Decreases in neutrophil count below normal were observed in 95% of patients treated wim PEGASYS $11;,1 and guhwqammg nam .r _‘
either alone or in combination with COPEGUS. Severe potentially life-threatening neutropenga AIDDEC11 2;; gg gg . gg 1
(Attic <0.5 x 10°r'(t1111gccurred in approximately 5% of patients receiving PEGASYS either alone or m p1111111_15 12 8 19 18 1 . _
combination with EGUS. Seventeen percent of patients receiving PEGASYS monothempy and 20% to DBm.1a1111S 8 3 16 13 1 » V V
1 24% of patients receivin PEGASYSJCDPEGLS combination therapy required modification of interferon 1 D 511111 4 3 11-1 13 g - ·
dosage for neutropenia tgvvo percent ot patients required permanent reductions of PEEASYS dosage and RW11 5 11 8 5 - 1 _
41% required pennanent discontinuation. Median neutrophil counts return to pre-treatment levels SaSa1. . 11 5 1 11 V 5 · 5 _
` 4 weeks alter cessation of therapy (see DDSAGE AND ADM1NlSTIt!tI10N: Dose Illlotllttsationst. g E36? i"'°'°aS" 1 1 11 11 1 .
l-v¤¤¤h¤¤yt¤=S · : . 1
Decreases in lymphocyte count are induced by interferon alpha memgngy Lympltopenia was observed g ‘·|'|§¤§| Ul tdm · r
during both monotherapy (86% and combination therapy with P ASYS and COPEGUS (94%). ( Vision ¤|tJ¤‘e¤ 4 2 `
Severe Iymphopenia (<0.5 x 10”.'L occurred in approitimately 5% of monotherapy patiems and 14% of - 1 pw1_,111 $11111111S 1 2 111111 3 _ _ 1
combination PEGASYS and CDP GUS therapy recipients. Dose adiustments were not requrredlby . E11111113 11,1111 111111;1‘1111111 1111;1D1;ERD111__11 .
protocol. Median tymphotgrte counts return to %t’B·ll'BHi1'|'lBl’li ievels after 4 to 12 weeks ofthe cessation 1.. 51111111 11 . E
ot therapy The clinical significance oi the lymp openia is not known. V . 1 _ 1 5111111111 11111111111111111111 a11111111_111111111s ;
Platelets r r ‘ .
Platelet counts decreased in 52% of patients treated with PEGASYS alone (median drop 45% from ~ ` ‘ · U 1
baseline}, 33% of patients receiving combination with GGPEGUS (median drop 30% tmm baseline). i Vt
Median platelet coums return to pre·treatrnem levels 4`weeks alter the oessathin of therapy. _ 1, , r
Trigtycerides Q — , K.
Triglyceride levels are elevated in patients receiving alla interteron therapy and were elevated in the rnaiority r ·V — »_ 1:
ot patients participating in clinical studies receiving either PEGASYS alone or in combination with , _ _ V ‘ V 1 1
CUPEGUS. Random levels higher a400 mg/dL were observed in about 20% of patients. · 1 · . . . ‘ . . . ;
All Elevations _ l 4 ` ` I
Less than 1% of patients experienced marked elevations (5- to 10-toid above baseIine1 in ALT levels . V ‘ 1 V 1
oemig treatment. These transaminase elevations were on occasion associated wiiii hyperbi Iruhinemia and · ` ‘ r · . 1 . .. ‘i
were managed by dose reduction or discontinuation ot study treatment. l.iver function test abnormalities · [.1
were generally hansierrl. One case was attributed to autoirrrnune hepatitis, whim persisted beyond study . l . (
medication disoorrtrnuation(see,00SAt¤tE AND it0NIHlSTFtttI10N: Dose Moditicatlons). _ V 1 ’ _ ,
- V if V Table 1 Sustained Response tn Munulhempy `I'l‘£¤11'M _ _ .7 V V J - I - ` :*-71
if HOFEROH·tt eeonsrs pier- norsnnir-it esensirs — ott=r· _ RDFERDN-A Pitchers; . ¤tFF* if
_ 1 _ _ tN=2tltl ntazoei (uazen rnazesi (uses) 1 (naar} .1 V. V. -—. . . . _ 1
C¤0‘lblt’lStt Wftllogltt and Btologtc Sustained Response 11% 24% 13 6120) 17% 35% 18 (11, 25 7% 23% - `16 (6- 26] 1 #1
Sustained Virologtc Ftesponse** 11% 25% 15 (8123) (gy, gay., 19 (1112B) 8% 30% 22 [1l.33l 5
' Percent difference between PEGASYS and Ft0FERDN—Atreau11ent · ' ’ _ li V ’ ° t
· "CDBAS AMPLICOR“ HCV Test, version 2.0 r = . ‘ ’ . ‘ i
Copyright @2003 by Hoffmann-La Roche inc. All rights reserved. - I 1 Q
‘ Case 2:03-cv—O1729—FtCB V Document 107-7 Filed O2/06/2006 Page 2 of 2 *
lt `. _ _ `

Case 2:03-cv-01729-RCB

Document 107-7

Filed 02/06/2006

Page 1 of 2

Case 2:03-cv-01729-RCB

Document 107-7

Filed 02/06/2006

Page 2 of 2