LIPITOR DC PM E 119535 18apr08

PRODUCT MONOGRAPH
PRLIPITOR*

(atorvastatin calcium tablets)

10 mg, 20 mg, 40 mg and 0 mg atorvastatin

LIPI! "#T$%OLI&" R#'(L$TOR

*T.M. Pfizer Ir eland Pharmaceuticals
Pfizer Canada Inc. !icensee
"# $%% Trans&Canada Hi'h(a)
*ir+land ,ue- ec H./ 0M1
Date 2f Pre3arati2n4
/anuar) "0 0%%"

Date 2f Re5isi2n4
A3ril "6 0%%6

7u-missi2n C2ntr2l N24 "".1$1

Page 1 of 50 LIPITOR* (atorvastatin calcium) Product Monograph

Table o) *ontents

P$RT I+ ,#$LT, PRO-#&&IO.$L I.-OR"$TIO./////////////////////////////////////////////////////////0
7UMMAR8 PRODUCT IN9ORMATION ........................................................................$
INDICATION7 AND C!INICA! U7:..............................................................................$
CONTRAINDICATION7 ...................................................................................................;
<ARNING7 AND PR:CAUTION7..................................................................................;
AD=:R7: R:ACTION7..................................................................................................""
DRUG INT:RACTION7 .................................................................................................."$
DO7AG: AND ADMINI7TRATION .............................................................................."6
O=:RDO7AG: ................................................................................................................0%
ACTION AND C!INICA! PHARMACO!OG8 ............................................................0%
7TORAG: AND 7TA>I!IT8..........................................................................................0?
7P:CIA! HAND!ING IN7TRUCTION7 .......................................................................0?
DO7AG: 9ORM7 COMPO7ITION AND PAC*AGING .............................................0?
P$RT II+ &*I#.TI-I* I.-OR"$TIO. ///////////////////////////////////////////////////////////////////////////////21
PHARMAC:UTICA! IN9ORMATION..........................................................................01
C!INICA! TRIA!7 ..........................................................................................................0;
D:TAI!:D PHARMAC O!OG8 .....................................................................................$.
TO@ICO!OG8 .................................................................................................................?0
R:9:R:NC:7 ..................................................................................................................?1
P$RT III+ *O.&("#R
I.-OR"$TIO.////////////////////////////////////////////////////////////////////////
//////4


LIPITOR*
$torvastatin *alcium Tablets

P$RT I+ ,#$LT, PRO-#&&IO.$L I.-OR"$TIO.

&(""$R2 PRO!(*T I.-OR"$TIO.

Route o)
$dministration
!osage -orm 3
&trengt4
*linicall5 Relevant
.onmedicinal Ingredients
Calcium car-2nate candelilla
(aA B"% 0% and ?% m'C
cr2scarmell2se s2dium
h)dr2A)3r23)l cellul2se
h)dr2A)3r23)l
meth)lcellul2se lact2se
m2n2h)drate ma'nesium
stearate micr2cr)stalline
cellul2se 32l)eth)lene 'l)c2l
32l)s2r-ate 6% simethic2ne
emulsi2n talc and titanium
di2Aide.
2ral Ta-lets4 "% m' 0% m'
?% m' and 6% m'
at2r5astatin

I.!I*$TIO.& $.! *LI.I*$L
(&#

,56erc4olesterolemia

!IPITOR Bat2r5astatin calciumC is indicated as an adDunct t2 lifest)le
chan'es includin' diet Bat
least eEui5alent t2 the Adult Treatment Panel III BATP IIIC T!C dietC
f2r the reducti2n 2f
ele5ated t2tal ch2lester2l Bt2tal&CC !D!&C TG and a32li323r2tein >
Ba32 >C in h)3erli3idemic
and d)sli3idemic c2nditi2ns (hen res32nse t2 diet and 2ther
n2n3harmac2l2'ical measures
al2ne has -een inadeEuate includin'4

Primar) h)3erch2lester2lemia BT)3e IIaCF
C2m-ined BmiAedC h)3erli3idemia BT)3e II-C includin' familial c2m-ined h)3erli3idemia
re'ardless 2f (hether ch2lester2l 2r tri'l)cerides are the li3id a-n2rmalit) 2f c2ncernF
D)s-etali323r2teinemia BT)3e IIICF
H)3ertri'l)ceridemia BT)3e I=CF
9amilial h)3erch2lester2lemia Bh2m2z)'2us and heter2z)'2usC. 92r h2m2z)'2us familial
h)3erch2lester2lemia !IPITOR sh2uld -e used as an adDunct t2 treatments such as !D!
a3heresis 2r as m2n2thera3) if such treatments ar e n2t a5aila-le.


An adDunct t2 diet t2 reduce t2tal&C !D!&C and a32 > le5els in -2)s and 32stmenarchal
'irls "% t2 "# )ears 2f a'e (ith heter2z)'2us familial h)3erch2lester2lemia if after an
adeEuate trial 2f diet thera3) the f2ll2(in' findin's are still 3resent4
a. !D!&C remains G?.. mm2lH! B".% m'Hd!C 2r
-. !D!&C remains G?." mm2lH! B";% m'Hd!C and4
Ithere is a 32siti5e famil) hist2r) 2f 3remature cardi25ascular disease
2r
It(2 2r m2re 2ther C=D ris+ fact2rs are 3resent in the 3ediatric 3atient

!IPITOR als2 raises HD!&ch2lester2l and theref2re l2(ers the !D!&
CHHD!&C and t2tal&
CHHD!&C rati2s in 3atients (ith 3rimar) h)3erch2lester2lemia and
c2m-ined BmiAedC
h)3erli3idemia B9redric+s2n T)3e IIa and II- d)sli3idemiaC. In 322led
data fr2m 0? c2ntr2lled
clinical trials !IPITOR raised HD!&C le5els 1J&#J in 3rimar)
h)3erch2lester2lemic Bt)3e IIaC
3atients and "%J&"1J in miAed Bt)3e II-C d)sli3idemic 3atients.

In clinical trials !IPITOR B"% t2 6% m'Hda)C si'nificantl) im3r25ed
li3id 3r2files in 3atients
(ith a (ide 5ariet) 2f h )3erli3idemic and d)sli3idemic c2nditi2ns. In
0 d2se&res32nse studies in
mildl) t2 m2deratel) h)3erli3idemic 3atients B9redric+s2n T)3es IIa
and II-C !IPITOR reduced
the le5els 2f t2tal ch2lester2l B0.&?1JC !D!&C B$.&;%JC a32 > B$0&
1%JC TG B".&$#JC and
increased hi'h densit) li323r2tein ch2lester2l BHD!&CC le5els B1&.JC.
C2m3ara-le res32nses
(ere achie5ed in 3atients (ith heter2z)'2us familial
h)3erch2lester2lemia n2n&familial f2rms
2f h)3erch2lester2lemia c2m-ined h)3erli3idemia includin' familial
c2m-ined h)3erli3idemia
and 3atients (ith n2n&insulin de3endent dia-etes mellitus. In 3atients
(ith h )3ertri'l)ceridemia
BT)3e I=C !IPITOR B"% t2 6% m' dail)C reduced TG B01 & 1;JC and
!D!& C le5els B0$ & ?%JC.
!IPITOR has n2t -een studied in c2nditi2ns (here the maD2r
a-n2rmalit) is ele5ati2n 2f
ch)l2micr2ns BTG le5els G "" mm2lH!C i.e. t)3es I and =.

In an 23en&la-el stud) in 3atients (ith d)s-etali323r2teinemia BT)3e
IIIC !IPITOR B"% t2 6% m'
dail)C reduced t2tal&C B?%&1#JC TG B?%&1;JC and ID!&C K =!D!&C
le5els B$?&16JC.


!D!&C Bmm2lH!C L t2tal&C & MB%.$# A BTGC K HD!&CCN
!D!&C Bm'Hd!C L t2tal&C & M B%.0 A BTGC K HD!&CCN"

92r 3atients (ith TG le5els G?.10 mm2lH! BG?%% m'Hd!C this eEuati2n
is less accurate and
!D!&C c2ncentrati2ns sh2uld -e measured directl) 2r -)
ultracentrifu'ati2n.

Patients (ith hi'h 2r 5er) hi'h tri'l)ceride le5els i.e. G 0.0 mm2lH!
B0%% m'Hd!C 2r G 1.;
mm2lH! B1%% m'Hd!C res3ecti5el) ma) reEuire tri'l)ceride&l2(erin'
thera3) Bfen2fi-rate
-ezafi-rate 2r nic2tinic acidC al2ne 2r in c2m-inati2n (ith !IPITOR.

In general, combination t4era65 7it4 )ibrates must be underta8en
cautiousl5 and onl5
a)ter ris89bene)it anal5sis (see :$R.I.'& $.! PR#*$(TIO.&,
"uscle #))ects,
P4armaco8inetic Interactions and !R(' I.T#R$*TIO.&)/

#levated serum trigl5cerides are most o)ten observed in 6atients
7it4 t4e metabolic s5ndrome
(abdominal obesit5, at4erogenic d 5sli6idemia ;elevated
trigl5cerides, small dense L!L 6articles
and lo7 ,!L9c4olesterol<, insulin resistance 7it4 or 7it4out
glucose intolerance, raised blood
6ressure and 6rot4rombic and 6roin)lammator5 states)/

(-or t4e treatment o) s6eci)ic d5sli6idemias re)er to t4e Re6ort o)
t4e *anadian :or8ing 'rou6
on ,56erc4olesterolemia and Ot4er !5sli6idemias or to t4e (&
.*#P #=6ert Panel on
!etection, #valuation, and Treatment o) ,ig4 %lood *4olesterol in
$dults >$dult Treatment
Panel III? , under R#-#R#.*#&)/

:4en drugs are 6rescribed attention to t4era6eutic li)est5le
c4anges (reduced inta8e o) saturated
)ats and c4olesterol, 7eig4t reduction, increased 645sical activit5,
ingestio n o) soluble )ibers)
s4ould al7a5s be maintained and rein)orced/

Prevention o) *ardiovascular !isease
!IPITOR is indicated t2 reduce th e ris+ 2f m)2cardial infarcti2n in adult h)3ertensi5e 3atients
(ith2ut clinicall) e5ident c2r2nar) heart disease -ut (ith at least three additi2nal ris+ fact2rs f2r
c2r2nar) heart disease such as a'e G11 )ears male seA sm2+in' t)3e 0 dia-etes left 5entricular
h)3ertr23h) 2ther s3ecified a-n2rmalities 2n :CG micr2al-uminuria 2r 3r2teinuria rati2 2f
3lasma t2tal ch2lester2l t2 HD!&ch2lester2l G; 2r 3remature famil) hist2r) 2f c2r2nar) heart
disease.

!IPITOR is als2 indicated t2 reduce the ris+ 2f m)2 cardial infarcti2n and str2+e in adult 3atients
(ith t)3e 0 dia-etes mellitus and h)3ertensi2n (ith2ut clinicall) e5ident c2r2nar ) heart disease
-ut (ith 2ther ris+ fact2rs such as a'e G11 )ears retin23ath) al-uminuria 2r sm2+in'.

!IPITOR is indicated t2 reduce the ris+ 2f m)2cardial infarcti2n in 3atients (ith clinicall)
e5ident c2r2nar) heart disease.

" 9riede(ald <.T. et al. Clin. Chem. ".#0F"6B;C4?6.&1%0.


*O.TR$I.!I*$TIO.&

,56ersensitivit5 to an5 com6onent o) t4is medication ()or a
com6lete listing o) t4e com6onents,
see !O&$'# -OR"&, *O"PO&ITIO. $.! P$*@$'I.')/

$ctive liver disease or une=6lained 6ersistent elevations o) serum
transaminases e=ceeding 0
times t4e u66er limit o) normal (see :$R.I.'& $.!
PR#*$(TIO.&)/

Pregnanc5 and nursing 7omen+ *4olesterol and ot4er 6roducts o)
c4olesterol bios5nt4esis are
essential com6onents )or )etal develo6ment (including s5nt4esis o)
steroids and cell membranes)/
LIPITOR s4ould be administered to 7omen o) c4ildbearing age
onl5 74en suc4 6atients ar e
4ig4l5 unli8el5 to conceive and 4ave been in)ormed o) t4e 6ossible
4arm/ (I) t4e 6atient
becomes 6regnant 74ile ta8ing LIPITOR, t4e drug s4ould be
discontinued immediatel5 and t4e
6atient a66rised o) t4e 6otential 4arm to t4e )etus/ $t4erosclerosis
being a c4ronic 6rocess,
discontinuation o) li6id metabolism regulating drugs during
6regnanc5 s4ould 4ave little im6act
on t4e outcome o) long9term t4era6 5 o) 6rimar 5
456erc4olesterolemia (see PR#*$(TIO.& A
(se in Pregnanc5, (se in .ursing "ot4ers)/

:$R.I.'& $.! PR#*$(TIO.&

'eneral

>ef2re institutin' thera3) (ith !IPITOR B at2r5astatin calciumC an
attem3t sh2uld -e made t2
c2ntr2l ele5ated serum li323r2tein le5els (ith a33 r23riate diet
eAercise an d (ei'ht reducti2n in
25er(ei'ht 3atients and t2 treat 2ther underl)in' medical 3r2-lems
Bsee INDICATION7 AND
C!INICA! U7:C. Patients sh2uld -e ad5ised t2 inf2rm su-seEuent
3h)sicians 2f the 3ri2r use 2f
!IPITOR 2r an) 2ther li3id&l2(erin' a'ents.

Pharmac2+inetic Interacti2ns
The use 2f HMG& C2A reductase inhi-it2rs has - een ass2ciated (ith se5ere m)23ath) includin'
rha-d2m)2l)sis (hich ma) - e m2re f reEuent (hen the) ar e c2&administered (ith dru 's that
inhi-it the c)t2chr2me P&?1% enz)me s)stem. At2r5astatin is meta-2lized -) c)t2 chr2me P&?1%
is2f2rm $A? and as such ma) interact (ith a'ents that inhi-it this enz)me. B7ee <ARNING7
AND PR:CAUTION7 Muscle effects and DRUG INT:RACTION7C.

Muscle :ffects
:ffects 2n s+eletal muscle such as m)al'ia m)23ath) and 5er) rarel)
rha-d2m)2l)sis ha5e
-een re32rted in 3atients treated (ith !IPITOR.

Ber5 rare cases o) r4abdom5ol5sis 7it4 acute renal )ailure secondar5 to m5oglobinuria,
4ave been re6orted 7it4 LIPITOR and 7it4 ot4er ,"'9*o$ reductase in4ibitors/

M)23ath) defined as muscle 3ain 2r muscle (ea+ness in c2nDuncti2n (ith increases in creatine
+inase BC*C 5alues t2 'reater than ten times the u33er limit 2f n2rmal sh2uld -e c2nsidered in
an) 3atient (ith diffuse m)al'ia muscle tenderness 2r (ea+ness andH2r mar+ed ele5ati2n 2f


C*. Patients sh2uld -e ad5ised t2 re32rt 3r2m3tl) an) uneA3lained muscle 3ain tenderness 2r
(ea+ness 3articularl) if acc2m3anied - ) malaise 2r fe5er. Patients (h2 de5el23 an) si'ns 2r
s)m3t2ms su''esti5e 2f m)23ath) sh2uld ha5e their C* le5els measured. !IPITOR thera3)
sh2uld -e disc2ntinued if mar+edl) ele5ated C* le5els are measured 2r m)23ath) is dia'n2sed
2r sus3ected.

Pre&dis32sin' 9act2rs f2r M)23ath)HRha-d2m)2l)sis4 !IPITOR as (ith 2ther HMG&C2A
reductase inhi-it2rs sh2uld -e 3rescri-ed (ith cauti2n in 3atients (ith 3re&dis32sin' fact2rs f2r
m)23ath)Hrha-d2m)2l)sis. 7uch fact2rs include4
I Pers2nal 2r famil) hist2r) 2f hereditar) muscular dis2rders
I Pre5i2us hist2r) 2f muscle t2Aicit) (ith an2ther HMG&C2A reductase inh i-it2r
I C2nc2mitant use 2f a fi-rate 2r niacin
I H)32th)r2idism
I Alc2h2l a-use
I :Acessi5e 3h)sical eAercise
I A'e G#% )ears
I Renal im3airment
I He3atic im3airment
I Dia-etes (ith he3atic fatt) chan'e
I 7ur'er) and trauma
I 9railt)
I 7ituati2ns (here an increase in 3lasma le5els 2f acti5e in'redient ma) 2ccur

The ris+ 2f m)23ath) and rha-d2m)2l)sis durin' treatment (ith HMG&C2A reductase
inhi-it2rs
is increased (ith c2ncurrent administrati2n 2f c)cl2s32rin fi-ric acid deri5ati5es
er)thr2m)cin
clarithr2m)cin niacin Bnic2tinic acidC az2le antifun'als 2r nefaz2d2ne. Theref2re l2(er
startin' and maintenance d2ses 2f at2r5astatin sh2uld als2 -e c2nsidered (hen ta+en
c2nc2mitantl) (ith the af2rementi2ned dru's. In cases (here c2&administrati2n 2f !IPITOR
(ith c)cl2s32rine is necessar ) the d2se 2f !IPITOR sh2uld n2t eAceed "%m' Bsee
PR:CAUTION7 Pharmac2+inetic Interacti2n 7tudies and P2tential Dru' Interacti2nsF
DRUG
INT:RACTION7 Dru'&Dru' Interacti2nsF D:TAI!:D PHARMACO!OG8 Human
Pharmac2+ineticsC.

!IPITOR thera3) sh2uld -e tem32raril) (ithheld 2r disc2ntinued in an) 3atient (ith an acute
seri2us c2nditi2n su''esti5e 2f m)23ath) 2r ha5in ' a ris+ fact2r 3redis32sin' t2 the
de5el23ment 2f renal failure sec2ndar) t2 rha-d2m)2l)sis Bsuch as se3sis se5ere acute infecti2n
h)32tensi2n maD2r sur'er) trauma se5ere meta-2lic end2crine and electr2l)te dis2rders and
unc2ntr2lled seizuresC.

!IPITOR thera3) sh2uld -e disc2ntinued if mar+edl) ele5ated CP* le5els 2ccur 2r m)23 ath) is
dia'n2sed 2r sus3ected.


*ardiovascular

:ffect 2n U-iEuin2ne BC2,"%C !e5els
7i'nificant decreases in circulatin' u-iEuin2ne le5els in 3atients treated (ith at2r5astatin and
2ther statins ha5e -een 2-ser5ed. The clinical si'nificance 2f a 32tential l2n'&term statin&
induced deficienc) 2f u-iEuin2ne has n2t -een esta-lished. It h as -een re32 rted that a decrease in
m)2cardial u-iEuin2ne le5els c2uld lead t2 im3aired cardiac functi2n in 3atients (ith -2rderline
c2n'esti5e heart failure Bsee R:9:R:NC:7C.

#ndocrine and "etabolism

#ndocrine -unction
,"'9*o$ reductase in4ibitors inter)ere 7it4 c4olesterol s5nt4esis and as suc4 mig4t
t4eoreticall5 blunt adrenal and3or gonadal steroid 6roduction/ *linical studies 7it4 atorvastatin
and ot4er ,"'9*o$ reductase in4ibitors 4ave suggested t4at t4ese agents do not reduce 6lasma
cortisol concentration or im6air adrenal reserve and do not reduce basal 6lasma testosterone
concentration/ ,o7ever, t4e e))ects o) ,"'9*o$ reductase in4ibitors on male )ertilit5 4ave not
been studied in adeCuate numbers o) 6atients/ T4e e))ects, i) an5, on t4e 6ituitar59 gonadal a=is in
6remeno6ausal 7omen are un8no7n/

Patients treated 7it4 atorvastatin 74o develo6 clinical evidence o) endocrine d5s)unction s4ould
be evaluated a66ro6riatel5/ *aution s4ould be e=ercised i) an ,"'9*o$ reductase in4ibitor or
ot4er agent used to lo7er c4olesterol levels is administered to 6atients receiving ot4er drugs (e/g/
8etoconaDole, s6ironolactone or cimetidine) t4at ma5 decrease t4e levels o) endogenous steroid
4ormones/

#))ect on Li6o6rotein (a)
In some 6atients, t4e bene)icial e))ect o) lo7ered total c4olesterol and L!L9* levels ma5 be
6artl5 blunted b5 a concomitant increase in L6( a) li6o6rotein concentrations/ Present 8no7ledge
suggests t4e im6ortan ce o) 4ig4 L6(a) levels as an emerging ris8 )actor )or coronar 5 4 eart
disease/ It is t4us desirable to maintain and rein)orce li)est5le c4anges in 4ig4 ris8 6atients
6laced on atorvastatin t4era65 (see R#-#R#.*#&)/

Patients 7it4 &evere ,56erc4olesterolemia

,ig4er drug dosages (0 mg3da5) reCuired )or some 6atients 7it4 severe 456erc4olesterolemia
(including )amilial 456erc4olesterolemia) are associated 7it4 increased 6lasma levels o)
atorvastatin/ *aution s4ould be e=ercised in suc4 6atients 74o are also severel5 renall5
im6aired, elderl5, or are concomitantl5 being administered digo=in or *2P 0$4 in4ibitors
Bsee <ARNING7 AND PR:CAUTION7 Pharmac2+inetic Interacti2ns Muscle :ffectsF DRUG
INT:RACTION7F DO7AG: AND ADMINI7TRATIONC.


,e6atic3%iliar53Pancreatic

,e6atic #))ects
In clinical trials, 6ersistent increases in serum tran saminases greater t4an t4 ree times t4e u66er
limit o) normal occurred in E1F o) 6atients 74o received LIPITOR/ :4en t4e dosage o)
LIPITOR 7as reduced, o r 74en dru g treatment 7as interru6ted or discontinued, serum
transaminase levels returned to 6retreatment levels/ T4e increases 7ere generall5 not associated
7it4 Gaundice or ot4er clinical signs or s5m6toms/ "ost 6atients continued treatment 7it4 a
reduced dose o) LIPITOR 7it4out clinical seCuelae/

Liver )unction tests s4ould be 6er)ormed be)ore t4 e initiation o) treatment, and 6eriodicall5
t4erea)ter/ &6ecial attention s4ould be 6aid to 6atients 74o develo6 elev ated serum transaminase
levels, and in t4ese 6atients measurements s4ould be re6eated 6rom6tl5 and t4en 6er)ormed more
)reCuentl5/
I) increases in alanine aminotrans)erase ($LT) or as6artate
aminotrans)erase ($&T) s4o7
evidence o) 6rogression, 6articularl5 i) t4e5 rise to greater t4an 0
times t4e u66er limit o)
normal and are 6ersistent, t4e dosage s4ould be reduced or t4e
drug discontinued/

LIPITOR, as 7ell as ot4er ,"'9*o$ reductase in4ibitors, s4ould
be used 7it4 caution in
6atients 74o consume substantial Cuantities o) alco4ol and3or 4ave
a 6ast 4istor5 o) liver
disease/ $ctive liver disease or une=6lained transaminase elevations
are contraindications to t4e
use o) LIPITORH i) suc4 a condition s4ould develo6 during t4era6
5, t4e drug s4ould be
discontinued/

O64t4almologic

:ffect 2n the !ens
Current l2n'&term data fr2m clinical trials d2 n2t indicate an ad5erse
effect 2f at2r5astatin 2n the
human lens.

Renal

Renal Insufficienc)
Plasma c2ncentrati2ns and !D!&C l2(erin' efficac) 2f !IPITOR (as
sh2(n t2 -e similar in
3atients (ith m2derate renal insufficienc) c2m3ared (ith 3atients (ith
n2rmal renal functi2n.
H2(e5er since se5eral cases 2f rha-d2m)2l)sis ha5e -een re32rted in
3atients (ith a hist2r) 2f
renal insufficienc) 2f un+n2(n se5erit) as a 3recauti2nar) measure
and 3endin' further
eA3erience in renal disease the l2(est d2se B"% m'Hda)C 2f !IPITOR
sh2uld -e used in these
3atients. 7imilar 3recauti2ns a33l) in 3atients (ith se5ere renal
insufficienc) Mcreatinine
clearance O$% m!Hmin BO%.1 m!HsecCNF the l2(est d2sa'e sh2uld -e
used and im3lemented
cauti2usl) Bsee <ARNING7 AND PR:CAUTION7 Muscle :ffectsF
DRUG
INT:RACTION7C. Refer als2 t2 DO7AG: AND
ADMINI7TRATION.


&ensitivit53Resistance

H)3ersensiti5it)
An a33arent h)3ersensiti5it) s)ndr2me has -een re32rted (ith 2ther
HMG&C2A reductase
inhi-it2rs (hich has included " 2r m2re 2f the f2ll2(in' features4
ana3h)laAis an'i2edema
lu3us er)th emat2us&li+e s)ndr2me 32l)m)al'ia rheumatica 5asculitis
3ur3ura
thr2m-2c)t23enia leu+23enia hem2l)tic anemia 32siti5e ANA :7R
increase e2sin23hilia
arthritis arthral'ia urticaria asthenia 3h2t2sensiti5it) fe5er chills
flushin' malaise d)s3n ea
t2Aic e3idermal necr2l)sis er)thema multif2rme includin' 7te5ens&
/2hns2n s)ndr2me.
Alth2u'h t2 date h)3ersensiti5it) s)ndr2me has n2t -een descri-ed as
such !IPITOR sh2uld -e
disc2ntinued if h)3ersensiti5it) is sus3ected.

&6ecial Po6ulations

(se in Pregnanc5+ LIPITOR is contraindicated during 6regnanc5 (see
*O.TR$I.!I*$TIO.&)/

There are n2 data 2n the use 2f !IPITOR durin' 3re'nanc). !IPITOR
sh2uld -e administered t2
(2men 2f child-earin' a'e 2nl) (hen such 3atients are hi'hl) unli+el)
t2 c2ncei5e and ha5e
-een inf2rmed 2f the 32tential hazards. If the 3atient -ec2mes 3re'nant
(hile ta+in' !IPITOR
the dru' sh2uld - e disc2ntinued and the 3atient a33rised 2f the
32tential ris+ t2 the fetus.

(se in .ursing "ot4ers+ In rats, mil8 concentrations o)
atorvastatin are similar to t4ose in
6lasma/ It is not 8no7n 74et4er t4is drug is e=creted in 4uman
mil8/ %ecause o) t4e 6otential
)or adverse reactions in nursing in)ants, 7omen ta8ing LIPITOR
s4ould not breast9)eed (see
*O.TR$I.!I*$TIO.&)/

Pediatric (se+ &a)et5 and e))ectiveness o) LIPITOR in 6atients 1091I 5ears o) age (.J140) 7it4
4eteroD5gous )amilial 456erc4olesterolemia 4ave been evaluated in a controlled clinical trial o) K
mont4s duration in adolescent bo5s and 6ostmenarc4al girls/ Patients treated 7it4 LIPITOR 4ad
a sa)et5 and tolerabilit5 6ro)ile generall5 similar to t4at o) 6lacebo/ !oses greater t4an 20 mg
4ave not been studied in t4is 6atient 6o6ulation/

&a)et5 and e))ectiven ess o) LIPITOR in 6ediatric 6atients 4as not been determined in t4e
6revention o) m5ocardial in)arction/

LIPITOR 4ad no e))ect on gro 7t4 or se=ual maturation in bo5s and in girls/ T4e e))ects on
menstrual c5cle 7ere not assessed >see P,$R"$*OLO'2, *linical &tudies sectionH
$!B#R&# R#$*TIO.&, Pediatric PatientsH and !O&$'# $.! $!"I.I&TR$TIO. )o r
,eteroD5gous -amilial ,56erc4olesterolemia in Pediatric Patients (1091I 5ears o) age)?/

$dolescent )emales s4ould be counselled on a66ro6riate contrace6tive met4ods 74ile on
LIPITOR t4era65 (see *O.TR$I.!I*$TIO.& and PR#*$(TIO.&, (se in Pregnanc5)/


!IPITOR has n2t -een studied in c2ntr2lled clinical trials in52l5in'
3re&3u-ertal 3atients 2r
3atients )2un'er than "% )ears 2f a'e.

D2ses 2f !IPITOR u3 t2 6% m'Hda) f2 r " )ear ha5e -een e5aluated in
6 3ediatric 3atients (ith
h2m2z)'2us familial h)3erch2lester2lemia Bsee Clinical 7tudies &
Heter2z)'2us 9amilial
H)3erch2lester2lemia in 3ediatric 3atientsC.

'eriatric (se+ Treatment e=6erience in adults I0 5ears or
older (.J221) 7it4 doses o)
LIPITOR u6 to 0 mg3da5 4as demonstrated t4at t4e
sa)et5 and e))ectiveness o) atorvastatin in
t4is 6o6ulation 7as similar to t4at o) 6atients EI0 5ears o)
age/ P4armaco8inetic evaluation o)
atorvastatin in subGects over t4e age o) K1 5ears indicates
an increased $(*/ $s a 6recautionar 5
measure, t4e lo7est dose s4ould be administered initiall5
(see !#T$IL#! P,$R"$*OLO'2,
,uman P4armaco8ineticsH R#-#R#.*#&)/

#lderl5 6atients ma5 be more susce6tible to m5o6at45 (see
:$R.I.'& A "uscle #))ects A Pre9
dis6osing -actors )or "5o6at453R4abdom5ol5sis)/

$!B#R&# R#$*TIO.&

$dverse !rug Reaction Overvie7
!IPITOR is 'enerall) (ell&t2lerated. Ad5erse reacti2ns ha5e usuall) -een mild and transient. In
c2ntr2lled clinical studies B3lace-2&c2ntr2lled and acti5e&c2ntr2lled c2m3arati5e studies (ith
2ther li3id l2(erin' a'entsC in52l5in' 01%0 3atients O0J 2f 3atients (ere disc2ntinued due t2
ad5erse eA3eriences attri-uta-le t2 !IPITOR. Of these 01%0 3atients "#0" (ere treated f2r at
least ; m2nths and "01$ f2r " )ear 2r m2re.

Ad5erse eA3eriences 2 ccurrin' at an incidence L"J in 3atients 3artici3atin' in 3lace-2&
c2ntr2lled clinical studies 2f !IPITOR and re32rted t2 -e 32ssi-l) 3r2-a-l) 2r definitel) dru'
related are sh2(n in Ta-le " -el2(4


TA>!: "4 Ass2ciated Ad5erse :5ents Re32rted in L "J
2f Patients in Place-2 C2ntr2lled Clinical Trials

Placebo F LIPITOR F
(nJ2I0) (nJ1122 )

'$&TROI.T#&TI.$L

"
"
0
0
%
"
"
"
"
"
C2nsti3ati2n
Diarrhea
D)s3e3sia
9latulence
Nausea

.#RBO(& &2&T#"
Headache 0 "

"I&*#LL$.#O(&
"
"
"
Pain
M)al'ia
Asthenia
O"
"

The f2ll2(in' additi2nal ad5erse e5ents (ere re32rted in clinical trialsF
n2t all e5ents listed
-el2( ha5e -een ass2ciated (ith a causal relati2nshi3 t2 !IPITOR
thera3)4 Muscle cram3s
m)2sitis m)23ath) 3aresthesia 3eri3heral neur23ath) 3ancreatitis
he3atitis ch2lestatic
Daundice an2reAia 52mitin' al23ecia 3ruritus rash im32tence h
)3er'l)cemia and
h)32'l)cemia.

O"
,eteroD5gous -amilial ,56erc4olesterolemia in Pediatric Patients (ages 1091I 5ears)+

In a 0;&(ee+ c2ntr2lled stud) in -2)s and 32stmenarchal 'irls BnL"6#
(here "?% 3atients
recei5ed !IPITORC the safet) and t2lera-ilit) 3r2file 2f !IPITOR "% t2
0% m' dail) (as similar
t2 that 2f 3lace-2. The ad5erse e5ents re32rted in G"J 2f 3atients (ere
as f2ll2(s4 a-d2minal
3ain de3ressi2n and headache Bsee PHARMACO!OG8 Clinical
7tudies and PR:CAUTION7
Pediatric UseC.

Laborator5 *4anges and $dverse #vents

The criteria f2r clinicall) si'nificant la-2rat2r) chan'es (ere G$ @ the u33er limit 2f n2rmal
BU!NC f2r li5er enz)mes and G1 @ U!N f2r creatine +inase. A t2tal 2f 6 uniEue su-Dects met
2ne 2r m2re 2f these criteria durin' the d2u-le&-lind 3hase. Hence the incidence 2f 3 atients
(h2 eA3erienced a-n2rmall) hi'h enz)matic le5els BA7THA!T and creatine +inaseC (as G ?J
B6H"6#C.

9i5e at2r5astatin and 2ne 3lace-2 su-Dects had increases in C* G1 @ U!N durin' the d2u-le&
-lind 3haseF t(2 2f the fi5e at2r5astatin treated su-Dects had increases in C* G "% @ U!N.

There (ere 0 su-Dects (h2 had clinicall) si'nificant increases in A!T.


$bnormal ,ematologic and *linical *4emistr5 -indings

Laborator5 Tests+ Increases in serum transaminase levels 4ave
been noted in clinical trials
(see :$R.I.'& $.! PR#*$(TIO.&)/

Post9"ar8et $dverse !rug Reactions
T4e )ollo7ing adverse events 4ave also been re6o rted during 6ost9
mar8eting e= 6erience 7it4
LIPITOR, regardless o) causalit5 assessment+

Ber5 rare re6orts+ severe m5o6at45 7it4 or 7it4ou t
r4abdom5ol5sis (see :$R.I.'& $.!
PR#*$(TIO.&, "uscle #))ects, Renal Insu))icienc5 and !R('
I.T#R$*TIO.&)/

Isolated re6orts+ '5necomastia, t4romboc5to6enia, art4ralgia and
allergic reactions including
urticaria, angioneurotic edema, ana645la=is and bullous ras4es
(including er5t4eme multi)orme,
&tevens9Lo4nson s5ndrome and to=ic e6idermal necrol5sis)?,
)atigue, bac8 6ain, c4est 6ain,
malaise, diDDiness, amnesia, 6eri64eral edema, 7eig4t gain,
abdominal 6ain, insomnia,
456oest4esia, tinnitus, tendon ru6ture, and d 5sgeusia/

T4ese ma5 4ave no causal relations4i6 to atorvastatin/

O64t4almologic observations+ see :$R.I.'& $.!
PR#*$(TIO.&/

!R(' I.T#R$*TIO.&

Overvie7

P4armaco8inetic interaction studies conducted 7it4 drugs in
4ealt45 subGects ma5 not detect t4e
6ossibilit5 o) a 6otential drug interaction in some 6atients due to
di))erences in underl5ing
diseases and use o) concomitant medications (see also :$R.I.'&
$.! PR#*$(TIO.&,
&6ecial Po6ulationsH Renal Insu))icienc5H Patients 7it4 &evere ,56
erc4olesterolemiaH 'eriatric
(se)/

*oncomitant T4era65 7it4 Ot4er Li6id "etabolism Regulators+
%ased on 6ost9mar8eting
surveillance, gem)ibroDil, )eno)ibrate, ot4er )ibrates, and li6id9
modi)5ing doses o) niacin
(nicotinic acid) ma5 increase t4e ris8 o) m5o6at45 74en given
concomitantl5 7it4 ,"'9*o$
reductase in4ibitors, 6robabl5 because t4e5 can 6roduce m5o6at45
74en given alone (see
:$R.I.'& A "uscle #))ects)/ T4ere)ore, combined drug t4era6
5 s4ould be a66roac4ed 7it4
cautionH lo7er starting and maintenance doses o) atorvastatin
s4ould be considered/

*5toc4rome P94109 mediated Interactions+ $torvastatin is metaboliDed b5 t4e c5toc4rome
P9410 isoenD5me, *2P 0$4/ #r5t4rom5cin, a *2P 0$4 in4ibitor, increased atorvastatin 6lasma
levels b5 40F/ *oadministration o) *2P 0$4 in4ibitors, suc4 as gra6e)ruit Guice, some
macrolide antibiotics (i/e/ er5t4rom5cin, clarit4rom5cin), immunosu66ressants (c5clos6orine),
aDole anti)ungal agents (i/e/ itraconaDole, 8eto conaDole), 6rotease in4ibitors, or t4e


antide3ressant nefaz2d2ne ma) ha5e the 32tential t2 increase 3lasma c2ncentrati2ns 2f HMG
C2A reductase inhi-it2rs includin' !IPITOR Bsee R:9:R:NC:7C. Cauti2n sh2uld thus -e
eAercised (ith c2nc2mitant use 2f these a'ents and l2(er startin' and maintenance d2ses 2f
at2r5astatin sh2uld -e c2 nsidered (hen ta+en c2n c2mitantl) (ith the af2rementi2ned dru's Bsee
<ARNING7 AND PR:CAUTION7 Pharmac2+inetic Interacti2ns Muscle :ffects Renal
Insu fficienc) and :nd2crine 9uncti2nF DO7AG: AND ADMINI7TRATIONF R:9:R:NC:7C.

Trans6orter In4ibitors+ $torvastatin and atorvastatin9metabolites are substrates o) t4e
O$TP1%1 trans6o rter/ In4ibitors o) t4e O$TP1%1 (e/g/ c5clos6orine) can increase t4e
bioavailabilit5 o) atorvastatin (see !#T$IL#! P,$R"$*OLO'2, ,uman P4armaco8inetics)/

Inducers o) c5toc4rome P410 0$+ *oncomitant administration o)
atorvastatin 7it4 inducers
o) c5to c4rome P410 0$4 (eg e) avirenD, ri)am6in) can lead to
variable reductions in 6lasma
concentrations o) atorvastatin/ !ue to t4e dual interaction
mec4anism o) ri)am6in, (c5toc4rome
P410 0$4 induction and in4ibition o) 4e6atoc5te u6ta8e
trans6orter O$TP1%1), simultaneous
co9administration o) atorvastatin 7it4 ri)am6in resulted in a mean
increase in *ma= and $(*
o) atorvastatin o) 12 and 1M0F, res6ectivel5/ In contrast, a dela5ed
administration o)
atorvastatin a)ter administration o) ri)am6in 4as been associated
7it4 a signi)icant reduction
(a66ro=imatel5 0F) in atorvastatin 6lasma concentrations/

!rug9!rug Interactions

&uggested+ T4e drugs listed in t4is table are based on eit4er drug interactions studies, case
re6orts, or 6otential interactions due to t4e e=6ected magnitude and seriousness o) t4e interaction
Bi.e.th2se identified as c2ntraindicatedC. Interacti2ns (ith 2ther dru 's ha5 e n2t -een esta-lished.


Table 29 #stablis4ed or Potential !rug9!rug Interactions
Pro6er name #))ect *linical comment
>ile Acid 7eEuestrants Patients (ith mild t2 m2derate HC4 <hen !IPITOR is used c2ncurrentl)
(ith c2lesti32l 2r an) 2ther resin an
inter5al 2f at least 0 h2urs sh2uld -e
maintained -et(een the t(2 dru's
since the a-s2r3ti2n 2f !IPITOR ma)
-e im3aired -) the resin.
!D!&C reducti2n B &?1JC (hen !IPITOR
"% m' and c2lesti32l 0% ' (ere
c2administered than (hen either dru' (as
administered al2ne B&$1J f2r !IPITOR
and &00J f2r c2lesti32lC.
Patients (ith se5ere HC4 !D!&C
reducti2n (as similar B&1$JC (hen
!IPITOR ?% m' and c2lesti32l 0% ' (ere
c2administered (hen c2m3ared t2 that
(ith !IPITOR 6% m' al2ne. 3lasma
c2ncentrati2n BP0;JC (hen !IPITOR ?%
m' 3lus c2lesti32l 0% ' (ere
c2administered c2m3ared (ith !IPITOR
?% m' al2ne.
H2(e5er the c2m-inati2n dru' thera3)
(as less effecti5e in l2 (erin' TG than
!IPITOR m2n2thera3) in -2th t)3es 2f
h)3erch2lester2lemic 3atients.
9i-ric Acid Deri5ati5es
BGemfi-r2zil 9en2fi-rate
>ezafi-rateC and Niacin
Bnic2tinic acidC
Alth2u'h there is limited eA3erience
(ith the use 2f !IPITOR 'i5en
c2ncurrentl) (ith fi-ric acid
deri5ati5es and niacin the -enefits
and ris+s 2f such c2m-ined thera3)
sh2uld -e carefull) c2nsidered Bsee
<ARNING7 AND PR:CAUTION7
Muscle :ffects and R:9:R:NC:7C.
in the ris+ 2 f m)23ath) durin' treatment
(ith 2ther dru's in this class includin'
at2r5astatin (ith c2ncurrent
administrati2n (ith a fi-ric acid deri5ati5e
C2umarin Antic2a'ulants N2 clinicall) si'nificant effect 2n !IPITOR had n2 clinicall)
si'nificant effect 2n 3r2thr2m-in
time (hen administered t2 3atients
recei5in' chr2nic (arfarin thera3)
Bsee R:9:R:NC:7C.
3r2thr2m-in time
Di'2Ain In health) su-Dects di'2Ain P* at stead)& Patients ta+in' di'2Ain sh2uld -e
m2nit2red a33r23riatel). state (ere n2t si'nificantl) altered -)
c2administrati2n 2f di'2Ain %.01 m' and
!IPITOR "% m' dail).
in di'2Ain stead)&state c2ncentrati2n s
-) P0%J f2ll2(in' c2administrati2n 2f
di'2Ain %.01 m' and !IPITOR 6% m'
dail) Bsee D:TAI!:D
PHARMACO!OG8 Human
Pharmac2+ineticsC.



7ee D:TAI!:D
PHARMACO!OG8 Q Human
Pharmac2+inetics

Antih)3ertensi5e A'ents4
Aml2di3ine

,uina3ril

In health) su-Dects at2r5astatin P* (ere
n2 t altered -) the c2ad ministrati2n 2f
!IPITOR 6% m' and aml2di3ine "% m' at
stead) state. N2 a33arent chan'es in >P
2r HR.

7tead)&state Euina3ril d2sin' 2f 6% m'
,D did n2t si'nificantl) affect the P*
3r2file 2f at2r5astatin ta-lets "% m' ,D.
These increases sh2uld -e c2nsidered
(hen selectin' an 2ral c2ntrace3ti5e.

Oral C2ntrace3ti5es and
H2rm2ne Re3lacement
Thera3)
3lasma c2ncentrati2ns BAUC le5elsC 2f
n2rethind2ne -) P$%J and ethin)l
estradi2l -) P0%J f2ll2(in'
c2administrati2n 2f !IPITOR (ith an 2ral
c2ntrace3ti5e c2ntainin' " m'
n2rethind2ne and $1 R' ethin)l estradi2l.
In clinical studies !IPITOR (as used
c2nc2mitantl) (ith estr2'en re3lacement
thera3 ) (ith2ut e5idence t2 d ate 2f
clinicall) si'nificant ad5erse interacti2ns.
Antacids in 3lasma c2ncentrati2ns 2f !IPITOR
-) P$1J f2ll2(in' administrati2n 2f
aluminum and ma'nesium -ased antacids
such as Maal2AS TC 7us3ensi2n.
!D!&C reducti2n (as n2t alteredF TG&
l2(erin' effect 2f !IPITOR ma) -e
affected.
Cimetidine N2 effect 2n 3lasma c2ncentrati2ns 2r
!D!&C l2(erin' efficac) 2f !IPITOR
in TG&l2(erin' effect 2f !IPITOR fr2m
$?J t2 0;J
Diltiazem H)dr2chl2ride 7tead)&state diltiazem increases the
eA32sure -ased 2n AUC! A 7 T s 2f a sin'le
d2se 2f at2r5astatin -) a33r2Aimatel)
1%J.
Anti3)rine !IPITOR had n2 effect 2n the P* 2f Anti3)rine (as used as a n2n&s3ecific
m2del f2r dru's meta-2lized -) the
micr2s2mal he3atic enz)me s)stem
Bc)t2chr2me P&?1% s)stemC.
Interacti2ns (ith 2ther dru's
meta-2lized 5ia the same c)t2chr2me
is2z)mes are n2t eA3ected.
anti3 )rine


Macr2lide Anti-i2tics
Bazithr2m)cin
clarithr2 m)cin
er)thr2m)cinC.
Clarithr2m)cin and
er)thr2m)cin are -2th
C8P$A? inhi-it2rs
In health) adults c2administrati2n 2f
!IPITOR B"% m' ,DC and azithr2m)cin
B1%% m' ,DC did n2t si'nificantl) alter
the 3lasma c2ncentrati2ns 2f at2r5astatin.
7ee <ARNING7 AND
PR:CAUTION7 Muscle :ffectsF
D:TAI!:D PHARMACO!OG8 Q
Human Pharmac2+inetics
3lasma c2ncentrati2n -) P?%J (ith
er)thr2m)cin B1%% m' ,IDC and P6%J
(ith clarithr2m)cin B1%% m' >IDC (hen
c2administered (ith at2r5astatin B"% m'
,DC
Pr2tease Inhi-it2rs
Bnelfina5ir mes)lateC
3lasma c2ncentrati2ns 2f at2r5astatin Nelfina5ir is a +n2(n C8P$A?
inhi-it2r. (hen at2r5astatin "% m' ,D is
c2administered (ith nelfina5ir mes)late
"01% m' >ID
AUC -) #?J and Cma A -) "00J
C)cl2s32rine C2nc2mitant administrati2n 2f In cases (here c2&administrati2n 2f
at2r5astatin (ith c)cl2s32rine is
necessar) the d2se 2f at2r5astatin
sh2uld n2t eAceed "%m'
7ee <ARNING7 and
PR:CAUTION7 & Muscle :ffectsF
D:TAI!:D PHARMACO!OG8 Q
Human Pharmac2+inetics
at2r5astatin "% m' and c)cl2s32rine 1.0
m'H+'Hda) resulted in a #.# f2ld increase
in eA32sure t2 at2r5astatin.
Itrac2naz2le C2nc2 mitant administrati2 n 2f 7ee D:TAI!:D
PHARMACO!OG8 Q Human
Pharmac2+inetics
at2r5astatin 0%&?%m' and itrac2naz2le
0%%m' dail) resulted in a 0.1&$.$&f2ld
increase in at2r5astatin AUC.
!e'end4 HC L h)3erch2lester2lemiaF TG L Tri'l)ceridesF P* L
3harmac2+ineticsF >P L >l22d PressureF HR L
Heart RateF AUC L Area under the cur5e

!rug9-ood Interactions
C2administrati2n 2f 'ra3 efruit Duice has the 32tential t2 increase 3lasma c2 ncentrati2ns 2f HMG
C2A reductase inhi-it2rs includin' !IPITOR. The eEui5alent 2f ".0 litres 3er da) resulted in a
0.1 f2ld increase in AUC 2f at2r5astatin.

!rug9,erb Interactions
Interacti2ns (ith her-al 3r2ducts ha5e n2t -een
esta-lished.

!IPITOR ma) ele5ate serum transaminase and creatine
+inase le5els Bfr2 m s+eletal muscleC. In
the differential dia'n2sis 2f chest 3ain in a 3atient 2n
thera3) (ith !IPITOR cardiac and
n2ncardiac fracti2ns 2f these enz)mes sh2uld -e
determined.

!rug3Laborator5 Test Interactions


!O&$'# $.! $!"I.I&TR$TIO.

Patients sh2uld -e 3laced 2n a standard ch2lester2l&l2(erin' diet Mat
least eEui5alent t2 the
Adult Treatment Panel III BATP IIIC T!C dietN -ef2re recei5in'
!IPITOR and sh2uld
c2ntinue 2n this diet durin' treatment (ith !IPITOR. If a33r23riate a
3r2'ram 2f (ei'ht
c2ntr2l and 3h)sical eA ercise sh2uld -e im3lemented.

Pri2r t2 initiatin' thera3) (ith !IPITOR sec2ndar) causes f2r
ele5ati2ns in 3lasma li3id
le5els sh2uld -e eAcluded. A li3id 3r2file sh2uld als2 -e 3erf2rmed.

Primar) H)3erch2lester2lemia and C2m-ined BMiAedC D)sli3idemia
Includin' 9amilial
C2m-ined H)3erli3idemia

The rec2mmended startin' d2se 2f !IPITOR is "% 2r 0% m' 2nce dail)
de3endin' 2n 3atientTs
!D!&C reducti2n r eEuired Bsee Ta-les $ and ?C. Patients (h2 reEuire a
lar'e reducti2n in !D!&
C Bm2re than ?1JC ma) -e started at ?% m' 2nce dail). The d2sa'e
ran'e 2f !IPITOR is "% t2
6% m' 2nce dail). D2ses can -e 'i5en at an) time 2f the da) (ith 2r
(ith2ut f22d and sh2uld
3refera-l) -e 'i5en in the e5enin'. A si'nificant thera3eutic res32nse is
e5ident (ithin 0 (ee+s
and the maAimum res32nse is usuall) achie5ed (ithin 0&? (ee+s. The
res32nse is maintained
durin' ch r2nic thera3). AdDustments 2f d2sa'e if necessar) sh2uld -e
made at inter5als 2f 0 t2
? (ee+s. The maAimum d2se is 6% m'Hda).

The f2ll2(in' reducti2ns in t2tal ch2lester2l and !D!&C le5els ha5e
-een 2-ser5ed in 0 d2se&
res32nse studies and ma) ser5e as a 'uide t2 treatment 2f 3atients (ith
mild t2 m2derate
h)3erch2lester2lemia4

TA>!: $. D2se&Res32nse in Patients (ith Mild t2 M2derate
H)3erch2lester2lemia
BMean Percent Chan 'e fr2m >aselineCa

LIPITOR !ose (mg3da5)
Li6id Parameter 10 20 40 0
(.J22) (.J20) (.J21) (.J20)
&0. &$$ &$# &?1 T2tal&C4 #." mm2lH!-
B0#$ m'Hd!C-
&$. &?$ &1% &;% !D!&C4 ?.. mm2lH!-
B".% m'Hd!C-
a Results are 322led fr2m 0 d2se&res32nse studies
- Mean -aseline 5alues

The d2sa'e 2f !IPITOR sh2uld -e indi5idualized acc2rdin' the -aseline !D!&C t2tal&CHHD!&C
rati2 andH2r TG le5els t2 achie5e the rec2mmended tar'et li3id 5alues at the l2(est d2se needed
t2 achie5e !D!&C tar'et Bsee Rec2mmendati2ns f2r the Mana'ement 2f D)sli3idemia and the
Pre5enti2n 2f Cardi25ascular Disease MCanad aN summarized -el2( in Ta-le ? andH2r the Third
Re32rt 2f the U7 Nati2nal Ch2lester2l :ducati2n Pr2'ram MNC:P Adult Treatment Panel IIINC


and the 3atientUs res32nse. !i3id le5els sh2uld -e m2nit2red 3eri2dicall) and if necessar) the
d2se 2f !IPITOR adDusted -ased 2n tar'et li3id le5els rec2mmended -) 'uidelines.

Ta-le ?4 Canadian Rec2mmendati2ns f2r the Tar 'et !i3id =alues -ased 2n !e5el 2f Ris+
Ris+ cate'2r) Tar 'et !e5els
!D!&C le5el Bmm2lH!C T2tal&CHHD!&C rati2
Hi'h*
B"%&)ear ris+ 2f CAD G0%J 2r a hist2r ) 2f
dia-etes mellitus** 2r an) ather2scler2tic
diseaseC
O 0.1 and O ?.%
M2derate
B"%&)ear ris+ ""JQ".J C
O $.1 and O 1.%
!2(***
B"%&)ear ris+ V"%JC
O ?.1 and O ;.%
N2te4 !D!&C L l2(&densit) li323r2tein ch2lester2l.

*A32li323r2tein > can -e used as an alternati5e measurement 3articularl) f2 r f2ll2(&u3 2f
3atients treated (ith statins. An 23timal le5el 2f a32li323r2tein > in a 3atient at hi'h ris+ is O%..
'H! in a 3atient at m2derate ris+ O".%1 'H! and in a 3atient at l2( ris+ O".0 'H!.

**Includes 3atients (ith chr2nic +idne) disease and th2se under'2in' l2n'&term dial)sis.

***In the W5er) l2(T ris+ stratum treatment ma) -e deferred if the "%&)ear estimate 2f
cardi25ascular disease is O1J and the !D!&C le5el is O1.% mm2lH!.

7e5ere D)sli3idemias

In 3atients (ith se5ere d)sli3idemias includin' h2m2z)'2us and
heter2z)'2us familial
h)3erch2lester2lemia and d)s-etali323r2teinemia BT)3 e IIIC hi'her
d2sa'es Bu3 t2 6% m'Hda)C
ma) - e reEuired Bsee <ARNING7 AND PR:CAUTION7
Pharmac2+inetic Interacti2ns
Muscle :ffectsF DRUG INT:RACTION7C.

,eteroD5gous -amilial ,56erc4olesterolemia in Pediatric Patients (1091I 5ears o) age)

In t4is 6o6ulation, t4e recommended starting dose o) LIPITOR is 10 mg3da5H t4e ma=imum
recommended dose is 20 mg3da5 (doses greater t4an 20 mg3da5 4ave not been studied in t4is
6atient 6o6ulation)/ !oses s4ould be individualiDed accordin g to t4e recommended go al o)
t4era65 (see .*#P Pediatric Panel 'uidelines, I.!I*$TIO.& $.! * LI.I*$L (&# and
P,$R"$*OLO'2, *linical &tudies)/ $dGustments s4ould be made at intervals o) 4 7ee8s or
more/


NC:P BNati2nal Ch2lester2l :ducati2n Pr2'ramC Pediatric Panel
Guidelines
Classificati2n 2f ch2lester2l le5els in 3ediatric 3atients (ith a familial
hist2r) 2f
h)3erch2lester2lemia 2r 3remature cardi25ascular disease is
summarized -el2(4

Cate'2r) T2tal&C Bmm2lH! !D!&C Bmm2lH! Mm'Hd !NC
Mm'Hd!NC
Acce3ta-le
>2rderline
Hi'h
O?.? M"#%N O0.6 M""%N
?.?&1." M"#%&"..N 0.6&$.$ M""%&"0.N
G1.0 M0%%N G$.? M"$%N

Prevention o) *ardiovascular !isease

*linical trials conducted t4at evaluated atorvastatin in t4e 6rimar
5 6revention o) m5ocardial
in)arction used a dose o) 10 mg atorvastatin once dail5/

-or secondar5 6revention o) m5ocardial in)arction, o6timal dosing
ma5 range )rom 10 mg to 0
mg atorvastatin once dail5, to be given at t4e discretion o) t4e
6rescriber, ta8ing into account t4e
e=6ected bene)it and sa)et5 considerations relevant to t4e 6atient to
be treated/

*oncomitant T4era65

7ee DRUG INT:RACTION7.

!osage in Patients 7it4 Renal Insu))icienc5

&ee :$R.I.'& $.! PR#*$(TIO.&/

OB#R!O&$'#

T4ere is no s6eci)ic treatment )or atorvastatin overdosage/ &4ould an overdose occur, t4e 6atient
s4ould be treated s5m6tomaticall5 and su66ortive measures instituted as reCuired/ !ue to
e=tensive drug binding to 6lasma 6roteins, 4emodial5sis is not e=6ected to signi)icantl5 en4ance
atorvastatin clearance/ (&ee $!B#R&# R#$*TIO.&)

-or t4e management o) a sus6ected drug ov erdose, contact 5our regional Poison *ontrol *entre/
$*TIO. $.! *LI.I*$L
P,$R"$*OLO'2

"ec4anism o) $ction
LIPITOR (atorvastatin calcium) is a s5nt4etic li6id9lo7ering agent/ It is a selective, com6etitive
in4ibitor o) 0945dro=5909met45lglutar5l9coenD5me $ (,"'9*o$) reductase/ T4is enD5me
catal5Des t4e conversion o) ,"'9*o$ to mevalo nate, 74ic4 is an earl5 an d rate9limiting ste6 in
t4e bios5nt4esis o) c4olesterol/


!IPITOR l2(ers 3lasma ch2lester2l and li323r2tein le5els -) inhi-itin'
HMG&C2A reductase
and ch2lester2l s)nthesis in the li5er and - ) increasin' the num-er 2f
he3atic !2( Densit)
!i323r2tein B !D!C rece3t2rs 2n the cell&surface f2r enhanced u3ta+e
and cata-2lism 2f !2(
Densit) !i323r2tein B!D!C.

!IPITOR reduces !D!&Ch2lester2l B!D!&CC and the num-er 2f !D!
3articles. !i3it2r als2
reduces =er) !2( Densit) !i323r2tein&Ch2lester2l B=!D!&CC serum
tri'l)cerides BTGC and
Intermediate Densit) !i323r2teins BID!C as (ell as the num-er 2f
a32li323r2tein > Ba32 >C
c2ntainin' 3 articles -ut increases Hi'h Densit) !i323r2tein&
Ch2lester2l BHD!&CC. :le5ated
serum ch2lester2l due t2 ele5ated !D!&C is a maD2r ris+ fact2r f2r the
de5el23ment 2f
cardi25ascular disease. !2( serum c2ncentrati2n 2f HD!&C is als2 an
inde3endent ris+ fact2r.
:le5ated 3lasma TG is als2 a ris+ fact2 r f2r cardi25ascular disease
3articularl) if due t2
increased ID! 2r ass2ciated (ith decreased HD!&C 2r increased !D!&
C.

:3idemi2l2'ic clinical and eA3erimental studies ha5e esta-lished that
hi'h !D!&C l2( HD!&C
and hi'h 3lasma TG 3r2m2te human ather2scler2sis and are ris+ f
act2rs f2r de5el23in'
cardi25ascular disease. 72me studies ha5e als2 sh2(n that the t2tal
BTCC4HD!&C rati2
BTC4HD!&CC is the -est 3redict2r 2f c2r2nar ) arter ) disease. In
c2ntrast increased le5els 2f
HD!&C are ass2ciated (ith decreased cardi25ascular ris+. Dru'
thera3ies that reduce le5els 2f
!D!&C 2r decrease TG (hile simultane2usl) increasin' HD!&C ha5e d
em2nstrated reducti2ns in
rates 2f cardi25ascular m2rtalit) and m2r-idit).

P4armacod5namics
T4e lo7ering o) total c4olesterol, L!L9* and $6o % 4ave been s4o7n to reduce t4e ris8 o)
cardiovascular events and mortalit5/

LIPITOR (atorvastatin calcium) is a selective, com6etitive in4ibitor o) ,"'9*o$ reductase/ In
bot4 subGects and in 6atients 7it4 4omoD5gous and 4eteroD5gous )amilial 456erc4olesterolemia,
non)amilial )orms o) 4 56erc4olesterolemia, mi=ed d5sli6idemia, 456ertrigl5ceridemia, and
d5sbetali6o6roteinemia, LIPITOR 4as been s4o7n to reduce levels o) total c4olesterol (total9*),
L!L9*, a6o % and total T', and raises ,!L9* levels/

#6idemiologic and clinical studies 4ave associated t4e ris8 o) coronar5 arter5 disease (*$!)
7it4 elevated levels o) total9*, L!L9* and decreased levels o) ,!L9*/ T4ese abnormalities o)
li6o6rotein metabolism are considered as maGor contributors to t4e develo6ment o) t4e disease/
Ot4er )actors, e/g/ interactions bet7een li6ids3li6o6roteins and endot4elium, 6latelets and
macro64ages, 4ave also been incriminated in t4e develo6ment o) 4uman at4erosclerosis and o)
its com6lications/ Regardless o) t4e intervention used (lo79)at3lo79c4olesterol diet, 6artial ileal
b56ass surger 5 or 64armacologic t4er a65), e))ective treatment o) 456erc4olesterolemia3
d5sli6idemia 4as consistentl5 been s4o7n to reduce t4e ris8 o) *$!/

LIPITOR reduces L!L9* and t4e number o) L!L 6articles, lo7ers Ber5 Lo7 !ensit5
Li6o6rotein9*4olesterol (BL!L9*) and serum trigl5ceride, reduces t4e number o) a6o %
containing 6articles, and also increases ,!L9*/ LIPITOR is e))ective in reducing L!L9* in


3atients (ith h2m2z)'2us familial h)3erch2lester2lemia a c2nditi2n that rarel) res32nds t2 an)
2ther li3id&l2(erin' medicati2n. In additi2n t2 the a-25e effects !IPITOR reduces ID!&C and
a32li323r2tein : Ba32 :C in 3atients (ith d)s-etali323r2teinemia BT)3e IIIC.

In 3atients (ith t)3e II h)3erli3idemia at2r5astatin im3r25ed end2thelial d)sfuncti2n.
At2r5astatin si'nificantl) im3r25ed fl2(&mediated end2thelium&de3endent dilatati2n induced -)
reacti5e h)3eremia as assessed - ) -rachial ultras2und B3O%.%"C.

P4armaco8inetics

$bsor6tion+ $torvastatin is ra6idl5 absorbed a)ter oral
administrationH ma=imal 6lasma
concentrations occur 7it4in 1 to 2 4ours/ #=tent o) absor6tion and
6lasma atorvastatin
concentrations increase in 6ro6ortion to atorvastatin dose/
$torvastatin tablets are M19MMF
bioavailable com6ared to solutions/ T4e absolute bioavailabilit5
(6arent drug) o) atorvastatin is
a66ro=imatel5 12F and t4e s5stemic availabilit5 o) ,"'9*o$
reductase in4ibitor5 activit5 is
a66ro=imatel5 00F/ T4e lo7 s5stemic availabilit5 is attributed to
6res5stemic clearance in
gastrointestinal mucosa and3or )irst96ass metabolism in t4e liver/
$lt4oug4 )ood decreases t4e
rate and e=tent o) drug absor6tion b 5 a66ro=imatel5 21 F and
MF, as assessed b5 *ma= and $(*
res6ectivel5, L!L9* reduction and ,!L9* elevation are similar
74en atorvastatin is given 7it4
and 7it4out )ood/ Plasma atorvastatin concentrations are lo7er
(a66ro=imatel5 00F )or *ma= and
$(*) )ollo7ing drug administration in t4e evening com6ared 7it4
morning dosing/ ,o7ever,
L!L9* reduction and ,!L9* elevation are t4e same regardless o)
t4e time o) drug
administration/

!istribution+ "ean volume o) distribution o) atorvastatin is a66ro=imatel5 01 liters/
$torvastatin is JMF bound to 6lasma 6roteins/ $ blood36lasma ratio o) a66ro=imatel5 0/21
indicates 6oor drug 6enetration into red blood cells/ %ased on observations in rats, atorvastatin is
li8el5 to be secreted in 4uman mil8/

"etabolism+ $torvastatin is e=tensivel5 metaboliDed to ort4o9 and
6ara945dro=5lated
derivatives b5 c5toc4rome P9410 0$4 (*2P 0$4) and to various
beta9o= idation 6roducts/
In vitro, in4ibition o) ,"'9*o$ reductase b5 ort4o9 and 6ara9
45dro=5lated metabolites is
eCuivalent to t4at o) atorvastatin/ $66ro=imatel5 I0F o)
circulating in4ibitor5 activit5 )o r ,"'9
*o$ reductase is attributed to active metabolites/ In animals, t4e
ort4o945dro=5 metabolite
undergoes )urt4er glucuronidation/ $torvastatin and its
metabolites are eliminated b5 biliar5
e=cretion/

#=cretion+ $torvastatin is eliminated 6rimaril5 in bile )ollo7ing
4e6atic and3or e=tra4e6atic
metabolismH 4o7ever, t4e drug does not a66ear to undergo
signi)icant entero4e6atic
recirculation/ "ean 6lasma elimination 4al)9li)e o) atorvastatin in
4umans is a66ro=imatel5
14 4ours, but t4e 4al)9li)e )or in4ibitor5 activit5 )o r ,"'9*o$
reductase is 20 to 00 4ours due to
t4e contribution o) longer9lived active metabolites/ Less t4an 2F o)
a dose o) atorvastatin is
recovered in urine )ollo7ing oral administration/

&6ecial Po6ulations and *onditions


Pediatrics+ $ssessment o) 64armaco8inetic 6arameters suc4 as
*ma=, $(* and bioavailabilit5
o) LIPITOR in 6ediatric 6atients (N109E1I 5ears old,
6ostmenarc4e) 7as not 6er)ormed during
t4e K9mont4, 6lacebo9 controlled trial re)erred to earlier (see
*linical &tudies 9 ,eteroD5gous
-amilial ,56erc4olesterolemia in Pediatric Patients and
PR#*$(TIO.& 9 Pediatric (se)/

'eriatrics+ Plasma concentrations o) atorvastatin are 4ig4er
(a66ro=imatel5 40F )or *ma= and
00F )or $(*) in 4 ealt45 elderl5 subGects (age K1 5ears or older)
com6ared 7it4 5ounger
individuals/ L!L9* r eduction, 4o7ever, is com6arable to t4at seen
in 5ounger 6atient
6o6ulations/

'ender+ Plasma concentrations o) atorvastatin in 7omen di))er
(a66ro=imatel5 20F 4ig4er )o r
*ma= and 10F lo7er )or $(*) )rom t4ose in menH 4o7ever, t4ere
is no clinicall5 signi)icant
di))erence in L!L9* reduction bet7een men and 7omen/

Race+ Plasma concentrations o) atorvastatin are similar in blac8
and 74ite subGects/

,e6atic Insu))icienc5+ Plasma concentrations o) atorvastatin are
mar8edl5 increased
(a66ro=imatel5 1K9)old in *ma= and 119)old in $(*) in 6atients
7it4 c4ronic alco4olic liver
disease (*4ilds9Pug4 %)/

Renal Insu))icienc5+ Plasma concentrations and L!L9* lo7ering e))icac5 o) LIPITOR are
similar in 6atients 7it4 moderate renal insu))icienc5 com6ared 7it4 6atients 7it4 normal renal
)unction/ ,o7ev er, since several cases o) r4abdom5ol5sis 4ave been re6orted in 6atients 7it4 a
4istor5 o) renal insu))icienc5 o) un8no7n severit5, as a 6recautionar5 measure and 6ending
)urt4er e=6erience in renal disease, t4e lo7est dose (10 mg3da5) o) LIPITOR s4ould be used in
t4ese 6atients/ &imilar 6recautions a66l5 in 6atients 7it4 severe renal insu))icienc5 >creatinine
clearance E00 mL3min (E0/1 mL3sec)?H t4e lo7est dosage s4ould be used and im6lemented
cautiousl5 (see :$R.I.'& $.! PR#*$(TIO.&, "uscle #))ectsH !R(' I.T#R$*TIO.&H
!O&$'# $.! $!"I.I&TR$TIO.)/


&TOR$'# $.! &T$%ILIT2

&tore at controlled room tem6erature 11 to 00O*/

&P#*I$L ,$.!LI.' I.&TR(*TIO.&

.ot a66licable/

!O&$'# -OR"&, *O"PO&ITIO. $.! P$*@$'I.'

!osage -orms
!IPITOR Bat2r5astatin calciumC ta-lets are f2rmulated f2r 2ral administrati2n and are a5aila-le
in ta-let d2ses 2f "% m' 0% m' ?% m' and 6% m'.

Tablet *om6osition
#ac4 tablet contains eit4er 10 mg, 20 mg, 40 mg or 0 mg
atorvastatin as t4e active ingredient/
#ac4 tablet also contains t4e )ollo7ing non9medicinal ingredients+
calcium carbonate,
croscarmellose sodium, 45dro=56ro65l cellulose, 45dro=56ro65l
met45lcellulose, lactose
mono45drate, magnesium stearate, microcr5stalline cellulose,
6ol5et45lene gl5col, 6ol5sorbate
0, simet4icone emulsion, talc, and titanium dio=ide/ T4e 10mg,
20mg, and 40mg tablets also
contain candelilla 7a=/

LIPITOR (atorvastatin calcium) is available in dosage strengt4s o)
10 mg, 20 mg, 40 mg and 0
mg atorvastatin 6er tablet/

Pac8aging
"% m'4 <hite elli3tical film&c2ated ta-let c2ded X"%X 2n 2ne side and
XPD "11X 2n the 2ther.
A5aila-le in -2ttles 2f .% ta-lets.

0% m'4 <hite elli3tical film&c2ated ta-let c2ded X0%X 2n 2ne side and
XPD "1;X 2n the 2ther.

?% m'4 <hite elli3tical film&c2ated ta-let c2ded X?%X 2n 2ne side and
XPD "1#X 2n the 2ther.

6% m'4 <hite elli3tical film&c2ated ta-let c2ded X6%X 2n 2ne side and
XPD "16X 2n the 2ther.
A5aila-le in -listers 2f $% ta-lets B$ stri3s @ "%C.


P$RT II+ &*I#.TI-I* I.-OR"$TIO.

P,$R"$*#(TI*$L
I.-OR"$TIO.

!rug &ubstance

Pro6er name+ $torvastatin calcium

*4emical name+ >R9(R*,R*)?929(49)luoro64en 5l)9P,d 9di45dro=5919(19met45let45l)9
$&3hen)l&?&MB3hen )lamin2Ccar-2n)lN&"H&3)rr2le&"&he3tan2ic acid calcium salt B04"C
trih)drate

:m3irical 92rmula4 BC$$H$?9N0O1C0CaI$H0O

M2lecular <ei'ht4 "0%..?0
7tructural f2rmula4
9
OH OH O
CaKK O& N
I$H0O
H
N
O
0

Descri3ti2n4 At2r5astatin calcium is a (hite t2 2ff&(hite cr)stalline
32(der that is 3racticall)
ins2lu-le in aEue2us s2luti2ns 2f 3H ? and -el2(. At2r5astatin calcium
is 5er) sli'htl) s2lu-le in
distilled (ater 3H #.? 3h2s3hate -uffer and acet2nitrile sli'htl)
s2lu-le in ethan2l and freel)
s2lu-le in methan2l.


*LI.I*$L TRI$L&

,56erc4olesterolemia

!IPITOR Bat2r5astatin calciumC has -een sh2(n t2 si'nificantl)
im3r25e li3id 3r2files in a
5ariet) 2f d )sli3idemic c2nditi2ns. !IPITOR has -een sh2(n t2 -e
hi'hl) effecti5e in reducin'
t2tal and !D!&ch2lester2l and tri'l)cerides and a32li323r2tein > in
3atients (ith 3rimar)
h)3erch2lester2lemia familial and n2n&familial h)3erch2lester2lemia
and miAed
h)3erli3idemia includin' familial c2m-ined h)3 erli3idemia and
3atients (ith n2n&insulin
de3endent dia-etes mellitus BNIDDMC.

In 0 multicenter 3lace-2&c2ntr2lled d2u-le&-lind d2se&res32nse studies
in 3atients (ith mild t2
m2derate h)3erch2lester2lemia B9redric+s2n t)3es IIa and II-C
!IPITOR 'i5en as a sin'le dail)
d2se 25er ; (ee+s reduced t2tal&C !D!&C a32 > and TGF HD! (as
increased BTa-le 1C. A
thera3eutic res32nse (as e5ident (ithin 0 (ee+s and the maAimum
res32nse (as usuall)
achie5ed (ithin 0&? (ee+s.

TA>!: 1. D2se&Res32nse in Patients (ith Mild t2 M2derate H)3erch2lester2lemia
B9redric+s2n T)3es IIa and II-C
BMean Percent Chan 'e fr2m >aselineCa
LIPITOR
!ose . Total9* L!L9* $6o % T' ,!L9*
(mg3da5)
0"
00
Place-2 K? K? K$ K"% &$
"% &0. &$. &$0 &". K;
0%
?%
6%
0%
0"
0$
K.
K;
K1
&$$
&$#
&?1
&?$
&1%
&;%
&$1
&?0
&1%
&0;
&0.
&$#
a Results are 322led fr2m 0 d2se&res32nse studies
In a 322led data set fr2m 0? c2ntr2lled clinical trials in 3atients (ith
3rimar)
h)3erch2lester2lemia Bt)3e IIaC and miAed Bc2m-inedC d)sli3idemia
Bt)3e II-C !IPITOR
increased HD! C -) 1J t2 6J fr2m -aseline at each d2se tested B"%
0% ?% and 6% m' ,DC
BTa-le ;C. In 3atients (ith HD! C O %.. mm2lH! Ba c2nditi2n 2ften
2-ser5ed in 3ers2ns (ith the
meta-2lic s)ndr2meC M see INDICATION7 AND C!INICA! U7:N
!IPITOR raised HD!&C #J
t2 "?J. These chan'es (ere inde3endent 2f the d2se administered.
!IPITOR als2 decreased
t2tal&CHHD!&C !D!&CHHD!&C and n2n&HD!&CHHD!&C rati2s fr2m
-aseline in a d2se
de3endent manner BTa-le ;C. !IPITOR B"% 0% ? % and 6% m' ,DC
increased HD!&C le5els
fr2m -aseline f2r -2th men and (2men.


TA>!: ;. AdDusteda Mean Percent Chan'es fr2m >aseline
in HD!&C T2tal&CHHD!&C !D!&CHHD!&C
N2n&HD!&CHHD!&C and HD! L C %.. mm2lH!
f2r Patients- <ith Mild t2 M2derate H)3erch2lester2lemia
B9redric+s2n T)3 es IIa and II-C

LIPITOR . ,!L9* To tal9*3 L!L9*3 .on ,!L9*3 ,!L9*
!ose (all 6atients) ,!L9* ,!L9* ,!L9*
(baseline J 0/M
(mg3da5) mmol3L) (.)
Place-2 01% K%.0Y K0.6Y
&0..$Z
&$;.%Z
&$6..Z
&?$.1Z
K$.6Y K$.1Y
&$1.1Z
&?$.%Z
&?#."Z
&10.?Z
K;.0* B"#C
"%
0%
?%
6%
"6#" K;.?
K#.6
K#."
K1.%
&$#.%Z
&??."Z
&?..;Z
&11.$Z
K"$.6 B0?6C
"?#
""1
$"6
K6.$ B0%C
K6.; B6C
K#." B16C

a !east sE uares means fr2m ANCO=A m2del (ith stud) treatment and -aseline
- Data 322led fr2m 0? c2ntr2lled studies
Zsi'nificant linear d2se trend
Y si'nificantl) different fr2m !IPITOR "% m' B3O%.%"C
* si'nficantl) different fr2m !IPITOR "% m' B3O%.%1C

In an2ther multicenter 3lace-2 c2ntr2lled d2u-le -lind trial in 3atients (ith
h)3ertri'l)ceridemia !IPITOR l2(ered tri'l)cerides in a d2se related manner (ith2ut causin'
a redistri-uti2n 2f tri'l)cerides int2 5ari2us li323r2tein fracti2ns BTa-le #C.

TA>!: #. :fficac) in Patients (ith H)3ertri'l)ceridemia
BMean Percent Chan'e fr2m >aselineC

LIPITOR . BL!L9* Total9 BL!L9 L!L9* T' ,!L9* $6o %
!ose * T'
(mg3da5)
Place-2 "0 &0.% K%.$ &;.; K".? &1.$ K0.? K0.#
1 "" &$?.%* &"...* &06.# &"0.#* &0#.$ K#." &"1.?*
0% "0 &?;.%* &$$."* &$1.#* &$"."* &$$.#* K"%.; &$0.#*
6% "" &1?&0* &?".$* &?$.;* &$;."* &?0.?* K"".6* &$6.#*
* 7i'nificantl) different fr2m 3lace-2 3O%.%1

C2m3aris2n 2f 322led data -) 9redric+s2n t)3es sh2(s similar
reducti2ns f2r T)3 e IIa and II-
3atients in t2tal&C !D!&C and a32 >F h2(e5er T)3e II- 3atients and
T)3es I= 3atients
eA3erience a 'reater 3ercent decr ease in =!D!&C and TG le5els
BTa-le 6C.


TA>!: 6. :fficac) in Patients -) 9redric+s2n T)3ea
LIPITOR 10 mg3da5
Li6id Parameter T56e IIa T56e IIb T56e IB
(. J M01) (. J 110) (. J 2M)
!D!&C &$; &$1 &0;
A32 >
&06 &06 &01
T2tal&Cl &0# &0# &01
TG
&"? &0? &0.
=!D!&C &"1 &06 &?"
HD!&C K; K"% K"$
A32 >HHD!&C &$" &$? &$$
N2n&HD!&CHHD!&C &$# &$6 &$6
a P22led dataset

In a 3il2t stud) 2f 6 3atients (ith h2m2z)'2us familial
h)3erch2lester2lemia the mean decrease
in !D!&C (ith 6% m'Hda) !IPITOR (as $%J f2r 3atients n2t 2n
3lasma3heresis and $"J f2r
3atients (h2 c2ntinued 3lasma3heresis. A !D!&C l2(erin' 2f $1J (as
2-ser5ed in rece3t2r
defecti5e 3atients BnL;C and 2f ".J in rece3t2r ne'ati5e 3atients BnL0C.
All 3atients als2
eA3erienced decreases in t2tal&C a32 > !D!&CHHD!&C and n2n&HD!&
CHHD!&C rati2s BTa-le
.C.

Ta-le .. Patients (ith H2m2z)'2us 9H
BMean Per cent Chan'e fr2m >aseline After 6 <ee+sC

Li6id Parameter
LIPITOR 0 mg3da5
$ll Patients
(.J)
Patients .ot on
Plasma64eresis
(.J0)
Patients on
Plasma64eresis
(.J1)
T2tal&C &0. &0. &0.
!D!&C &$" &$% &$"
A32 > &06 &"# &$?
TG &0% &?" &6
!D!&CHHD!&C Rati2 &0$ &". &01
N2n HD!&CHHD!&C
Rati2
&00 &". &0?

In an 23en la-el stud) ;. 3atients B0&;" )ears 2f a'eC (ith h2m2z)'2us familial
h)3erch2lester2lemia and .0 3atients (ith se5ere h)3erch2lester2lemia (h2 had L"1J res32nse
t2 maAimum c2m-inati2n thera3) recei5 ed !IPITOR "% t2 6% m'Hda). M2st 3atients -e'an
!IPITOR treatment (ith ?% m'Hda) -ut se5erel) de-ilitated and 5er) )2un' 3atients -e'an
treatment (ith "% m'Hda). !IPITOR (as titrated at ?&(ee+ inter5als t2 L6 % m'Hda). The mean
reducti2n in !D!&C f2r ;. 3atients dia'n2sed (ith h2m2z)'2us familial h)3erch2lester2lemia
(as 00J. Ta-le "% sh2(s the mean 3ercent chan'e in li3id 3arameters. In 0 rece3t2r&ne'ati5e
3atients mean !D!&C reducti2n (as ".J. 7iA 3atients had less than a "%J res32nse t2
treatment.


Ta-le "%. Patients (ith H2m2z)'2us 9H 2r 7e5ere
N2nres32nsi5e H)3erch2lester2lemia
BMean Percent Chan'e fr2m >aseline after 6 <ee+sC

!IPITOR 6% m'Hda)

7e5ere Unres32nsi5e
H)3erch2lester2lemia BNL.0C
Li6id Parameter
H2m2z)'2us 9H
BNL;.a C

T2tal&C

&0"J

&$?J
!D!&C

&00J

&$.J
TG

&.J

&0.J
HD!&C

K$J

K;J
a Data a5aila-le fr2 m ;6 3atients

In a "&)ear stud) in 3atients (ith heter2z)'2us familial h)3erch2lester2lemia !IPITOR
m2n2thera3 ) B6% m'Hda)C (as c2m3ared (ith c2m-inati2n thera3) 2f c2lesti32l B"% ' >IDC 3lus
!IPITOR B?% m'Hd a). The 0 treatments 3r2duced similar effects 2n t2tal&C !D!&C TG
=!D!&C a32 > and HD!&CF h2(e5er !IPITOR m2n2thera3 ) (as m2re effecti5e than
!IPITOR 3lus c2lesti32l in decreasin' TG le5els BTa-le ""C.

TA>!: "". :fficac) in Patients (ith Heter2z)'2us 9amilial
BMean Percent Chan 'e fr2m >aseline after 10 <ee+sC

LIPITOR LIPITOR 40 mg3da5
Li6id Parameter 0 mg3da5 Plus
*olesti6ol 10 g %I!
BNL"6.C BNL"0?C
TOTA!&C &?? &?0
!D!&C &1$ &1$
=!D!&C &$$ &"#
HD!&C K# K.
TG &$$a &"#
n2n&HD!HHD!&C Rati2 &1$ &10
A32 > &?; &?1
a 7i'nificantl) different fr2m !IPITOR 3lus c2lesti32l B3 O%.%1C
ANCO=A.

A c2m3aris2n 2f results in 3atients (ith heter2z)'2us familial and n2n&
familial
h)3erch2lester2lemia sh2(s similar ma'nitudes 2f reducti2ns in !D!&
C a32 > and n2n&HD!&
CHHD!&C rati2 in -2th 3atient 323ulati2ns BTa-le "0C.


Ta-le "0. :fficac) in Heter2z)'2us 9H and N2n 9H PatientsZ
BMean Percent Chan'e fr2m -aselineC

Li6id Parameter P4enot56e LIPITOR
"%Hm'Hda) 6% m'Hda)
!D!&C Heter2z)'2us 9H &$; BNL"?%C
&$; BNL"0"1C
&1$ BNL"1?C
&10 BNL";;C
N2n 9H

A32 > Heter2z)'2us 9H &0# BNL"$?C
&06 BNL""?.C
&?; BNL"1$C
&?; BNL"??C N2n 9H

N2n HD!&CHHD!&C
Rati2
Heter2z)'2us 9H
N2n 9H
&$# BNL"?%C
&$# BNL"0"1C
&1$ BNL"$0C
&1? BNL";;C

ZData fr2m se5eral studies

C2m3aris2n 2f results in 3atients (ith and (ith2ut familial c2m-ined
h)3 erli3idemia B9CHC
dem2nstrated that !IPITOR l2(ered !D!&C a32 > t2tal&C =!D!&C
TG and the n2n&
HD!&CHHD!&C r ati2 t2 a similar eAtent in -2th 3atient 323ulati2ns
BTa-le "$C.

Ta-le "$. :fficac) in Patients <ith and <ith2ut 9CHZa

Li6id Parameter LIPITOR 10 mg3da5
-*,
(. J I94)
.on9-*,
(. J 10491224)
T2tal&C
!D!&C
TG
HD!&C
A32 >
=!D!&C
N2n HD!&CHHD!&C
Rati2
!D!&CHA32 > rati2
&0;J
&$?J
&0"J
K6J
&0;J
&01J
&$;J
&.J
&0#J
&$;J
&"#J
K#J
&06J
&"6J
&$#J
&""J
ZData fr2m se5eral studies
a The f2ll2(in' criteria (ere used t2 define 3atients (ith 9CH4 first de'ree relati5e (ith li3id
dis2rder TG G01% m'Hd! BG0.6 mm2lH!C =!D! G?1 m'Hd! BG"."; mm2lH!C HD! O$1 m'Hd!
BO%.. mm2lH!C BmenC 2r O?1 m'Hd! BO"."; mm2lH!C B(2menC.


In an 23en&la-el rand2mised cr2ss&25er stud) in 3atients (ith
d)s-etali323r2teinemia
BT)3e IIIC !IPITOR 6% m'Hda) resulted in a si'nificantl) 'reater
reducti2n in serum li3ids than
either !IPITOR "% m'Hda) 2r 'emfi-r2zil "0%% m'Hda) BTa-le "?C.

Ta-le "?. :fficac) in Patients (ith T)3e III H)3erli323r2teinemia B9amilial
D)s-etali323r2teinemiaC
Mean Percent Chan'e fr2m >aseline
LIPITOR LIPITOR 'em)ibroDil
Li6id 6arameter 10 mg3da5 0 mg3da5 1200 mg3da5
. J 11 . J 1K . J 1K
T2tal&C
!D!&C
TG
=!D!&C
&?% &$? &1#a
K6; K0%a &;a
&1; &10
&$1
&?%a
&$0 &1.a
ID!&C
ID!&C K =!D!&C
HD!&C
A32 > Bt2talC
&"$ &06a &1%a
&16a
K"$
&;;a
&$? &$$
K""
K$
&?# &1$
A32&C III
A32&:
&";
&0#
&$" &"0
&0?
&?"a
a si'nificantl) different fr2m 'emfi-r2zil 3O%.%1 BANO=AC

In a ;&m2nth d2u-le&-lind stud ) in 3atients (ith h)3erli3idemia and
n2n&insulin de3endent
dia-etes mellitus BNIDDMC !IPITOR B"% 2r 0% m'Hda)C l2(ered t2tal
ch2lester2l -) 0#J
!D!&C -) $?J a32 > -) $%J TG -) 0?J and increased HD!&C -)
"0J BTa-le "1C.

TA>!: "1. :fficac) in Patients (ith NIDDM
BMean Percent Chan'e 9r2m >aselineC
LIPITOR
Li6id Parameter 10 or 20 mg3da5
NL6?
T2tal&C &0#
!D!&C &$?
=!D!&C &$1
TG &0?
=!D!&TG &0;
HD!&C K"0
A32 > &$%

In three d2u-le&-lind multicenter studies in 3atients (ith mild t2 m2derate
h)3erch2lester2lemia the num-er 2f 3atients meetin' NC:P tar'et !D!&C le5els 2n !IPITOR


(as assessed 25er a "&)ear 3eri2d. After "; (ee+s -et(een ?;&#?J 2f
3atients recei5in'
"% m'Hda) !IPITOR reached tar'et !D!&C le5els. The efficac) 2f
!IPITOR B"% 2r 0% m'Hda)C
(as maintained 25er 10 (ee+s (ith -et(een 1%&#6J 2f 3atients
achie5in' their !D!&C tar 'et
le5els.

The effect 2f !IPITOR (as e5aluated in c2m3arati5e clinical trials (ith
l25astatin sim5astatin
and 3ra5astatin. 92r inf2rmati2n 2n these results 3lease refer t2
R:9:R:NC:7.

In a "&)ear stud) in 32stmen23ausal (2men (ith 3rimar)
h)3erli3idemia !IPITOR
m2n2thera3 ) B"% m'Hda)C (as c2m3ared (ith estradi2l m2n2thera3)
B" m'Hda)C and (ith
c2m-inati2n thera3) 2f !IPITOR "% m'Hda) 3lus estradi2l " m'Hda)
BTa-le ";C. !IPITOR
m2n2thera3) B"% m'Hda)C (as si'nificantl) m2re effecti5e in l2(erin'
t2tal&C !D!&C =!D!&
C TG a32 > and n2n&HD!&CHHD!&C rati2 than estradi2l m2n2thera3)
B" m'Hda)C. 92r
c2m-inati2n thera3) B!IPITOR 3lus estradi2lC reducti2ns in t2tal&C
!D!&C =!D!&C !3BaC
a32 > and n2n HD!&CHHD!&C rati2 (ere similar c2m3ared (ith
!IPITOR m2n2thera3).
H2(e5er HD!&C le5els (ere si'nificantl) hi'her f2r c2m-inati2n
thera3) c2m3ared (ith
!IPITOR m2n2thera3). TG le5els (ere l2(er (ith !IPITOR
m2n2thera3 ) c2m3ared (ith
c2m-inati2n thera3). Ad5erse reacti2ns (ere similar in t)3e and
incidence f2ll2(in'
c2m-inati2n thera3) B!IPITOR 3lus estradi2lC c2m3ared (ith estradi2l
m2n2thera3).

TA>!: ";. :fficac) in P2st&men23ausal <2men
BMean Per cent C han'e fr2m >aseline After 10 <ee+sC

LIPITOR #stradiol Li6itor 10 mg3da5
Li6id Parameter 10 mg3da5 1 mg3da5 Plus
#stradiol (1mg3da5)
BNL$6C BNL";C BNL0"C
TOTA!&C &0. &"a &0#
!D!&C &?% &1a &?0
=!D!&C &$0 K"$a &0%
HD!&C K6 K"" K0%a
TG &0# K1a &"$a
n2n&HD!HHD!&C Rati2 &?$ &"0a &?6
A32 > &$? &$a &$?

In a c2m3arati5e stud) (ith niacin in 3atients (ith
h)3erch2lester2lemia and miAed
h)3erli3idemia B9redric+s2n t)3es IIa and II-C and
h)3ertri'l)ceridemia B9rederic+s2n T)3e I=C
!IPITOR B"% m'Hd a)C had 'reater ch2lester2l&l2(erin'
efficac) B 'reater decreases in !D!&C
a32 > !D!&a32 >C (hile niacin B$ 'Hda)C had 'reater
tri'l)ceride&l2(erin' efficac) B'reater
decreases in TG =!D!&TG HD!&TG =!D!&a32 >C.
!IPITOR (as -etter t2lerated -) 3atients
c2m3ared (ith niacin BTa-le "#C.

a 7i'nificantl) different fr2 m !IPITOR m2n2thera3 ) B3 O%.%1C ANCO=A.


Ta-le "#. !IPITOR 5ersus Niacin

-redric8son T56es IIa and IIb -redric8son T56e IB

Parameter $torvastatin .iacin $torvastatin .iacin
10 mg 0 g3da5 10 mg 0 g3da5
(. J 40) (. J 0M) (. J 11) (. J 12)

!D!&C &$$* &6 &"1* K"?
A32 >

&$%* &"; &0$* &$
T2tal&C

&06* &"" &0;* %
TG

&"; &0.* &$; &0.
HD!&C

K? K0#* K? K01
=!D!&C

&06 &$. &?$ &$;
N2n&HD!&CHHD!&C

&$? &$0 &$? &".
A32 >HHD!

&$0 &$" &06 &"6
* 7i'nificant difference -et(een treatments ANCO=A 3 O%.%1.

In a c2m3arati5e stud) (ith fen2fi-rate in 3atients (ith c2m-ined
h)3erli3idemia 2r
h)3ertri'l)ceridemia !IPITOR B0% m'Hda)C (as m2re effecti5e in
l2(erin' !D!&C a32 > and
t2tal ch2lester2l le5els c2m3ared t2 fen2fi-rate B"%% m' TIDC.
Treatment (ith !IPITOR als2
resulted in clinicall) si'nificant reducti2ns in TG and =!D!&C and
increases in HD!&C le5els
alth2u'h n2t t2 the same eAtent as (as seen (ith f en2fi-rate. !IPITOR
thera3) resulted in a
-etter reducti2n 2f the n2n&HD!&CHHD!&C rati2 (hich ma) -e a '22d
indicat2r 2f 25erall li3id&
re'ulatin' -enefit. !IPITOR (as als2 -etter t2lerated c2m3ared (ith
fen2fi-rate BTa-le "6C.

Ta-le "6. !IPITOR 5ersus 9en2fi-rate
Mean Percent Chan'e 9r2m >aseline After 0? <ee+s
-redric8son T56es IIa and IIb -redric8son T56e IB
Parameter $torvastatin -eno)ibra te $torvastatin -eno)ibrate
20 mg 000 mg 20 mg 000 mg
(. J 0K) (. J 00) (. J M) (. J )
!D!&C &$.* &# &06 * K0#
A32 > &$;* &"# &0# &.
T2tal&C &$?* &"? &0; &"$
TG &0# &$. &$? &1#*
HD!&C K. K00* K6 K$%*
=!D!&C &$. &1% &$; &#$*
N2n&HD!&CHHD!&C &??* &$0 &$; &$1
* 7i'nificant difference -et(een treatments ANCO=A 3 O%.%1.

Heter2z)'2us 9amilial H)3erch2lester2lemia in Pediatric Patients4

In a d2u-le&-lind 3lace-2&c2ntr2lled stud ) f2 ll2(ed -) an 23en&la-el 3hase "6# -2)s and
32stmenarchal 'irls "%&"# )ears 2f a'e Bmean "?." )earsC (ith heter2z)'2us familial


h)3erch2lester2lemia B9HC 2r se5 ere h)3erch2lester2lemia (ere rand2mized t2 !IPITOR
BnL"?%C 2r 3lace-2 BnL?#C f2r 0; (ee+s after that all recei5ed !IPITOR f2r 0; (ee+s.
Inclusi2n in the stud) reEuired "C a -aseline !D!&C le5el G ?.. mm2lH! B".% m'Hd!C 2r 0C a
-aseline G ?." mm2lH! B";% m'Hd!C and 32siti5e famil) hist2r) 2f 9H 2r d2cumented 3remature
cardi25ascular disease in a first& 2r sec2nd&de'ree relati5e.

Ta-le ".4 :ffect 2f !IPITOR 2n !D!&C TC and TG in a c2ntr2lled trial 2f
; m2nths durati2n in ad2lescent -2)s and 32stmenarchal 'irls "%&"#
)ears 2f a'e BNL"6#C (ith heter2z)'2us familial
h)3erch2lester2lemia at a d2se 2f "% and 0% m'.
. $ge !ose F *4ange
L!L9* T* T'
22 10910 10 mg 90I/1 92M/0 9M/2
40 1491I 10 mg 90/2 92M/4 9K/M

00 10910 20 mg 942/1 904/0 910/0
40 1491I 20 mg 940/0 900/0 91/0

The mean -aseline !D!&C 5alue (as 1.# mm2lH! B0"6.; m'Hd!C Bran'e4 $.;&"%.% mm2lH!
M"$6.1&$61.% m'Hd!NC in the !IPITOR 'r2u3 c2m3ared t2 1.. mm2lH! B0$%.% m'Hd!C Bran'e4
?."&6.? mm2lH! M";%.%&$0?.1 m'Hd!NC in 3lace-2 'r2u3. The d2sa'e 2f !IPITOR B2nce dail)C
(as "% m' f2r the first ? (ee+s and u3&titrated t2 0% m' if the !D!&C le5el (as G$.? mm2lH!
B"$% m'Hd!C. The num-er 2f !IPITOR&treated 3atients (h2 reEuired u3&titrati2n t2 0% m' after
<ee+ ? durin' the d2u-le&-lind 3hase (as 6% B1#."JC.

!IPITOR si'nificantl) decreased 3lasma le5els 2f t2tal&C !D!&C
tri'l)cerides and
a32li323r2tein > durin' the 0; (ee+ d2u-le&-lind 3hase Bsee Ta-le ".
and Ta-le 0%C.

TA>!: 0%. !i3id&l2(erin' :f fects 2f At2r5astatin in Ad2lescent >2)s
and Girls (ith
Heter2z)'2us 9amilial H)3erch2lester2lemia 2r 7e5ere
BMean Percent Chan'e fr2m >aseline at :nd32int in Intenti2n&t2&Treat
P23ulati2nC

!osage . Total9* L!L9* ,!L9* T' $6oli6o6rotein %
Place-2 ?# &".1 &%.? &".. " %.#
At2r5astatin "?% &$".? &$..; 0.6 &"0 &$?

The mean achie5ed !D!&C 5alue (as $.6 mm2lH! B"$%.# m'Hd !C Bran'e4 ".6&;.$ mm2lH! M#%.%&
0?0.% m'Hd!NC in the !IPITOR 'r2u3 c2m3ared t2 1.. mm2lH! B006.1 m'Hd!C Bran'e4 $..&"%.%
mm2lH! M"10.%&$61.% m'Hd!N C in the 3lace-2 'r2u3 durin' the 0; (ee+ d2u-le&-lind 3hase. The
safet) and t2lera-ilit) 3r2file 2f !IPITOR "% t2 0% m' dail) (as similar t2 that 2f 3lace-2.

In this c2ntr2lled stud) there (as n2 effect 2n 'r2(th 2r seAual maturati2n in -2)s and in 'irls
as measured -) Tanner sta'in' durin' 0; (ee+s. The 3r232rti2n 2f su-Dects (h2 had an increase
in Tanner sta'e -et(een -aseline and (ee+ 0; 2f the d2u-le&-lind 3hase (as similar f2r the


at2r5astatin and 3lace-2 'r2u3s B06J and $" J res3ecti5el)F P L %.#C. N2 s3ecific
d2cumentati2n 2f menstrual c)cle (as rec2rded. !IPITOR had n2 effect 2n 3lasma le5els 2f !H
97H c2rtis2l test2ster2ne and deh)dr2e3iandr2ster2ne. :ffect 2f treatment 2n c2'niti5e
functi2n (as n2t ca3tured durin' the c2urse 2f this stud).

!IPITOR has n2t -een studied in c2ntr2lled clinical trials in52l5in' 3re&3u-ertal 3atients 2r
3atients )2un'er than "% )ears 2f a'e. Th e safet) and efficac) 2f d2ses a-25e 0% m' ha5e n2t
-een studied in c2ntr2lled trials in children.

Prevention o) *ardiovascular
!isease

In the An'l2&7candina5ian Cardiac Outc2mes Trial BA7COTC the
effect 2f !IPITOR
Bat2r5astatin calciumC 2n fatal and n2n& fatal c2r2nar) heart disease (as
assessed in "%$%1
h)3ertensi5e 3atients ?%&6% )ears 2f a'e Bmean 2f ;$ )earsC (ith2ut a
3re5i2us m)2cardial
infarcti2n and (ith TC le5els O;.1 mm2lH!. Additi2nall) all 3atients
had at least $ 2f the
f2ll2(in' cardi25ascular ris+ fact2rs4 male 'ender B6"."JC a'e G11
)ears B6?.1JC sm2+in'
B$$.0JC dia-etes B0?.$JC hist2r) 2f CHD in a first&de'ree relati5e
B0;JC TC4HD! G ;
B"?.$JC 3eri3heral 5ascular disease B1."JC left 5entricular
h)3ertr23h) B"?.?JC 3ri2r
cere-r25ascular e5ent B..6JC s3ecific :CG a-n2r malit) B"?.$JC
3r2teinuriaHal-uminuria
B;0.?JC. In this d2u-le&-lind 3lace-2&c2ntr2lled stud) 3atients (ere
tr eated (ith anti&
h)3ertensi5e thera3 ) BG2al >P O"?%H.% mm H' f2r n2n&dia-etic
3atients O"$%H6% mm H' f2r
dia-etic 3atientsC and all2cated t2 either !IPITOR "% m' dail)
BnL1";6C 2r 3lace-2 BnL1"$#C
usin' a c25ariate ada3ti5e meth2d (hich t22+ int2 acc2unt the
distri-uti2n 2f nine -aseline
characteristics 2f 3atients alread) enr2lled and minimized the
im-alance 2f th2se characteristics
acr2ss the 'r2u3s. Patients (ere f2ll2(ed f2r a median durati2n 2f $.$
)ears.

The effect 2f "% m'Hda) 2f !IPITOR 2n li3id le5els (as similar t2 that
seen in 3re5i2us clinical
trials.

!IPITOR si'nificantl) reduced the rate 2f c2r2nar) e5ents Meither fatal
c2r2nar) heart disease
B?; e5ents in the 3lace-2 'r2u3 5s ?% e5ents in the !IPITOR 'r2u3C 2r
n2nfatal MI B"%6 e5ents
in the 3lace-2 'r2u3 5s ;% e5ents in the !IPITOR 'r2u3 CN (ith an
a-s2lute ris+ reducti2n 2f
"."J and a relati5e ris+ reducti2n 2f $;J B-ased 2n incidences 2f "..J
f2r !IPITOR 5s $.%J
f2r 3lace-2C 3L%.%%%1 Bsee 9i'ure "CN. This ris+ reducti2n )ields a


-igure 1+ #))ect o) LIPITOR 10 mg3da5 on *umulative Incidence o) .on)atal "5ocardial
In)arction or *oronar5 ,eart !isease !eat4 (in $&*OT9LL$)

In the C2lla-2r ati5e At2R5astatin Dia-etes 7tud) BCARD7C the effect 2f !IPITOR Bat2r5astatin
calciumC 2n c2r2nar) heart disease BCHDC and n2n&CHD end32ints (as assessed in 06$6 men
B;6JC and (2men B$0JC a'es ?%&#1 (ith t)3e 0 dia-etes -ased 2n <HO criteria (ith2ut 3ri2r
hist2r) 2f cardi25ascular disease and (ith !D! O ?."? mm2lH! and TG O ;.#6 mm2lH!. In
additi2n t2 t)3e 0 dia-etes su-Dects had 2ne 2r m2re 2f the f2ll2(in' CHD ris+ fact2rs4 cu rrent
sm2+in' B0$JC h)3ertensi2n B6%JC retin23ath) B$%JC micr2al-uminuria B.JC 2r
macr2al-uminuria B$JC. In this multicenter 3lace-2&c2ntr2lled d2u-le -lind clinical trial 2f
3rimar) 3re5enti2n 2f fatal and n2nfatal cardi25ascular and cere-r25ascular disease in su-Dects
(ith t)3e 0 dia- etes and " 2ther CHD ris+ fact2r 3atients (ere rand2ml) all2cated t2 either
!IPITOR "% m' dail) B"?0.C 2r 3lace-2 B"?""C in a "4" rati2.

Patients (ere f2ll2(ed f2r a median durati2n 2f $.. )ears. Due t2 si'nificant treatment -enefits
B3O%.%%%1 2ne&sided in fa52r 2f !IPITORC seen earl) in the stud ) the stud) (as st233ed -) the
CARD7 7teerin' C2mmittee t(2 )ears earlier than antici3ated.

>aseline characteristics 2f su-Dects (ere4 mean a'e 2f ;0 )ears mean H-A"c #.#JF median
!D!&C $."% mm2lH!F median TC 1.$1 mm2lH!F median TG ".#% mm2lH!F median HD!&C ".$?
mm2lH!.

The effect 2f !IPITOR "% m'Hda) 2n li3id le5els (as similar t2 that seen in 3re5i2us clinical
trials.

Treatment (ith !IPITOR (as ass2ciated (ith a statisticall) si'nificant $#J relati5e ris+
reducti2n BRRRC 2r $.0J a-s2lute ris+ reducti2n BARRC in the rate 2f maD2r cardi25ascular
e5ents. :fficac) anal)sis sh2(ed that 6$ B1.6JC 2 f !IPITOR treated 3atients and "0# B..%JC 2f

3lace-2 treated 3atients eA3erienced their first 3rimar) clinical
end32int. C2m3aris2n 2f the
time t2 the first 3rimar) end32int in the t(2 'r2u 3s )ielded the hazard
rati2 BHRC 2f %.;$ (ith
.1J CI %.?6 %.6$ and 3L%.%%" in fa52ur 2f !IPITOR. The num-er
needed t2 treat BNNTC f2r
2ne )ear t2 3re5ent 2ne case eA 3eriencin' the 3rimar) clinical
end32int -ased 2n the ARR $.0J
)ields "01 3atients. The effect 2f !IPITOR (as seen re'ardless 2f a'e
seA 2r -aseline li3id
le5els.

-igure 2/ Time to Occurrence o) -irst Primar5 #nd6oint

<hen cardi25ascular e5ents (ere e5aluated se3aratel) !IPITOR si'nificantl) reduced the
relati5e ris+ 2f str2+e - ) ?6J BARR 2f ".$JC. There (ere 0" cases 2f str2+e B".1JC in the
!IPITOR 'r2u3 5s $. cases B0.6JC in the 3lace-2 'r2u3 HR %.10 .1J CI %.$" %.6. 3L%.%";.
T2 3re5ent 2ne case 2f str2+e $%# 3atients are needed t2 -e treated f2r 2ne )ear.


-igure 0/ Time to Occurrence o) -irst
&tro8e

Relati5e ris+ 2f m)2cardial infarcti2n (as redu ced -) ?0J 2r ARR -) ".6J (ith $6 cases
B0.#JC in the !IPITOR 'r2u3 5s ;? cases B?.1JC in the 3lace-2 'r2u3 HR %.16 .1J CI %.$.
%.6; 3 L %.%%#. T2 3re5ent 2ne case 2f m)2cardial infarcti2n 000 3atients ha5e t2 -e treated f2r
2ne )ear.

N2 si'nificant ris+ reducti2n (as 2-ser5ed in the time t2 first CA>G PTCA 2r 2ther c2r2nar)
re5ascularizati2n 3r2cedure time t2 first unsta-le an'ina 2r time t2 acute C HD death. N2
si'nificant reducti2n (as 2-ser5ed in time t2 death due t2 all causes B;" deaths in the !IPITOR
'r2u3 5s 60 deaths in the 3lace-2 'r2u3 HR %.#$ .1J CI %.10 ".%" 3L%.%1.C cardi25ascular
causes 2r n2n&cardi25ascular causes.


!#T$IL#! P,$R"$*OLO'2

(I) ,uman P4armacolog5

,uman P4armaco8inetics

P4armaco8inetic interaction studies 4ave been conducted in 4ealt45 subGects 7it4 0 macrolide
antibiotics+ er5t4rom5cin and clarit4rom5cin (bot4 o) 74ic4 in4ibit *2P 0$4), and 7it4
aDit4rom5cin/ *oadministration o) atorvastatin 7it4 er5t4rom5cin or clarit4rom5cin, resulted in
moderatel5 increased atorvastatin 6lasma levels but atorvastatin 6lasma levels 7ere not altered
b5 aDit4rom5cin/ T7elve 4ealt45 subGects 7ere administered atorvastatin 10 mg on da5s 1 and
11H er5t4rom5cin 100 mg QI! 7as administered )rom da5s to 1M/ #r5t4rom5cin increased
atorvastatin *ma= and $(* a66ro=imatel5 40F/ In a second stud 5, atorvastatin 10 mg 7as
administered dail5 )or da5sH clarit4rom5cin (100 mg %I!) or aDit4rom5cin (100 mg Q!) 7as
coadministered )rom da5s K 9 (.J123treatment)/ *oadministration 7it4 clarit4rom5cin
increased atorvastatin $(* R0F and *ma= R10F, but atorvastatin 6lasma levels 7ere not
signi)icantl5 altered b5 coadministration 7it4 aDit4rom5cin/

&tead59state, o6en9label, 64armaco8inetic studies 7it4 digo=in 4ave been 6er)ormed in 4ealt45
subGects 7it4 bot4 lo7 and 4ig4 doses o) atorvastatin/ $torvastatin (10 mg or 0 mg Q!H .J11
and .J12, res6ectivel5), 7as administered )rom da5s 1 9 20 and digo=in (0/21 mg Q!) )rom
da5s 11 9 20/ $t stead59state, atorvastatin 10 mg dail5 4ad no signi)icant e))ect on stead59state
digo=in 64armaco8inetics/ ,o7ever, )ollo7ing co9administration 7it4 atorvastatin 0 mg Q!,
t4e mean stead59state digo=in $(* and *ma= increased 11F and 20F, res6ectivel5/ Patients
ta8ing digo=in s4ould be monitored a66ro6riatel5/

T4e e))ect o) amlodi6ine on t4e 64armaco8inetics o) atorvastatin 7as assessed at stead59state in
a randomiDed, o6en9label, 6lacebo9controlled, crossover stud5 in 4ealt45 male subGects (.J1K)/
$torvastatin (0 mg Q!) 7as administered 7it4 amlodi6ine (10 mg Q!) or 6lacebo )rom da5s
1 9 / -ollo7ing a 14 da5 7as4out, t4e alternate combination 7as administered )rom da5s 22 9
2M/ $t stead59state, t4e coadministration o) ma=imum doses o) atorvastatin and amlodi6ine did
not signi)icantl5 alter t4e 64armaco8inetics o) atorvastatin and t4ere 7ere no a66arent c4anges in
blood 6ressure or 4eart rate/

T4e e))ect o) Cuina6ril on t4e 64armaco8in etics o) atorvastatin 7as assessed in a randomiDed,
o6en9label stud5 in 4ealt45 volunteers (.J22)/ &ingle doses o) atorvastatin (10 mg) 7ere
administered on da5s 1 to 14, and single doses o) Cuina6ril (0 mg) 7ere administered on da5s 1
to I or da5s to 14/ T4e mean Tma= value )or atorvastatin during stead 5 state Cuina6ril
administration 7as s4ortened b5 1/21 4ours com6ared to t4at o) atorvastatin administered alone
but 7it4 no c4ange in absor6tion3$(* or *ma=/ .o signi)icant c4anges in blood 6ressure or
4eart rates 7ere observed/

*oncomitant administration o) atorvastatin 20940mg and itraconaDole 200mg dail5 resulted in a
2/190/09)old increase in atorvastatin $(*/

C2nc2mitant administrati2n 2f at2r5astatin "% m' and c)cl2s32rine 1.0
m'H+'Hda) r esulted in a
#.# f2ld increase in eA32sure t2 at2r5astatin.

BIIC Animal Pharmac2l2')

The h)32li3idemic 32tential 2f at2r5astatin (as e5aluated in
n2rm2ch2lester2lemic animals
m2dels 2f diet&induced h )3erch2lester2lemia and a m2del 2f !D!
rece3t2r deficienc).

In !D! rece3t2r deficient mice at2r5astatin l2(ered 3lasma t2tal and
!D!&C le5els "?J t2 ?.J
25er the d2se ran'e 2f "% t2 $%% m'H+' after 0 (ee+s. At2r5astatin
l2(ered 3lasma ch2lester2l in
ch2(&fed rats irres3ecti5e 2f (hether the c2m32und (as admiAed in
the diet 2r administered -)
2ral 'a5a'e. In ch2(&fed 'uinea 3i's a m2del in (hich !D! is the
maD2r li323r2tein
at2r5astatin 'i5en at $ "% 2r $% m'H+' -) 'a5a'e dail) f2r 0 (ee+s
d2se&de3endentl) decreased
3lasma t2tal ch2lester2l $?J t2 1#J.

The a-ilit) 2f at2r5astatin t2 l2(er 3lasma t2tal and li323r2tein
ch2lester2l le5els (as als2
e5aluated in t(2 ra--it m2dels 2f h)3erch2lester2lemia. In the
end2'en2us h)3erch2lester2lemic
ra--it m2del B(here m2st 2f the 3lasma ch2lester2l is trans32rted in
!D!C administrati2n 2f
at2r5astatin in the diet at " $ and "% m'H+' f2r ; t2 # (ee+s l2(ered
3lasma t2tal ch2lester2l
$6J t2 1?J. The efficac) 2f at2r5astatin (as due t2 a 1;J decrease in
!D! 3r2ducti2n and
?#J reducti2n in a32 >. In the ch2lester2l&fed ra--it m2del B(here
h)3erch2lester2lemia is
m2stl) du e t2 the accumulati2n 2f -eta&mi'ratin' =!D!C at2r5astatin
administered at 0.1 m'H+'
in a %.1J ch2lester2l $J 3eanut 2il $J c2c2nut 2il diet f2r 0 (ee+s
reduced 3lasma t2tal
=!D!&C and !D!&C le5els $1J ??J and 0"J res3ecti5el).

In ch2lest)ramine&3rimed d2's 2ral administrati2n 2f at2r5astatin f2r $
(ee+s d2se&de3endentl)
l2(ered 3lasma t2tal ch2lester2l "1J t2 ?"J 25er the d2se ran'e 2f %.$
t2 "% m'H+'. In
miniature 3i's fed a diet (here $?J 2f cal2ries (ere deri5ed fr2m fat
su33lemented (ith
?%% m' ch2lester2lHda) at2r5astatin 'i5en at $ m'H+' in 'elatin


In intact 2leate&treated H:P&G0 cells a human he3at2c)te cell line at2r5astatin reduced the
2leate&stimulated secreti2n 2f a32 > -) 0"J and decreased the am2unt 2f intracellular a32 >
remainin' (ithin the cells -) 01J. At2r5astatin increased the intracellular de'radati2n 2f a32 >
and im3aired the transl2cati2n 2f a32 > int2 the lumen 2f the end23lasmic reticulum B:RC in
3ermea-ilized H:P&G0 cellsF this (as ass2ciated (ith a decrease in the am2unt 2f a32 >
3articles 3resent in the micr2s2mal fracti2n.

92ll2(in' a sin'le 2ral d2se t2 rats at2r5astatin inhi-ited ster2l s)nthesis Bassessed -)
M"?CNacetate inc2r32rati2n int2 li3idsCF the d2se 2f at2r5astatin that inhi-ited ster2l s)nthesis -)
1%J B:D1%C ran'ed fr2m %.;" t2 $.? m'H+'. The d urati2n 2f inhi-iti2n f2r at2r5astatin (as
similar t2 2ther HMG&C2A reductase inhi-it2rsF h2(e5er at2r5astatin m2re c2nsistentl)
inhi-ited ster2l s)nthesis an a5era'e 2f $?J 25er the first 6 h2urs 32std2se. At2r5astatin and its
meta-2lites (ere relati5el) eEui32tent in inhi-iti2n 2f HMG&C2A reductase Bas assessed -)
measurin' the inc2r32rati2n 2f radi2la-elled HMG&C2A int2 me5al2nateC.

Antiather2scler2tic P2tential 2f At2r5astatin

The antiather2scler2tic 32tential 2f at2r5astatin (as determined in ra--it m2dels 2f
ather2scler2tic lesi2n 3r2'ressi2n and re'ressi2n. A c2mm2n feature 2f the m2dels is that
ather2scler2tic lesi2ns (ere induced -) a c2m-in ati2n 2f h)3 erch2lester2lemia and chr2nic
end2thelial denudati2n 2f the arteries.

Ather2scler2tic lesi2n de5el23ment (as assessed in the th2racic a2rta and chr2nicall) denuded
iliac&fem2ral arter) 2f h)3erch2lester2lemic Ne( [ealand <hite ra--its fed a %.1J ch2lester2l
$J 3eanut 2il $J c2c2nut 2il diet either al2ne 2r c2ntainin' 0.1 m'H+' at2r5astatin l25astatin
3ra5astatin 2r sim5astatin f2r 6 (ee+s. The li3id c2ntent 2f the iliac&fem2ral arter) (as
unaffected -) treatmentF h2(e5er at2r5astatin si'nificantl) reduced the th2racic a2rtic
ch2lester2l ester c2ntent -) 11J and free ch2lester2l c2ntent ?1J. At2r5astatin si'nificantl)
decreased the cr2ss&secti2nal area 2f the iliac&fem2ral lesi2n - ) ;.J and m2n2c)te&macr23ha'e
c2ntent -) #"J. In the descendin' th2racic a2rta a site 2f s32ntane2us diet&induced
ather2scler2tic lesi2ns at2r5astatin si'nificantl) reduced the 3ercenta'e 2f 'r2ssl) discerni-le
ather2scler2tic lesi2ns.

The a-ilit) 2f at2r5astatin t2 -lunt the de5el23ment 2f c2m3leA ather2scler2tic lesi2ns and
3r2m2te re'ressi2n 2f a li3id&enriched lesi2n (as assessed in an additi2nal ra--it m2del 2f
ather2scler2sis. In ra--its after a "1&(ee+ lesi2n inducti2n 3hase c2nsistin' 2f feedin' a %.1J
ch2lester2l $J 3eanut 2il $J c2c2nut 2il diet f2r . (ee+s and a %J ch2lester2l $J 3eanut 2il
$J c2c2nut 2il diet f2r ; (ee+s t2 nearl) n2rmalize 3lasma ch2lester2l le5els in all treatment
'r2u3s 1 m'H+' at2r5astatin administrati2n f2r 6 (ee+s in the ch2(Hfat diet reduced the
ch2lester2l ester enrichment 2f the iliac&fem2ral arter) and th2racic a2rta -) 0#J t2 ?"J (ith2ut
chan'in' the 'r2ss eAtent 2f th2racic a2rtic lesi2ns and incidence 2f fi-r2us 3laEues. At2r5astatin
als2 reduced the ch2lester2l ester c2ntent 2f the iliac&fem2ral arter) -) $#J relati5e t2 initiati2n
2f dru' inter5enti2n ie a 'r2u3 2f animals necr23sied 3ri2r t2 dru' treatment. M2r3h2metric
anal)sis 2f the iliac&fem2ral arter ) re5ealed that at2r5astatin reduced the lesi2n cr2ss&secti2nal
area -) ?%J and m2n2c)te&macr23ha'e c2ntent -) ;%J.

TOSI*OLO'2

$cute To=icit5

T4e acute to=icit5 o) atorvastatin )ollo7ing single doses 7as
evaluated in mice, rats and do gs b5
oral and intravenous routes, and t4e results are summariDed belo7+

TA>!: 0". Acute Oral and Intra5en2us T2Aicit) 7tudies (ith At2r5astatin

Route

&6ecies &e= !ose Range (mg38g) Results

M2use MaleH9emale Oral 0%%&1%%% N2 Deaths
M2use

MaleH9emale I= %.? & ? N2 Deaths

Rat

MaleH9emale Oral 0%%&1%%% N2 Deaths
Rat


D2'

MaleH9emale Oral "% & ?%% N2 Deaths
D2'

The acute t2Aicit) 2f at2r5astatin in r2dents and d2's is l2(. Oral median lethal d2ses in mice
and rats are 'reater than 1%%% m'H+'.

7u-acute and Chr2nic T2Aicit) 7tudies
The tar'et 2r'ans affected -) at2r5astatin in multi3le d2se t2Aicit) studies in rats B0 (ee+s t2 10
(ee+sC and d2's B0 (ee+s t2 "%? (ee+sC are summarized in the ta-le -el2(. The s3ectrum 2f
effects 2-ser5ed is n2t uneA3ected in 5ie( 2f the ma'nitude 2f th e d2se le5els used 32tenc) 2f
at2r5astatin in inhi-itin' me5al2nate s)nthesis and the essential r2le 2f HMG&C2A reductase in
maintainin' cellular h2me2stasis.

TA>!: 00. At2 r5astatin4 Tar'et Or'ans Affected in Animal
7tudies

!og
Rat
!i5er !i5er
7t2 mach Bn2n&'land ularC Gall-ladder
7+eletal Muscle 7+eletal Muscle

Intestine
>rainHO3tic Ner5e*

* Occurred after administrati2n 2f hi'h int2lera-le d2ses B06% m'H+'C


The f2ll2(in' ta-le summarizes the si'nificant ad5erse chan'es 2-ser5ed durin' l2n '&term
t2Aic2l2') studies in rats B10 (ee+sC and d2's B"%? (ee+sC4

TA>!: 0$. At2r5astatin4 7i'nificant Ad5erse Chan'es in
Chr2nic 7tudies

"inimal
To=ic !ose .o9#))ect !ose
&6ecies3Results (mg38g3da5) (mg38g3da5)
RAT
He3at2cellular at)3ia #% 1
>ile Duct h)3er3lasia" "01 #%
N2n'landular st2mach acanth2sis "01 #%
DOG

"0% ?% Death0
He3at2cellular 'ranul2mata$ "% ND
He3at2cellular necr2sis$ "0% ?%
Gall-ladder edemaHhem2rrha'e$ "0% ?%
>ile duct h)3er3lasia$ "0% "%
Intestinal ulcers and sin'le cell
necr2sis$ "0% ?%
"0% ?% 7+eletal muscle Bt2n'ueC
necr2sis0

" Present 2nl) at <ee+ 0;F n2t 2-ser5ed at <ee+ 10.
0 9indin's 2ccurred in <ee+ # 2r ..
$ 9indin's 2ccurred at <ee+ 10 2r in m2ri-und d2's (ere less 3r2n2unced after a "0& (ee+
(ithdra(al 3eri2d B<ee+ ;?C and (ere n2t 2-ser5ed after "%? (ee+s 2f d2sin'.
ND L N2t determined

The results 2f the l2n'&term t2Aic2l2') studies (ith at2r5astatin indicated that similar t2 2ther
HMG&C2A reductase inhi-it2rs the li5er is the 3rimar ) tar'et 2r'an. This is eA3ected since the
li5er is the 3rimar) site 2f the 3harmac2l2'ic acti2n 2f at2r5astatin and it is su-Dect t2 the
'reatest dru' eA32sure f2ll2(in' 2ral administrati2n. In -2th the rat and d2' studies the he3 atic
chan'es diminished (ith time Bi.e. effects (ere less 3r2n2unced at the end 2f the 10&(ee+ and
"%?&(ee+ studiesC su''estin' an ad a3ti5e res32nse.

>rain hem2rrha'e 23tic ner5e de'enerati2n lenticular 23acities and testicular de'enerati2n (ere
n2t seen in d2's treated f2r "%?&(ee+s (ith at2r5astatin u3 t2 "0% m'H+'Hda).

Carcin2'enicit) and Gen2t2Aicit) 7tudies

At2r5astatin (as n2t carcin2'enic in rats 'i5en "% $% 2r "%% m'H+ 'Hda) f2r 0 )ears. The
"%% m'H+' d2se is ;$&f2ld hi'her than the maAimum rec2mmended human d2se 2f 6% m'
B".; m'H+' -ased 2n a 1% +' humanC and AUC B%&0? hrC 5alues (ere 6& t2 ";&f2ld hi'h er.

In a 0&)ear stud) in mice 'i5en "%% 0%% 2r ?%% m'H+'Hda) incidences 2f he3at2cellular
aden2ma in males and he3at2cellular carcin2ma in females (ere increased at ?%% m'H+'. This
d2se is 01% times the maAimum rec2mmended human d2se 2n a m'H+' -asis and s)stemic
eA32sure -ased 2n AUC B%&0? hrC (as ; t2 "" times hi'her. There (as n2 e5idence 2f treatment&


related increases in tum2r incidences at the l2(er d2ses 2f "%% and 0%%
m'H+'Hda) Bi.e. u3 t2 "01
times the maAimum rec2mmended human d2se 2n a m'H+' -asis and
s)stemic eA 32sures 2f $
times hi'her -ased 2n AUC B%&0? hrC.

At2r5astatin did n2t dem2nstrate muta'enic 2r clast2'enic 32tential in
f2ur in 5itr2 tests (ith and
(ith2ut meta-2lic acti5ati2n 2r in 2ne in 5i52 assa). It (as ne'ati5e in
the Ames test (ith
7alm2nella t)3himurium and :scherichia c2li and in the in 5itr2
HGPRT f2r(ard mutati2n
assa) in Chinese hamster lun' cells. At2r5astatin did n2t 3r2duce
si'nificant increases in
chr2m2s2mal a-errati2ns in the in 5itr2 Chinese hamster lun' cell assa)
and (as ne'ati5e in the
in 5i52 m2use micr2nucleus test.

Re3r2ducti5e and Terat2'enicit) 7tudies

N2 ad5erse effects 2n fertilit) 2r re3r2ducti2n (ere 2-ser5ed in male
rats 'i5en d2ses 2f
at2r5astatin u3 t2 "#1Hm'H+'Hda) 2r in female rats 'i5en d2ses u3 t2
001 m'H+'Hda). These d2ses
are "%% t2 "?% times the maAimum rec2mmended human d2se 2n a
m'H+' -asis. At2r5astatin did
n2t cause an) ad5erse effects 2n s3erm 2r semen 3arameters 2r in
re3r2ducti5e 2r'an
hist23ath2l2') in d2 's 'i5en d2ses 2f "% ?% 2r "0% m'H+' f2r 0 )ears.
At2r5astatin (as n2t
terat2'enic in either rats 2r ra--its.


R#-#R#.*#&

1/ $lau6ovic P, ,einonen T, &4urDins8e L, %lac8 !"/ #))ect o) a ne7 ,"'9*oa
reductase inhi-it2r at2r5astatin 2n li3ids a32li323r2teins and li3232tein 3articles in
3atients (ith ele5ated serum ch2lester2l and tri'l)ceride le5els. Ather2scler2sis "..#F
"$$4"0$&"$$.
0. >a++er&Ar+ema RG Da5ids2n MH G2ldstein R/ Da5i'n2n / Isaacs2hn /! <eiss 7R
*eils2n !M >r2(n = Miller =T 7hurzins+e !/ >lac+ DM. :fficac) and 7afet) 2f a
Ne( HMG&C2A Reductase Inhi-it2r At2r5astatin in Patients <ith
H)3 ertri'l)ceridemia. /AMA "..;F0#14"06&"$$.
$. >arter P/ OT>rien RC. Achie5ement 2f tar 'et 3lasma ch2lester2l le5els in
h)3erch2lester2laemic 3atients -ein' treated in 'eneral 3ractice. Ather2scler2sis 0%%%
"?.4"..&0%1.
?. >ert2lini 7 >it2ll2 >2n G Cam3-ell !M 9arnier M. !an'an / Mahla G Pauciull2 P
7irt2ri C :'r2s 9 9a))ad R Na(r2c+i /. The efficac) and safet) 2f at2r5astatin
c2m3ared t2 3ra5astatin in 3atients (ith h)3erch2lester2lemia. Ather2scler2sis "..#F
"$%4"."&".#.
1. >est /D Nich2ls2n GC OUNeal DN *2t2(icz M Te--utt NC Chan *&< 7anders *.
At2r5astatin and sim5astatin reduce ele5ated ch2lester2l in n2n&insulin de3endent
dia-etes. Dia-etes Nutriti2n and Meta-2lism "..;F.4#?&6%.
;. >lac+ DM. At2r5astatin4 a ste3 ahead f2r HMG&C2A reductase inhi-it2rs.
Ather2scler2sis "..1F"%4$%#&$"%.
#. >r2(n A7 >a++er&Ar+ema RG 8ellen ! et al. Treatin' 3atients (ith d2cumented
ather2scler2sis t2 Nati2nal Ch2lester2l :ducati2n Pr2'ram&rec2mmended l2(&densit)&
li323r2tein ch2lester2l '2als (ith at2r5astatin flu5astatin l25astatin and sim5astatin.
/ACC "..6F $0B$C4;;1&;#0.
6. C2lh2un HM >etterid'e D/ Durrin't2n PN Hitman GA Andre( H Neil <
!i5in'st2ne 7/ Th2mas2n M/ Mac+ness MI Charlt2n&Men)s = 9uller /H 2n -ehalf 2f
the CARD7 in5esti'at2rs. Primar) 3re5enti2n 2f cardi25ascular disease (ith at2r5astatin
in t)3e 0 dia- etes in the C2lla-2rati5e At2r5astatin Dia-etes 7tud) BCARD7C4
multicentre rand2mised 3lace-2&c2ntr2lled trial. !ancet 0%%? Au' 0"F $;?4;61&;.;.
.. Dart A /erums G Nich2ls2n G dU:mden M Hamilt2n&Crai' I Tallis G >est / <est M
7ulli5an D >racs P >lac+ D. A multicenter d2u-le&-lind "&)ear stud ) c2m3arin' safet)
and efficac) 2f at2r5astatin 5ersus sim5astatin in 3atients (ith h)3erch2lester2lemia. Am
/ Cardi2l "..#F6%4$.&??.
"%. Da5ids2n MM Mc*enn) /M 7tein :A 7chr2tt HG >a++er&Ar+ema RG 9a))ad R
>lac+ DM f2r the At2r5astatin 7tud) Gr2u3 I. C2m3aris2n 2f 2ne )ear efficac) and
safet) 2f at2r5astatin 5ersus l25astatin in 3rimar) h)3erch2lester2lemia Am / Cardi2l
"..#F #.4"?#1&"?6".
"". Da5i'n2n /. At2r5astatin4 a statin (ith a lar'e s3ectrum 2f acti2n. Ather2scler2sis "..#F
0B;C40?$&010.


"0. Da5i'n2n /. Pr2s3ects f2r Dru' Thera3) f2r H)3erli323r2teinemia. Dia- Meta-
"..1F0"4"$.&"?;.
"$. Duell P> C2nn2r <: Illin'(2rth DR. Rha-d2m)2l)sis after ta+in' at2r5astatin (ith
'emfi-r2zil. Am / Cardi2l "..6F6"4$;6&$;..
"?. :d(ards D/ >elle5ue 9H <2ster PM. Identificati2n 2f ;U#U&Dih)dr2-er'am2ttin a
C)t2chr2me P&?1% Inhi-it2r in Gra3efruit /uice. Dru' Meta-2lism and Dis32siti2n
"..;F0?4"06#&.%.
"1. :Aecuti5e 7ummar) 2f the Third Re32rt 2n the Nati2nal Ch2lester2l :ducati2n Pr2'ram
BNC:PC :A3ert Panel 2n Detecti2n :5aluati2n and Treatment 2f Hi'h >l22d
Ch2lester2l in Adults BAdult Treatment Panel IIIC. /AMA 0%%"F061B".C40?6;&0?.#.
";. Genest / 9r2lich / 92d2r G McPhers2n R f2r th e <2r+in' Gr2u3 2n
H)3erch2lester2lemia and Other D)sli3idemias. Rec2mmendati2ns f2r the Mana'ement
2f D)sli3idemia and the Pre5enti2n 2f Cardi25ascular Disease4 0%%$ U3date. CMA/
0%%$F ";.B.C4 htt34HH(((.cmaD.caHc'iHc2ntentHfullH";.H.H.0"HDC"
"#. Gi-s2n DM >r2n N/ Richens A H2unsl2( N/ 7edman A/ <hitfield !R. :ffect 2f
A'e and Gender 2n Pharmac2+inetics 2f At2r5astatin in Humans. / Clin Pharmac2l
"..;F$;40?0&0?;.
"6. Hein2nen TM 7chr2tt H Mc*enne) /M 7niderman AD >r2)les 9: [a52ral /H *i5el
* >lac+ DM. At2r5astatin a Ne( HMG&C2A Reductase Inhi-it2r as M2n2thera3) and
C2m-ined <ith C2lesti32l. / Cardi25asc Pharmac2l Thera3eut "..;F"B0C4""#&"00.
".. Hein2nen TM 7tein : <eiss 7R Mc*enne) /M Da5ids2n M 7hurzins+e ! >lac+
DM. The li3id&l2(erin' effects 2f at2r5astatin a ne( HMG C2A reductase inhi-it2r4
results 2f a rand2mised d2u-le&-lind stud). Clin Ther "..;F"6B1C461$&;$.
0%. Hermann M. et al. 7u-stantiall) ele5ated le5els 2f at2r5astatin and meta-2lites in
c)cl2s32rine&treated renal trans3lant reci3ients B!etters t2 the :dit2rC Clinical
Pharmac2l2') \ Thera3eutics 52l. #; n2. ?4 $66&$." BOct2-er 0%%?C
0". /2nes P *af2ne+ 7 !aur2ra I Hunnin'ha+ e D et al. C2m3arati5e d2se efficac) stud )
2f at2r5astatin 5ersus sim5astatin 3ra5astatin l25astatin and flu5astatin in 3atients (ith
h)3erch2lester2lemia BThe CUR=:7 7tud)C. Am / Card "..6F 6"4160&16#.
00. *ant2la T *i5ist2 * Neu52nen P/4 :ffect 2f itrac2naz2le 2n the 3harmac2+inetics 2f
at2r5astatin Clinical Pharmac2l2') \ Thera3 eutics 52l. ;? n2. "4 16&;1 B/ul) "..6C
0$. !aas+2nen R ODala /P Ti+anen M/ Him-er' //. 7erum u-iEuin2ne c2ncentrati2ns after
sh2rt& and l2n'&term treatment (ith HMG&C2A reductase inhi-it2rs. :ur / Clin
Pharmac2l "..?F?;4$"$&"#.
0?. !aR2sa /C Grund) 7M <aters DD et alF Treatin' t2 Ne( Tra'ets BTNTC In5esti'at2rs.
Intensi5e li3id l2(erin' (ith at2r5astatin in 3atients (ith sta-le c2r2nar) disease. N :n'l
/ Med 0%%1F$104"?01&$1.
01. !eiter ! >halla P. At2r5astatin calcium4 A ne( HMG&C2A reductase inhi-it2r. Can /
Clin Pharmac2l "..6F1B$C4"$6&"1?.


0;. M]rz < <2llschl]'er H *lein G et. al. 7afet) 2f !2(&Densit) !i323r2tein Ch2lester2l
Reducti2n <ith At2r5astatin =ersus 7im5astatin in a C2r2nar ) Heart Disease P23ulati2n
Bthe TARG:T TANGI>!: TrialC. Amer /2ur Card "...F 6?4#&"$.
0#. Marais AD 9irth /C >ateman M /2nes / M2untne) / Martens C. At2r5astatin4 an
effecti5e li3id l2(erin' a'ent in familial h)3erch2lester2lemia. Arteri2scler Thr2m-
=asc >i2l "..#F "6B6C4"10#&"1$".
06. Mazzu A! !asseter *C 7ham-len :C A'ar(al = !ettieri / 7undaresen P4
Itrac2naz2le alters the 3harmac2+inetics 2 f at2r5astatin t2 a 'reater eAtent than either
ceri5astatin 2r 3ra5astatin Clinical Pharmac2l2') \ Thera3eutics 52l. ;6 n2. ?4 $."&?%%
BOct2-er 0%%% C
0.. McPhers2n R An'us C Murra) P Gen est /r. / f2r the <ATCH In5esti'at2rs. :fficac)
2f At2r5astatin in Achie5in' Nati2nal Ch2lester2l :ducati2n Pr2'ram !D!&Ch2lester2l
Tar'ets in <2men (ith 7e5ere D)sli3idemia and C=D 2r Ris+ 9act2rs f2r C=D4 The
<2menUs At2r5astatin Trial 2n Ch2lester2l B<ATCHC. American Heart /2urnal 0%%"F
"?"4.?.&1;
$%. Na2um25a RP Marais AD M2untne) / 9irth /C Rendell N> Ta)l2r G< Th2m3s2n
GR. Plasma me5al2nic acid an indeA 2f ch2lester2l s)nthesis in 5i52 and res32nsi5eness
t2 HMG&C2A reductase inhi-it2rs in familial h)3erch2lester2lemia. Ather2scler2sis
"..;F"".40%$&0"$.
$". Na(r2c+i /< <eiss 7R Da5ids2n MH 73recher D! 7ch(artz 7! !u3ien P&/ /2hnes
PH Ha-er H: >lac+ DM. Reducti2n 2f !D!&ch2lester2l -) 01J t2 ;%J in 3atients
(ith 3rimar) h)3erch2lester2lemia -) at2r5astatin a ne( HMG&C2A reductase inhi-it2r.
Arteri2scler Thr2m- =asc >i2l "..1F "14;#6&;60 .6"&%?.
$0. O2i T Hein2nen T Alau 325ich P Da5i'n2n / !eiter ! !u3ien P 7niderman A Tan M
Trem-la) G 72ris+) A 7hurzins+e ! >lac+ D. :fficac) and safet) 2f a ne( HMG&C2A
reductase inhi-it2r at2r5astatin in 3atients (ith c2m-ined h)3erli3idemia4 C2m3aris2n
(ith fen2fi-rate. Arteri2 scler Thr2m- =asc >i2l "..#F "#B.C4"#.$&"#...
$$. Pedersen TR 9aer'eman O *astelein // et alF Incremental Decrease in :nd P2ints
Thr2u'h A''ressi5e !i3id !2(erin' BID:A!C 7tud) Gr2u3. Hi'h&d2se at2r5astatin 5s
usual&d2se sim5astatin f2r sec2ndar ) 3re5enti2n after m)2cardial infarcti2n4 the ID:A!
stud)4 a r and2mized c2ntr2lled trial. /AMA 0%%1F0.?40?$#&?1. MC 2rrecti2n4 /AMA
0%%1F0.?4$%.0.N
$?. Radul25ic !! Cilla DD P2s5ar :! 7edman A/ <hitfield !R. :ffect 2f 922d 2n the
>i2a5aila-ilit) 2f At2r5astatin an HMG&C2A Reductase Inhi-it2r. / Clin Pharmac2l
"..1F$14..%&..?.
$1. 7canu AM. !i323r2teinBaC as a cardi25ascular ris+ fact2r. Trends Cardi25asc Med
".."F"40.?&...
$;. 7tern R A-el R Gi-s2n G! >esserer /. At2r5astatin d2es n2t alter the antic2a'ulant
acti5it) 2f (arfarin. / Clin Pharmac2l "..#F $#4"%;0&"%;?.

I"PORT$.T+ PL#$&# R#$!
P$RT III+ *O.&("#R I.-OR"$TIO. !IPITOR als2 reduces the ris+ 2f heart attac+s and str2+es in
3e23le (ith multi3le ris+ fact2rs f2r c2r2nar) heart disease such
as hi'h -l22d 3ressure and dia-etes. <hen used -) 3e23le (h2
ha5e suffered a heart attac+ in the 3ast !IPITOR reduces the ris+
2f ha5in' an2ther heart attac+.

!IPITOR is 2nl) a5aila-le -) 3rescri3ti2n after seein' a d2ct2r.

P r!IPITOR
($torvastatin *alcium Tablets)

T4is lea)let is 6art III o) a t4ree96art TProduct
"onog ra64T 6ublis4ed 74en LIPITOR 7as a66roved )or
sale in *anada and is designed s6eci)icall5 )or *onsumers/
T4is lea)let is a summar5 a nd 7ill not tell 5ou ever5t4ing
about LIPITOR/ *ontact 5our doctor or 64armacist i)
5ou35our c4ild 4ave an5 Cuestions about t4e drug/ Please
read t4is in)ormation care)ull5/

:4en LIPITOR s4o uld not be used+
D2 n2t ta+e !IPITOR if )2uH)2ur child4
I AreHis aller'ic t2 an) in'redient 2f this medicati2 n Bsee (hat
the med icinal in'redient is and (hat the im32rtant n2n
medicinal in'redients areC.
I Ha5e acti5e li5er disease 2r uneA3lained increases in li5er
$%O(T T,I& "#!I*$TIO.
enz)mes.

:4at LIPITOR is used )or+
I AreHis 3re'nant 2r -reast&feedin'.
82ur d2ct2r has 3rescri-ed these 3ills t2 hel3 l2(er )2ur
ch2lester2l 2r 2ther fats in the -l22d Bsuch as tri'l)ceridesC
and t2 3re5ent cardi25ascular disease such as heart attac+s.
Hi'h le5els 2f ch2lester2l and 2ther fats can cause heart
disease -) cl2''in' the -l22d 5essels that feed -l22d and
2A)'en t2 the heart.

Children "%&"# )ears 2ld (ith heter2z)'2us familial
h)3erch2lester2lemia Bhi'h ch2lester2l inherited fr2m 2ne 2f
the 3arentsC and a famil) hist2r) 2f cardi25ascular disease 2r 0
2r m2re ris+ fact2rs 2f cardi25ascular disease as determined
-) )2ur d2ct2r can als2 -enefit fr2m ta+in' !IPITOR.

!IPITOR is Dust 3art 2f the treatment )2ur d2ct2r (ill 3lan
(ith )2uH)2ur child t2 hel3 +ee3 )2 u health). De3endin' 2n
)2urH)2 ur childTs health and lifest)le )2ur d2 ct2r ma)
rec2mmend 4

:4at t4e medicinal ingredient is+
at2r5astatin calcium.

:4at t4e im6ortant nonmedicinal ingredients are+

!i3it2r ta-lets c2ntain4 calcium car-2nate candelilla (aA B"% 0%
and ?%m'C cr2scarmell2se s2dium h)dr2A)3r23)l cellul2se
h)dr2A)3r23)l meth)lcellul2se lact2se m2n2h)drate ma'nesium
stearate micr2cr)stalline cellul2se 23adr) (hite 8s&"&#%?%
32l)eth)lene 'l)c2l 32l)s2r-ate 6% simethic2ne mulsi2n talc
titanium di2Aide.

:4at dosage )orms it comes in+
!IPITOR ta-lets are a5aila-le in ? stren'ths4 "%m'
0%m' ?%m'
and 6%m'.

:$R.I.'& $.! PR#*$(TIO.&
a chan'e in diet t2 c2ntr2l (ei'ht and reduce ch2lester2l

reduce inta+e 2f saturated fats and increase fi-er
&erious :arnings and Precautions
eAercise that is ri'ht f2r )2uH)2ur child
Tell )2ur d2ct2r if )2uH)2ur child ha5e an) muscle 3ain
tenderness s2reness 2r (ea+ness durin' treatment (ith
!IPITOR.
Euittin' sm2+in' 2r a52idin' sm2+) 3laces
'i5in' u3 alc2h2l 2r drin+in' less

92ll2 ( )2ur d2ct2rTs instructi2ns carefull).

%e)ore using t4is medicine+
%e)ore ta8ing LIPITOR, tell 5our doctor or 64armacist i)
5ou35our c4ild+

:4at LIPITOR does+
!IPITOR -el2n's t2 the class 2f medicines +n2 (n as
^statins_ m2re s3ecificall) called HMG&C2 A reductase
inhi-it2rs. HMG&C2A reductase is an enz)me in52l5ed in
re'ulatin' ch2lester2l le5els in )2ur -2d). 7tatins are used
al2n' (ith chan'es t2 eAercise and diet t2 hel3 c2ntr2l the
am2unt 2f ch2lester2l 3r2duced -) the -2d).

!IPITOR can hel3 )2ur -2d)4
areHis 3re'nant intend t2 -ec2me 3re'nant. Ch2lester2l
c2m32unds are essential elements f2r the de5el23ment
2f a fetus. Ch2lester2l&l2(erin' dru's can harm the
fetus. 9emales 2f child&-earin' a'e sh2uld discuss
(ith their d2ct2r the 32tential hazards t2 the fetus and
the im32rtance 2f -irth c2ntr2l meth2ds. !IPITOR
sh2uld n2t -e used -) 3re'nant (2men. If )2uH)2ur
child -ec2me 3re'nant disc2ntinue use immediatel)
and discuss (ith )2ur d2ct2r.
Decrease !D! B-adC ch2lester2l tri'l)ceride le5els
and 2ther li3ids Hfats in the -l22d.
Increase HD! .'22dC ch2lester2l.
areHis -reast&feedin' 2r intend t2 -reast&feed. This
Decrease the T2tal Ch2lester2l HD!&Ch2lester2l
medicine ma) -e 3resent in -reast mil+.
Rati2 BTC4HD!&C Rati2C. This rati2 re3resents the
-alance -et(een -ad and '22d ch2lester2l.
ha5e th)r2id 3r2-lems
re'ularl) drin+ three 2r m2re alc2h2lic drin+s dail)

Page 48 of 50 LIPITOR (atorvastatin calcium) Product Monograph
child and )2ur d2ct2r (ill -e (atchin' )2urH)2ur
childTs
ch2lester2l le5els t2 'et them d2(n t2 a safe ran'e.
Here are
s2me im32rtant ti3s.

are ta+in' an) 2ther ch2lester2l l2(erin'
medicati2n such as fi-rates B'emfi-r2zil
fen2fi-rateC niacin 2r ezetimi-e
ha5e a famil) hist2r) 2f muscular dis2rders
had an) 3ast 3r2-lems (ith the muscles B3ain 92ll2( the 3lan that )2uH)2ur child and )2ur d2ct2r ma+e f2r
tendernessC after usin' an HMG&C2A reductase inhi-it2r
B^statin_C such as at2r5astatin B!IPITORC flu5astatin
B!esc2 lC l25astatin BMe5ac2rC 3ra5astatin BPra5ac2lC
r2su5astatin BCrest2rC 2r sim5astatin B[2c2rC 2r ha5e
de5el23ed an aller') 2r int2lerance t2 them.
diet eAercise and (ei'ht c2ntr2l.
Ta+e !IPITOR as a sin'le d2se. It d2es n2t matter if
!IPITOR is ta+en (ith f22d 2r (ith2ut f22d -ut it sh2uld n2t
-e ta+en (ith 'ra3efruit Duice. 82ur d2ct2r (ill usuall) tell
)2uH)2ur child t2 ta+e it in the e5enin's.
ha5e +idne) 2r li5er 3r2-lems D2 n2t chan'e the d2se unless directed -) a d2ct2r.
ha5e dia-etes Bas the d2sa'e 2f !IPITOR ma) need t2 -e If )2uH)2ur child 'et sic+ ha5e an 23erati2n 2r need medical
adDustedC treatment inf2rm )2ur d2ct2r 2r 3harmacist that )2uH)2ur
child are ta+in' !IPITOR. ha5e under'2ne sur'er) 2r 2ther tissue inDur)
d2 eAcessi5e 3h)sical eAercise If )2uH)2ur child ha5e t2 ta+e an) 2ther medicine &

!IPITOR (as studied in -2)s and 'irls B'irls (h2 alread)
started their 3eri2dC "%&"# )ears at a d2se 2f "% and 0% m'.
!IPITOR has n2t -een studied in 3re&3u-ertal 3atients 2r
3atients )2un'er than "% )ears 2f a'e. Ad2lescent 'irls
sh2uld discuss (ith their d2ct2r the 32tential hazards t2 the
fetus and the im32rtance 2f -irth c2ntr2l (hile 2n !IPITOR
thera3).

3rescri3ti2n 2r n2n&3rescri3 ti2n & (hile ta+in' !IPITOR tal+
t2 )2ur d2ct2r 2r 3harmacist first.
If )2 uH)2ur child ha5e t2 see a different d2ct2r f2r an)
reas2n -e sure t2 inf2rm himHher that )2uH)2ur child areHis
ta+in' !IPITOR.
!IPITOR (as 3rescri-ed f2r )2uH)2ur child 2nl). D2nUt
'i5e these 3ills t2 an)2ne else.

(sual !ose+
Adults4 The rec2mmended startin' d2se 2f !IPITOR is "% 2r 0%
m' 2nce dail) de3endin' 2n )2ur reEuired !D!&C reducti2n.
Patients (h2 need a lar'e reducti2n in !D!&C Bm2re than ?1JC
ma) -e started at ?% m' 2nce dail). The d2sa'e ran'e 2f
!IPITOR is "% t2 6% m' 2nce dail). The maAimum d2se is 6%
m'Hda).

The rec2mmended d2se 2f !IPITOR is "% t2 6% m'Hda) f2r
3e23le (h2 ha5e alread) suffered a heart attac+.
I.T#R$*TIO.& :IT, T,I& "#!I*$TIO.
As (ith m2st medicines interacti2 n (ith 2ther dru's is
32ssi-le. Tell )2ur d 2ct2r 2r 3harmacist if )2u are ta+in' an)
2ther medicati2ns includin' 3rescri3ti2n n2n&3rescri3ti2n
and natural health 3r2ducts. In 3articular these dru's ma)
interact (ith !IPITOR4
c2rtic2ster2ids Bc2rtis2ne&li+e medicinesC
c)cl2s32rine B7ANDIMMUN:SC
'emfi-r2zil B!OPIDSC
fen2fi-rate B!IPIDI! MICROSC 2r -ezafi-rate Children B"%&"# )ears 2ldC4 the rec2mmended startin' d2se 2f
!IPITOR is "% m'Hda)F the maAimum rec2mmended d2se is 0%
m'Hda)
B>:[A!IPS C
li3id&l2(erin' d2ses 2f niacin Bnic2tinic acidC
er)thr2m)cin clarithr2m)cin 2r az2le antifun'al
Overdose+ a'ents B+et2c2naz2le 2r itrac2naz2leC
There is n2 s3ecific treatment f2r at2r5astatin 25erd2sa'e. 7h2uld
an 25erd2se 2ccur see )2ur d2ct2r ri'ht a(a).
nefaz2d2ne B7:R[ON:SC
indina5ir sulfate BCRI@I=ANSC nelfina5ir

"issed !ose+
mes)late B=IRAC:PTSC rit2na5ir
BNOR=IRSC saEuina5ir mes)late
BIN=IRA7:`C
If )2uH)2ur child miss ta+in' a 3ill ta+e it as
s22n as 32ssi-le.
>ut if it is alm2st time f2r the neAt d2se s+i3
the missed d2se and
Dust ta+e the neAt d2se. D2nUt ta+e a d2u-le
d2se.

di'2Ain
diltiazem
efa5irenz rifam3in
antacids BfreEuent useC and !IPITOR sh2uld -e
ta+en 0 h2urs a3art
&I!# #--#*T& $.! :,$T TO !O $%O(T T,#"
'ra3efruit Duice & es3eciall) if in'estin' u3(ards

2f ".0 litres 2f 'ra3efruit Duice at 2nce

M2st 3e23le d2 n2t ha5e an) 3r2-lems (ith side effects (hen
ta+in' this medicine. H2(e5er all medicines can cause un(anted
side effects. Chec+ (ith )2ur d2ct2r 2r 3harmacist 3r2m3tl) if
an) 2f the f2ll2(in' 3ersist 2r -ec2me tr2u-les2me4 PROP#R (&# O- T,I& "#!I*$TIO.

c2nsti3ati2nHdiarrheaH'as
<e 2ften cann2t see 2r feel the 3r2-lems that hi'h ch2lester2l
causes until a l2t 2f time has 3assed . ThatUs (h) it is
im32rtant t2 ta+e these 3ills Dust as 3rescri-ed. 82uH)2ur
de3ressi2n Bin childrenC
headache

R#PORTI.' &(&P#*T#! &I!# #--#*T&

s+in rash
st2mach 3ain 2r u3set
52mitin' 2r thr2(in' u3
T2 m2nit2r dru' safet) Health Canada thr2u'h the Canada
=i'ilance Pr2'ram c2llects inf2rmati2n 2n seri2us and
uneA3ected side effects 2f dru's. If )2u sus3 ect )2u ha5e had a
seri2us 2r uneA3ected reacti2n t2 this dru' )2u ma) n2tif)
Canada =i'ilance4

>) t2ll&free tele3h2ne4 6;;&0$?&0$?1
>) t2ll&free faA4 6;;&;#6&;#6.
Online4 (((.healthcanada.'c.caHmedeffect
>) email4 Canada=i'ilanceahc&sc.'c.ca

=er) rarel) a fe( 3e23le ma) suffer fr2m Daundice fr2m a
li5er c2nditi2n called he3atitis.

This is n2t a c2m3lete list 2f side effects. If )2uH)2ur child
n2tice an)thin' unusual 2r an) uneA3ected effects (hile
ta+in' !i3it2r c2ntact )2ur d2ct2r 2r 3harmacist

&#RIO(& &I!# #--#*T&, ,O: O-T#. T,#2
,$PP#. $.! :,$T !O $%O(T T,#"
>) re'ular mail4
Canada =i'ilance Nati2nal Office
Mar+eted Health Pr2ducts 7afet) and
:ffecti5eness Inf2rmati2n >ureau
Mar+eted Health Pr2ducts Direct2rate
Health Pr2ducts and 922d >ranch
Health Canada
Tunne)Ts Pasture A! %#%"C
Otta(a ON *"A %*.

Tal+ (ith )2ur 7t23 ta+in'
d2ct2r 2r 3harmacist dru' and call
7)m3t2mH:ffect Onl) if In all
cases
)2ur d2ct2r 2r
se5ere 3harmacist
Muscle 3ain that )2u
cann2t eA3lain

Rare
Muscle tenderness 2r
(ea+ness

Generalized
(ea+ness es3eciall)
if )2u d2nTt feel (ell

NOTE: Sho uld ou r!"uir! in#ormation r!lat!d to th!
manag!m!nt o# th! sid! !##!ct$ pl!as! contact our h!alth car!
provid!r %!#or! noti#ing &anada 'igilanc!( Th! &anada
'igilanc! Program do!s not provid! m!dical advic!(
>r2(nish 2r
disc2l2ured urine

,O: TO &TOR# IT
"OR# I.-OR"$TIO.

$l7a5s 8ee6 medicine 7ell out o) t4e reac4 o) c4ildren/
Patients can refer t2 (((.!i3it2r.ca f2r
further inf2rmati2n.

This d2cument 3lus the full 3r2duct
m2n2'ra3h 3re3ared f2r
health 3r2fessi2nals can -e f2und at4
htt34HH(((.3 fizer.ca
2r -) c2ntactin' the s32ns2r Pfizer
Canada Inc. at4
"&6%%&?;$&;%%"
This leaflet (as 3re3ared -) Pfizer
Canada Inc.
!ast re5ised4 A3ril 0%%6

*ee3 !IPITOR at r22m tem3erature B"1&$%2CC a(a) fr2m
(arm and dam3 3laces li+e the -athr22m 2r +itchen.


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