Product Monograph: Biodot Pharmaceuticals

PRODUCT MONOGRAPH
DYSLIP - 10
(atorvastatin calci! ta"l#ts$
10 !%& '0 !%& (0 !% atorvastatin
LIPID M)TA*OLISM R)GULATOR
BIODOT PHARMACEUTICALS
+,-1(0(& .IRST .LOOR& THAILA NAGAR&
PUDU//OTTAI - 0'' 00(1
TAMILNADU& INDIA
P2on# 3 451-(6''-',06,6
Mo"il# 3 55((7-7(550
Table of Contents
PART I:
H)ALTH PRO.)SSIONAL IN.ORMATION
SUMMARY PRODUCT IN.ORMATION
INDICATIONS AND CLINICAL US)
CONTRAINDICATIONS
8ARNINGS AND PR)CAUTIONS
AD9)RS) R)ACTIONS
DRUG INT)RACTIONS
DOSAG) AND ADMINISTRATION
O9)RDOSAG)
ACTION AND CLINICAL PHARMACOLOGY
STORAG) AND STA*ILITY
SP)CIAL HANDLING INSTRUCTIONS
DOSAG) .ORMS& COMPOSITION AND PAC/AGING
PART II:
SCI)NTI.IC IN.ORMATION
PHARMAC)UTICAL IN.ORMATION
:UALITY CONTROL
MSDS
CLINICAL TRIALS
D)TAIL)D PHARMACOLOGY
TO;ICOLOGY
R).)R)NC)S
PART III
CONSUM)R IN.ORMATION
DYSLIP - 10
Atorvastatin Calciu Tablets
PART I: HEALTH PRO!ESSIO"AL I"!ORMATIO"
SUMMAR# PRODUCT I"!ORMATIO"
Rot# o<
A=!inistration
Dosa%# .or! -
Str#n%t2
Clinicall> R#l#vant
Non!#=icinal In%r#=i#nts
oral Ta"l#ts3 10 !%& '0 !%&
atorvastatin
Calci! car"onat#&
can=#lilla ?a@ (10& '0 an=
(0 !%$& croscar!#llos#
so=i!& 2>=ro@>AroA>l
c#lllos# 2>=ro@>AroA>l
!#t2>lc#lllos#& lactos#
!ono2>=rat#& !a%n#si!
st#arat#& !icrocr>stallin#
c#lllos#& Aol>#t2>l#n#
%l>col& Aol>sor"at# 70&
si!#t2icon# #!lsion&
talc& an= titani! =io@i=#1
I"DICATIO"S A"D CLI"ICAL USE
H$%erc&olesteroleia
DYSLIP - 10 (atorvastatin calci!$ is in=icat#= as an a=Bnct to li<#st>l#
c2an%#s& incl=in% =i#t& (at l#ast #Cival#nt to t2# A=lt Tr#at!#nt Pan#l III (ATP III$
TLC =i#t$& <or t2# r#=ction o< #l#vat#= total c2ol#st#rol (total-C$& LDL-C& TG an=
aAoliAoArot#in * (aAo *$ in 2>A#rliAi=#!ic an= =>sliAi=#!ic con=itions& ?2#n
r#sAons# to =i#t an= ot2#r nonA2ar!acolo%ical !#asr#s alon# 2as "##n ina=#Cat#&
incl=in%3
1
Pri!ar> 2>A#rc2ol#st#rol#!ia (T>A# IIa$D
Co!"in#= (!i@#=$ 2>A#rliAi=#!ia (T>A# II"$& incl=in% <a!ilial co!"in#=
2>A#rliAi=#!ia&
r#%ar=l#ss o< ?2#t2#r c2ol#st#rol or tri%l>c#ri=#s ar# t2# liAi= a"nor!alit> o<
conc#rnD
D>s"#taliAoArot#in#!ia (T>A# III$D
H>A#rtri%l>c#ri=#!ia (T>A# I9$D
.a!ilial 2>A#rc2ol#st#rol#!ia (2o!oE>%os an= 2#t#roE>%os$1 .or
2o!oE>%os
<a!ilial
2>A#rc2ol#st#rol#!ia& LIPITOR s2ol= "# s#= as an a=Bnct to tr#at!#nts sc2
as
LDL aA2#r#sis& or as !onot2#raA> i< sc2 tr#at!#nts ar# not availa"l#1
An a=Bnct to =i#t to r#=c# total-C& LDL-C& an= aAo * l#v#ls in "o>s an=
Aost!#narc2al %irls& 10 to 1, >#ars o< a%# ?it2 2#t#roE>%os <a!ilial
2>A#rc2ol#st#rol#!ia& i< a<t#r an a=#Cat# trial o< =i#t t2#raA> t2# <ollo?in% <in=in%s
ar# still Ar#s#nt3
a1 LDL-C r#!ains F(15 !!ol-L (150 !%-=L$ or
"1 LDL-C r#!ains F(11 !!ol-L (100 !%-=L$ an=3
t2#r# is a Aositiv# <a!il> 2istor> o< Ar#!atr# car=iovasclar =is#as# or
t?o or !or# ot2#r C9D risG <actors ar# Ar#s#nt in t2# A#=iatric Aati#nt
DYSLIP - 10 also rais#s HDL-c2ol#st#rol an= t2#r#<or# lo?#rs t2# LDL-
C-HDL-C an= total- C-HDL-C ratios in Aati#nts ?it2 Ari!ar> 2>A#rc2ol#st#rol#!ia
an= co!"in#= (!i@#=$ 2>A#rliAi=#!ia (.r#=ricGson T>A# IIa an= II" =>sliAi=#!ia$1 In
Aool#= =ata <ro! '( controll#= clinical trials& LIPITOR rais#= HDL-C l#v#ls +H-,H
in Ari!ar> 2>A#rc2ol#st#rol#!ic (t>A# IIa$ Aati#nts an= 10H-1+H in !i@#= (t>A# II"$
=>sliAi=#!ic Aati#nts1
In clinical trials& DYSLIP - 10 (10 to 70 !%-=a>$ si%ni<icantl> i!Arov#= liAi=
Aro<il#s in Aati#nts ?it2 a ?i=# vari#t> o< 2>A#rliAi=#!ic an= =>sliAi=#!ic con=itions1
In ' =os#-r#sAons# st=i#s in !il=l> to !o=#rat#l> 2>A#rliAi=#!ic Aati#nts
(.r#=ricGson T>A#s IIa an= II"$& DYSLIP - 10 r#=c#= t2# l#v#ls o< total c2ol#st#rol
('5-(+H$& LDL-C (65-00H$& aAo * (6'-+0H$& TG (15-6,H$& an= incr#as#= 2i%2
=#nsit> liAoArot#in c2ol#st#rol (HDL-C$ l#v#ls (+-5H$1 Co!Aara"l# r#sAons#s ?#r#
ac2i#v#= in Aati#nts ?it2 2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia& non-<a!ilial
<or!s o< 2>A#rc2ol#st#rol#!ia& co!"in#= 2>A#rliAi=#!ia& incl=in% <a!ilial
co!"in#= 2>A#rliAi=#!ia an= Aati#nts ?it2 non-inslin =#A#n=#nt =ia"#t#s !#llits1
In Aati#nts ?it2 2>A#rtri%l>c#ri=#!ia (T>A# I9$& DYSLIP - 10 (10 to 70 !% =ail>$
r#=c#= TG ('+ - +0H$ an= LDL-C l#v#ls ('6 - (0H$1 DYSLIP - 10 2as not "##n
st=i#= in con=itions ?2#r# t2# !aBor a"nor!alit> is #l#vation o< c2>lo!icrons (TG
l#v#ls F 11 !!ol-L$& i1#1 t>A#s I an= 91
In an oA#n-la"#l st=> in Aati#nts ?it2 =>s"#taliAoArot#in#!ia (T>A# III$&
DYSLIP - 10 (10 to 70 !% =ail>$ r#=c#= total-C ((0-+,H$& TG ((0-+0H$ an= IDL-C
4 9LDL-C l#v#ls (6(-+7H$1
In an oA#n la"#l st=> in Aati#nts ?it2 2o!oE>%os <a!ilial
2>A#rc2ol#st#rol#!ia (.H$ DYSLIP - 10 (10 to 70 !% =ail>$ r#=c#= !#an LDL-C
l#v#ls (''H$1 In a Ailot st=>&DYSLIP - 10 70 !%-=a> s2o?#= a !#an LDL-C
lo?#rin% o< 60H <or Aati#nts not on Alas!aA2#r#sis an= o< 61H o"s#rv#= in r#c#Ator
=#<#ctiv# Aati#nts an= o< 15H in r#c#Ator n#%ativ# Aati#nts (s## CLINICAL TRIALS$1
.or !or# =#tails on #<<icac> r#slts "> Ar#-=#<in#= classi<ication an= Aool#=
=ata "> .r#=ricGson t>A#s& s## CLINICAL TRIALS1
Prior to initiatin% t2#raA> ?it2 DYSLIP - 10 s#con=ar> cas#s s2ol= "#
#@cl=#= <or #l#vations in Alas!a liAi= l#v#ls (#1%1 Aoorl> controll#= =ia"#t#s !#llits&
2>Aot2>roi=is!& n#A2rotic s>n=ro!#& =>sArot#in#!ias& o"strctiv# liv#r =is#as#& an=
alco2olis!$& an= a liAi= Aro<il# A#r<or!#= to !#asr# total c2ol#st#rol& LDL-C& HDL-
C& an= TG1 .or Aati#nts ?it2 TG I(1+' !!ol-L (I(00 !%-=L$& LDL-C can "#
#sti!at#= sin% t2# <ollo?in% #Cation3
LDL-C (!!ol-L$ J total-C - K(016, @ (TG$ 4 HDL-C$L
LDL-C (!%-=L$ J total-C - K(01' @ (TG$ 4 HDL-C$L1
.or Aati#nts ?it2 TG l#v#ls F(1+' !!ol-L (F(00 !%-=L$& t2is #Cation is l#ss
accrat# an= LDL-C conc#ntrations s2ol= "# !#asr#= =ir#ctl> or ">
ltrac#ntri<%ation1
Pati#nts ?it2 2i%2 or v#r> 2i%2 tri%l>c#ri=# l#v#ls& i1#1 F '1' !!ol-L ('00
!%-=L$ or F +10 !!ol-L (+00 !%-=L$& r#sA#ctiv#l>& !a> r#Cir# tri%l>c#ri=#-lo?#rin%
t2#raA> (<#no<i"rat#& "#Ea<i"rat# or nicotinic aci=$ alon# or in co!"ination ?it2
DYSLIP - 10
In 'eneral( cobination t&era%$ )it& fibrates ust be un*erta+en
cautiousl$ an* onl$ after ris+,benefit anal$sis (s## 8ARNINGS AND
PR)CAUTIONS& Mscl# )<<#cts& P2ar!acoGin#tic Int#ractions an= DRUG
INT)RACTIONS$1
)l#vat#= s#r! tri%l>c#ri=#s ar# !ost o<t#n o"s#rv#= in Aati#nts ?it2 t2#
!#ta"olic s>n=ro!# (a"=o!inal o"#sit>& at2#ro%#nic =>sliAi=#!ia M#l#vat#=
tri%l>c#ri=#s& s!all =#ns# LDL Aarticl#s an= lo? HDL-c2ol#st#rolN& inslin r#sistanc#
?it2 or ?it2ot %lcos# intol#ranc#& rais#= "loo= Ar#ssr# an= Arot2ro!"ic an=
Aroin<la!!ator> stat#s$1
(.or t2# tr#at!#nt o< sA#ci<ic =>sliAi=#!ias r#<#r to t2# R#Aort o< t2# Cana=ian
8orGin% GroA on H>A#rc2ol#st#rol#!ia an= Ot2#r D>sliAi=#!ias or to t2# )@A#rt
Pan#l on D#t#ction& )valation& an= Tr#at!#nt o< Hi%2 *loo= C2ol#st#rol in A=lts
KA=lt Tr#at!#nt Pan#l IIIL& n=#r R).)R)NC)S$1
82#n =r%s ar# Ar#scri"#= att#ntion to t2#raA#tic li<#st>l# c2an%#s (r#=c#=
intaG# o< satrat#= <ats an= c2ol#st#rol& ?#i%2t r#=ction& incr#as#= A2>sical activit>&
in%#stion o< sol"l# <i"#rs$ s2ol= al?a>s "# !aintain#= an= r#in<orc#=1
Prevention of Car*iovascular Disease
DYSLIP - 10 is in=icat#= to r#=c# t2# risG o< !>ocar=ial in<arction in a=lt
2>A#rt#nsiv# Aati#nts ?it2ot clinicall> #vi=#nt coronar> 2#art =is#as#& "t ?it2 at
l#ast t2r## a==itional risG <actors <or coronar> 2#art =is#as# sc2 as a%# F++ >#ars&
!al# s#@& s!oGin% t>A# ' =ia"#t#s& l#<t v#ntriclar 2>A#rtroA2>& ot2#r sA#ci<i#=
a"nor!aliti#s on )CG& !icroal"!inria or Arot#inria& ratio o< Alas!a total
c2ol#st#rol to HDL-c2ol#st#rol F0& or Ar#!atr# <a!il> 2istor> o< coronar> 2#art
=is#as#1
DYSLIP - 10 is also in=icat#= to r#=c# t2# risG o< !>ocar=ial in<arction an=
stroG# in a=lt Aati#nts ?it2 t>A# ' =ia"#t#s !#llits an= 2>A#rt#nsion ?it2ot
clinicall> #vi=#nt coronar> 2#art =is#as#& "t ?it2 ot2#r risG <actors sc2 as a%# F++
>#ars& r#tinoAat2>& al"!inria or s!oGin%1
DYSLIP - 10 is in=icat#= to r#=c# t2# risG o< !>ocar=ial in<arction in Aati#nts
?it2clinicall> #vi=#nt coronar> 2#art =is#as#1

CO"TRAI"DICATIO"S
H>A#rs#nsitivit> to an> co!Aon#nt o< t2is !#=ication (<or a co!Al#t# listin% o<
t2# co!Aon#nts& s## DOSAG) .ORMS& COMPOSITION AND PAC/AGING$1
Activ# liv#r =is#as# or n#@Alain#= A#rsist#nt #l#vations o< s#r!
transa!inas#s #@c##=in% 6 ti!#s t2# AA#r li!it o< nor!al (s## 8ARNINGS AND
PR)CAUTIONS$1
Pr#%nanc> an= nrsin% ?o!#n3 C2ol#st#rol an= ot2#r Aro=cts o< c2ol#st#rol
"ios>nt2#sis ar# #ss#ntial co!Aon#nts <or <#tal =#v#loA!#nt (incl=in% s>nt2#sis o<
st#roi=s an= c#ll !#!"ran#s$1 DYSLIP - 10 s2ol= "# a=!inist#r#= to ?o!#n o<
c2il="#arin% a%# onl> ?2#n sc2 Aati#nts ar# 2i%2l> nliG#l> to conc#iv# an= 2av#
"##n in<or!#= o< t2# Aossi"l# 2ar!1 (I< t2# Aati#nt "#co!#s Ar#%nant ?2il# taGin%
DYSLIP - 10 t2# =r% s2ol= "# =iscontin#= i!!#=iat#l> an= t2# Aati#nt aAAris#=
o< t2# Aot#ntial 2ar! to t2# <#ts1 At2#roscl#rosis "#in% a c2ronic Aroc#ss&
=iscontination o< liAi= !#ta"olis! r#%latin% =r%s =rin% Ar#%nanc> s2ol= 2av#
littl# i!Aact on t2# otco!# o< lon%-t#r! t2#raA> o< Ari!ar> 2>A#rc2ol#st#rol#!ia
(s## PR)CAUTIONS O Us# in Pr#%nanc>& Us# in Nrsin% Mot2#rs$1
-AR"I".S A"D PRECAUTIO"S
.eneral
*#<or# instittin% t2#raA> ?it2 DYSLIP - 10 (atorvastatin calci!$& an att#!At
s2ol= "# !a=# to control #l#vat#= s#r! liAoArot#in l#v#ls ?it2 aAAroAriat# =i#t&
#@#rcis#& an= ?#i%2t r#=ction in ov#r?#i%2t Aati#nts& an= to tr#at ot2#r n=#rl>in%
!#=ical Aro"l#!s (s## INDICATIONS AND CLINICAL US)$1 Pati#nts s2ol= "#
a=vis#= to in<or! s"s#C#nt A2>sicians o< t2# Arior s# o< DYSLIP - 10 or an>
ot2#r liAi=-lo?#rin% a%#nts1
P&araco+inetic Interactions
T2# s# o< HMG- CoA r#=ctas# in2i"itors 2as "##n associat#= ?it2 s#v#r#
!>oAat2>& incl=in% r2a"=o!>ol>sis& ?2ic2 !a> "# !or# <r#C#nt ?2#n t2#> ar# co-
a=!inist#r#= ?it2 =r%s t2at in2i"it t2# c>toc2ro!# P-(+0 #nE>!# s>st#!1
Atorvastatin is !#ta"oliE#= "> c>toc2ro!# P-(+0 iso<or! 6A( an= as sc2 !a>
int#ract ?it2 a%#nts t2at in2i"it t2is #nE>!#1 (S## 8ARNINGS AND
PR)CAUTIONS& Mscl# #<<#cts& an= DRUG INT)RACTIONS$1
Muscle Effects
)<<#cts on sG#l#tal !scl# sc2 as !>al%ia& !>oAat2> an= v#r> rar#l>&
r2a"=o!>ol>sis 2av# "##n r#Aort#= in Aati#nts tr#at#= ?it2 DYSLIP - 10
/er$ rare cases of r&ab*o$ol$sis )it& acute renal failure secon*ar$ to
$o'lobinuria( &ave been re%orte* )it& D#SLIP , 01 an* )it& ot&er HM.,
CoA re*uctase in&ibitors2
M>oAat2>& =#<in#= as !scl# Aain or !scl# ?#aGn#ss in conBnction
?it2 incr#as#s in cr#atin# Ginas# (C/$ val#s to %r#at#r t2an t#n ti!#s
t2# AA#r li!it o< nor!al& s2ol= "# consi=#r#= in an> Aati#nt ?it2 =i<<s#
!>al%ia& !scl# t#n=#rn#ss or ?#aGn#ss& an=-or !arG#= #l#vation o<
C/1 Pati#nts s2ol= "# a=vis#= to r#Aort Aro!Atl> an> n#@Alain#= !scl# Aain&
t#n=#rn#ss or ?#aGn#ss& Aarticlarl> i< acco!Aani#= "> !alais# or <#v#r1 Pati#nts ?2o
=#v#loA an> si%ns or s>!Ato!s s%%#stiv# o< !>oAat2> s2ol= 2av# t2#ir C/ l#v#ls
!#asr#=1 DYSLIP - 10 t2#raA> s2ol= "# =iscontin#= i< !arG#=l> #l#vat#= C/
l#v#ls ar# !#asr#= or !>oAat2> is =ia%nos#= or ssA#ct#=1
Pr#-=isAosin% .actors <or M>oAat2>-R2a"=o!>ol>sis3 DYSLIP - 10 as ?it2
ot2#r HMG-CoA r#=ctas# in2i"itors& s2ol= "# Ar#scri"#= ?it2 cation in Aati#nts
?it2 Ar#-=isAosin% <actors <or !>oAat2>-r2a"=o!>ol>sis1 Sc2 <actors incl=#3
P P#rsonal or <a!il> 2istor> o< 2#r#=itar> !sclar =isor=#rs
P Pr#vios 2istor> o< !scl# to@icit> ?it2 anot2#r HMG-CoA r#=ctas#
in2i"itor
P Conco!itant s# o< a <i"rat#& or niacin
P H>Aot2>roi=is!
P Alco2ol a"s#
P )@c#ssiv# A2>sical #@#rcis#
P A%# F,0 >#ars
P R#nal i!Aair!#nt
P H#Aatic i!Aair!#nt
P Dia"#t#s ?it2 2#Aatic <att> c2an%#
P Sr%#r> an= tra!a
P .railt>
P Sitations ?2#r# an incr#as# in Alas!a l#v#ls o< activ# in%r#=i#nt !a> occr
T2# risG o< !>oAat2> an= r2a"=o!>ol>sis =rin% tr#at!#nt ?it2 HMG-CoA
r#=ctas# in2i"itors is incr#as#= ?it2 concrr#nt a=!inistration o< c>closAorin& <i"ric
aci= =#rivativ#s& #r>t2ro!>cin& clarit2ro!>cin& niacin (nicotinic aci=$& aEol#
anti<n%als or n#<aEo=on#1 T2#r#<or#& lo?#r startin% an= !aint#nanc# =os#s o<
atorvastatin s2ol= also "# consi=#r#= ?2#n taG#n conco!itantl> ?it2 t2#
a<or#!#ntion#= =r%s1 In cas#s ?2#r# co-a=!inistration o<
DYSLIP - 10 ?it2 c>closAorin# is n#c#ssar>& t2# =os# o< DYSLIP - 10 s2ol= not
#@c##= 10!% (s## PR)CAUTIONS& P2ar!acoGin#tic Int#raction St=i#s an=
Pot#ntial Dr% Int#ractionsD DRUG INT)RACTIONS& Dr%-Dr% Int#ractionsD
D)TAIL)D PHARMACOLOGY& H!an P2ar!acoGin#tics$1
DYSLIP - 10 t2#raA> s2ol= "# t#!Aoraril> ?it22#l= or =iscontin#= in an>
Aati#nt ?it2 an act# s#rios con=ition s%%#stiv# o< !>oAat2> or 2avin% a risG <actor
Ar#=isAosin% to t2# =#v#loA!#nt o< r#nal <ailr# s#con=ar> to r2a"=o!>ol>sis (sc2
as s#Asis& s#v#r# act# in<#ction& 2>Aot#nsion& !aBor sr%#r>& tra!a& s#v#r# !#ta"olic&
#n=ocrin# an= #l#ctrol>t# =isor=#rs& an= ncontroll#= s#iEr#s$1
DYSLIP - 10 t2#raA> s2ol= "# =iscontin#= i< !arG#=l> #l#vat#= CP/ l#v#ls
occr or !>oAat2> is =ia%nos#= or ssA#ct#=1
Car*iovascular
)<<#ct on U"iCinon# (Co:10$ L#v#ls
Si%ni<icant =#cr#as#s in circlatin% "iCinon# l#v#ls in Aati#nts tr#at#= ?it2
atorvastatin an= ot2#r statins 2av# "##n o"s#rv#=1 T2# clinical si%ni<icanc# o< a
Aot#ntial lon%-t#r! statinin=c#= =#<ici#nc> o< "iCinon# 2as not "##n #sta"lis2#=1 It
2as "##n r#Aort#= t2at a =#cr#as# in !>ocar=ial "iCinon# l#v#ls col= l#a= to
i!Aair#= car=iac <nction in Aati#nts ?it2 "or=#rlin# con%#stiv# 2#art <ailr# (s##
R).)R)NC)S$1
En*ocrine an* Metabolis
)n=ocrin# .nction
HMG-CoA r#=ctas# in2i"itors int#r<#r# ?it2 c2ol#st#rol s>nt2#sis an= as sc2
!i%2t t2#or#ticall> "lnt a=r#nal an=-or %ona=al st#roi= Aro=ction1 Clinical st=i#s
?it2 atorvastatin an= ot2#r HMG-CoA r#=ctas# in2i"itors 2av# s%%#st#= t2at t2#s#
a%#nts =o not r#=c# Alas!a cortisol conc#ntration or i!Aair a=r#nal r#s#rv# an= =o
not r#=c# "asal Alas!a t#stost#ron# conc#ntration1 Ho?#v#r& t2# #<<#cts o< HMG-
CoA r#=ctas# in2i"itors on !al# <#rtilit> 2av# not "##n st=i#= in a=#Cat# n!"#rs
o< Aati#nts1 T2# #<<#cts& i< an>& on t2# Aititar>-%ona=al a@is in Ar#!#noAasal ?o!#n
ar# nGno?n1
Pati#nts tr#at#= ?it2 atorvastatin ?2o =#v#loA clinical #vi=#nc# o< #n=ocrin#
=>s<nction s2ol= "# #valat#= aAAroAriat#l>1 Cation s2ol= "# #@#rcis#= i< an
HMG-CoA r#=ctas# in2i"itor or ot2#r a%#nt s#= to lo?#r c2ol#st#rol l#v#ls is
a=!inist#r#= to Aati#nts r#c#ivin% ot2#r =r%s (#1%1 G#toconaEol#& sAironolacton# or
ci!#ti=in#$ t2at !a> =#cr#as# t2# l#v#ls o< #n=o%#nos st#roi= 2or!on#s1
)<<#ct on LiAoArot#in (a$
In so!# Aati#nts& t2# "#n#<icial #<<#ct o< lo?#r#= total c2ol#st#rol an= LDL-C
l#v#ls !a> "# Aartl> "lnt#= "> a conco!itant incr#as# in LA(a$ liAoArot#in
conc#ntrations1 Pr#s#nt Gno?l#=%# s%%#sts t2# i!Aortanc# o< 2i%2 LA(a$ l#v#ls as an
#!#r%in% risG <actor <or coronar> 2#art =is#as#1 It is t2s =#sira"l# to !aintain an=
r#in<orc# li<#st>l# c2an%#s in 2i%2 risG Aati#nts Alac#= on atorvastatin t2#raA> (s##
R).)R)NC)S$1
Pati#nts ?it2 S#v#r# H>A#rc2ol#st#rol#!ia
Hi%2#r =r% =osa%#s (70 !%-=a>$ r#Cir#= <or so!# Aati#nts ?it2 s#v#r#
2>A#rc2ol#st#rol#!ia (incl=in% <a!ilial 2>A#rc2ol#st#rol#!ia$ ar# associat#= ?it2
incr#as#= Alas!a l#v#ls o< atorvastatin1 Cation s2ol= "# #@#rcis#= in sc2 Aati#nts
?2o ar# also s#v#r#l> r#nall> i!Aair#=& #l=#rl>& or ar# conco!itantl> "#in%
a=!inist#r#= =i%o@in or CYP 6A( in2i"itors (s## 8ARNINGS AND
PR)CAUTIONS& P2ar!acoGin#tic Int#ractions& Mscl# )<<#ctsD DRUG
INT)RACTIONSD DOSAG) AND ADMINISTRATION$1
He%atic3Biliar$3Pancreatic
H#Aatic )<<#cts
In clinical trials& A#rsist#nt incr#as#s in s#r! transa!inas#s %r#at#r t2an t2r##
ti!#s t2# AA#r li!it o< nor!al occrr#= in I1H o< Aati#nts ?2o r#c#iv#= DYSLIP -
10 1 82#n t2# =osa%# o< DYSLIP - 10 ?as r#=c#=& or ?2#n =r% tr#at!#nt ?as
int#rrAt#= or =iscontin#=& s#r! transa!inas# l#v#ls r#trn#= to Ar#tr#at!#nt l#v#ls1
T2# incr#as#s ?#r# %#n#rall> not associat#= ?it2 Ban=ic# or ot2#r clinical si%ns or
s>!Ato!s1 Most Aati#nts contin#= tr#at!#nt ?it2 a r#=c#= =os# o< DYSLIP - 10
?it2ot clinical s#C#la#1
Liv#r <nction t#sts s2ol= "# A#r<or!#= "#<or# t2# initiation o< tr#at!#nt& an=
A#rio=icall> t2#r#a<t#r1 SA#cial att#ntion s2ol= "# Aai= to Aati#nts ?2o =#v#loA
#l#vat#= s#r! transa!inas# l#v#ls& an= in t2#s# Aati#nts !#asr#!#nts s2ol= "#
r#A#at#= Aro!Atl> an= t2#n A#r<or!#= !or# <r#C#ntl>1
If increases in alanine ainotransferase 4ALT5 or as%artate
ainotransferase 4AST5 s&o) evi*ence of %ro'ression( %articularl$ if t&e$ rise to
'reater t&an 6 ties t&e u%%er liit of noral an* are %ersistent( t&e *osa'e
s&oul* be re*uce* or t&e *ru' *iscontinue*2
D#SLIP , 01 as )ell as ot&er HM.,CoA re*uctase in&ibitors( s&oul* be
use* )it& caution in %atients )&o consue substantial 7uantities of alco&ol
an*3or &ave a %ast &istor$ of liver *isease2 Activ# liv#r =is#as# or n#@Alain#=
transa!inas# #l#vations ar# contrain=ications to t2# s# o< DYSLIP - 10 i< sc2 a
con=ition s2ol= =#v#loA =rin% t2#raA>& t2# =r% s2ol= "# =iscontin#=1
O%&t&alolo'ic
)<<#ct on t2# L#ns
Crr#nt lon%-t#r! =ata <ro! clinical trials =o not in=icat# an a=v#rs# #<<#ct
o< atorvastatin on t2# 2!an l#ns1
Renal
R#nal Ins<<ici#nc>
Plas!a conc#ntrations an= LDL-C lo?#rin% #<<icac> o< DYSLIP - 10 ?as
s2o?n to "# si!ilar in Aati#nts ?it2 !o=#rat# r#nal ins<<ici#nc> co!Aar#= ?it2
Aati#nts ?it2 nor!al r#nal <nction1 Ho?#v#r& sinc# s#v#ral cas#s o< r2a"=o!>ol>sis
2av# "##n r#Aort#= in Aati#nts ?it2 a 2istor> o< r#nal ins<<ici#nc> o< nGno?n
s#v#rit>& as a Ar#cationar> !#asr# an= A#n=in% <rt2#r #@A#ri#nc# in r#nal =is#as#&
t2# lo?#st =os# (10 !%-=a>$ o< DYSLIP - 10 s2ol= "# s#= in t2#s# Aati#nts1 Si!ilar
Ar#cations aAAl> in Aati#nts ?it2 s#v#r# r#nal ins<<ici#nc> Kcr#atinin# cl#aranc# I60
!L-!in (I01+ !L-s#c$LD t2# lo?#st =osa%# s2ol= "# s#= an= i!Al#!#nt#=
catiosl> (s## 8ARNINGS AND PR)CAUTIONS& Mscl# )<<#ctsD DRUG
INT)RACTIONS$1 R#<#r also to DOSAG) AND ADMINISTRATION1
Sensitivit$3Resistance
H>A#rs#nsitivit>
An aAAar#nt 2>A#rs#nsitivit> s>n=ro!# 2as "##n r#Aort#= ?it2 ot2#r HMG-
CoA r#=ctas#in2i"itors ?2ic2 2as incl=#= 1 or !or# o< t2# <ollo?in% <#atr#s3
anaA2>la@is& an%io#=#!a& lAs #r>t2#!atos-liG# s>n=ro!#& Aol>!>al%ia
r2#!atica& vasclitis& ArAra& t2ro!"oc>toA#nia& l#GoA#nia& 2#!ol>tic an#!ia&
Aositiv# ANA& )SR incr#as#& #osinoA2ilia& art2ritis& art2ral%ia& rticaria& ast2#nia&
A2otos#nsitivit>& <#v#r& c2ills& <ls2in%& !alais#& =>sAn#a& to@ic #Ai=#r!al n#crol>sis&
#r>t2#!a !lti<or!#& incl=in% St#v#ns-Qo2nson s>n=ro!#1 Alt2o%2 to =at#
2>A#rs#nsitivit> s>n=ro!# 2as not "##n =#scri"#= as sc2& DYSLIP - 10 s2ol= "#
=iscontin#= i< 2>A#rs#nsitivit> is ssA#ct#=1
S%ecial Po%ulations
Use in Pre'nanc$: D#SLIP , 01 is contrain*icate* *urin' %re'nanc$ (s##
CONTRAINDICATIONS$1
T2#r# ar# no =ata on t2# s# o< DYSLIP - 10 =rin% Ar#%nanc>1 DYSLIP - 10
s2ol= "# a=!inist#r#= to ?o!#n o< c2il="#arin% a%# onl> ?2#n sc2 Aati#nts ar#
2i%2l> nliG#l> to conc#iv# an= 2av# "##n in<or!#= o< t2# Aot#ntial 2aEar=s1 I< t2#
Aati#nt "#co!#s Ar#%nant ?2il# taGin% DYSLIP - 10 t2# =r% s2ol= "# =iscontin#=
an= t2# Aati#nt aAAris#= o< t2# Aot#ntial risG to t2# <#ts1
Use in "ursin' Mot&ers : In rats& !ilG conc#ntrations o< atorvastatin ar#
si!ilar to t2os# in Alas!a1 It is not Gno?n ?2#t2#r t2is =r% is #@cr#t#= in 2!an
!ilG1 *#cas# o< t2# Aot#ntial <or a=v#rs# r#actions in nrsin% in<ants& ?o!#n taGin%
DYSLIP - 10 s2ol= not "r#ast-<##= (s## CONTRAINDICATIONS$1
Pe*iatric Use : Sa<#t> an= #<<#ctiv#n#ss o< DYSLIP - 10 in Aati#nts 10-1,
>#ars o< a%# (NJ1(0$ ?it2 2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia 2av# "##n
#valat#= in a controll#= clinical trial o< 0 !ont2s =ration in a=ol#sc#nt "o>s an=
Aost!#narc2al %irls1 Pati#nts tr#at#= ?it2 DYSLIP - 10 2a= a sa<#t> an= tol#ra"ilit>
Aro<il# %#n#rall> si!ilar to t2at o< Alac#"o1 Dos#s %r#at#r t2an '0 !% 2av# not "##n
st=i#= in t2is Aati#nt AoAlation1
Sa<#t> an= #<<#ctiv#n#ss o< DYSLIP - 10 in A#=iatric Aati#nts 2as not "##n
=#t#r!in#= in t2# Ar#v#ntion o< !>ocar=ial in<arction1
DYSLIP - 10 2a= no #<<#ct on %ro?t2 or s#@al !atration in "o>s an= in
%irls1 T2# #<<#cts on !#nstral c>cl# ?#r# not ass#ss#= Ks## PHARMACOLOGY&
Clinical St=i#s s#ctionD AD9)RS) R)ACTIONS& P#=iatric Pati#ntsD an= DOSAG)
AND ADMINISTRATION <or H#t#roE>%os .a!ilial H>A#rc2ol#st#rol#!ia in
P#=iatric Pati#nts (10-1, >#ars o< a%#$L1
A=ol#sc#nt <#!al#s s2ol= "# cons#ll#= on aAAroAriat# contrac#Ativ# !#t2o=s
?2il# on DYSLIP - 10 t2#raA> (s## CONTRAINDICATIONS an= PR)CAUTIONS&
Us# in Pr#%nanc>$1
DYSLIP - 10 2as not "##n st=i#= in controll#= clinical trials involvin% Ar#-
A"#rtal Aati#nts or Aati#nts >on%#r t2an 10 >#ars o< a%#1
Dos#s o< DYSLIP - 10 A to 70 !%-=a> <or 1 >#ar 2av# "##n #valat#= in 7
A#=iatric Aati#nts ?it2 2o!oE>%os <a!ilial 2>A#rc2ol#st#rol#!ia (s## Clinical
St=i#s - H#t#roE>%os .a!ilial H>A#rc2ol#st#rol#!ia in A#=iatric Aati#nts$1
.eriatric Use : Tr#at!#nt #@A#ri#nc# in a=lts ,0 >#ars or ol=#r (NJ''1$ ?it2
=os#s o< DYSLIP - 10 A to 70 !%-=a> 2as =#!onstrat#= t2at t2# sa<#t> an=
#<<#ctiv#n#ss o< atorvastatin in t2is AoAlation ?as si!ilar to t2at o< Aati#nts I,0
>#ars o< a%#1 P2ar!acoGin#tic #valation o< atorvastatin in s"B#cts ov#r t2# a%# o< 0+
>#ars in=icat#s an incr#as#= AUC1 As a Ar#cationar> !#asr#& t2# lo?#st =os# s2ol=
"# a=!inist#r#= initiall> (s## D)TAIL)D PHARMACOLOGY& H!an
P2ar!acoGin#ticsD R).)R)NC)S$1
)l=#rl> Aati#nts !a> "# !or# ssc#Ati"l# to !>oAat2> (s## 8ARNINGS O
Mscl# )<<#cts O Pr#=isAosin% .actors <or M>oAat2>-R2a"=o!>ol>sis$1
AD/ERSE REACTIO"S
A*verse Dru' Reaction Overvie)
DYSLIP - 10 is %#n#rall> ?#ll-tol#rat#=1 A=v#rs# r#actions 2av# sall> "##n
!il= an= transi#nt1 In controll#= clinical st=i#s (Alac#"o-controll#= an= activ#-
controll#= co!Aarativ# st=i#s ?it2 ot2#r liAi= lo?#rin% a%#nts$ involvin% '+0'
Aati#nts& I'H o< Aati#nts ?#r# =iscontin#= =# to a=v#rs# #@A#ri#nc#s attri"ta"l# to
DYSLIP - 10 O< t2#s# '+0' Aati#nts& 1,'1 ?#r# tr#at#= <or at l#ast 0 !ont2s an=
1'+6 <or 1 >#ar or !or#1
A=v#rs# #@A#ri#nc#s occrrin% at an inci=#nc# J1H in Aati#nts AarticiAatin% in
Alac#"o- controll#= clinical st=i#s o< DYSLIP - 10 an= r#Aort#= to "# Aossi"l>&
Aro"a"l> or =#<init#l> =r% r#lat#= ar# s2o?n in Ta"l# 1 "#lo? 3
TA*L) 13 Associat#= A=v#rs# )v#nts R#Aort#= in J 1H
o< Pati#nts in Plac#"o Controll#= Clinical Trials
Plac#"o H DYSLIP - 10 H
(nJ',0$ (nJ11'' $
.ASTROI"TESTI"AL
ConstiAation 1 1
Diarr2#a 1 1
D>sA#Asia ' 1
.latl#nc# ' 1
Nas#a 0 1
"ER/OUS S#STEM
H#a=ac2# ' 1
MISCELLA"EOUS
Pain I1 1
M>al%ia 1 1
Ast2#nia I1 1
T2# <ollo?in% a==itional a=v#rs# #v#nts ?#r# r#Aort#= in clinical trialsD not all
#v#nts list#= "#lo? 2av# "##n associat#= ?it2 a casal r#lations2iA to DYSLIP - 10
t2#raA>3 Mscl# cra!As& !>ositis& !>oAat2>& Aar#st2#sia& A#riA2#ral n#roAat2>&
Aancr#atitis& 2#Aatitis& c2ol#static Ban=ic#& anor#@ia& vo!itin%& aloA#cia& Arrits&
ras2& i!Aot#nc#& 2>A#r%l>c#!ia& an= 2>Ao%l>c#!ia1
Hetero8$'ous !ailial H$%erc&olesteroleia in Pe*iatric Patients 4a'es 01,09
$ears5:
In a '0-?##G controll#= st=> in "o>s an= Aost!#narc2al %irls (nJ17,& ?2#r#
1(0 Aati#nts r#c#iv#= DYSLIP - 10 $& t2# sa<#t> an= tol#ra"ilit> Aro<il# o< DYSLIP -
10 10 to '0 !% =ail> ?as si!ilar to t2at o< Alac#"o1 T2# a=v#rs# #v#nts r#Aort#= in
F1H o< Aati#nts ?#r# as <ollo?s3 a"=o!inal Aain& =#Ar#ssion an= 2#a=ac2# (s##
PHARMACOLOGY& Clinical St=i#s an= PR)CAUTIONS& P#=iatric Us#$1
Laborator$ C&an'es an* A*verse Events
T2# crit#ria <or clinicall> si%ni<icant la"orator> c2an%#s ?#r# F6 ; t2# AA#r
li!it o< nor!al (ULN$ <or liv#r #nE>!#s& an= F+ ; ULN <or cr#atin# Ginas#1 A total
o< 7 niC# s"B#cts !#t on# or !or# o< t2#s# crit#ria =rin% t2# =o"l#-"lin= A2as#1
H#nc#& t2# inci=#nc# o< Aati#nts ?2o #@A#ri#nc#= a"nor!all> 2i%2 #nE>!atic l#v#ls
(AST-ALT an= cr#atin# Ginas#$ ?as F (H (7-17,$1
.iv# atorvastatin an= on# Alac#"o s"B#cts 2a= incr#as#s in C/ F+ ; ULN
=rin% t2# =o"l#- "lin= A2as#D t?o o< t2# <iv# atorvastatin tr#at#= s"B#cts 2a=
incr#as#s in C/ F 10 ; ULN1
T2#r# ?#r# ' s"B#cts ?2o 2a= clinicall> si%ni<icant incr#as#s in ALT1
Abnoral Heatolo'ic an* Clinical C&eistr$ !in*in's
La"orator> T#sts3 Incr#as#s in s#r! transa!inas# l#v#ls 2av# "##n not#= in
clinical trials (s## 8ARNINGS AND PR)CAUTIONS$1
Post,Mar+et A*verse Dru' Reactions
T2# <ollo?in% a=v#rs# #v#nts 2av# also "##n r#Aort#= =rin% Aost-!arG#tin%
#@A#ri#nc# ?it2 DYSLIP - 10 & r#%ar=l#ss o< casalit> ass#ss!#nt3
9#r> rar# r#Aorts3 s#v#r# !>oAat2> ?it2 or ?it2ot r2a"=o!>ol>sis (s##
8ARNINGS AND PR)CAUTIONS& Mscl# )<<#cts& R#nal Ins<<ici#nc> an= DRUG
INT)RACTIONS$1
Isolat#= r#Aorts3 G>n#co!astia& t2ro!"oc>toA#nia& art2ral%ia an= all#r%ic
r#actions incl=in% rticaria& an%ion#rotic #=#!a& anaA2>la@is an= "llos ras2#s
(incl=in% #r>t2#!# !lti<or!#& St#v#ns-Qo2nson s>n=ro!# an= to@ic #Ai=#r!al
n#crol>sis$L& <ati%#& "acG Aain& c2#st Aain& !alais#& =iEEin#ss& a!n#sia& A#riA2#ral
#=#!a& ?#i%2t %ain& a"=o!inal Aain& inso!nia& 2>Ao#st2#sia& tinnits& t#n=on rAtr#&
an= =>s%#sia1
T2#s# !a> 2av# no casal r#lations2iA to atorvastatin1
OA2t2al!olo%ic o"s#rvations3 s## 8ARNINGS AND PR)CAUTIONS1
DRU. I"TERACTIO"S
Overvie)
P2ar!acoGin#tic int#raction st=i#s con=ct#= ?it2 =r%s in 2#alt2> s"B#cts
!a> not =#t#ct t2# Aossi"ilit> o< a Aot#ntial =r% int#raction in so!# Aati#nts =# to
=i<<#r#nc#s in n=#rl>in% =is#as#s an= s# o< conco!itant !#=ications (s## also
8ARNINGS AND PR)CAUTIONS& SA#cial PoAlationsD R#nal Ins<<ici#nc>D
Pati#nts ?it2 S#v#r# H>A#rc2ol#st#rol#!iaD G#riatric Us#$1
Concoitant T&era%$ )it& Ot&er Li%i* Metabolis Re'ulators : *as#=
on Aost-!arG#tin% srv#illanc#& %#!<i"roEil& <#no<i"rat#& ot2#r <i"rat#s& an= liAi=-
!o=i<>in% =os#s o< niacin (nicotinic aci=$ !a> incr#as# t2# risG o< !>oAat2> ?2#n
%iv#n conco!itantl> ?it2 HMG-CoA r#=ctas# in2i"itors& Aro"a"l> "#cas# t2#> can
Aro=c# !>oAat2> ?2#n %iv#n alon# (s## 8ARNINGS O Mscl# )<<#cts$1 T2#r#<or#&
co!"in#= =r% t2#raA> s2ol= "# aAAroac2#= ?it2 cationD lo?#r startin% an=
!aint#nanc# =os#s o< atorvastatin s2ol= "# consi=#r#=1
C$toc&roe P,:;1,e*iate* Interactions : Atorvastatin is !#ta"oliE#= ">
t2# c>toc2ro!# P-(+0 iso#nE>!#& CYP 6A(1 )r>t2ro!>cin& a CYP 6A( in2i"itor&
incr#as#= atorvastatin Alas!a l#v#ls "> (0H1 Coa=!inistration o< CYP 6A(
in2i"itors& sc2 as %raA#<rit Bic#& so!# !acroli=# anti"iotics (i1#1 #r>t2ro!>cin&
clarit2ro!>cin$& i!!nosAAr#ssants (c>closAorin#$& aEol# anti<n%al a%#nts (i1#1
itraconaEol#& G#toconaEol#$& Arot#as# in2i"itors& or t2#
anti=#Ar#ssant& n#<aEo=on#& !a> 2av# t2# Aot#ntial to incr#as# Alas!a
conc#ntrations o< HMG CoA r#=ctas# in2i"itors& incl=in% DYSLIP - 10 (s##
R).)R)NC)S$1 Cation s2ol= t2s "# #@#rcis#= ?it2 conco!itant s# o< t2#s#
a%#nts an= lo?#r startin% an= !aint#nanc# =os#s o< atorvastatin s2ol= "# consi=#r#=
?2#n taG#n conco!itantl> ?it2 t2# a<or#!#ntion#= =r%s (s## 8ARNINGS AND
PR)CAUTIONS& P2ar!acoGin#tic Int#ractions& Mscl# )<<#cts& R#nal Ins<<ici#nc>
an= )n=ocrin# .nctionD DOSAG) AND ADMINISTRATIOND R).)R)NC)S$1
TransAort#r In2i"itors3 Atorvastatin an= atorvastatin-!#ta"olit#s ar# s"strat#s
o< t2# OATP1*1 transAort#r1 In2i"itors o< t2# OATP1*1 (#1%1 c>closAorin#$ can
incr#as# t2# "ioavaila"ilit> o< atorvastatin (s## D)TAIL)D PHARMACOLOGY&
H!an P2ar!acoGin#tics$1
In=c#rs o< c>toc2ro!# P(+0 6A3 Conco!itant a=!inistration o< atorvastatin
?it2 in=c#rs o< c>toc2ro!# P(+0 6A( (#% #<avir#nE& ri<a!Ain$ can l#a= to varia"l#
r#=ctions in Alas!a conc#ntrations o< atorvastatin1 D# to t2# =al int#raction
!#c2anis! o< ri<a!Ain& (c>toc2ro!# P(+0 6A( in=ction an= in2i"ition o<
2#Aatoc>t# AtaG# transAort#r OATP1*1$& si!ltan#os co-a=!inistration o<
atorvastatin ?it2 ri<a!Ain r#slt#= in a !#an incr#as# in C!a@ an= AUC o<
atorvastatin o< 1' an= 150H& r#sA#ctiv#l>1 In contrast& a =#la>#= a=!inistration o<
atorvastatin a<t#r a=!inistration o< ri<a!Ain 2as "##n associat#= ?it2 a si%ni<icant
r#=ction (aAAro@i!at#l> 70H$ in atorvastatin Alas!a conc#ntrations1
Dru',Dru' Interactions
S%%#st#=3 T2# =r%s list#= in t2is ta"l# ar# "as#= on #it2#r =r% int#ractions
st=i#s& cas# r#Aorts& or Aot#ntial int#ractions =# to t2# #@A#ct#= !a%nit=# an=
s#riosn#ss o< t2# int#raction (i1#1&t2os# i=#nti<i#= as contrain=icat#=$1 Int#ractions
?it2 ot2#r =r%s 2av# not "##n #sta"lis2#=1
Table <, Establis&e* or Potential Dru',Dru' Interactions
ProA#r na!# )<<#ct Clinical co!!#nt
*il# Aci= S#C#strants Pati#nts ?it2 !il= to !o=#rat# HC3 82#n DYSLIP - 10 iss#=
concrr#ntl> LDL-C r#=ction ( -(+H$
?2#n DYSLIP - 10 ?it2 col#stiAol or an> ot2#r r#sin& an
10 !% an= col#stiAol '0 % ?#r# int#rval o< at l#ast ' 2ors s2ol= "#
coa=!inist#r#= t2an ?2#n #it2#r =r% ?as !aintain#= "#t?##n t2# t?o =r%s&
a=!inist#r#= alon# (-6+H <or DYSLIP - 10 sinc# t2# a"sorAtion o< DYSLIP - 10
!a>
an= -''H <or col#stiAol$1 "# i!Aair#= "> t2# r#sin1
Pati#nts ?it2 s#v#r# HC3 LDL-C
r#=ction ?as si!ilar (-+6H$ ?2#n
DYSLIP - (0 !% an= col#stiAol '0 % ?#r#
coa=!inist#r#= ?2#n co!Aar#= to t2at
?it2 DYSLIP - 70 !% alon#1 1 Alas!a
conc#ntration (R'0H$ ?2#n DYSLIP - 10
(0 !% Als col#stiAol '0 % ?#r#
coa=!inist#r#= co!Aar#= ?it2 DYSLIP -
(0 !% alon#1
Ho?#v#r& t2# co!"ination =r% t2#raA>
?as l#ss #<<#ctiv# in lo?#rin% TG t2an
DYSLIP - 10 !onot2#raA> in "ot2 t>A#s o<
2>A#rc2ol#st#rol#!ic Aati#nts1
.i"ric Aci= D#rivativ#s in t2# risG o< !>oAat2> =rin% tr#at!#nt Alt2o%2 t2#r# is li!it#= #@A#ri#nc#
(G#!<i"roEil& .#no<i"rat#& ?it2 ot2#r =r%s in t2is class& incl=in% ?it2 t2# s# o< DYSLIP - 10 %iv#n
*#Ea<i"rat#$ an= Niacin atorvastatin& ?it2 concrr#nt concrr#ntl> ?it2 <i"ric aci=
(nicotinic aci=$ 1 a=!inistration ?it2 a <i"ric aci= =#rivativ# =#rivativ#s an= niacin& t2# "#n#<its
an= risGs o< sc2 co!"in#= t2#raA>
s2ol= "# car#<ll> consi=#r#= (s##
8ARNINGS AND PR)CAUTIONS&
Mscl# )<<#cts an= R).)R)NC)S$
Co!arin Anticoa%lants No clinicall> si%ni<icant #<<#ct on DYSLIP - 10 2a= no clinicall>
Arot2ro!"in ti!# si%ni<icant #<<#ct on Arot2ro!"in
ti!# ?2#n a=!inist#r#= to Aati#nts
r#c#ivin% c2ronic ?ar<arin t2#raA>
(s## R).)R)NC)S$1
Di%o@in In 2#alt2> s"B#cts& =i%o@in P/ at st#a=>- Pati#nts taGin% =i%o@in s2ol= "#
stat# ?#r# not si%ni<icantl> alt#r#= "> !onitor#= aAAroAriat#l>
coa=!inistration o< =i%o@in 01'+ !% an=
DYSLIP - 10 !% =ail>1
1 in =i%o@in st#a=>-stat# conc#ntrations
"> R'0H <ollo?in% coa=!inistration o<
=i%o@in 01'+ !% an= DYSLIP - 70 !%
=ail> (s## D)TAIL)D
PHARMACOLOGY& H!an
P2ar!acoGin#tics$1

Anti2>A#rt#nsiv# In 2#alt2> s"B#cts& atorvastatin P/ ?#r# S## D)TAIL)D
A%#nts3 DYSLIP - 70 !% an= a!lo=iAin# 10 !% at PHARMACOLOGY
O A!lo=iAin# st#a=> stat#1 No aAAar#nt
c2an%#s in *P H!an
or HR1
l :inaAri St#a=>-stat# CinaAril =osin% o< 70 !%
:D =i= not si%ni<icantl> a<<#ct t2# P/
Aro<il# o< atorvastatin ta"l#ts 10 !% :D1
Oral Contrac#Ativ#s Alas!a conc#ntrations (AUC l#v#ls$ o< T2#s#
incr#as#s s2ol=
an= Hor!on# nor#t2in=on# "> R60H an= #t2in>l "# consi=#r#=
R#Alac#!#nt #stra=iol "> R'0H <ollo?in% ?2#n s#l#ctin% an oral
T2#raA> coa=!inistration o< DYSLIP - 10 ?it2 an oral contrac#Ativ#1
contrac#Ativ# containin% 1 !%
nor#t2in=on# an= 6+ S% #t2in>l #stra=iol1
1 In clinical st=i#s& DYSLIP - 10 ?as s#=
conco!itantl> ?it2 #stro%#n r#Alac#!#nt
t2#raA> ?it2ot #vi=#nc# to =at# o<
clinicall> si%ni<icant a=v#rs# int#ractions1
Antaci=s 1 in Alas!a conc#ntrations o< DYSLIP - 10
"> R6+H <ollo?in% a=!inistration o<
al!in! an= !a%n#si! "as#= antaci=s&
sc2 as Maalo@T TC SsA#nsion1
LDL-C r#=ction ?as not alt#r#=D TG-
lo?#rin% #<<#ct o< DYSLIP - 10 !a> "#
a<<#ct#=1
Ci!#ti=in# No #<<#ct on Alas!a conc#ntrations or
LDL-C lo?#rin% #<<icac> o< DYSLIP - 10
in TG-lo?#rin% #<<#ct o< DYSLIP - 10 <ro!
6(H to '0H
DiltiaE#!
H>=roc2lori=# St#a=>-stat# =iltiaE#! incr#as#s t2#
#@Aosr#& "as#= on AUCLASTs& o< a sin%l#
=os# o< atorvastatin "> aAAro@i!at#l>
+0H1
AntiA>rin# DYSLIP - 10 2a= no #<<#ct on t2# P/ o< AntiA>rin#
?as s#= as
antiA>rin# a non-sA#ci<ic !o=#l <or
=r%s
!#ta"oliE#= "> t2# !icroso!al
2#Aatic #nE>!# s>st#!
c>toc2ro!# P-(+0 s>st#!$1
Int#ractions ?it2 ot2#r
=r%s
!#ta"oliE#= via t2# sa!#
c>toc2ro!# isoE>!#s ar# not
#@A#ct#=1
Macroli=# Anti"ioticsIn 2#alt2> a=lts& coa=!inistration o< S##
8ARNINGS AND
(aEit2ro!>cin& DYSLIP (10 !% :D$ an= aEit2ro!>cin PR)CAUTIONS& Mscl#
clarit2ro!>cin& (+00 !% :D$ =i= not si%ni<icantl> alt#r )<<#ctsD
#r>t2ro!>cin$1 t2# Alas!a conc#ntrations o< atorvastatin D)TAIL)D
Clarit2ro!>cin an= Alas!a conc#ntration "> R(0H ?it2 PHARMACOLOGY
O
#r>t2ro!>cin ar# "ot2 #r>t2ro!>cin (+00 !% :ID$
an= R70H H!an P2ar!acoGin#tics
CYP6A( in2i"itors ?it2 clarit2ro!>cin (+00 !% *ID$ ?2#n
coa=!inist#r#= ?it2 atorvastatin (10 !%
:D$
Prot#as# in2i"itors Alas!a conc#ntrations o< atorvastatin N#l<inavir is a
Gno?n CYP6A(
(n#l<inavir !#s>lat#$ ?2#n atorvastatin 10 !% :D is in2i"itor1
coa=!inist#r#= ?it2 n#l<inavir !#s>lat#
1'+0 !% *ID
1 AUC "> ,(H an= 1 C!a@ "> 1''H

C>closAorin# Conco!itant a=!inistration o< In cas#s ?2#r# co-
a=!inistration o<
atorvastatin 10 !% an= c>closAorin# atorvastatin ?it2 c>closAorin#
is +1' !%-G%-=a> r#slt#= in a ,1, <ol= n#c#ssar>& t2# =os# o<
atorvastatin
incr#as# in #@Aosr# to atorvastatin1 s2ol= not #@c##= 10!%
S## 8ARNINGS an=
PR)CAUTIONS - Mscl#
)<<#ctsD
D)TAIL)D
PHARMACOLOGY O H!an
P2ar!acoGin#tics

ItraconaEol# Conco!itant a=!inistration o< S## D)TAIL)D
atorvastatin '0-(0!% an= PHARMACOLOGY O H!an
itraconaEol# '00!% =ail> r#slt#= P2ar!acoGin#tics
in a '1+-616-<ol= incr#as# in
atorvastatin AUC1

L#%#n=3 HC J 2>A#rc2ol#st#rol#!iaD TG J Tri%l>c#ri=#sD P/ J A2ar!acoGin#ticsD *P J
*loo= Pr#ssr#D HR J H#art Rat#D AUC J Ar#a n=#r t2# crv#
Dru',!oo* Interactions
Coa=!inistration o< %raA#<rit Bic# 2as t2# Aot#ntial to incr#as# Alas!a
conc#ntrations o< HMG CoA r#=ctas# in2i"itors incl=in% DYSLIP - 101 T2#
#Cival#nt o< 11' litr#s A#r =a> r#slt#= in a '1+ <ol= incr#as# in AUC o< atorvastatin1
Dru',Herb Interactions
Int#ractions ?it2 2#r"al Aro=cts 2av# not "##n #sta"lis2#=1
Dru'3Laborator$ Test Interactions
DYSLIP - 10 !a> #l#vat# s#r! transa!inas# an= cr#atin# Ginas# l#v#ls (<ro!
sG#l#tal !scl#$1 In t2# =i<<#r#ntial =ia%nosis o< c2#st Aain in a Aati#nt on t2#raA> ?it2
DYSLIP - 10 car=iac an= noncar=iac <ractions o< t2#s# #nE>!#s s2ol= "#
=#t#r!in#=1 0100000,0+006,U110UAAArov#=U06-Qn-'007 07306
DOSA.E A"D ADMI"ISTRATIO"
Pati#nts s2ol= "# Alac#= on a stan=ar= c2ol#st#rol-lo?#rin% =i#t Kat l#ast
#Cival#nt to t2# A=lt Tr#at!#nt Pan#l III (ATP III$ TLC =i#tL "#<or# r#c#ivin%
DYSLIP - 10 an= s2ol= contin# on t2is =i#t =rin% tr#at!#nt ?it2 DYSLIP - 10 I<
aAAroAriat#& a Aro%ra! o< ?#i%2t control an= A2>sical #@#rcis# s2ol= "#
i!Al#!#nt#=1
Prior to initiatin% t2#raA> ?it2 DYSLIP - 10 s#con=ar> cas#s <or #l#vations in
Alas!a liAi= l#v#ls s2ol= "# #@cl=#=1 A liAi= Aro<il# s2ol= also "# A#r<or!#=1
Priar$ H$%erc&olesteroleia an* Cobine* 4Mi=e*5 D$sli%i*eia( Inclu*in'
!ailial Cobine* H$%erli%i*eia
T2# r#co!!#n=#= startin% =os# o< DYSLIP - 10 is 10 or '0 !% onc# =ail>&
=#A#n=in% on Aati#ntVs LDL-C r#=ction r#Cir#= (s## Ta"l#s 6 an= ($1 Pati#nts ?2o
r#Cir# a lar%# r#=ction in LDLC (!or# t2an (+H$ !a> "# start#= at (0 !% onc#
=ail>1 T2# =osa%# ran%# o< DYSLIP - 10 is 10 to 70 !% onc# =ail>1 Dos#s can "#
%iv#n at an> ti!# o< t2# =a> ?it2 or ?it2ot <oo=& an= s2ol= Ar#<#ra"l> "# %iv#n in
t2# #v#nin%1 A si%ni<icant t2#raA#tic r#sAons# is #vi=#nt ?it2in ' ?##Gs& an= t2#
!a@i!! r#sAons# is sall> ac2i#v#= ?it2in '-( ?##Gs1 T2# r#sAons# is !aintain#=
=rin% c2ronic t2#raA>1 A=Bst!#nts o< =osa%#& i< n#c#ssar>& s2ol= "# !a=# at
int#rvals o< ' to ( ?##Gs1 T2# !a@i!! =os# is 70 !%-=a>1
T2# <ollo?in% r#=ctions in total c2ol#st#rol an= LDL-C l#v#ls 2av# "##n
o"s#rv#= in ' =os#- r#sAons# st=i#s& an= !a> s#rv# as a %i=# to tr#at!#nt o< Aati#nts
?it2 !il= to !o=#rat# 2>A#rc2ol#st#rol#!ia3
TA*L) 61 Dos#-R#sAons# in Pati#nts ?it2 Mil= to Mo=#rat#
H>A#rc2ol#st#rol#!ia
(M#an P#rc#nt C2an%# <ro! *as#lin#$ a
DYSLIP - 10 Dos# (!%-=a>$
LiAi= Para!#t#r 10 '0 (0 70 (NJ''$ (NJ'0$ (NJ'1$ (NJ'6$
Total-C3 ,11 !!ol-L"
(',6 !%-=L$" -'5 -66 -6, -(+
LDL-C3 (15 !!ol-L"
(150 !%-=L$" -65 -(6 -+0 -00
a R#slts ar# Aool#= <ro! ' =os#-r#sAons# st=i#s
" M#an "as#lin# val#s
T2# =osa%# o< DYSLIP - 10 s2ol= "# in=ivi=aliE#= accor=in% t2# "as#lin#
LDL-C& total-C-HDL-C ratio an=-or TG l#v#ls to ac2i#v# t2# r#co!!#n=#= tar%#t
liAi= val#s at t2# lo?#st =os# n##=#= to ac2i#v# LDL-C tar%#t (s##
R#co!!#n=ations <or t2# Mana%#!#nt o< D>sliAi=#!ia an= t2# Pr#v#ntion o<
Car=iovasclar Dis#as# KCana=aL s!!ariE#= "#lo? in Ta"l# (& an=-or t2# T2ir=
R#Aort o< t2# C2ol#st#rol )=cation Pro%ra! KNC)P A=lt Tr#at!#nt Pan#l IIIL$&
an= t2# Aati#ntVs r#sAons#1 LiAi= l#v#ls s2ol= "# !onitor#= A#rio=icall> an=& i<
n#c#ssar>& t2# =os# o< DYSLIP - 10 a=Bst#= "as#= on tar%#t liAi= l#v#ls
r#co!!#n=#= "> %i=#lin#s1
Ta"l# (3 Cana=ian R#co!!#n=ations <or t2# Tar%#t LiAi= 9al#s "as#= on L#v#l o<
RisG
RisG cat#%or> Tar%#t L#v#ls
LDL-C l#v#l (!!ol-L$ Total-C-HDL-C
ratio
Hi%2W I '1+ an= I (10
(10->#ar risG o< CAD F'0H& or a 2istor> o<
=ia"#t#s !#llitsWW or an> at2#roscl#rotic
=is#as#$
Mo=#rat# I 61+ an= I +10
(10->#ar risG 11HO15H $
Lo?WWW I (1+ an= I 010
(10->#ar risG X10H $
Not#3 LDL-C J lo?-=#nsit> liAoArot#in c2ol#st#rol1
WAAoliAoArot#in * can "# s#= as an alt#rnativ# !#asr#!#nt& Aarticlarl> <or
<ollo?-A o< Aati#nts tr#at#= ?it2 statins1 An oAti!al l#v#l o< aAoliAoArot#in * in a
Aati#nt at 2i%2 risG is I015 %-L& in a Aati#nt at !o=#rat# risG I110+ %-L an= in a Aati#nt
at lo? risG I11' %-L1
WWIncl=#s Aati#nts ?it2 c2ronic Gi=n#> =is#as# an= t2os# n=#r%oin% lon%-t#r!
=ial>sis1
WWWIn t2# Yv#r> lo?V risG strat!& tr#at!#nt !a> "# =#<#rr#= i< t2# 10->#ar #sti!at# o<
car=iovasclar =is#as# is I+H an= t2# LDL-C l#v#l is I+10 !!ol-L1
Severe D$sli%i*eias
In Aati#nts ?it2 s#v#r# =>sliAi=#!ias& incl=in% 2o!oE>%os an= 2#t#roE>%os
<a!ilial 2>A#rc2ol#st#rol#!ia an= =>s"#taliAoArot#in#!ia (T>A# III$& 2i%2#r =osa%#s
(A to 70 !%-=a>$ !a> "# r#Cir#= (s## 8ARNINGS AND PR)CAUTIONS&
P2ar!acoGin#tic Int#ractions& Mscl# )<<#ctsD DRUG INT)RACTIONS$1
Hetero8$'ous !ailial H$%erc&olesteroleia in Pe*iatric Patients 401,09
$ears of a'e5
In t2is AoAlation& t2# r#co!!#n=#= startin% =os# o< DYSLIP - 10 is 10
!%-=a>D t2# !a@i!! r#co!!#n=#= =os# is '0 !%-=a> (=os#s %r#at#r t2an '0
!%-=a> 2av# not "##n st=i#= in t2is Aati#nt AoAlation$1 Dos#s s2ol= "#
in=ivi=aliE#= accor=in% to t2# r#co!!#n=#= %oal o< t2#raA> (s## NC)P P#=iatric
Pan#l Gi=#lin#s& INDICATIONS AND CLINICAL US) an= PHARMACOLOGY&
Clinical St=i#s$1 A=Bst!#nts s2ol= "# !a=# at int#rvals o< ( ?##Gs or !or#1
NC)P (National C2ol#st#rol )=cation Pro%ra!$ P#=iatric Pan#l Gi=#lin#s
Classi<ication o< c2ol#st#rol l#v#ls in A#=iatric Aati#nts ?it2 a <a!ilial 2istor> o<
2>A#rc2ol#st#rol#!ia or Ar#!atr# car=iovasclar =is#as# is s!!ariE#= "#lo?3
Cat#%or> Total-C (!!ol-L LDL-C (!!ol-L K!%-=LL$
K!%-=LL$
Acc#Ata"l# I(1( K1,0L I'17 K110L
*or=#rlin# (1(-+11 K1,0-155L '17-616 K110-1'5L
Hi%2 F+1' K'00L F61( K160L
Clinical trials con=ct#= t2at #valat#= atorvastatin in t2# Ari!ar> Ar#v#ntion
o< !>ocar=ial in<arction s#= a =os# o< 10 !% atorvastatin onc# =ail>1
.or s#con=ar> Ar#v#ntion o< !>ocar=ial in<arction& oAti!al =osin% !a> ran%#
<ro! 10 !% to 70 !% atorvastatin onc# =ail>& to "# %iv#n at t2# =iscr#tion o< t2#
Ar#scri"#r& taGin% into accont t2# #@A#ct#= "#n#<it an= sa<#t> consi=#rations r#l#vant
to t2# Aati#nt to "# tr#at#=1
Concoitant T&era%$
S## DRUG INT)RACTIONS1
Dosa'e in Patients )it& Renal Insufficienc$
S## 8ARNINGS AND PR)CAUTIONS1
O/ERDOSA.E
T2#r# is no sA#ci<ic tr#at!#nt <or atorvastatin ov#r=osa%#1 S2ol= an ov#r=os#
occr& t2# Aati#nt s2ol= "# tr#at#= s>!Ato!aticall> an= sAAortiv# !#asr#s
institt#= as r#Cir#=1 D# to #@t#nsiv# =r% "in=in% to Alas!a Arot#ins& 2#!o=ial>sis
is not #@A#ct#= to si%ni<icantl> #n2anc# atorvastatin cl#aranc#1 (S## AD9)RS)
R)ACTIONS$
.or t2# !ana%#!#nt o< a ssA#ct#= =r% ov#r=os#& contact >or r#%ional
Poison Control C#ntr#1
ACTIO" A"D CLI"ICAL PHARMACOLO.#
Mec&anis of Action
DYSLIP - 10 (atorvastatin calci!$ is a s>nt2#tic liAi=-lo?#rin% a%#nt1 It is a
s#l#ctiv#& co!A#titiv# in2i"itor o< 6-2>=ro@>-6-!#t2>l%ltar>l-co#nE>!# A (HMG-
CoA$ r#=ctas#1 T2is #nE>!# catal>E#s t2# conv#rsion o< HMG-CoA to !#valonat#&
?2ic2 is an #arl> an= rat#-li!itin% st#A in t2# "ios>nt2#sis o< c2ol#st#rol1
DYSLIP - 10 lo?#rs Alas!a c2ol#st#rol an= liAoArot#in l#v#ls "> in2i"itin%
HMG-CoA r#=ctas# an= c2ol#st#rol s>nt2#sis in t2# liv#r an= "> incr#asin% t2#
n!"#r o< 2#Aatic Lo? D#nsit> LiAoArot#in (LDL$ r#c#Ators on t2# c#ll-sr<ac# <or
#n2anc#= AtaG# an= cata"olis! o< Lo? D#nsit> LiAoArot#in (LDL$1
DYSLIP - 10 r#=c#s LDL-C2ol#st#rol (LDL-C$ an= t2# n!"#r o< LDL
Aarticl#s1 LiAitor also r#=c#s 9#r> Lo? D#nsit> LiAoArot#in-C2ol#st#rol (9LDL-C$&
s#r! tri%l>c#ri=#s (TG$ an= Int#r!#=iat# D#nsit> LiAoArot#ins (IDL$& as ?#ll as t2#
n!"#r o< aAoliAoArot#in * (aAo *$ containin% Aarticl#s& "t incr#as#s Hi%2 D#nsit>
LiAoArot#in-C2ol#st#rol (HDL-C$1 )l#vat#= s#r! c2ol#st#rol =# to #l#vat#= LDL-C
is a !aBor risG <actor <or t2# =#v#loA!#nt o< car=iovasclar =is#as#1 Lo? s#r!
conc#ntration o< HDL-C is also an in=#A#n=#nt risG <actor1 )l#vat#= Alas!a TG is also
a risG <actor <or car=iovasclar =is#as#& Aarticlarl> i< =# to incr#as#= IDL& or
associat#= ?it2 =#cr#as#= HDL-C or incr#as#= LDL-C1
)Ai=#!iolo%ic& clinical an= #@A#ri!#ntal st=i#s 2av# #sta"lis2#= t2at 2i%2
LDL-C& lo? HDL-C an= 2i%2 Alas!a TG Aro!ot# 2!an at2#roscl#rosis an= ar# risG
<actors <or =#v#loAin% car=iovasclar =is#as#1 So!# st=i#s 2av# also s2o?n t2at t2#
total (TC$3HDL-C ratio (TC3HDL-C$ is t2# "#st Ar#=ictor o< coronar> art#r> =is#as#1
In contrast& incr#as#= l#v#ls o<
HDL-C ar# associat#= ?it2 =#cr#as#= car=iovasclar risG1 Dr% t2#raAi#s t2at
r#=c# l#v#ls o< LDL-C or =#cr#as# TG ?2il# si!ltan#osl> incr#asin% HDL-C 2av#
=#!onstrat#= r#=ctions in rat#s o< car=iovasclar !ortalit> an= !or"i=it>1
P&araco*$naics
T2# lo?#rin% o< total c2ol#st#rol& LDL-C an= AAo* 2av# "##n s2o?n to r#=c#
t2# risG o< car=iovasclar #v#nts an= !ortalit>1
DYSLIP - 10 (atorvastatin calci!$ is a s#l#ctiv#& co!A#titiv# in2i"itor o<
HMG-CoA r#=ctas#1 In "ot2 s"B#cts an= in Aati#nts ?it2 2o!oE>%os an=
2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia& non<a!ilial <or!s o<
2>A#rc2ol#st#rol#!ia& !i@#= =>sliAi=#!ia& 2>A#rtri%l>c#ri=#!ia& an=
=>s"#taliAoArot#in#!ia& DYSLIP - 10 2as "##n s2o?n to r#=c# l#v#ls o< total
c2ol#st#rol (total-C$& LDL-C& aAo * an= total TG& an= rais#s HDL-C l#v#ls1
)Ai=#!iolo%ic an= clinical st=i#s 2av# associat#= t2# risG o< coronar> art#r>
=is#as# (CAD$ ?it2 #l#vat#= l#v#ls o< total-C& LDL-C an= =#cr#as#= l#v#ls o< HDL-
C1 T2#s# a"nor!aliti#s o< liAoArot#in !#ta"olis! ar# consi=#r#= as !aBor contri"tors
to t2# =#v#loA!#nt o< t2# =is#as#1 Ot2#r <actors& #1%1 int#ractions "#t?##n
liAi=s-liAoArot#ins an= #n=ot2#li!& Alat#l#ts an= !acroA2a%#s& 2av# also "##n
incri!inat#= in t2# =#v#loA!#nt o< 2!an at2#roscl#rosis an= o< its co!Alications1
R#%ar=l#ss o< t2# int#rv#ntion s#= (lo?-<at-lo? c2ol#st#rol =i#t& Aartial il#al ">Aass
sr%#r> or A2ar!acolo%ic t2#raA>$& #<<#ctiv# tr#at!#nt o< 2>A#rc2ol#st#rol#!ia
=>sliAi=#!ia 2as consist#ntl> "##n s2o?n to r#=c# t2# risG o< CAD1
DYSLIP - 10 r#=c#s LDL-C an= t2# n!"#r o< LDL Aarticl#s& lo?#rs 9#r>
Lo? D#nsit> LiAoArot#in-C2ol#st#rol (9LDL-C$ an= s#r! tri%l>c#ri=#& r#=c#s t2#
n!"#r o< aAo * containin% Aarticl#s& an= also incr#as#s HDL-C1 DYSLIP - 10 is
#<<#ctiv# in r#=cin% LDL-C in Aati#nts ?it2 2o!oE>%os <a!ilial
2>A#rc2ol#st#rol#!ia& a con=ition t2at rar#l> r#sAon=s to an> ot2#r liAi=-lo?#rin%
!#=ication1 In a==ition to t2# a"ov# #<<#cts&
DYSLIP - 10 r#=c#s IDL-C an= aAoliAoArot#in ) (aAo )$ in Aati#nts ?it2
=>s"#taliAoArot#in#!ia (T>A# III$1
In Aati#nts ?it2 t>A# II 2>A#rliAi=#!ia& atorvastatin i!Arov#= #n=ot2#lial
=>s<nction1 Atorvastatin si%ni<icantl> i!Arov#= <lo?-!#=iat#= #n=ot2#li!-
=#A#n=#nt =ilatation in=c#= "> r#activ# 2>A#r#!ia& as ass#ss#= "> "rac2ial
ltrason= (AI0101$1
P&araco+inetics
A"sorAtion3 Atorvastatin is raAi=l> a"sor"#= a<t#r oral a=!inistrationD !a@i!al
Alas!a conc#ntrations occr ?it2in 1 to ' 2ors1 )@t#nt o< a"sorAtion an= Alas!a
atorvastatin conc#ntrations incr#as# in AroAortion to atorvastatin =os#1 Atorvastatin
ta"l#ts ar# 5+-55H "ioavaila"l# co!Aar#= to soltions1 T2# a"solt# "ioavaila"ilit>
(Aar#nt =r%$ o< atorvastatin is aAAro@i!at#l> 1'H an= t2# s>st#!ic availa"ilit> o<
HMG-CoA r#=ctas# in2i"itor> activit> is aAAro@i!at#l> 60H1 T2# lo? s>st#!ic
availa"ilit> is attri"t#= to Ar#s>st#!ic cl#aranc# in %astroint#stinal !cosa an=-or
<irst-Aass !#ta"olis! in t2# liv#r1 Alt2o%2 <oo= =#cr#as#s t2# rat# an= #@t#nt o< =r%
a"sorAtion "> aAAro@i!at#l> '+H an= 5H& as ass#ss#= "> C!a@ an= AUC
r#sA#ctiv#l>& LDL-C r#=ction an= HDL-C #l#vation ar# si!ilar ?2#n atorvastatin is
%iv#n ?it2 an= ?it2ot <oo=1 Plas!a atorvastatin conc#ntrations ar# lo?#r
(aAAro@i!at#l> 60H <or C!a@ an= AUC$ <ollo?in% =r% a=!inistration in t2#
#v#nin% co!Aar#= ?it2 !ornin% =osin%1 Ho?#v#r& LDL-C r#=ction an= HDL-C
#l#vation ar# t2# sa!# r#%ar=l#ss o< t2# ti!# o< =r% a=!inistration1
Distribution: M#an vol!# o< =istri"tion o< atorvastatin is aAAro@i!at#l> 671 lit#rs1
Atorvastatin is J57H "on= to Alas!a Arot#ins1 A "loo=-Alas!a ratio o< aAAro@i!at#l>
01'+ in=icat#s Aoor =r% A#n#tration into r#= "loo= c#lls1 *as#= on o"s#rvations in
rats& atorvastatin is liG#l> to "# s#cr#t#= in 2!an !ilG1
Metabolis: Atorvastatin is #@t#nsiv#l> !#ta"oliE#= to ort2o- an= Aara-2>=ro@>lat#=
=#rivativ#s "> c>toc2ro!# P-(+0 6A( (CYP 6A($ an= to varios "#ta-o@i=ation
Aro=cts1 In vitro& in2i"ition o< HMG-CoA r#=ctas# "> ort2o- an= Aara-2>=ro@>lat#=
!#ta"olit#s is #Cival#nt to t2at o< atorvastatin1 AAAro@i!at#l> ,0H o< circlatin%
in2i"itor> activit> <or HMG- CoA r#=ctas# is attri"t#= to activ# !#ta"olit#s1 In
ani!als& t2# ort2o-2>=ro@> !#ta"olit# n=#r%o#s <rt2#r %lcroni=ation1 Atorvastatin
an= its !#ta"olit#s ar# #li!inat#= "> "iliar> #@cr#tion1
E=cretion: Atorvastatin is #li!inat#= Ari!aril> in "il# <ollo?in% 2#Aatic an=-or
#@tra2#Aatic !#ta"olis!D 2o?#v#r& t2# =r% =o#s not aAA#ar to n=#r%o si%ni<icant
#nt#ro2#Aatic r#circlation1 M#an Alas!a #li!ination 2al<-li<# o< atorvastatin in
2!ans is aAAro@i!at#l> 1( 2ors& "t t2# 2al<-li<# <or in2i"itor> activit> <or HMG-
CoA r#=ctas# is '0 to 60 2ors =# to t2# contri"tion o< lon%#r-liv#= activ#
!#ta"olit#s1 L#ss t2an 'H o< a =os# o< atorvastatin is r#cov#r#= in rin# <ollo?in%
oral a=!inistration1
S%ecial Po%ulations an* Con*itions
Pe*iatrics3 Ass#ss!#nt o< A2ar!acoGin#tic Aara!#t#rs sc2 as C!a@& AUC an=
"ioavaila"ilit> o< DYSLIP - 10 in A#=iatric Aati#nts (F10-I1, >#ars ol=&
Aost!#narc2#$ ?as not A#r<or!#= =rin% t2# 0-!ont2& Alac#"o-controll#= trial
r#<#rr#= to #arli#r (s## Clinical St=i#s - H#t#roE>%os .a!ilial H>A#rc2ol#st#rol#!ia
in P#=iatric Pati#nts an= PR)CAUTIONS -P#=iatric Us#$1
.eriatrics: Plas!a conc#ntrations o< atorvastatin ar# 2i%2#r (aAAro@i!at#l> (0H <or
C!a@ an= 60H <or AUC$ in 2#alt2> #l=#rl> s"B#cts (a%# 0+ >#ars or ol=#r$ co!Aar#=
?it2 >on%#r in=ivi=als1 LDL-C r#=ction& 2o?#v#r& is co!Aara"l# to t2at s##n in
>on%#r Aati#nt AoAlations1
.en*er: Plas!a conc#ntrations o< atorvastatin in ?o!#n =i<<#r (aAAro@i!at#l> '0H
2i%2#r <or C!a@ an= 10H lo?#r <or AUC$ <ro! t2os# in !#nD 2o?#v#r& t2#r# is no
clinicall> si%ni<icant =i<<#r#nc# in LDL-C r#=ction "#t?##n !#n an= ?o!#n1
Race: Plas!a conc#ntrations o< atorvastatin ar# si!ilar in "lacG an= ?2it# s"B#cts1
He%atic Insufficienc$: Plas!a conc#ntrations o< atorvastatin ar# !arG#=l> incr#as#=
(aAAro@i!at#l> 10-<ol= in C!a@ an= 11-<ol= in AUC$ in Aati#nts ?it2 c2ronic
alco2olic liv#r =is#as# (C2il=s-P%2 *$1
Renal Insufficienc$: Plas!a conc#ntrations an= LDL-C lo?#rin% #<<icac> o<
DYSLIP - 10 ar# si!ilar in Aati#nts ?it2 !o=#rat# r#nal ins<<ici#nc> co!Aar#= ?it2
Aati#nts ?it2 nor!al r#nal <nction1 Ho?#v#r& sinc# s#v#ral cas#s o< r2a"=o!>ol>sis
2av# "##n r#Aort#= in Aati#nts ?it2 a 2istor> o< r#nal ins<<ici#nc> o< nGno?n
s#v#rit>& as a Ar#cationar> !#asr# an= A#n=in% <rt2#r #@A#ri#nc# in r#nal =is#as#&
t2# lo?#st =os# (10 !%-=a>$ o< DYSLIP - 10 s2ol= "# s#= in t2#s# Aati#nts1 Si!ilar
Ar#cations aAAl> in Aati#nts ?it2 s#v#r# r#nal ins<<ici#nc> Kcr#atinin# cl#aranc# I60
!L-!in (I01+ !L-s#c$LD t2# lo?#st =osa%# s2ol= "# s#= an= i!Al#!#nt#= catiosl>
(s## 8ARNINGS AND PR)CAUTIONS& Mscl# )<<#ctsD DRUG INT)RACTIONSD
DOSAG) AND ADMINISTRATION$1
STORA.E A"D STABILIT#
Stor# at controll#= roo! t#!A#ratr# 1+ to 60ZC1
SPECIAL HA"DLI". I"STRUCTIO"S
Not aAAlica"l#1
DOSA.E !ORMS( COMPOSITIO" A"D PAC>A.I".
Dosa'e !ors
DYSLIP - 10 (atorvastatin calci!$ ta"l#ts ar# <or!lat#= <or oral
a=!inistration an= ar# availa"l# in ta"l#t =os#s o< 10 !%& '0 !%& (0 !% an= 70 !%1
Tablet Co%osition
)ac2 ta"l#t contains #it2#r 10 !%& '0 !%& (0 !% or 70 !% atorvastatin as t2#
activ# in%r#=i#nt1 )ac2 ta"l#t also contains t2# <ollo?in% non-!#=icinal in%r#=i#nts3
calci! car"onat#& croscar!#llos# so=i!& 2>=ro@>AroA>l c#lllos#& 2>=ro@>AroA>l
!#t2>lc#lllos#& lactos# !ono2>=rat#& !a%n#si! st#arat#& !icrocr>stallin# c#lllos#&
Aol>#t2>l#n# %l>col& Aol>sor"at# 70& si!#t2icon# #!lsion& talc& an= titani! =io@i=#1
T2# 10!%& '0!%& an= (0!% ta"l#ts also contain can=#lilla ?a@1
DYSLIP - 10 (atorvastatin calci!$ is availa"l# in =osa%# str#n%t2s o< 10 !%&
'0 !%& (0 !% an= 70 !% atorvastatin A#r ta"l#t1
Pac+a'in'
01 ': 10 @ 10Vs *list#r PacGin%
<1 ': 10 @ 10Vs *list#r PacGin%
:1 ': 10 @ 10Vs *list#r PacGin%
?1 ': 10 @ 10Vs *list#r PacGin%
PART II: SCIE"TI!IC I"!ORMATIO"
PHARMACEUTICAL I"!ORMATIO"
Dru' Substance
ProA#r na!#3 Atorvastatin calci!
C2#!ical na!#3 KR-(RW&RW$L-'-((-<loroA2#n>l$-[&=-=i2>=ro@>-+-(1-
!#t2>l#t2>l$6- A2#n>l-(-K(A2#n>la!ino$car"on>lL-1H-A>rrol#-1-2#Atanoic aci=&
calci! salt ('31$ tri2>=rat#
)!Airical .or!la3 (C66H6(.N'O+$'CaP6H'O
Mol#clar 8#i%2t3 1'051('
Strctral <or!la3
D#scriAtion3 Atorvastatin calci! is a ?2it# to o<<-?2it# cr>stallin# Ao?=#r
t2at is Aracticall> insol"l# in aC#os soltions o< AH ( an= "#lo?1 Atorvastatin
calci! is v#r> sli%2tl> sol"l# in =istill#= ?at#r& AH ,1( A2osA2at# "<<#r an=
ac#tonitril#& sli%2tl> sol"l# in #t2anol& an= <r##l> sol"l# in !#t2anol1
DE/ELOPME"T A"D /ALIDATIO" O! A METHOD
!OR SIMULTA"EOUS DE"SITOMETRIC
ESTIMATIO" O! ATOR/ASTATI" CALCIUM
AS THE BUL> DRU.
A"D I" TABLET DOSA.E !ORMS
S1 S1 D2an#s2?arW& S1 R1 D2an#s2?ar& P1 D#s2Aan=#& an= M1 Patil
D#Aart!#nt o< P2ar!ac#tical C2#!istr>& Poona Coll#%# o< P2ar!ac>&
*2arati 9i=>aA##t2 Univ#rsit>& )ran=?an#& Pn#-(11 067& In=ia
SUMMAR#
Atorvastatin calci! is a s#l#ctiv# HMG-CoA r#=ctas# in2i"itor an= 2as
liAi=-lo?#rin% activit>1 *ot2 ar# Aot#ntial anti-liAi=a#- !ic a%#nts s#= in co!"ination
to r#=c# t2# a!ont o< c2ol#st#rol an= tri%l>c#ri=#s in s>st#!ic circlation1 T2is
AaA#r =#scri"#s a si!Al#& Ar#cis#& an= accrat# HPTLC !#t2o= <or si!ltan#os
Canti<ication o< t2#s# co!- Aon=s as t2# "lG =r% an= in ta"l#t =osa%# <or!s1
C2ro!ato%raA2ic s#- Aaration o< t2# =r%s ?as A#r<or!#= on al!ini! Alat#s
Ar#coat#= ?it2 silica %#l 00 .'+(& ?it2 tol#n#O!#t2anol 73' (v-v$ as !o"il# A2as#1
D#nsi- to!#tric #valation o< t2# s#Aarat#= Eon#s ?as A#r<or!#= at '(0 n!1 T2# t?o
=r%s ?#r# satis<actoril> r#solv#= ?it2 R. val#s 01'6 \ 0101 an= 0165 \ 0101 <or
atorvastatin calci! an= r#sA#ctiv#l>1 T2# accrac> an= r#- lia"ilit> o< t2# !#t2o= ?as
ass#ss#= "> #valation o< lin#arit> (01(O'1( S%-Eon# <or "ot2 atorvastatin calci!$&
Ar#cision (intra-=a> RSD 1110O11'+H an= int#r-=a> RSD 1110O11((H <or atorvastatin
calci!& an= intra-=a> RSD 01(,O0106H an= int#r-=a> RSD 01(,O0177H $& accrac>
(571+1 \ 01'6H <or atorvastatin calci! an= 55101 \ 011+H <or$& an= sA#ci<icit>& in
accor=anc# ?it2 ICH %i=#lin#s1 T2# !#t2o= can "# s#= <or anal>sis o< t#n or !or#
<or!lations on a sin%l# Alat# an= is a raAi= an= cost-#<<#ctiv# Calit>-control tool <or
rotin# si!ltan#os anal>sis o< atorvastatin calci! an= #E#ti!i"# as t2# "lG =r%
an= in ta"l#t <or!lations1
I"TRODUCTIO"
Atorvastatin calci! (KR-(RW&RW$L-('-((-<loroA2#n>l$-[&=-=i2>=ro- @>-+-(1-
!#t2>l#t2>l$-6-A2#n>l-(-K(A2#n>la!ino$car"on>lL-1H-A>rrol#-1-2#- Atanoic aci=&
calci! salt ('31$ tri2>=rat#$ is a s>nt2#tic liAi=-lo?#rin% a%#nt1 It is a s#l#ctiv#
co!A#titiv# in2i"itor o< t2# #nE>!# HMG-CoA r#=ctas#& ?2ic2 catal>s#s t2#
conv#rsion o< HMG-CoA to !#valonat#& an i!Aortant rat#-li!itin% st#A in c2ol#st#rol
"ios>nt2#sis K1&'L1 (1-((-<loroA2#n>l$-6(R$-K6-((-<loroA2#n>l$-
6(S$!2>=ro@>lAroA>lL-((S$- ((-2>=ro@>A2#n>l$-'-aE#ti=inon#$ is anot2#r liAi=-
lo?#rin% a%#nt K6L1 Lit#ratr# r#vi#? r#v#als t2at !#t2o=s 2av# "##n r#Aort#= <or ana-
l>sis o< atorvastatin calci! "> 2i%2-A#r<or!anc# liCi= c2ro!ato%raA2> (HPLC$ K(O
,L an= 2i%2-A#r<or!anc# t2in-la>#r c2ro!ato%raA2> (HPTLC$ K7L& an= <or #sti!ation
"> HPLC K5L& #it2#r alon# or in co!- "ination ?it2 ot2#r =r%s& "t no HPTLC !#t2o=
2as >#t "##n r#Aort#= <or si!ltan#os #sti!ation o< atorvastatin calci!1 T2# ArAo-
s# o< t2is r#s#arc2 ?as to #sta"lis2 an= vali=at#& in accor=anc# ?it2 Int#r- national
Con<#r#nc# on Har!oniEation (ICH$ %i=#lin#s K10L& a si!Al#& accrat#& #cono!ical&
an= r#Aro=ci"l# Aroc#=r# <or Cantitativ# TLC ana-l>sis o< atorvastatin calci! as
t2# "lG =r% an= in ta"l#t =osa%# <or!s1
E@PERIME"TAL
C&eicals an* Rea'ents
8orGin% stan=ar=s o< A2ar!ac#tical %ra=# atorvastatin calci! ("atc2 no1
AT9-0+050,($ ("atc2 no1 )]- 07'0+0$ ?#r# o"- tain#= as %#n#ros %i<ts *io-=ot
P2ar!ac#ticals r#sA#ctiv#l>1 Assa> o< t2# sa!Al#s s2o?#= t2#> contain#= 5510'H
an= 55160H atorvastatin calci! r#sA#ctiv#l>1 .i@#=-=os# ta"l#ts (*i- torva$
containin% 10 !% atorvastatin calci! an= 10 !% ?#r# Arocr#= <ro! )v#r%r##n
r#s#arc2 la" C2#!icals an= r#a%#nts o< anal>tical-%ra=# ?#r# Arc2as#= <ro! M#rcG
C2#!icals& M!"ai& In=ia1
Pre%aration of Stan*ar* an* Sa%le Solutions
Atorvastatin calci! (10 !% #ac2$ ?#r# ?#i%2#= accrat#l>& trans<#rr#= to
t?o 10-!L vol!#tric <lasGs& an= =issolv#= in 10 !L !#t2anol1 *ot2 soltions ('
!L$ ?#r# <rt2#r =ilt#= ?it2 !#t2anol to <rnis2 <inal conc#ntrations o< 01' S% SL-11
.or anal>sis o< t2# ta"l#t =osa%# <or!& t?#nt> ta"l#ts& #ac2 containin% 10 !%
atorvastatin calci! an= 10 !%& ?#r# ?#i%2#= an= t2#ir av#ra%# ?#i%2t ?as calc-
lat#=1 T2# ta"l#ts ?#r# <in#l> Ao?=#r#= an= Ao?=#r #Cival#nt to 10 !% atorvastatin
calci! an= 10 !% #E#ti!i"# ?as accrat#l> ?#i%2#= an= =issolv#= in 10 !L
!#t2anol1 T2# soltion ?as c#ntri<%#= <or 1+ !in at 000 rA!& <ilt#r#= t2ro%2
82at!an no1 (1 <ilt#r AaA#r& an= t2# r#si=# ?as ?as2#= ?it2 !#t2anol1 T2# vol!#
o< t2# <iltrat# ?as a=Bst#= to 10 !L ?it2 t2# sa!# solv#nt1 T2is soltion (' !L$ ?as
<rt2#r =ilt#= ?it2 !#t2anol so t2# conc#ntration ?as t2# sa!# as t2at o< t2# <inal
stan=ar= soltion1
T&in,La$er C&roato'ra%&$
Anal>sis ?as A#r<or!#= on '0 c! ^ '0 c! al!ini! Alat#s Ar#- coat#= ?it2
silica %#l 00 .'+(1 *#<or# s#& Alat#s ?#r# ?as2#= ?it2 !#- t2anol& activat#= in an
ov#n at 10+ZC <or '0 !in& t2#n l#<t to cool at roo! t#!A#ratr#1 Stan=ar= soltions o<
atorvastatin calci!
(01' S% SL-1& ( SL$ ?#r# aAAli#= to Ar#-?as2#= activat#= Alat#s& as 0-!! "an=s& 0
!! aAart& n=#r a str#a! o< nitro%#n& "> !#ans o< a Ca!a% Lino!at I9
.i%1 1
Ov#rlai= U9 sA#ctra o< atorvastatin calci! ato!at#= sAra>-on "an=
aAAlicator #CiAA#= ?it2 a Ha!ilton 100-SL s>- rin%#1 T2# Alat#s ?#r# =#v#loA#=&
?it2 '0 !L tol#n#O!#t2anol 73' (v-v$ as !o"il# A2as#& in a Ca!a% t?in-tro%2
c2a!"#r Ar#viosl> satrat#= ?it2 !o"il# A2as# vaAor <or '0 !in1 T2# =#v#loA!#nt
=istanc# an= ti!# ?#r# 1+ c! an= '+ !in& r#sA#ctiv#l>1 A<t#r =#v#loA!#nt t2# Alat#s
?#r# r#!ov#= <ro! t2# c2a!"#r an= =ri#= in air1 D#nsito!#tr> ?as A#r<or!#= at '(0
n! (.i%1 1$& in r#<l#ctanc# !o=#& ?it2 a Ca!a% TLC Scann#r 6 sin% CATS (
so<t?ar# incorAoratin% tracG-Aosition oAti!iEation1 T2# slit =i!#nsions ?#r# 0100 !!
^ 01(+ !!1
.or Ar#Aaration o< a cali"ration Alot& '& (& 0& 7& 10& an= 1' SL o< stan-=ar=
soltions o< atorvastatin calci! an= #E#ti!i"# (01' S% SL-1$ ?#r# aAAli#= to t2# TLC
Alat#s1 Anal>sis ?as t2#n A#r<or!#= as =#scri"#= a"ov#1
Assa$ of t&e Mar+ete* !orulation
Assa> o< t2# !arG#t#= <or!lation ?as A#r<or!#= "> t2# !#t2o= #sta"lis2#=
in t2is ?orG1 Stan=ar= an= sa!Al# soltions (0 SL$ ?#r# aAAli#= to t2# Alat# an=
anal>sis ?as A#r<or!#= as =#scri"#= a"ov#1 T2# a!onts o< atorvastatin calci! an=
#E#ti!i"# A#r ta"l#t ?#r# calclat#= "> co!- Aarin% t2# ar#as o"tain#= <ro! stan=ar=
an= sa!Al# (Ta"l# I$1
Ta"l# I
R#slts <ro! assa> o< atorvastatin calci! in t2# <or!lation *itorva (H#t#ro
Dr%s& Solan (H1P1$ In=ia$
Dr% La"#l clai! A!ont <on= Dr% cont#nt
RSD
(!%-ta"l#t$a (!%$ (H$a (H$
Atorvastatin calci! 10 517' 5710' \ 01+0 01+0
)E#ti!i"# 10 5150 5510+ \ 0160 0160
aAv#ra%# \ stan=ar= =#viation <ro! t2r## =#t#r!inations
/ali*ation
T2# !#t2o= ?as vali=at#= <or lin#arit>& accrac> an= sA#ci<icit>& intra-=a> an=
int#r-=a> Ar#cision& r#A#ata"ilit> o< !#asr#!#nt o< A#aG ar#a& an= r#A#ata"ilit> o<
sa!Al# aAAlication& in accor=anc# ?it2 ICH %i=#li- n#s K11&1'L (Ta"l# II$1 Accrac>
?as #valat#= "> con=ctin% a r#cov#r> st=> at t2r## =i<<#r#nt l#v#ls O 70& 100& an=
1'0H1 Intra-=a> Ar#cision ?as =#t#r!in#= "> anal>sis o< stan=ar= soltions o<
atorvastatin calci! in ran%# 01(O'1( S%-Eon# t2r## ti!#s on t2# sa!# =a>1 Int#r-=a>
Ar#cision ?as =#t#r!in#= "> anal>sis o< si!ilar stan=ar=s on t2r## =i<<#r#nt =a>s ov#r
a A#rio= o< on# ?##G1 R#lativ# stan=ar= =#viation (RSD$ ?as calclat#= <or "ot2 s#ri#s
o< anal>s#s1 T2# ro"stn#ss o< t2# !#t2o= ?as st- =i#=& =rin% !#t2o= =#v#loA!#nt&
"> =#t#r!inin% t2# #<<#cts o< s!all variations o< !o"il# A2as# co!Aosition (\'H$&
=ration o< Alat# Ar#-?as2in%& c2a!"#r satration A#rio=& =#v#loA!#nt =istanc#& an=
scannin% ti!# (10H variation o< #ac2$1
Table II
S!!ar> o< vali=ation =ata
M#t2o= c2aract#ristic Atorvastatin
calci!
Lin#ar ran%# (S%$ 01(O'1(
Corr#lation co#<<ici#nt (r$ 01555+
Stan=ar= =#viation (n J 0$ 1110
Accrac> (H& n J 0$ 571+1 \ 01'6
R#A#ata"ilit> o< sa!Al# aAAlication
(RSD& H& n J 0$ 11+0
R#A#ata"ilit> o< !#asr#!#nt o< A#aG ar#a
(RSD& H& n J 0$
110'
Pr#cision (RSD& H$
Int#r-=a> (n J 6$ 1110O11((
Intra-=a> (n J 6$ 1110O11'+
SA#ci<icit>
RESULTS A"D DISCUSSIO"
Ta"l#t Ao?=#r ?as #@tract#= ?it2 !#t2anol "#cas# "ot2 atorvastatin
calci! an= #E#ti!i"# ar# <r##l> sol"l# in t2is solv#nt1 C#ntri<%a- tion <or 1+ !in at
000 rA! <acilitat#= co!Al#t# #@traction o< atorvastatin calci! <ro! t2# ta"l#t
!atri@1 A vari#t> o< !o"il# A2as#s& <or #@a!Al# c2loro<or!O!#t2anol& c2loro<or!O
tol#n#Oac#tic aci=& an= "#n-E#n#O!#t2anolOtol#n# !i@tr#s& ?#r# inv#sti%at#= <or
s#Aaration o< atorvastatin calci! <ro! t2#ir i!Ariti#s an= <ro! #@ciAi#nts in t2#
<or!lation1 Tol#n#O!#t2anol 73' (v-v$ ?as <on= to r#slt in t2# "#st A#aG s2aA#1
Atorvastatin calci! an= #E#ti!i"# ?#r# satis<actoril> r#- solv#= ?it2 R. val#s 01'6
\ 0101 an= 0165 \ 0101& r#sA#ctiv#l> (.i%1 '$1 Pr#-satration o< t2# TLC c2a!"#r ?it2
!o"il# A2as# vaAor <or 60 !in #nsr#= !or# r#Aro=ci"l# !i%ration o< t2# =r%s an=
"#tt#r r#soltion1
.i%1 '
D#nsito%ra! o"tain#= <ro! atorvastatin calci!
cali"ration Alots ?#r# #sta"lis2#= <or atorvastatin calci! stan=ar=s sin% si@
conc#ntrations (01(& 017& 11'& 110& '10& an= '1( S% A#r "an=$1 T2# corr#lation
co#<<ici#nts <or t2# Alots ?#r# 01555+ <or atorvastatin calci! an= 0155551 R#slts
<ro! t2# r#cov#r> st=> in=icat#= t2# !#t2o= #na"l#= accrat# Canti<ication o< t2#
=r%s in t2# ta"l#t =osa%# <or! (Ta"l# III$1
Table III
R#cov#r> o< atorvastatin calci! <ro! t2# <or!lation *itorva ()v#r%r##n
r#s#arc2 La" In=ia$
Dr% La"#l clai! A!ont Total a!ont A!ont R#cov#r>
(!%-ta"l#t$ a==#= (H$ (!%$ r#cov#r#= (H$a
(!%$
Atorvastatin 70 17 1,1, 571+7 \ 01',
calci! 10 100 '0 1510 571'+ \ 01'0
1'0 '' '11, 571,0 \ 01''
aAv#ra%# val# \ stan=ar= =#viation o< si@ =#t#r!inations
T2# intra-=a> an= int#r-=a> r#lativ# stan=ar= =#viations ?#r# in t2# ran%#s
1110O11'+H an= 1110O11((H <or atorvastatin calci! an= 01(,O0106H an= 01(,O
0177H <or #E#ti!i"#1 T2#s# s!all val#s in=icat# t2# !#t2o= is Ar#cis#1 R#lativ#
stan=ar= =#viation (RSD$ <or !#asr#!#nt o< A#aG ar#a ?as 110'H an= 11,0H <or
atorvastatin calci! r#sA#ctiv#- l>& an= RSD <or r#A#ata"ilit> o< sa!Al# aAAlication
?as 11+0H an= 0101H <or atorvastatin calci! r#sA#ctiv#l>1 RSD <or !#asr#!#nt
o< A#aG ar#a an= sa!Al# aAAlication ?#r# "#tt#r t2an t2# sA#ci<ications o< t2#
instr!#nt& in=icatin% AroA#r <nctionin% o< t2# TLC s>st#!1 To con<ir! t2#
sA#ci<icit> o< t2# !#t2o=& atorvastatin calci! ?#r# aAAli#= to a TLC Alat# an=
=#v#loA#= an= scann#= as =#scri"#= a"ov#1 )@ciAi#nts Ar#s#nt in t2# <or!lation =i=
not int#r<#r# ?it2 t2# A#aGs o< atorvastatin calci! T2# sA#ctra acCir#= <or
atorvastatin calci! #@tract#= <ro! t2# ta"l#t ?#r# also co!Aar#= ?it2 t2os#
acCir#= <ro! atorvastatin calci! stan=ar=sD
corr#lation ?as %oo=1 82#n s!all c2an%#s ?#r# !a=# to t2# !#t2o= con=itions
t2#r# ?#r# no !arG#= c2an%#s in c2ro!ato%raA2ic "#2avior& in=icatin% t2# !#t2o= is
ro"st1
CO"CLUSIO"
It is s2o?n a"ov# t2at t2# n#? TLCO=#nsito!#tric !#t2o= ac2i#v#= accrac>&
r#Aro=ci"ilit>& r#A#ata"ilit>& lin#arit>& an= s#l#ctivit> t2at co!Aar#s <avora"l> ?it2
t2os# o< HPLC& HPTLC& sA#ctroA2oto!#tr>& an= ot2#r !#t2o=s r#Aort#= r#%larl> in
t2# lit#ratr#1 T2# r#slts also !##t ICH %i=#lin#s K11&1'L <or vali=ation o<
A2ar!ac#tical TLC !#t2o=s1 T2# AroAos#= TLC !#t2o= is l#ss #@A#nsiv#& si!Al#r&
!or# raAi=& an= !or# <l#@i"l# t2an HPLC1
AC>"O-LED.EME"TS
*io-=ot P2ar!ac#ticals& +,-1(0(& .irst .loor& T2aila Na%ar& PUDU//OTTAI
- 0'' 00(1 TAMILNADU& INDIA P2on# 3 451-(6''-',06,6 Mo"il# 3 55((7-7(550
<or Arovi=in% sa!Al#s o< atorvastatin calci! r#sA#ctiv#l>& as %i<ts1 T2#> ar# also
%rat#<l to *2arati 9i=>aA##t2 Univ#rsit>Vs Poona Coll#%# o< P2ar!ac>& Pn#& In=ia&
<or Arovi=in% #@c#ll#nt <aciliti#s <or car- r>in% ot t2is r#s#arc2 ?orG1
MATERIAL SA!ET# DATA SHEET
CHEMICAL I"DE"TI!ICATIO"
Pro*uct Co*e SRP19661a
Pro*uct "ae ATOR/ASTATI" Calciu
S$non$s
COMPOSITIO"3I"!ORMATIO" O"I".REDIE"TS
C2A2S2 "o 06:;<6,16,?
Molecular !orula CAAHA?Ca!<":O01
!orula -ei'&t 00;26A
Merc+ In*e= ?A?
Pro*uct .rou% Statins
HABARDS IDE"TI!ICATIO"
Not consi=#r#= 2aEar=os ?2#n 2an=l#= n=#r nor!al con=itions ?it2 %oo=
2os#G##Ain%1
Label %recautionar$ stateents:
S60-6, 8#ar sita"l# Arot#ctiv# clot2in% an= %lov#s1
R'0-'1-'' Har!<l "> in2alation& in contact ?it2 sGin an= i< s?allo?#=1
!IRST,AID MEASURES
In case of in&alation:
R#!ov# to <r#s2 air1 I< not "r#at2in% %iv# arti<icial r#sAiration1 I< "r#at2in%
is=i<<iclt& %iv# o@>%#n1 S##G !#=ical att#ntion1
In case of contact )it& s+in:
I!!#=iat#l> ?as2 sGin ?it2 soaA an= coAios a!onts o< ?at#r <or at l#ast
1+!int#s1 I< irritation A#rsists& s##G !#=ical att#ntion1
In case of contact )it& e$es:
I!!#=iat#l> <ls2 #>#s ?it2 coAios a!onts o< ?at#r <or at l#ast 1+ !int#s1
S##G!#=ical a=vic#1
In case of in'estion:
I< s?allo?#=& ?as2 ot !ot2 ?it2 ?at#r& Arovi=#= A#rson is concios1
S##G!#=ical a=vic#1
Reove an* )as&3*is%ose of containate* clot&in' %ro%tl$2
!IRE !I.HTI". MEASURES
E=tin'uis&in' Me*ia:
Car"on =io@i=#& =r> c2#!ical Ao?=#r or aAAroAriat# <oa!1 8at#r sAra>1
Unusual fire an* e=%losion &a8ar*s:
)!its to@ic <!#s n=#r <ir# con=itions
S%ecial fire fi'&tin' %roce*ures:
8#ar s#l<-contain#= "r#at2in% aAAarats an= Arot#ctiv# clot2in% to Ar#v#nt
contact?it2 t2# sGin an= #>#s1
ACCIDE"TAL RELEASE MEASURES
)nsrin% A#rsonal sa<#t>& !arG ot conta!inat#= ar#a ?it2 si%ns an=
Ar#v#ntnat2oris#= acc#ss1 Trn l#aGin% contain#rs A to Ar#v#nt <rt2#r )vaclat#
ar#a1 8#ar s#l<-contain#= "r#at2in% aAAarats& r""#r "oots _ 2#av> r""#r %lov#s1
S?##A-A-a"sor" in sita"l# !at#rial& Alac# in a contain#r an= 2ol= <or =isAosal1 Avoi=
raisin% =st1 9#ntilat# ar#a an= ?as2 sAill sit# a<t#r AicG-A co!Al#t#1
HA"DLI". A"D STORA.E
Stor# n=#r t2# <ollo?in% con=itions3 Stor# cool& =arG an= =r>1
E@POSURE CO"TROL3PERSO"ALPROTECTIO"
Res%irator$ %rotection:
r#Cir#= ?2#n =sts ar# %#n#rat#=1
E$e %rotection:
r#Cir#=1
Han* %rotection:
r#Cir#=1
In*ustrial &$'iene:
I!!#=iat#l> c2an%# conta!inat#= clot2in%1 8as2 2an=s an= <ac# a<t#r
?orGin%?it2 s"stanc#1
PH#SICAL A"D CHEMICAL PROPERTIES
A%%earance 82it# Ao?=#r
O*our Non#
Meltin' Point
Solubilit$
STABILIT# A"D REACTI/IT#
Con*itions to be avoi*e*:
UnGno?n
Substances to be avoi*e*:
UnGno?n
Ha8ar*ous *eco%osition %ro*ucts:
UnGno?n
TO@ICOLO.ICAL I"!ORMATIO"
ECOLO.ICAL I"!ORMATIO"
Do not allo? Aro=ct to #nt#r =rinGin% ?at#r sAAli#s& ?ast# ?at#r or soil`
DISPOSAL CO"SIDERATIO"S
Dissolv# or !i@ !at#rial ?it2 a sita"l# co!"sti"l# solv#nt an= incin#rat# in
a c2#!ical incin#rator #CiAA#= ?it2 an a<t#r"rn#r an= scr""#r1 Mat#rial s2ol= "#
=isAos#= o< in G##Ain% ?it2 all local an= national l#%islation1 PacGa%in% s2ol= "#
=isAos#= o< in G##Ain% ?it2 all local an= national l#%islation1 Han=l# conta!inat#=
contain#rs as Aro=ct1
TRA"SPORT I"!ORMATIO"
Classification:
U" "uber:
RE.ULATOR# I"!ORMATIO"
OTHER I"!ORMATIO"
82il# t2# in<or!ation 2#r#in is "#li#v#= to "# r#lia"l#& it is <rnis2#=
?it2ot?arrant> o< an> Gin=1 It s2all "# s#= onl> as a %i=#1 8# ass!# no
lia"iliti#s<ro! t2# s# o< t2is Aro=ct or in<or!ation contain#= 2#r#in1
H$%erc&olesteroleia
DYSLIP - 10 (atorvastatin calci!$ 2as "##n s2o?n to si%ni<icantl> i!Arov#
liAi= Aro<il#s in a vari#t> o< =>sliAi=#!ic con=itions1 DYSLIP - 10 2as "##n s2o?n to
"# 2i%2l> #<<#ctiv# in r#=cin% total an= LDL-c2ol#st#rol& an= tri%l>c#ri=#s an=
aAoliAoArot#in * in Aati#nts ?it2 Ari!ar> 2>A#rc2ol#st#rol#!ia& <a!ilial an= non-
<a!ilial 2>A#rc2ol#st#rol#!ia& an= !i@#= 2>A#rliAi=#!ia& incl=in% <a!ilial co!"in#=
2>A#rliAi=#!ia an= Aati#nts ?it2 non-inslin =#A#n=#nt =ia"#t#s !#llits (NIDDM$1
In ' !ltic#nt#r& Alac#"o-controll#=& =o"l#-"lin= =os#-r#sAons# st=i#s in
Aati#nts ?it2 !il= to !o=#rat# 2>A#rc2ol#st#rol#!ia (.r#=ricGson t>A#s IIa an= II"$&
DYSLIP - 10 %iv#n as a sin%l# =ail> =os# ov#r 0 ?##Gs r#=c#= total-C& LDL-C& aAo
*& an= TGD HDL ?as incr#as#= (Ta"l# +$1 A t2#raA#tic r#sAons# ?as #vi=#nt ?it2in '
?##Gs& an= t2# !a@i!! r#sAons# ?as sall> ac2i#v#= ?it2in '-( ?##Gs1
TABLE ;2 Dose,Res%onse in Patients )it& Mil* to Mo*erate
H$%erc&olesteroleia
4!re*ric+son T$%es IIa an* IIb5
4Mean Percent C&an'e fro Baseline5 a
DYSLIP - 10
Dos# N Total-C LDL-C AAo * TG
HDL-C (!%-=a>$
Plac#"o '1 4( 4( 46 410 -6
10 '' -'5 -65 -6' -15 40
'0 '0 -66 -(6 -6+ -'0 45
(0 '1 -6, -+0 -(' -'5 40
70 '6 -(+ -00 -+0 -6, 4+
a R#slts ar# Aool#= <ro! ' =os#-r#sAons# st=i#s
In a Aool#= =ata s#t <ro! '( controll#= clinical trials in Aati#nts ?it2 Ari!ar>
2>A#rc2ol#st#rol#!ia (t>A# IIa$ an= !i@#= (co!"in#=$ =>sliAi=#!ia (t>A# II"$&
DYSLIP - 10 incr#as#= HDL C "> +H to 7H <ro! "as#lin# at #ac2 =os# t#st#= (10& '0&
(0& an= 70 !% :D$ (Ta"l# 0$1 In Aati#nts ?it2 HDL C I 015 !!ol-L (a con=ition o<t#n
o"s#rv#= in A#rsons ?it2 t2# !#ta"olic s>n=ro!#$ Ks## INDICATIONS AND
CLINICAL US)L& DYSLIP - 10 rais#= HDL-C ,H to 1(H1 T2#s# c2an%#s ?#r#
in=#A#n=#nt o< t2# =os# a=!inist#r#=1 DYSLIP - 10 also =#cr#as#= total-C-HDL-C&
LDL-C-HDL-C& an= non-HDL-C-HDL-C ratios <ro! "as#lin# in a =os# =#A#n=#nt
!ann#r (Ta"l# 0$1 DYSLIP - 10 (10& '0& (0 an= 70 !% :D$ incr#as#= HDL-C l#v#ls
<ro! "as#lin# <or "ot2 !#n an= ?o!#n1
TA*L) 01 A=Bst#=a M#an P#rc#nt C2an%#s <ro! *as#lin#
in HDL-C& Total-C-HDL-C& LDL-C-HDL-C&
Non-HDL-C-HDL-C& an= HDL J C 1 015 !!ol-L
<or Pati#nts" 8it2 Mil= to Mo=#rat#
H>A#rc2ol#st#rol#!ia
(.r#=ricGson T>A#s IIa an= II"$
DYSLIP - 10 N HDL-C Total-C- LDL-C- Non HDL-C-
HDL-C
Dos# (all Aati#nts$ HDL-C HDL-C HDL-C ("as#lin# 1 J
015
(!%-=a>$ !!ol-L$
(N$
Plac#"o '+0 401'a 4'17a 4617a 461+a 401'W (1,$
10 17,1 401( -'516b -6,10b -6+1+b 41617 ('(7$
'0 1(, 4,17 -6010b -((11b -(610b 4716 ('0$
(0 11+ 4,11 -6715b -(510b -(,11b 4710 (7$
70 617 4+10 -(61+b -++16b -+'1(b
4,11 (+7$
a L#ast sCar#s !#ans <ro! ANCO9A !o=#l ?it2 st=>& tr#at!#nt an=
"as#lin#
" Data Aool#= <ro! '( controll#= st=i#s
bsi%ni<icant lin#ar =os# tr#n=
a si%ni<icantl> =i<<#r#nt <ro! DYSLIP - 10 !% (AI0101$
W si%n<icantl> =i<<#r#nt <ro! DYSLIP - 10 !% (AI010+$
In anot2#r !ltic#nt#r& Alac#"o controll#=& =o"l# "lin= trial in Aati#nts ?it2
2>A#rtri%l>c#ri=#!ia& DYSLIP - 10 lo?#r#= tri%l>c#ri=#s in a =os# r#lat#=
!ann#r& ?it2ot casin% a r#=istri"tion o< tri%l>c#ri=#s into varios liAoArot#in
<ractions (Ta"l# ,$1
TABLE 92 Efficac$ in Patients )it& H$%ertri'l$ceri*eia
4Mean Percent C&an'e fro Baseline5
DYSLIP - 10 N 9LDL-C Total- 9LDL LDL-C TG HDL-C
AAo *
Dos# C TG
(!%-=a>$
Plac#"o 1' -'10 4016 -010 411( -+16 4'1( 4'1,
+ 11 -6(10W -1515W -'71, -1'1,W -',16 4,11 -1+1(W
'0 1' -(010W -6611W -6+1,W -6111W -661,W 41010 -6'1,W
70 11 -+(-'W -(116W -(610W -6011W -('1(W 41117W -671,W
W Si%ni<icantl> =i<<#r#nt <ro! Alac#"o& AI010+
Co!Aarison o< Aool#= =ata "> .r#=ricGson t>A#s s2o?s si!ilar r#=ctions <or
T>A# IIa an= II" Aati#nts in total-C& LDL-C an= aAo *D 2o?#v#r& T>A# II" Aati#nts&
an= T>A#s I9 Aati#nts #@A#ri#nc# a %r#at#r A#rc#nt =#cr#as# in 9LDL-C an= TG l#v#ls
(Ta"l# 7$1
TABLE ?2 Efficac$ in Patients b$ !re*ric+son T$%ea
DYSLIP - 10 !%-=a>
LiAi= Para!#t#r T>A# IIa T>A# II" T>A# I9
(N J 56+$ (N J ++0$ (N J '5$
LDL-C -60 -6+ -'0
AAo * -'7 -'7 -'+
Total-Cl -', -', -'+
TG -1( -'( -'5
9LDL-C -1+ -'7 -(1
HDL-C 40 410 416
AAo *-HDL -C -61 -6( -66
Non-HDL-C-HDL-C -6, -67 -67
a Pool#= =atas#t
In a Ailot st=> o< 7 Aati#nts ?it2 2o!oE>%os <a!ilial 2>A#rc2ol#st#rol#!ia&
t2# !#an =#cr#as# in LDL-C ?it2 70 !%-=a> DYSLIP - 10 ?as 60H <or Aati#nts not
on Alas!aA2#r#sis& an= 61H <or Aati#nts ?2o contin#= Alas!aA2#r#sis1 A LDL-C
lo?#rin% o< 6+H ?as o"s#rv#= in r#c#Ator =#<#ctiv# Aati#nts (nJ0$ an= o< 15H in
r#c#Ator n#%ativ# Aati#nts (nJ'$1 All Aati#nts also #@A#ri#nc#= =#cr#as#s in total-C&
aAo *& LDL-C-HDL-C an= non-HDL-C-HDL-C ratios (Ta"l# 5$1
Table C2 Patients )it& Hoo8$'ous !H
4Mean Percent C&an'e fro Baseline After ? -ee+s5
DYSLIP - 70 !%-=a>
LiAi= Para!#t#r All Pati#nts Pati#nts Not on Pati#nts on
(NJ7$ Plas!aA2#r#sis
Plas!aA2#r#sis
(NJ6$ (NJ+$
Total-C -'5 -'5 -'5
LDL-C -61 -60 -61
AAo * -'7 -1, -6(
TG -'0 -(1 -7
LDL-C-HDL-C Ratio -'6 -15 -'+
Non HDL-C-HDL-C -'' -15 -'(
Ratio
In an oA#n la"#l st=>& 05 Aati#nts ('-01 >#ars o< a%#$ ?it2 2o!oE>%os
<a!ilial 2>A#rc2ol#st#rol#!ia& an= 5' Aati#nts ?it2 s#v#r# 2>A#rc2ol#st#rol#!ia ?2o
2a= J1+H r#sAons# to !a@i!! co!"ination t2#raA>& r#c#iv#= DYSLIP - 10 to 70
!%-=a>1 Most Aati#nts "#%an DYSLIP - 10 tr#at!#nt ?it2 (0 !%-=a>& "t s#v#r#l>
=#"ilitat#= an= v#r> >on% Aati#nts "#%an tr#at!#nt ?it2 10 !%-=a>1 DYSLIP - 10
?as titrat#= at (-?##G int#rvals to J70 !%-=a>1 T2# !#an r#=ction in LDL-C <or 05
Aati#nts =ia%nos#= ?it2 2o!oE>%os <a!ilial 2>A#rc2ol#st#rol#!ia ?as ''H1 Ta"l#
10 s2o?s t2# !#an A#rc#nt c2an%# in liAi= Aara!#t#rs1 In ' r#c#Ator-n#%ativ# Aati#nts
!#an LDL-C r#=ction ?as 15H1 Si@ Aati#nts 2a= l#ss t2an a 10H r#sAons# to
tr#at!#nt1
Table 012 Patients )it& Hoo8$'ous !H or Severe
"onres%onsive H$%erc&olesteroleia
4Mean Percent C&an'e fro Baseline after ? -ee+s5
DYSLIP - 10 !%-=a>
LiAi= Para!#t#r Ho!oE>%os .H S#v#r# Unr#sAonsiv#
(NJ05a$ H>A#rc2ol#st#rol#!ia
(NJ5'$
Total-C -'1H -6(H
LDL-C -''H -65H
TG - 5H -'5H
HDL-C 46H 40H
a Data availa"l# <ro! 07 Aati#nts
In a 1->#ar st=> in Aati#nts ?it2 2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia&
DYSLIP - 10 !onot2#raA> (70 !%-=a>$ ?as co!Aar#= ?it2 co!"ination t2#raA> o<
col#stiAol (10 % *ID$ Als DYSLIP - 10 ((0 !%-=a>1 T2# ' tr#at!#nts Aro=c#=
si!ilar #<<#cts on total-C& LDL-C& TG& 9LDL-C& aAo * an= HDL-CD 2o?#v#r&
DYSLIP - 10 !onot2#raA> ?as !or# #<<#ctiv# t2an DYSLIP - 10 Als col#stiAol in
=#cr#asin% TG l#v#ls (Ta"l# 11$1
TABLE 002 Efficac$ in Patients )it& Hetero8$'ous !ailial
H$%erc&olesteroleia
4Mean Percent C&an'e fro Baseline after ;< -ee+s5
DYSLIP - 10 DYSLIP - (0 !%-=a>
LiAi= Para!#t#r 70 !%-=a> Pls
Col#stiAol 10 % *ID
(NJ175$ (NJ1'($
TOTAL-C -(( -('
LDL-C -+6 -+6
9LDL-C -66 -1,
HDL-C 4, 45
TG -66a -1,
non-HDL-HDL-C Ratio -+6 -+'
AAo * -(0 -(+
a Si%ni<icantl> =i<<#r#nt <ro! LIPITOR Als col#stiAol (A I010+$&
ANCO9A1
A co!Aarison o< r#slts in Aati#nts ?it2 2#t#roE>%os <a!ilial an= non-<a!ilial
2>A#rc2ol#st#rol#!ia s2o?s si!ilar !a%nit=#s o< r#=ctions in LDL-C& aAo * an=
non-HDLC- HDL-C ratio& in "ot2 Aati#nt AoAlations (Ta"l# 1'$1
Table 0<2 Efficac$ in Hetero8$'ous !H an* "on !H PatientsD
4Mean Percent C&an'e fro baseline5
LiAi= Para!#t#r P2#not>A# DYSLIP - 10
10-!%-=a> 70 !%-=a>
LDL-C H#t#roE>%os .H -60 (NJ1(0$ -+6 (NJ1+($
Non .H -60 (NJ1'1+$ -+' (NJ100$
AAo * H#t#roE>%os .H -', (NJ16($ -(0 (NJ1+6$
Non .H -'7 (NJ11(5$ -(0 (NJ1(($
Non HDL-C-HDL-C H#t#roE>%os .H -6, (NJ1(0$ -+6 (NJ16'$
Ratio Non .H -6, (NJ1'1+$ -+( (NJ100$
bData <ro! s#v#ral st=i#s
Co!Aarison o< r#slts in Aati#nts ?it2 an= ?it2ot <a!ilial co!"in#=
2>A#rliAi=#!ia (.CH$ =#!onstrat#= t2at DYSLIP - 10 lo?#r#= LDL-C& aAo *& total-
C& 9LDL-C& TG& an= t2# non- HDL-C-HDL-C ratio to a si!ilar #@t#nt in "ot2 Aati#nt
AoAlations (Ta"l# 16$1
Table 062 Efficac$ in Patients -it& an* -it&out !CHD(
LiAi= Para!#t#r DYSLIP - 10 !%-=a>
.CH Non-.CH
(N J ,7-7($ (N J 107(-1''($
Total-C -'0H -',H
LDL-C -6(H -60H
TG -'1H -1,H
HDL-C 47H 4,H
AAo * -'0H -'7H
9LDL-C -'+H -17H
Non HDL-C-HDL-C -60H -6,H
Ratio -5H -11H
LDL-C-AAo * ratio
bData <ro! s#v#ral st=i#s
a T2# <ollo?in% crit#ria ?#r# s#= to =#<in# Aati#nts ?it2 .CH3 <irst =#%r##
r#lativ# ?it2 liAi= =isor=#r& TG F'+0 !%-=L (F'17 !!ol-L$& 9LDL F(+ !%-=L (F1110
!!ol-L$& HDL I6+ !%-=L (I015 !!ol-L$ (!#n$ or I(+ !%-=L (I1110 !!ol-L$
(?o!#n$1
In an oA#n-la"#l& ran=o!is#=& cross-ov#r st=> in Aati#nts ?it2
=>s"#taliAoArot#in#!ia (T>A# III$& DYSLIP - 70 !%-=a> r#slt#= in a si%ni<icantl>
%r#at#r r#=ction in s#r! liAi=s t2an #it2#r DYSLIP - 10 10 !%-=a> or %#!<i"roEil
1'00 !%-=a> (Ta"l# 1($1
Table 0:2 Efficac$ in Patients )it& T$%e III H$%erli%o%roteineia
4!ailial
D$sbetali%o%roteineia5
Mean Percent C&an'e fro Baseline
DYSLIP - 10 DYSLIP - 10 G#!<i"roEil
LiAi= Aara!#t#r 10 !%-=a> 70 !%-=a> 1'00 !%-=a>
N J 1+ N J 10 N J
10
Total-C -(0 -+,a -6(
LDL-C 4'0a -0a 470
TG -(0a -+0 -+'
9LDL-C -6' -+5a -6+
IDL-C -'7a -+0a -16
IDL-C 4 9LDL-C -6( -+7a -66
HDL-C 46 416 411
AAo * (total$ -(, -00a -+6
AAo-C III -10 -61 -1'
AAo-) -', -(1a -'(
a si%ni<icantl> =i<<#r#nt <ro! %#!<i"roEil& AI010+ (ANO9A$
In a 0-!ont2& =o"l#-"lin=& st=> in Aati#nts ?it2 2>A#rliAi=#!ia an= non-
inslin =#A#n=#nt =ia"#t#s !#llits (NIDDM$& DYSLIP - 10 (10 or '0 !%-=a>$
lo?#r#= total c2ol#st#rol "> ',H& LDL-C "> 6(H& aAo * "> 60H& TG "> '(H& an=
incr#as#= HDL-C "> 1'H (Ta"l# 1+$1
TABLE 0;2 Efficac$ in Patients )it& "IDDM
4Mean Percent C&an'e !ro Baseline5
DYSLIP - 10
LiAi= Para!#t#r 10 or '0 !%-=a>
NJ7(
Total-C -',
LDL-C -6(
9LDL-C -6+
TG -'(
9LDL-TG -'0
HDL-C 41'
AAo * -60
In t2r##& =o"l#-"lin=& !ltic#nt#r st=i#s in Aati#nts ?it2 !il= to !o=#rat#
2>A#rc2ol#st#rol#!ia& t2# n!"#r o< Aati#nts !##tin% NC)P tar%#t LDL-C l#v#ls on
?as ass#ss#= ov#r a 1->#ar A#rio=1 A<t#r 10 ?##Gs& "#t?##n (0-,(H o< Aati#nts
r#c#ivin% 10 !%-=a> DYSLIP - 10 r#ac2#= tar%#t LDL-C l#v#ls1 T2# #<<icac> o<
DYSLIP - 10 (10 or '0 !%-=a>$ ?as !aintain#= ov#r +' ?##Gs& ?it2 "#t?##n +0-,7H
o< Aati#nts ac2i#vin% t2#ir LDL-C tar%#t l#v#ls1
T2# #<<#ct o< DYSLIP - 10 ?as #valat#= in co!Aarativ# clinical trials ?it2
lovastatin& si!vastatin an= Aravastatin1 .or in<or!ation on t2#s# r#slts Al#as# r#<#r to
R).)R)NC)S1
In a 1->#ar st=> in Aost!#noAasal ?o!#n ?it2 Ari!ar> 2>A#rliAi=#!ia&
DYSLIP - 10 !onot2#raA> (10 !%-=a>$ ?as co!Aar#= ?it2 #stra=iol !onot2#raA> (1
!%-=a>$ an= ?it2 co!"ination t2#raA> o< DYSLIP - 10 !%-=a> Als #stra=iol 1
!%-=a> (Ta"l# 10$1 DYSLIP - 10 !onot2#raA> (10 !%-=a>$ ?as si%ni<icantl> !or#
#<<#ctiv# in lo?#rin% total-C& LDL-C& 9LDLC& TG& aAo * an= non-HDL-C-HDL-C
ratio t2an #stra=iol !onot2#raA> (1 !%-=a>$1 .or co!"ination t2#raA> (DYSLIP - 10
Als #stra=iol$& r#=ctions in total-C& LDL-C& 9LDL-C& LA(a$& aAo * an= non HDL-
C-HDL-C ratio ?#r# si!ilar co!Aar#= ?it2 LIPITOR !onot2#raA>1 Ho?#v#r& HDL-
C l#v#ls ?#r# si%ni<icantl> 2i%2#r <or co!"ination t2#raA> co!Aar#= ?it2 DYSLIP -
10 !onot2#raA>1 TG l#v#ls ?#r# lo?#r ?it2
DYSLIP - 10!onot2#raA> co!Aar#= ?it2 co!"ination t2#raA>1 A=v#rs# r#actions
?#r# si!ilar in t>A# an= inci=#nc# <ollo?in% co!"ination t2#raA> (DYSLIP - 10 Als
#stra=iol$ co!Aar#= ?it2 #stra=iol !onot2#raA>1
TABLE 0A2 Efficac$ in Post,eno%ausal -oen
4Mean Percent C&an'e fro Baseline After ;< -ee+s$
DYSLIP - 10 )stra=iol DYSLIP - 10 !%-=a>
LiAi= Para!#t#r 10 !%-=a> 1 !%-=a> Pls
)stra=iol (1!%-=a>$
(NJ67$ (NJ10$ (NJ'1$
TOTAL-C -'5 -1a -',
LDL-C -(0 -+a -('
9LDL-C -6' 416a -'0
HDL-C 47 411 4'0a
TG -', 4+a -16a
non-HDL-HDL-C Ratio -(6 -1'a -(7
AAo * -6( -6a -6(
aSi%ni<icantl> =i<<#r#nt <ro! DYSLIP - 10 !onot2#raA> (A I010+$& ANCO9A1
In a co!Aarativ# st=> ?it2 niacin in Aati#nts ?it2 2>A#rc2ol#st#rol#!ia an=
!i@#= 2>A#rliAi=#!ia (.r#=ricGson t>A#s IIa an= II"$ an= 2>A#rtri%l>c#ri=#!ia
(.r#=#ricGson T>A# I9$& DYSLIP - 10 (10 !%-=a>$ 2a= %r#at#r c2ol#st#rol-lo?#rin%
#<<icac> (%r#at#r =#cr#as#s in LDL-C& aAo *& LDL-aAo *$& ?2il# niacin (6 %-=a>$ 2a=
%r#at#r tri%l>c#ri=#-lo?#rin% #<<icac> (%r#at#r =#cr#as#s in TG& 9LDL-TG& HDL-TG&
9LDL-aAo *$1 LIPITOR ?as "#tt#r tol#rat#= "> Aati#nts co!Aar#= ?it2 niacin (Ta"l#
1,$1
Table 092 D#SLIP , 01 versus "iacin
.r#=ricGson T>A#s IIa an= II" .r#=ricGson T>A# I9
Para!#t#r Atorvastatin Niacin Atorvastatin
Niacin
10 !% 6 %-=a> 10 !% 6
%-=a>
(N J (6$ N J 65$ (N J 11$ (N J 1'$
LDL-C -66W -7 -1+W 41(
AAo * -60W -10 -'6W -6
Total-C -'7W -11 -'0W 0
TG -10 -'5W -60 -'5
HDL-C 4( 4',W 4( 4'+
9LDL-C -'7 -65 -(6 -60
Non-HDL-
C-HDL-C -6( -6' -6( -15
AAo *-HDL -6' -61 -'7 -17
W Si%ni<icant =i<<#r#nc# "#t?##n tr#at!#nts& ANCO9A A I010+1
In a co!Aarativ# st=> ?it2 <#no<i"rat# in Aati#nts ?it2 co!"in#=
2>A#rliAi=#!ia or 2>A#rtri%l>c#ri=#!ia& DYSLIP - 10 ('0 !%-=a>$ ?as !or#
#<<#ctiv# in lo?#rin% LDL-C& aAo * an= total c2ol#st#rol l#v#ls co!Aar#= to
<#no<i"rat# (100 !% TID$1 Tr#at!#nt ?it2
DYSLIP - 10also r#slt#= in clinicall> si%ni<icant r#=ctions in TG an= 9LDL-C& an=
incr#as#s in HDL-C l#v#ls& alt2o%2 not to t2# sa!# #@t#nt as ?as s##n ?it2
<#no<i"rat#1 DYSLIP - 10 t2#raA> r#slt#= in a "#tt#r r#=ction o< t2# non-HDL-
C-HDL-C ratio& ?2ic2 !a> "# a %oo= in=icator o< ov#rall liAi=-r#%latin% "#n#<it1
DYSLIP - 10 ?as also "#tt#r tol#rat#= co!Aar#= ?it2 <#no<i"rat# (Ta"l# 17$1
Table 0?2 D#SLIP , 01versus !enofibrate
Mean Percent C&an'e !ro Baseline After <: -ee+s
.r#=ricGson T>A#s IIa an= II" .r#=ricGson T>A# I9
Para!#t#r Atorvastatin .#no<i"rat# Atorvastatin
.#no<i"rat#
'0 !% 600 !% '0 !% 600
!%
(N J 60$ (N J 66$ (N J 5$ (N J
7$
LDL-C -65W -, -'7W 4',
AAo * -60W -1, -', -5
Total-C -6(W -1( -'0 -16
TG -', -65 -6( -+,W
HDL-C 45 4''W 47 460W
9LDL-C -65 -+0 -60 -,6W
Non-HDL-
C-HDL-C -((W -6' -60 -6+
W Si%ni<icant =i<<#r#nc# "#t?##n tr#at!#nts& ANCO9A A I010+1
H#t#roE>%os .a!ilial H>A#rc2ol#st#rol#!ia in P#=iatric Pati#nts3
In a =o"l#-"lin=& Alac#"o-controll#= st=> <ollo?#= "> an oA#n-la"#l A2as#&
17, "o>s an= Aost!#narc2al %irls 10-1, >#ars o< a%# (!#an 1(11 >#ars$ ?it2
2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia (.H$ or s#v#r# 2>A#rc2ol#st#rol#!ia
?#r# ran=o!iE#= to DYSLIP - 10
(nJ1(0$ or Alac#"o (nJ(,$ <or '0 ?##Gs a<t#r t2at& all r#c#iv#= DYSLIP - 10 <or '0
?##Gs1 Inclsion in t2# st=> r#Cir#= 1$ a "as#lin# LDL-C l#v#l F 1 (15 !!ol-L (150
!%-=L$ or '$ a "as#lin# F (11 !!ol-L (100 !%-=L$ an= Aositiv# <a!il> 2istor> o< .H
or =oc!#nt#= Ar#!atr# car=iovasclar =is#as# in a <irst- or s#con=-=#%r## r#lativ#1
Table 0C: )<<#ct o< DYSLIP - 10 on LDL-C& TC an= TG in a
controll#= trial o<
0 !ont2s =ration in a=ol#sc#nt "o>s an= Aost!#narc2al %irls 10-
1,
>#ars o< a%# (NJ17,$ ?it2 2#t#roE>%os <a!ilial
2>A#rc2ol#st#rol#!ia at a =os# o< 10 an= '0 !%1
N A%# Dos# H C2an%#
LDL-C TC TG
'' 10-16 10 !% -6,17+ -'516 -51'
(0 1(-1, 10 !% -671' -'51( -015
66 10-16 '0 !% -('11 -6(10 -1616
(6 1(-1, '0 !% -(016 -6610 -1716
T2# !#an "as#lin# LDL-C val# ?as +1, !!ol-L ('1710 !%-=L$ (ran%#3 610-
1010 !!ol-L K1671+-67+10 !%-=LL$ in t2# DYSLIP - 10 %roA co!Aar#= to +15
!!ol-L ('6010 !%-=L$ (ran%#3 (11-71( !!ol-L K10010-6'(1+ !%-=LL$ in Alac#"o
%roA1 T2# =osa%# o<
DYSLIP - 10 (onc# =ail>$ ?as 10 !% <or t2# <irst ( ?##Gs an= A-titrat#= to '0 !% i<
t2#
LDL-C l#v#l ?as F61( !!ol-L (160 !%-=L$1 T2# n!"#r o< DYSLIP - 10-tr#at#=
Aati#nts ?2o r#Cir#= A-titration to '0 !% a<t#r 8##G ( =rin% t2# =o"l#-"lin=
A2as# ?as 70 (+,11H$1
DYSLIP - 10 si%ni<icantl> =#cr#as#= Alas!a l#v#ls o< total-C& LDL-C&
tri%l>c#ri=#s& an= aAoliAoArot#in * =rin% t2# '0 ?##G =o"l#-"lin= A2as# (s## Ta"l#
15& an= Ta"l# '0$1
TA*L) '01 LiAi=-lo?#rin% )<<#cts o< Atorvastatin in A=ol#sc#nt *o>s an=
Girls ?it2 H#t#roE>%os .a!ilial H>A#rc2ol#st#rol#!ia or S#v#r#
H>A#rc2ol#st#rol#!ia (M#an P#rc#nt C2an%# <ro! *as#lin# at )n=Aoint in Int#ntion-
to-Tr#at PoAlation$
Dosa'e " Total,C LDL,C HDL,C T. A%oli%o%rotein B
Plac#"o (, -11+ -01( -115 1 01,
Atorvastatin 1(0 -611( -6510 '17 -1' -6(
T2# !#an ac2i#v#= LDL-C val# ?as 617 !!ol-L (1601, !%-=L$ (ran%#3 117-
016 !!ol-L K,010 '('10 !%-=LL$ in t2# DYSLIP - 10 %roA co!Aar#= to +15 !!ol-L
(''71+ !%-=L$ (ran%#3 615-1010 !!ol-L K1+'10-67+10 !%-=LL$ in t2# Alac#"o %roA
=rin% t2# '0 ?##G =o"l#-"lin= A2as#1 T2# sa<#t> an= tol#ra"ilit> Aro<il# o< DYSLIP
- 10 to '0 !% =ail> ?as si!ilar to t2at o< Alac#"o1 In t2is controll#= st=>& t2#r# ?as
no #<<#ct on %ro?t2 or s#@al !atration in "o>s an= in %irls& as !#asr#= "> Tann#r
sta%in% =rin% '0 ?##Gs1 T2# AroAortion o< s"B#cts ?2o 2a= an incr#as# in Tann#r
sta%# "#t?##n "as#lin# an= ?##G '0 o< t2# =o"l#-"lin= A2as# ?as si!ilar <or t2#
atorvastatin an= Alac#"o %roAs ('7H an= 61H& r#sA#ctiv#l>D P J 01,$1 No
sA#ci<ic =oc!#ntation o< !#nstral c>cl# ?as r#cor=#=1 DYSLIP - 10 2a= no #<<#ct
on Alas!a l#v#ls o< LH& .SH& cortisol& t#stost#ron# an= =#2>=ro#Aian=rost#ron#1
)<<#ct o< tr#at!#nt on co%nitiv# <nction ?as not caAtr#= =rin% t2# cors# o< t2is
st=>1
DYSLIP - 10 2as not "##n st=i#= in controll#= clinical trials involvin% Ar#-
A"#rtal Aati#nts or Aati#nts >on%#r t2an 10 >#ars o< a%#1 T2# sa<#t> an= #<<icac> o<
=os#s a"ov# '0 !% 2av# not "##n st=i#= in controll#= trials in c2il=r#n1
In t2# An%lo-Scan=inavian Car=iac Otco!#s Trial (ASCOT$& t2# #<<#ct o<
DYSLIP - 10(atorvastatin calci!$ on <atal an= non-<atal coronar> 2#art =is#as# ?as
ass#ss#= in 10&60+ 2>A#rt#nsiv# Aati#nts (0-70 >#ars o< a%# (!#an o< 06 >#ars$&
?it2ot a Ar#vios !>ocar=ial in<arction an= ?it2 TC l#v#ls I01+ !!ol-L1
A==itionall> all Aati#nts 2a= at l#ast 6 o< t2# <ollo?in% car=iovasclar risG <actors3
!al# %#n=#r (7111H$& a%# F++ >#ars (7(1+H$& s!oGin% (661'H$& =ia"#t#s ('(16H$&
2istor> o< CHD in a <irst-=#%r## r#lativ# ('0H$& TC3HDL F 0 (1(16H$& A#riA2#ral
vasclar =is#as# (+11H$& l#<t v#ntriclar 2>A#rtroA2> (1(1(H$& Arior c#r#"rovasclar
#v#nt (517H$& sA#ci<ic )CG a"nor!alit> (1(16H$& Arot#inria-al"!inria (0'1(H$1 In
t2is =o"l#-"lin=& Alac#"o-controll#= st=>& Aati#nts ?#r# tr#at#= ?it2 anti2>A#rt#nsiv#
t2#raA> (Goal *P I1(0-50 !! H% <or non-=ia"#tic Aati#nts& I160-70 !! H% <or
=ia"#tic Aati#nts$ an= allocat#= to #it2#r DYSLIP - 10 !% =ail> (nJ+107$ or Alac#"o
(nJ+16,$& sin% a covariat# a=aAtiv# !#t2o= ?2ic2 tooG into accont t2# =istri"tion
o< nin# "as#lin# c2aract#ristics o< Aati#nts alr#a=> #nroll#= an= !ini!iE#= t2#
i!"alanc# o< t2os# c2aract#ristics across t2# %roAs1 Pati#nts ?#r# <ollo?#= <or a
!#=ian =ration o< 616 >#ars1
T2# #<<#ct o< 10 !%-=a> o< DYSLIP - 10 on liAi= l#v#ls ?as si!ilar to t2at
s##n in Ar#vios clinical trials1
DYSLIP - 10 si%ni<icantl> r#=c#= t2# rat# o< coronar> #v#nts K#it2#r <atal
coronar> 2#art =is#as# ((0 #v#nts in t2# Alac#"o %roA vs (0 #v#nts in t2# DYSLIP -
10 %roA$ or non<atal MI (107 #v#nts in t2# Alac#"o %roA vs 00 #v#nts in t2#
DYSLIP - 10 %roA$L ?it2 an a"solt# risG r#=ction o< 111H an= a r#lativ# risG
r#=ction o< 60H ("as#= on inci=#nc#s o< 115H <or DYSLIP - 10 vs 610H <or
Alac#"o$& AJ01000+ (s## .i%r# 1$L1 T2is risG r#=ction >i#l=s a N!"#r N##=#= to
Tr#at o< 611 Aati#nts A#r >#ar1 T2# risG r#=ction ?as consist#nt r#%ar=l#ss o< a%#&
s!oGin% stats& o"#sit> or Ar#s#nc# o< r#nal =>s<nction1 T2# #<<#ct o< DYSLIP - 10
?as s##n r#%ar=l#ss o< "as#lin# LDL l#v#ls1 D# to t2# s!all n!"#r o< #v#nts& r#slts
<or ?o!#n ?#r# inconclsiv#1
!i'ure 0: Effect of D#SLIP , 01 '3*a$ on Cuulative Inci*ence of "onfatal
M$ocar*ial Infarction or Coronar$ Heart Disease Deat& 4in ASCOT,LLA5
In t2# Colla"orativ# AtoRvastatin Dia"#t#s St=> (CARDS$& t2# #<<#ct o<
DYSLIP - 10(atorvastatin calci!$ on coronar> 2#art =is#as# (CHD$ an= non-CHD
#n=Aoints ?as ass#ss#= in '767 !#n (07H$ an= ?o!#n (6'H$& a%#s (0-,+ ?it2 t>A# '
=ia"#t#s "as#= on 8HO crit#ria& ?it2ot Arior 2istor> o< car=iovasclar =is#as# an=
?it2 LDL I (11( !!ol-L an= TG I 01,7 !!ol-L1 In a==ition to t>A# ' =ia"#t#s&
s"B#cts 2a= on# or !or# o< t2# <ollo?in% CHD risG <actors3 crr#nt s!oGin% ('6H$&
2>A#rt#nsion (70H$& r#tinoAat2> (60H$& !icroal"!inria (5H$ or !acroal"!inria
(6H$1 In t2is !ltic#nt#r& Alac#"o-controll#=& =o"l# "lin= clinical trial o< Ari!ar>
Ar#v#ntion o< <atal an= non<atal car=iovasclar an= c#r#"rovasclar =is#as# in s"B#cts
?it2 t>A# ' =ia"#t#s an= 1 ot2#r CHD risG <actor& Aati#nts ?#r# ran=o!l> allocat#= to
#it2#r DYSLIP - 10 !% =ail> (1('5$ or Alac#"o (1(11$ in a 131 ratio1
Pati#nts ?#r# <ollo?#= <or a !#=ian =ration o< 615 >#ars1 D# to si%ni<icant
tr#at!#nt "#n#<its (AI01000+& on#-si=#=& in <avor o< DYSLIP - 10$ s##n #arl> in t2#
st=>& t2# st=> ?as stoAA#= "> t2# CARDS St##rin% Co!!itt## t?o >#ars #arli#r t2an
anticiAat#=1
*as#lin# c2aract#ristics o< s"B#cts ?#r#3 !#an a%# o< 0' >#ars& !#an H"A1c
,1,HD !#=ian LDL-C 6110 !!ol-LD !#=ian TC +16+ !!ol-LD !#=ian TG 11,0
!!ol-LD !#=ian HDL-C 116( !!ol-L1
T2# #<<#ct o< DYSLIP - 10 !%-=a> on liAi= l#v#ls ?as si!ilar to t2at s##n in
Ar#vios clinical trials1
Tr#at!#nt ?it2 DYSLIP - 10 ?as associat#= ?it2 a statisticall> si%ni<icant 6,H
r#lativ# risG r#=ction (RRR$& or 61'H a"solt# risG r#=ction (ARR$ in t2# rat# o<
!aBor car=iovasclar #v#nts1 )<<icac> anal>sis s2o?#= t2at 76 (+17H$ o< DYSLIP - 10
tr#at#= Aati#nts an= 1', (510H$ o< Alac#"o tr#at#= Aati#nts #@A#ri#nc#= t2#ir <irst
Ari!ar> clinical #n=Aoint1 Co!Aarison o< t2# ti!# to t2# <irst Ari!ar> #n=Aoint in t2#
t?o %roAs >i#l=#= t2# 2aEar= ratio (HR$ o< 0106 ?it2 5+H CI 01(7& 0176 an= AJ01001
in <avor o< DYSLIP - 101 T2# n!"#r n##=#= to tr#at (NNT$ <or on# >#ar to Ar#v#nt
on# cas# #@A#ri#ncin% t2# Ari!ar> clinical #n=Aoint& "as#= on t2# ARR 61'H >i#l=s
1'+ Aati#nts1 T2# #<<#ct o< DYSLIP - 10 ?as s##n r#%ar=l#ss o< a%#& s#@& or "as#lin#
liAi= l#v#ls1
!i'ure <2 Tie to Occurrence of !irst Priar$ En*%oint
82#n car=iovasclar #v#nts ?#r# #valat#= s#Aarat#l>& DYSLIP - 10
si%ni<icantl> r#=c#= t2# r#lativ# risG o< stroG# "> (7H (ARR o< 116H$1 T2#r# ?#r# '1
cas#s o< stroG# (11+H$ in t2# DYSLIP - 10 %roA vs 65 cas#s ('17H$ in t2# Alac#"o
%roA& HR 01+'& 5+H CI 0161& 0175& AJ010101 To Ar#v#nt on# cas# o< stroG# 60,
Aati#nts ar# n##=#= to "# tr#at#= <or on# >#ar1
!i'ure 62 Tie to Occurrence of !irst Stro+e
R#lativ# risG o< !>ocar=ial in<arction ?as r#=c#= "> ('H& or ARR "> 117H&
?it2 67 cas#s ('1,H$ in t2# DYSLIP - 10 %roA vs 0( cas#s ((1+H$ in t2# Alac#"o
%roA& HR 01+7& 5+H CI 0165& 0170& A J 0100,1 To Ar#v#nt on# cas# o< !>ocar=ial
in<arction ''' Aati#nts 2av# to "# tr#at#= <or on# >#ar1
No si%ni<icant risG r#=ction ?as o"s#rv#= in t2# ti!# to <irst CA*G& PTCA or
ot2#r coronar> r#vasclariEation Aroc#=r#& ti!# to <irst nsta"l# an%ina or ti!# to
act# CHD =#at21 No si%ni<icant r#=ction ?as o"s#rv#= in ti!# to =#at2 =# to all
cas#s (01 =#at2s in t2# DYSLIP - 10 %roA vs 7' =#at2s in t2# Alac#"o %roA& HR
01,6& 5+H CI 01+'& 1101& AJ010+5$& car=iovasclar cas#s& or non-car=iovasclar
cas#s1
DETAILED PHARMACOLO.#
4I5 Huan P&aracolo'$
Huan P&araco+inetics
P2ar!acoGin#tic int#raction st=i#s 2av# "##n con=ct#= in 2#alt2> s"B#cts
?it2 6 !acroli=# anti"iotics3 #r>t2ro!>cin an= clarit2ro!>cin ("ot2 o< ?2ic2 in2i"it
CYP 6A($& an= ?it2 aEit2ro!>cin1 Coa=!inistration o< atorvastatin ?it2
#r>t2ro!>cin or clarit2ro!>cin& r#slt#= in !o=#rat#l> incr#as#= atorvastatin Alas!a
l#v#ls "t atorvastatin Alas!a l#v#ls ?#r# not alt#r#= "> aEit2ro!>cin1 T?#lv# 2#alt2>
s"B#cts ?#r# a=!inist#r#= atorvastatin 10 !% on =a>s 1 an= 1+D #r>t2ro!>cin +00 !%
:ID ?as a=!inist#r#= <ro! =a>s 7 to 151 )r>t2ro!>cin incr#as#= atorvastatin C!a@
an= AUC aAAro@i!at#l> (0H1 In a s#con= st=>& atorvastatin 10 !% ?as a=!inist#r#=
=ail> <or 7 =a>sD clarit2ro!>cin (+00 !% *ID$ or aEit2ro!>cin (+00 !% :D$ ?as
coa=!inist#r#= <ro! =a>s 0 - 7 (NJ1'-tr#at!#nt$1 Coa=!inistration ?it2
clarit2ro!>cin incr#as#= atorvastatin AUC R70H an= C!a@ R+0H& "t atorvastatin
Alas!a l#v#ls ?#r# not si%ni<icantl> alt#r#= "> coa=!inistration ?it2 aEit2ro!>cin1
St#a=>-stat#& oA#n-la"#l& A2ar!acoGin#tic st=i#s ?it2 =i%o@in 2av# "##n
A#r<or!#= in 2#alt2> s"B#cts ?it2 "ot2 lo? an= 2i%2 =os#s o< atorvastatin1
Atorvastatin (10 !% or 70 !% :DD NJ11 an= NJ1'& r#sA#ctiv#l>$& ?as a=!inist#r#=
<ro! =a>s 1 - '0 an= =i%o@in (01'+ !% :D$ <ro! =a>s 11 - '01 At st#a=>-stat#&
atorvastatin 10 !% =ail> 2a= no si%ni<icant #<<#ct on st#a=>-stat# =i%o@in
A2ar!acoGin#tics1 Ho?#v#r& <ollo?in% co-a=!inistration ?it2 atorvastatin 70 !% :D&
t2# !#an st#a=>-stat# =i%o@in AUC an= C!a@ incr#as#= 1+H an= '0H& r#sA#ctiv#l>1
Pati#nts taGin% =i%o@in s2ol= "# !onitor#= aAAroAriat#l>1
T2# #<<#ct o< a!lo=iAin# on t2# A2ar!acoGin#tics o< atorvastatin ?as ass#ss#=
at st#a=>-stat# in a ran=o!iE#=& oA#n-la"#l& Alac#"o-controll#=& crossov#r st=> in
2#alt2> !al# s"B#cts (NJ10$1 Atorvastatin (70 !% :D$ ?as a=!inist#r#= ?it2
a!lo=iAin# (10 !% :D$ or Alac#"o <ro! =a>s 1 - 71 .ollo?in% a 1( =a> ?as2ot& t2#
alt#rnat# co!"ination ?as a=!inist#r#= <ro! =a>s '' - '51 At st#a=>-stat#& t2#
coa=!inistration o< !a@i!! =os#s o< atorvastatin an= a!lo=iAin# =i= not
si%ni<icantl> alt#r t2# A2ar!acoGin#tics o< atorvastatin an= t2#r# ?#r# no aAAar#nt
c2an%#s in "loo= Ar#ssr# or 2#art rat#1
T2# #<<#ct o< CinaAril on t2# A2ar!acoGin#tics o< atorvastatin ?as ass#ss#= in
a ran=o!iE#=& oA#n-la"#l st=> in 2#alt2> volnt##rs (NJ''$1 Sin%l# =os#s o<
atorvastatin (10 !%$ ?#r# a=!inist#r#= on =a>s 1 to 1(& an= sin%l# =os#s o< CinaAril
(70 !%$ ?#r# a=!inist#r#= on =a>s 1 to , or =a>s 7 to 1(1 T2# !#an T!a@ val# <or
atorvastatin =rin% st#a=> stat# CinaAril a=!inistration ?as s2ort#n#= "> 11'+ 2ors
co!Aar#= to t2at o< atorvastatin a=!inist#r#= alon# "t ?it2 no c2an%# in
a"sorAtion-AUC or C!a@1 No si%ni<icant c2an%#s in "loo= Ar#ssr# or 2#art rat#s ?#r#
o"s#rv#=1
Conco!itant a=!inistration o< atorvastatin '0-(0!% an= itraconaEol# '00!%
=ail> r#slt#= in a '1+-616-<ol= incr#as# in atorvastatin AUC1
Conco!itant a=!inistration o< atorvastatin 10 !% an= c>closAorin# +1'
!%-G%-=a> r#slt#= in a ,1, <ol= incr#as# in #@Aosr# to atorvastatin1
4II5 Anial P&aracolo'$
T2# 2>AoliAi=#!ic Aot#ntial o< atorvastatin ?as #valat#= in
nor!oc2ol#st#rol#!ic ani!als& !o=#ls o< =i#t-in=c#= 2>A#rc2ol#st#rol#!ia an= a
!o=#l o< LDL r#c#Ator =#<ici#nc>1
In LDL r#c#Ator =#<ici#nt !ic#& atorvastatin lo?#r#= Alas!a total an= LDL-C
l#v#ls 1(H to (5H ov#r t2# =os# ran%# o< 10 to 600 !%-G% a<t#r ' ?##Gs1 Atorvastatin
lo?#r#= Alas!a c2ol#st#rol in c2o?-<#= rats irr#sA#ctiv# o< ?2#t2#r t2# co!Aon=
?as a=!i@#= in t2# =i#t or a=!inist#r#= "> oral %ava%#1 In c2o?-<#= %in#a Ai%s& a
!o=#l in ?2ic2 LDL is t2# !aBor liAoArot#in& atorvastatin %iv#n at 6& 10& or 60 !%-G%
"> %ava%# =ail> <or ' ?##Gs& =os#-=#A#n=#ntl> =#cr#as#= Alas!a total c2ol#st#rol 6(H
to +,H1
T2# a"ilit> o< atorvastatin to lo?#r Alas!a total an= liAoArot#in c2ol#st#rol
l#v#ls ?as also #valat#= in t?o ra""it !o=#ls o< 2>A#rc2ol#st#rol#!ia1 In t2#
#n=o%#nos 2>A#rc2ol#st#rol#!ic ra""it !o=#l (?2#r# !ost o< t2# Alas!a c2ol#st#rol
is transAort#= in LDL$& a=!inistration o< atorvastatin in t2# =i#t at 1& 6& an= 10 !%-G%
<or 0 to , ?##Gs lo?#r#= Alas!a total c2ol#st#rol 67H to +(H1 T2# #<<icac> o<
atorvastatin ?as =# to a +0H =#cr#as# in LDL Aro=ction an= (,H r#=ction in aAo
*1 In t2# c2ol#st#rol-<#= ra""it !o=#l (?2#r# 2>A#rc2ol#st#rol#!ia is !ostl> =# to
t2# acc!lation o< "#ta-!i%ratin% 9LDL$& atorvastatin a=!inist#r#= at '1+ !%-G% in
a 01+H c2ol#st#rol& 6H A#ant oil& 6H cocont oil =i#t <or ' ?##Gs r#=c#= Alas!a
total& 9LDL-C& an= LDL-C l#v#ls 6+H& ((H& an= '1H& r#sA#ctiv#l>1
In c2ol#st>ra!in#-Ari!#= =o%s& oral a=!inistration o< atorvastatin <or 6 ?##Gs
=os#-=#A#n=#ntl> lo?#r#= Alas!a total c2ol#st#rol 1+H to (1H ov#r t2# =os# ran%# o<
016 to 10 !%-G%1 In !iniatr# Ai%s <#= a =i#t ?2#r# 6(H o< calori#s ?#r# =#riv#= <ro!
<at& sAAl#!#nt#= ?it2 (00 !% c2ol#st#rol-=a>& atorvastatin %iv#n at 6 !%-G% in
%#latin caAsl#s <or 6 ?##Gs r#=c#= Alas!a total an= LDL-C 1+H an= ',H&
r#sA#ctiv#l>1 T2#s# =#cr#as#s ?#r# associat#= ?it2 a '6H to '5H r#=ction in Alas!a
9LDL an= LDL aAo * l#v#ls an= aAo * Aool siE#s an= a '1H an= '0H =#cr#as# in
9LDL-aAo * an= LDL-aAo * Aro=ction rat#s& r#sA#ctiv#l>1
Atorvastatin r#=c#= Alas!a TG l#v#ls A to 65H in !al# an= <#!al# LDL
r#c#Ator =#<ici#nt !ic# at =os#s o< 10& 60& 100& an= 600 !%-G% an= t2# c2an%#s ?#r#
nr#lat#= to =os# an= not associat#= ?it2 c2an%#s in TG Aro=ction rat#s1 In c2o?-<#=
rats& atorvastatin =#cr#as#= Alas!a TG l#v#ls 60H ?2#n a=!inist#r#= in t2# =i#t at
100 !%-G%D 2o?#v#r& Aon oral %ava%# a=!inistration TG l#v#ls ?#r# r#=c#= 66H
an= ,+H at '+ an= 100 !%-G%& r#sA#ctiv#l>1 In t2# scros#-<#= rat& a !o=#l o<
2>A#rtri%l>c#ri=#!ia =# to #n2anc#= 9LDL-TG Aro=ction& atorvastatin r#=c#=
Alas!a TG l#v#ls '0H to +6H at 1 to 60 !%-G% an= TG s#cr#tion rat#s (6H an= 00H
at 10 an= 60 !%-G%& r#sA#ctiv#l>1 C2an%#s in Alas!a TG l#v#ls ?#r# also not#= in
%in#a Ai%s& ra""its& an= !iniatr# s?in#1
In intact& ol#at#-tr#at#= H)P-G' c#lls& a 2!an 2#Aatoc>t# c#ll lin#&
atorvastatin r#=c#= t2# ol#at#-sti!lat#= s#cr#tion o< aAo * "> '1H an= =#cr#as#=
t2# a!ont o< intrac#lllar aAo * r#!ainin% ?it2in t2# c#lls "> '+H1 Atorvastatin
incr#as#= t2# intrac#lllar =#%ra=ation o< aAo * an= i!Aair#= t2# translocation o< aAo
* into t2# l!#n o< t2# #n=oAlas!ic r#ticl! ()R$ in A#r!#a"iliE#= H)P-G' c#llsD
t2is ?as associat#= ?it2 a =#cr#as# in t2# a!ont o< aAo * Aarticl#s Ar#s#nt in t2#
!icroso!al <raction1
.ollo?in% a sin%l# oral =os# to rats& atorvastatin in2i"it#= st#rol s>nt2#sis
(ass#ss#= "> K1(CLac#tat# incorAoration into liAi=s$D t2# =os# o< atorvastatin t2at
in2i"it#= st#rol s>nt2#sis "> +0H ()D+0$ ran%#= <ro! 0101 to 61( !%-G%1 T2# =ration
o< in2i"ition <or atorvastatin ?as si!ilar to ot2#r HMG-CoA r#=ctas# in2i"itorsD
2o?#v#r& atorvastatin !or# consist#ntl> in2i"it#= st#rol s>nt2#sis an av#ra%# o< 6(H
ov#r t2# <irst 7 2ors Aost=os#1 Atorvastatin an= its !#ta"olit#s ?#r# r#lativ#l>
#CiAot#nt in in2i"ition o< HMG-CoA r#=ctas# (as ass#ss#= "> !#asrin% t2#
incorAoration o< ra=iola"#ll#= HMG-CoA into !#valonat#$1
Antiat&erosclerotic Potential of Atorvastatin
T2# antiat2#roscl#rotic Aot#ntial o< atorvastatin ?as =#t#r!in#= in ra""it
!o=#ls o< at2#roscl#rotic l#sion Aro%r#ssion an= r#%r#ssion1 A co!!on <#atr# o< t2#
!o=#ls is t2at at2#roscl#rotic l#sions ?#r# in=c#= "> a co!"ination o<
2>A#rc2ol#st#rol#!ia an= c2ronic #n=ot2#lial =#n=ation o< t2# art#ri#s1
At2#roscl#rotic l#sion =#v#loA!#nt ?as ass#ss#= in t2# t2oracic aorta an=
c2ronicall> =#n=#= iliac-<#!oral art#r> o< 2>A#rc2ol#st#rol#!ic N#? ]#alan= 82it#
ra""its <#= a 01+H c2ol#st#rol& 6H A#ant oil& 6H cocont oil =i#t #it2#r alon# or
containin% '1+ !%-G% atorvastatin& lovastatin& Aravastatin& or si!vastatin <or 7 ?##Gs1
T2# liAi= cont#nt o< t2# iliac-<#!oral art#r> ?as na<<#ct#= "> tr#at!#ntD 2o?#v#r&
atorvastatin si%ni<icantl> r#=c#= t2# t2oracic aortic c2ol#st#rol #st#r cont#nt "> ++H
an= <r## c2ol#st#rol cont#nt (+H1 Atorvastatin si%ni<icantl> =#cr#as#= t2# cross-
s#ctional ar#a o< t2# iliac-<#!oral l#sion "> 05H an= !onoc>t#-!acroA2a%# cont#nt
"> ,1H1 In t2# =#sc#n=in% t2oracic aorta& a sit# o< sAontan#os& =i#t-in=c#=
at2#roscl#rotic l#sions& atorvastatin si%ni<icantl> r#=c#= t2# A#rc#nta%# o< %rossl>
=isc#rni"l# at2#roscl#rotic l#sions1
T2# a"ilit> o< atorvastatin to "lnt t2# =#v#loA!#nt o< co!Al#@ at2#roscl#rotic
l#sions an= Aro!ot# r#%r#ssion o< a liAi=-#nric2#= l#sion ?as ass#ss#= in an a==itional
ra""it !o=#l o< at2#roscl#rosis1 In ra""its a<t#r a 1+-?##G l#sion in=ction A2as#
consistin% o< <##=in% a 01+H c2ol#st#rol& 6H A#ant oil& 6H cocont oil =i#t <or 5
?##Gs an= a 0H c2ol#st#rol& 6H A#ant oil& 6H cocont oil =i#t <or 0 ?##Gs to n#arl>
nor!aliE# Alas!a c2ol#st#rol l#v#ls in all tr#at!#nt %roAs& + !%-G% atorvastatin
a=!inistration <or 7 ?##Gs in t2# c2o?-<at =i#t r#=c#= t2# c2ol#st#rol #st#r
#nric2!#nt o< t2# iliac-<#!oral art#r> an= t2oracic aorta "> ',H to (1H ?it2ot
c2an%in% t2# %ross #@t#nt o< t2oracic aortic l#sions an= inci=#nc# o< <i"ros AlaC#s1
Atorvastatin also r#=c#= t2# c2ol#st#rol #st#r cont#nt o< t2# iliac-<#!oral art#r> ">
6,H r#lativ# to initiation o< =r% int#rv#ntion& i#& a %roA o< ani!als n#croAsi#= Arior
to =r% tr#at!#nt1 MorA2o!#tric anal>sis o< t2# iliac-<#!oral art#r> r#v#al#= t2at
atorvastatin r#=c#= t2# l#sion cross-s#ctional ar#a "> (0H an= !onoc>t#-
!acroA2a%# cont#nt "> 00H1
TO@ICOLO.#
Acute To=icit$
T2# act# to@icit> o< atorvastatin <ollo?in% sin%l# =os#s ?as #valat#= in !ic#&
rats an= =o%s "> oral an= intrav#nos rot#s& an= t2# r#slts ar# s!!ariE#= "#lo?3
TA*L) '11 Act# Oral an= Intrav#nos To@icit> St=i#s ?it2 Atorvastatin
SA#ci#s S#@ Rot# Dos# Ran%# (!%-G%$ R#slts
Mos# Mal#-.#!al# Oral '00-+000 No D#at2s
Mos# Mal#-.#!al# I9 01 ( - ( No D#at2s
Rat Mal#-.#!al# Oral '00-+000 No D#at2s
Rat Mal#-.#!al# I9 01( - ( No D#at2s
Do% Mal#-.#!al# Oral 10 - (00 No D#at2s
Do% Mal#-.#!al# I9 01( - ( No D#at2s
T2# act# to@icit> o< atorvastatin in ro=#nts an= =o%s is lo?1 Oral !#=ian l#t2al
=os#s in !ic# an= rats ar# %r#at#r t2an +000 !%-G%1
Subacute an* C&ronic To=icit$ Stu*ies
T2# tar%#t or%ans a<<#ct#= "> atorvastatin in !ltiAl# =os# to@icit> st=i#s in
rats
(' ?##Gs to +' ?##Gs$& an= =o%s (' ?##Gs to 10( ?##Gs$ ar# s!!ariE#= in t2# ta"l#
"#lo?1 T2# sA#ctr! o< #<<#cts o"s#rv#= is not n#@A#ct#= in vi#? o< t2# !a%nit=#
o< t2# =os# l#v#ls s#=& Aot#nc> o< atorvastatin in in2i"itin% !#valonat# s>nt2#sis an=
t2# #ss#ntial rol# o< HMG-CoA r#=ctas# in !aintainin% c#lllar 2o!#ostasis1
TABLE <<2 Atorvastatin: Tar'et Or'ans Affecte* in Anial
Stu*ies
Rat Do%
Liv#r Liv#r
Sto!ac2 (non-%lan=lar$ Gall"la==#r
SG#l#tal Mscl# SG#l#tal Mscl#
Int#stin#
*rain-OAtic N#rv#W
W Occrr#= a<t#r a=!inistration o< 2i%2& intol#ra"l# =os#s ('70 !%-G%$
T2# <ollo?in% ta"l# s!!ariE#s t2# si%ni<icant a=v#rs# c2an%#s o"s#rv#=
=rin% lon%-t#r! to@icolo%> st=i#s in rats (+' ?##Gs$ an= =o%s (10( ?##Gs$3
TABLE <62 Atorvastatin: Si'nificant A*verse C&an'es in
C&ronic Stu*ies
Mini!al
SA#ci#s-R#slts To@ic Dos# No-)<<#ct Dos#
(!%-G%-=a>$ (!%-G%-=a>$
RAT
H#Aatoc#lllar at>Aia ,0 +
*il# Dct 2>A#rAlasia1 1'+ ,0
Non%lan=lar sto!ac2 acant2osis 1'+ ,0
DOG
D#at2' 1'0 (0
H#Aatoc#lllar %ranlo!ata6 10 ND
H#Aatoc#lllar n#crosis6 1'0 (0
Gall"la==#r #=#!a-2#!orr2a%#6 1'0 (0
*il# =ct 2>A#rAlasia6 1'0 10
Int#stinal lc#rs an= sin%l# c#ll 1'0 (0
n#crosis6
SG#l#tal !scl# (ton%#$ 1'0 (0
n#crosis'
1 Pr#s#nt onl> at 8##G '0D not o"s#rv#= at 8##G +'1
' .in=in%s occrr#= in 8##G , or 51
6 .in=in%s occrr#= at 8##G +' or in !ori"n= =o%s& ?#r# l#ss Arononc#=
a<t#r a 1'-?##G ?it2=ra?al A#rio= (8##G 0($& an= ?#r# not o"s#rv#= a<t#r 10( ?##Gs
o< =osin%1 ND J Not =#t#r!in#=
T2# r#slts o< t2# lon%-t#r! to@icolo%> st=i#s ?it2 atorvastatin in=icat#= t2at
si!ilar to ot2#r HMG-CoA r#=ctas# in2i"itors& t2# liv#r is t2# Ari!ar> tar%#t or%an1
T2is is #@A#ct#= sinc# t2# liv#r is t2# Ari!ar> sit# o< t2# A2ar!acolo%ic action o<
atorvastatin an= it is s"B#ct to t2# %r#at#st =r% #@Aosr# <ollo?in% oral
a=!inistration1 In "ot2 t2# rat an= =o% st=i#s& t2# 2#Aatic c2an%#s =i!inis2#= ?it2
ti!# (i1#1 #<<#cts ?#r# l#ss Arononc#= at t2# #n= o< t2# +'-?##G an= ! 10(-?##G
st=i#s$ s%%#stin% an a=aAtiv# r#sAons#1
*rain 2#!orr2a%#& oAtic n#rv# =#%#n#ration& l#nticlar oAaciti#s an= t#sticlar
=#%#n#ration ?#r# not s##n in =o%s tr#at#= <or 10(-?##Gs ?it2 atorvastatin A to 1'0
!%-G%-=a>1
Carcino'enicit$ an* .enoto=icit$ Stu*ies
Atorvastatin ?as not carcino%#nic in rats %iv#n 10& 60 or 100 !%-G%-=a> <or '
>#ars1 T2# 100 !%-G% =os# is 06-<ol= 2i%2#r t2an t2# !a@i!! r#co!!#n=#= 2!an
=os# o< 70 !% (110 !%-G%& "as#= on a +0 G% 2!an$ an= AUC (0-'( 2r$ val#s ?#r#
7- to 10-<ol= 2i%2#r1
In a '->#ar st=> in !ic# %iv#n 100& '00 or (00 !%-G%-=a>& inci=#nc#s o<
2#Aatoc#lllar a=#no!a in !al#s an= 2#Aatoc#lllar carcino!a in <#!al#s ?#r#
incr#as#= at (00 !%-G%1 T2is =os# is '+0 ti!#s t2# !a@i!! r#co!!#n=#= 2!an
=os# on a !%-G% "asis an= s>st#!ic #@Aosr# "as#= on AUC (0-'( 2r$ ?as 0 to 11
ti!#s 2i%2#r1 T2#r# ?as no #vi=#nc# o< tr#at!#nt- r#lat#= incr#as#s in t!or
inci=#nc#s at t2# lo?#r =os#s o< 100 an= '00 !%-G%-=a> (i1#1 A to 1'+ ti!#s t2#
!a@i!! r#co!!#n=#= 2!an =os# on a !%-G% "asis an= s>st#!ic #@Aosr#s o< 6
ti!#s 2i%2#r "as#= on AUC (0-'( 2r$1
Atorvastatin =i= not =#!onstrat# !ta%#nic or clasto%#nic Aot#ntial in <or in
vitro t#sts ?it2 an= ?it2ot !#ta"olic activation or in on# in vivo assa>1 It ?as
n#%ativ# in t2# A!#s t#st ?it2 in c2ro!oso!al a"#rrations in t2# in vitro C2in#s#
2a!st#r ln% c#ll assa> an= ?as n#%ativ# in t2# in vivo !os# !icroncl#s t#st1
Re%ro*uctive an* Terato'enicit$ Stu*ies
No a=v#rs# #<<#cts on <#rtilit> or r#Aro=ction ?#r# o"s#rv#= in !al# rats %iv#n
=os#s o< atorvastatin A to 1,+-!%-G%-=a> or in <#!al# rats %iv#n =os#s A to ''+
!%-G%-=a>1 T2#s# =os#s ar# 100 to 1(0 ti!#s t2# !a@i!! r#co!!#n=#= 2!an
=os# on a !%-G% "asis1 Atorvastatin =i= not cas# an> a=v#rs# #<<#cts on sA#r! or
s#!#n Aara!#t#rs& or in r#Aro=ctiv# or%an 2istoAat2olo%> in =o%s %iv#n =os#s o< 10&
(0 or 1'0 !%-G% <or ' >#ars1 Atorvastatin ?as not t#rato%#nic in #it2#r rats or ra""its1
PART III: CO"SUMER I"!ORMATIO"
D#SLIP , 01
4ATOR/ASTATI" CALCIUM TABLETS5
T2is l#a<l#t is Aart III o< a t2r##-Aart cPro=ct Mono%raA2d A"lis2#= ?2#n
DYSLIP - 10 ?as aAArov#= <or sal# in Cana=a an= is =#si%n#= sA#ci<icall> <or
Cons!#rs1 T2is l#a<l#t is a s!!ar> an= ?ill not t#ll >o #v#r>t2in% a"ot DYSLIP
- 101 Contact >or =octor or A2ar!acist i< >o->or c2il= 2av# an> C#stions a"ot t2#
=r%1 Pl#as# r#a= t2is in<or!ation car#<ll>1
ABOUT THIS MEDICATIO"
-&at LIPITOR is use* for3
Yor =octor 2as Ar#scri"#= t2#s# Aills to 2#lA lo?#r >or c2ol#st#rol or ot2#r
<ats in t2# "loo= (sc2 as tri%l>c#ri=#s$ an= to Ar#v#nt car=iovasclar =is#as# sc2 as
2#art attacGs1 Hi%2 l#v#ls o< c2ol#st#rol an= ot2#r <ats can cas# 2#art =is#as# ">
clo%%in% t2# "loo= v#ss#ls t2at <##= "loo= an= o@>%#n to t2# 2#art1
C2il=r#n 10-1, >#ars ol= ?it2 2#t#roE>%os <a!ilial 2>A#rc2ol#st#rol#!ia
(2i%2 c2ol#st#rol in2#rit#= <ro! on# o< t2# Aar#nts$ an= a <a!il> 2istor> o<
car=iovasclar =is#as# or ' or !or# risG <actors o< car=iovasclar =is#as#& as
=#t#r!in#= "> >or =octor& can also "#n#<it <ro! taGin% DYSLIP - 101
DYSLIP - 10 is Bst Aart o< t2# tr#at!#nt >or =octor ?ill Alan ?it2 >o->or
c2il= to 2#lA G##A >o 2#alt2>1 D#A#n=in% on >or->or c2il=Vs 2#alt2 an= li<#st>l#&
>or =octor !a>
r#co!!#n=3
a c2an%# in =i#t to control ?#i%2t an= r#=c# c2ol#st#rol&
r#=c# intaG# o< satrat#= <ats an= incr#as# <i"#r
#@#rcis# t2at is ri%2t <or >o->or c2il=
Cittin% s!oGin% or avoi=in% s!oG> Alac#s
%ivin% A alco2ol or =rinGin% l#ss
.ollo? >or =octorVs instrctions car#<ll>1
-&at D#SLIP , 01 *oes:
DYSLIP - 10 "#lon%s to t2# class o< !#=icin#s Gno?n as cstatinsd& !or#
sA#ci<icall> call#= HMG-CoA r#=ctas# in2i"itors1 HMG-CoA r#=ctas# is an #nE>!#
involv#= in r#%latin% c2ol#st#rol l#v#ls in >or "o=>1 Statins ar# s#= alon% ?it2
c2an%#s to #@#rcis# an= =i#t to 2#lA control t2# a!ont o< c2ol#st#rol Aro=c#= "> t2#
"o=>1
D#SLIP , 01 can &el% $our bo*$:
D#cr#as# LDL ("a=$ c2ol#st#rol& tri%l>c#ri=# l#v#ls an= ot2#r liAi=s -<ats in t2#
"loo=1
Incr#as# HDL 5%oo=$ c2ol#st#rol1
D#cr#as# t2# Total C2ol#st#rol HDL-C2ol#st#rol Ratio (TC3HDL-C Ratio$1
T2is ratio r#Ar#s#nts t2# "alanc# "#t?##n "a= an= %oo= c2ol#st#rol1
DYSLIP - 10 also r#=c#s t2# risG o< 2#art attacGs an= stroG#s in A#oAl# ?it2
!ltiAl# risG <actors <or coronar> 2#art =is#as# sc2 as 2i%2 "loo= Ar#ssr# an=
=ia"#t#s1 82#n s#= "> A#oAl# ?2o 2av# s<<#r#= a 2#art attacG in t2# Aast& DYSLIP -
10 r#=c#s t2# risG o< 2avin% anot2#r 2#art attacG1
DYSLIP - 10 is onl> availa"l# "> Ar#scriAtion a<t#r s##in% a =octor1
-&en D#SLIP , 01 s&oul* not be use*:
Do not taG# DYSLIP - 10 i< >o->or c2il=3
P Ar#-is all#r%ic to an> in%r#=i#nt o< t2is !#=ication (s## ?2at t2# !#=icinal
in%r#=i#nt is an= ?2at t2# i!Aortant non !#=icinal in%r#=i#nts ar#$1
P Hav# activ# liv#r =is#as# or n#@Alain#= incr#as#s in liv#r #nE>!#s1
P Ar#-is Ar#%nant or "r#ast-<##=in%1
-&at t&e e*icinal in're*ient is:
atorvastatin calci!1
-&at t&e i%ortant none*icinal in're*ients are:
LiAitor ta"l#ts contain3 calci! car"onat#& can=#lilla ?a@ (10& '0 an= (0!%$&
croscar!#llos# so=i!& 2>=ro@>AroA>l c#lllos#& 2>=ro@>AroA>l !#t2>lc#lllos#&
lactos# !ono2>=rat#& !a%n#si! st#arat#& !icrocr>stallin# c#lllos#& oAa=r> ?2it#&
Ys-1-,0(0& Aol>#t2>l#n# %l>col& Aol>sor"at# 70& si!#t2icon# !lsion& talc& titani!
=io@i=#1
-&at *osa'e fors it coes in:
DYSLIP - 10 ta"l#ts ar# availa"l# in ( str#n%t2s3 10!%& '0!%& (0!% an=
70!%1
-AR"I".S A"D PRECAUTIO"S
Serious -arnin's an* Precautions
T#ll >or =octor i< >o->or c2il= 2av# an> !scl# Aain& t#n=#rn#ss& sor#n#ss
or ?#aGn#ss =rin% tr#at!#nt ?it2 DYSLIP - 10
Before usin' t&is e*icine:
*#<or# taGin% DYSLIP - 10 t#ll >or =octor or A2ar!acist i< >o->or c2il=3
ar#-is Ar#%nant& int#n= to "#co!# Ar#%nant1 C2ol#st#rol co!Aon=s ar#
#ss#ntial #l#!#nts <or t2# =#v#loA!#nt o< a <#ts1 C2ol#st#rol-lo?#rin% =r%s can
2ar! t2# <#ts1 .#!al#s o< c2il=-"#arin% a%# s2ol= =iscss ?it2 t2#ir =octor t2#
Aot#ntial 2aEar=s to t2# <#ts an= t2# i!Aortanc# o< "irt2 control !#t2o=s1 DYSLIP -
10 s2ol= not "# s#= "> Ar#%nant ?o!#n1 I< >o->or c2il= "#co!# Ar#%nant&
=iscontin# s# i!!#=iat#l> an= =iscss ?it2 >or =octor1
1 ar#-is "r#ast-<##=in% or int#n= to "r#ast-<##=1 T2is !#=icin# !a> "# Ar#s#nt
in "r#ast !ilG1
1 2av# t2>roi= Aro"l#!s
r#%larl> =rinG t2r## or !or# alco2olic =rinGs =ail>
ar# taGin% an> ot2#r c2ol#st#rol lo?#rin% !#=ication sc2 as <i"rat#s
(%#!<i"roEil& <#no<i"rat#$& niacin or #E#ti!i"#
1 2av# a <a!il> 2istor> o< !sclar =isor=#rs
1 2a= an> Aast Aro"l#!s ?it2 t2# !scl#s (Aain& t#n=#rn#ss$& a<t#r sin% an
HMG-CoA r#=ctas# in2i"itor (cstatind$ sc2 as atorvastatin (DYSLIP - 10$&
<lvastatin (L#scol$& lovastatin (M#vacor$& Aravastatin (Pravacol$& rosvastatin
(Cr#stor$ or si!vastatin (]ocor$ or 2av# =#v#loA#= an all#r%> or intol#ranc# to t2#!1
2av# Gi=n#> or liv#r Aro"l#!s
2av# =ia"#t#s (as t2# =osa%# o< DYSLIP - 10 !a> n##= to "# a=Bst#=$
2av# n=#r%on# sr%#r> or ot2#r tiss# inBr>
=o #@c#ssiv# A2>sical #@#rcis#
DYSLIP - 10 ?as st=i#= in "o>s an= %irls (%irls ?2o alr#a=> start#= t2#ir
A#rio=$ 10-1, >#ars at a =os# o< 10 an= '0 !%1 DYSLIP - 10 2as not "##n st=i#= in
Ar#-A"#rtal Aati#nts or Aati#nts >on%#r t2an 10 >#ars o< a%#1 A=ol#sc#nt %irls s2ol=
=iscss ?it2 t2#ir =octor t2# Aot#ntial 2aEar=s to t2# <#ts an= t2# i!Aortanc# o< "irt2
control ?2il# on
DYSLIP - 10 t2#raA>1
I"TERACTIO"S -ITH THIS MEDICATIO"
As ?it2 !ost !#=icin#s& int#raction ?it2 ot2#r =r%s is Aossi"l#1 T#ll >or
=octor or A2ar!acist i< >o ar# taGin% an>
in=inavir sl<at#& n#l<inavir !#s>lat# & ritonavir& saCinavir !#s>lat#
=i%o@in
=iltiaE#!
#<avir#nE& ri<a!Ain
antaci=s (<r#C#nt s#$ an= DYSLIP - 10 s2ol= "# taG#n ' 2ors aAart
%raA#<rit Bic# - #sA#ciall> i< in%#stin% A?ar=s o< 11' litr#s o< %raA#<rit
Bic# at onc#
PROPER USE O! THIS MEDICATIO"
8# o<t#n cannot s## or <##l t2# Aro"l#!s t2at 2i%2 c2ol#st#rol cas#s ntil a
lot o< ti!# 2as Aass#=1 T2atVs ?2> it is i!Aortant to taG# t2#s# Aills Bst as Ar#scri"#=1
Yo->or c2il= an= >or =octor ?ill "# ?atc2in% >or->or c2il=Vs c2ol#st#rol l#v#ls
to %#t t2#! =o?n to a sa<# ran%#1 H#r# ar# so!# i!Aortant tiAs1
.ollo? t2# Alan t2at >o->or c2il= an= >or =octor !aG# <or =i#t& #@#rcis#
an= ?#i%2t control1
1TaG# DYSLIP - 10 as a sin%l# =os#1 It =o#s not !att#r i< DYSLIP - 10 is
taG#n ?it2 <oo= or ?it2ot <oo=& "t it s2ol= not "# taG#n ?it2 %raA#<rit Bic#1 Yor
=octor ?ill sall> t#ll >o->or c2il= to taG# it in t2# #v#nin%s1
1 Do not c2an%# t2# =os# nl#ss =ir#ct#= "> a =octor1
1 I< >o->or c2il= %#t sicG& 2av# an oA#ration& or n##= !#=ical tr#at!#nt&
in<or! >or =octor or A2ar!acist t2at >o->or c2il= ar# taGin% DYSLIP - 10
1 I< >o->or c2il= 2av# to taG# an> ot2#r !#=icin# Ar#scriAtion or non-
Ar#scriAtion -?2il# taGin% DYSLIP - 10& talG to >or =octor or A2ar!acist <irst1
1 I< >o->or c2il= 2av# to s## a =i<<#r#nt =octor <or an> r#ason& "# sr# to
in<or! 2i!-2#r t2at >o->or c2il= ar#-is taGin% DYSLIP - 10
DYSLIP - 10 ?as Ar#scri"#= <or >o->or c2il= onl>1 DonVt %iv# t2#s# Aills to
an>on# #ls#1
Usual Dose:
A*ults: T2# r#co!!#n=#= startin% =os# o< DYSLIP - 10 is 10 or '0 !% onc# =ail>&
=#A#n=in% on >or r#Cir#= LDL-C r#=ction1 Pati#nts ?2o n##= a lar%# r#=ction in
LDL-C (!or# t2an (+H$ !a> "# start#= at (0 !% onc# =ail>1 T2# =osa%# ran%# o<
DYSLIP - 10 is 10 to 70 !% onc# =ail>1 T2# !a@i!! =os# is 70 !%-=a>1
T2# r#co!!#n=#= =os# o< DYSLIP - 10 is 10 to 70 !%-=a> <or A#oAl# ?2o 2av#
alr#a=> s<<#r#= a 2#art attacG1
C2il=r#n (10-1, >#ars ol=$3 t2# r#co!!#n=#= startin% =os# o< DYSLIP - 10 is 10
!%-=a>D t2# !a@i!! r#co!!#n=#= =os# is '0 !%-=a>
Over*ose: T2#r# is no sA#ci<ic tr#at!#nt <or atorvastatin ov#r=osa%#1 S2ol= an
ov#r=os# occr& s## >or =octor ri%2t a?a>1
Misse* Dose: I< >o->or c2il= !iss taGin% a Aill& taG# it as soon as Aossi"l#1 *t i< it
is al!ost ti!# <or t2# n#@t =os#& sGiA t2# !iss#= =os# an= Bst taG# t2# n#@t =os#1
DonVt taG# a =o"l# =os#1
SIDE E!!ECTS A"D -HAT TO DO ABOUT THEM
Most A#oAl# =o not 2av# an> Aro"l#!s ?it2 si=# #<<#cts ?2#n taGin% t2is
!#=icin#1 Ho?#v#r& all !#=icin#s can cas# n?ant#= si=# #<<#cts1 C2#cG ?it2 >or
=octor or A2ar!acist Aro!Atl> i< an> o< t2# <ollo?in% A#rsist or "#co!# tro"l#so!#3
constiAation-=iarr2#a-%as
=#Ar#ssion (in c2il=r#n$
12#a=ac2#
sGin ras2
1 sto!ac2 Aain or As#t
1 vo!itin% or t2ro?in% A
9#r> rar#l>& a <#? A#oAl# !a> s<<#r <ro! Ban=ic#& <ro! a liv#r con=ition
call#= 2#Aatitis1
T2is is not a co!Al#t# list o< si=# #<<#cts1 I< >o->or c2il= notic# an>t2in%
nsal or an> n#@A#ct#= #<<#cts ?2il# taGin% DYSLIP - 10 contact >or =octor or
A2ar!acist
SERIOUS SIDE E!!ECTS( HO- O!TE" THE# HAPPE" A"D -HAT DO
ABOUT THEM
TalG ?it2 >or StoA taGin%
=octor or A2ar!acist =r% an= call
S>!Ato!-)<<#ct Onl> i< In all >or =octor or
s#v#r# cas#s A2ar!acist
Mscl# Aain t2at >o
cannot #@Alain
Mscl# t#n=#rn#ss or
?#aGn#ss
G#n#raliE#=
?#aGn#ss& #sA#ciall>
Rar# i< >o =onVt <##l ?#ll
*ro?nis2 or
=iscolor#= rin#
HO- TO STORE IT
Al)a$s +ee% e*icine )ell out of t&e reac& of c&il*ren2
/##A DYSLIP - 10 at roo! t#!A#ratr# (1+-60oC$& a?a> <ro! ?ar! an=
=a!A Alac#s& liG# t2# "at2roo! or Gitc2#n1

MORE I"!ORMATIO"
Pati#nts can r#<#r to DYSLIP - 10 <or <rt2#r in<or!ation1
T2is =oc!#nt Als t2# <ll Aro=ct !ono%raA2& Ar#Aar#= <or 2#alt2 Aro<#ssionals1

Product Monograph: Biodot Pharmaceuticals

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Product Monograph: Biodot Pharmaceuticals

Uploaded by

Copyright:

Available Formats

PRODUCT MONOGRAPH

You might also like