Attachment 1: Product information for AusPAR Daivobet 50/500;

calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;

"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
PRODUCT INFORMATION
Daivobet

50/500 gel
Calcipotriol 50 microgram/g
Betamethasone 500 microgram/g present as dipropionate AUST R 161936
NAME OF THE MEDICINE:
Daivobet

50/500 gel
OH
OH O H
H
H
H
2
O
Calcipotriol
Betaet!a"o#e $ipropio#ate
Calcipotriol i" %&'( )R( 5*( +,( 22,( 2-'. /2-/C0cloprop0l/1( &0/"ecoc!ola/5(+(&0%&1.(
22/tetrae#e/&()(2-/triol %CA' #o23 &&2424/00/1.2 T!e olec5lar 6eig!t o7 calcipotriol
!0$rate i" -)0282
Betaet!a"o#e $ipropio#ate i" 1/7l5oro/&&( &+( 2&/tri!0$ro90/&8/et!0lpreg#a/&(-/
$ie#e/)(20/$io#e &+(2&/$ipropio#ate %CA' #o23 551)/20/-.2 T!e epirical 7or5la i"
C
24
H
)+
FO
+
2 T!e olec5lar 6eig!t o7 betaet!a"o#e $ipropio#ate i" 50-282
D,'CRIPTION
Daivobet
:
gel i" a# alo"t clear( colo5rle"" to "lig!tl0 o77/6!ite gel a#$ co#tai#" 50
icrogra/g calcipotriol a#$ 500 icrogra/g betaet!a"o#e %a" $ipropio#ate.2
Calcipotriol i" a 6!ite or alo"t 6!ite cr0"talli#e "5b"ta#ce2 It i" 7reel0 "ol5ble i#
et!a#ol( "ol5ble i# c!loro7or a#$ prop0le#e gl0col( partic5larl0 i#"ol5ble i# li;5i$
para77i#2 'ol5bilit0 i# 6ater i" 028 g/< a#$ t!e elti#g poi#t i" &88 to &84=C2
Calcipotriol i" a vitai# D $erivative a#$ be!ave" i# a "iilar a##er to vitai# D(
7ori#g a rever"ible teperat5re/$epe#$e#t e;5ilibri5 bet6ee# calcipotriol a#$ pre/
calcipotriol2
Betaet!a"o#e $ipropio#ate i" a 6!ite or alo"t 6!ite( cr0"talli#e po6$er( practicall0
i#"ol5ble i# 6ater( 7reel0 "ol5ble i# aceto#e a#$ i# et!0le#e c!lori$e( "pari#gl0 "ol5ble
i# alco!ol2
& o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
Daivobet
:
gel al"o co#tai#" para77i#/li;5i$( PP>/&5 "tear0l et!er( !0$roge#ate$ ca"tor
oil( b5t0late$ !0$ro90l tol5e#e %,)2&. a#$ alp!a tocop!erol2
PHARMACO<O>?
P!araco$0#aic"
Calcipotriol i" a #o#/"teroi$al a#tip"oriatic age#t( $erive$ 7ro vitai# D2 Calcipotriol
e9!ibit" a vitai# D/li@e e77ect b0 copeti#g 7or t!e &( 25%OH.
2
D
)
receptor2 Calcipotriol
i" a" pote#t a" &(25%OH.
2
D
)
( t!e #at5rall0 occ5rri#g active 7or o7 vitai# D( i#
reg5lati#g cell proli7eratio# a#$ cell $i77ere#tiatio#( b5t 5c! le"" active t!a#
&(25%OH.
2
D
)
i# it" e77ect o# calci5 etaboli"2 Calcipotriol i#$5ce" $i77ere#tiatio# a#$
"5ppre""e" proli7eratio# %6it!o5t a#0 evi$e#ce o7 a c0toto9ic e77ect. o7 @erati#oc0te"(
t!5" rever"i#g t!e ab#oral @erati#oc0te c!a#ge" i# p"oria"i"2 T!e t!erape5tic goal
e#vi"age$ 6it! calcipotriol i" t!5" a #orali"atio# o7 epi$eral gro6t!2
Betaet!a"o#e $ipropio#ate i" a pote#t topicall0/active cortico"teroi$ pro$5ci#g
propt( ar@e$ a#$ prolo#ge$ a#ti/i#7laator0( a#tipr5ritic( va"oco#"trictive a#$
i5#o"5ppre""ive propertie"( 6it!o5t c5ri#g t!e 5#$erl0i#g co#$itio#2 T!e"e e77ect"
ca# be e#!a#ce$ 5#$er occl5"ive co#$itio#" $5e to i#crea"e$ pe#etratio# o7 "trat5
cor#e5 %b0 appro9iatel0 a 7actor o7 &0.2 T!e ec!a#i" o7 t!e a#ti/i#7laator0
activit0 o7 t!e topical "teroi$"( i# ge#eral( i" 5#clear2
P!araco@i#etic"
T!e "0"teic e9po"5re to calcipotriol a#$ betaet!a"o#e $ipropio#ate 7ro topicall0
applie$ Daivobet
:
gel i" &) A -5B le"" t!a# Daivobet
:
oi#te#t i# rat" a#$ i#ipig"2
Cli#ical "t5$ie" 6it! ra$iolabelle$ oi#te#t i#$icate t!at t!e "0"teic ab"orptio# o7
calcipotriol a#$ betaet!a"o#e 7ro Daivobet
:
oi#te#t 7or5latio# i" le"" t!a# &B o7
t!e $o"e %225 g. 6!e# applie$ to #oral "@i# %825 c
2
. 7or &2 !o5r"2 Applicatio# to
p"oria"i" pla;5e" a#$ 5#$er occl5"ive $re""i#g" a0 i#crea"e t!e ab"orptio# o7 topical
cortico"teroi$"2
Follo6i#g "0"teic e9po"5re( bot! active i#gre$ie#t" A calcipotriol a#$ betaet!a"o#e
$ipropio#ate A are rapi$l0 a#$ e9te#"ivel0 etaboli"e$2 T!e ai# ro5te o7 e9cretio# o7
calcipotriol a#$ betaet!a"o#e $ipropio#ate i" via 7aece" %rat"( ice a#$ i#ipig".2
Calcipotriol a#$ betaet!a"o#e $ipropio#ate 6ere belo6 t!e lo6er liit o7
;5a#ti7icatio# i# all bloo$ "aple" o7 )- patie#t" treate$ 7or - or 4 6ee@" 6it! bot!
Daivobet
:
gel a#$ Daivobet
:
oi#te#t 7or e9te#"ive p"oria"i" i#volvi#g t!e bo$0 a#$
"calp2 O#e etabolite o7 calcipotriol a#$ o#e etabolite o7 betaet!a"o#e $ipropio#ate
6ere ;5a#ti7iable i# "oe o7 t!e patie#t"2
CLINICAL TRIALS
,77icac0
T!e e77icac0 o7 o#ce $ail0 5"e o7 Daivobet
:
gel 6a" i#ve"tigate$ i# t6o ra#$oi"e$(
$o5ble/bli#$( 4/6ee@ cli#ical "t5$ie" i#cl5$i#g a total o7 ore t!a# 2(100 patie#t" 6it!
"calp p"oria"i" o7 at lea"t il$ "everit0 accor$i#g to t!e I#ve"tigatorC" >lobal
A""e""e#t o7 $i"ea"e "everit0 %I>A.2 Coparator" 6ere betaet!a"o#e $ipropio#ate
i# t!e gel ve!icle( calcipotriol i# t!e gel ve!icle a#$ %i# o#e o7 t!e "t5$ie". t!e gel
2 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
ve!icle alo#e( all 5"e$ o#ce $ail02 Re"5lt" 7or t!e priar0 re"po#"e criterio# %ab"e#t or
ver0 il$ $i"ea"e accor$i#g to t!e I>A at 6ee@ 4. "!o6e$ t!at Daivobet
:
gel 6a"
"tati"ticall0 "ig#i7ica#tl0 ore e77ective t!a# t!e coparator"2 Re"5lt" 7or "pee$ o7 o#"et
ba"e$ o# "iilar $ata at 6ee@ 2 al"o "!o6e$ Daivobet
:
gel to be "tati"ticall0
"ig#i7ica#tl0 ore e77ective t!a# t!e coparator"2
Table 1: Effia! of o"e #ail! $%e of Daivobet gel i" a#$lt% o&'a(e# to t)e i"#ivi#$al
ative o&'o"e"t% i" t)e %a&e gel fo(&$latio"
* of 'atie"t% +it)
ab%e"t o( ve(! &il#
#i%ea%e
Daivobet

gel
,"-1.10/0
1eta&et)a%o"e
#i'(o'io"ate
,"-1.11/0
Cali'ot(iol
,"-55/0
2el ve)ile
,"-1340
6ee@ 2 5)22B -224B
&
&+22B
&
&&24B
&
6ee@ 4 8124B 8225B
&
-02&B
&
2224B
&
&
'tati"ticall0 "ig#i7ica#tl0 le"" e77ective t!a# Daivobet
:
gel %PD0200&.
A#ot!er ra#$oi"e$( i#ve"tigator/bli#$e$ cli#ical "t5$0 i#cl5$i#g )&2 patie#t" 6it! "calp
p"oria"i" o7 at lea"t o$erate "everit0 accor$i#g to t!e I>A i#ve"tigate$ 5"e o7
Daivobet
:
gel o#ce $ail0 copare$ 6it! Daivo#e9
:
'calp 'ol5tio# t6ice $ail0 7or 5p to 4
6ee@"2 Re"5lt" 7or t!e priar0 re"po#"e criterio# %clear or i#ial $i"ea"e accor$i#g to
t!e I>A at 6ee@ 4. "!o6e$ t!at Daivobet
:
gel 6a" "tati"ticall0 "ig#i7ica#tl0 ore
e77ective t!a# Daivo#e9
:
'calp 'ol5tio#2
Table 5: Effia! of Daivobet

gel i" a#$lt% o&'a(e# to Daivo"e6

Sal' Sol$tio"
* of 'atie"t% +it) lea( o(
&i"i&al #i%ea%e
Daivobet

gel
,"-5070
Daivo"e6

Sal' Sol$tio"
,"-1050
6ee@ 4 8428B )&2-B
&
&
'tati"ticall0 "ig#i7ica#tl0 le"" e77ective t!a# Daivobet: gel %PD0200&.
O#e 5ltice#ter( ra#$oi"e$( $o5ble/bli#$ "t5$0 6a" co#$5cte$ i# "5bEect" 6it!
p"oria"i" v5lgari" o# bo$0 area"2 I# t!i" "t5$0( &&52 "5bEect" 6ere ra#$oi"e$ to o#e
o7 7o5r treate#t gro5p"3 Daivobet
:
gel( betaet!a"o#e $ipropio#ate i# t!e "ae
optii"e$ ve!icle( calcipotriol i# t!e "ae optii"e$ ve!icle( or t!e optii"e$ ve!icle
alo#e2 T!e "t5$0 e#rolle$ "5bEect" 6it! il$ to o$erate p"oria"i" v5lgari" o# t!e bo$02
T!e aEorit0 o7 "5bEect" !a$ $i"ea"e o7 o$erate "everit0 at ba"eli#e2 '5bEect" 6ere
treate$ o#ce $ail0 7or 4 6ee@"2
,77icac0 6a" a""e""e$ a" t!e proportio# o7 "5bEect" at 6ee@ - a#$ 6ee@ 4 6!o 6ere
FclearG or Falo"t clearG a#$ iprove$ at lea"t t6o "tep" accor$i#g to a# I#ve"tigatorC"
>lobal A""e""e#t o7 Di"ea"e" 'everit02 Table ) co#tai#" t!e re"po#"e rate" i# t!i"
trial2
) o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
Table 3: 8e(e"tage of 8atie"t% +it) Clea( o( Al&o%t Clea( Di%ea%e a"# at lea%t T+o Ste'%
I&'(ove&e"t Ao(#i"g to t)e I"ve%tigato(9% 2lobal A%%e%%&e"t of Di%ea%e Seve(it!
Daivobet
gel
,"-:/50
1eta&et)a%o"e
Di'(o'io"ate i"
ve)ile
,"-:7;0
Cali'ot(iol
i" ve)ile
,"-;40
<e)ile
,"-;50
Hee@ - &)2)B &225B
&
522B
2
22&B
2
Hee@ 4 2120B 2&25B
2
&-28B
2
82)B
2
&
No "tati"ticall0 "ig#i7ica#t $i77ere#ce to Daivobet
:
gel %PI0242.
2
'tati"ticall0 "ig#i7ica#tl0 le"" e77ective t!a# Daivobet
:
gel %PJ020&1.
'a7et0
A ra#$oi"e$( $o5ble/bli#$ lo#g/ter cli#ical "t5$0 i#cl5$i#g 481 patie#t" 6it! "calp
p"oria"i" o7 at lea"t o$erate "everit0 %accor$i#g to t!e I>A. i#ve"tigate$ t!e 5"e o7
Daivobet
:
gel copare$ 6it! calcipotriol i# t!e gel ve!icle2 Bot! treate#t" 6ere
applie$ o#ce $ail0( i#teritte#tl0 a" re;5ire$( 7or 5p to 52 6ee@"2 A$ver"e eve#t"
po""ibl0 relate$ to lo#g/ter 5"e o7 cortico"teroi$" o# t!e "calp( 6ere i$e#ti7ie$ b0 a#
i#$epe#$e#t( bli#$e$ pa#el o7 $eratologi"t"2 T!ere 6a" #o $i77ere#ce i# t!e
perce#tage" o7 patie#t" e9perie#ci#g "5c! a$ver"e eve#t" bet6ee# t!e treate#t
gro5p" %228B i# t!e Daivobet
:
gel gro5p a#$ )20B i# t!e calcipotriol gro5pK PI02+).2 No
ca"e" o7 "@i# atrop!0 6ere reporte$2
A$re#al re"po#"e to ACTH 6a" $eteri#e$ b0 ea"5ri#g "er5 corti"ol level" i#
patie#t" 6it! bot! e9te#"ive "calp a#$ bo$0 p"oria"i"( 5"i#g 5p to &08 g per 6ee@
cobi#e$ Daivobet
:
gel a#$ Daivobet
:
oi#te#t2 A bor$erli#e $ecrea"e i# corti"ol
re"po#"e at )0 i#5te" po"t ACTH c!alle#ge 6a" "ee# i# 5 o7 )2 patie#t" %&528B.
a7ter - 6ee@" o7 treate#t a#$ i# 2 o7 && patie#t" %&422B. 6!o co#ti#5e$ treate#t
5#til 4 6ee@"2 I# all ca"e"( t!e "er5 corti"ol level" 6ere #oral at 80 i#5te" po"t
ACTH c!alle#ge2 T!ere 6a" #o evi$e#ce o7 c!a#ge o7 calci5 etaboli" ob"erve$ i#
t!e"e patie#t"2
I# a#ot!er "t5$0( -) "5bEect" 6ere treate$ 6it! Daivobet
:
gel o# bo$0 area" a#$ a#0
a77ecte$ area" o# t!e "calp2 A$re#al "5ppre""io# 6a" i$e#ti7ie$ i# ) o7 -) "5bEect" %+B.
a7ter - 6ee@" o7 treate#t a#$ i# 0 o7 )8 "5bEect" 6!o provi$e$ $ata a7ter 4 6ee@"
treate#t2 T!e re"5lt" 7ro t!i" liite$ #5ber o7 "5bEect" $eo#"trate$ t!at Daivobet
:
gel a0 !ave e77ect" o# t!e HPA a9i" b5t t!e i#ci$e#ce 6a" lo6 a#$ $i$ #ot i#crea"e
over tie eve# i# a a9i5 5"e "etti#g2 'ee Over$o"age "ectio# 7or a$$itio#al
i#7oratio#2
T!e e77ect" o# calci5 etaboli" 6ere al"o "t5$ie$ i# t!e"e patie#t"2 T!e re"5lt"
$eo#"trate$ t!at t!ere 6ere #o c!a#ge" o7 cli#ical co#cer# regar$i#g t!e e77ect o#
calci5 etaboli"2
INDICATIONS
Topical treate#t o7 "calp p"oria"i"2
- o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
Topical treate#t o7 il$ to o$erate pla;5e p"oria"i" o# t!e bo$0 i# a$5lt"2
CONTRAINDICATIONS
i H0per"e#"itivit0 to t!e active "5b"ta#ce" or to a#0 o7 t!e e9cipie#t"2
ii Patie#t" 6it! @#o6# $i"or$er" o7 calci5 etaboli"2
iii D5e to t!e cortico"teroi$ co#te#t3 viral le"io#" o7 t!e "@i# %eg !erpe" or
varicella.( 75#gal or bacterial "@i# i#7ectio#"( para"itic i#7ectio#"( "@i#
a#i7e"tatio#" i# relatio# to t5berc5lo"i" or "0p!ili"( perioral $eratiti"( ac#e
v5lgari"( atrop!ic "@i#( "triae atrop!icae( 7ragilit0 o7 "@i# vei#"( ic!t!0o"i"( ac#e
ro"acea( ro"acea( 5lceratio# a#$ 6o5#$"( peria#al a#$ ge#ital pr5rit5"2
iv >5ttate( er0t!ro$eric( e97oliative a#$ p5"t5lar p"oria"i"
v Patie#t" 6it! "evere re#al i#"577icie#c0 or "evere !epatic $i"or$er"2
8RECA=TIONS
Treate#t o7 ore t!a# )0B o7 t!e bo$0 "5r7ace "!o5l$ be avoi$e$2 Repeate$
treate#t o7 large bo$0 "5r7ace area" a0 re"5lt i# a$ver"e e77ect"2
U#coo# local a$ver"e reactio#" %"5c! a" e0e irritatio# or irritatio# o7 7acial "@i#.
6ere ob"erve$( 6!e# t!e $r5g 6a" acci$e#tall0 a$i#i"tere$ i# t!e area o7 7ace( or
acci$e#tall0 to t!e e0e" or co#E5#ctive" %"ee A$ver"e ,77ect" "ectio#.2 T!e patie#t 5"t
be i#"tr5cte$ i# correct 5"e o7 t!e pro$5ct to avoi$ applicatio# a#$ acci$e#tal tra#"7er
to t!e 7ace( o5t! a#$ e0e"2 Ha#$" 5"t be 6a"!e$ a7ter eac! applicatio# to avoi$
acci$e#tal tra#"7er to t!e"e area" 5#le"" a77ecte$ "@i# o# t!e !a#$" i" bei#g treate$2
H!e# treati#g p"oria"i" 6it! topical cortico"teroi$"( t!ere a0 be a ri"@ o7 ge#erali"e$
p5"t5lar p"oria"i" or o7 rebo5#$ e77ect" 6!e# $i"co#ti#5i#g treate#t2 Me$ical
"5pervi"io# "!o5l$ t!ere7ore co#ti#5e i# t!e po"t/treate#t perio$2
Daivobet
:
gel co#tai#" a pote#t HHO gro5p III "teroi$ a#$ co#c5rre#t treate#t 6it!
ot!er "teroi$" o# t!e "calp 5"t be avoi$e$2 A$ver"e e77ect" 7o5#$ i# co##ectio# 6it!
"0"teic cortico"teroi$ treate#t( "5c! a" a$re#ocortical "5ppre""io# or ipact o# t!e
etabolic
co#trol o7 $iabete" ellit5"( a0 occ5r al"o $5ri#g topical cortico"teroi$ treate#t $5e
to "0"teic ab"orptio#2 Applicatio# 5#$er occl5"ive $re""i#g" "!o5l$ be avoi$e$ "i#ce
it i#crea"e" t!e "0"teic ab"orptio# o7 cortico"teroi$"2
I# a "t5$0 i# patie#t" 6it! bot! e9te#"ive "calp a#$ e9te#"ive bo$0 p"oria"i" 5"i#g a
cobi#atio# o7 !ig! $o"e" o7 Daivobet
:
gel %"calp applicatio#. a#$ !ig! $o"e" o7
Daivobet
:
oi#te#t %bo$0 applicatio#.( 5 o7 )2 patie#t" "!o6e$ a bor$erli#e $ecrea"e i#
corti"ol re"po#"e to a$re#ocorticotropic !oro#e %ACTH. c!alle#ge a7ter - 6ee@" o7
treate#t2
Applicatio# o# large area" o7 $aage$ "@i# or o# 5co5" ebra#e" or i# "@i# 7ol$"
"!o5l$ be avoi$e$ "i#ce it i#crea"e" t!e "0"teic ab"orptio# o7 cortico"teroi$"2 '@i# o7
t!e 7ace a#$ ge#ital" are ver0 "e#"itive to cortico"teroi$"2 T!e"e area" "!o5l$ o#l0 be
treate$ 6it! 6ea@er cortico"teroi$"2
5 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
T!e gel "!o5l$ be applie$ to t!e a77ecte$ area" o7 t!e "calp o#ce $ail0 7or 5p to -
6ee@" a#$ a77ecte$ area" o7 t!e bo$0 o#ce $ail0 7or 5p to 4 6ee@"2 I7 #o re"po#"e i"
ob"erve$ a7ter - 6ee@" t!e# treate#t o7 t!e bo$0 p"oria"i" "!o5l$ be cea"e$2
Treate#t o7 bo$0 p"oria"i" "!o5l$ be cea"e$ a7ter 4 6ee@"( a" t!ere are #o lo#g/ter
e77icac0 $ata available be0o#$ 4 6ee@" i# patie#t" treate$ 6it! Daivobet
:
gel o# t!e
bo$02 Ho6ever( t!ere are "a7et0 $ata o# i#teritte#t co5r"e" o7 Daivobet
:
gel 5"e$ 7or
5p to 52 6ee@" 7or "calp p"oria"i"2 Hit! lo#g/ter 5"e t!ere i" a# i#crea"e$ ri"@ o7
local a#$ "0"teic cortico"teroi$ 5#$e"irable e77ect"( i#cl5$i#g !0pot!alaic pit5itar0
a$re#al %HPA. a9i" "5ppre""io#2 T!e treate#t "!o5l$ be $i"co#ti#5e$ i# ca"e o7
5#$e"irable e77ect" relate$ to lo#g/ter 5"e o7 cortico"teroi$ %"ee A$ver"e ,77ect"
"ectio#.2 T!ere a0 be a ri"@ o7 rebo5#$ 6!e# $i"co#ti#5i#g lo#g/ter treate#t 6it!
cortico"teroi$"2 Me$ical "5pervi"io# "!o5l$ t!ere7ore co#ti#5e i# t!e po"t/treate#t
perio$2
H!e# le"io#" becoe "eco#$aril0 i#7ecte$( t!e0 "!o5l$ be treate$ 6it!
a#tiicrobiological t!erap02 Ho6ever( i7 i#7ectio# 6or"e#"( treate#t 6it! cortico"teroi$"
"!o5l$ be "toppe$2
D5e to t!e co#te#t o7 calcipotriol( !0percalcaeia a0 occ5r i7 t!e a9i5 6ee@l0
$o"e %&00 g. i" e9cee$e$2 'er5 calci5 i"( !o6ever( ;5ic@l0 #orali"e$ 6!e#
treate#t i" $i"co#ti#5e$2 T!e ri"@ o7 !0percalcaeia i" i#ial 6!e# t!e
recoe#$atio#" releva#t to calcipotriol are 7ollo6e$2
T!e "tabilit0 o7 calcipotriol i# "5#lig!t a#$ UL lig!t !a" #ot bee# $eo#"trate$2 No
cli#ical trial" !ave bee# co#$5cte$ 6it! calcipotriol/co#tai#i#g pro$5ct" i# A5"tralia(
6!ere t!ere i" a partic5larl0 !ig! pote#tial to be e9po"e$ to !ig! level" o7 UL ra$iatio#2
I# a$$itio#( t!e p!ototo9ic e77ect" o7 Daivobet
:
gel !ave #ot bee# "t5$ie$ i# p"oria"i"
patie#t"2 T!ere7ore( treate$ "@i# area" "!o5l$ be protecte$ 7ro "5#lig!t a#$ UL lig!t
%5"i#g p!0"ical coveri#g a#$/or "5#"cree#".( partic5larl0 6!ere e9po"5re a0 be
co#"i$erable 7or rea"o#" "5c! a" occ5patio#2
Daivobet
:
gel co#tai#" b5t0late$ !0$ro90l tol5e#e %,)2&. 6!ic! a0 ca5"e local "@i#
reactio#" %e2g2 co#tact $eratiti".( or irritatio# to t!e e0e" a#$ 5co5" ebra#e"2
Carci#oge#icit0
A $eral carci#oge#icit0 "t5$0 6it! calcipotriol i# ice "!o6e$ #o i#$icatio#" o7
i#crea"e$ carci#oge#ic ri"@"2 Calcipotriol "ol5tio# 6a" applie$ topicall0 7or 5p to 2-
o#t!" at $o"e" o7 )( &0 a#$ )0 Mg/@g/$a0 %corre"po#$i#g to 1( )0 a#$ 10 Mg/
2
/$a0.2
T!e !ig!/$o"e 6a" co#"i$ere$ to be t!e Ma9i5 Tolerate$ Do"e 7or $eral treate#t
o7 ice 6it! calcipotriol2 '5rvival 6a" $ecrea"e$ at &0 a#$ )0 Mg/@g/$a0( partic5larl0 i#
t!e ale"2 T!e re$5ce$ "5rvival 6a" a""ociate$ 6it! a# i#crea"e$ i#ci$e#ce o7 re#al
le"io#"2 T!i" i" a# e9pecte$ e77ect o7 treate#t 6it! !ig! $o"e" o7 calcipotriol or ot!er
vitai# D a#alog5e"2 T!ere 6ere #o $eral e77ect" a#$ #o $eral or "0"teic
carci#oge#icit02
I# a "t5$0 6!ere albi#o !airle"" ice 6ere repeate$l0 e9po"e$ to bot! 5ltraviolet %UL.
ra$iatio# a#$ topicall0 applie$ calcipotriol 7or -0 6ee@" at t!e "ae $o"e level" a" i#
t!e $eral calcipotriol carci#oge#icit0 "t5$0( a re$5ctio# i# t!e tie re;5ire$ 7or UL
ra$iatio# to i#$5ce t!e 7oratio# o7 "@i# t5o5r" 6a" ob"erve$ %"tati"ticall0 "ig#i7ica#t
i# ale" o#l0.( "5gge"ti#g t!at calcipotriol a0 e#!a#ce t!e e77ect o7 UL ra$iatio# to
i#$5ce "@i# t5o5r"2 I# a "5pplee#tar0 "t5$0( ice o7 t!e "ae "trai# 6ere treate$
8 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
repeate$l0 6it! eit!er calcipotriol "ol5tio# or calcipotriol/betaet!a"o#e gel( 7ollo6e$ b0
irra$iatio# 6it! ULR a#$ ea"5ree#t o7 recog#i"e$ cell5lar i#$icator" o7 "@i#
p!otocarci#oge#icit02 T!i" "t5$0 "!o6e$ a "iilar e#!a#ci#g e77ect o7 calcipotriol alo#e
o# t!e p!otobiological re"po#"e o7 t!e "@i# calcipotriol/betaet!a"o#e gel i#crea"e$
cell5lar proli7eratio# b5t $i$ #ot i#crea"e ot!er ar@er" i#$icative o7 e#!a#cee#t o7
p!otocarci#oge#e"i"2 T!e cli#ical releva#ce o7 t!e"e 7i#$i#g" i" 5#@#o6#2
No carci#oge#icit0 or p!otocarci#oge#icit0 "t5$ie" !ave bee# per7ore$ 6it!
betaet!a"o#e $ipropio#ate2
>e#oto9icit0
Calcipotriol 6a" #ot ge#oto9ic i# a""a0" 7or ge#e 5tatio#" %Ae" te"t a#$ o5"e
l0p!oa TN loc5" a""a0. or c!roo"oal $aage %!5a# l0p!oc0te c!roo"oal
aberratio# or o5"e icro#5cle5" te"t.2 Betaet!a"o#e $ipropio#ate 6a" #ot
ge#oto9ic i# t!e Ae" 5tage#icit0 a""a0( t!e o5"e l0p!oa TN loc5" a""a0 or i#
t!e rat icro#5cle5" te"t2
U"e i# Preg#a#c0 %Categor0 B&.
T!ere are #o a$e;5ate $ata 7ro t!e 5"e o7 Daivobet
:
gel i# preg#a#t 6oe#2
Daivobet
:
gel "!o5l$ o#l0 be 5"e$ $5ri#g preg#a#c0 6!e# t!e pote#tial be#e7it clearl0
o5t6eig!" t!e pote#tial ri"@2
't5$ie" o7 cortico"teroi$" i# a#ial" !ave "!o6# repro$5ctive to9icit0 %cle7t palate(
"@eletal al7oratio#".2 I# repro$5ctio# to9icit0 "t5$ie" 6it! lo#g/ter oral
a$i#i"tratio# o7 cortico"teroi$" to rat"( prolo#ge$ ge"tatio# a#$ prolo#ge$ a#$ $i77ic5lt
labo5r 6ere $etecte$2 Moreover( re$5ctio# i# o77"pri#g "5rvival( bo$0 6eig!t a#$ bo$0
6eig!t gai# 6a" ob"erve$2 't5$ie" o7 calcipotriol i# a#ial" !ave "!o6# a# i#crea"e i#
t!e i#ci$e#ce o7 "@eletal variatio#" i# rat" %6av0 rib"( e9tra rib"( i#coplete
$evelope#t o7 "@5ll bo#e". at oral $o"e" o7 &4 g/@g $a0 a#$ i# rabbit" %re$5ce$
"@eletal o""i7icatio#. at oral $o"e" o7 )8 g/@g $a02 T!e releva#ce o7 t!e"e 7i#$i#g" 7or
!5a#" i" 5#@#o6#2
,77ect" o# Fertilit0
Po""ible e77ect" o7 betaet!a"o#e i# cobi#atio# 6it! calcipotriol o# 7ertilit0 !ave #ot
bee# i#ve"tigate$ i# a#ial"2 't5$ie" o7 t!e oral a$i#i"tratio# o7 calcipotriol i# rat"
!ave "!o6# #o ipaire#t o7 7ertilit02
U"e i# <actatio#
Betaet!a"o#e i" e9crete$ i#to brea"t il@2 It i" 5#@#o6# i7 topical applicatio# o7
Daivobet
:
gel co5l$ re"5lt i# "577icie#t "0"teic ab"orptio# to pro$5ce "ig#i7ica#t
;5a#titie" o7 t!i" cortico"teroi$ i# !5a# brea"t il@2 T!ere are #o $ata o# t!e
e9cretio# o7 calcipotriol i# brea"t il@2
Ca5tio# "!o5l$ be e9erci"e$ 6!e# pre"cribi#g Daivobet
:
gel to brea"t/7ee$i#g 6oe#2
Applicatio# o7 Daivobet
:
gel to t!e brea"t area "!o5l$ be avoi$e$2 Daivobet
:
gel "!o5l$
o#l0 be 5"e$ $5ri#g lactatio# i7 t!e pote#tial be#e7it" clearl0 o5t6eig! t!e pote#tial
ri"@"2
+ o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
NOT,3 A7ter appl0i#g Daivobet
:
gel( ot!er" "!o5l$ 6a"! t!eir !a#$" t!oro5g!l0 prior
to !a#$li#g t!eir c!il$2
U"e i# C!il$re#
Daivobet
:
gel i" #ot recoe#$e$ 7or 5"e i# c!il$re# a#$ a$ole"ce#t" belo6 &4 0ear"
o7 age a" t!e "a7et0 a#$ e77ective#e"" o7 Daivobet
:
gel i# t!i" pop5latio# !a" #ot bee#
e"tabli"!e$2
Beca5"e o7 a !ig!er ratio o7 "@i# "5r7ace area to bo$0 a""( c!il$re# 5#$er t!e age o7
&2 0ear" a0 be at partic5lar ri"@ o7 "0"teic a$ver"e e77ect" 6!e# t!e0 are treate$
6it! topical cortico"teroi$"2
Re#al Ipaire#t
'a7et0 !a" #ot bee# e"tabli"!e$ i# patie#t" 6it! re#al ipaire#t2 Daivobet
:
i"
co#trai#$icate$ i# patie#t" 6it! "evere re#al ipaire#t2
Hepatic Ipaire#t
'a7et0 !a" #ot bee# e"tabli"!e$ i# patie#t" 6it! !epatic ipaire#t2 Daivobet
:
i"
co#trai#$icate$ i# patie#t" 6it! "evere !epatic ipaire#t2
I#teractio#" 6it! ot!er $r5g"
No i#teractio# "t5$ie" !ave bee# per7ore$2
T!ere i" #o e9perie#ce 6it! co#c5rre#t 5"e o7 ot!er a#ti/p"oriatic pro$5ct"
a$i#i"tere$ "0"teicall0 or 6it! p!otot!erap02
Effet% o" Labo(ato(! Te%t%
T!ere are #o $ata available o# t!e e77ect" o7 Daivobet
:
gel o# laborator0 te"t"2
AD<ERSE EFFECTS
Cli"ial T(ial%
De7i#itio# o7 7re;5e#c0 o7 a$ver"e eve#t"3
Ler0 coo# O&/&0
Coo# O&/&00 a#$ D&/&0
U#coo# O&/&(000 a#$ D&/&00
Rare O&/&0(000 a#$ D&/&(000
Ler0 Rare D&/&0(000
T!e cli#ical trial prograe 7or Daivobet
:
gel !a" "o 7ar i#cl5$e$ ore t!a# 8( 000
patie#t" o7 6!o ore t!a# )(000 6ere treate$ 6it! Daivobet
:
gel2
4 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
'calp P"oria"i"
Appro9iatel0 4B o7 patie#t" treate$ 6it! Daivobet
:
gel o# t!e "calp e9perie#ce$ a
#o#/"erio5" a$ver"e $r5g reactio# %po""ibl0 relate$ to "t5$0 e$icatio#.2
Ba"e$ o# t!e above 7re;5e#c0 $e7i#itio#( $ata 7ro cli#ical trial" "!o6 t!at t!e o#l0
coo# a$ver"e $r5g reactio# i" pr5rit5"2 T!e 5#coo# a$ver"e eve#t" are b5r#i#g
"e#"atio# o7 t!e "@i#( "@i# pai# or irritatio#( 7ollic5liti"( $eratiti"( er0t!ea( ac#e( $r0
"@i#( e9acerbatio# o7 p"oria"i"( ra"!( p5"t5lar ra"! a#$ e0e irritatio#2 T!e"e a$ver"e
eve#t" 6ere all #o#/"erio5" local reactio#"2
Bo$0 P"oria"i"
A$ver"e $r5g reactio#" t!at occ5rre$ i# ore t!a# &B o7 patie#t" treate$ 6it!
Daivobet
:
gel o# t!e bo$0 area" are li"te$ i# Table -2
Table :: A#ve(%e #($g (eatio"% o$((i"g i" >1* of %$b?et% i" t)e Daivobet

gel g(o$'
of o"t(olle# %t$#ie% i" bo#! '%o(ia%i%: %afet! a"al!%i% %et
8(efe((e# te(&
Daivobet

gel
,N-/5:0
" ,*0
1eta&et)a%o"e
gel
,N-5450
" ,*0
Cali'ot(iol
gel
,N-1750
" ,*0
2el ve)ile
,N-5540
" ,*0
Pr5rit5" &2 %&25. 2 %02-. 5 %221. &5 %828.
I# a ra#$oi"e$( 5ltice#tre( active a#$ ve!icle co#trolle$ "t5$0 6!ere -42 patie#t"
applie$ Daivobet
:
gel to a77ecte$ bo$0 area" 7or 4 6ee@"( #o "tati"ticall0 "ig#i7ica#t
$i77ere#ce" i# i#ci$e#ce o7 a$ver"e $r5g reactio#" bet6ee# t!e Daivobet
:
gel a#$
ve!icle 6ere recor$e$2
T!ere are i#a$e;5ate $ata o# relap"e a#$ rebo5#$ 6it! Daivobet
:
gel2 A$ver"e eve#t"
ob"erve$ 7or calcipotriol a#$ betaet!a"o#e are provi$e$ belo62
Calcipotriol
Pote#tial a$ver"e eve#t" i#cl5$e applicatio# "ite reactio#"( pr5rit5"( "@i# irritatio#(
b5r#i#g a#$ "ti#gi#g "e#"atio#( $r0 "@i#( er0t!ea( ra"!( $eratiti"( ecPea(
aggravatio# o7 p"oria"i"( tra#"ie#t p!oto"e#"itivit0( tra#"ie#t c!a#ge" i# "@i#
pige#tatio# a#$ allergic a#$ !0per"e#"itivit0 reactio#" i#cl5$i#g ver0 rare ca"e" o7
a#gioe$ea a#$ 7acial oe$ea2 A7ter topical 5"e( "0"teic e77ect"( ca5"i#g
!0percalcaeia or !0percalci5ria a0 appear ver0 rarel02
Betaet!a"o#e
T!i" pro$5ct co#tai#" a pote#t cortico"teroi$2
<ocal reactio#" ca# occ5r a7ter topical cortico"teroi$ 5"e( e"peciall0 $5ri#g prolo#ge$
applicatio#( i#cl5$i#g "@i# atrop!0( tela#giecta"ia( "triae( 7ollic5liti"( !0pertric!o"i"(
perioral $eratiti"( allergic co#tact $eratiti"( $epige#tatio# a#$ colloi$ ilia2 H!e#
1 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
5"e$ 7or t!e treate#t o7 p"oria"i"( t!ere a0 be t!e ri"@ o7 ge#erali"e$ p5"t5lar
p"oria"i"2 T!ere a0 be a ri"@ o7 rebo5#$ 6!e# $i"co#ti#5i#g lo#g ter treate#t 6it!
cortico"teroi$"2
'0"teic e77ect" $5e to topical cortico"teroi$" are rare i# a$5lt"( !o6ever( t!e0 ca# be
"evere2 HPA "5ppre""io#( !0percalcaeia( cataract( i#7ectio#" a#$ i#crea"e i# i#tra/
oc5lar pre""5re ca# occ5r( e"peciall0 a7ter lo#g ter treate#t2 '0"teic e77ect" occ5r
ore 7re;5e#tl0 6!e# applie$ 5#$er occl5"io#( 6!e# applie$ o# large area" or $5ri#g
lo#g treate#t2
Po"t Mar@eti#g ,9perie#ce
'i#ce eve#t" 7ro po"t ar@et 5"e are reporte$ vol5#taril0 7ro a pop5latio# o7
5#certai# "iPe( it i" ge#erall0 #ot po""ible to reliabl0 e"tiate t!eir 7re;5e#c0 or
e"tabli"! a ca5"al relatio#"!ip to $r5g e9po"5re2 T!e o"t 7re;5e#tl0 reporte$ eve#t"
are e#tio#e$ regar$le"" o7 li"te$#e""2
Ba"e$ o# $ata 7ro po"t ar@et 5"e Daivobet
:
gel o# bo$0 a#$ "calp p"oria"i"( t!e
o"t 7re;5e#tl0 reporte$ a$ver"e eve#t" are e9acerbatio# o7 p"oria"i"( pr5rit5"(
alopecia( b5r#i#g "e#"atio# a#$ er0t!ea2
DOSA2E AND ADMINISTRATION
Daivobet
:
gel i" FOR TOPICA< U', ON<?2 Daivobet
:
gel i" NOT FOR OPHTHA<MIC
U',2
T!e p!ototo9ic e77ect" o7 Daivobet
:
gel !ave #ot bee# "t5$ie$ i# p"oria"i" patie#t" i#
A5"tralia2 All p"oria"i"/a77ecte$ area" treate$ 6it! Daivobet
:
gel "!o5l$ be( 6!ere
po""ible( protecte$ 7ro $irect "5#lig!t a#$ UL/lig!t 6it! ite" o7 clot!i#g2
A$5lt"
Bo$0 p"oria"i"3 Daivobet
:
gel "!o5l$ be applie$ o#ce $ail0 7or 5p to 4 6ee@"2
I7 t!ere i" #o re"po#"e a7ter - 6ee@"( treate#t "!o5l$ be cea"e$2 Treate#t o7 bo$0
p"oria"i" "!o5l$ be cea"e$ a7ter 4 6ee@"2
'calp p"oria"i"3 Daivobet
:
gel "!o5l$ be applie$ o#ce $ail0 7or 5p to - 6ee@"2 A7ter t!i"
perio$( Daivobet
:
gel a0 be 5"e$ accor$i#g to #ee$ 5#$er e$ical "5pervi"io#2 T!ere
i" e9perie#ce 6it! i#teritte#t co5r"e" o7 Daivobet
:
gel 5p to 52 6ee@" 7or "calp
p"oria"i"2
All t!e a77ecte$ "calp area" a0 be treate$ 6it! Daivobet
:
gel2 U"5all0 a# ao5#t
bet6ee# & g a#$ - g per $a0 i" "577icie#t 7or treate#t o7 t!e "calp %- g corre"po#$" to
o#e tea"poo#.2
H!e# 5"i#g calcipotriol co#tai#i#g pro$5ct"( t!e a9i5 $ail0 $o"e "!o5l$ #ot
e9cee$ &5 g a#$ t!e a9i5 6ee@l0 $o"e "!o5l$ #ot e9cee$ &00 g2
T!e total bo$0 "5r7ace area treate$ 6it! calcipotriol %)o$l# "ot e6ee# )0B2
Repeate$ treate#t o7 large bo$0 "5r7ace area" a0 re"5lt i# a$ver"e e77ect"2
'!a@e t!e bottle be7ore 5"e2
&0 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
I# or$er to ac!ieve optial e77ect( it i" recoe#$e$ t!at t!e !air i" #ot 6a"!e$
ie$iatel0 a7ter applicatio# o7 Daivobet
:
gel2 Daivobet
:
gel "!o5l$ reai# o# t!e "calp
$5ri#g t!e #ig!t or $5ri#g t!e $a02
&& o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
C!il$re#
Daivobet
:
gel i" #ot recoe#$e$ 7or 5"e i# c!il$re# a#$ a$ole"ce#t" belo6 t!e age o7
&4 0ear" $5e to t!e lac@ o7 $ata o# "a7et0 a#$ e77icac02
O<ERDOSA2E
U"e at ore t!a# t!e recoe#$e$ $o"e a0 ca5"e elevate$ "er5 calci5( 6!ic!
rapi$l0 "5b"i$e" 6!e# treate#t i" $i"co#ti#5e$2
,9ce""ive prolo#ge$ 5"e o7 topical cortico"teroi$" a0 "5ppre"" t!e !0pot!alaic
pit5itar0 a$re#al a9i" %HPA. re"5lti#g i# "eco#$ar0 a$re#al i#"577icie#c0( 6!ic! i" 5"5all0
rever"ible2 I# "5c! ca"e" "0ptoatic treate#t i" i#$icate$2
I# ca"e o7 c!ro#ic to9icit0 t!e topical cortico"teroi$ treate#t 5"t be 6it!$ra6#
gra$5all02
It !a" bee# reporte$ t!at $5e to i"5"e o#e patie#t 6it! e9te#"ive er0t!ro$eric
p"oria"i" treate$ 6it! 2-0 g o7 Daivobet
:
oi#te#t 6ee@l0 %a9i5 $o"e &00 g
6ee@l0. 7or 5 o#t!" $evelope$ C5"!i#gC" "0#$roe a#$ a7ter abr5ptl0 "toppi#g
treate#t $evelope$ p5"t5lar p"oria"i"2
Co#tact t!e Poi"o#" I#7oratio# Ce#tre o# &)& &28 7or 75rt!er a$vice o# over$o"e
a#agee#t2
8RESENTATION AND STORA2E CONDITIONS
Daivobet
:
gel co#tai#" 50 icrogra" calcipotriol per gra a#$ 500 icrogra"
betaet!a"o#e %a" $ipropio#ate. per gra i# a# alo"t clear( colo5rle"" to "lig!tl0 o77/
6!ite gel2 It i" available i# bottle" o7 )0 a#$ 80 g2
Sto(age: 'tore belo6 25QC2 Do #ot re7rigerate2
Neep t!e bottle i# t!e o5ter carto# i# or$er to protect 7ro lig!t2
'!el7 li7e3 2 0ear" 7ro $ate o7 a#57act5re
U"e 6it!i# ) o#t!" o7 ope#i#g2
Do #ot 5"e be0o#$ t!e e9pir0 $ate o# t!e pac@age2
Do #ot 5"e i7 t!e pac@ "!o6" "ig#" o7 $aage or taperi#g2
NAME AND ADDRESS OF S8ONSOR
I# A5"tralia3
<,O P!ara Pt0 <t$(
<evel )( To6er &(
25 Mo#tpelier Roa$(
Bo6e# Hill"( R<D -008(
AU'TRA<IA
&2 o7 &)
Attachment 1: Product information for AusPAR Daivobet 50/500;
calcipotriol 50 g/g and betamethasone as dipropionate! 500 g/g gel;
"eo Pharma Pt# "td; P$%&011%0'1''%(%5; Date of )inalisation * August
&01(+ ,his Product -nformation .as approved at the time this AusPAR .as
published+
AU'T R &8&1)8
MAN=FACT=RER
<,O P!ara A/'
Baller5p D,NMARN
A#$
<,O <aboratorie" <t$ %<,O P!ara.
D5bli# IR,<AND
8OISON SCHED=LE OF MEDICINE
'-
DATE OF A88RO<AL
I#itial Date o7 Approval3 &-t! S5l0 20&0
Date o7 o"t rece#t ae#$e#t3 22#$ Marc! 20&)
Daivobet i" a regi"tere$ tra$ear@ o7 <,O P!ara A/'( De#ar@
&) o7 &)
<P'/&2/055