ADVAIR DISKUS 100/50 (futicasone propionate) ,

ADVAIR DISKUS (futicasone propionate) 250/50

ADVAIR DISKUS 500/50 are combinations o futicasone propionate and salmeterol
xinafoate!
"ne acti#e component o ADVAIR DISKUS is futicasone propionate, a corticosteroi$ %a#in&
t%e c%emica' name S(('uoromet%)') *+,,($i'uoro(11-,1.($i%)$ro/)(1*+(met%)'(0(
o/oan$rosta(1,1($iene(1.-(carbot%ioate, 1.(propionate an$ t%e o''o2in& c%emica'
structure3
4'uticasone propionate is a 2%ite po2$er 2it% a mo'ecu'ar 2ei&%t o 500!*, an$ t%e
empirica' ormu'a is 5
25
6
01
4
0
"
5
S! It is practica'') inso'ub'e in 2ater, ree') so'ub'e in
$imet%)' su'o/i$e an$ $imet%)'ormami$e, an$ s'i&%t') so'ub'e in met%ano' an$ ,57
et%ano'!
8%e ot%er acti#e component o ADVAIR DISKUS (futicasone propionate) is sa'metero'
/inaoate, a beta
2
(a$rener&ic bronc%o$i'ator! Sa'metero' /inaoate is t%e racemic orm o
t%e 1(%)$ro/)(2nap%t%oic aci$ sa't o sa'metero'! 8%e c%emica' name o sa'metero'
/inaoate is 1(%)$ro/)(+1999*((1(p%en)'buto/))%e/)':amino:met%)':(1,0(
ben;ene$imet%ano', 1(%)$ro/)(2nap%t%a'enecarbo/)'ate, an$ it %as t%e o''o2in& c%emica'
structure3
Sa'metero' /inaoate is a 2%ite po2$er 2it% a mo'ecu'ar 2ei&%t o *00!<, an$ t%e empirica'
ormu'a is 5
25
6
0.
="
1
>5
11
6
<
"
0
! It is ree') so'ub'e in met%ano'? s'i&%t') so'ub'e in et%ano',
c%'oroorm, an$ isopropano'? an$ sparin&') so'ub'e in 2ater!
ADVAIR DISKUS 100/50 (futicasone propionate) , ADVAIR DISKUS (futicasone propionate)
250/50, an$ ADVAIR DISKUS (futicasone propionate) 500/50 are specia'') $esi&ne$ p'astic
$e#ices containin& a $oub'e(oi' b'ister strip o a po2$er ormu'ation o futicasone
propionate an$ sa'metero' /inaoate inten$e$ or ora' in%a'ation on')! @ac% b'ister on t%e
$oub'e(oi' strip 2it%in t%e $e#ice contains 100, 250, or 500 mc& o microAne futicasone
propionate an$ .2!5 mc& o microAne sa'metero' /inaoate sa't, eBui#a'ent to 50 mc& o
sa'metero' base, in 12!5 m& o ormu'ation containin& 'actose (2%ic% contains mi'C
proteins)! @ac% b'ister contains 1 comp'ete $ose o bot% me$ications! Ater a b'ister
containin& me$ication is opene$ b) acti#atin& t%e $e#ice, t%e me$ication is $isperse$ into
t%e airstream create$ b) t%e patient in%a'in& t%rou&% t%e mout%piece!
Un$er stan$ar$i;e$ in vitro test con$itions, ADVAIR DISKUS $e'i#ers ,0, 200, an$ 1*5 mc&
o futicasone propionate an$ 15 mc& o sa'metero' base per b'ister rom ADVAIR DISKUS
100/50 (futicasone propionate) , 250/50, an$ 500/50, respecti#e'), 2%en teste$ at a fo2
rate o *0 D/min or 2 secon$s! In a$u't patients 2it% obstructi#e 'un& $isease an$ se#ere')
compromise$ 'un& unction (mean 4@V
1
207 to 007 o pre$icte$), mean peaC inspirator)
fo2 (EI4) t%rou&% a DISKUSF in%a'ation $e#ice 2as <2!1 D/min (ran&e3 1*!1 to 115!0
D/min)!
In%a'ation proA'es or a$o'escent (= G 10, a&e$ 12 to 1. )ears) an$ a$u't (= G 1., a&e$ 1<
to 50 )ears) patients 2it% ast%ma in%a'in& ma/ima'') t%rou&% t%e DISKUS $e#ice s%o2
mean EI4 o 122!2 D/min (ran&e3 <1!* to 152!1 D/min)! In%a'ation proA'es or pe$iatric
patients 2it% ast%ma in%a'in& ma/ima'') t%rou&% t%e DISKUS $e#ice s%o2 a mean EI4 o
.5!5 D/min (ran&e3 1,!0 to 101!< D/min) or t%e 1()ear(o'$ patient set (= G 20) an$ 10.!0
D/min (ran&e3 <2!< to 125!* D/min) or t%e <()ear(o'$ patient set (= G 20)!
8%e actua' amount o $ru& $e'i#ere$ to t%e 'un& 2i'' $epen$ on patient actors, suc% as
inspirator) fo2 proA'e!
WARNING
ASTHMA-RELATE EATH
Lon!-actin! "eta
#
-adrener!ic a!onists $LA%A&' suc( as salmeterol' one of t(e
acti)e in!redients in A*AIR IS+,S $futicasone propionate& -' increase t(e
ris. of ast(ma-related deat(/ ata from a lar!e place"o-controlled ,S stud0 t(at
compared t(e safet0 of salmeterol $SERE*ENT- In(alation Aerosol& or place"o
added to usual ast(ma t(erap0 s(o1ed an increase in ast(ma-related deat(s in
patients recei)in! salmeterol $23 deat(s out of 23'245 patients treated for #6
1ee.s on salmeterol )ersus 3 deat(s out of 23'247 patients on place"o&/
8urrentl0 a)aila"le data are inade9uate to determine 1(et(er concurrent use of
in(aled corticosteroids or ot(er lon!-term ast(ma control dru!s miti!ates t(e
increased ris. of ast(ma-related deat( from LA%A/ A)aila"le data from controlled
clinical trials su!!est t(at LA%A increase t(e ris. of ast(ma-related
(ospitali:ation in pediatric and adolescent patients/
T(erefore' 1(en treatin! patients 1it( ast(ma' p(0sicians s(ould onl0 prescri"e
A*AIR IS+,S $futicasone propionate& for patients not ade9uatel0 controlled
on a lon!-term ast(ma control medication' suc( as an in(aled corticosteroid or
1(ose disease se)erit0 clearl0 1arrants initiation of treatment 1it( "ot( an
in(aled corticosteroid and LA%A/ ;nce ast(ma control is ac(ie)ed and
maintained' assess t(e patient at re!ular inter)als and step do1n t(erap0 $e/!/
discontinue A*AIR IS+,S $futicasone propionate& & if possi"le 1it(out loss of
ast(ma control and maintain t(e patient on a lon!-term ast(ma control
medication' suc( as an in(aled corticosteroid/ o not use A*AIR IS+,S
$futicasone propionate& for patients 1(ose ast(ma is ade9uatel0 controlled on
lo1 or medium dose in(aled corticosteroids/
A$#air 64A is appro#e$ or t%e 'on&(term, t2ice($ai') maintenance treatment o ast%ma in
patients 12 )ears o a&e an$ o'$er! Hecause DAHAs ma) increase t%e risC o ast%ma(re'ate$
$eat%, A$#air is or patients not a$eBuate') contro''e$ on ot%er ast%ma(contro''er
me$ications (e!&!, 'o2( to me$ium($ose in%a'e$ corticosteroi$s) or 2%ose $isease se#erit)
c'ear') 2arrants initiation o treatment 2it% t2o maintenance t%erapies! A$#air is not
appro#e$ or patients 2%ose ast%ma can be successu'') mana&e$ 2it% an I5S a'on& 2it%
occasiona' use o s%ort(actin& beta(a&onists! A$#air is not in$icate$ or t%e re'ie o acute
bronc%ospasm!
8%e acti#e component o <L;*ENT 64A 11 mc&
In%a'ation Aeroso', 4D"V@=8 64A 110 mc& In%a'ation Aeroso'
4D"V@=8 64A 220 mc& In%a'ation Aeroso'
is futicasone propionate, a corticosteroid %a#in& t%e c%emica' name S((fuoromet%)')
*+,,($i'uoro(11-,1. $i%)$ro/)(1*+(met%)'(0(o/oan$rosta(1,1($iene(1.-(carbot%ioate, 1.(
propionate an$ t%e o''o2in& c%emica' structure3
4'uticasone propionate is a 2%ite po2$er 2it% a mo'ecu'ar 2ei&%t o 500!*, an$ t%e
empirica' ormu'a is 5
25
6
01
4
0
"
5
S! It is practica'') inso'ub'e in 2ater, ree') so'ub'e in
$imet%)' su'o/i$e an$ $imet%)'ormami$e, an$ s'i&%t') so'ub'e in met%ano' an$ ,57
et%ano'!
4D"V@=8 64A 11 mc& In%a'ation Aeroso', 4D"V@=8 64A 110 mc& In%a'ation Aeroso', an$
4D"V@=8 64A 220 mc& In%a'ation Aeroso' are pressuri;e$ metere$($ose aeroso' units Atte$
2it% a counter! 4D"V@=8 64A is inten$e$ or ora' in%a'ation on')! @ac% unit contains a
microcr)sta''ine suspension o futicasone propionate (microni;e$) in prope''ant 64A 101a
(1,1,1,2(tetrafuoroet%ane)! It contains no ot%er e/cipients!
Ater primin&, eac% actuation o t%e in%a'er $e'i#ers 50, 125, or 250 mc& o futicasone
propionate in *0 m& o suspension (or t%e 11(mc& pro$uct) or in .5 m& o suspension (or
t%e 110( an$ 220(mc& pro$ucts) rom t%e #a'#e! @ac% actuation $e'i#ers 11, 110, or 220
mc& o futicasone propionate rom t%e actuator! 8%e actua' amount o $ru& $e'i#ere$ to
t%e 'un& ma) $epen$ on patient actors, suc% as t%e coor$ination bet2een t%e actuation o
t%e $e#ice an$ inspiration t%rou&% t%e $e'i#er) s)stem!
@ac% 10!*(& canister (11 mc&) an$ eac% 12(& canister (110 an$ 220 mc&) pro#i$es 120
in%a'ations!
4D"V@=8 64A s%ou'$ be prime$ beore usin& or t%e Arst time b) re'easin& 1 test spra)s
into t%e air a2a) rom t%e ace, s%aCin& 2e'' or 5 secon$s beore eac% spra)! In cases
2%ere t%e in%a'er %as not been use$ or more t%an . $a)s or 2%en it %as been $roppe$,
prime t%e in%a'er a&ain b) s%aCin& 2e'' or 5 secon$s an$ re'easin& 1 test spra) into t%e air
a2a) rom t%e ace!
8%is pro$uct $oes not contain an) c%'orofuorocarbon (545) as t%e prope''ant!
8orticosteroids are a c'ass o steroi$ %ormones t%at are pro$uce$ in t%e a$rena' corte/!
5orticosteroi$s are in#o'#e$ in a 2i$e ran&e o p%)sio'o&ic s)stems suc% as stress
response, immune response an$ re&u'ation o infammation, carbo%)$rate metabo'ism,
protein catabo'ism, b'oo$ e'ectro')te 'e#e's, an$ be%a#ior!
Glucocorticoids suc% as cortiso' contro' carbo%)$rate, at an$ protein metabo'ism
an$ are anti(infammator) b) pre#entin& p%osp%o'ipi$ re'ease, $ecreasin& eosinop%i'
action an$ a number o ot%er mec%anisms!
Mineralocorticoids suc% as a'$osterone contro' e'ectro')te an$ 2ater 'e#e's, main')
b) promotin& so$ium retention in t%e Ci$ne)!
S)nt%etic p%armaceutica' $ru&s 2it% corticosteroi$('iCe eIect are use$ in a #ariet) o
con$itions, ran&in& rom brain tumors to sCin $iseases! De/amet%asone an$ its $eri#ati#es
are a'most pure &'ucocorticoi$s, 2%i'e pre$nisone an$ its $eri#ati#es %a#e some
minera'ocorticoi$ action in a$$ition to t%e &'ucocorticoi$ eIect! 4'u$rocortisone (4'orine) is
a s)nt%etic minera'ocorticoi$! 6)$rocortisone (cortiso') is a#ai'ab'e or rep'acement
t%erap), e.g. in a$rena' insuJcienc) an$ con&enita' a$rena' %)perp'asia!
DeAnition o CORTICOSTEROID an0 of )arious adrenal-cortex steroids $as
corticosterone' cortisone' and aldosterone& used medicall0 especiall0 as
anti-infammator0 a!ents = compare !lucocorticoid' mineralocorticoid
8orticosteroids %a#e been use$ as $ru& treatment or some time! De2is Sarett o KercC L
5o! 2as t%e Arst to s)nt%esi;e cortisone, usin& a comp'icate$ 0*(step process t%at starte$
2it% $eo/)c%o'ic aci$, 2%ic% 2as e/tracte$ rom o/ bi'e!
912:
8%e 'o2 eJcienc) o con#ertin&
$eo/)c%o'ic aci$ into cortisone 'e$ to a cost o US M200 per &ram! Russe'' KarCer, at
S)nte/, $isco#ere$ a muc% c%eaper an$ more con#enient startin& materia', $ios&enin rom
2i'$ Ke/ican )ams! 6is con#ersion o $ios&enin into pro&esterone b) a our(step process
no2 Cno2n as KarCer $e&ra$ation 2as an important step in mass pro$uction o a'' steroi$a'
%ormones, inc'u$in& cortisone an$ c%emica's use$ in %ormona' contraception!
910:
In 1,52,
D!6! Eeterson an$ 6!5! Kurra) o UpNo%n $e#e'ope$ a process t%at use$ R%i;opus mo'$ to
o/i$i;e pro&esterone into a compoun$ t%at 2as rea$i') con#erte$ to cortisone!
911:
8%e
abi'it) to c%eap') s)nt%esi;e 'ar&e Buantities o cortisone rom t%e $ios&enin in )ams
resu'te$ in a rapi$ $rop in price to US M* per &ram, a''in& to M0!1* per &ram b) 1,<0! Eerc)
Ou'ianPs researc% a'so ai$e$ pro&ress in t%e Ae'$!
915:
8%e e/act nature o cortisonePs anti-
infammator0 action remaine$ a m)ster) or )ears ater, %o2e#er, unti' t%e 'euCoc)te
a$%esion casca$e an$ t%e ro'e o p%osp%o'ipase A2 in t%e pro$uction o prosta&'an$ins an$
'euCotrienes 2as u'') un$erstoo$ in t%e ear') 1,<0s!
Salmeterol is a 'on&(actin& beta2(a$rener&ic receptor a&onist $ru& t%at is current')
prescribe$ or t%e treatment o ast%ma an$ c%ronic obstructi#e pu'monar) $isease(5"ED)!
It is current') a#ai'ab'e as a $r) po2$er in%a'er t%at re'eases a po2$ere$ orm o t%e $ru&!
Heore 200<, it 2as a'so a#ai'ab'e as a metere$($ose in%a'er (KDI)
It is a 'on&(actin& beta(a$renoceptor a&onist (DAHA), usua'') prescribe$ on') or se#ere
persistent ast%ma o''o2in& pre#ious treatment 2it% a s%ort(actin& beta a&onist suc% as
sa'butamo' an$ is prescribe$ concurrent') 2it% a corticosteroi$, suc% as bec'omet%asone!
8%e primar) noticeab'e $iIerence o sa'metero' to sa'butamo' is t%at t%e $uration o action
'asts appro/imate') 12 %ours in comparison 2it% 1Q* %ours o sa'butamo'!
In%a'e$ sa'metero' 2orCs 'iCe ot%er beta 2(a&onists, causin! "ronc(odilation "0
relaxin! t(e smoot( muscle in t(e air1a0 so as to treat t(e exacer"ation of
ast(ma! 8%e 'on& $uration o action occurs b) t%e mo'ecu'es initia'') $iIusin& into t%e
p'asma membrane o t%e 'un& ce''s, an$ t%en s'o2') bein& re'ease$ bacC outsi$e t%e ce''
2%ere t%e) can come into contact 2it% t%e beta(2 a$renoceptors, 2it% t%e 'on& carbon
c%ain ormin& an anc%or in t%e membrane! Interestin&'), sa'metero' bin$in& to t%e beta(
a$renoceptor $oes not in$uce $esensitisation or interna'isation o receptors 2%ic% ma) a'so
contribute to its 'on& t%erapeutic $uration o action! 4ormotero' %as been $emonstrate$ to
%a#e a aster onset o action t%an sa'metero' as a resu't o a 'o2er 'ipop%i'icit), an$ %as
a'so been $emonstrate$ to be more potent!