MONTE+LEVO

Montelukast 10 mg + Levocetirizine 5 mg for SEASONAL ALLERG ! R" N # S

Todays Discussion
Overvie$ of Allergic R%initis &%armacot%era'( of Allergic R%initis Nee) for t%e com*ination of MON#E+LE+O !linical Efficac( of MON#E+LE+O &lace in t%era'(

DEFINITION OF AR
Allergic r%initis is clinicall( )efine) as a s(m'tomatic )isor)er of t%e nose in)uce) *( an gE,me)iate) inflammation after allergen e-'osure.

PROBLEM STATEMENT
Allergic r%initis is one of t%e most common allergic )iseases Affects 15,/0 0 of t%e $orl)1s 'o'ulation n t%e last five )eca)es2 t%e 'revalence of allergic r%initis %as tri'le) from 30 to 140 $orl)$i)e AR is t%e commonest allerg( encountere) in clinical 'ractice in n)ia #%e 'revalence rate is estimate) to *e 50,/00 in n)ia

Priniples & practise of Tropical Allergy & Asthma 2006 Wiqar Shaikh

CAUSES OF AR

CLINICAL FEATURES
Nasal o*struction Nasal )isc%arge &ost,nasal )ri' Sneezing E'ista-is 6ater( e(es Re) e(es tc%ing aroun) e(es
"ea)ac%e or facial 'ain S$elling or )eformit( 7istur*ances of smell Snoring !%ange in voice 8%('er or %('onasalit(9

NASAL ANATOMY
&icture of nose $it%

THE ALLER IC REACTION

ALLER IC REACTION( EARLY PHASE

Allergen

gE anti*o)(

C$#"o!ac!ic Fac!o%s

His!a"in#
Sneezing tc%ing R%inorr%oea

EARLY ALLER IC RESPONSE &EAR'

ROLE OF HISTAMINE IN AR
&la(s a ke( role in t%e 'at%ogenesis or AR Secrete) *( mast cells an) *aso'%ils nfluences t%e activation of several ot%er me)iators of inflammation 8inclu)ing neutro'%ils2 eosino'%ils2 macro'%ages9

Levels increase) in nasal secretions of 'atients of AR !ontri*utes to nasal o*struction 2 sneezing an) r%inorr%oea in AR #%us e-erts a )irect as $ell as in)irect effect
Ref: clinical therapeutics 200 !2":#"#$##2

ALLER IC REACTION( LATE PHASE

C$#"o!ac!ic *ac!o%s

L#u)o!%i#n#s

Nasal congestion nflammation

LATE &LAR' ALLER IC RESPONSE

INFLAMMATORY CASCADE
P$os+$o,i+ids P$os+$o,i+as# AA%ac$idonic acid Cyc,oo.y/#nas# P%os!a/,andins 12Li+oo.y/#nas# LTA4 LTB4 C$#"o!a.is o* n#u!%o+$i,s LTC40 LTD40 LTE4

Cysteinyl Leukotrienes

Mast cells2 :aso'%ils2 Eosino'%ils

Cysteinyl leukotrienes

Effects t%e nasal vasculature +ascular 'ermea*ilit( +aso)ilation Mucosal s$elling Con/#s!ion3s!u**in#ss
Ann Pharmacother 2001;35:1274-7

ROLE OF LEU4OTRIENES IN AR
7ilatation of nasal *loo) vessels2 increase vascular 'ermea*ilit( $it% e)ema formation congestion ncrease mucus 'ro)uction Recruitment of inflammator( cells into t%e tissue &romote inflammation *( en%ancing t%e activit( of inflammator( cells 5000 times more 'otent t%an %istamine

HO5 ARE THE SYMPTOMS CAUSED6

rritation of free nerve en)ings,,,,,,,,,,,,,I!c$in/ and sn##7in/
%histamine&

ncrease) mucus 'ro)uction,,,,,,,,R$ino%%$o#a 8histamine & leukotriene& +aso)ilation ,,,,,,,,,,,,,,,Con/#s!ion

%leukotrienes&

ncrease) vascular 'ermea*ilit(,,,O#d#"a

%leukotrienes&

CLASSIFICATION OF AR
S#asona, A,,#%/ic R$ini!is &SAR' S(m'toms increase )uring certain times of t%e (ear an) cause) *( out)oor allergens 8e.g; trees2 grasses < $ee)s9 P#%#nnia, A,,#%/ic R$ini!is &PAR' S(m'tom t%at occur (ear,roun)2 causes= )ust, mites an) animal )an)er 8'ets9

ARIA CLASSIFICATION
In!#%"i!!#n! > ? )a(s 'er $eek or > ? $eeks P#%sis!#n! @ ? )a(s 'er $eek an) @ ? $eeks

Mi,d Normal slee' an) No im'airment of )ail( activities2 s'ort2 leisure an) Normal $ork an) sc%ool an) No trou*lesome s(m'toms

Mod#%a!#2S#8#%# One or more terms; A*normal slee' m'airment of )ail( activities2 s'ort2 leisure A*normal $ork an) sc%ool #rou*lesome s(m'toms

ARIA report 2001

UNTREATED AR CAN LEAD TO9

Ast%ma Sinusitis Otitis Me)ia Nasal 'ol('s AR#

APPROACH TO TREATMENT OF AR
Avoi)ance of allergens
Environmental control

&%armacot%era'( mmunot%era'(

TREATMENT OPTIONS FOR AR

An!i$is!a"in#s B #%e( *lock t%e action of %istamine an)
control sneezing2 itc%ing an) r%inorr%oea

D#con/#s!an!s B #%e( cause vasoconstriction an) o'en

t%e *locke) nose

Mas! c#,, s!a:i,i7#%s ; #%e( 'revent t%e mast cells

from ru'turing2 %ence 'revent t%e me)iators from coming out

 Antic%olinergic agents B #%e( )ecrease t%e

nasal secretions %ence give relief from r%inorr%oea

ntranasal steroi)s B #%e( %ave anti

inflammator( activit(

Antileukotrienes B #%e( in%i*it t%e effects of

leukotrienes $%ic% are t%e un)erl(ing cause of inflammation in AR

FALACIES IN CURRENT TREATMENT

Anti%istamines control all s(m'toms e-ce't congestion Ol)er generation 8A"9 )rugs cause se)ation ntranasal steroi)s are currentl( 1st line Not Cuick acting Not effective on ocular s(m'toms

5HAT SHOULD BE THE IDEAL TREATMENT6

A d%u/ <$ic$ <ou,d o8#%co"# !$# cu%%#n! *a,,aci#s in !$# !%#a!"#n!

HO5 CAN 5E ACHIEVE THAT6

COMBININ AN ANTIHISTAMINE 5ITH AN ANTILEU4OTRIENE THAT 5ILL TA4E CARE OF BOTH0 THE EARLY AS 5ELL AS THE LATE SYMPTOMS OF AR

ASSAULT ON THE MEDIATORS OF AR

Allergen

gE anti*o)(

C$#"o!ac!ic Fac!o%s

L#u)o!%#in#s
His!a"in#

Sneezing tc%ing R%inorr%oea

L#8oc#!i%i7in#

Mon!#,u)as!
Nasal congestion Inflammation
LATE ALLER IC RESPONSE &LAR'

EARLY ALLER IC RESPONSE &EAR'

PHARMACOTHERAPY FOR AR
Nasa, P%#+a%a!ion An!i$is!a"in#s Sn##7in/ I!c$in/ R$ino%%$o#a Con/#s!ion Ey# sy"+!o" s ++ 0 ++ 0 ++

+++++

++++ 0 +++++ 0 ++

+++ +++++ +++ + ++

0 0 +++ +++++ +++++

An!ic$o,in#%/ics 0 Co%!icos!#%oids D#con/#s!an!s +++++ 0

An!i,#u)o!%i#n#s ++

ARIA report 2001

't is thus reasona(le to consi)er that com(ine) me)iator (locka)e may re)uce the symptoms of allergic rhinitis
ARIA report 2001

ROLE OF MONTELU4AST IN AR
t *elongs to t%at class of )rug $%ic% s'ecificall( *locks leukotrienes2 an un)erl(ing cause of allerg( s(m'toms

:locks L#!? $%ic% is a''ro-imatel( 10 times as 'otent as %istamine :locks L#7? $%ic% $as s%o$n to *e 5000 times as 'otent as %istamine Offers relief from congestion an) stuffiness Gives )a(,time as $ell as nig%t,time s(m'tom relief

ROLE OF LEVOCETRI=INE IN AR
Levocetrizine acts *( *in)ing to t%e "1 rece'tors t%ere*( antagonising t%e effects of %istamine in AR Levocetirizine significantl( attenuate) t%e %istamine in)uce) increases in t%e nasal air$a( resistance $it% almost 500 re)uction over 'lace*o Levocetirizine also significantl( 8&>0.019 re)uce) %istamine in)uce) sneezes Levocetirizine in%i*its eota-in,in)uce) eosino'%il migration t%roug% *ot% )ermal an) lung microvascular en)ot%elial cells suggesting 'otential anti, inflammator( effects

Allergy 200*+ 6: ,##$,-, .lin /0p Allergy 2002+ ,2: **1"$**#2

MONTE+LEVO( COMPREHESIVE TREATMENT OF AR

An!i$is!a"in# LEVOCETRI=INE An!i,#u)o!%#in# MONTELU4AST

Sn##7in/ I!c$in/ R$ino%%$o#a

Nasa, con/#s!ion In*,a""a!ion

Ea%,y +$as# %#ac!ions &Visi:,# sy"+!o"s'

La!# +$as# %#ac!ions &Hidd#n in*,a""a!ion'

CLINICAL EFFICACY o* UNIAIR L

COMBINATION OF MONTELU4AST AND LORATIDINE BETTER THAN MONOTHERAPY

7a(time Nasal Mean !%ange of Score Irom :aseline 0 ,0.1 ,0.5 ,0./ ,0.? ,0.5
:aseline G5.1

Nig%ttime S(m
8:aseline G 1.59

!om'osite S(m

7a(time E(e

87a(Hnig%t nasal9< 8:aseline G1.?9

Co":ina!ion $as :##n s$o<n !o :# si/ni*ican!,y su+#%io% !o &lace*o "ono!$#%a+y in %#,i#* o* a,, !$# sy"+!o"s o* SAR Montelukast 10 mg
+ + + + Lorata)ine 10 mg

* *

Montelukast + Lorata)ine
N"#$0 % wee!s

,0.3 DE ,0.F

* P < 0.05 compared with placebo; + P <0.001 compared with placebo; # p < 0.001 compared with montel !ast or loratadine alone

J Allergy Clin Imm nol 2000;105!5":#17-22

IMPROVEMENT IN SYMPTOM SCORE 5ITH COMBINATION AS PROPHYLA>IS

IMPROVEMENT IN SYMPTOM SCORE 5ITH COMBINATION AS PROPHYLA>IS

5.5 5 1.5 1 0.5 0
&lace*o Montelukast 10 mg !etirizine 10 mg Montelukast 10

S(m'tom score

DDE J

DDD

E DD

E DDD

mgHcetirizine 10 mg

! on ge st io n R %i no rr% ea Sn ee zi ng N os e itc %i ng E( e itc %i ng

P%#!%#a!"#n! <i!$ co":ina!ion #**#c!i8# in +%#8#n!in/ SAR and su+#%io% !o "ono!$#%a+y?

*P<0.05 &s p

P<0.01 &s p P%#!%#a!"#n! a,so d#,ays a++#a%anc# o* ** sy"+!o"s? ***P<0.001 &s p + P<0.05 &s 'on # P<0.05 &s (et

Allergy 200-+ #:210$1

N"$0 )"1% wee!s

COMBINATION OF MONTELU4AST AND CETIRI=INE AS EFFECTIVE AS INCS

N"%%

#otal nasal s(m'toms score

? /.5 / 5.5 5 1.5 0.5 0 &lace*o Mometasone furoate

*

)"% wee!s &>0.05

Bo!$ !$#%a+i#s <#%# #@ua,,y #**#c!i8# *o% AR 1

Montelukast + cetirizine

.lin & /0p Allergy200*!,*+6*$61

LUN

FUNCTION IMPROVEMENT IN PATIENTS 5ITH P<0.05 CONCOMITANT ASTHMA

?45 * ?F4 * ?40 N"1# )"% wee!s &lace*o :A7 ?35 ?35 MON+!K

&eak e-'irator( flo$ 8lHmin9

?40 ?F5 ?F0

Co":ina!ion $as :##n s$o<n !o :# as #**#c!i8# as :ud#sonid# in !$# %#,i#* o* sy"+!o"s o* AR <i!$ as!$"a ?30
?55 &lace*o :A7 MON+!K

Am J Re$pir Crit Care %e& 2000;1'2:12#7-1301

DOSA E AND ADMINISTRATION

Montelukast 10 mg + Levocetirizine 5 mg

One ta*let of MONTE+LEVO0 once )ail( in a)ults

ADVERSE EVENTS REPORTED

Mon!#,u)as! P,ac#:o

"ea)ac%e A*)ominal 'ain 7(s'e'cia !oug% 7izziness

14.?0 5.L0 5.10 5.F0 1.L0

14.10 5.50 1.10 5.?0 1.?0

P2R 200"

ADVERSE EVENTS con!d9

L#8oc#!i%i7in# P,ac#:o

Se)ation Naso'%ar(n gitis Iatigue 7r( mout%

30 ?0 ?0 50

50 /0 50 10

Prescri(ing 'nformation+ 3y4al

COMMON SIDE2EFFECTS E>PECTED

7r( Mout% Nausea Se)ation

PLACE IN THERAPY
In "od#%a!#2!o2s#8#%# sy"+!o"s o* in!#%"i!!#n! %$ini!is As "ono!$#%a+y in "i,d +#%sis!#n! AR As "ono!$#%a+y in "i,d in!#%"i!!#n! AR P%o+$y,ac!ic !$#%a+y in SAR In as!$"a co2#.is!in/ <i!$ AR

HI HLI HTS OF MONTE+LEVO

n%i*its *ot% earl( an) late '%ase reactions Ra'i) onset of action Acts for longer )uration,gives com'lete control Once )ail( com're%ensive treatment Safe an) $ell tolerate)
Allergy an) Asthma Proc 200 + 26%*&: --$-6 'nt 5 .lin Pract 200-+ 1%2&: *0#$**1 5 Allergy .lin 'mmunol 2000+ *0 : #*" 6 22 .lin /0p Allergy 2000+ ,*: 6*$61

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