8/11/2019 Bromhexina Info Total
1/231
DRUGDEX DRUG EVALUATIONS
BROMHEXINE
0.0 OVERVIEW
A. BROMHEXINE is an expectorant/mucolytic agent.
B. DOSIN IN!ORMA"ION# $sual %oses o& BROMHEXINE
in c'ronic (ronc'itis 'a)e (een * to +, milligrams -mg
orally t'ree times %aily or 0 mg t1ice %aily2 'ig'er %oses
-30 mg %aily 'a)e (een use% 1it' anti(iotics in
(ronc'iectasis2 in patients 1it' S4ogren5s syn%rome6 %oses
o& +, mg orally t'ree times %aily 'a)e (een a%ministere%.
7. 8HARMA7O9INE"I7S# !ollo1ing oral a%ministration o&
BROMHEXINE6 pea: serum concentrations occur in
approximately + 'our2 t'e %rug is meta(oli;e% in t'e li)er
an% excrete% in t'e urine primarily as meta(olites2 t'e
elimination 'al&
8/11/2019 Bromhexina Info Total
2/231
(ronc'iectasis6 S4ogren5s syn%rome6 an% in com(ination use
1it' anti(iotics.
1.0 DOSING INFORMATION
1.1 DOSAGE FORMS
A. In&ormation on speci@c pro%ucts an% %osage &orms
can (e o(taine% (y re&erring to t'e 8ro%uct In%ex.
B. SNONMS
1. NA-274
2. NA-872
3. Bisolvon(R)
7. OR8HAN DR$ S"A"$S
+. BROMHEXINE 'as (een %esignate% an
orp'an pro%uct &or use in t'e treatment o& mil%ecti)e in t'e treatment o& O"I"IS
MEDIA 1it' e>usion in c'il%ren - to +0
years o& age -Ste1art et al6 +3*=2 Elcoc:
F ?or%6 +3.
2.0 PHARMACOKINETICS
2.2 DRUG CONCENTRATION LEVELS
2.2.1 THERAPEUTIC
A. "IME "O 8EA9 7ON7EN"RA"ION#
+. Oral6 un:no1n# + 'our -Bec'gaar% F
Nielsen6 +3*2 auc' F Han:1it;6 +3=.
a. 8ea: serum concentrations o&
BROMHEXINE occur approximately +
'our &ollo1ing oral a%ministration
-Bec'gaar% F Nielsen6 +3*2 auc' F
Han:1it;6 +3=.
(. !ollo1ing a G mg oral %ose o&
BROMHEXINE6 plasma le)els %ecline%
to approximately 0.+G an% 0.=
mcg/m? at * an% G 'ours postects 'a)e necessitate%
1it'%ra1al o& t'erapy in some patients
-?anglan%s6 +302 Ayl1ar%6 +32
"'ompson F Ree)e6 +32 Armstrong6
+3,2 alenti F Marenco6 +3*3.
3.3.! KIDNEY"GENITOURINARY
A. ENURESIS
+. Enuresis -1it' or 1it'out %iarr'ea
necessitate% %iscontinuation o&
BROMHEXINE t'erapy in o& c'il%ren
1it' otitis me%ia in + stu%y -Ste1art et al6
+3*=. Ho1e)er6 it is unclear i& t'is e>ect
1as %e@nitely attri(uta(le to BROMHEXINE.
3.3.# LIVER
A. HEPATOTOXICITY
+. "ransient ele)ations in serum aspartate
aminotrans&erase -SO" le)els 'a)e (een
8/11/2019 Bromhexina Info Total
10/231
%escri(e% in&reJuently %uring BROMHEXINE
t'erapy -Hamilton et al6 +302 Anon6 +3+2
Se'gal F Mo'an6 +330. Some
in)estigators suggest t'at SO" rises are
attri(uta(le to an e>ect o& BROMHEXINE
on (ronc'ial glan%s as oppose% to 'epatic
%ys&unction -Anon6 +3+.
3.3.$ OCULAR
A. OCULAR EFFECTS
+. Brom'exine - mg/%ay &or + %ays
'a% NO E!!E7" on rate o& tear secretion
in =, 'ealt'y )olunteers 1it' normal tear
secretion. alues on Sc'irmer5s test I 1ere
t'e same -+. mm/= min (e&ore an% a&ter
(rom'exine use -A)isar et al6 +33,.
3.3.10 SKIN
A. RASH
+. Rarely6 S9IN RASH 'as (een reporte%
in BROMHEXINE
8/11/2019 Bromhexina Info Total
11/231
. Australian Drug E)aluation 7ommittee -ADE7
7ategory A -ADE76 +33,.
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. 8HSI7A? EXAMINA"ION
+. In patients 1it' c'ronic (ronc'itis6
%ecrease% %iLculty o& expectoration6
increase% sputum )olume6 a re%uction in
coug' an% %yspnea6 an% impro)ement in
pulmonary &unction tests are in%icati)e o& a
t'erapeutic response to BROMHEXINE.
4.1.2 TOXIC
A. ?ABORA"OR 8ARAME"ERS
+. Hepatic &unction tests -especially %uring
long
8/11/2019 Bromhexina Info Total
12/231
or Necti)e
in se)ere %isease. "'e use o& t'is agent mig't t'us
(e consi%ere% in com(ination t'erapy an% in less
se)erely a>ecte% patients to en'ance expectoration
an% possi(ly )entilatory capacity. Ho1e)er6 it 1ill not
replace more con)entional mo%es o& t'erapy. "'e
a%%ition o& BROMHEXINE to t'e 'ospital &ormulary &or
t'is in%ication mig't (e 4usti@e% i& excessi)e cost is
not a &actor. !urt'er stu%ies in)estigating t'e use o&
'ig'er %oses o& BROMHEXINE -eg6 to 30 mg
%aily in (ot' mo%erate an% se)ere (ronc'itis appear
1arrante%. A%%itional comparati)e stu%ies 1it' ot'er
mucolytic agents -eg6 Secti)e in otitis me%ia 1it' e>usion.
4.4 MECHANISM OF ACTION"PHARMACOLOGY
A. MECHANISM OF ACTION
8/11/2019 Bromhexina Info Total
13/231
+. BROMHEXINE is an expectorant/mucolytic
agent 1'ic' 'as (een in)estigate% in t'e
treatment o& respiratory %isor%ers6 S4ogren5s
syn%rome6 an% otitis me%ia -Se'gal F Mo'an6
+3302 Mant'orpe F 8rause6 +3*,2 Anon6 +3+.
"'e %rug is a (en;ylamine %eri)ati)e -
8/11/2019 Bromhexina Info Total
14/231
(ronc'itis patients appear secon%ary to easier
expectoration -alenti F Marenco6 +3*3.
. Ot'er p'armacological e>ects o&
BROMHEXINE 'a)e (een reporte%6 inclu%ing
en'ancement o& secretion &rom exocrine glan%s
-eg6 tear pro%uction -Se'gal F Mo'an6 +3302
!rost
8/11/2019 Bromhexina Info Total
15/231
+. A (rie& re)ie1 o& t'e mec'anism o& action6
eLcacy6 an% toxicity o& BROMHEXINE is
a)aila(le -Be'gal F Mo'an6 +330.
. An in&ormati)e e%itorial regar%ing t'e use o&
BROMHEXINE in c'ronic (ronc'itis is a)aila(le
-Anon6 +3+.
4.5 THERAPEUTIC USES
A. ASTHMA
+. OERIE#FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult in#++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#
- '++i&$&/ is &ont%ov#%si$l
. AD$?"#
a. Oral or intra)enous BROMHEXINE 'as
not (een associate% 1it' clinical or
)entilatory impro)ement in patients 1it'
mo%erate
8/11/2019 Bromhexina Info Total
16/231
. S$MMAR#
- Aus&ult$to%/ +indins $nd +o%d
#"i%$to%/
volu# in 1 s#&ond (F'V-1) ("ositiv#
&$n#
o+ $""%oi$t#l/ 155 illilit#%s) &$n#sdo not
$""#$% &lini&$ll/ %#l#v$nt
. AD$?"#
a. "'e com(ination o& oral BROMHEXINE
0 milligrams t'ree times %aily &or += %ays
in com(ination 1it' intramuscular
7E!"ACIDIME -+ gram t1ice %aily &or t'e
@rst %ays 1as reporte% more e>ecti)e
t'an t'e intramuscular 7E!"ACIDIME
regimen alone in t'e treatment o& acute
exacer(ations o& (ronc'iectasis in a
%ou(le
8/11/2019 Bromhexina Info Total
17/231
not %i>er (et1een groups. !urt'er stu%ies
are nee%e% to con@rm t'e potential (ene@ts
o& 'ig'ecti)e in increasing )entilatory
capacity6 re%ucing %iLculty in
expectoration6 an% pro%ucing clinical
impro)ement as compare% to place(o
in patients 1it' c'ronic (ronc'itis an%
8/11/2019 Bromhexina Info Total
18/231
some patients 1it' (ronc'itis an%
ast'ma -ent et al6 +3,32 alenti F
Marenco6 +3*3. Ho1e)er6 ot'er
similarly %esigne% stu%ies &aile% to
%emonstrate signi@cant or consistent
(ene@ts 1it' oral BROMHEXINE G
to G* milligrams %aily in c'ronic
(ronc'itis patients -Armstrong6 +3,2
Anon6 +32 "'ompson F Ree)e6
+32 7lar:e et al6 +32 ?anglan%s6
+302 Hamilton et al6 +30. In some
o& t'ese latter stu%ies6 lac: o& (ene@t
1as o(ser)e% %espite signi@cant
increases in sputum )olume an%
%ecreases in sputum )iscosity
-Hamilton et al6 +30. 7linical
response to t'e %rug is usually seen
only in patients 1it' slig't
8/11/2019 Bromhexina Info Total
19/231
- Discrepancies in t'ese trials are
most li:ely explaine% (y patient
selection. Most stu%ies reporting no
signi@cant (ene@t o& BROMHEXINE
enrolle% patients 1it' more se)ere
c'ronic (ronc'itis6 as e)i%ence% (y
lo1 (aseline &orce% expiratory )olume
-!E
8/11/2019 Bromhexina Info Total
20/231
some (ut not all patients 1it' slig'tect o&
mucoi% secretions6 an% possi(ly
&acilitate a more rapi% response
-Matts6 +3G2 Boner et al6 +3*G2
Dattoli F ?ec'i6 +3*. Some stu%ies
'a)e also reporte% t'at
BROMHEXINE can increase sputum
8/11/2019 Bromhexina Info Total
23/231
concentrations o& )arious anti(iotics
-Bergogne
8/11/2019 Bromhexina Info Total
24/231
BROMHEXINE an% 7E8HA?EXIN 1as
reporte% superior to 7E8HA?EXIN
alone in treating acute exacer(ations
o& c'ronic (ronc'opulmonary %iseases
in + comparati)e trial2 )entilatory
&unction an% clinical symptoms 1ere
impro)e% to a greater %egree in t'e
com(ination group -8almieri et al6
+3*.
-G A &urt'er stu%y reporte%
statistically similar response rates 1it'
t'e com(ination o&
OX"E"RA77?INE =0 milligrams
&our times %aily plus BROMHEXINE *
milligrams &our times %aily -, an%
OX"E"RA77?INE alone -=+ in
patients 1it' exacer(ations o& c'ronic
(ronc'itis or acute (ronc'itis2 'ospital
stay 1as s'ortene% in t'e
BROMHEXINE group -3 )ersus ++
%ays -Matts6 +3G. Ho1e)er6
met'o%s o& treatment allocation an%
(aseline clinical c'aracteristics o&
eac' treatment group 1ere not
pro)i%e%2 it 1as unclear i& t'e se)erity
o& %isease in eac' group 1as
8/11/2019 Bromhexina Info Total
25/231
compara(le6 1'ic' coul% 'a)e
a>ecte% 'ospital stay. Ot'ers reporte%
poor response to (ot' t'e
com(ination o& ER"HROM7IN an%
BROMHEXINE an% ER"HROM7IN
alone in c'ronic (ronc'itis patients2
BROMHEXINE %i% not &acilitate
sputum penetration o&
ER"HROM7IN in t'is stu%y
-Maesen et al6 +3*. 7linical
response in relation to pulmonary
&unction 1as not a%%resse% in any o&
t'ese stu%ies.
D. OTITIS MEDIA
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult in#++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#
- n#++#&tiv#
. AD$?"#
a. In t1o controlle% stu%ies6 oral
BROMHEXINE in %oses o& +, to G*
milligrams %aily &or G to , 1ee:s 1as
ine>ecti)e in t'e treatment o& otitis me%ia
1it' e>usion -secretory otitis me%ia in
c'il%ren - to +0 years o& age -Ste1art et
al6 +3*=2 Elcoc: F ?or%6 +3.
E. POSTOPERATIVE RESPIRATORY INFECTIONS
8/11/2019 Bromhexina Info Total
26/231
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult #++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#- $/ #n$n $nti0ioti& $&tivit/ 0/ its
u&ol/ti& "%o"#%ti#s #n$0lin i#%
0%on&i$l &onnt%$tions to 0# $&i#v#d
- $/ "%#v#nt u&us "luin $nd %#sult$nt
"$%#n&/$l &o"li&$tions
. AD$?"#
a. 7om(ination t'erapy 1it' 7E8HA?EXIN
an% BROMHEXINE 'as (een reporte%
e>ecti)e in treating an% pre)enting
respiratory in&ections &ollo1ing surgery
-primarily a(%ominal in uncontrolle% stu%ies
in)ol)ing patients 1it' acute or c'ronic
(ronc'itis or ot'ers at ris: o& respiratory
complications -Busca et al6 +3*2 8almieri
et al6 +3*. BROMHEXINE may en'ance
anti(iotic acti)ity in t'ese patients (y its
mucolytic properties6 ena(ling 'ig'er
(ronc'ial concentrations to (e ac'ie)e%6
an% pre)ent mucus plugging an% resultant
parenc'ymal complications. Ho1e)er6 in t'e
a(sence o& a control group recei)ing
anti(iotic t'erapy alone6 it is %iLcult to
assess t'e eLcacy o& com(ination t'erapy.
(. One stu%y 'as reporte% t'e eLcacy o&
intramuscular &ollo1e% (y oralBROMHEXINE in re%ucing t'e inci%ence o&
8/11/2019 Bromhexina Info Total
27/231
postoperati)e (ronc'opneumonia in 'ig'ects 1ere o(ser)e%6
it is unclear i& t'e com(ination o>ers a
signi@cant a%)antage o)er 7E8HA?EXIN
alone6 an% controlle% stu%ies are nee%e%.
G. S%OGREN&S SYNDROME
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult #++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#
- 'n$nd l$&%i$l s#&%#tion $s 0##n
o0s#%v#d in "$ti#nts 6it 9o%#ns s/nd%o# in so#
&ont%oll#d studi#s 0ut not ot#%s
. AD$?"#
a. An impro)ement in op't'almological
tests in%icati)e o& en'ance% lacrimal
secretion 'as (een o(ser)e% in patients
1it' S4ogren5s syn%rome %uring oral
BROMHEXINE t'erapy in some controlle%
stu%ies (ut not ot'ers2 su(4ecti)e
8/11/2019 Bromhexina Info Total
29/231
impro)ement 1as not reporte% (y t'e
patient in any o& t'ese stu%ies6 nor 1as
t'e rate o& tear secretion in 'ealt'y
su(4ects a>ecte% (y (rom'exine -A)isar et
al6 +33,. AMBROXO?6 a meta(olite o&
BROMHEXINE6 'as not (een e>ecti)e in
pro%ucing o(4ecti)e impro)ement2 a%%itional
stu%ies are nee%e% to clari&y t'e role o&
BROMHEXINE in S4ogren5s syn%rome.
"1o place(o
8/11/2019 Bromhexina Info Total
30/231
impro)ement in t'is parameter 1it' place(o.
BROMHEXINE 1as not associate% 1it'
su(4ecti)e impro)ement.
c. Early stu%ies employe% relati)ely small
num(ers o& patients6 an% o& t'e stu%ies
-"apper
8/11/2019 Bromhexina Info Total
31/231
1. RESPIRATORY TRACT INFECTIONS
a. 7om(ination BROMHEXINE plus
AMOXI7I??IN is more e>ecti)e t'an
AMOXI7I??IN alone in t'e treatment o&
(ronc'itis or pneumonia.
(. A%%ing BROMHEXINE to AMOXI7I??IN
pro%uces a 'ig'er cure rate an% &aster
resolution o& symptoms t'an AMOXI7I??IN
alone in patients 1it' acute (ronc'itis
-n3+ or pneumonia -n+0+ -1it' clinical
assessment &or (acterial etiology6
accor%ing to a multi
8/11/2019 Bromhexina Info Total
32/231
an% sputum )olume 1ere signi@cantly (etter
among t'ose treate% 1it'
(rom'exine/amoxicillin -)isual analog scale2
p less t'an 0.00+. Six patients in t'e
com(ination group experience% a%)erse
e)ents6 compare% 1it' = patients in t'e
amoxicillin only group.
B. CARBOXYMETHYLCYSTEINE
1. BRONCHITIS
a. ENERA? IN!ORMA"ION# 7ysteine
compoun%s6 suc' as N
8/11/2019 Bromhexina Info Total
33/231
(. Secti)e
as (rom'exine syrup -+, mg t'ree times
%aily in impro)ing sputum consistency an%
some clinical symptoms. "ren%s to1ar% t'e
superiority o& S< car(oxymet'ylcysteine
1ere o(ser)e% in t'is stu%y6 inclu%ing a
more rapi% onset o& action. Ho1e)er6
neit'er agent pro%uce% impro)ement in
)entilatory )olumes or pea: expiratory o1
rates -Ayl1ar%6 +3.
C. CEPHALEXIN
1. SUMMARY
a. 7om(inations o& (rom'exine an%
cep'alexin 1ere more e>ecti)e t'an
cep'alexin alone.
2. RESPIRATORY DISORDERS
8/11/2019 Bromhexina Info Total
34/231
8/11/2019 Bromhexina Info Total
35/231
)ersus ++ %ays -Matts6 +3G. Ho1e)er6
met'o%s o& treatment allocation an%
(aseline clinical c'aracteristics o& eac'
treatment group 1ere not pro)i%e%2 it 1as
unclear i& t'e se)erity o& %isease in eac'
group 1as compara(le6 1'ic' coul% 'a)e
a>ecte% 'ospital stay.
E. SALINE SOLUTION
1. SINUSITIS
a. A small ran%omi;e%6 %ou(le
8/11/2019 Bromhexina Info Total
36/231
impro)ement t'an (rom'exine -p less t'an
0.0=.
F. SOBREROL
1. RESPIRATORY DISORDERS PEDIATRICS
a. So(rerol %rops in %oses o& =0 to +00
milligrams -mg t1ice %aily 1as reporte% at
least as e>ecti)e as (rom'exine %rops -
to G mg orally t'ree times %aily in treating
c'il%ren un%er = years o& age 1it' acute
'ypersecretory (ronc'opulmonary %isease
-A;;ollini et al6 +330.
!.0 REFERENCES
+. ADE7# Australian Drug E)aluation 7ommittee# Me%icines
in 8regnancy < An Australian 7ategorisation o& Ris: o& Drug
$se in 8regnancy6 r% e%. Australian o)ernment
8u(lis'ing Ser)ice6 7an(erra6 Australia2 +33,.
. AMA Department o& Drugs# Drug E)aluations
Su(scription. American Me%ical Association6 7'icago6 I?6
+33+.
. Anon# A controlle% trial o& t'e e>ects o& (rom'exine on
t'e symptoms o& out
8/11/2019 Bromhexina Info Total
37/231
=. Armstrong M?# Dou(leect on tear secretion in 'ealt'y su(4ects -letter.
Ann 8'armacot'erapy +33,2 0#+G3*.
. Ayl1ar% M# A (et1een
8/11/2019 Bromhexina Info Total
38/231
com(ination o& cep'alexin plus (rom'exine# a report on +00
cases. Drugs Exptl 7lin Res +3*G2 +0#G==
8/11/2019 Bromhexina Info Total
39/231
+. ent M6 9no1lson 8A F 8rime !# E>ect o&
(rom'exine on )entilatory capacity in patients 1it' a )ariety
o& c'est %iseases. ?ancet +3,32 #+03G
8/11/2019 Bromhexina Info Total
40/231
*. ?anglan%s HM# Dou(le
8/11/2019 Bromhexina Info Total
41/231
8/11/2019 Bromhexina Info Total
42/231
G. Se'gal S9 F Mo'an M# Brom'exine -re)ie1. In%ian
8e%iatr +3302 #G3
8/11/2019 Bromhexina Info Total
43/231
E'( )* D)+,-'/
DRUGDEX DRUG EVALUATIONS
ACETYLCYSTEINE
0.0 OVERVIEW
A. Acetylcysteine is a %eri)ati)e o& t'e amino aci% cysteine.
B. DOSIN IN!ORMA"ION# As a mucolytic6 t'e &ollo1ing
%osing is recommen%e%# ne(uli;e% %oses o& to = m? o&
a +0 solution2 orally &or a%ults an% a%olescents o)er +G
years o& age6 ,00 mg %aily in + to %i)i%e% %oses. !or
acetaminop'en o)er%ose6 an oral loa%ing %ose o& +G0
mg/:g is &ollo1e% (y 0 mg/:g e)ery G 'ours &or +
a%%itional %oses in a%ult an% pe%iatric patients2 alternati)ely6
t'e erman manu&acturer recommen%s I a%ministration o&
a +=0 mg/:g loa%ing %ose6 &ollo1e% (y =0 mg/:g in&use%
o)er G 'ours6 &ollo1e% (y +00 mg/:g in&use% o)er +, 'ours
&or a total %ose o& 00 mg/:g in&use% o)er 0 'ours an%
+= minutes.
7. 8HARMA7O9INE"I7S# "'e %rug is 1ellects occur 1it'in G= min an% persist &or +00
min2 some %egree o& 'epatic meta(olism occurs6 1it' renal
excretion o& meta(olites an% unc'ange% compoun%.
D. 7A$"IONS# "'e primary toxicity o& N
8/11/2019 Bromhexina Info Total
44/231
reporte%. A%)erse e>ects primarily consist o& allergic
reactions6 ras'6 nausea6 'ypotension6 (ronc'oconstriction6
(ronc'ospasm6 angioe%ema6 tac'ycar%ia6 an% respiratory
%istress.
E. 7?INI7A? A88?I7A"IONS# Acetylcysteine is a mucolytic
agent use% in t'e treatment o& pulmonary %iseases
associate% 1it' increase% )iscosity o& (ronc'ial secretions.
More importantly6 acetylcysteine is )ery e>ecti)e an%
extensi)ely use% in re)ersing t'e 'epatotoxicity in%uce% (y
acetaminop'en poisoning2 it is also recommen%e% as a
secon% line agent in acrylonitrile an% met'acrylonitrile
poisonings.
1.0 DOSING INFORMATION
1.1 DOSAGE FORMS
A. In&ormation on speci@c pro%ucts an% %osage &orms
can (e o(taine% (y re&erring to t'e 8ro%uct In%ex.
B. SNONMS#
1. Atil&ist#in$
2. At/l&/st#in n$t%iu
3. A ?1?-
8/11/2019 Bromhexina Info Total
45/231
+. Acetylcysteine is inacti)ate% (y pure O-
-?a1son F Saggers6 +3,=6 (ut t'is is pre)ente%
in t'e commercial pro%uct (y inclu%ing ED"A.
. Solutions &or oral use retain t'eir potency &or
at least 3, 'ours un%er re&rigeration 1'en preecti)e an% to
re%uce t'e mean treatment %uration
to + 'ours -oo et al6 000.
2. MUCOLYTIC
a. Oral acetylcysteine e>er)escent
ta(lets are recommen%e% &or a%ults
an% a%olescents &rom age +G years in
a %ose o& G00 to ,00 milligrams -mg
%aily in + to %i)i%e% %oses
-!ac'in&o !luimucil-R a:ut6 +33.
B. ORAL SOLUTION PREPARATION
+. "'e 0 acetylcysteine solution s'oul%
(e %ilute% 1it' cola %rin:s6 !resca-R6 or
ot'er so&t %rin:s to a @nal concentration o&
=. I& a%ministere% )ia gastric tu(e or
8/11/2019 Bromhexina Info Total
51/231
Miller
8/11/2019 Bromhexina Info Total
52/231
D. INTERPRETATION OF ACETAMINOPHEN
ASSAY
+. 'en results o& t'e plasma
acetaminop'en assay are a)aila(le6 t'e
Rumac:/Matt'e1 nomogram -a)aila(le in
Mucomyst-R pac:age inserts s'oul% (e
utili;e% to %etermine i& plasma
concentrations are in t'e potentially toxic
range. alues a(o)e t'e soli% line
connecting 00 micrograms/milliliter at G
'ours 1it' =0 micrograms/milliliter at +
'ours are associate% 1it' a possi(ility o&
'epatic toxicity i& acetylcysteine is not
a%ministere%. I& t'e plasma le)el is a(o)e
t'e (ro:en line on t'e nomogram6 continue
1it' maintenance %oses o& acetylcysteine.
I& t'e initial plasma le)el is (elo1 t'e
(ro:en line on t'e nomogram6 t'ere is
minimal ris: o& 'epatic toxicity an%
acetylcysteine treatment can (e
%iscontinue% -8ro% In&o Mucomyst-R6
+33,.
E. INTRAVENOUS
1. ACETAMINOPHEN POISONING
. SUMMARY
8/11/2019 Bromhexina Info Total
53/231
-+ "'ere is NO !DA
8/11/2019 Bromhexina Info Total
54/231
- "EN" HO$R
8RO"O7O?# A%minister +=0
milligrams/:ilogram in 00
milliliters = %extrose -D=
o)er += minutes6 &ollo1e% (y =0
milligrams/:ilogram in =00
milliliters D= o)er G 'ours6
&ollo1e% (y +00
milligrams/:ilogram in + liter
D= o)er t'e next +, 'ours
-8rescott et al6 +332 estman6
+3*3.
-G "'ere %oes appear to (e a
slig't increase% ris: o& a%)erse
reactions &ollo1ing intra)enous
a%ministration -primarily urticaria
an%/or (ronc'ospasm 1'ic' are
rate
8/11/2019 Bromhexina Info Total
55/231
Base% on a)aila(le %ata6 it is eJual
to
8/11/2019 Bromhexina Info Total
56/231
presenting early 1it' toxic le)els o&
acetaminop'en an% se)ere aci%osis6
presenting early 1it' extremely 'ig'
le)els o& acetaminop'en -G000
nmol/liter or more an% patients
presenting more t'an += 'ours a&ter
t'e ingestion 1it' serum le)els
excee%ing +000 nmol/liter.
%. "'e manu&acturer o& !luimucil-R
Anti%ot recommen%s t'e &ollo1ing
intra)enous %osing# +=0
milligrams/:ilogram -mg/:g in 00 m?
= Dextrose 1it' electrolyte a%%iti)e
o)er += minutes6 &ollo1e% (y =0
mg/:g in =00 m? = Dextrose 1it'
electrolyte a%%iti)e o)er G 'ours6
&ollo1e% (y +00 mg/:g in +000 m?
= Dextrose 1it' electrolyte a%%iti)e
o)er +, 'ours6 &or a total %ose o&
00 mg/:g o)er 0 'ours an% +=
minutes. IM8OR"AN" NO"E# "'e
amount o& = Dextrose 1it'
electrolyte a%%iti)e is calculate% &or a
0 :g person6 s'oul% t'e patient
1eig' less6 t'is amount must (e
a%4uste% accor%ing to t'e gui%elines
8/11/2019 Bromhexina Info Total
57/231
&or intra)enous glucose a%ministration
-!ac'in&o !luimucil-R Anti%ote6 +33.
e. "'e manu&acturer o& !luimucil-R
Anti%ot recommen%s treatment 1it'in
+0 'ours o& acetaminop'en o)er%ose2
a%ministration o& acetylcysteine +=
'ours a&ter t'e o)er%ose 1ill most
li:ely not pro%uce %esire% results6
alt'oug' reports o& &a)ora(le results
to a%ministration +, to G 'ours a&ter
o)er%ose can (e &oun% in t'e
literature. "'e anti%ote protocol s'oul%
(e &ollo1e%6 i& acetaminop'en serum
le)els excee% 00 nanograms per
milliliter -ng/m? a&ter G 'ours or 0
ng/m? += 'ours a&ter acetaminop'en
ingestion2 as long as t'e se)erity o&
t'e poisoning is un:no1n6 anti%ote
t'erapy s'oul% (e initiate% -!ac'in&o
!luimucil-R Anti%ot6 +33.
2. ACRYLONITRILE POISONING
. INHALATIVE OR DERMAL
POISONING
1 NONSEVERE POISONING
-a "reatment o& nonecti)e in
pre)enting acetaminop'en
8/11/2019 Bromhexina Info Total
65/231
ingestion o& an o)er%ose. Do not 1ait
&or t'e result o& la(oratory assays &or
acetaminop'en le)els. "'e &ollo1ing
proce%ures are recommen%e% -8ro%
In&o Mucomyst-R6 +33,#
-+ "'e stomac' s'oul% (e
emptie% (y la)age or emesis
1it' syrup o& ipecac. Syrup o&
ipecac s'oul% (e gi)en in a
%ose o& += to 0 milliliters &or
c'il%ren an% 0 to G0 milliliters
&or a%ults accompanie% (y G to
, ounces o& 1ater. "'e %ose
s'oul% (e repeate% i& emesis
%oes not occur in 0 minutes.
- In t'e cases o& a mixe%
%rug o)er%ose6 acti)ate%
c'arcoal may (e in%icate%. I&
acti)ate% c'arcoal is
a%ministere%6 it is recommen%e%
t'at t'e patient (e la)age%
(e&ore a%ministration o&
acetylcysteine since acti)ate%
c'arcoal a%sor(s acetylcysteine
in )itro an% may also %o so in
)i)o.
8/11/2019 Bromhexina Info Total
66/231
- Bloo% s'oul% (e %ra1n &or
acetaminop'en plasma assay
an% &or (aseline SO"6 S8"6
(iliru(in6 prot'rom(in time6
creatinine6 B$N6 (loo% sugar6
an% electrolytes. 8lasma or
serum acetaminop'en
concentrations s'oul% (e
%etermine% as early as possi(le
(ut no sooner t'an G 'ours
&ollo1ing acute o)er%ose. "'ese
le)els are essential in assessing
t'e potential ris: o&
'epatotoxicity. I& an assay &or
acetaminop'en cannot (e
o(taine%6 it is necessary to
assume t'e o)er%ose is
potentially toxic.
-G A%minister t'e loa%ing %ose
o& acetylcysteine -+G0
milligrams/:ilogram o& (o%y
1eig't.
-= !our 'ours a&ter t'e loa%ing
%ose6 a%minister t'e @rst
maintenance %ose o& 0
milligrams/:ilogram. Maintenance
8/11/2019 Bromhexina Info Total
67/231
%oses s'oul% (e repeate% at Gers a more
rapi% onset o& action in c'ronic (ronc'itis
an% (ronc'iectasis compare% 1it' oral an%
intramuscular routes. "'e intramuscular
route is eJui)alent to t'e oral route -rassi
et al6 +3.
B. 8EA9 RES8ONSE#
+. Mucolytic6 in'alation# G= minutes -Hurst et al6
+3,.
2.1.2 DURATION
A. SIN?E DOSE#
+. Mucolytic6 in'alation# +00 minutes -Hurst et al6
+3,.
2.2 DRUG CONCENTRATION LEVELS
2.2.1 THERAPEUTIC
A. "IME "O 8EA9 7ON7EN"RA"ION#
+. In'alation6 ne(uli;er# + to 'ours -Hol%iness6
+33+.
8/11/2019 Bromhexina Info Total
78/231
a. An intra)enous %ose o& +=0 mg/:g gi)en
in += minutes resulte% in a mean
maximum plasma concentration o& ==G
mg/? -8rescott et al6 +3*3.
B. AREA $NDER "HE 7$RE -A$7# 3.3 mg/?/'r
-'ealt'y su(4ects -ones et al6 +33.
+. Mean A$7 1as +=. mg/?/'r in patients
1it' cirr'osis as compare% to 3.3 mg/?/'r in
'ealt'y controls6 &ollo1ing an intra)enous %ose
o& ,00 mg in&use% o)er minutes -ones et al6
+33.
2.3 ADME
2.3.1 ABSORPTION
A. BIOAAI?ABI?I" -!#
+. Oral6 ta(lets# , to +0 -Hol%iness6 +33+.
a. Oral (ioa)aila(ility is similar &or a single
,00ect o& acti)ate% c'arcoal on oral
(ioa)aila(ility -atson F Mc9inney6 +33+.
One stu%y &oun% no %i>erence in total area
un%er t'e cur)e -Nort' et al6 +3*+. In
)itro %ata %emonstrate% signi@cant
a%sorption o& t'e %rug to acti)ate% c'arcoal
8/11/2019 Bromhexina Info Total
79/231
-9lein
8/11/2019 Bromhexina Info Total
80/231
A. DIS"RIB$"ION HA?! ?I!E# 0.++ ?/:g/'our
-Olsson et al6 +3**.
B. O?$ME O! DIS"RIB$"ION -%# 0. to
0.G ?/:g -Olsson et al6 +3**2 Borgstrom et al6
+3*,.
2.3.3 METABOLISM
2.3.3.1 METABOLISM SITES AND KINETICS
A. ?i)er6 rapi% an% extensi)e -Hol%iness6 +33+.
+. !ollo1ing %e
8/11/2019 Bromhexina Info Total
81/231
7. It is not precisely :no1n 'o1 muc' o& t'e
%rug is excrete% unc'ange% )ersus meta(oli;e%.
"'e ma4or excretory meta(olite is inorganic
sul&ate2 t'e sul&ate eJuate% to * o& t'e
a%ministere% %ose an% some taurine 1as also
present -Hol%iness6 +33+2 Barte: et al6 +32
S'i' F Sc'ulman6 +3,3.
D. !ollo1ing intra)enous %oses o& ra%ioacti)ely
la(ele% acetylcysteine6 urinary ra%ioacti)ity coul%
(e %etecte% &or up to = %ays -Barte: et al6
+32 S'i' F Sc'ulman6 +3,3.
2.3.4.3 OTHER
A. "O"A? BOD 7?EARAN7E# ,.= ?/'r -'ealt'y
su(4ects -ones et al6 +33.
+. A)erage o& G.= ?/'r in patients 1it'
cirr'osis as compare% to ,.= ?/'our in
'ealt'y controls6 &ollo1ing an intra)enous
%ose o& ,00 mg in&use% o)er minutes
-ones et al6 +33.
B. O"HER EX7RE"ION#
+. !eces6 -Hol%iness6 +33+.
a. In animal mo%els6 only o& Nect# loss o& anti(iotic eLcacy
. Se)erity# not speci@e%
. Onset# not speci@e%
G. Documentation# poor
=. ?iterature Reports#
a. A signi@cant increase in MI7 1as
o(ser)e% in an in )itro stu%y o& t'e
com(ine% use o& acetylcysteine an%
ampicillin6 penicillin 6 cloxacillin6 met'icillin6
oxacillin6 Juinacillin6 cep'alori%ine6 or
tetracycline -?a1son F Saggers6 +3,=.
Ho1e)er6 t'e results o& one in )i)o stu%y
8/11/2019 Bromhexina Info Total
117/231
on t'e use o& com(ination t'erapy in
respiratory tract in&ections &oun% no
inacti)ation o& t'e anti(iotic 1'en
aerosoli;e% acetylcysteine 1as use% 1it'
ampicillin6 cep'alori%ine6 cloxacillin6
eryt'romycin6 &usi%ic aci%6 gentamicin6
lincomycin6 met'icillin6 no)o(iocin6
sul&a%ia;ine6 sul&amet'a;ine6 or tetracycline
-Saggers F ?a1son6 +3,*. 7linical reports
o& suc' an interaction are lac:ing6
suggesting t'at it is unli:ely to (e o&
clinical importance.
L. 6UINACILLIN
+. 7linical Management# Acetylcysteine s'oul%
not (e mixe% in t'e same solution as Juinacillin
&or ne(uli;ation.
. Se)erity# not speci@e%
. Onset# not speci@e%
G. Documentation# poor
=. ?iterature Reports#
a. A signi@cant increase in MI7 1as
o(ser)e% in an in )itro stu%y o& t'e
com(ine% use o& acetylcysteine an%
ampicillin6 penicillin 6 cloxacillin6 met'icillin6
oxacillin6 Juinacillin6 cep'alori%ine6 or
tetracycline -?a1son F Saggers6 +3,=.
8/11/2019 Bromhexina Info Total
118/231
Ho1e)er6 t'e results o& one in )i)o stu%y
on t'e use o& com(ination t'erapy in
respiratory tract in&ections &oun% no
inacti)ation o& t'e anti(iotic 1'en
aerosoli;e% acetylcysteine 1as use% 1it'
ampicillin6 cep'alori%ine6 cloxacillin6
eryt'romycin6 &usi%ic aci%6 gentamicin6
lincomycin6 met'icillin6 no)o(iocin6
sul&a%ia;ine6 sul&a%imi%ine6 or tetracycline
-Saggers F ?a1son6 +3,*. 7linical reports
o& suc' an interaction are lac:ing6
suggesting t'at it is unli:ely to (e o&
clinical importance.
M. TETRACYCLINE
+. A%)erse E>ect# loss o& anti(iotic eLcacy
. 7linical Management# Acetylcysteine s'oul%
not (e mixe% in t'e same solution as
tetracycline &or ne(uli;ation.
. Se)erity# not speci@e%
G. Onset# not speci@e%
=. Documentation# poor
,. 8ro(a(le Mec'anism# un:no1n
. ?iterature Reports#
a. A signi@cant increase in MI7 1as
o(ser)e% in an in )itro stu%y o& t'e
com(ine% use o& acetylcysteine an%
8/11/2019 Bromhexina Info Total
119/231
ampicillin6 penicillin 6 cloxacillin6 met'icillin6
oxacillin6 Juinacillin6 cep'alori%ine6 or
tetracycline -?a1son F Saggers6 +3,=.
Ho1e)er6 t'e results o& one in )i)o stu%y
on t'e use o& com(ination t'erapy in
respiratory tract in&ections &oun% no
inacti)ation o& t'e anti(iotic 1'en
aerosoli;e% acetylcysteine 1as use% 1it'
ampicillin6 cep'alori%ine6 cloxacillin6
eryt'romycin6 &usi%ic aci%6 gentamicin6
lincomycin6 met'icillin6 no)o(iocin6
sul&a%ia;ine6 sul&a%imi%ine6 or tetracycline
-Saggers F ?a1son6 +3,*. 7linical reports
o& suc' an interaction are lac:ing6
suggesting t'at it is unli:ely to (e o&
clinical importance.
3.5.3 DRUGLAB MODIFICATIONS
A. NITROPRUSSIDE TEST
+. Summary# Acetylcysteine may inter&ere 1it'
t'e nitroprussi%e test6 resulting in a &alse
8/11/2019 Bromhexina Info Total
120/231
1it' suspecte% 'epatocellular in4ury -7sa:o F
Elin6 +33.
. Se)erity# minor
. Onset# rapi%
G. Documentation# poor
B. SALICYLATE ASSAY
+. Summary# "'e e>ects o& =G commonly use%
me%ications on t'e assay o& salicylate
concentration 1ere e)aluate%. Only acetylcysteine
an% cysteamine cause% a signi@cant inter&erence
1it' t'e salicylate measurement. "'e assay
met'o% &or salicylate 1as colorimetric -a reaction
1it' Gect# unrelia(le salicylate
concentrations
. 7linical Management# "'e colorimetric assay
met'o% &or salicylate measurement s'oul% not
(e use% in patients recei)ing acetylcysteine.
G. Se)erity# minor
=. Onset# rapi%
,. Documentation# &air
. 8ro(a(le Mec'anism# salicylate assay
inter&erence
3.5.4 INTRAVENOUS ADMIXTURES
3.5.4.2 COMPATIBILITIES DRUGS
8/11/2019 Bromhexina Info Total
121/231
A. BACITRACIN
+. Acetylcysteine +0 1it' (acitracin =000
$/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
B. CARBENICILLIN
+. 7ar(enicillin -+= mg/m? 1it'
acetylcysteine +06 compati(le (ut mixture
s'oul% (e use% at once -8ro% In&o
Mucomyst-R6 +33,
C. CEPHALORIDINE
+. Acetylcysteine +0 1it' cep'alori%ine G,
mg/m?6 compati(le (ut mixture (ecame a
slig'tly %ar:er yello1 color t'an a control
solution -8ro% In&o Mucomyst-R6 +33+
D. CEPHALOTHIN
+. Acetylcysteine +0 1it' cep'alot'in ++0
mg/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
E. CHLORAMPHENICOL
+. Acetylcysteine 0 1it' c'loramp'enicol
0 mg/m?6 compati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
F. COCAINE
8/11/2019 Bromhexina Info Total
122/231
+. Acetylcysteine +0 1it' cocaine =6
compati(le2 con%itions not speci@e% -8ro%
In&o Mucomyst-R6 +33+
G. COLISTIN
+. Acetylcysteine +0 1it' colistin .=
mg/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
H. CROMOLYN
+. Acetylcysteine 1it' cromolyn so%ium
ne(uli;er solution +6 p'ysically an%
c'emically compati(le -sta(le &or up to ,0
minutes 1'en mixe% in )itro -?es:o F
Miller6 +3*G
I. DEXAMETHASONE
+. Acetylcysteine +, 1it' %examet'asone
0.* mg/m?6 compati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
%. EPINEPHRINE
+. Acetylcysteine +. - parts 1it'
epinep'rine 0. -+ part6 compati(le2
con%itions not speci@e% -8ro% In&o
Mucomyst-R6 +33+
K. GENTAMICIN
8/11/2019 Bromhexina Info Total
123/231
+. Acetylcysteine +0 1it' gentamicin 0
mg/m?6 compati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R6 +33+
L. ISOPROTERENOL
+. Acetylcysteine 1it' isoproterenol
0.=6 compati(le2 con%itions not speci@e%
an% %rug concentrations liste% (elo1 -8ro%
In&o Mucomyst-R6 +33+
. Acetylcysteine +0 1it' isoproterenol
0.0=6 compati(le2 con%itions not speci@e%
an% %rug concentrations liste% (elo1 -8ro%
In&o Mucomyst-R6 +33+
. Acetylcysteine 0 1it' isoproterenol
0.0=6 compati(le2 con%itions not speci@e%
an% %rug concentrations liste% (elo1 -8ro%
In&o Mucomyst-R6 +33+
G. Acetylcysteine +. - parts 1it'
isoproterenol 0. -+ part6 compati(le2
con%itions not speci@e% an% %rug
concentrations liste% (elo1 -8ro% In&o
Mucomyst-R6 +33+
M. KANAMYCIN
+. Acetylcysteine +0 1it' :anamycin +,
mg/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
8/11/2019 Bromhexina Info Total
124/231
. Acetylcysteine + 1it' :anamycin *=
mg/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
N. LIDOCAINE
+. Acetylcysteine +0 1it' li%ocaine 6
compati(le2 con%itions not speci@e% -8ro%
In&o Mucomyst-R6 +33+
O. LINCOMYCIN
+. Acetylcysteine +0 1it' lincomycin +=0
mg/m?6 compati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R6 +33+
P. NEOMYCIN
+. Acetylcysteine +0 1it' neomycin +00
mg/m?6 compati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R6 +33+
6. NOVOBIOCIN
+. Acetylcysteine +0 1it' no)o(iocin =
mg/m?6 compati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R6 +33+
R. PANCREATIC DORNASE
+. Acetylcysteine +,. 1it' pancreatic
%ornase *000 $/m?6 compati(le (ut mixture
s'oul% (e use% at once -8ro% In&o
Mucomyst-R6 +33+
S. PENICILLIN G
8/11/2019 Bromhexina Info Total
125/231
8/11/2019 Bromhexina Info Total
126/231
+. Acetylcysteine 0 1it' so%ium
(icar(onate G.6 compati(le2 con%itions
not speci@e% -8ro% In&o Mucomyst-R6
+33+
Y. TETRACAINE
+. Acetylcysteine +0 1it' tetracaine +6
compati(le2 con%itions not speci@e% -8ro%
In&o Mucomyst-R6 +33+
. VANCOMYCIN
+. Acetylcysteine +0 1it' )ancomycin =
mg/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R6
+33+
3.5.4.4 INCOMPATIBILITIES DRUGS
A. AMPHOTERICIN B
+. Acetylcysteine G to += 1it'
amp'otericin B + to G mg/m?6 incompati(le2
con%itions not speci@e% -8ro% In&o
Mucomyst-R6 +33+
B. AMPICILLIN
+. Acetylcysteine +0 1it' ampicillin =0
mg/m?6 incompati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
C. CHLORTETRACYCLINE
8/11/2019 Bromhexina Info Total
127/231
+. Acetylcysteine +0 1it' c'lortetracycline
+.= mg/m?6 incompati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
D. ERYTHROMYCIN
1. ERYTHROMYCIN LACTOBIONATE
a. Acetylcysteine +0 1it'
eryt'romycin lacto(ionate += mg/m?6
incompati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R6 +33+
E. IODIED OI
+. Acetylcysteine 0 m? o& a 0 solution
1it' io%i;e% oil +0 m? o& a G0 solution6
incompati(le2 con%itions not speci@e% -8ro%
In&o Mucomyst-R6 +33+
F. OXYTETRACYCLINE
+. Acetylcysteine +0 1it' oxytetracycline
+.= mg/m?6 incompati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
G. TETRACYCLINE
+. Acetylcysteine +0 1it' tetracycline +.=
mg/m?6 incompati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R6 +33+
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. A7E"AMINO8HEN OERDOSE
8/11/2019 Bromhexina Info Total
128/231
+. ?i)er &unction tests
4.1.2 TOXIC
A. A7E"AMINO8HEN OERDOSE
+. Nausea6 )omiting
4.2 PATIENT INSTRUCTIONS
A'*L*'N' ($-s#-t##l--t##n) (NALAON):
#l"s /ou to 0%#$t# 0#tt#% 0/ tinnin o% dissolvin
ti& lun u&us &$us#d 0/ #"/s#$ "n#uoni$
&/sti& +i0%osis o% ot#% lun "%o0l#s.
BRAND NA'(): u&o/st(R) u&osil(R)
'N *O, O,LD NO ,' 'DN':
*ou sould not us# tis #di&in# i+ /ou $v# $d $n
$ll#%i& %#$&tion to $t/l&/st#in#.O O ,' AND OR' 'DN'
olution:
- *ou% do&to% 6ill t#ll /ou o6 u& #di&in# to us#
$nd o6 o+t#n to $v# /ou% t%#$t#nts.
- $%#+ull/ %#$d $nd +ollo6 t# inst%u&tions t$t
&o# 6it t# #di&in#. #/ 6ill t#ll /ou o6 to
us# t# n#0uliE#% (t# d#vi t$t /ou us# to
0%#$t# in t# #di&in#) $nd &o"%#sso% $nd o6 to
&$%# +o% $nd &l#$n t# n#0uliE#% it.
- # &o"%#sso% tu%ns t# #di&in# into $ +in#
s"%$/ t$t /ou 6ill 0%#$t into /ou% out usin
t# n#0uliE#%.
- ,s# t# out"i# t$t &o#s 6it t# n#0uliE#%.- $s /ou% $nds 6it so$" $nd 6$t#% 0#+o%# "uttin
t# n#0uliE#% to#t#%.
- O"#n t# vi$l (s$ll 0ottl# o+ #di&in#) $nd "ou%
t# #di&in# into t# n#0uliE#% &u". Put t# &$"
0$& on t# &u". # #di&in# $/ $v# $ 0$d s#ll
$t +i%st. # odo% sould o $6$/ soon $+t#% /ou
st$%t /ou% t%#$t#nt.
- u%n on t# &o"%#sso% so ist is &oin out o+
t# n#0uliE#%.
- Put t# out"i# in /ou% out &los# /ou% li"s
$%ound it $nd 0%#$t# in $nd out t%ou /ou%
out. $# su%# /ou% t##t $nd tonu# do not
0lo& t# $i%+lo6.- ##" 0%#$tin until t# n#0uliE#% &u" is #"t/ o%
no o%# ist is &oin out. *ou $/ #$% $
s"utt#%in sound 6#n t# &u" is #"t/.
- #n +inis#d tu%n o++ t# &o"%#sso% $nd &l#$n
t# n#0uliE#% $nd &o"%#sso%.
- *ou $/ n##d to &ou u" $nd s"it out u&us t$t
&oll#&ts in /ou% t%o$t.
- nst#$d o+ $ out"i# $t/l&/st#in# is
so#ti#s iv#n t%ou $ +$ $s.
- o#ti#s $ t#nt is "l$d $%ound t# #$d o%
u""#% 0od/ $nd t# #di&in# is "ut into t# $i%
o+ t# t#nt +o% 0%#$tin.
- $l to /ou% do&to% o% "$%$&ist i+ /ou $v#Gu#stions $0out /ou% #di&in# $nd 6#t#% /ou $%#
usin it &o%%#&tl/.
- to%# uno"#n#d vi$ls o+ #di&in# $t %oo
8/11/2019 Bromhexina Info Total
129/231
t#"#%$tu%# $6$/ +%o #$t $nd di%#&t lit.
A+t#% t# vi$l $s 0##n o"#n#d ##" it in t#
%#+%i#%$to% $nd us# it 6itin 4 d$/s. Do not
+%##E#.
- *ou sould not us# vi$ls o+ $t/l&/st#in# t$t
$v# "$ss#d t# #"i%$tion d$t#.
- ##" $ll #di&in# out o+ t# %#$& o+ &ild%#n.+ /ou iss $ dos#:
- $# t# iss#d dos# $s soon $s "ossi0l# unl#ss
it is $lost ti# +o% /ou% n#t dos#.
- i" t# iss#d dos# i+ it is $lost ti# +o% /ou%
n#t %#ul$% dos#.
- *ou sould not us# t6o dos#s $t t# s$# ti#.
DR,= AND FOOD O AVOD:
As /ou% do&to% o% "$%$&ist 0#+o%# usin $n/ ot#%
#di&in# in&ludin ov#%-t#-&ount#% #di&in#s
vit$ins $nd #%0$l "%odu&ts.
- Do not i ot#% #di&in#s in t# n#0uliE#% 6it
$t/l&/st#in# unl#ss /ou% do&to% t#lls /ou to.
ARNN=:
- + /ou $%# "%#n$nt o% 0%#$st+##din t$l to /ou%
do&to% 0#+o%# usin $t/l&/st#in#
- #ll /ou% do&to% 0#+o%# usin tis #di&in# i+ /ou
$v# $st$ o% i+ it is $%d +o% /ou to &ou.
D' 'FF'
$ll /ou% do&to% %it $6$/ i+ /ou $v# $n/ o+ t#s#
sid# #++#&ts:
- n&%#$s#d 6##Ein o% t%ou0l# 0%#$tin
- #st "$in o% titn#ss
- ouin u" 0lood
- F#v#% sin %$s o% iv#s
+ /ou $v# "%o0l#s 6it t#s# l#ss s#%ious sid#
#++#&ts t$l 6it /ou% do&to%.
- o%# out o% t%o$t
- o$%s#n#ss
- N$us#$ voitin
- Runn/ nos#
F *O, AV' AN* O'R D' 'FF' A *O, N AR'
A,'D B* 'DN' 'LL *O,R DOOR.
4.3 PLACE IN THERAPY
A. Oral acetylcysteine is consi%ere% t'e %rug o& c'oice &or
pre)ention against li)er %amage in se)ere acetaminop'en
intoxication. One clinician -Smil:stein6 +3** re)ie1e%
++6+3= cases o& suspecte% acetaminop'en o)er%ose. He
conclu%e% t'at N
8/11/2019 Bromhexina Info Total
130/231
as t'e 0ecti)e muco:inetic agent
an% is use&ul in %ecreasing t'e num(er o& exacer(ations in
patients 1it' c'ronic (ronc'itis. 'en gi)en in com(ination
1it' ce&uroxime6 acetylcysteine increases t'e anti(iotic5s
penetration into (ronc'ial secretion.
7. Ot'er potential uses o& acetylcysteine inclu%e protection
against oxi%ant -&ree ra%icals %amage an% as protection
against cytotoxic agents suc' as i&os&ami%e an%
cyclop'osp'ami%e.
D. Acetylcysteine s'oul% (e inclu%e% on t'e 'ospital
&ormulary.
4.4 MECHANISM OF ACTION"PHARMACOLOGY
A. MECHANISM OF ACTION
+. Acetylcysteine -NA7 is t'e N
8/11/2019 Bromhexina Info Total
131/231
8/11/2019 Bromhexina Info Total
132/231
. Nect on patients 1it' &ulminant
'epatic &ailure cause% (y acetaminop'en -Harrison et
al6 +33+.
G. Nerent %iseases6
all o& 1'ic' 'a)e one &eature in common6 t'e loss o&
SH.
=. "'e a(ility o& Nects. "'e cellular %amage associate% 1it' sepsis6
trauma6 (urns6 pancreatitis6 'epatic &ailure6
'emorr'age6 an% tissue reper&usion &ollo1ing acute
myocar%ial in&arction may (e me%iate% (y t'e
&ormation an% release o& large Juantities o& &ree
8/11/2019 Bromhexina Info Total
133/231
8/11/2019 Bromhexina Info Total
134/231
. A re)ie1 o& t'e p'armaco:inetics an% mec'anism
o& action o& t'iol compoun%s6 inclu%ing acetylcysteine6
is pro)i%e% -Broc: et al6 +3*G.
G. Role o& cysteine an% glutat'ione in HI in&ection
an% cancer cac'exia# "'erapeutic inter)ention 1it' Nerence (et1een
NA7 an% place(o treatments 1as statistically
signi@cant -relati)e (ene@t+.=,6 3= con@%ence
inter)al6 +.ect o& long
8/11/2019 Bromhexina Info Total
147/231
to (e -3= con@%ence inter)al# ering &rom
c'ronic (ronc'itis 1ere ran%omi;e% to recei)e
eit'er acetylcysteine 00 milligrams times a
%ay or place(o %uring a ,ecti)e t'an place(o in
impro)ing %iLculty in expectoration an% coug'
se)erity in c'ronic (ronc'itis patients in a
controlle% stu%y -ac:son et al6 +3*G. "oxicity
1as minimal.
e. "'e results o& a general practice stu%y o&
+,*, patients suggest t'at acetylcysteine
8/11/2019 Bromhexina Info Total
148/231
a%ministere% orally -00 milligrams t'ree times
%aily &or mont's to patients 1it' c'ronic
(ronc'itis e>ecti)ely c'anges t'e )iscosity an%
c'aracter o& sputum 1it' resultant ease o&
expectoration an% coug' se)erity. "'ere 1as a
nota(le impro)ement in associate% a(normal
p'ysical signs suc' as t'e presence o& r'onc'i6
cripitations6 an% %yspnea at rest. "olera(ility 1as
goo%6 1it' *+ o& patients experiencing no si%e
e>ects2 gastrointestinal e>ects -ie6 nausea an%
)omiting 1ere most &reJuent -"attersall et al6
+3*.
H. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
FDA L$0#l#d ndi&$tion
+. OERIE#
FDA APPROVAL: Adult /#s! "#di$t%i& /#s
'FFA*: Adult "ossi0l/ #++#&tiv#! "#di$t%i&
"ossi0l/ #++#&tiv#
DO,'NAON: Adult +$i%! "#di$t%i& +$i%
. S$MMAR#
- At/l&/st#in# is FDA-$""%ov#d $s $
u&ol/ti& 0/ di%#&t instill$tion o% n#0uliE$tion
- Adinist#%#d o%$ll/ o% lo&$ll/ in studi#s
- At/l&/st#in# %#dus t# &onsist#n&/ o+
s"utu in "ulon$%/ dis#$s#
- ts &ont%i0ution to i"%ov##nt in "ulon$%/+un&tion $nd &lini&$l &ondition $/ 0# liit#d
. AD$?"#
a. Once
8/11/2019 Bromhexina Info Total
149/231
7O8D -(eta
8/11/2019 Bromhexina Info Total
150/231
'a)e6 in general6 (een unsatis&actory. "'e only
(ene@cial response attri(uta(le to NA7 'as (een
a %ecrease in sputum consistency -Hirsc' et al6
+302 Hirsc' F 9ory6 +3,6 1it' no
impro)ement in pulmonary &unction tests or
su(4ecti)e response. NA7 'as (een s'o1n to
pro%uce 'ypoxemia an% 'ypercar(ia 1it' a
%ecrease in )ital capacity an% increase in air1ay
resistance in t'ese patients -Rao et al6 +30.
G. 8EDIA"RI7#
a. Intratrac'eal a%ministration o& NA7 to liJui&y
air1ay mucus neit'er impro)es t'e clinical
con%ition nor 'astens reco)ery in premature
in&ants 1it' 7HRONI7 ?$N DISEASE an% its
a%ministration may lea% to increase% total air1ay
resistance an% cyanotic spells -Bi(i et al6 +33.
I. COMMON BILE DUCT OBSTRUCTION
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: P#di$t%i& "ossi0l/ #++#&tiv#
DO,'NAON: P#di$t%i& "oo%
. S$MMAR#- $s# %#"o%ts d#s&%i0# &l#$%$n o+ 0il# du&t
o0st%u&tion usin $t/l&/st#in# in in+$nts
. 8EDIA"RI7#
a. "'e use o& N
8/11/2019 Bromhexina Info Total
151/231
c'ole%oc'otomy an% may (e o& use in ot'er
in&ants 1it' %uctal o(struction.
(. N
8/11/2019 Bromhexina Info Total
152/231
)ital capacity -!7 (elo1 = or a pea:
expiratory o1 rate -8E!R o& 0 or lo1er
-Sta&anger et al6 +3**2 Sta&anger F 9oc'6 +3*32
Steil F Niessen6 +3*0. Most o& t'e reports
pro)i%e only su(4ecti)e e)aluations an% t'ere are
&e1 controlle% stu%ies -Denton et al6 +3,2
Stamm F Docter6 +3,=2 Reas6 +3,G. In one
stu%y6 acetylcysteine 'a% a %eleterious e>ect on
pulmonary &unction tests an% no (ene@cial e>ect
on su(4ecti)e response -"e:lin F Holscla16
+3,.
(. A systematic re)ie1 o& literature (et1een
+3,, an% +33 on t'e use o& Nerence in t'e
proportion o& patients s'o1ing greater t'an 0
impro)ement in lung &unction. it' oral NA76
t'ere 1as a ten%ency to1ar% impro)ement o&
!E+6 (ut t'e e>ect 1as small -. an% its
clinical rele)ance is Juestiona(le. !ollo1
8/11/2019 Bromhexina Info Total
153/231
goo% e)i%ence t'at NA7 impro)es lung &unction
-Dui4)esti4n F Bran%6 +333.
c. "'e e>ect o& oral acetylcysteine 1as
eJui)ocal in patients 1it' cystic @(rosis an%
c'ronic pulmonary 8seu%omonas aeruginosa
in&ection. O)erall6 = patients 1ere enrolle% in a
%ou(le
8/11/2019 Bromhexina Info Total
154/231
G. 8EDIA"RI7#
a. Acetylcysteine %oes not appear to impro)e
!A" MA?ABSOR8"ION in cystic @(rosis. A
%ou(leerent. "'e only conclusion 1'ic' can (e
ma%e is t'at t'e t'ic:ene% mucus co)ering t'e
)illi is an insigni@cant &actor in &at mala(sorption
associate% 1it' cystic @(rosis or t'at t'e %ose
o& acetylcysteine use% in t'is stu%y 1as
insuLcient.
K. CYSTINOSIS
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult "ossi0l/ #++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#
- At/l&/st#in# $s 0##n us#d su&ss+ull/ in
"$ti#nts 6it &/stinosis
8/11/2019 Bromhexina Info Total
155/231
8/11/2019 Bromhexina Info Total
156/231
protect against car%iotoxicity &rom %oxoru(icin
an% a%riamycin6 lung %amage &rom (leomycin6
an% 'epatotoxicity &rom nitrogen mustar%s.
Acetylcysteine %oes NO" appear to (e e>ecti)e
in re)ersing a%)ance% le&t )entricular %ys&unction
&rom DOXOR$BI7IN
8/11/2019 Bromhexina Info Total
157/231
8/11/2019 Bromhexina Info Total
158/231
an% carries a 'ig' mortality rate. "'e cellular
%amage associate% 1it' SIRS is me%iate% (y
t'e &ormation o& large Juantities o& acti)e &ree
ra%icals (y iname% cells t'at o)er1'elm an%
%eplete en%ogenous antioxi%ants -eg6
glutat'ione. Acetylcysteine is a glutat'ione
precursor capa(le o& replenis'ing %eplete%
intracellular glutat'ione an% in t'eory augment
antioxi%ant %e&enses. A (olus %ose o& +=0 mg/:g
in %extrose = in&use% o)er 0 minutes &ollo1e%
(y += mg/:g/' &or G %ays 'as (een use% in
'umans. Initial reports appear to in%icate t'at
acetylcysteine may impro)e renal &unction6
re%uce ui% reJuirements6 an% lessen tissue
e%ema. Acetylcysteine may (e a use&ul a%4u)ant
t'erapy &or SIRS associate% 1it' se)ere sepsis
-Hen%erson F Hayes6 +33G2 Ba::er et al6 +33G2
Dinarello et al6 +332 Bone6 +332 epsen et al6
+332 el(ourn F oung6 +332 Repine F
Bee'ler6 +33+2 Rac:o1 F Asti;6 +33+2 lauser et
al6 +33+2 Ellen'orn F Barceloux6 +3**2 Bragan;a
et al6 +3*,2 9eller et al6 +3*=2 Boro;otta F 8ol:6
+3*.
e. In animals an% 'umans6 acetylcysteine 'as
(een s'o1n to %iminis' t'e extent o& reper&usion
in4ury &ollo1ing A7$"E MO7ARDIA?
8/11/2019 Bromhexina Info Total
159/231
IN!AR7"ION (y re%ucing myocar%ial stunning6
re%ucing in&arct si;e (y to G36 increasing
le&t )entricular e4ection &raction6 an% re%ucing t'e
se)erity o& )entricular arr'yt'mias %uring
reper&usion -Soc'man et al6 +33,2 Arstall et al6
+33=2 rec' et al6 +332 oung et al6 +332
Da)ies et al6 +332 !ar( et al6 +332
9irs'en(aum et al6 +332 !errari et al6 +3302
Soc'man et al6 +3302 Blaustein et al6 +3*32
Sing' et al6 +3*32 Aruoma et al6 +3*32 !orman
et al6 +3**2 7econi et al6 +3**2 estlin F
Mullane6 +3**.
&. Acetylcysteine 1as not e>ecti)e treatment &or
patients 1it' AMO"RO8HI7 ?A"ERA?
S7?EROSIS -A?S. In a ran%omi;e%6 %ou(leects o& nausea an% )omiting6
compliance may 'a)e (een less t'an reporte%.
it' t'e %ose an% &ormulation use%6 NA7
cannot (e recommen%e% to pre)ent
H8ERSENSI"II" REA7"ION "O "M8
8/11/2019 Bromhexina Info Total
163/231
pre)ent 'emorr'agic cystitis (y neutrali;ing
t'ese al:ylating agents. Acetylcysteine
pro)i%es t'iol groups &or t'e al:ylator5s
meta(olites to react 1it'6 t'ere(y sparing
t'e (la%%er -atson6 +3*G.
- !actors contri(uting to t'e limite%
acceptance o& oral acetylcysteine as a
uroprotecti)e agent inclu%e nausea an%
)omiting associate% 1it' 'ig' %oses6 poor
taste6 an% un%esira(le p'armaco:inetic
properties -less t'an +0 is excrete% in
t'e urine -Sc'oeni:e F Dana6 +330.
7omparati)e stu%ies in%icate t'at mesna
-mercaptoet'ane sul&onate6 anot'er t'iol
compoun% capa(le o& (in%ing 1it' acrolein6
is more e>ecti)e t'an acetylcysteine &or
'emorr'agic cystitis -illiams et al6 +3302
?eg'a et al6 +330. Ho1e)er6 mesna
treatment 'as not (een s'o1n in controlle%
stu%ies to (e superior to 'yper'y%ration
1it' &orce% %iuresis &or protection against
cyclop'osp'ami%e
8/11/2019 Bromhexina Info Total
164/231
-+ Oral acetylcysteine 1as e>ecti)e in
pre)enting i&os&ami%e
8/11/2019 Bromhexina Info Total
165/231
8/11/2019 Bromhexina Info Total
166/231
increase% -p less t'an 0.00+6 serum creatinine
%ecrease% -p less t'an 0.06 urine output
increase% -p less t'an 0.00+6 an% so%ium
excretion increase% -p less t'an 0.0=. "'ere
1ere no signi@cant c'anges in li)er &unction or
(loo% pressure. "'e sur)i)al rates at + an%
mont's 1ere , an% =*6 respecti)ely
-inclu%ing patients 1'o 'a% recei)e% li)er
transplants a&ter impro)ement o& renal &unction.
NA7 may o>er a (ri%ging t'erapy6 exten%ing t'e
time a)aila(le &or li)er transplantation -Holt et al6
+333.
6. HIV INFECTION
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult "ossi0l/ #++#&tiv#
DO,'NAON: Adult +$i%
. S$MMAR#
- $/ d#&%#$s# tuo% n#&%osis +$&to% l#v#ls
- $/ d#&%#$s# $&tiv$t#d su""%#sso% lls
- Do#s not $""#$% to #n$n lut$tion#
"%odu&tion
. AD$?"#
a. 'en N
8/11/2019 Bromhexina Info Total
167/231
asymptomatic HIects s'o1e% t'at HIecti)ely
treate% 1it' acetylcysteine +0 eye%rops -Mars'
F 7ooper6 +3*.
(. Se)enteen patients 1it' :eratocon4uncti)itis
an% corneal mucus plaJues respon%e% 1ell to
ocular a%ministration o& acetylcysteine +0 &our
times %aily. 'en acetylcysteine treatment 1as
8/11/2019 Bromhexina Info Total
171/231
%iscontinue%6 plaJues generally %i% not recur
-!raun&el%er et al6 +3.
c. Acetylcysteine to +0 eye%rops -%ilute%
1it' anti(iotic solution 'as also (een reporte%
to (e success&ul in one patient 1it' 9ERA"I"IS
M$7OSA (ut 1it' normal tear secretion an% no
o)ert systemic %isease -S'a1 F asset6 +3G.
"'e patient 1as also treate% 1it' a 'y%rop'ilic
contact lens.
%. Acetylcysteine 0 applie% to t'e eyes e)ery
'ours resulte% in mar:e% impro)ement in
)isual acuity6 relie& o& &oreign (o%y sensation an%
(lep'arospasm6 an% pre)ention o& mucus
accumulation in a patient 1it' :eratocon4uncti)itis
-Messner F ?ei(o1it;6 +3+.
e. A %ou(le
8/11/2019 Bromhexina Info Total
172/231
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult in#++#&tiv#
DO,'NAON: Adult ood
. S$MMAR#- At/l&/st#in# is not #++#&tiv# +o% %#du&in
s#%u li"o"%ot#in &onnt%$tions
. AD$?"#
a. One report in%icate% a =0 to = re%uction
in t'e plasma concentration o& lipoprotein -A
-?p-A in t1o patients gi)en an% G grams Necti)eness o&
t'e com(ination o& A7E"?7S"EINE an%7E!$ROXIME in t'e treatment o& respiratory
tract in&ections in in&ants -Rameng'i et al6 +3*36
c'il%ren -Santagelo et al6 +3*=2 Rameng'i et al6
+3*G an% a%ults -!ogliar%i et al6 +3*G2 Dal
Negro et al6 +3*=2 Bona)ita6 +3*=.
(. Acetylcysteine 1as eLcacious in com(ination
1it' ce&uroxime in curing respiratory tract
in&ections. Sixty
8/11/2019 Bromhexina Info Total
190/231
com(ination o& + g ce&uroxime an% 00 mg
acetylcysteine. 8atients 1ere %i)i%e% into
groups accor%ing to t'e acute or c'ronic nature
o& t'eir respiratory tract %iseases. 8ositi)e
clinical results 1ere o(taine% in , o& t'e ,=
patients. O& a total o& = pat'ogens isolate% in
pretreatment (acteriological tests on sputum
cultures6 only 1ere still %etecta(le a&ter
treatment. "olerance o& t'e treatment 1as goo%
in all patients2 no si%e e>ects o& any :in% 1ere
o(ser)e% -Dal Negro et al6 +3*=.
c. In el%erly an%/or %e(ilitate% patients -n,6
oral N
8/11/2019 Bromhexina Info Total
191/231
1'at (ene@t6 i& any6 acetylcysteine mig't o>er to
patients 1'o are appropriately immuni;e% against
inuen;a -De !lora et al6 +33.
%. A7E"?7S"EINE may (e (ene@cial as an
a%4unct to anti
8/11/2019 Bromhexina Info Total
192/231
-IM. E)i%ence o& o(4ecti)e reco)ery or
impro)ement occurre% in +00 o& +0 c'il%ren6
1it' no toxicity (eing o(ser)e%. It is speculate%
t'at mucolytic t'erapy 1it' acetylcysteine
re%uces trac'eo(ronc'ial secretions 1'ic' coul%
accumulate in t'e perip'eral (ronc'i6 resulting in
mucus plugs 1'ic' &acilitate implantation o&
(acterial organisms -Santangelo et al6 +3*=.
Ho1e)er6 it is unclear i& t'is regimen is superior
to ce&uroxime alone.
(. In an uncontrolle% stu%y6 0 in&ants ranging in
age &rom +0 mont's to years su>ering &rom
recurrent catarr'al (ronc'ial %isease o& (acterial
origin 1ere success&ully treate% 1it' a
com(ination o& acetylcysteine an% ce&uroxime6
a%ministere% intramuscularly at %oses o& += an%
=0 milligrams/:ilogram/%ay6 respecti)ely6 &or a
mean perio% o& +0.G P/< . %ays. 7linical
controls s'o1e% t'at t'e com(ination pro%uce% a
prompt6 mar:e% re%uction in (ronc'ial
'ypersecretion. "'e clinical e>ects6 1'ic' are
%escri(e% in %etail6 an% t'e excellent local an%
systemic tolera(ility o& t'e com(ination s'o1 it
to (e a )ali% &orm o& treatment &or (acterial
(ronc'ial %isease in early in&ancy -Rameng'i et
al6 +3*G.
8/11/2019 Bromhexina Info Total
193/231
AF. S%OGREN&S SYNDROME
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult in#++#&tiv#
DO,'NAON: Adult ood
. S$MMAR#
- At/l&/st#in# $""#$%s to l$& #++i&$&/ in t#
t%#$t#nt o+ 9o%#ns s/nd%o#
. AD$?"#
a. One controlle% stu%y points to a limite% role
&or acetylcysteine in treating S4ogren5s syn%rome.
A trial 1as con%ucte% in +0 patients 1it'
S4ogren5s syn%rome treate% orally 1it' Nects
1ere reporte%.
(. Among 0 patients 1it' SOREN5S
SNDROME 1'ose :eratocon4uncti)itis %i% not
respon% to replacement t'erapy 1it' arti@cial
tears6 , patients impro)e% 1it' + mont's o&
topical treatment 1it' acetylcysteine =6 +
s'o1e% no c'ange6 an% one 1orsene%
-illiamson et al6 +3G.
8/11/2019 Bromhexina Info Total
194/231
AG. SURGERY CARDIOPULMONARY
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult "ossi0l/ #++#&tiv#
DO,'NAON: Adult ood
. S$MMAR#
- On# stud/ so6#d "ositiv# #++#&ts o+
$t/l&/st#in# t%#$t#nt 0#+o%# su%#%/
. AD$?"#
a. 8re
8/11/2019 Bromhexina Info Total
195/231
AH. UNVERRICHTLUNDBORG DISEASE
+. OERIE#
FDA APPROVAL: Adult no! "#di$t%i& no
'FFA*: Adult "ossi0l/ #++#&tiv#
DO,'NAON: Adult "oo%
. S$MMAR#
- n isol$t#d &$s#s $t/l&/st#in# t%#$t#nt $s
%#sult#d in $%#dl/ i"%ov#d +un&tion in
"$ti#nts 6it ,nv#%%i&t-Lund0o% dis#$s#
. AD$?"#
a. A G0
8/11/2019 Bromhexina Info Total
196/231
notice% re%uce% uency o& speec' an%
%eterioration o& 'is a(ility to 1al:. He restarte%
me%ication an% impro)ement 1as e)i%ent in
%ays. 8rior to NA7 treatment6 'e 'a%
experience% a(out +0 generali;e% sei;ures per
year2 %uring +0 mont's o& ta:ing NA76 'e 'a%
only atypical6 (rie& -=< to +0
8/11/2019 Bromhexina Info Total
197/231
acetylcysteine orally G times a %ay -Ben%ere)6
+3**.
4.! COMPARATIVE EFFICACY AND EVALUATION WITH OTHER
SIMILAR THERAPEUTIC AGENTS
A. AMBROXOL
1. CYSTIC FIBROSIS
a. A clinical trial compare% t'e eLcacy o& oral
am(roxol an% N
8/11/2019 Bromhexina Info Total
198/231
a. Intra)enous Necti)e t'an intra)enous cysteamine in
pre)enting 'epatic complications o& se)ere
acetaminop'en o)er%ose in one stu%y -8rescott6
+3*+. Ot'er a%)antages o& Nects6 *6 t'an acetylcysteine6 * -Melica6
+3*. Bot' agents 'a% similar e>ects on
su(4ecti)e an% o(4ecti)e clinical parameters an%
respiratory &unction in patients 1it' c'ronic
(ronc'itis.
!.0 REFERENCES
+. ADE7# Australian Drug E)aluation 7ommittee# Me%icine in
8regnancy < An Australian 7ategorisation o& Ris: o& Drug A(use
in 8regnancy6 r% e%. Australian o)ernment 8u(lis'ing Ser)ice6
7an(erra6 Australia2 +33,.
. AH!S# American Hospital !ormulary Ser)ice Drug In&ormation
+3*3. American Society o& Hospital 8'armacists6 Bet'es%a6 MD6
+3*3.
8/11/2019 Bromhexina Info Total
199/231
. A:erlun% B6 arstan% 76 ?in%e:e B et al# E>ect o& N