Bromhexina Info Total

DRUGDEX DRUG EVALUATIONS
BROMHEXINE
0.0 OVERVIEW
A. BROMHEXINE is an expectorant/mucolytic agent.
B. DOSIN IN!ORMA"ION# $sual %oses o& BROMHEXINE
in c'ronic (ronc'itis 'a)e (een * to +, milligrams -mg.
orally t'ree times %aily or /0 mg t1ice %aily2 'ig'er %oses
-30 mg %aily. 'a)e (een use% 1it' anti(iotics in
(ronc'iectasis2 in patients 1it' S4ogren5s syn%rome6 %oses
o& +, mg orally t'ree times %aily 'a)e (een a%ministere%.
7. 8HARMA7O9INE"I7S# !ollo1ing oral a%ministration o&
BROMHEXINE6 pea: serum concentrations occur in
approximately + 'our2 t'e %rug is meta(oli;e% in t'e li)er
an% excrete% in t'e urine primarily as meta(olites2 t'e
elimination 'al&<li&e o& BROMHEXINE is approximately ,.=
'ours.
D. 7A$"IONS# A%)erse e>ects o& BROMHEXINE inclu%e
gastrointestinal symptoms -nausea6 epigastric pain6
)omiting.6 'ea%ac'e6 %i;;iness6 an% s:in ras'2 ele)ations in
li)er &unction tests 'a)e (een reporte% in a &e1 patients.
E. 7?INI7A? A88?I7A"IONS# Oral BROMHEXINE 'as
pro%uce% clinical (ene@t in some patients 1it' mil% or
mo%erate c'ronic (ronc'itis2 &urt'er stu%ies are nee%e% to
assess its potential role in ot'er con%itions6 inclu%ing
(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. SANONAMS
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%<
to<mo%erate :eratocon4uncti)itis sicca associate%
1it' S4ogren5s syn%rome.
B. Brom'exine is not a)aila(le in t'e $nite%
States. It is mar:ete% un%er t'e tra%e name
Bisol)on-R. in ermany6 Englan%6 Belgium6
!rance6 Italy6 Net'erlan%s6 Nor1ay6 S1e%en6
Australia6 an% Sout' A&rica.
1.2 STORAGE AND STABILITY
A. ORAL
+. BROMHEXINE preparations s'oul% (e
protecte% &rom lig't -Reynol%s6 +33+..
B. SOLUBILITY
+. BROMHEXINE is insolu(le in 1ater. "'e %rug
is sparingly solu(le in alco'ol an% slig'tly
solu(le in c'loro&orm -Reynol%s6 +33+..
1.3 ADULT DOSAGE
1.3.1 NORMAL DOSE
A. ORAL
+. BROMHEXINE /0 milligrams t'ree times
%aily &or += %ays 'as (een gi)en in
com(ination 1it' 7E!"ACIDIME -+ gram
intramuscularly t1ice %aily &or t'e @rst D
%ays. in patients 1it' acute exacer(ations
o& BRON7HIE7"ASIS -Oli)ieri et al6 +33+..
B. $sual %oses o& BROMHEXINE in c'ronic
BRON7HI"IS 'a)e (een * to +,
milligrams orally t'ree times %aily
-Reynol%s6 +33+2 ent et al6 +3,32 Anon6
+3D/2 Hamilton et al6 +3D0.. An alternati)e
%ose is /0 milligrams t1ice %aily -Ealenti F
Marenco6 +3*3.. "'ere is e)i%ence t'at DB
milligrams %aily may pro)i%e some %egree
o& (ene@t in patients 1it' se)ere %isease
-Armstrong6 +3D,..
/. BROMHEXINE * milligrams t'ree times
%aily orally 'as (een com(ine% 1it'
7E8HA?EXIN + gram orally t'ree times
%aily &or t'e treatment o& acute respiratory
tract in&ections in patients 1it' acute or
c'ronic (ronc'itis -Dattoli F ?ec'i6 +3*/2
'i%ini F "om(a6 +3*/.. A %ose o& *
milligrams &our times %aily 'a)e also (een
use% in com(ination 1it'
OXA"E"RA7A7?INE B=0 milligrams &our
times %aily -Matts6 +3DG..
G. "'e usual %ose o& oral BROMHEXINE in
t'e treatment o& SHOREN5S SANDROME
'as (een +, milligrams orally t'ree times
%aily -!rost<?arsen et al6 +3D*2 Mant'orpe
et al6 +3*+..
B. PARENTERAL
+. BROMHEXINE 'as (een (een
a%ministere% intramuscularly an%
intra)enously in usual %oses o& * to BG
milligrams %aily -Reynol%s6 +33+2 Hargra)e
et al6 +3D=.. "'e %rug 'as (een %ilute% in
normal saline -up to G0 milligrams/=00
milliliters. an% =I %extrose in 1ater -up to
B0 milligrams/=00 milliliters. an% gi)en as a
slo1 intra)enous in&usion -Reynol%s6 +33+..
Ho1e)er6 BROMHEXINE appears to (e
1ell a(sor(e% orally6 an% t'e oral route is
pre&erre% 1'ene)er possi(le.
B. A%ministration o& G* milligrams o)er BG
'ours )ia intra)enous in&usion -&ollo1e% (y
oral t'erapy. 1as ine>ecti)e in t'e
treatment o& se)ere ast'ma in + stu%y
-Ru%ol& et al6 +3D*..
1.4 PEDIATRIC DOSAGE
1.4.1 NORMAL DOSE
A. ORAL
+. "'e recommen%e% oral %ose o&
BROMHEXINE &or t'e treatment o&
RES8IRA"ORA DISORDERS is G
milligrams t1ice %aily &or c'il%ren un%er =
years o& age an% G milligrams &our times
%aily &or c'il%ren = to +0 years o& age
-Reynol%s6 +33+..
B. BROMHEXINE B to G milligrams orally
t'ree times %aily -as %rops. 1as reporte%
(ene@cial in treating c'il%ren -un%er =
years o& age. 1it' acute 'ypersecretory
BRON7HO8$?MONARA DISEASE in +
ran%omi;e% stu%y -A;;ollini et al6 +330..
/. Oral BROMHEXINE 0., to 0.*
milligram/:ilogram/%ay6 in / %i)i%e% %oses6
'as (een use% in com(ination 1it'
7E8HA?EXIN -*0 to +00
milligrams/:ilogram/%ay. in t'e treatment o&
upper an% lo1er RES8IRA"ORA "RA7"
IN!E7"IONS in c'il%ren -+ mont' to +G
years o& age. -Boner et al6 +3*G2 7aramia
et al6 +3*G..
G. Oral BROMHEXINE in %oses o& +, to
G* milligrams %aily &or G to , 1ee:s 'as
(een ine>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 +3DB..
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*B2 Hauc' F Han:1it;6 +3D=..
a. 8ea: serum concentrations o&
BROMHEXINE occur approximately +
'our &ollo1ing oral a%ministration
-Bec'gaar% F Nielsen6 +3*B2 Hauc' F
Han:1it;6 +3D=..
(. !ollo1ing a G mg oral %ose o&
BROMHEXINE6 plasma le)els %ecline%
to approximately 0.+G an% 0.=
mcg/m? at * an% BG 'ours post<
a%ministration6 respecti)ely -Hauc' F
Han:1it;6 +3D=..
2.3 ADME
2.3.1 ABSORPTION
A. BIOAEAI?ABI?I"A -!.#
+. Oral6 1ell a(sor(e% -Bec'gaar% F
Nielsen6 +3*B2 Hauc' F Han:1it;6 +3D=2
Se'gal F Mo'an6 +330..
2.3.3 METABOLISM
2.3.3.1 METABOLISM SITES AND KINETICS
A. ?IEER6 extensi)ely -Hauc' F Han:1it;6
+3D=..
2.3.3.2 METABOLITES
A. Am(roxol6 acti)e -Mant'orpe et al6 +3*G2
Mant'orpe F 8rause6 +3*,..
+. At least +0 meta(olites o&
BROMHEXINE 'a)e (een i%enti@e%
-Hauc' F Han:1it;6 +3D=2 Mant'orpe
et al6 +3*G..
2.3.4 EXCRETION
2.3.4.1 BREAST MILK
A. BREAS"!EEDIN# $n:no1n
2.3.4.2 KIDNEY
A. BROMHEXINE is excrete% primarily in
t'e urine as meta(olites -Reynol%s6 +33+2
Bec'gaar% F Nielsen6 +3*B2 Hauc' F
Han:1it;6 +3D=.. Only small amounts
appear as unc'ange% %rug -Bec'gaar% F
Nielsen6 +3*B..
B. Approximately D0I an% **I o& an oral
%ose o& BROMHEXINE 'as (een reco)ere%
in t'e urine 1it'in BG 'ours an% = %ays6
respecti)ely -Hauc' F Han:1it;6 +3D=..
2.3.4.3 OTHER
A. O"HER EX7RE"ION#
+. !E7ES6 GI -Hauc' F Han:1it;6
+3D=..
2.3.5 HALFLIFE
2.3.5.1 PARENT COMPOUND
A. E?IMINA"ION HA?!<?I!E# ,.= 'ours
-Bec'gaar% F Nielsen6 +3*B..
3.0 CAUTIONS
3.1 CONTRAINDICATIONS
A. Hypersensiti)ity to BROMHEXINE
3.2 PRECAUTIONS
A. astric ulcer
3.3 ADVERSE REACTIONS
3.3.3 CENTRAL NERVOUS SYSTEM
A. CENTRAL NERVOUS SYSTEM EFFECTS
+. DICCINESS an% HEADA7HE 'a)e (een
associate% 1it' BROMHEXINE t'erapy in
some patients -Se'gal F Mo'an6 +3302
ent et al6 +3,32 Armstrong6 +3D,..
Di;;iness 'as respon%e% to %ose re%uction
-Armstrong6 +3D,..
3.3.5 GASTROINTESTINAL
A. GASTROINTESTINAL EFFECTS
+. NA$SEA6 E8IAS"RI7 8AIN6
EOMI"IN6 an% DIARRHEA 'a)e (een
reporte% occasionally %uring BROMHEXINE
t'erapy -Se'gal F Mo'an6 +3302 Ste1art et
al6 +3*=2 "'ompson F Ree)e6 +3DB2 ent
et al6 +3,32 Armstrong6 +3D,2 Ealenti F
Marenco6 +3*3.. Alt'oug' in&reJuent6 t'ese
a%)erse e>ects 'a)e necessitate%
1it'%ra1al o& t'erapy in some patients
-?anglan%s6 +3D02 Ayl1ar%6 +3D/2
"'ompson F Ree)e6 +3DB2 Armstrong6
+3D,2 Ealenti F Marenco6 +3*3..
3.3.! KIDNEY"GENITOURINARY
A. ENURESIS
+. Enuresis -1it' or 1it'out %iarr'ea.
necessitate% %iscontinuation o&
BROMHEXINE t'erapy in /I 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
%escri(e% in&reJuently %uring BROMHEXINE
t'erapy -Hamilton et al6 +3D02 Anon6 +3D+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 +3D+..
3.3.$ OCULAR
A. OCULAR EFFECTS
+. Brom'exine -/B mg/%ay &or B+ %ays.
'a% NO E!!E7" on rate o& tear secretion
in =, 'ealt'y )olunteers 1it' normal tear
secretion. Ealues on Sc'irmer5s test I 1ere
t'e same -+/.D 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<treate% patients -Oli)ieri
et al6 +33+2 Ste1art et al6 +3*=..
3.4 TERATOGENICITY"EFFECTS IN PREGNANCY
A. TERATOGENICITY
+. No $.S. !oo% an% Drug A%ministration -!DA.
8regnancy 7ategory a)aila(le.
See Drug 7onsult re&erence# K8RENAN7A
RIS9 7A"EORIESK
B. Australian Drug E)aluation 7ommittee -ADE7.
7ategory A -ADE76 +33,..
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. 8HASI7A? 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"ORA 8ARAME"ERS
+. Hepatic &unction tests -especially %uring
long<term t'erapy.
4.3 PLACE IN THERAPY
A. "'e mainstays o& t'erapy in patients 1it' c'ronic
(ronc'itis are 'y%ration6 'umi%i@cation o& inspire% air6
an% anti(iotics to treat (acterial in&ections. Drug
t'erapy 1it' (eta<B agonists6 "HEO8HA??INE6
antic'olinergics6 an% possi(ly steroi%s may 'elp some
patients6 (ut prolonge% sur)i)al 'as (een ac'ie)e%
only 1it' continuous oxygen t'erapy in se)ere %isease
-AMA6 +33+.. Mucolytic agents suc' as BROMHEXINE
or N<A7E"A?7AS"EINE 'a)e not 'a% a 1ell<%e@ne%
role in t'e treatment o& c'ronic (ronc'itis.
B. "'e mucolytic/expectorant actions o& BROMHEXINE
'a)e (een reporte% to (ene@t some patients 1it' mil%
or mo%erate c'ronic (ronc'itis. It is usually ine>ecti)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 DB 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 S<7ARBOXAME"HA?7AS"EINE.
are also nee%e%6 as are stu%ies to clari&y t'e potential
(ene@ts o& com(ining BROMHEXINE 1it' an anti(iotic.
7. !or ot'er in%ications6 inclu%ing (ronc'iectasis6
S4ogren5s syn%rome6 an% postoperati)e in&ections6
a%%itional controlle% stu%ies are nee%e% to %etermine
t'e role o& BROMHEXINE. "'e %rug appears
ine>ecti)e in otitis me%ia 1it' e>usion.
4.4 MECHANISM OF ACTION"PHARMACOLOGY
A. MECHANISM OF ACTION
+. 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 +3D+..
"'e %rug is a (en;ylamine %eri)ati)e -B<amino<
/6=<%i(romo<N<cyclo'exyl N<met'yl(en;ylamine
'y%roc'lori%e. an% also a %eri)ati)e o&
EASI7INE an% ADHA"ODI7 A7ID6 al:aloi%s
o(taine% &rom t'e plant A%'ato%a )asica. "'e
lea)es o& A%'ato%a )asica 'a)e (een use% &or
t'e treatment o& coug' in In%ia &or o)er =00
years -Reynol%s6 +33+2 Mant'orpe F 8rause6
+3*,..
B. !ollo1ing oral a%ministration6 BROMHEXINE
'as increase% sputum )olume an% re%uce% t'e
)iscosity o& (ronc'ial secretions in c'ronic
(ronc'itis patients -Se'gal F Mo'an6 +3302
Bergogne<Bere;in et al6 +3*=2 Anon6 +3D+.. "'e
%rug 'as (een reporte% to in%uce 'y%rolytic
%epolymeri;ation o& mucoprotein @(ers an%
stimulate acti)ity o& t'e ciliate% epit'elium
-Oli)ieri et al6 +33+2 Ealenti F Marenco6 +3*3..
An increase in lysosomal acti)ity &acilitate% (y
BROMHEXINE 'as (een postulate% -Anon6
+3D+.. Impro)ements in pulmonary &unction in
(ronc'itis patients appear secon%ary to easier
expectoration -Ealenti 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<?arsen et al6 +3D*. an% an increase in
pulmonary sur&actant pro%uction -Se'gal F
Mo'an6 +330.. An e>ect o& BROMHEXINE on
increasing sputum concentrations o& )arious
anti(iotics -eg6 OXA"E"RA7A7?INE6
ERA"HROMA7IN6 AM8I7I??IN6 AMOXI7I??IN.
'as also (een reporte% -Reynol%s6 +33+2 Se'gal
F Mo'an6 +3302 Bergogne<Bere;in et al6 +3*=2
Bac' F ?eary6 +3DB.. Ho1e)er6 some o& t'ese
e>ects -exocrine stimulation6 increase% sputum
concentrations. 'a)e not (een con@rme% in
some stu%ies -A)isar et al6 +33,2 "apper<Hones
et al6 +3*02 Ingol% F S'aylor6 +3D+..
G. It 'as (een suggeste% t'at a meta(olite o&
BROMHEXINE6 am(roxol -NA<*DB.6 may
contri(ute to en'ance% secretion &rom exocrine
glan%s %uring BROMHEXINE a%ministration
-Mant'orpe F 8rause6 +3*,2 Mant'orpe et al6
+3*G..
B. REVIEW ARTICLES
+. 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..
B. An in&ormati)e e%itorial regar%ing t'e use o&
BROMHEXINE in c'ronic (ronc'itis is a)aila(le
-Anon6 +3D+..
4.5 THERAPEUTIC USES
A. ASTHMA
+. OEEREIEM#
FDA APPROVAL: Adult no! "#di$t%i& no
'FF()A)*: Adult in#++#&tiv#
DO),-'N.A.(ON: Adult "oo%
B. S$MMARA#
- '++i&$&/ 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<to<se)ere or se)ere ast'ma
-Heil(orn et al6 +3D,2 Ru%ol& et al6 +3D*..
"'ere is some e)i%ence6 'o1e)er6 t'at
patients 1it' mil% ast'ma or mil%
ast'ma/c'ronic (ronc'itis may experience
some impro)ement 1it' oral BROMHEXINE
-ent et al6 +3,3..
B. BRONCHIECTASIS
+. OEEREIEM#
'FF()A)*: Adult "ossi0l/ #++#&tiv#
B. S$MMARA#
- Aus&ult$to%/ +indin1s $nd +o%&#d
#2"i%$to%/
volu3# in 1 s#&ond (F'V-1) ("ositiv#
&4$n1#
o+ $""%o2i3$t#l/ 155 3illilit#%s) &4$n1#s
do not
$""#$% &lini&$ll/ %#l#v$nt
/. AD$?"#
a. "'e com(ination o& oral BROMHEXINE
/0 milligrams t'ree times %aily &or += %ays
in com(ination 1it' intramuscular
7E!"ACIDIME -+ gram t1ice %aily &or t'e
@rst D %ays. 1as reporte% more e>ecti)e
t'an t'e intramuscular 7E!"ACIDIME
regimen alone in t'e treatment o& acute
exacer(ations o& (ronc'iectasis in a
%ou(le<(lin%6 place(o<controlle% stu%y
in)ol)ing ** patients -Oli)ieri et al6 +33+..
"'e com(ination pro)e% statistically
superior to 7E!"ACIDIME alone 1it'
regar% to expectoration6 sputum Juantity6
an% ascultatory @n%ings. !orce% expiratory
)olume in + secon% -!EE<+. 1as also
impro)e% signi@cantly 1it' t'e com(ination.
Ho1e)er6 many o& t'ese c'anges %i% not
appear to (e rele)ant clinically6 particularly
&or auscultatory @n%ings an% !EE<+
-positi)e c'ange o& approximately +00
milliliters.. 7oug' an% sputum Juality %i%
not %i>er (et1een groups. !urt'er stu%ies
are nee%e% to con@rm t'e potential (ene@ts
o& 'ig'<%ose BROMHEXINE in
exacer(ations o& (ronc'iectasis.
C. BRONCHITIS
+. OEEREIEM#
DO),-'N.A.(ON: Adult 1ood
B. S$MMARA#
- Asso&i$t#d 6it4 &lini&$l 0#n#+it
(in&%#$s#d v#ntil$to%/ &$"$&it/ #$si#%
#2"#&to%$tion&lini&$l i3"%ov#3#nt) in so3# 0ut not
$ll "$ti#nts 6it4 3ild o% 3od#%$t# &4%oni& 0%on&4itis
- (n#++#&tiv# in s#v#%# )7RON() BRON)7(.(8
(+o%&#d #2"i%#d volu3# in 1 s#&ond (F'V-1) o+ l#ss
t4$n 1 lit#%) $lt4ou14 4i14#% dos#s 3$/ "%ovid#
0#n#+it to so3# o+ t4#s# "$ti#nts
- )o30in$tion 6it4 $nti0ioti&s 4$s "%odu&#d
$ddition$l &lini&$l 0#n#+it $nd $ s4o%t#% 4os"it$l
st$/ $s &o3"$%#d to $nti0ioti&s $lon# in so3# %#"o%ts
/. AD$?"#
a. MONO"HERA8A#
-+. 8lace(o<controlle% stu%ies
in)estigating t'e eLcacy o&
BROMHEXINE in c'ronic (ronc'itis
'a)e pro)i%e% conNicting results. In
some trials6 BROMHEXINE in %oses
o& BG to ,0 milligrams orally %aily 'as
(een e>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%
some patients 1it' (ronc'itis an%
ast'ma -ent et al6 +3,32 Ealenti F
Marenco6 +3*3.. Ho1e)er6 ot'er
similarly %esigne% stu%ies &aile% to
%emonstrate signi@cant or consistent
(ene@ts 1it' oral BROMHEXINE BG
to G* milligrams %aily in c'ronic
(ronc'itis patients -Armstrong6 +3D,2
Anon6 +3D/2 "'ompson F Ree)e6
+3DB2 7lar:e et al6 +3DB2 ?anglan%s6
+3D02 Hamilton et al6 +3D0.. 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 +3D0.. 7linical
response to t'e %rug is usually seen
only in patients 1it' slig't<to<mo%erate
air1ay o(struction -ent et al6 +3,32
7'ristiansen et al6 +3D0.2 t'e %rug is
relati)ely ine>ecti)e in se)ere
7HRONI7 BRON7HI"IS -&orce%
expire% )olume in + secon% -!EE<+.
o& less t'an + liter. -7'ristiansen et
al6 +3D02 7'ristiansen et al6 +3D+2
Anon6 +3D+..
-B. 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
-!EE<+. )alues. "'is contention is
supporte% (y anot'er group o&
clinicians -7'ristiansen et al6 +3D02
7'ristiansen et al6 +3D+.6 1'o
reporte% clinical impro)ement in
patients 1it' mo%erate (ronc'itis (ut
not t'ose 1it' more se)ere %isease
-eg6 mean !EE<+ o& less t'an + liter..
In contrast6 respon%ing patients 'a)e
generally 'a% !EE<+ )alues o& greater
t'an +.= liters -ent et al6 +3,32
Ealenti F Marenco6 +3*32 7'ristiansen
et al6 +3D+.. Ho1e)er6 not all patients
1it' mil%er %isease respon%e% in one
stu%y -ent et al6 +3,3.2 in + trial
%emonstrating negati)e results 1it'
BROMHEXINE6 most patients %i% not
'a)e se)ere (ronc'itis -Anon6 +3D/..
"'us6 a)aila(le %ata suggest t'at
some (ut not all patients 1it' slig't<
to<mo%erate air1ay o(struction 1ill
respon% to BROMHEXINE6 1'ereas
patients 1it' !EE<+ )alues o& less
t'an + liter are unli:ely to experience
any clinical (ene@t.
-/. "'e %ose o& BROMHEXINE may
also (e a &actor. In + small +0<1ee:
%ou(le<(lin%6 cross<o)er stu%y6
statistically signi@cant impro)ements
1ere o(ser)e% in pea: expiratory No1
rate -8E!R. an% auscultatory @n%ings6
an% sputum )olume 1as increase%6 in
some patients 1it' mo%erately se)ere
or se)ere (ronc'itis treate% 1it'
BROMHEXINE DB milligrams %aily
-Armstrong6 +3D,.. 8retreatment
&orce% expiratory )olume in + secon%
-!EE<+. )alues in = o& t'e +0
e)alua(le patients range% &rom 0., to
+.B liters. Ot'er parameters o&
eLcacy -!EE<+6 %yspnea6 &reJuency
o& coug'6 ease o& expectoration6
sputum consistency. 1ere not
signi@cantly impro)e% as compare% to
place(o in t'is stu%y. Ho1e)er6
o)erall results %o suggest t'at 'ig'er
%oses o& BROMHEXINE may pro)i%e
some (ene@t to patients 1it' more
se)ere %isease.
(. 7OMBINA"ION "HERA8A#
-+. 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
-nOB3+. or pneumonia -nO+0+. -1it'
clinical assessment &or (acterial
etiology.6 accor%ing to a multi<center6
ran%omi;e%6 %ou(le<(lin% trial -Roa F
Dantes6 +33=.. Enrollees recei)e%
eit'er amoxicillin B=0 milligrams -mg.
1it' (rom'exine * mg -nO+3B. or
amoxicillin alone -B=0 mg2 nOB00.6
(ot' G times a %ay &or D %ays. 7ure
rates a&ter D %ays 1ere G,I &or t'e
(rom'exine/amoxicillin group an% /GI
&or t'e amoxicillin group -pO0.0BB.. O&
t'e patients 1it' pneumonia6 cure
rates 1ere GDI an% BBI6
respecti)ely6 &or t'e com(ination an%
monot'erapy groups -pO0.00*.. By
%ay / o& treatment6 mean symptom
scores &or coug' %iscom&ort6 coug'
&reJuency6 ease o& expectoration6 an%
sputum )olume 1ere signi@cantly
(etter among t'ose treate% 1it'
(rom'exine/amoxicillin -)isual analog
scale.2 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. Se)eral stu%ies 'a)e in)estigate%
t'e (ene@ts o& com(ine%
BROMHEXINE an% anti(iotic
regimens6 &or t'e treatment o&
(acterial in&ection in patients 1it'
exacer(ations o& c'ronic (ronc'itis6
1it' t'e rationale t'at BROMHEXINE
can en'ance anti(iotic acti)ity (y
re%ucing t'e inter&ering e>ect o&
mucoi% secretions6 an% possi(ly
&acilitate a more rapi% response
-Matts6 +3DG2 Boner et al6 +3*G2
Dattoli F ?ec'i6 +3*/.. Some stu%ies
'a)e also reporte% t'at
BROMHEXINE can increase sputum
concentrations o& )arious anti(iotics
-Bergogne<Bere;in et al6 +3*=2 Bac'
F ?eary6 +3DB2 Reynol%s6 +33+2
Se'gal F Mo'an6 +330.6 alt'oug'
ot'er in)estigators 'a)e not con@rme%
t'ese @n%ings -Ingol% F S'aylor6
+3D+..
-/. In uncontrolle% stu%ies6 t'e
com(ination o& BROMHEXINE *
milligrams t'ree times %aily orally plus
7E8HA?EXIN + gram orally t'ree
times %aily 'as (een e>ecti)e in
treating respiratory tract in&ections in
a%ults 1it' acute or c'ronic (ronc'itis
-Dattoli F ?ec'i6 +3*/2 'i%ini F
"om(a6 +3*/.. In t'ese stu%ies6
clinical response 1as consi%ere%
rapi%6 patients expectorate% more
easily6 an% coug'ing 1as re%uce%
1it' t'e com(ination. Similar (ene@ts
in c'il%ren 1it' acute (ronc'itis
recei)ing BROMHEXINE 0., to 0.*
milligram/:ilogram/%ay plus
7E8HA?EXIN *0 to +00
milligrams/:ilogram/%ay -Boner et al6
+3*G.. "'e com(ination o&
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&
OXA"E"RA7A7?INE B=0 milligrams
&our times %aily plus BROMHEXINE *
milligrams &our times %aily -,DI. an%
OXA"E"RA7A7?INE alone -=+I. 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 +3DG.. 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. Ot'ers reporte%
poor response to (ot' t'e
com(ination o& ERA"HROMA7IN an%
BROMHEXINE an% ERA"HROMA7IN
alone in c'ronic (ronc'itis patients2
BROMHEXINE %i% not &acilitate
sputum penetration o&
ERA"HROMA7IN in t'is stu%y
-Maesen et al6 +3*B.. 7linical
response in relation to pulmonary
&unction 1as not a%%resse% in any o&
t'ese stu%ies.
D. OTITIS MEDIA
+. OEEREIEM#
B. S$MMARA#
- (n#++#&tiv#
/. AD$?"#
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 +3DB..
E. POSTOPERATIVE RESPIRATORY INFECTIONS
+. OEEREIEM#
'FF()A)*: Adult #++#&tiv#
B. S$MMARA#
- -$/ #n4$n&# $nti0ioti& $&tivit/ 0/ its
3u&ol/ti& "%o"#%ti#s #n$0lin1 4i14#%
0%on&4i$l &on&#nt%$tions to 0# $&4i#v#d
- -$/ "%#v#nt 3u&us "lu11in1 $nd %#sult$nt
"$%#n&4/3$l &o3"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 oral
BROMHEXINE in re%ucing t'e inci%ence o&
postoperati)e (ronc'opneumonia in 'ig'<
ris: patients un%ergoing a(%ominal surgery.
Hig'<ris: patients 1ere consi%ere% to (e
'ea)y smo:ers an% t'ose 1it' a persistent
pro%ucti)e coug' prior to surgery or a
&orce% expiratory )olume in + secon% as a
percentage o& &orce% )ital capacity o& less
t'an D0 -Hargra)e et al6 +3D=.. Ho1e)er6
t'e num(er o& patients treate% 1as small6
an% a%%itional stu%ies are nee%e% to
con@rm t'ese @n%ings.
F. RESPIRATORY DISORDERS PEDIATRICS
+. OEEREIEM#
'FF()A)*: P#di$t%i&s #++#&tiv#
DO),-'N.A.(ON: P#di$t%i&s +$i%
B. S$MMARA#
- 8i1ni+i&$nt i3"%ov#3#nts in d/s"n#$ $nd
s"utu3 vis&osit/ 4$v# 0##n o0s#%v#d
/. 8EDIA"RI7#
a. BROMHEXINE B to G milligrams orally
t'ree times %aily -as %rops. 1as reporte%
(ene@cial in treating c'il%ren -un%er =
years o& age. 1it' acute 'ypersecretory
(ronc'opulmonary %isease in + ran%omi;e%
stu%y -A;;ollini et al6 +330.. Signi@cant
impro)ements in %yspnea an% sputum
)iscosity 1ere o(ser)e%. In t'is stu%y6
SOBRERO?-R. %rops in %oses o& =0 to
+00 milligrams t1ice %aily 1ere at least as
e>ecti)e as BROMHEXINE.
(. In uncontrolle% stu%ies6 t'e com(ination
o& oral BROMHEXINE 0., to 0.*
milligram/:ilogram/%ay plus 7E8HA?EXIN
*0 to +00 milligrams/:ilogram/%ay 'as (een
e>ecti)e in t'e treatment o& upper an%
lo1er respiratory tract in&ections in c'il%ren
-+ mont' to +G years o& age. -Boner et al6
+3*G2 7aramia et al6 +3*G.. Alt'oug'
(ene@cial mucolytic e>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
+. OEEREIEM#
B. S$MMARA#
- 'n4$n&#d l$&%i3$l s#&%#tion 4$s 0##n
o0s#%v#d in "$ti#nts 6it4 89o1%#n:s s/nd%o3# in so3#
&ont%oll#d studi#s 0ut not ot4#%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
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<controlle% stu%ies 'a)e reporte% t'e
eLcacy o& BROMHEXINE +, milligrams orally
t'ree times %aily in stimulating tear pro%uction in
patients 1it' S4ogren5s syn%rome -Mant'orpe et
al6 +3*+2 !rost<?arsen et al6 +3D*.. In (ot'
trials6 Sc'irmer test an% (rea:<up time -1etting
time. )alues 1ere 'ig'er a&ter BROMHEXINE
treatment as compare% to place(o. Ho1e)er6 no
su(4ecti)e impro)ement 1it' regar% to %ryness o&
t'e eyes or mout' 1as reporte% (y t'e patient
in t'ese stu%ies. One ot'er ran%omi;e% stu%y
-"apper<Hones et al6 +3*0. reporte% no c'ange
in eit'er Sc'irmer test )alues or lacrimal
lyso;yme concentrations in comparison 1it'
place(o in patients 1it' S4ogren5s syn%rome.
Sali)ary No1 rates increase% 1it' (ot' place(o
an% BROMHEXINE6 1it' a tren% to1ar% greater
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% B o& t'e stu%ies
-"apper<Hones et al6 +3*02 !rost<?arsen et al6
+3D*. 'a)e (een critici;e% &or possi(ly
incorporating patients not meeting t'e %iagnostic
criteria &or S4ogren5s syn%rome -eg6 com(ine%
presence o& :eratocon4uncti)itis sicca6 a
connecti)e tissue %isor%er6 an% xerostomia.
-Mac:ie F Seal6 +3D*2 Mant'orpe et al6 +3*0..
%. A meta(olite o& BROMHEXINE6 AMBROXO?
-NA<*DB.6 'as also (een in)estigate% in t'e
treatment o& S4ogren5s syn%rome. It 1as
speculate% t'at t'is meta(olite may (e partly or
1'olly responsi(le &or exocrine stimulatory e>ects
%uring BROMHEXINE a%ministration -Mant'orpe
F 8rause6 +3*,2 Mant'orpe et al6 +3*G..
Ho1e)er6 AMBROXO? ,0 milligrams %aily 1as
ine>ecti)e in impro)ing o(4ecti)e op't'almological
tests in + controlle% stu%y in)ol)ing /, patients
1it' S4ogren5s syn%rome -Mant'orpe et al6 +3*G..
4.! COMPARATIVE EFFICACY AND EVALUATION WITH
OTHER SIMILAR THERAPEUTIC AGENTS
A. AMOXICILLIN
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
-nOB3+. or pneumonia -nO+0+. -1it' clinical
assessment &or (acterial etiology.6
accor%ing to a multi<center6 ran%omi;e%6
%ou(le<(lin% trial -Roa F Dantes6 +33=..
Enrollees recei)e% eit'er amoxicillin B=0
milligrams -mg. 1it' (rom'exine * mg
-nO+3B. or amoxicillin alone -B=0 mg2
nOB00.6 (ot' G times a %ay &or D %ays.
7ure rates a&ter D %ays 1ere G,I &or t'e
(rom'exine/amoxicillin group an% /GI &or
t'e amoxicillin group -pO0.0BB.. O& t'e
patients 1it' pneumonia6 cure rates 1ere
GDI an% BBI6 respecti)ely6 &or t'e
com(ination an% monot'erapy groups
-pO0.00*.. By %ay / o& treatment6 mean
symptom scores &or coug' %iscom&ort6
coug' &reJuency6 ease o& expectoration6
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<acetylcysteine an%
S<car(oxymet'ylcysteine6 'a)e (een
in)estigate% in t'e treatment o& respiratory
%isor%ers. Bot' agents appear to split
%isul@%e (on%s o& mucus glycoproteins6
resulting in re%uce% )iscosity -Marriot6
+3*32 8a)ia et al6 +3*/.. N<Acetylcysteine
'as (een use% (ot' orally an% )ia aerosol6
1'ereas S<car(oxymet'ylcysteine is usually
gi)en orally. N<acetylcysteine %oes not
pro%uce signi@cant impro)ement in patients
1it' c'ronic o(structi)e air1ays %isease
-Marriot6 +3*3.6 may trigger reNex
(ronc'ospasm6 an% is not recommen%e%
&or t'e treatment o& ast'ma -AMA6 +33+..
(. S<7ar(oxymet'ylcysteine is as e>ecti)e
as (rom'exine in impro)ing sputum
consistency an% some symptoms. Ho1e)er6
neit'er agent impro)e% in%ices o&
respiratory &unction. In + %ou(le<(lin% stu%y
in)ol)ing /0 patients 1it' c'ronic (ronc'itis
-//I pre%icte% (aseline &orce% expiratory
)olume in + secon% -!EE<+..6 S<
car(oxymet'ylcysteine syrup -D=0 milligrams
t'ree times %aily. 1as at least as e>ecti)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 No1
rates -Ayl1ar%6 +3D/..
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
a. "'e com(ination o& (rom'exine *
milligrams orally t'ree times %aily an%
cep'alexin + gram orally t'ree times %aily
1as reporte% superior to cep'alexin alone
in t'e same %oses in treating acute
exacer(ations o& c'ronic (ronc'opulmonary
%iseases in + comparati)e trial. Eentilatory
&unction an% clinical symptoms 1ere
impro)e% to a greater %egree in t'e
com(ination group -"urco et al6 +3*/2
8almieri et al6 +3*/..
D. OXYTETRACYCLINE
1. SUMMARY
a. Oxytetracycline plus (rom'exine 1as
similar in response rates as oxytetracycline
alone.
2. BRONCHITIS
a. "'e com(ination o& oxytetracycline B=0
milligrams -mg. &our times %aily plus
(rom'exine * mg &our times %aily 1as
associate% 1it' statistically similar response
rates as oxytetracycline alone -,DI an%
=+I6 respecti)ely. in patients 1it'
exacer(ations o& acute or c'ronic (ronc'itis
in a controlle% stu%y. Hospital stay 1as
s'ortene% in t'e (rom'exine group -3
)ersus ++ %ays. -Matts6 +3DG.. 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<(lin% stu%y
s'o1e% t'at SA?INE SO?$"ION 1as as
e>ecti)e as BROMHEXINE as a ne(uli;ing
agent &or t'e treatment o& c'ronic sinusitis
in ast'matic c'il%ren -nOB0. -Ean Be)er et
al6 +3*D.. "1o milliliters -m?. o& saline or
(rom'exine -B milligrams/m?. 1ere
a%ministere% )ia a porta(le 'ome ne(uli;er
/ to G times a %ay &or B 1ee:s. Ra%iologic
outcomes in%icate% t'at (ot' treatments
in%uce% signi@cant impro)ement compare%
1it' (aseline -p less t'an 0.0+.. Symptom
scores rate% (y in)estigators 1ere eJually
re%uce% &or (ot' types o& ne(uli;ation.
Ho1e)er6 (ase% on X<ray e)i%ence6 saline
solution pro%uce% signi@cantly more
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 -B
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,.
B. 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<patients 1it' c'ronic (ronc'itis -A
report to t'e researc' committee o& t'e Britis' "'oracic
an% "u(erculosis Association.. Br H Dis 7'est +3D/2 ,D#G3<
,0.
G. Anon# Brom'exine -e%itorial.. ?ancet +3D+2 +#+0=*.
=. Armstrong M?# Dou(le<(lin% crosso)er trial o& (rom'exine
-Bisol)on. in t'e treatment o& c'ronic (ronc'itis. Me% H
Aust +3D,2 +#,+B<,+D.
,. A)isar R6 Ro(inson A6 Sa)ir H et al# Oral (rom'exine
'as no e>ect on tear secretion in 'ealt'y su(4ects -letter..
Ann 8'armacot'erapy +33,2 /0#+G3*.
D. Ayl1ar% M# A (et1een<patient6 %ou(le<(lin% comparison
o& S<car(oxymet'ylcysteine an% (rom'exine in c'ronic
o(structi)e (ronc'itis. 7urr Me% Res Opin +3D/2 +#B+3<BBD.
*. A;;ollini E6 Mantega;;a M6 8iceci E et al# So(rerol
-So(repim-R.. a%ministere% %rop1ise to c'il%ren 1it' acute
'ypersecretory (ronc'opulmonary %isease. A controlle% trial
). (rom'exine. 7lin "rials H +3302 BD#BG+<BG3.
3. Bac' 8H F ?eary M88# "'e e>ects o& (rom'exine on
oxytetracycline penetrance into sputum. S A&r Me% H +3DB2
G,#+=+B<+=+G.
+0. Bec'gaar% E F Nielsen A# Bioa)aila(ility o& (rom'exine
ta(lets an% preliminary p'armaco:inetics in 'umans.
Biop'arm Drug Disposit +3*B2 /#//D</GG.
++. Bergogne<Bere;in E6 Bert'elot 6 9a&e H et al#
InNuence o& a Nui%i&ying agent -(rom'exine. on t'e
penetration o& anti(iotics into respiratory secretions. Int H
7lin 8'arm Res +3*=2 =#/G+</GG.
+B. Boner A?6 Antolini I6 Ealletta EA et al# "reatment o&
upper an% lo1er respiratory tract in&ections in c'il%ren (y a
com(ination o& cep'alexin plus (rom'exine# a report on +00
cases. Drugs Exptl 7lin Res +3*G2 +0#G==<G=*.
+/. Busca 6 !ogliar%i !6 Sanc'ioni A et al# 8ost<surgical
(ronc'ial complications. "reatment 1it' cep'alexin plus
(rom'exine. 7lin "rials H +3*/2 B0#++=<++*.
+G. 7aramia 6 7ompagnoni ?6 Eugeni 7E et al#
Respiratory tract in&ections in pae%iatrics. Simultaneous
a%ministration o& cep'alexin an% (rom'exine. Drugs Exptl
7lin Res +3*G2 +0#G=+<G=/.
+=. 7'ristiansen !6 94er H6 Rys:4aer S et al# Brom'exine in
c'ronic (ronc'itis. Br Me% H +3D02 G-DBD.#++D.
+,. 7'ristiansen SB6 94er H6 Rys:4aer S et al# Mucolytic
treatment o& c'ronic (ronc'itis %uring t1o 1inter perio%s.
Scan% H Resp Dis +3D+2 =B#G*<=+.
+D. 7lar:e SM6 7raig M F Ma:in EHB# 7linical trial o&
(rom'exine in se)ere c'ronic (ronc'itis %uring 1inter.
"'orax +3DB2 BD#GB3<G/B.
+*. Dattoli R F ?ec'i A# "'erapy o& acute an% c'ronic
(ronc'itis 1it' cep'alexin an% (rom'exine. 7lin "rials H
+3*/2 B0#+G+<+GD.
+3. Elcoc: HM F ?or% IH# Brom'exine 'y%roc'lori%e in
c'ronic secretory otitis me%ia < a clinical trial. Br H 7lin
8ract +3DB2 B,#BD,<BD*.
B0. !rost<?arsen 96 Isager H F Mant'orpe R# S4ogren5s
syn%rome treate% 1it' (rom'exine# a ran%omise% clinical
stu%y. Br Me% H +3D*2 +#+=D3<+=*+.
B+. ent M6 9no1lson 8A F 8rime !H# E>ect o&
(rom'exine on )entilatory capacity in patients 1it' a )ariety
o& c'est %iseases. ?ancet +3,32 B#+03G<+03,.
BB. 'i%ini O F "om(a A# 7ep'alexin plus (rom'exine in
t'e treatment o& lo1er respiratory tract in&ections.
O(ser)ations on a group o& *0 &emale patients. 7lin "rials
H +3*/2 B0#BG*<B=G.
B/. Hamilton M!D6 8almer 9NE F ent M# Expectorant
action o& (rom'exine in c'ronic o(structi)e (ronc'itis. Br
Me% H +3D02 /#B,0<B,+.
BG. Hargra)e SA6 8almer 9 F Ma:in E# E>ect o&
(rom'exine on t'e inci%ence o& postoperati)e
(ronc'opneumonia a&ter upper a(%ominal surgery. Br H Dis
7'est +3D=2 ,3#+3=<+3*.
B=. Heil(orn H6 8egelo1 9O F O%e(la% E# E>ect o&
(rom'exine an% guaip'enesine on clinical state6 )entilatory
capacity an% sputum )iscosity in c'ronic ast'ma. Scan% H
Resp Dis +3D,2 =D#**<3,.
B,. Ingol% A F S'aylor HM# "'e inNuence o& (rom'exine
-Biosol)on. on t'e le)els o& ampicillin an% oxytetracycline in
sputum. Br H Dis 7'est +3D+2 ,=#BG/<BG,.
BD. Hauc' R F Han:1it; R# "'e a(sorption6 excretion an%
meta(olic pattern o& (rom'exine in man a&ter oral an% i.).
a%ministration. Ar;neim !orsc' +3D=2 B=#+3=G<+3=*.
B*. ?anglan%s HHM# Dou(le<(lin% clinical trial o& (rom'exine
as a mucolytic %rug in c'ronic (ronc'itis. ?ancet +3D02
+#GG*<G=0.
B3. Mac:ie I F Seal DE# S4ogren5s syn%rome6 (rom'exine6
an% tear secretion -letter.. Br Me% H +3D*2 B#,/*.
/0. Maesen !8E6 Da)ies BI6 Brou1ers H et al#
Eryt'romycin an% (rom'exine in acute exacer(ations o&
c'ronic (ronc'itis. Eur H Respir Dis +3*B2 ,/#/B=</B3.
/+. Mant'orpe R6 !rost<?arsen 96 Ho4 ? et al# Brom'exine
treatment o& S4ogren5s syn%rome# e>ect on lacrimal an%
sali)ary secretion6 an% on proteins in tear Nui% an% sali)a.
Scan% H R'eumatol +3*+2 +0#+DD<+*0.
/B. Mant'orpe R6 !rost<?arsen 96 Isager H et al# S4ogren5s
syn%rome treate% 1it' (rom'exine# a reassessment -letter..
Br Me% H +3*02 B*+#+B+,.
//. Mant'orpe R6 Hagen 8etersen S F 8rause H$#
Mucosol)an in t'e treatment o& patients 1it' primary
S4ogren5s syn%rome# results &rom a %ou(le<(lin% cross<o)er
in)estigation. Acta Op't'almologica +3*G2 ,B#=/D<=G+.
/G. Mant'orpe R F 8rause H$# "reatment o& S4ogren5s
syn%rome# an o)er)ie1 -re)ie1.. Scan% H R'eumatol +3*,2
Suppl. ,+#B/D<BG+.
/=. Marriot 7# Drug<mucus actions an% interactions6 in
7'antler E F Ratcli>e NA -e%s.# Mucus an% Relate% "opics
-Symposia o& t'e Society &or Experimental Biology.6 Num(er
X?III. Society &or Experimental Biology6 7am(ri%ge6 +3*32
pp +,/<+DD.
/,. Matts S!# A comparati)e trial o& (rom'exine H7l an%
oxytetracycline in acute an% c'ronic (ronc'itis. Br H 7lin
8ract +3DG2 B*#G0/<G0=.
/D. Oli)ieri D6 7iaccia A6 Marangio E et al# Role o&
(rom'exine in exacer(ations o& (ronc'iectasis. Dou(le<(lin%
ran%omi;e% multicenter stu%y )ersus place(o. Respiration
+33+2 =*#++D<+B+.
/*. 8almieri B6 Monni S6 Misella A et al# "'erapeutic an%
prop'ylactic e>ects o& cep'alexin an% (rom'exine in
respiratory tract complications o& a(%ominal surgery. Int H
7lin 8'armacol "'er "oxicol +3*/2 B+#+G/<+G,.
/3. 8a)ia D6 Sutton 886 ?ope;<Ei%riero M" et al# Drug
e>ects on mucociliary &unction. Eur H Respir Dis +3*/2
,G-suppl +B*.#/0G</+D.
G0. Reynol%s HE! -e%.# Martin%ale# "'e Extra
8'armacopoeia -electronic )ersion.. Microme%ex6 Inc6
Den)er6 7O6 +33+.
G+. Roa 77 Hr F Dantes RB# 7linical e>ecti)eness o& a
com(ination o& (rom'exine an% amoxicillin in lo1er
respiratory tract in&ection2 a ran%omi;e% controlle% trial.
Ar;neim !orsc'/Drug Res +33=2 G=-+.#B,D<BDB.
GB. Ru%ol& M6 Rior%an H!6 rant BHB et al# Brom'exine in
se)ere ast'ma. Br H Dis 7'est +3D*2 DB#/0D</+B.
G/. Se'gal S9 F Mo'an M# Brom'exine -re)ie1.. In%ian
8e%iatr +3302 BD#GD3<G*/.
GG. Ste1art IA6 uy AM6 Allison RS et al# Brom'exine in
t'e treatment o& otitis me%ia 1it' e>usion. 7lin Otolaryngol
+3*=2 +0#+G=<+G3.
G=. "apper<Hones ?M6 Al%re% MH6 7a%ogan SH et al#
S4ogren5s syn%rome treate% 1it' (rom'exine# a
reassessment. Br Me% H +3*02 B*0#+/=,.
G,. "'ompson 9H F Ree)e H# A clinical trial o& (rom'exine.
N C Me% H +3DB2 D,#D/<D,.
GD. "urco 86 8om%ri 76 Coccatellio et al# "'erapy &or
intercurrent respiratory in&ections in 7O?D patients# report
on B00 patients. Int H 7lin 8'armacol +3*/2 B+#B,0<B,B.
G*. Ealenti S F Marenco # Italian multicenter stu%y on t'e
treatment o& c'ronic o(structi)e lung %isease 1it'
(rom'exine. A %ou(le<(lin%6 place(o<controlle% trial.
Respiration +3*32 =,#++<+=.
G3. Ean Be)er H8S6 Bosmans H F Ste)ens MH#
Ne(uli;ation treatment 1it' saline compare% to (rom'exine
in treating c'ronic sinusitis in ast'matic c'il%ren. Allergy
+3*D2 GB#//</,.
#.0 AUTHOR INFORMATION
O%i1in$l "u0li&$tion: 53;1<<2
-ost %#&#nt %#vision: 12;2555
List o+ &ont%i0uto%s:
1. DR,=D'>(R) 'dito%i$l 8t$++
Fo% +u%t4#% in+o%3$tion on &ont%i0utin1 $ut4o%s
s## #dito%i$l 0o$%d listin1s.
-DE+GB3.
E'( )* D)+,-.'/
DRUGDEX DRUG EVALUATIONS
ACETYLCYSTEINE
0.0 OVERVIEW
A. Acetylcysteine is a %eri)ati)e o& t'e amino aci% cysteine.
B. DOSIN IN!ORMA"ION# As a mucolytic6 t'e &ollo1ing
%osing is recommen%e%# ne(uli;e% %oses o& B to = m? o&
a +0I solution2 orally &or a%ults an% a%olescents o)er +G
years o& age6 ,00 mg %aily in + to / %i)i%e% %oses. !or
acetaminop'en o)er%ose6 an oral loa%ing %ose o& +G0
mg/:g is &ollo1e% (y D0 mg/:g e)ery G 'ours &or +D
a%%itional %oses in a%ult an% pe%iatric patients2 alternati)ely6
t'e erman manu&acturer recommen%s IE a%ministration o&
a +=0 mg/:g loa%ing %ose6 &ollo1e% (y =0 mg/:g in&use%
o)er G 'ours6 &ollo1e% (y +00 mg/:g in&use% o)er +, 'ours
&or a total %ose o& /00 mg/:g in&use% o)er B0 'ours an%
+= minutes.
7. 8HARMA7O9INE"I7S# "'e %rug is 1ell<a(sor(e% orally2
mucolytic e>ects occur 1it'in G= min an% persist &or +00
min2 some %egree o& 'epatic meta(olism occurs6 1it' renal
excretion o& meta(olites an% unc'ange% compoun%.
D. 7A$"IONS# "'e primary toxicity o& N<acetylcysteine
-NA7. consists o& nausea an% )omiting6 particularly a&ter
oral t'erapy. Many cases o& anap'ylaxis 'a)e (een
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. SANONAMS#
1. A&#til&ist#in$
2. A&#t/l&/st#in n$t%iu3
3. )A8 ?1?-<1-1
4. D$&ist#in
7. OR8HAN DR$ S"A"$S
+. Acetylcysteine intra)enous -IE. 'as (een
%esignate% an orp'an pro%uct &or use in t'e
treatment o& mo%erate to se)ere acetaminop'en
o)er%ose.
1.2 STORAGE AND STABILITY
A. ORAL
+. Acetylcysteine is inacti)ate% (y pure O-B.
-?a1son F Saggers6 +3,=.6 (ut t'is is pre)ente%
in t'e commercial pro%uct (y inclu%ing ED"A.
B. Solutions &or oral use retain t'eir potency &or
at least 3, 'ours un%er re&rigeration 1'en pre<
pac:e% in unit %ose containers. lass (ottles
1it' polyet'ylene line% scre1 caps s'oul% (e
use% &or oral unit %ose storage -8ers 7omm6
+3*/..
/. Acetylcysteine e>er)escent ta(lets s'oul% (e
store% in a %ry place (elo1 B= %egrees 7elsius
-DD %egrees !a'ren'eit.2 t'e s'el& li&e is / years
(eyon% 1'ic' use is not recommen%e% -!ac'in&o
!luimucil-R. a:ut6 +33D..
B. PARENTERAL
+. Acetylcysteine anti%ote solution 'as a s'el&
li&e o& / years at room temperature -!ac'in&o
!luimucil-R. Anti%ot6 +33D..
C. RESPIRATORY
+. Solutions &or respiratory t'erapy retain t'eir
potency &or + mont' 1'en &ro;en in syringes
1it'out ru((er plungers or ot'er parts -8ers
7omm6 +3*/..
B. "'ere are se)eral reports on t'e clinical use
o& acetylcysteine an% isoproterenol -Barton6 +3DG2
7'o%as' et al6 +3D=2 rater F 7ato6 +3D/..
Acetylcysteine 1it' t'is particular (ronc'o%ilator
'as (een e)aluate% an% sta(ility 1as retaine%
&or , mont's -"alley et al6 +3D/..
D. OPHTHALMIC SOLUTIONS
+. An extemporaneous op't'almic solution
containing acetylcysteine +0I6 %iso%ium e%etate
0.0B=I6 an% c'loro(utanol 0.=I -in an arti@cial<
tear (ase. 1as sta(le &or ,0 %ays at B to *
%egrees 7. "'e same solution store% at room
temperature -B/ to B= %egrees 7. 1as sta(le &or
less t'an D %ays. Similar solutions in 1'ic' t'e
concentration o& %iso%ium e%etate 1as 0.D=I or
0.+I 1ere sta(le at room temperature &or G0
an% =0 %ays6 respecti)ely -Anai;i et al6 +33D..
1.3 ADULT DOSAGE
1.3.1 NORMAL DOSE
A. ORAL
1. ACETAMINOPHEN POISONING
a. "'e acute ingestion o&
acetaminop'en in Juantities o& +=0
milligrams/:ilogram or greater may
result in 'epatic toxicity.
Acetylcysteine is most e>ecti)e in
pre)enting acetaminop'en<in%uce%
li)er in4ury &ollo1ing o)er%ose i&
a%ministere% 1it'in +, 'ours
postingestion. ?oa%ing %ose is +G0
milligrams/:ilogram orally &ollo1e% (y
D0 milligrams/:ilogram orally e)ery G
'ours &or +D a%%itional %oses
-8eterson F Rumac:6 +3DD2 8eterson
F Rumac:6 +3D*..
(. "'e manu&acturer recommen%s t'at
regar%less o& t'e Juantity o&
acetaminop'en reporte% to 'a)e (een
ingeste%6 acetylcysteine s'oul% (e
a%ministere% i& BG 'ours or less 'a)e
elapse% &rom t'e time o& t'e reporte%
ingestion o& an o)er%ose. Do not 1ait
&or t'e result o& t'e la(oratory assays
&or acetaminop'en le)els. "'e
&ollo1ing proce%ures are
recommen%e% -8ro% In&o
Mucomyst-R.6 +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 B0 minutes.
-B. 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.
-/. 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& D0
milligrams/:ilogram. Maintenance
%oses s'oul% (e repeate% at G<
'our inter)als &or a total o& +D
%oses unless t'e acetaminop'en
assay re)eals a nontoxic le)el.
-,. I& t'e patient )omits t'e
loa%ing %ose or any
maintenance %ose 1it'in + 'our
o& a%ministration6 repeat t'at
%ose. I& t'e patient is
persistently una(le to retain t'e
acetylcysteine6 it may (e
a%ministere% (y %uo%enal
intu(ation.
-D. Repeat SO"6 S8"6
an% electrolytes %aily i& t'e
acetaminop'en plasma le)el is
in t'e potentially toxic range.
c. An alternati)e protocol recommen%s
t'e same %oses (ut continuing e)ery
G 'ours only until acetaminop'en is
no longer %etecta(le in t'e serum. A
retrospecti)e case series -nOD=.
s'o1e% t'is to (e e>ecti)e an% to
re%uce t'e mean treatment %uration
to /+ 'ours -Moo et al6 B000..
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 +33D..
B. ORAL SOLUTION PREPARATION
+. "'e B0I acetylcysteine solution s'oul%
(e %ilute% 1it' cola %rin:s6 !resca-R.6 or
ot'er so&t %rin:s to a @nal concentration o&
=I. I& a%ministere% )ia gastric tu(e or
Miller<A((ott tu(e6 1ater may (e use% as
t'e %iluent. "'e %ilution s'oul% (e &res'ly
prepare% an% utili;e% 1it'in one 'our.
C. ORAL DOSAGE GUIDE AND PREPARATION
+. Doses o& oral acetylcysteine in relation
to (o%y 1eig't are -8ro% In&o
Mucomyst-R.6 +33,.#
LOAD(N= DO8'@@
A#i14t A&#t- -u&o- Dilu- .ot$l
(B1) /l&/s- 3/st #nt CD sol-
t#in# 25D (3L) ution
(1) (3L) (3L)
---------------------------------------
155-15< 1C 7C 22C 355
<5-<< 14 75 215 285
85-8< 13 ?C 1<C 2?5
75-7< 11 CC 1?C 225
?5-?< 15 C5 1C5 255
C5-C< 8 45 125 1?5
45-4< 7 3C 15C 145
35-3< ? 35 <5 125
25-2< 4 25 ?5 85
-A(N.'NAN)' DO8'@@
(1) (3L) (3L)
---------------------------------------
155-15< 7.C 37 113 1C5
<5-<< 7 3C 15C 145
85-8< ?.C 33 <7 135
75-7< C.C 28 82 115
?5-?< C 2C 7C 155
C5-C< 4 25 ?5 85
45-4< 3.C 18 C2 75
35-3< 3 1C 4C ?5
25-2< 2 15 35 45
@@(+ "$ti#nt 6#i14s l#ss t4$n 25 B1
(usu$ll/ "$ti#nts /oun1#% t4$n ?
/#$%s)
&$l&ul$t# t4# dos# o+ -u&o3/st(R).
'$&4 3illilit#% o+ 25D -/&o3/st(R)
&ont$ins
255 3illi1%$3s o+ $&#t/l&/st#in#. .4#
lo$din1
dos# is 145 3illi1%$3s;Bilo1%$3. .4#
3$int#n$n&#
dos# is 75 3illi1%$3s;Bilo1%$3. .4%##
(3) 3illilit#%s
o+ dilu#nt $%# $dd#d to #$&4 3illilit#%
o+ 25D -u&o3/st(R). Do not d#&%#$s#
t4#
"%o"o%tion o+ dilu#nt.
D. INTERPRETATION OF ACETAMINOPHEN
ASSAY
+. M'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. Ealues a(o)e t'e soli% line
connecting B00 micrograms/milliliter at G
'ours 1it' =0 micrograms/milliliter at +B
'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-R.6
+33,..
E. INTRAVENOUS
0. SUMMARY
-+. "'ere is NO !DA<appro)e%
commercially a)aila(le
intra)enous -IE. &ormulation o&
acetylcysteine in t'e $nite%
States. "'e oral/in'alation
preparation is NO" oLcially
appro)e% &or IE use2 'o1e)er6
t'e oral &ormulation o&
acetylcysteine 'as (een
a%ministere% intra)enously in
patients una(le to tolerate
acetylcysteine orally.
-B. !OR"A<EIH" HO$R
8RO"O7O?# Dilute B0I solution
+#= in %extrose =I in 1ater
-D=M. an% gi)e slo1ly o)er one
'our. I& an a%)erse reaction
occurs6 %ip'en'y%ramine is
gi)en an% su(seJuent %oses are
gi)en o)er B 'ours. "'e initial
%ose is +G0 milligrams/:ilogram6
&ollo1e% (y D0
milligrams/:ilogram e)ery G
'ours &or a total o& +/ %oses
-Smil:stein et al6 +33+..
-/. "MEN"A HO$R
8RO"O7O?# A%minister +=0
milligrams/:ilogram in B00
milliliters =I %extrose -D=M.
o)er += minutes6 &ollo1e% (y =0
milligrams/:ilogram in =00
milliliters D=M o)er G 'ours6
&ollo1e% (y +00
milligrams/:ilogram in + liter
D=M o)er t'e next +, 'ours
-8rescott et al6 +3D32 Mestman6
+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<relate%6 (ut anap'ylactoi%
reactions 'a)e occurre%..
(. One stu%y e)aluate% a G*<'our
intra)enous N<acetylcysteine treatment
protocol -Smil:stein et al6 +33+.. "'e
protocol calle% &or a loa%ing %ose o&
+G0 milligrams/:ilogram intra)enously
&ollo1e% (y +B %oses o& D0
milligrams/:ilogram e)ery G 'ours.
Base% on a)aila(le %ata6 it is eJual
to DB<'our oral an% B0<'our IE
treatment protocols 1'en starte% early
an% superior to t'e B0<'our IE
regimen 1'en treatment is %elaye%.
c. Dosing in&ormation is as &ollo1s
-Mestman6 +3*3.# 8atients 1'o
present 1it' toxic le)els o&
acetaminop'en less t'an +0 'ours
a&ter ingestion s'oul% recei)e
acetylcysteine intra)enously -IE. &or
B0 'ours -+=0 milligrams/:ilogram o&
(o%y 1eig't as a (olus %ose6
&ollo1e% (y =0 milligrams/:ilogram &or
G 'ours an% t'en +00
milligrams/:ilogram &or +, 'ours..
8atients 1'o present 1it' toxic le)els
o& acetaminop'en more t'an +0 'ours
acetylcysteine IE &or G* 'ours -+=0
milligrams/:ilogram as a (olus %ose6
G 'ours an% t'en B*,
milligrams/:ilogram &or GG 'ours..
Hemoper&usion may (e o& )alue an%
s'oul% (e consi%ere% &or patients
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 B00 m?
=I Dextrose 1it' electrolyte a%%iti)e
o)er += minutes6 &ollo1e% (y =0
mg/:g in =00 m? =I Dextrose 1it'
electrolyte a%%iti)e o)er G 'ours6
&ollo1e% (y +00 mg/:g in +000 m?
=I Dextrose 1it' electrolyte a%%iti)e
o)er +, 'ours6 &or a total %ose o&
/00 mg/:g o)er B0 'ours an% +=
minutes. IM8OR"AN" NO"E# "'e
amount o& =I Dextrose 1it'
electrolyte a%%iti)e is calculate% &or a
D0 :g person6 s'oul% t'e patient
1eig' less6 t'is amount must (e
a%4uste% accor%ing to t'e gui%elines
&or intra)enous glucose a%ministration
-!ac'in&o !luimucil-R. Anti%ote6 +33D..
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 BG '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% B00 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 +33D..
2. ACRYLONITRILE POISONING
0. INHALATIVE OR DERMAL
POISONING
112 NONSEVERE POISONING
-a. "reatment o& non<
se)ere in'alati)e or %ermal
poisoning s'oul% (egin
1it' +=0 milligram/:ilogram
acetylcysteine in B00 m?
=I Dextrose 1it'
electrolyte a%%iti)e IE o)er
+= minutes2 t'e patient
s'oul% t'en (e o(ser)e%
&or se)eral 'ours e)en i&
'e/s'e &eels @ne2 i&
necessary6 t'e remain%er
o& t'e !luimucil-R. Anti%ot
protocol &or acetaminop'en
poisoning may (e &ollo1e%
-!ac'in&o !luimucil-R.
Anti%ot6 +33D..
122 SEVERE POISONING
-a. "reatment gui%elines
&or se)ere in'alati)e or
%ermal acrylonitrile
poisoning are i%entical to
t'ose &or IE treatment o&
acetaminop'en poisoning
-!ac'in&o !luimucil-R.6
+33D..
3. ORAL POISONING
-+. !irst<line treatment &or oral
acrylonitrile poisoning s'oul% (e
treatment 1it' G<
%imet'ylaminop'enol -DMA8. at
a %ose o& / to G
milligrams/:ilogram IE6 &ollo1e%
(y so%ium t'iosul&ate +00
milligrams/:ilogram slo1 IE
in&usion2 t'en acetylcysteine IE
anti%ote t'erapy may (e
employe% -!ac'in&o
!luimucin-R.Anti%ot6 +33D..
3. METHACRYLONITRILE POISONING
a. !irst<line t'erapy &or
met'acrylonitrile poisoning s'oul% (e
treatment 1it' G<%imet'ylaminop'enol
-DMA8. at a %ose o& / to G
milligrams/:ilogram IE6 &ollo1e% (y
so%ium t'iosul&ate +00
milligrams/:ilogram slo1 IE in&usion2
t'en acetylcysteine IE anti%ote
t'erapy may (e employe% -!ac'in&o
!luimucin-R. Anti%ot6 +33D..
F. INTRAVENOUS RATE OF ADMINISTRATION
+. A%)erse reactions to intra)enous
acetylcysteine appear to (e rate<%epen%ent.
Intra)enous acetylcysteine s'oul% (e
a%ministere% slo1ly o)er + 'our2 'o1e)er i&
an a%)erse reaction occurs6
%ip'en'y%ramine is gi)en an% su(seJuent
%oses are gi)en o)er B 'ours to minimi;e
complications -Smil:stein et al6 +33+2
"enen(ein6 +3*G..
G. RECTAL
a. "'ere are no reports o&
acetylcysteine (eing a%ministere%
rectally &or treatment o&
acetaminop'en poisoning. "'e extent
o& its a(sorption )ia t'e rectum is not
:no1n -8ers 7omm6 +3*/2 8ers
7omm6 +3*/a.. Rectal a%ministration
o& acetylcysteine solution is not
recommen%e% &or treatment o&
acetaminop'en o)er%ose. !or patients
not a(le to retain oral %oses o&
acetylcysteine6 a%ministration o&
%ilute% %oses )ia nasogastric tu(e or
(y slo1 intra)enous in&usion may (e
trie%. An intra)enous &ormulation o&
acetylcysteine is a)aila(le in t'e
$nite% States un%er an in)estigational
protocol t'roug' participating poison
centers.
2. MECONIUM ILEUS
a. Acetylcysteine enemas toget'er
1it' acetylcysteine orally 'a)e (een
use% 1it' apparent success in
neonates6 c'il%ren6 an% a%ults 1it'
(o1el o(struction %ue to meconium
ileus or meconium ileus eJui)alent. A
GI to ,I acetylcysteine enema
-%ilute% in +00 to /00 milliliters o&
1ater or normal saline. a%ministere%
e)ery , to +B 'ours appears to (e
e>ecti)e an% sa&e6 (ut 'ig'er
concentrations 'a)e (een use% -Spiro6
+3DD2 Ho%son et al6 +3D,2 Derman et
al6 +3D=2 S'a16 +3,32 Simpson et al6
+3,*..
H. RESPIRATORY ADMINISTRATION
1. PULMONARY DISORDERS
a. Acetylcysteine 'as (een
a%ministere% )ia trac'eostomy6
intratrac'eal cat'eter6 ne(uli;er6
intermittent positi)e pressure (reat'ing
-I88B.6 en%otrac'eal tu(e an%
cannula -Me((6 +3,B.. It is generally
&elt t'at %irect instillation or I88B are
muc' superior to ne(uli;ation -8oppe6
+3,G2 Miller6 +3D/.. M'en
a%ministere% (y %irect instillation6 + to
B milliliters o& a +0I to B0I solution
may (e gi)en as o&ten as e)ery 'our.
M'en use% &or t'e routine care o&
patients 1it' trac'eostomy6 + to B
milliliters o& a +0I to B0I solution
may (e a%ministere% e)ery + to G
'ours (y instillation into t'e
trac'eostomy -8ro% In&o Mucomyst-R.6
+33,.. A %osage o& B to = milliliters
o& t'e +0I solution is as e>ecti)e
an% pro%uces less (ronc'oconstriction
t'an 'ig'er -B0I. concentrations
-Hirsc' F 9ory6 +3,D..
(. M'en ne(uli;e% into a &ace mas:6
mout' piece6 or trac'eostomy6 + to
+0 milliliters o& t'e B0I solution or B
to B0 milliliters o& t'e +0I solution
may (e gi)en e)ery B to , 'ours.
"'e recommen%e% %ose &or most
patients is / to = milliliters o& t'e
B0I solution or , to +0 milliliters o&
t'e +0I solution / to G times %aily
-8ro% In&o Mucomyst-R.6 +33,..
c. "'e B0I solution may (e %ilute%
to a lesser concentration 1it' eit'er
so%ium c'lori%e &or in4ection6 so%ium
c'lori%e &or in'alation6 sterile 1ater &or
in4ection6 or sterile 1ater &or
in'alation. "'e +0I solution may (e
use% un%ilute%. Any unuse% portion o&
t'e solution s'oul% (e store% in t'e
re&rigerator an% use% 1it'in 3, 'ours
-8ro% In&o Mucomyst-R.6 +33,..
%. !or treatment o& pulmonary
complications o& surgery or
posttraumatic c'est con%itions6 + to B
milliliters o& B0I acetylcysteine
solution or B to G milliliters o& +0I
solution may (e gi)en e)ery + to G
'ours )ia a syringe attac'e% to t'e
intratrac'eal cat'eter2 B to = milliliters
o& t'e B0I solution may (e
intro%uce% 1it' a syringe t'roug' a
trac'eal cat'eter 1'en contact 1it' a
particular segment o& t'e
(ronc'opulmonary tree is %esire%
-8ro% In&o Mucomyst-R.6 +33,2 AH!S6
+3*3..
1.4 PEDIATRIC DOSAGE
1.4.1 NORMAL DOSE
A. ORAL
a. "'e acute ingestion o&
acetaminop'en in Juantities o& +=0
milligrams/:ilogram or greater may
result in 'epatic toxicity.
Acetylcysteine is most e>ecti)e in
pre)enting acetaminop'en<in%uce%
li)er in4ury &ollo1ing o)er%ose i&
a%ministere% 1it'in +, 'ours
postingestion. ?oa%ing %ose is +G0
milligrams/:ilogram orally &ollo1e% (y
D0 milligrams/:ilogram orally e)ery G
'ours &or +D a%%itional %oses
-8eterson F Rumac:6 +3DD2 8eterson
F Rumac:6 +3D*..
(. "'e manu&acturer recommen%s t'at
regar%less o& t'e Juantity o&
acetaminop'en reporte% to 'a)e (een
ingeste%6 acetylcysteine s'oul% (e
a%ministere% i& BG 'ours or less 'a)e
elapse% &rom t'e time o& t'e reporte%
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-R.6 +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 B0 minutes.
-B. 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.
-/. Bloo% s'oul% (e %ra1n &or
acetaminop'en plasma assay
an% &or (aseline SO"6 S8"6
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& D0
milligrams/:ilogram. Maintenance
%oses s'oul% (e repeate% at G<
'our inter)als &or a total o& +D
%oses unless t'e initial
acetaminop'en assay re)eals a
nontoxic le)el.
-,. I& t'e patient )omits t'e
loa%ing %ose or any
maintenance %ose 1it'in + 'our
o& a%ministration6 repeat t'at
%ose. I& t'e patient is
persistently una(le to retain t'e
acetylcysteine6 it may (e
a%ministere% (y %uo%enal
intu(ation.
-D. Repeat SO"6 S8"6
an% electrolytes %aily i& t'e
acetaminop'en plasma le)el is
in t'e potentially toxic range.
2. MUCOLYTIC
a. 7'il%ren , to +G years6 /00 to G00
mg %aily in / to G %i)i%e% %oses2 an%
c'il%ren B to = years o& age6 B00 to
/00 mg %aily in B to / %i)i%e% %oses
-!ac'in&o !luimucil-R. a:ut6 +33D..
B. ORAL SOLUTION PREPARATION
+. "'e B0I acetylcysteine solution s'oul%
(e %ilute% 1it' cola %rin:s6 !resca-R.6 or
ot'er so&t %rin:s to a @nal concentration o&
=I. I& a%ministere% )ia gastric tu(e or
Miller<A((ott tu(e6 1ater may (e use% as
t'e %iluent. "'e %ilution s'oul% (e &res'ly
prepare% an% utili;e% 1it'in one 'our.
C. ORAL DOSAGE GUIDE AND PREPARATION
+. Doses o& oral acetylcysteine in relation
to (o%y 1eig't are -8ro% In&o
Mucomyst-R.6 +33,.#
LOAD(N= DO8'@@
(1) (3L) (3L)
---------------------------------------
155-15< 1C 7C 22C 355
<5-<< 14 75 215 285
85-8< 13 ?C 1<C 2?5
75-7< 11 CC 1?C 225
?5-?< 15 C5 1C5 255
C5-C< 8 45 125 1?5
45-4< 7 3C 15C 145
35-3< ? 35 <5 125
25-2< 4 25 ?5 85
-A(N.'NAN)' DO8'@@
(1) (3L) (3L)
---------------------------------------
155-15< 7.C 37 113 1C5
<5-<< 7 3C 15C 145
85-8< ?.C 33 <7 135
75-7< C.C 28 82 115
?5-?< C 2C 7C 155
C5-C< 4 25 ?5 85
45-4< 3.C 18 C2 75
35-3< 3 1C 4C ?5
25-2< 2 15 35 45
@@(+ "$ti#nt 6#i14s l#ss t4$n 25 B1
(usu$ll/ "$ti#nts /oun1#% t4$n ?
/#$%s) &$l&ul$t# t4# dos# o+ -u&o3/st(R). '$&4
3illilit#% o+ 25D -/&o3/st(R) &ont$ins 255
3illi1%$3s o+ $&#t/l&/st#in#. .4# lo$din1 dos#
is 145 3illi1%$3s;Bilo1%$3. .4# 3$int#n$n&#
dos# is 75 3illi1%$3s;Bilo1%$3. .4%## (3)
3illilit#%s o+ dilu#nt $%# $dd#d to #$&4
3illilit#% o+ 25D -u&o3/st(R). Do not d#&%#$s#
t4# "%o"o%tion o+ dilu#nt.
D. INTERPRETATION OF ACETAMINOPHEN
ASSAY
+. M'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. Ealues a(o)e t'e soli% line
connecting B00 micrograms/milliliter at G
'ours 1it' =0 micrograms/milliliter at +B
'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-R.6
+33,..
E. INTRAVENOUS
0. SUMMARY
-+. "'ere is NO !DA<appro)e%
commercially a)aila(le sterile6
pyrogen<&ree6 intra)enous -IE.
&ormulation o& acetylcysteine in
t'e $nite% States. "'e
oral/in'alation preparation is
NO" oLcially appro)e% &or IE
use. 8yrogen<&ree intra)enous
acetylcysteine is a)aila(le
in)estigationally ON?A t'roug'
participating poison centers.
"'ere are B intra)enous
protocols currently un%er
in)estigation.
-B. !OR"A<EIH" HO$R
8RO"O7O?# Dilute B0I solution
+#= in %extrose =I in 1ater
-D=M. an% gi)e slo1ly o)er one
'our. I& an a%)erse reaction
occurs6 %ip'en'y%ramine is
gi)en an% su(seJuent %oses are
gi)en o)er B 'ours. "'e initial
%ose is +G0 milligrams/:ilogram6
&ollo1e% (y D0
milligrams/:ilogram e)ery G
'ours &or a total o& +/ %oses
-Smil:stein et al6 +33+..
-/. "MEN"A HO$R
8RO"O7O?# A%minister +=0
milligrams/:ilogram in B00
milliliters D=M o)er += minutes6
&ollo1e% (y =0
milligrams/:ilogram in =00
milliliters D=M o)er G 'ours6
&ollo1e% (y +00
milligrams/:ilogram in + liter
D=M o)er t'e next +, 'ours
-8rescott et al6 +3D32 Mestman6
+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<relate%6 (ut anap'ylactoi%
reactions 'a)e occurre%..
(. Intra)enous acetylcysteine is sa&e
an% e>ecti)e &or pre)enting t'e
'epatic an% renal toxicities &ollo1ing
o)er%ose o& acetaminop'en -8rescott6
+3*+.. Similar @n%ings 1ere reporte%
else1'ere -S'en&el% F O'6 +3*0..
c. Dosing in&ormation is as &ollo1s
-Mestman6 +3*3.# 8atients 1'o
present 1it' toxic le)els o&
acetaminop'en less t'an +0 'ours
acetylcysteine intra)enously &or B0
'ours -+=0 milligrams/:ilogram o&
(o%y 1eig't as a (olus %ose6
G 'ours an% t'en +00
milligrams/:ilogram &or +, 'ours..
8atients 1'o present 1it' toxic le)els
o& acetaminop'en more t'an +0 'ours
acetylcysteine IE &or G* 'ours -+=0
milligrams/:ilogram as a (olus %ose6
G 'ours an% t'en B*,
milligrams/:ilogram &or GG 'ours..
Hemoper&usion may (e o& )alue an%
s'oul% (e consi%ere% &or patients
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.
F. INTRAVENOUS RATE OF ADMINISTRATION
+. A%)erse reactions to intra)enous
acetylcysteine appear to (e rate<%epen%ent.
Intra)enous acetylcysteine s'oul% (e
a%ministere% slo1ly o)er + 'our2 'o1e)er i&
an a%)erse reaction occurs6
%ip'en'y%ramine is gi)en an% su(seJuent
%oses are gi)en o)er B 'ours to minimi;e
complications -Smil:stein et al6 +33+2
"enen(ein6 +3*G..
G. RECTAL
a. "'ere are no reports o&
acetylcysteine (eing a%ministere%
rectally &or treatment o&
acetaminop'en poisoning. "'e extent
o& its a(sorption )ia t'e rectum is not
:no1n -8ers 7omm6 +3*/2 8ers
7omm6 +3*/a.. Rectal a%ministration
o& acetylcysteine solution is not
recommen%e% &or treatment o&
acetaminop'en o)er%ose. !or patients
not a(le to retain oral %oses o&
acetylcysteine6 a%ministration o&
%ilute% %oses )ia nasogastric tu(e or
(y slo1 intra)enous in&usion may (e
trie%. An intra)enous &ormulation o&
acetylcysteine is a)aila(le in t'e
$nite% States un%er an in)estigational
protocol t'roug' participating poison
centers.
2. MECONIUM ILEUS
a. Acetylcysteine enemas toget'er
1it' acetylcysteine orally 'a)e (een
use% 1it' apparent success in
neonates6 c'il%ren6 an% a%ults 1it'
(o1el o(struction %ue to meconium
ileus or meconium ileus eJui)alent. A
GI to ,I acetylcysteine enema
-%ilute% in +00 to /00 milliliters o&
1ater or normal saline. a%ministere%
e)ery , to +B 'ours appears to (e
e>ecti)e an% sa&e6 (ut 'ig'er
concentrations 'a)e (een use% -Spiro6
+3DD2 Ho%son et al6 +3D,2 Derman et
al6 +3D=2 S'a16 +3,32 Simpson et al6
+3,*..
H. RESPIRATORY ADMINISTRATION
1. PULMONARY DISORDERS
a. Acetylcysteine 'as (een a%ministere% )ia
trac'eostomy6 intratrac'eal cat'eter6
ne(uli;er6 intermittent positi)e pressure
(reat'ing -I88B.6 en%otrac'eal tu(e an%
cannula -Me((6 +3,B.. It is generally &elt
t'at %irect instillation or intermittent positi)e
pressure (reat'ing -I88B. are muc'
superior to ne(uli;ation -8oppe6 +3,G2
Miller6 +3D/.. M'en a%ministere% (y %irect
instillation6 + to B milliliters o& a +0I to
B0I solution may (e gi)en as o&ten as
e)ery 'our. M'en use% &or t'e routine care
o& patients 1it' trac'eostomy6 + to B
milliliters o& a +0I to B0I solution may (e
a%ministere% e)ery + to G 'ours (y
instillation into t'e trac'eostomy -8ro% In&o
Mucomyst-R.6 +33,.. A %osage o& B to =
milliliters o& t'e +0I solution is as e>ecti)e
an% pro%uces less (ronc'oconstriction t'an
'ig'er -B0I. concentrations -Hirsc' F 9ory6
+3,D..
(. M'en ne(uli;e% into a &ace mas:6
mout' piece6 or trac'eostomy6 + to +0
milliliters o& t'e B0I solution or B to B0
milliliters o& t'e +0I solution may (e gi)en
e)ery B to , 'ours. "'e recommen%e%
%ose &or most patients is / to = milliliters
o& t'e B0I solution or , to +0 milliliters o&
t'e +0I solution / to G times %aily -8ro%
In&o Mucomyst-R.6 +33,..
c. "'e B0I solution may (e %ilute% to a
lesser concentration 1it' eit'er so%ium
c'lori%e &or in4ection6 so%ium c'lori%e &or
in'alation6 sterile 1ater &or in4ection6 or
sterile 1ater &or in'alation. "'e +0I
solution may (e use% un%ilute%. Any
unuse% portion o& t'e solution s'oul% (e
store% in t'e re&rigerator an% use% 1it'in
3, 'ours -8ro% In&o Mucomyst-R.6 +33,..
%. !or treatment o& pulmonary
complications o& surgery or posttraumatic
c'est con%itions6 + to B milliliters o& B0I
acetylcysteine solution or B to G milliliters
o& +0I solution may (e gi)en e)ery + to G
'ours )ia a syringe attac'e% to t'e
intratrac'eal cat'eter2 B to = milliliters o&
t'e B0I solution may (e intro%uce% 1it' a
syringe t'roug' a trac'eal cat'eter 1'en
contact 1it' a particular segment o& t'e
(ronc'opulmonary tree is %esire% -8ro%
In&o Mucomyst-R.6 +33,2 AH!S6 +3*3..
2.0 PHARMACOKINETICS
2.1 ONSET AND DURATION
2.1.1 ONSET
A. INI"IA? RES8ONSE#
+. Bronc'itis# onset not reporte%
a. "'e intra)enous route o>ers 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 +3D/..
B. 8EA9 RES8ONSE#
+. Mucolytic6 in'alation# G= minutes -Hurst et al6
+3,D..
2.1.2 DURATION
A. SIN?E DOSE#
+. Mucolytic6 in'alation# +00 minutes -Hurst et al6
+3,D..
2.2 DRUG CONCENTRATION LEVELS
2.2.1 THERAPEUTIC
A. "IME "O 8EA9 7ON7EN"RA"ION#
+. In'alation6 ne(uli;er# + to B 'ours -Hol%iness6
+33+..
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 $NDER "HE 7$REE -A$7.# 3/.3 mg/?/'r
-'ealt'y su(4ects. -Hones et al6 +33D..
+. Mean A$7 1as +=B./ mg/?/'r in patients
1it' cirr'osis as compare% to 3/.3 mg/?/'r in
'ealt'y controls6 &ollo1ing an intra)enous %ose
o& ,00 mg in&use% o)er / minutes -Hones et al6
+33D..
2.3 ADME
2.3.1 ABSORPTION
A. BIOAEAI?ABI?I"A -!.#
+. Oral6 ta(lets# ,I to +0I -Hol%iness6 +33+..
a. Oral (ioa)aila(ility is similar &or a single
,00<mg %ose an% t'ree B00<mg %oses -De
7aro et al6 +3*3..
(. 7onNicting %ata exist concerning t'e
e>ect o& acti)ate% c'arcoal on oral
(ioa)aila(ility -Matson F Mc9inney6 +33+..
One stu%y &oun% no %i>erence in total area
un%er t'e cur)e -Nort' et al6 +3*+.. In
)itro %ata %emonstrate% signi@cant
a%sorption o& t'e %rug to acti)ate% c'arcoal
-9lein<Sc'1art; F O%er%a6 +3*+2 7'inout'
F 7;a4:a6 +3*0..
B. "opical6 less t'an /I -Barte: et al6 +3DB..
2.3.2 DISTRIBUTION
2.3.2.1 DISTRIBUTION SITES
A. "O"A? 8RO"EIN BINDIN# =0I -Hol%iness6
+33+..
+. =0I6 oral %osing2 B0I to =0I6
intra)enous -Hol%iness6 +33+..
B. 8rotein (in%ing a&ter intra)enous %osing
increase% 1it' time to a maximum o&
approximately =0I at G 'ours6 a&ter 1'ic'
it %ecrease% to approximately B0I at +B
'ours -Hol%iness6 +33+..
B. O"HER DIS"RIB$"ION SI"ES#
+. ?ung6 G*I -Ro%enstein et al6 +3D*..
a. !ollo1ing a +00<mg oral %ose6
G*I 1as present in lung tissue
-Ro%enstein et al6 +3D*..
B. Extracellular 1ater
a. Eolume o& %istri(ution 1as
consistent 1it' %istri(ution mainly to
extracellular 1ater -Borgstrom et al6
+3*,..
2.3.2.2 DISTRIBUTION KINETICS
A. DIS"RIB$"ION HA?! ?I!E# 0.++ ?/:g/'our
-Olsson et al6 +3**..
B. EO?$ME O! DIS"RIB$"ION -E%.# 0.// to
0.GD ?/: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<acetylation in t'e li)er6 it
enters t'e normal meta(olic pat'1ay o& t'e
amino aci% cysteine -S'e>ner6 +3,=.. An
apprecia(le ele)ation in total serum
sul&'y%ryl concentration occurs -Ma%%oc:6
+3*0..
B. Intestinal 1all6 rapi% an% extensi)e -Hol%iness6
+33+..
2.3.3.2 METABOLITES
A. Re%uce% acetylcysteine -Hol%iness6 +33+..
2.3.4 EXCRETION
2.3.4.1 BREAST MILK
A. BREAS"!EEDIN# $N9NOMN
2.3.4.2 KIDNEY
A. RENA? 7?EARAN7E# 0.B+ ?/'our/:g
-Borgstrom et al6 +3*,..
B. RENA? EX7RE"ION# /0I -Borgstrom et al6
+3*,..
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 /*I o& t'e
a%ministere% %ose an% some taurine 1as also
present -Hol%iness6 +33+2 Barte: et al6 +3DB2
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
+3DB2 S'i' F Sc'ulman6 +3,3..
2.3.4.3 OTHER
A. "O"A? BODA 7?EARAN7E# ,.= ?/'r -'ealt'y
su(4ects. -Hones et al6 +33D..
+. 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
-Hones et al6 +33D..
B. O"HER EX7RE"ION#
+. !eces6 /I -Hol%iness6 +33+..
a. In animal mo%els6 only /I o& N<
acetylcysteine is excrete% in &eces
-Hol%iness6 +33+..
2.3.5 HALFLIFE
2.3.5.1 PARENT COMPOUND
A. E?IMINA"ION HA?!<?I!E# B.BD 'ours
+. !ollo1ing intra)enous %osing6 t'e
elimination 'al&<li&e 1as B.BD 'ours
B. Hal&<li&e a)erage% G.3 'ours in patients
1it' cirr'osis as compare% to B.D 'ours in
'ealt'y controls6 &ollo1ing an intra)enous
%ose o& ,00 mg in&use% o)er / minutes
-Hones et al6 +33D..
/. No acetylcysteine 1as in t'e plasma +B
'ours a&ter oral inta:e o& a single %ose o&
&ast<release acetylcysteine -Borgstrom et al6
+3*,..
2.3.5.2 METABOLITES
A. Re%uce% acetylcysteine6 ,.B= 'ours -Olsson
et al6 +3**..
+. ,.B= 'ours -oral.2 =.=* 'ours
-intra)enous. -Olsson et al6 +3**..
3.0 CAUTIONS
3.1 CONTRAINDICATIONS
A. Hypersensiti)ity to acetylcysteine
3.2 PRECAUTIONS
A. Ast'ma -Dano6 +3D+2 Anon6 +3D02 Bernstein F
Aus%enmoore6 +3,G.
B. Acti)ate% c'arcoal s'oul% not (e routinely
coa%ministere% 1it' oral acetylcysteine
3.3 ADVERSE REACTIONS
3.3.1 BLOOD
A. HEMATOLOGIC EFFECTS
+. Decrease% eryt'rocyte turno)er an% %ecrease%
prot'rom(in time are %escri(e% 1it'
acetylcysteine use.
B. DECREASED ERYTHROCYTE TURNOVER
+. S$MMARA#
a. Acetylcysteine can %ecrease eryt'rocyte
turno)er in patients 1it' 'ere%itary
glutat'ione %e@ciency (y increasing
glutat'ione le)els -Hain et al6 +33G..
C. DECREASED PROTHROMBIN TIME
+. S$MMARA#
a. A %ose<%epen%ent e>ect on t'e
measurement o& t'e prot'rom(in time is
%escri(e% -Hepsen F Hansen6 +33G..
B. ?I"ERA"$RE RE8OR"S#
a. Intra)enous in&usion o& acetylcysteine
'as (een s'o1n to signi@cantly %ecrease
prot'rom(in time in 'ealt'y su(4ects. Six
male su(4ects 1ere a%ministere% an
intra)enous loa%ing %ose o& acetylcysteine
+0 milligrams/:ilogram -mg/:g. &ollo1e% (y
a continuous in&usion o& +0 mg/:g/'our &or
/B 'ours. Acetylcysteine 1as &oun% to 'a)e
a %ose<%epen%ent e>ect on t'e
measurement o& prot'rom(in time.
Acetylcysteine 'a% no e>ect on t'e intrinsic
coagulation pat'1ay2 'o1e)er6 t'e
coagulation &actors II6 EII6 an% X 1ere
%ecrease% signi@cantly. "'e total %ose o&
acetylcysteine use% in t'is stu%y 1as
%esigne% to (e similar to t'e total %ose
use% in t'e treatment o& acetaminop'en
poisoning. "'e aut'ors suggest t'at in
patients 1it' acetaminop'en<in%uce%
'epatic &ailure6 1'o recently recei)e%
acetylcysteine6 treatment s'oul% not (e
(ase% on prot'rom(in time alone -Hepsen
F Hansen6 +33G..
3.3.2 CARDIOVASCULAR
A. CARDIOVASCULAR EFFECTS
+. Hypotension6 tac'ycar%ia6 %epresse% car%iac
&unction6 circulatory &ailure 1it' car%io)ascular
collapse6 tac'ycar%ia6 an% a(normal E9s are
%escri(e%.
B. ABNORMAL BLOOD PRESSURE
+. S$MMARA#
a. Bot' HA8ER"ENSION an%
HA8O"ENSION 1it' acetylcysteine t'erapy
are %escri(e% %ue to %i>erent mec'anisms.
-Sunman et al6 +33B2 Mant et al6 +3*G..
a. "'e intra)enous a%ministration o&
acetylcysteine may result in 'ypotension.
"'is reaction appears to (e relate% to a
)aso%ilatory e>ect o& acetylcysteine an%
may (e %ose<%epen%ent -Sunman et al6
+33B..
C. DEPRESSED CARDIAC FUNCTION
+. S$MMARA#
a. In t'e setting o& septic s'oc:6
acetylcysteine resulte% in %epresse% car%iac
&unction. -8ea:e et al6 +33,..
a. Acetylcysteine a%4uncti)e treatment in
septic s'oc: patients resulte% in %epresse%
car%iac &unction6 an% %i% not &a)ora(ly
a>ect organ in4ury or mortality rates. In a
prospecti)e6 ran%omi;e%6 %ou(le (lin%
stu%y6 patients 1it' ne1ly %iagnose% septic
s'oc: 1ere gi)en a G*<'our in&usion o&
acetylcysteine -nO+0. or place(o -nO+0..
Relati)e to t'e place(o group6 t'e
acetylcysteine<treate% group s'o1e%
signi@cant6 progressi)e %ecreases in car%iac
in%ex -+*I.6 le&t )entricular stro:e 1or:
-G/I.6 an% mean arterial pressure -B/I..
Hypotension increase% in t'e acetylcysteine
group6 (ut )aso%ilation 1as rule% out as
t'e cause since systemic )ascular
resistance occurre% in (ot' groups. "'e
total %ose gi)en eac' patient in t'e
acetylcysteine group 1as approximately /*/
mg/:g o& acetylcysteine o)er G* 'ours
-8ea:e et al6 +33,..
D. TACHYCARDIA
+. S$MMARA#
a. "ac'ycar%ia an% (urning c'est pain
associate% 1it' an anap'ylactoi% reaction
1ere reporte% &ollo1ing t'e intra)enous
in&usion o& acetylcysteine -Bon@glio et al6
+33B..
E. ABNORMAL ECG
+. S$MMARA#
a. S" segment %epression an% "<1a)e
in)ersion 1ere associate% 1it' an
anap'ylactoi% reaction &ollo1ing t'e IE
in&usion o& acetylcysteine. Ho1e)er6 a clear
relations'ip coul% not (e esta(lis'e%
-Bon@glio et al6 +33B..
3.3.3 CENTRAL NERVOUS SYSTEM
A. NEUROLOGIC EFFECTS
+. Intracranial 'ypertension6 %i;;iness an%
sei;ures 'a)e occurre% 1it' acetylcysteine use.
B. DI44INESS
+. S$MMARA#
a. During Intra)enous acetylcysteine
a%ministration6 %i;;iness 'as (een reporte%
-Mant et al6 +3*G2 Bon@glio et al6 +33B..
C. INTRACRANIAL HYPERTENSION
+. S$MMARA#
a. Ele)ation o& intracranial pressure %uring
in'alational acetylcysteine t'erapy 'as (een
reporte% -Eenturelli F "ein6 +3*G..
D. STATUS EPILECTICUS
+. S$MMARA#
a. Status epilepticus occurre% &ollo1ing
intra)enous acetylcysteine treatment &or
acetaminop'en o)er%ose in a B<year<ol%
girl -Hers':o)it; et al6 +33,..
3.3.4 ENDOCRINE"METABOLIC
A. METABOLIC EFFECTS
+. !e)er an% c'ills 'a)e occurre% %uring
in'alational or intra)enous acetylcystein
a%ministration in some patients.
B. ABNORMAL TEMPERATURE
+. S$MMARA#
a. !EEER an% 7HI??S 'a)e (een reporte%
%uring in'alational or intra)enous
acetylcycstein a%ministration in some
patients -7'an F 7ritc'ley6 +33G2 Massey
F 7arpenter6 +3*,..
3.3.5 GASTROINTESTINAL
A. GASTROINTESTINAL EFFECTS
+. Nausea an% )omiting6 %iarr'ea6 an%
gastrointestinal irritation are %escri(e%.
B. DIARRHEA
+. S$MMARA#
a. Diarr'ea a&ter acetylcysteine
a%ministration 'as occurre% -!errari6 +3*0..
M'en +, to +* %oses o& acetylcysteine
1ere a%ministere%6 G/.=I o& t'e patients
experience% %iarr'ea -Hol%iness6 +33+..
C. GASTROINTESTINAL IRRITATION
+. S$MMARA#
a. Hig' %oses o& acetylcysteine 1ere an
irritant to t'e gastrointestinal tract6 causing
HA8EREMIA an% HEMORRHAES
-Bonanomi F a;;aniga6 +3*02 Marini et
al6 +3*02 S'a16 +3,3..
a. Hig' acetylcysteine %oses in soli% or
suspension 1ere irritating to t'e
gastrointestinal tract -Bonanomi F
a;;aniga6 +3*0..
(. !ull strengt' -B0I. acetylcysteine
causes 'yperemia an% 'emorr'ages o&
(o1el mucosa an% t'ere&ore s'oul% (e
%ilute% to at least a 3I solution prior to
oral a%ministration -S'a16 +3,3..
c. Acetylcysteine gi)en as B00<milligram
granules in sac'ets %i% not result in any
pat'ologic c'anges o& t'e gastrointestinal
mucosa 1'en examine% 'istologically an%
(y en%oscopy -Marini et al6 +3*0..
%. Irritation or soreness o& t'e mout' may
occur %uring in'alational t'erapy 1it'
acetylcysteine -$S8DI6 +3*=..
D. NAUSEA AND VOMITING
+. S$MMARA#
a. Nausea an% )omiting is common6
especially a&ter oral a%ministration o&
acetylcysteine. Diarr'ea may also occur
-Bon@glio et al6 +33B2 !errari6 +3*02
Hol%iness6 +33+.
a. M'en +, to +* %oses o& acetylcysteine
1ere a%ministere%6 =0I o& t'e patients
experience% )omiting -Hol%iness6 +33+..
3.3.# LIVER
A. HEPATIC EFFECTS
+. Increase% li)er en;ymes are %escri(e%.
B. ELEVATED HEPATIC EN4YMES
+. S$MMARA#
a. In t'e setting o& cystic @(rosis6 'epatic
en;yme ele)ations 'a)e occurre% -Bailey F
An%res6 +3*D..
a. A /<year<ol% male 1it' cystic @(rosis
1as treate% 1it' oral an% rectal
acetylcysteine &or meconium ileus
eJui)alent an% %e)elope% li)er en;yme
ele)ations on t1o separate occasions -pea:
SO" G6*=0 I$/? an% B6D00 I$/?. -Bailey
F An%res6 +3*D.. "'e total %oses o&
acetylcysteine %eli)ere% 1ere +0, grams
an% D=0 grams6 respecti)ely6 1'ic' are
su(stantially 'ig'er t'an 1'at 1oul% 'a)e
(een a%ministere% in a c'il% t'is si;e &or
t'e treatment o& acetaminop'en o)er%ose
-+,., grams o)er / %ays. -Bailey F
An%res6 +3*D.. /./.D.B.B.B A cystic @(rosis
patient 1as %escri(e% as %e)eloping li)er
&unction a(normalities a&ter recei)ing +0,
grams an% B=0 grams o& oral an% rectal
acetylcysteine on t1o separate occasions
-Bailey F An%res6 +3*D.. In a%%ition6
'epato(iliary %isease &rom cystic @(rosis
itsel& coul% not (e rule% out in t'is case
-Bailey F An%res6 +3*D..
3.3.$ OCULAR
A. EYE EFFECTS
+. 7ortical (lin%ness is reporte% &ollo1ing a
sei;ure a&ter Intra)enous acetylcysteine
a%ministration.
B. CORTICAL BLINDNESS
+. S$MMARA#
a. In a B<year ol% girl2 cortical (lin%ness
occurre% &ollo1ing a sei;ure a&ter
intra)enous acetylcysteine a%ministration.
Sei;ure 1as t'e suspecte% cause o&
(lin%ness. Eision 1as almost completely
reco)ere% a&ter +* mont's -Hers':o)it; et
al6 +33,..
3.3.5 RESPIRATORY
A. RESPIRATORY EFFECTS
+. Ast'ma6 (ronc'ospasm6 (ronc'oconstriction6
coug'6 'emoptysis6 an% respiratory %istress are
reporte%.
B. ASTHMA
+. S$MMARA#
a. "'e $9 7ommittee on Sa&ety o&
Me%icines %uring t'e perio% !e(ruary +3DD
an% August +33+ recei)e% +, reports o&
ast'ma or (ronc'ospasm6 none o& 1'ic'
1ere li&e t'reatening. Ho1e)er6 since t'en
one case o& se)ere ast'ma an% respiratory
arrest 1as reporte% &ollo1ing intra)enous
a%ministration o& acetylcysteine. "'e patient
reJuire% imme%iate inter)ention an%
placement on a )entilator &or /, 'ours2 (ut
reco)ere% totally 1it'in +0 %ays a&ter
treatment 1it' intra)enous sal(utamol an%
steroi%s -Reynau% et al6 +33B..
C. BRONCHOCONSTRICTION
+. S$MMARA#
a. Bronc'oconstriction 'as occurre% 1it'
acetylcysteine use -Mactemat' F Bergman6
+3D/2 Dano6 +3D+2 Rao et al6 +3D02 Hurst
et al6 +3,D2 Hirsc' F 9ory6 +3,D2
Semer%4ian et al6 +3,D2 Bernstein F
Aus%enmoore6 +3,G..
a. "'e most commonly reporte% a%)erse
reaction 1it' serious potential is t'e a(ility
o& acetylcysteine -NA7. to pro%uce
(ronc'oconstriction as e)i%ence% (y
alterations in pulmonary &unction tests
-Hurst et al6 +3,D2 Bernstein F
Aus%enmoore6 +3,G2 Dano6 +3D+2 Hirsc' F
9ory6 +3,D2 Rao et al6 +3D02 Semer%4ian et
al6 +3,D2 Mactemat' F Bergman6 +3D/..
"'is appears to (e a concentration
%epen%ent response6 since it is consistently
reporte% 1it' use o& B0I NA7 -Hirsc' F
9ory6 +3,D2 Rao et al6 +3D0. an% rarely
1it' +0I NA7 -8ulle et al6 +3D02 9ory et
al6 +3,*2 Dano6 +3D+.. "'is response is
rea%ily re)erse% 1it' concomitant
(ronc'o%ilator use -8ulle et al6 +3D02 9ory
et al6 +3,*.. "'e clinical importance o& t'e
(ronc'oconstriction is %iLcult to e)aluate.
D. BRONCHOSPASM
+. S$MMARA#
a. "'e $9 7ommittee on Sa&ety o&
Me%icines %uring t'e perio% !e(ruary +3DD
an% August +33+ recei)e% +, reports o&
ast'ma or (ronc'ospasm6 none o& 1'ic'
1ere li&e t'reatening. Ho1e)er6 since t'en
one case o& se)ere ast'ma an% respiratory
arrest 1as reporte% &ollo1ing intra)enous
a%ministration o& acetylcysteine. "'e patient
reJuire% imme%iate inter)ention an%
placement on a )entilator &or /, 'ours2 (ut
reco)ere% totally 1it'in +0 %ays a&ter
treatment 1it' intra)enous sal(utamol an%
steroi%s -Reynau% et al6 +33B..
a. Se)ere (ronc'ospasm 'as occurre%
%uring intra)enous acetylcysteine t'erapy o&
acetaminop'en poisoning in ast'matic
patients -Ho F Beilen6 +3*/.. It may also
occur a&ter acetylcysteine in'alation -Dano6
+3D+..
E. COUGH
+. S$MMARA#
a. Excessi)e coug' 'as (een reporte% an%
is t'oug't to (e %ue to su%%en liJue&action
an% mo(ili;ation o& secretions6 -Hirsc' et
al6 +3D02 Anon6 +3D02 Hurst et al6 +3,D..
a. Excessi)e coug' -Hurst et al6 +3,D.6
tig'tness o& t'e c'est -Hirsc' et al6 +3D0.
an% RHINORRHEA 'a)e also (een
reporte%. A common caution associate%
1it' use o& acetylcysteine 'as (een t'at in
some patients su%%en liJue&action an%
mo(ili;ation o& secretions may partially
o(struct t'e (ronc'i -Anon6 +3D0.. No
cases 'a)e (een reporte% in t'e literature.
F. HEMOPTYSIS
+. S$MMARA#
a. Hemoptysis occurs rarely -8ro%.In&o
Mucomyst-R.6 B000..
G. RESPIRATORY DISTRESS
+. S$MMARA#
a. Respiratory %istress 'as occurre% 1it'
t'e respiratory rate increasing initially6 t'en
%ecreasing. Increase in (ronc'ial secretions
or (ronc'ospasm may occur. Su%%en
respiratory %istress lea%ing to car%iac arrest
an% %eat' 'as (een %escri(e% in one
patient recei)ing intra)enous acetylcysteine
-Dono)an6 +3*,2 Bon@glio et al6
+33B2Reynar% et al6 +33B..
a. Su%%en onset o& respiratory %istress
resulting in car%iac arrest an% %eat'
occurre% in a patient 1it' c'ronic
o(structi)e pulmonary %isease (eing treate%
1it' intra)enous acetylcysteine &or an
acetaminop'en o)er%ose -Dono)an6 +3*,..
(. DAS8NEA associate% 1it' an
anap'ylactoi% reaction 1as reporte%
&ollo1ing t'e intra)enous in&usion o&
acetylcysteine -Bon@glio et al6 +33B..
c. A +D<year<ol% girl 1it' a 'istory o& mil%
ast'ma %e)elope% a(rupt RES8IRA"ORA
ARRES" 1'ile recei)ing 'er loa%ing %ose
o& intra)enous acetylcysteine &or
acetaminop'en o)er%ose -Reynar% et al6
+33B.. S'e 'a% mil% 1'ee;ing on
presentation to t'e 'ospital an% 'a% no
e)i%ence o& respiratory %istress prior to
respiratory arrest.
H. RHINITIS
+. S$MMARA#
a. R'initis 'as occurre% %uring in'alational
use o& acetylcysteine -$S8DI6 +3*=..
3.3.10 SKIN
A. DERMATOLOGIC EFFECTS
+. 7utaneous pain6 angioe%ema6 ras'6 urticaria6
an% s:in Nus'ing are %escri(e%.
B. CUTANEOUS PAIN
+. S$MMARA#
a. A patient experience% se)ere cutaneous
pain an% excoriation %uring acetylcysteine
in&usion -B0I solution. at percutaneous
a(scess %rainage. "'e mucolytic agent
lea:e% (ac: along t'e cat'eter trac:6
causing t'e local reaction. 7essation o& t'e
acetylcysteine treatment an% cat'eter
exc'ange resulte% in impro)ement 1it'in a
&e1 %ays -7asola F )anSonnen(erg6 +3*G..
C. ANGIOEDEMA
+. S$MMARA#
a. Angioe%ema 'as (een reporte% 1it' oral
acetylcysteine use -Mro; et al6 +33D..
D. RASH
+. S$MMARA#
a. Ras' 'as occurre%. !acial Nus'ing an%
c'est Nus'ing %uring intra)enous
a%ministration is common -7'an F
7ritc'ley6 +33G2 Dono)an6 +3*D2 Dono)an6
+3*,2 Bon@glio et al6 +33B..
a. Mil% ras' occurre% in / o& +/3 -B.BI.
patients recei)ing intra)enous acetylcysteine
in one series -Dono)an6 +3*,. an% D o& =,
patients -+/I. in anot'er -7'an F
7ritc'ley6 +33G..
(. 8ruritic ras' %e)elope% in anot'er
patient recei)ing intra)enous acetylcysteine
-NA7. &rom anot'er series -+ o& +*6 ,I.6
1'ile +0 o& +* -=,I. %e)elope% &acial
an%/or c'est Nus'ing. "'e s:in reactions
(egan += to D= minutes a&ter t'e onset o&
t'e in&usion6 correlate% 1it' t'e pea:
plasma acetylcysteine le)els6 resol)e%
spontaneously 1it'in G 'ours6 an% %i% not
correlate 1it' 'istory o& atopy -Dono)an6
+3*D..
c. !lus'ing associate% 1it' an
anap'ylactoi% reaction 1as reporte%
acetylcysteine -Bon@glio et al6 +33B..
E. URTICARIA
+. S$MMARA#
a. Oral acetylcysteine may result in
generali;e% ras'6 urticaria6 or angioe%ema
1'ic' may respon% to %ip'en'y%ramine
t'erapy -Mro; et al6 +33=..
Dip'en'y%ramine B= milligrams
intra)enously a%ministere% prior to t'e %ose
o& acetylcysteine 1as success&ul in
pre)enting urticaria in one patient -7'arley
et al6 +3*D..
3.3.12 OTHER
A. OVERDOSE See 8OISINDEX-R. Management KN<
A7E"A?7AS"EINEK
B. ANAPHYLACTOID REACTIONS
+. S$MMARA#
a. Anap'ylactoi% reactions6 inclu%ing
cutaneous eruptions6 Nus'ing6 c'est pain6
tac'ycar%ia6 urticaria6 angioe%ema6
(ronc'ospasm6 ast'ma6 'ypotension an%
&e)er 'a)e (een reporte% in up to /I o&
patients recei)ing intra)enous acetylcysteine
-Bon@glio et al6 +33B.. "'e nature o& t'ese
reactions an% e)i%ence concerning t'eir
etiology suggeste% a 'istamine<release
p'enomenon. "'e aut'or notice%
impro)ement in one patient &ollo1ing t'e
a%ministration o& %ip'en'y%ramine2 'o1e)er6
'e cautione% t'at impro)ement may 'a)e
also (een relate% to %ecrease% serum
acetylcysteine concentration. -Bailey F
Mcuigan6 +33*2 Mro; et al6 +33D2
Sunman et al6 +33B2 Massey F 7arpenter6
+3*,2 Dono)an6 +3*D2 Dono)an6 +3*,2
er)ais et al6 +3*G2 "enen(ein6 +3*G2
Bateman et al6 +3*Ga2 Bateman et al6
+3*G(2 er)ais6 +3*G2 Mant et al6 +3*G2
Ho F Berlin6 +3*/2 Eale F M'eeler6 +3*B2
Malton et al6 +3D3..
a. An anap'ylactoi% reaction 1as reporte%
acetylcysteine +=0 milligrams/:ilogram in a
B0<year<ol% 1oman -Bon@glio et al6 +33B..
(. "'e clinical &eatures o& anap'ylactoi%
reactions associate% 1it' t'e a%ministration
o& intra)enous acetylcysteine may )ary
accor%ing to 1'et'er t'e reaction occurs
a&ter an o)er%ose o& acetylcysteine or a&ter
a correct %ose. In /* cases6 &ollo1ing t'e
correct intra)enous %ose o& acetylcysteine6
t'e inci%ence o& anap'ylaxis 1as 0./ to
/I 1it' clinical &eatures resem(ling
immune system acti)ation suc' as pruritus
an% (ronc'ospasm. In contrast6 ++ o& +=
patients 1'o recei)e% an o)er%ose o& IE
acetylcysteine experience% anap'ylaxis 1it'
'ypotension as t'e most prominent clinical
&eature -Sunman et al6 +33B..
c. A%)erse reactions 1'ic' are anap'ylactoi% in
nature 'a)e (een attri(ute% to t'e a(ility o&
acetylcysteine to cause 'istamine release
-Bateman et al6 +3*G(.. In )i)o an% in )itro
tests in%icate acetylcysteine is an in'i(itor o&
allergen tac'yp'ylaxis (y in'i(ition o&
prostaglan%in E synt'esis -Dorsc' et al6 +3*D..
C. HYPERSENSITIVITY REACTIONS
+. S$MMARA#
a. A%)erse %rug reactions reporte% to
t'e Australian A%)erse Drug
Reactions A%)isory 7ommittee
(et1een Hanuary +6 +3D3 an%
Septem(er /06 +3*D inclu%e% ras'
-B, o& /0.6 pruritus -+, o& /0.6
angioe%ema -3 o& /0.6 nausea an%
)omiting -3 o& /0.6 (ronc'ospasm -*
o& /0.6 tac'ycar%ia -G o& /0.6
'ypotension -/ o& /0.6 an%
'ypertension -B o& /0..
-+. ONSE"# "'e a)erage time to
onset o& a%)erse e>ect &ollo1ing
commencement o& t'e in&usion
o& acetylcysteine 1as /0
minutes6 range = to D0 minutes
-Da1son et al6 +3*3..
-B. IN7IDEN7E# Intra)enous
acetylcysteine is reporte% to
cause a%)erse reactions in up
to 3I o& patients6 inclu%ing
suc' se)ere symptoms as
angioe%ema6 (ronc'ospasm6 an%
'ypotension -Da1son et al6
+3*3.. Burning c'est pain6
tac'ycar%ia6 %yspnea6 %i;;iness6
an% Nus'ing 1ere relie)e% 1it'
an intra)enous %ose o&
%ip'en'y%ramine B= milligrams.
A(normal E9 c'anges 1ere
associate% 1it' t'e reaction6 (ut
a clear relations'ip coul% not (e
esta(lis'e% -Bon@glio et al6
+33B..
-/. Mil% 'ypersensiti)ity
reactions 1ere associate% 1it'
pea: acetylcysteine plasma
concentrations o& =/G.3 P/<
+=3.+ milligrams/liter -mg/?. an%
all su(si%e% 1'en acetylcysteine
plasma concentrations &ell (elo1
+00 mg/? -Dono)an et al6
+3**..
D. SERUM SICKNESS
+. S$MMARA#
a. One case o& a serum sic:ness<li:e
illness 'as (een reporte% &ollo1ing
treatment 1it' acetylcysteine. !e)er6
%i>use a(%ominal ten%erness6 (ilateral
s1elling o& t'e :nee an% el(o1 4oints6
an% a eryt'ematous maculopapular
ras' %e)elope% in a patient a&ter /
%ays o& t'erapy 1it' acetylcysteine -=
grams e)ery , 'ours.. Symptoms
resol)e% 1it'in +B 'ours &ollo1ing
%iscontinuation o& acetylcysteine an%
use o& supporti)e t'erapy -Mo'amme%
et al6 +33G..
3.4 TERATOGENICITY"EFFECTS IN PREGNANCY
A. TERATOGENICITY
+. $.S. !oo% an% Drug A%ministration5s 8regnancy
7ategory B -8ro% In&o Mucomyst-R.6 +33,..
See Drug 7onsult re&erence# K8RENAN7A
RIS9 7A"EORIESK
B. Australian Drug E)aluation 7ommittee5s -ADE7.
7ategory BB -ADE76 +33,..
B. EFFECTS IN PREGNANCY
+. One stu%y conclu%e% t'at acetylcysteine -NA7.
coul% (e gi)en to pregnant acetaminop'en<o)er%ose
patients -Hol%iness6 +33+.. $se o& NA7 1as re)ie1e%
in cases o& acetaminop'en o)er%ose %uring )arious
stages o& pregnancy -Hol%iness6 +33+.. "'e complete
&ollo1<up o& =3 patients -+* 1ere +st trimester6 B/
1ere secon% trimester6 an% +* 1ere t'ir% trimester.
re)eale% t'at GB patients %eli)ere% in&ants 1it' no
%ocumente% neonatal a(normalities2 +B 1omen 'a%
electi)e or spontaneous a(ortions6 + &etal/natural %eat'
occurre%2 an% + patient %eli)ere% a /B<1ee: still(orn
&etus -%ata missing &or /..
3.5 DRUG INTERACTIONS
3.5.1 DRUGDRUG COMBINATIONS
A. ACTIVATED CHARCOAL
+. Summary# One stu%y 1as una(le to
%emonstrate a re%uction o& acetylcysteine (loo%
le)els 1'en acti)ate% c'arcoal an%
acetylcysteine 1ere coa%ministere% -Nort' et al6
+3*+.. "'is stu%y in)ol)e% only t'ree su(4ects
an% its @n%ings must (e consi%ere% preliminary.
"'e aut'ors caution against coa%ministration until
more %ata are reporte%.
B. Se)erity# not speci@e%
/. Onset# not speci@e%
G. Documentation# poor
B. AMPICILLIN
+. Se)erity# not speci@e%
B. Onset# not speci@e%
/. Documentation# poor
G. ?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
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.
C. AMPICILLIN"SULBACTAM
D. CARBAMA4EPINE
+. Summary# One 1oman experience% %ecrease%
car(ama;epine troug' le)els t'ree %ays a&ter
starting N<acetylcysteine t'erapy6 1'ic' le% to
t'ree consecuti)e tonic<clonic sei;ures. It 1as
propose% t'at 'ig' %oses o& N<acetylcysteine
may increase t'e clearance o& car(ama;epine
an% its meta(olites to inacti)e %eri)ati)es6
lea)ing t'e patient at an increase% ris: &or
sei;ure acti)ity -Simonart et al6 +33*..
B. A%)erse E>ect# an increase% ris: o&
su(t'erapeutic car(ama;epine le)els
/. 7linical Management# 7losely monitor
car(ama;epine le)els in patients also recei)ing
N<acetylcysteine.
G. Se)erity# mo%erate
=. Onset# %elaye%
,. Documentation# poor
D. 8ro(a(le Mec'anism# increase% clearance o&
car(ama;epine
*. ?iterature Reports#
a. A =3<year<ol% &emale (eing treate% &or
t1o years 1it' car(ama;epine *00 mg
%aily 'a% serum troug' le)els a(o)e +0
mcg/m?. ?amotrigine 1as a%%e% to 'er
t'erapeutic regimen to allo1 a slo1
1it'%ra1al o& car(ama;epine. As t'e %ose
o& lamotrigine increase% to D= mg %aily6 t'e
patient %e)elope% &e)er6 lymp'a%enopat'y6
con4uncti)itis6 an% maculopapular eruptions
on t'e &ace an% upper torso.
7ar(ama;epine troug' le)el at t'is time
1as ++.+ mcg/m?. "'e patient 1as
%iagnose% 1it' lamotrigine<in%uce%
'ypersensiti)ity6 an% N<acetylcysteine B g
e)ery six 'ours 1as initiate% 1it' rapi%
clinical impro)ement. Ho1e)er6 on t'e t'ir%
%ay o& N<acetylcysteine t'erapy6 t'e patient
'a% t'ree tonic<clonic sei;ures 1it'in @)e
'ours. Alt'oug' 'er car(ama;epine %ose
'a% not c'ange%6 t'e troug' le)el 1as *.+
mcg/m?. It 1as propose% t'at t'e 'ig'
%oses o& N<acetylcysteine increase% t'e
clearance o& car(ama;epine an% its
meta(olites to inacti)e %eri)ati)es6 lea)ing
t'e patient at an increase% ris: &or sei;ure
acti)ity -Simonart et al6 +33*..
E. CEPHALORIDINE
F. CLOXACILLIN
G. METHICILLIN
H. NITROGLYCERIN
+. Summary# 7oncurrent a%ministration o&
nitroglycerin an% N<acetylcysteine 'as (een
s'o1n to cause signi@cant 'ypotension an%
en'ance temporal artery %ilation -Horo1it; et al6
+3**2 I)ersen6 +33B.. Ho1e)er6 t'e intra)enous
com(ination o& nitroglycerin an% N<acetylcysteine
may also re%uce t'e inci%ence o& an acute
myocar%ial in&arction in patients 1it' se)ere
unsta(le angina pectoris -Horo1it; et al6 +3**..
B. A%)erse E>ect# en'ance% 'ypotension an%
nitroglycerin<in%uce% 'ea%ac'e
/. 7linical Management# I& concurrent
nitroglycerin an% N<acetylcysteine t'erapy is
necessary6 monitor patients &or 'ypotension6
1'ic' can (e se)ere6 an% 1arn t'em o& t'e
possi(ility o& 'ea%ac'es.
G. Se)erity# mo%erate
=. Onset# rapi%
,. Documentation# &air
D. 8ro(a(le Mec'anism# a%%iti)e )aso%ilation
*. ?iterature Reports#
a. N<acetylcysteine 1as s'o1n to potentiate
t'e 'emo%ynamic e>ects o& nitroglycerin in
a ran%omi;e%6 %ou(le<(lin% stu%y in)ol)ing
G, patients 1it' se)ere unsta(le angina
pectoris. "'e e>ects o& intra)enous
nitroglycerin 1ere compare% to t'ose o&
intra)enous nitroglycerin an% intra)enous N<
acetylcysteine -= grams e)ery six 'ours..
"'e BG patients 1'o recei)e% com(ination
t'erapy 'a% a signi@cantly lo1er inci%ence
o& acute myocar%ial in&arction -nO/. t'an
t'e BB patients 1'o recei)e% nitroglycerin
an% place(o -nO+0.. Ho1e)er6 com(ination
t'erapy 1it' intra)enous nitroglycerin an%
N<acetylcysteine pro%uce% symptomatic
'ypotension &reJuently -Horo1it; et al6
+3**..
(. "'e e>ects o& N<acetylcysteine on
nitroglycerin<in%uce% 'ea%ac'es 1ere
analy;e% in ele)en 'ealt'y )olunteers6
using a %ou(le<(lin%6 ran%omi;e%6 place(o<
controlle%6 crosso)er %esign. N<
acetylcysteine +00 mg/:g or place(o 1as
%ilute% an% in&use% intra)enously o)er a
perio% o& += minutes6 &ollo1e% (y a
nitroglycerin in&usion -0.0, mcg/:g/min. o)er
a B0 minute perio%. "'e nitroglycerin
in&usion 1as t'en repeate% +B0 minutes
a&ter t'e initial in&usion. N<acetylcysteine
potentiate% t'e nitroglycerin<in%uce%
'ea%ac'e an% also en'ance% t'e temporal
artery %ilation 1'en compare% to place(o
-+/3I )s +BDI o& (aseline.. "'e ra%ial
artery 1as not a>ecte% -I)ersen6 +33B..
c. Hogan et al -+330. in)estigate% t'e
e>ect o& c'ronic oral N<acetylcysteine on
t'e %e)elopment o& nitrate tolerance in
patients 1it' sta(le angina pectoris treate%
1it' %aily trans%ermal nitroglycerin. Eig't
su(4ects recei)e% nitroglycerin +0 mg
trans%ermally %aily an% N<acetylcysteine
G00 mg t'ree times %aily or place(o in a
prospecti)e6 %ou(le<(lin%6 ran%omi;e%
crosso)er manner &or &our %ays6 1it' a
1as'out inter)al o& t'ree %ays. Heart rate6
(loo% pressure6 an% trea%mill 1al:ing time
measurements s'o1e% t'e %e)elopment o&
tolerance to t'e anti<anginal an%
'emo%ynamic e>ects o& nitroglycerin a&ter
&our %ays o& treatment6 an% t'e
coa%ministration o& N<acetylcysteine 'a% no
%emonstra(le e>ect on t'is. "'is stu%y also
s'o1e% t'at oral N<acetylcysteine %i% not
potentiate t'e )aso%ilator e>ects o&
nitroglycerin. "'e aut'ors postulate% t'at
oral N<acetylcysteine may (e a less
e>ecti)e %onor o& sul&'y%ryl groups t'an
intra)enous N<acetylcysteine an% t'at
nitroglycerin tolerance may (e %ue to
mec'anisms ot'er t'an sul&'y%ryl group
%epletion.
I. OXACILLIN
%. PENICILLIN G
+. A%)erse E>ect# loss o& anti(iotic eLcacy
=. ?iterature Reports#
K. PENICILLIN G PROCAINE
L. 6UINACILLIN
+. 7linical Management# Acetylcysteine s'oul%
not (e mixe% in t'e same solution as Juinacillin
&or ne(uli;ation.
sul&a%ia;ine6 sul&a%imi%ine6 or tetracycline
M. TETRACYCLINE
B. 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
D. ?iterature Reports#
sul&a%ia;ine6 sul&a%imi%ine6 or tetracycline
3.5.3 DRUGLAB MODIFICATIONS
A. NITROPRUSSIDE TEST
+. Summary# Acetylcysteine may inter&ere 1it'
t'e nitroprussi%e test6 resulting in a &alse<positi)e
reaction &or :etone (o%ies in (loo% an%/or urine.
"'e &ree<sul&'y%ryl groups o& acetylcysteine react
1it' a purple color similar to t'at o& :etone
(o%ies in t'e nitroprussi%e test. "'is inter&erence
is particularly important in %ia(etics an% patients
1it' suspecte% 'epatocellular in4ury -7sa:o F
Elin6 +33/..
B. Se)erity# minor
/. Onset# rapi%
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' G<aminop'enol to gi)e a (lue<colore%
pro%uct. -7'u(( et al6 +3*,..
B. A%)erse E>ect# 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
D. 8ro(a(le Mec'anism# salicylate assay
inter&erence
3.5.4 INTRAVENOUS ADMIXTURES
3.5.4.2 COMPATIBILITIES DRUGS
A. BACITRACIN
+. Acetylcysteine +0I 1it' (acitracin =000
$/m?6 compati(le (ut mixture s'oul% (e
use% at once -8ro% In&o Mucomyst-R.6
+33+.
B. CARBENICILLIN
+. 7ar(enicillin -+B= mg/m? 1it'
acetylcysteine +0I6 compati(le (ut mixture
s'oul% (e use% at once. -8ro% In&o
Mucomyst-R.6 +33,.
C. CEPHALORIDINE
+. Acetylcysteine +0I 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-R.6 +33+.
D. CEPHALOTHIN
+. Acetylcysteine +0I 1it' cep'alot'in ++0
mg/m?6 compati(le (ut mixture s'oul% (e
+33+.
E. CHLORAMPHENICOL
+. Acetylcysteine B0I 1it' c'loramp'enicol
B0 mg/m?6 compati(le2 con%itions not
speci@e% -8ro% In&o Mucomyst-R.6 +33+.
F. COCAINE
+. Acetylcysteine +0I 1it' cocaine =I6
compati(le2 con%itions not speci@e% -8ro%
In&o Mucomyst-R.6 +33+.
G. COLISTIN
+. Acetylcysteine +0I 1it' colistin /D.=
+33+.
H. CROMOLYN
+. Acetylcysteine 1it' cromolyn so%ium
ne(uli;er solution +I6 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 +,I 1it' %examet'asone
0.* mg/m?6 compati(le2 con%itions not
%. EPINEPHRINE
+. Acetylcysteine +/./I -B parts. 1it'
epinep'rine 0.//I -+ part.6 compati(le2
con%itions not speci@e% -8ro% In&o
Mucomyst-R.6 +33+.
K. GENTAMICIN
+. Acetylcysteine +0I 1it' gentamicin B0
mg/m?6 compati(le2 con%itions not speci@e%
-8ro% In&o Mucomyst-R.6 +33+.
L. ISOPROTERENOL
+. Acetylcysteine /I 1it' isoproterenol
0.=I6 compati(le2 con%itions not speci@e%
an% %rug concentrations liste% (elo1 -8ro%
B. Acetylcysteine +0I 1it' isoproterenol
0.0=I6 compati(le2 con%itions not speci@e%
/. Acetylcysteine B0I 1it' isoproterenol
0.0=I6 compati(le2 con%itions not speci@e%
G. Acetylcysteine +/./I -B parts. 1it'
isoproterenol 0.//I -+ part.6 compati(le2
con%itions not speci@e% an% %rug
concentrations liste% (elo1 -8ro% In&o
Mucomyst-R.6 +33+.
M. KANAMYCIN
+. Acetylcysteine +0I 1it' :anamycin +,D
+33+.
B. Acetylcysteine +DI 1it' :anamycin *=
+33+.
N. LIDOCAINE
+. Acetylcysteine +0I 1it' li%ocaine BI6
O. LINCOMYCIN
+. Acetylcysteine +0I 1it' lincomycin +=0
P. NEOMYCIN
+. Acetylcysteine +0I 1it' neomycin +00
6. NOVOBIOCIN
+. Acetylcysteine +0I 1it' no)o(iocin B=
R. PANCREATIC DORNASE
+. Acetylcysteine +,.DI 1it' pancreatic
%ornase *000 $/m?6 compati(le (ut mixture
s'oul% (e use% at once -8ro% In&o
Mucomyst-R.6 +33+.
S. PENICILLIN G
+. Acetylcysteine +0I 1it' penicillin
potassium B=6000 or +006000 $/m?6
compati(le (ut mixture s'oul% (e use% at
once -8ro% In&o Mucomyst-R.6 +33+.
T. PHENYLEPHRINE
+. 8'enylep'rine 0.B=I 1it' acetylcysteine
/I6 compati(le2 con%itions not speci@e%
B. 8'enylep'rine 0.+DI -+ part. 1it'
acetylcysteine +/./I -B parts.6 compati(le2
Mucomyst-R.6 +33+.
U. POLYMYXIN B
+. Acetylcysteine +0I 1it' polymyxin B
=06000 $/m?6 compati(le2 con%itions not
V. PREDNISOLONE
+. Acetylcysteine +,.DI 1it' pre%nisolone
/./ mg/m?6 compati(le2 con%itions not
W. ROLITETRACYCLINE
+. Acetylcysteine +0I 1it' rolitetracycline
*D.= mg/m?6 compati(le (ut mixture s'oul%
(e use% at once -8ro% In&o Mucomyst-R.6
+33+.
X. SODIUM BICARBONATE
+. Acetylcysteine B0I 1it' so%ium
(icar(onate G.BI6 compati(le2 con%itions
not speci@e% -8ro% In&o Mucomyst-R.6
+33+.
Y. TETRACAINE
+. Acetylcysteine +0I 1it' tetracaine +I6
4. VANCOMYCIN
+. Acetylcysteine +0I 1it' )ancomycin B=
+33+.
3.5.4.4 INCOMPATIBILITIES DRUGS
A. AMPHOTERICIN B
+. Acetylcysteine GI to +=I 1it'
amp'otericin B + to G mg/m?6 incompati(le2
Mucomyst-R.6 +33+.
B. AMPICILLIN
+. Acetylcysteine +0I 1it' ampicillin =0
mg/m?6 incompati(le2 con%itions not
C. CHLORTETRACYCLINE
+. Acetylcysteine +0I 1it' c'lortetracycline
+B.= mg/m?6 incompati(le2 con%itions not
D. ERYTHROMYCIN
1. ERYTHROMYCIN LACTOBIONATE
a. Acetylcysteine +0I 1it'
eryt'romycin lacto(ionate += mg/m?6
incompati(le2 con%itions not speci@e%
E. IODI4ED OI
+. Acetylcysteine B0 m? o& a B0I solution
1it' io%i;e% oil +0 m? o& a G0I solution6
incompati(le2 con%itions not speci@e% -8ro%
F. OXYTETRACYCLINE
+. Acetylcysteine +0I 1it' oxytetracycline
+B.= mg/m?6 incompati(le2 con%itions not
G. TETRACYCLINE
+. Acetylcysteine +0I 1it' tetracycline +B.=
mg/m?6 incompati(le2 con%itions not
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. A7E"AMINO8HEN OEERDOSE
+. ?i)er &unction tests
4.1.2 TOXIC
A. A7E"AMINO8HEN OEERDOSE
+. Nausea6 )omiting
4.2 PATIENT INSTRUCTIONS
A)'.*L)*8.'(N' ($-s#-t##l-8(8-t##n) ((N7ALA.(ON):
7#l"s /ou to 0%#$t4# 0#tt#% 0/ t4innin1 o% dissolvin1
t4i&B lun1 3u&us &$us#d 0/ #3"4/s#3$ "n#u3oni$
&/sti& +i0%osis o% ot4#% lun1 "%o0l#3s.
BRAND NA-'(8): -u&o3/st(R) -u&osil(R)
A7'N *O, 87O,LD NO. ,8' .7(8 -'D()(N':
*ou s4ould not us# t4is 3#di&in# i+ /ou 4$v# 4$d $n
$ll#%1i& %#$&tion to $&#t/l&/st#in#.
7OA .O ,8' AND 8.OR' .7(8 -'D()(N'
8olution:
- *ou% do&to% 6ill t#ll /ou 4o6 3u&4 3#di&in# to us#
$nd 4o6 o+t#n to 4$v# /ou% t%#$t3#nts.
- )$%#+ull/ %#$d $nd +ollo6 t4# inst%u&tions t4$t
&o3# 6it4 t4# 3#di&in#. .4#/ 6ill t#ll /ou 4o6 to
us# t4# n#0uliE#% (t4# d#vi&# t4$t /ou us# to
0%#$t4# in t4# 3#di&in#) $nd &o3"%#sso% $nd 4o6 to
&$%# +o% $nd &l#$n t4# n#0uliE#% Bit.
- .4# &o3"%#sso% tu%ns t4# 3#di&in# into $ +in#
s"%$/ t4$t /ou 6ill 0%#$t4 into /ou% 3out4 usin1
t4# n#0uliE#%.
- ,s# t4# 3out4"i#&# t4$t &o3#s 6it4 t4# n#0uliE#%.
- A$s4 /ou% 4$nds 6it4 so$" $nd 6$t#% 0#+o%# "uttin1
t4# n#0uliE#% to1#t4#%.
- O"#n t4# vi$l (s3$ll 0ottl# o+ 3#di&in#) $nd "ou%
t4# 3#di&in# into t4# n#0uliE#% &u". Put t4# &$"
0$&B on t4# &u". .4# 3#di&in# 3$/ 4$v# $ 0$d s3#ll
$t +i%st. .4# odo% s4ould 1o $6$/ soon $+t#% /ou
st$%t /ou% t%#$t3#nt.
- .u%n on t4# &o3"%#sso% so 3ist is &o3in1 out o+
t4# n#0uliE#%.
- Put t4# 3out4"i#&# in /ou% 3out4 &los# /ou% li"s
$%ound it $nd 0%#$t4# in $nd out t4%ou14 /ou%
3out4. -$B# su%# /ou% t##t4 $nd ton1u# do not
0lo&B t4# $i%+lo6.
- F##" 0%#$t4in1 until t4# n#0uliE#% &u" is #3"t/ o%
no 3o%# 3ist is &o3in1 out. *ou 3$/ 4#$% $
s"utt#%in1 sound 64#n t4# &u" is #3"t/.
- A4#n +inis4#d tu%n o++ t4# &o3"%#sso% $nd &l#$n
t4# n#0uliE#% $nd &o3"%#sso%.
- *ou 3$/ n##d to &ou14 u" $nd s"it out 3u&us t4$t
&oll#&ts in /ou% t4%o$t.
- (nst#$d o+ $ 3out4"i#&# $&#t/l&/st#in# is
so3#ti3#s 1iv#n t4%ou14 $ +$&# 3$sB.
- 8o3#ti3#s $ t#nt is "l$&#d $%ound t4# 4#$d o%
u""#% 0od/ $nd t4# 3#di&in# is "ut into t4# $i%
o+ t4# t#nt +o% 0%#$t4in1.
- .$lB to /ou% do&to% o% "4$%3$&ist i+ /ou 4$v#
Gu#stions $0out /ou% 3#di&in# $nd 64#t4#% /ou $%#
usin1 it &o%%#&tl/.
- 8to%# uno"#n#d vi$ls o+ 3#di&in# $t %oo3
t#3"#%$tu%# $6$/ +%o3 4#$t $nd di%#&t li14t.
A+t#% t4# vi$l 4$s 0##n o"#n#d B##" it in t4#
%#+%i1#%$to% $nd us# it 6it4in 4 d$/s. Do not
+%##E#.
- *ou s4ould not us# vi$ls o+ $&#t/l&/st#in# t4$t
4$v# "$ss#d t4# #2"i%$tion d$t#.
- F##" $ll 3#di&in# out o+ t4# %#$&4 o+ &4ild%#n.
(+ /ou 3iss $ dos#:
- .$B# t4# 3iss#d dos# $s soon $s "ossi0l# unl#ss
it is $l3ost ti3# +o% /ou% n#2t dos#.
- 8Bi" t4# 3iss#d dos# i+ it is $l3ost ti3# +o% /ou%
n#2t %#1ul$% dos#.
- *ou s4ould not us# t6o dos#s $t t4# s$3# ti3#.
DR,=8 AND FOOD8 .O AVO(D:
AsB /ou% do&to% o% "4$%3$&ist 0#+o%# usin1 $n/ ot4#%
3#di&in# in&ludin1 ov#%-t4#-&ount#% 3#di&in#s
vit$3ins $nd 4#%0$l "%odu&ts.
- Do not 3i2 ot4#% 3#di&in#s in t4# n#0uliE#% 6it4
$&#t/l&/st#in# unl#ss /ou% do&to% t#lls /ou to.
AARN(N=8:
- (+ /ou $%# "%#1n$nt o% 0%#$st+##din1 t$lB to /ou%
do&to% 0#+o%# usin1 $&#t/l&/st#in#
- .#ll /ou% do&to% 0#+o%# usin1 t4is 3#di&in# i+ /ou
4$v# $st43$ o% i+ it is 4$%d +o% /ou to &ou14.
8(D' 'FF').8
)$ll /ou% do&to% %i14t $6$/ i+ /ou 4$v# $n/ o+ t4#s#
sid# #++#&ts:
- (n&%#$s#d 64##Ein1 o% t%ou0l# 0%#$t4in1
- )4#st "$in o% ti14tn#ss
- )ou14in1 u" 0lood
- F#v#% sBin %$s4 o% 4iv#s
(+ /ou 4$v# "%o0l#3s 6it4 t4#s# l#ss s#%ious sid#
#++#&ts t$lB 6it4 /ou% do&to%.
- 8o%# 3out4 o% t4%o$t
- 7o$%s#n#ss
- N$us#$ vo3itin1
- Runn/ nos#
(F *O, 7AV' AN* O.7'R 8(D' 'FF').8 .7A. *O, .7(NF AR'
)A,8'D B* .7(8 -'D()(N' .'LL *O,R DO).OR.
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<acetylcysteine treatment s'oul% (e starte%
1it'in eig't 'ours o& o)er%ose (ut is still in%icate% at least
as late as BG 'ours a&ter ingestion. He also conclu%e% t'at
a DB<'our regimen o& oral N<acetylcysteine is as e>ecti)e
as t'e B0<'our intra)enous regimen an% may (e superior
1'en treatment is %elaye%.
B. Oral acetylcysteine is a )ery e>ecti)e muco:inetic agent
an% is use&ul in %ecreasing t'e num(er o& exacer(ations in
patients 1it' c'ronic (ronc'itis. M'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<acetyl %eri)ati)e o&
t'e amino aci% cysteine. It 'as (een promote% as a
mucolytic agent &or use in t'e a%4u)ant treatment o&
pulmonary %iseases associate% 1it' increase%
)iscosity o& (ronc'ial secretions -8etty F Mitc'ell6
+3,D2 7'o%os'6 +3,D.. NA7 'as (een %emonstrate%
to cause a %ecrease in sputum consistency6 to
&acilitate easier expectoration6 an% to increase sputum
)olume. Bronc'ial mucus is compose% o& o)er 3=I
1ater2 'o1e)er6 t'e p'ysical c'aracteristics o& t'e
mucus are %ue to glycoproteins. "'ese glycoproteins
(in% to eac' ot'er (y 1ay o& %isul@%e (on%s an%
gi)e t'e mucus )iscosity. NA7 ruptures t'ese %isul@%e
(on%s causing %epolymeri;ation an% a rapi% %ecrease
in mucus )iscosity. It also pro%uces an irritati)e
(ronc'orr'eic e>ect on t'e mucosa6 stimulating
mucociliary clearance2 t'is irritati)e e>ect may cause
(ronc'ospasm6 t'us acetylcysteine is not
recommen%e% in ast'matics -ilman et al6 +3302
Ciment6 +3*,2 Bar(ieri6 +3*/2 Ric'ar%son6 +3*0.. "'e
in<)itro a(ility o& NA7 to %ecrease t'e )iscosity o&
sputum is unc'allenge% an% 'as (een %emonstrate%
in stu%ies using %e)ices %esigne% to o(4ecti)ely
e)aluate t'e a(ility o& c'emicals to re%uce t'e
)iscosity o& mucopurulent solutions -Hirsc' et al6 +3,32
S'e>ner et al6 +3,G2 Hurst et al6 +3,D..
B. N<Acetylcysteine5s -NA7. action is concentration
an% pH %epen%ent. A concentration o& less t'an =I
'as (een &oun% to (e little more e>ecti)e t'an 1ater
or saline -Hirsc' et al6 +3,3.. "'e pH %epen%ency is
important 1it' initial application6 (ut 1it'in + 'our
t'ere is no large %i>erence (et1een acti)ity at pH =
an% pH * -S'e>ner et al6 +3,G.. It is generally
t'oug't t'at 'ig'er pH5s are more (ene@cial. NA7
apparently %oes not inNuence secretory glan%s
-Sturgess F Rei%6 +3DB. or pulmonary sur&ace acti)ity
-"'omas F "reasure6 +3,,. at normal concentrations.
/. N<Acetylcysteine -NA7. is (elie)e% to act as a
glutat'ione su(stitute an% %irectly com(ine 1it' t'e
toxic acetaminop'en meta(olite -8eterson F Rumac:6
+3**2 8eterson F Rumac:6 +3D*.. One stu%y reports
t'at NA7 increases oxygen %eli)ery6 t'is may account
&or its (ene@cial e>ect on patients 1it' &ulminant
'epatic &ailure cause% (y acetaminop'en -Harrison et
al6 +33+..
G. N<acetylcyteine -NA7. en'ances t'e le)els o&
glutat'ione -SH. in t'e li)er6 in plasma6 an% nota(ly
in (ronc'ioal)eolar la)age Nui% -Ru>mann F Men%el6
+33+.. NA7 s'oul% (e consi%ere% as an in%epen%ent
treatment mo%ality &or an array o& %i>erent %iseases6
all o& 1'ic' 'a)e one &eature in common6 t'e loss o&
SH.
=. "'e a(ility o& N<acetylcysteine to en'ance
'epatosplanc'nic per&usion is t'oug't to arise &rom its
potential &or stimulating en%ot'elium<%eri)e% relaxing
&actor6 t'ere(y impro)ing micro)ascular (loo% No1
-Ran: et al6 B000..
,. Acetylcysteine may 'a)e signi@cant cytoprotecti)e
e>ects. "'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
ra%icals t'at o)er1'elm an% %eplete en%ogenous
antioxi%ants -eg6 glutat'ione.. Acetylcysteine is a
sca)enger o& oxygen &ree ra%icals. In a%%ition6
acetylcysteine is a glutat'ione precursor capa(le o&
replenis'ing %eplete% intracellular glutat'ione an% in
t'eory augment antioxi%ant %e&enses -Hen%erson F
Hayes6 +33G2 Ba::er et al6 +33G2 Dinarello et al6
+33/2 rec' et al6 +33/2 Aoung et al6 +33/2 Da)ies et
al6 +33/2 !ar( et al6 +33/2 9irs'en(aum et al6 +33B2
Bone6 +33B2 Hepsen et al6 +33B2 Mel(ourn F Aoung6
+33B2 Repine F Bee'ler6 +33+2 Rac:o1 F Asti;6 +33+2
lauser et al6 +33+2 !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 Mestlin F Mullane6 +3**2 Ellen'orn F
Barceloux6 +3**2 9eller et al6 +3*=2 Boro;otta F 8ol:6
+3*/..
B. REVIEW ARTICLES
+. "'e use o& acetylcysteine is inclu%e% in a
compre'ensi)e re)ie1 o& acetaminop'en<in%uce%
'epatotoxicity an% its management -Ma:in F Milliams6
+33D..
B. "'e use o& acetylcysteine as a muco:inetic agent
is re)ie1e% -Ciment6 +3**2 Ciment6 +3*,..
/. 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 HIE in&ection
an% cancer cac'exia# "'erapeutic inter)ention 1it' N<
Acetylcysteine -Droge et al6 +33D..
4.5 THERAPEUTIC USES
A. ACETAMINOPHEN POISONING
FDA L$0#l#d (ndi&$tion
+. OEEREIEM#
FDA APPROVAL: Adult /#s! "#di$t%i& /#s
'FF()A)*: Adult #++#&tiv#! "#di$t%i& #++#&tiv#
DO),-'N.A.(ON: Adult #2&#ll#nt! "#di$t%i&
#2&#ll#nt
B. S$MMARA#
- A1#nt o+ &4oi&# to "%#v#nt 4#"$toto2i&it/ +%o3
$&#t$3ino"4#n to2i&it/ (P#t#%son H Ru3$&B 1<88)
- -ost #++#&tiv# i+ 0#1un 6it4in 25 4ou%s o+
in1#stion
- Also #++#&tiv# u" to 24 4ou%s o% 3o%# (P#t#%son
H
Ru3$&B 1<77! P#t#%son H Ru3$&B 1<78)
- O%$l %out# is t4# onl/ on# $""%ov#d 0/ FDA
- (nt%$v#nous %out# $lso us#d
/. AD$?"#
a. In a comparison o& stu%ies using oral or
intra)enous -IE. N<acetylcysteine -NA7. &or t'e
treatment o& acetaminop'en o)er%ose6 t'ere 1as
no clear %i>erence in eLcacy o& t'e t1o mo%es
o& a%ministration2 t'e intra)enous route o>ers
a%)antages in re%uce% 'ospital stay as 1ell as
in (eing una>ecte% (y )omiting an% (y oral
a%ministration o& c'arcoal. A%)erse reactions to
IE NA7 usually occur %uring or s'ortly a&ter t'e
loa%ing %ose an% can pro(a(ly (e a)oi%e% (y a
slo1er -/0 to ,0 minute. in&usion o& t'e loa%ing
%ose. Mit' eit'er mo%e o& a%ministration6 t'e
earlier t'e a%ministration o& NA7 a&ter ingestion
o& toxic amounts o& acetaminop'en6 t'e greater
t'e li:eli'oo% o& pre)enting 'epatotoxicity.
Ho1e)er6 a%ministration o& NA7 e)en a&ter t'e
%e)elopment o& 'epatotoxicity is associate% 1it'
some (ene@ts -Buc:ley et al6 +333..
(. Intra)enous a%ministration o& oral
acetylcysteine 1as e>ecti)e &or treating
acetaminop'en o)er%ose in an +*<year<ol%
1oman 1'en oral a%ministration 1as not6
(ecause o& se)ere )omiting. "'e 1oman 1as
treate% 1it'in G 'ours o& ingesting B= grams o&
acetaminop'en. $na(le to retain t'e initial oral
%ose o& acetylcysteine6 t'e 1oman 1as gi)en
oral acetylcysteine intra)enously6 1it' a loa%ing
%ose o& *D= milligrams -mg. per 'our &or t'e
@rst G 'ours an% t'en a maintenance %ose o&
GB0 mg/'our &or t'e next /0 'ours. S'e
reco)ere% completely -Amir;a%e' F Mc7otter6
B00B..
c. In a national6 multicenter stu%y &rom +3D, to
+3*=6 oral N<acetylcysteine 1as e>ecti)e in t'e
treatment o& acetaminop'en o)er%ose6 especially
i& starte% 1it'in * 'ours o& acetaminop'en
ingestion6 (ut treatment 1as still in%icate% as
late as BG 'ours a&ter ingestion -Smil:stein et al6
+3**.. 8atients 1ere categori;e% into groups
accor%ing to initial plasma acetaminop'en
concentrations %uring t'e @rst * 'ours a&ter
ingestion an% time to treatment 1it' respect to
acetaminop'en ingestion. In patients treate%
1it'in +0 'ours o& ingestion6 ,.+I -/B o& =BD.
o& patients at pro(a(le ris: o& toxicity -plasma
acetaminop'en concentrations o& B00
micrograms/milliliter or greater at G 'ours an% =0
micrograms/milliliter at +B 'ours. an% *./I -+D
o& B0,. o& patients in t'e 'ig' ris: group
-plasma acetaminop'en concentrations o& /00
micrograms/milliliter or greater at G 'ours an% D=
micrograms/milliliter at +B 'ours. 'a% aspartate
or alanine aminotrans&erase le)els a(o)e +000
international units/liter. I& initial treatment 1as
(et1een +0 an% BG 'ours6 B,.GI -BGD o& 3/=.
o& pro(a(le ris: patients an% /G.GI -+33 o& =D*.
o& 'ig' ris: patients 'a% ele)ate% li)er &unction
tests. Among 'ig' ris: patients treate% +, to BG
'ours a&ter acetaminop'en ingestion6 G+I o&
patients %e)elope% 'epatotoxicity. M'en patients
1ere analy;e% accor%ing to initial plasma
acetaminop'en le)els6 it 1as &oun% t'at i&
patients 1ere treate% 1it'in * 'ours o&
acetaminop'en ingestion6 N<acetylcysteine 1as
e>ecti)e in pre)enting 'epatotoxicity regar%less
o& t'e initial plasma acetaminop'en
concentration. "'ere 1as no %i>erence among
patients 1'en N<acetylcysteine 1as starte% ;ero
to G 'ours or G to * 'ours2 'o1e)er6 1it'
&urt'er treatment %elays t'ere 1as a statistically
signi@cant increase in aminotrans&erase le)els.
%. Acetylcysteine 1as eLcacious in
acetaminop'en<in%uce% &ulminant 'epatic &ailure
in +00 patients stu%ie% -Harrison6 +330..
Mortality 1as /DI in patients recei)ing
acetylcysteine -NA7. +0 to /, 'ours a&ter
o)er%ose6 compare% 1it' =*I not recei)ing
NA7. In patients gi)en NA76 progression to
gra%e III/IE coma 1as signi@cantly less common
t'an in t'ose 1'o %i% not recei)e t'e anti%ote
-=+I )ersus D=I..
e. ?A"E ADMINIS"RA"ION o& acetylcysteine
-NA7. a&ter acetaminop'en o)er%ose may (e
sa&e an% eLcacious in patients 1it' &ulminant
'epatic &ailure. In a prospecti)e controlle% stu%y6
patients 1ere ran%omi;e% to recei)e NA7 -nOB=.
or %extrose =I -nOB=. a%ministere% /, to *0
'ours a&ter t'eir acetaminop'en o)er%ose -9eays
et al6 +33+.. "1el)e patients -G*I. in t'e NA7
group sur)i)e% compare% to = -B0I. in t'e
control group -pO0.0/D.. No a%)erse e>ects 1ere
attri(ute% to NA7 treatment. ?ess cere(ral
e%ema an% 'ypotension reJuiring inotropic
t'erapy occurre% in NA7<treate% patients t'an in
controls. "'e %eterioration rate an% reco)ery o&
li)er &unction6 'o1e)er6 %i% not %i>er (et1een
groups. Ot'er clinicians suggest t'at e)en
t'oug' it mig't (e late in t'e course o&
acetaminop'en poisoning6 acetylcysteine s'oul%
(e a%ministere% unless time o& o)er%ose an% a
su(<toxic acetaminop'en plasma le)el can (e
Juic:ly %etermine% -Delanty F !it;geral%6 +33,..
&. A retrospecti)e stu%y o& acetaminop'en
o)er%ose cases %etermine% t'at IN"RAEENO$S
ADMINIS"RA"ION o& oral acetylcysteine
pro%uces limite% a%)erse reactions6 none
in)ol)ing 'emo%ynamic6 car%io)ascular6 or
pulmonary e>ects. M'en oral a%ministration o&
acetylcysteine is not possi(le6 intra)enous
a%ministration may represent a potentially li&e<
sa)ing alternati)e -Aip et al6 +33*..
G. 8EDIA"RI7#
a. In pe%iatric patients 1it' acetaminop'en
o)er%ose6 intra)enous N<acetylcysteine -NA7.
a%ministere% o)er =B 'ours 1as as e>ecti)e as
oral NA7 a%ministere% o)er DB 'ours. "1enty<
@)e patients -a)erage age +=., years. presenting
1it'in BG 'ours o& a single o)er%ose o&
acetaminop'en an% in t'e pro(a(le or 'ig' ris:
category &or 'epatotoxicity 1ere treate% 1it'
intra)enous NA7 -+G0 milligrams -mg./:g loa%ing
%ose6 &ollo1e% (y +B maintenance %oses o& D0
mg/:g e)ery G 'ours. an% compare% 1it' similar
'istorical controls 1'o 'a% (een treate% 1it'
oral NA7 in t'e same %osing regimen6 except
t'at t'ere 1ere +D maintenance %oses. Alt'oug'
mean treatment %elay 1as longer in t'e
intra)enous group6 t'ere 1ere no signi@cant
%i>erences (et1een groups &or any o& t'e pea:
measures o& 'epatotoxicity. A%)erse reactions
occurre% in B patients o& eac' group -8erry F
S'annon6 +33*..
B. ANGINA UNSTABLE
+. OEEREIEM#
,8P RA.(N=: A&&#"t$n&# not #st$0lis4#d
B. S$MMARA#
- .4# &o30in$tion o+ N(.RO=L*)'R(N 6it4
N-A)'.*L)*8.'(N' 3$/ 0# o+ t4#%$"#uti& v$lu# in
,N8.ABL' AN=(NA "#&to%is $nd $&ut# 3/o&$%di$l
in+$%&tion (7o%o6itE 1<<1)
- .4# 4i14 in&id#n&# o+ intol#%$0l# 4#$d$&4# 3$/
li3it 6id#s"%#$d &lini&$l $""li&$tion
/. AD$?"#
0. COMBINATION THERAPY
-+. 7om(ine% intra)enous nitroglycerin -=
micrograms/minute initially. an% N<
acetylcysteine intra)enously -= grams o)er
+= minutes e)ery , 'ours. in patients 1it'
se)ere unsta(le angina pectoris
unresponsi)e to con)entional t'erapy
resulte% in a lo1er inci%ence o& acute
myocar%ial in&arction as compare% to
nitroglycerin gi)en alone. In a%%ition6 t'ere
1as a tren% to1ar%s a re%uction in t'e
num(er o& c'anges in t'e nitroglycerin
in&usion rate reJuire% &or pain control.
Ho1e)er6 symptomatic 'ypotension 1as
o(ser)e% &reJuently in t'e
nitroglycerin/acetylcysteine group as
compare% to nitroglycerin gi)en alone -D
)ersus 0 patients.. "1enty ot'er patients
treate% 1it' intra)enous nitroglycerin an%
lo1er %ose acetylcysteine -as a continuous
in&usion o& +0 grams %aily. 1ere &ree o&
symptomatic 'ypotension an% s'o1e% no
increase in t'e inci%ence o& myocar%ial
in&arction. More stu%ies are reJuire% to
&urt'er e)aluate t'e eLcacy o& com(ine%
t'erapy 1it' continuous acetylcysteine
in&usions -at lo1er %oses. in com(ination
1it' intra)enous nitroglycerin -Horo1it; et
al6 +3**2 Horo1it; et al6 +3**a..
-B. In +B0 patients 1it' unsta(le angina6
t'e com(ination o& oral N<acetylcysteine
,00 milligrams -mg. t'ree times %aily plus
trans%ermal nitroglycerin -+0 mg. a%%e% to
con)entional t'erapy signi@cantly re%uce%
t'e occurrence o& clinical en%points -car%iac
%eat'6 Q<1a)e or non<Q<1a)e in&arction6
re)asculari;ation proce%ures. to +/I -D o&
=G patients. o)er G mont's. Outcomes
1ere not c'ange% &rom con)entional
t'erapy alone -/3I. i& only nitroglycerin
-/+I. or N<acetylcysteine -GBI. 1as
a%%e% to t'e regimen. Ho1e)er6 intolera(le
'ea%ac'e 1as t1ice as common %uring
com(ination nitroglycerin plus N<
acetylcysteine as 1it' nitroglycerin alone6
1it' one<t'ir% o& t'e patients %iscontinuing
treatment6 ma:ing t'is approac' less
accepta(le at t'e %ose le)els use%
-Ar%issino et al6 +33D..
C. ATELECTASIS
+. OEEREIEM#
'FF()A)*: Adult "ossi0l/ #++#&tiv#! "#di$t%i&
"ossi0l/ #++#&tiv#
DO),-'N.A.(ON: Adult "oo%! "#di$t%i& "oo%
B. S$MMARA#
- (ndi&$t#d +o% $t#l#&t$sis du# to 3u&ous
o0st%u&tion
/. AD$?"#
a. "1o reports %escri(e t'e use o& acetylcysteine
-NA7. in pre)enting 8OS"O8ERA"IEE
A"E?E7"ASIS 1it' conNicting results. "'e @rst
report 1as (ase% on a ran%omi;e% non<(lin%e%
stu%y o& NA7 an% saline in post<t'oracic an%
a(%ominal surgery patients -"'omas et al6 +3,,..
"o o(tain (aseline control )alues6 t'e group 1as
e)aluate% prior to (eginning t'e acti)e %rug
stu%y. "'e aut'ors reporte% 'al& as many cases
o& atelectasis 1it' NA76 (ut 1ere una(le to
su(stantiate t'ese @n%ings in a su(seJuent
report o& post<t'oracotomy patients -"'omas et
al6 +3,D..
D. BLEPHARITIS
+. OEEREIEM#
B. S$MMARA#
- O%$l $&#t/l&/st#in# i3"%ov#d t#$% Gu$ntit/ $nd
Gu$lit/ in "$ti#nts 6it4 "ost#%io% 0l#"4$%itis
/. AD$?"#
a. Oral acetylcysteine impro)e% tear Juantity an%
Juality in patients 1it' posterior (lep'aritis. A
control group o& +* patients -/, eyes. 1it'
posterior (lep'aritis 1ere treate% 1it' topical
steroi%s -pre%nisolone acetate. G times %aily &or
G 1ee:s6 anti(iotic -to(ramycin sul&ate. G times
%aily &or G 1ee:s6 1arm compresses t1ice %aily
&or B mont's6 an% arti@cial tears -poly)i%one. G
times %aily &or / mont's. "'e t'erapy group o&
BB similar patients -G/ eyes. recei)e% t'e same
treatment plus oral N<acetylcysteine +00
milligrams / times %aily &or * 1ee:s. In t'e
acetylcysteine group6 Sc'irmer )alues -a
measure o& tear Juantity. increase% in B/ eyes6
%ecrease% in +D eyes6 an% 1ere unc'ange% in /
eyes. In t'e control group6 )alues increase% &or
+0 eyes6 %ecrease% in B/ eyes6 an% 1ere
unc'ange% in B eyes. Impro)ement in tear
Juality 1as signi@cantly greater in t'e
acetylcysteine group6 as measure% (y t'e
Nuorescein (rea:<up test -p less t'an 0.000+.
an% (y t'e mucous &ern test -pO0.003,.. "'e
aut'ors (elie)e t'at acetylcysteine impro)es tear
Juality (y acting not only as a mucolytic agent
(ut (y a>ecting lipi% meta(olism -Aalcin et al6
B00B..
E. CANCER
1. OVERVIEW
DO),-'N.A.(ON: Adult #2&#ll#nt
2. SUMMARY
- A&#t/l&/st#in# did not i3"%ov# su%viv$l o%
%#du&# ti3# to %#&u%%#n&# in "$ti#nts 6it4 4#$d $nd n#&B
&$n&#% o% lun1 &$n&#%
3. ADULT
a. Neit'er )itamin A nor N<acetylcysteine -NA7.6
singly or toget'er6 'a% a positi)e e>ect on
outcome in patients 1it' 'ea% an% nec: cancer
or lung cancer. 8atients -nOB=D/. -3/.=I o&
1'om 'a% smo:e% at some time in t'eir li)es.
1ere ran%omly assigne% to recei)e retinyl
palmitate -/006000 international units -I$. %aily
&or + year &ollo1e% (y +=06000 I$ &or t'e
secon% year.6 NA7 alone -,00 units %aily &or B
years.6 t'e same %oses o& retinyl palmitate an%
NA7 toget'er6 or no a%%itional treatment. !ollo1<
up continue% &or , years &rom ran%omi;ation. At
= years6 =*I o& t'e patients 1it' lung cancer6
*/I o& patients 1it' cancer o& t'e larynx6 an%
DDI o& patients 1it' oral cancer 1ere ali)e.
"'ere 1ere no %i>erences in sur)i)al attri(uta(le
to t'e treatment compoun%s. ?i:e1ise6 t'ere
1ere no statistically signi@cant %i>erences (y
treatment in time to @rst e)ent or to t'e
occurrence o& a secon% primary tumor -)an
Can%1i4: et al6 B000..
F. CARBON MONOXIDE TOXICITY
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# 3$/ 0# 4#l"+ul in &$%0on 3ono2id#
into2i&$tion
/. AD$?"#
a. N<acetylcysteine may 'elp pre)ent t'e
neuropsyc'iatric seJuelae o& acute car(on
monoxi%e poisoning an% s'oul% (e researc'e%
&urt'er -!lanagan F Mere%it'6 +33+..
G. CHRONIC BRONCHITIS
+. OEEREIEM#
'FF()A)*: Adult #++#&tiv#! "#di$t%i& "ossi0l/
#++#&tiv#
DO),-'N.A.(ON: Adult 1ood! "#di$t%i& "oo%
B. S$MMARA#
- R#du&#s t4i&Bn#ss o+ s"utu3
- Lon1-t#%3 us# %#du&#s #2$&#%0$tion %$t# in
"$ti#nts 6it4 &4%oni& 0%on&4itis (Bo3$n #t $l 1<83)
- A &on&o3it$nt 0%on&4odil$to% #n4$n&#s
#++#&tiv#n#ss
- Ad3inist#%#d o%$ll/ int%$v#nousl/ o% $s
$#%osol
/. AD$?"#
a. A meta<analysis o& pu(lis'e% stu%ies
examining t'e e>ects o& N<acetylcysteine -NA7.
on c'ronic (ronc'itis conclu%e% t'at oral NA7 is
more eLcacious an% no more 'arm&ul t'an
place(o &or treating (ronc'itis. Ele)en trials met
inclusion criteria6 inclu%ing 'a)ing a place(o
control group6 a%eJuate ran%omi;ation an%
(lin%ing6 an% %escription o& 1it'%ra1als. M'en
%ata &rom all stu%ies reporting exacer(ations
-nO3. 1ere com(ine%6 t'e %i>erence (et1een
NA7 an% place(o treatments 1as statistically
signi@cant -relati)e (ene@tO+.=,6 3=I con@%ence
inter)al6 +./D<+.DD.. "'e num(er nee%e% to treat
to pre)ent an exacer(ation in + person 1as =.*.
8atient assessment o& eLcacy 1as superior 1it'
NA7 compare% to place(o6 1it' t'e num(er<
nee%e%<to<treat &or one patient reporting
impro)ement compare% to place(o (eing /.D.
A%)erse e>ects 1ere no more common 1it'
NA7 t'an 1it' place(o. "'e clinical rele)ance o&
t'e (ene@t o& NA7 remains to (e esta(lis'e%
-Stey et al6 B000..
(. A meta<analysis o& ran%omi;e%6 %ou(le<(lin%6
place(o< controlle% trials -nO*. stu%ying t'e
e>ect o& long<term oral acetylcysteine on
pre)ention o& acute exacer(ations o& c'ronic
(ronc'itis s'o1e% a (ene@cial e>ect o&
acetylcysteine6 relati)e to place(o. Dosages o&
acetylcysteine range% &rom ,00 milligrams -mg.
/ times per 1ee: to +B00 mg/%ay. Alt'oug'
statistical signi@cance 1as not attaine% in any
in%i)i%ual trial6 meta< analysis s'o1e% t'e
1eig'te% a)erage re%uction in t'e num(er o&
acute exacer(ations 1it' acetylcysteine treatment
to (e B/I -3=I con@%ence inter)al# <+BI to
<//I.. Alt'oug' t'is re%uction is not %ramatic6 it
may signi@cantly %ecrease mor(i%ity an% 'ealt'
care costs -ran%4ean et al6 B000..
c. 7'ronic (ronc'itis patients ta:ing
acetylcysteine s'o1e% a signi@cant re%uction in
t'e num(er o& %ays %uring 1'ic' t'ey 1ere
incapacitate%. O)erall6 =B, patients su>ering &rom
c'ronic (ronc'itis 1ere ran%omi;e% to recei)e
eit'er acetylcysteine B00 milligrams / times a
%ay or place(o %uring a ,<mont' perio%. "'e
aut'ors &aile% to @n% any statistically signi@cant
%i>erence in t'e num(er o& acute exacer(ations
(et1een t'e B treatment groups6 alt'oug' t'ere
1as a slig't tren% to1ar% impro)ement in t'e
acetylcysteine group %uring t'e @rst / mont's o&
t'e trial. "'e tolera(ility 1as similar &or (ot'
treatments -8arr F Huitson6 +3*D..
%. N<acetylcysteine B00 milligrams / times a %ay
-sac'ets. 1as more e>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 -Hac:son et al6 +3*G.. "oxicity
1as minimal.
e. "'e results o& a general practice stu%y o&
+,*, patients suggest t'at acetylcysteine
a%ministere% orally -B00 milligrams t'ree times
%aily &or B 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' *+I 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
+. OEEREIEM#
"ossi0l/ #++#&tiv#
DO),-'N.A.(ON: Adult +$i%! "#di$t%i& +$i%
B. S$MMARA#
- A&#t/l&/st#in# is FDA-$""%ov#d $s $
3u&ol/ti& 0/ di%#&t instill$tion o% n#0uliE$tion
- Ad3inist#%#d o%$ll/ o% lo&$ll/ in studi#s
- A&#t/l&/st#in# %#du&#s t4# &onsist#n&/ o+
s"utu3 in "ul3on$%/ dis#$s#
- (ts &ont%i0ution to i3"%ov#3#nt in "ul3on$%/
+un&tion $nd &lini&$l &ondition 3$/ 0# li3it#d
/. AD$?"#
a. Once<per<%ay N<acetylcysteine -NA7. re%uce%
t'e exacer(ation rate in patients 1it' c'ronic
o(structi)e pulmonary %isease -7O8D. %uring an
open6 ,<mont' trial. One<'un%re% sixty nine
patients recei)e% eit'er stan%ar% t'erapy &or
7O8D -(etaB<agonists6 antic'olinergics6
t'eop'ylline6 an% in'ale% an%/or oral
corticosteroi%s. or stan%ar% t'erapy plus NA7
,00 milligrams per %ay orally in a single %ose.
"'e rate o& occurrence o& exacer(ations o)er ,
mont's 1as G+I less in t'e NA7 group t'an in
t'e stan%ar%<treatment<only group -p less t'an
0.00/.. ?ung &unction 1as not %i>erent &or t'e B
groups6 eit'er at t'e (eginning or t'e en% o& t'e
stu%y. "'ere 1ere no %i>erences (et1een t'e
groups in t'e num(er o& si%e e>ects reporte%
-8ela et al6 +333..
(. Acetylcysteine %i% not contri(ute to
impro)ement in c'ronic o(structi)e pulmonary
%isease -7O8D. patients in a controlle% stu%y.
One 'un%re% eig'ty<one patients 1it' c'ronic
(ronc'itis an% se)ere air1ay o(struction recei)e%
eit'er acetylcysteine -B00 milligrams / times a
%ay. or place(o orally &or @)e mont's in a
%ou(le<(lin%6 parallel<group stu%y. 8atients :ept
%etaile% %aily symptom<%iaries an% 1ere
assesse% mont'ly. No statistical %i>erences 1ere
note% in mean num(er o& exacer(ations (et1een
groups -Anon6 +3*=..
c. "'e reports o& use o& acetylcysteine -NA7. in
c'ronic o(structi)e pulmonary %isease -7O8D.
'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
+3D02 Hirsc' F 9ory6 +3,D.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 +3D0..
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 ?$N DISEASE an% its
a%ministration may lea% to increase% total air1ay
resistance an% cyanotic spells -Bi(i et al6 +33B..
I. COMMON BILE DUCT OBSTRUCTION
+. OEEREIEM#
'FF()A)*: P#di$t%i& "ossi0l/ #++#&tiv#
DO),-'N.A.(ON: P#di$t%i& "oo%
B. S$MMARA#
- )$s# %#"o%ts d#s&%i0# &l#$%$n&# o+ 0il# du&t
o0st%u&tion usin1 $&#t/l&/st#in# in in+$nts
/. 8EDIA"RI7#
a. "'e use o& N<acetylcysteine -NA7. to relie)e
(ile plug syn%rome in an in&ant 1as reporte%
-Bro1n et al6 +330.. "'is proce%ure o()iate%
c'ole%oc'otomy an% may (e o& use in ot'er
in&ants 1it' %uctal o(struction.
(. N<acetylcysteine 1as use% to treat
extra'epatic (iliary o(struction in a /.=<mont'<ol%
male cystic @(rosis patient. "'e o(struction 1as
relie)e% (y 'y%rostatic in&usion o& BI NA7 into
t'e (iliary tree o)er a ,<%ay perio% -E)ans et al6
+33+..
%. CYSTIC FIBROSIS
+. OEEREIEM#
"ossi0l/ #++#&tiv#
DO),-'N.A.(ON: Adult 1ood! "#di$t%i& "oo%
B. S$MMARA#
- R#"o%ts $0out #++i&$&/ o+ $&#t/l&/st#in# in
&/sti& +i0%osis $%# in&onsist#nt
/. AD$?"#
a. ENERA?# "'e use o& acetylcysteine -NA7.
in cystic @(rosis 'as (een generally
recommen%e%2 'o1e)er6 %ata are inconsistent.
Alt'oug' some aut'ors 'a)e reporte%
impro)ement in pulmonary &unction tests -Steil F
Niessen6 +3*02 Ben4amin6 +3D+2 Reas6 +3,G.6
ot'ers 'a)e &oun% no e>ect -Mitc'ell F Elliott6
+3*B2 ot; et al6 +3*0.. In ot'er stu%ies6
signi@cant impro)ement is usually seen in
patients -1it' or 1it'out c'ronic 8seu%omonas
aeruginosa in&ection. 1'o 'a)e an initial &orce%
)ital capacity -!E7. (elo1 D=I or a pea:
expiratory No1 rate -8E!R. o& D0I 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,D2
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
+3D,..
(. A systematic re)ie1 o& literature (et1een
+3,, an% +33D on t'e use o& N<acetylcysteine
-NA7. in cystic @(rosis re)eale% / controlle%
clinical stu%ies 1it' ne(uli;e% NA7 an% , 1it'
oral NA7. 7omparing ne(uli;e% NA7 1it'
place(o6 t'ere 1as no %i>erence in t'e
proportion o& patients s'o1ing greater t'an B0I
impro)ement in lung &unction. Mit' oral NA76
t'ere 1as a ten%ency to1ar% impro)ement o&
!EE+6 (ut t'e e>ect 1as small -B./I. an% its
clinical rele)ance is Juestiona(le. !ollo1<up in
t'ese stu%ies 1as limite% to / mont's2 'ence6 a
(ene@cial e>ect 1it' longer use cannot (e
exclu%e%. 8atients reporte% t'at NA7 treatment
ease% t'e elimination o& sputum6 (ut t'ere is not
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 =B patients 1ere enrolle% in a
%ou(le<(lin%6 place(o<controlle%6 cross<o)er trial
o& t1o /<mont' %urations. Acti)e treatment
consiste% o& acetylcysteine B00 milligrams t'ree
times %aily -patients 1eig'ing less t'an /0 :g.
or G00 milligrams t1ice %aily -greater t'an /0
:g.. E>ect 1as e)aluate% (y a su(4ecti)e clinical
score6 1eig't6 sputum (acteriology6 (loo%
leucocyte count6 se%imentation rate6 titers o&
speci@c antimicro(ial anti(o%ies6 lung &unction
parameters an% measurement o& nasal ciliary
&unction in )itro. "'irty<one patients complete%
t'e stu%y. No signi@cant %i>erences in lung
&unction or su(4ecti)e clinical scores 1ere seen
(et1een acetylcysteine an% place(o. 8atients
1it' 8E!R (elo1 D0I o& pre%icte% normal
)alues s'o1e% a signi@cant increase in 8E!R6
!E76 an% &orce% expiratory )olume in one
secon% -!EE<+. %uring treatment. No e>ect o&
acetylcysteine on ciliary acti)ity 1as o(ser)e%
-Sta&anger F 9oc'6 +3*3..
G. 8EDIA"RI7#
a. Acetylcysteine %oes not appear to impro)e
!A" MA?ABSOR8"ION in cystic @(rosis. A
%ou(le<(lin%6 cross<o)er6 place(o<controlle% trial
1as con%ucte% in +B c'il%ren 1it' cystic @(rosis
an% a 'ig' &ecal &at content %espite en;yme
t'erapy -Mitc'ell F Elliot6 +3*+.. 8atients
recei)e% B00 milligrams o& acetylcysteine or
place(o / times a %ay6 eac' &or a B*<%ay
perio%. E>ecti)eness o& t'erapy 1as (ase% on
&ecal &at excretion collecte% o)er t'e last = %ays
o& eac' treatment perio%. Mean &ecal &at
excretion 1as +3.= grams/BG 'ours in t'e
acetylcysteine group an% +*.3 g/BG 'ours in t'e
place(o group6 1'ic' 1as not signi@cantly
%i>erent. "'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
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# 4$s 0##n us#d su&&#ss+ull/ in
"$ti#nts 6it4 &/stinosis
/. AD$?"#
a. Six patients 1it' 7AS"EINE S"ONES
impro)e% a&ter treatment 1it' oral acetylcysteine
-Mul)aney et al6 +3D=.. "'e %oses utili;e% 1ere
B0 to =00 milligrams/:ilogram/%ay in %i)i%e%
%oses. "'e usual a%ult %ose 1as 0.D gram G
times a %ay. All , patients impro)e% -passe%
&e1er an%/or smaller stones.. "'e aut'ors
speculate% t'at acetylcysteine is e>ecti)e in
re%ucing cysteine to cystine %isul@%e 1'ic' is
more solu(le. No systemic si%e e>ects 1ere
reporte% in t'ese patients.
L. CYTOTOXICITY PROPHYLAXIS"TREATMENT
+. OEEREIEM#
B. S$MMARA#
- 8o3# #++i&$&/ in t4# t%#$t3#nt o+ to2i&it/
$sso&i$t#d 6it4 &4lo%$3"4#ni&ol $nd
sul+$s$l$Ein#
- P%ot#&tiv# $1$inst &/toto2i&it/ in s#v#%# s#"sis
$nd s/st#3i& in+l$33$to%/ %#s"ons# s/nd%o3#
- Not #++#&tiv# $1$inst $3/ot%o"4i& l$t#%$l
s&l#%osis
/. AD$?"#
a. Acetylcysteine 'as (een %emonstrate% to
exert a protecti)e e>ect against cytotoxic agents
in animal mo%els an% some patients.
Acetylcysteine inacti)ates acrolein6 t'e cause o&
'emorr'agic cystitis %uring cyclop'osp'ami%e
an% i&os&ami%e t'erapy. Acetylcysteine may also
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<IND$7ED
7ARDIOMAO8A"HA. Ho1e)er6 acetylcysteine
may protect against %oxoru(icin car%iomyopat'y
1'en a%ministere% prior to or %uring
c'emot'erapy -Dres%ale et al6 +3*B.. 8rotection
against c'loramp'enicol<in%uce% (one<marro1
toxicity 'as also (een %emonstrate% -Aunis et al6
+3*,..
(. A%ministration o& glutat'ione -SH. an% N<
acetylcysteine -NA7. to patients 1it' early septic
s'oc: re%uce% in%icators o& &ree ra%ical acti)ity
more e>ecti)ely t'an %i% SH alone. "'irty
patients in septic s'oc: 1ere treate% 1it'
con)entional t'erapy an% ran%omly assigne% to
recei)e no a%%itional treatment6 intra)enous SH
D0 milligrams/:ilogram/%ay -mg/:g/%ay.6 or SH
D0 mg/:g/%ay plus NA7 D= mg/:g/%ay6 &or =
%ays. By %ay =6 patients in (ot' groups
recei)ing SH s'o1e% a signi@cant %ecrease in
lipoperoxi%ati)e in%exes -expire% et'ane6 plasma
malon%ial%e'y%e. relati)e to (asal )alues -p less
t'an 0.0+. an% relati)e to t'ose o& t'e control
group -p less t'an 0.0+.. !urt'ermore6 )alues &or
t'e group recei)ing (ot' SH an% NA7 1ere
signi@cantly more impro)e% t'an t'ose o& t'e
group recei)ing SH only -p less t'an 0.0+.. At
%ay =6 mortality o& t'e t'ree groups 1as similar6
(ut (y %ay +06 t'e mortality rate in t'e control
group 1as %ou(le t'at o& t'e ot'er t1o -p less
t'an 0.0+.. "'ere 1ere no a%)erse e)ents
associate% 1it' t'e 'ig' %oses o& SH an%
NA7 -Ortolani et al6 B000..
c. Acetylcysteine 1as use% success&ully to treat
S$?!ASA?ACINE "OXI7I"A -a(ay et al6 +33/..
"'e patient %e)elope% se)ere 'epatitis6
%isseminate% intra)ascular coagulation6 'ig'
spi:ing &e)er6 a mononucleosis<li:e syn%rome
an% a %i>use cutaneous ras'. Symptoms
resol)e% &ollo1ing %iscontinuation o& sul&asala;ine
an% IE a%ministration o& N<acetylcysteine.
%. 8reliminary 'uman an% animal reports suggest
t'at acetylcysteine may 'a)e a cytoprotecti)e
e>ect in patients 1it' se)ere SE8SIS an%
associate% systemic inNammatory response
syn%rome -SIRS.. SIRS is an acute illness
c'aracteri;e% (y generali;e% acti)ation o& t'e
en%ot'elium 1'ic' lea%s to multiorgan &ailure
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 inName% 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 =I 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 Nui% 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 +33/2 Bone6 +33B2 Hepsen et al6
+33B2 Mel(ourn F Aoung6 +33B2 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$"E MAO7ARDIA?
IN!AR7"ION (y re%ucing myocar%ial stunning6
re%ucing in&arct si;e (y /BI to G3I6 increasing
le&t )entricular e4ection &raction6 an% re%ucing t'e
se)erity o& )entricular arr'yt'mias %uring
reper&usion -Soc'man et al6 +33,2 Arstall et al6
+33=2 rec' et al6 +33/2 Aoung et al6 +33/2
Da)ies et al6 +33/2 !ar( et al6 +33/2
9irs'en(aum et al6 +33B2 !errari et al6 +3302
Soc'man et al6 +3302 Blaustein et al6 +3*32
Sing' et al6 +3*32 Aruoma et al6 +3*32 !orman
et al6 +3**2 7econi et al6 +3**2 Mestlin F
Mullane6 +3**..
&. Acetylcysteine 1as not e>ecti)e treatment &or
patients 1it' AMAO"RO8HI7 ?A"ERA?
S7?EROSIS -A?S.. In a ran%omi;e%6 %ou(le<
(lin%6 place(o<controlle% stu%y in)ol)ing ++0
patients 1it' A?S6 treatment 1it' acetylcysteine
-=0 mg/:g su(cutaneously. &or +B mont's %i%
not increase sur)i)al or re%uce %isease
progression. Alt'oug' &ree ra%icals are t'oug't
to play a role in t'e pat'ogenesis o& A?S6
treatment 1it' acetylcysteine 1as no more
e>ecti)e t'an place(o in t'is stu%y -?ou1erse et
al6 +33=..
M. DENTAL HYGIENE
+. OEEREIEM#
B. S$MMARA#
- On# stud/ s4o6s $ "ossi0l# %ol# +o%
$&#t/l&/st#in# in d#nt$l 4/1i#n#
/. AD$?"#
a. Dental plaJue 1as re%uce% in patients treate%
1it' acetylcysteine. A %ou(le<(lin% clinical trial
1as con%ucte% in 1'ic' B* )olunteer su(4ects
1ere pro)i%e% a complete oral prop'ylaxis6 t'en
as:e% to per&orm no ot'er oral 'ygiene
measures except to rinse G times per %ay &or a
perio% o& D %ays 1it' eit'er a place(o solution
or t'e test mout'1as' containing a +0I
aJueous solution o& acetylcysteine (u>ere% to
pH ,.=. Su(4ect5s teet' 1ere rescale% an%
repolis'e%. Su(4ects 1ere t'en instructe% to rinse
&or a su(seJuent D<%ay perio% 1it' t'e alternate
mout'1as' so t'at eac' su(4ect ser)e% as t'eir
o1n control. 7omparison o& plaJue in%ices &or
control an% test perio%s s'o1e% a statistically
signi@cant -p less t'an 0.0+. B=.,I re%uction in
plaJue attri(uta(le to t'e presence o&
acetylcysteine -Bo1les F oral6 +3*=..
N. DRUGINDUCED HYPERSENSITIVITY
+. OEEREIEM#
DO),-'N.A.(ON: Adult +$i%
B. S$MMARA#
- A&#t/l&/st#in# 4$s 0##n us#d to t%#$t
"4#n/toin-indu&#d 4/"#%s#nsitivit/
(R#dondo #t $l 1<<7)
- (n#++#&tiv# +o% "%#v#ntin1 4/"#%s#nsitivit/
%#$&tions to t%i3#t4o"%i3-sul+$3#t4o2$Eol#
in 7(V "$ti#nts
/. AD$?"#
a. Acetylcysteine -NA7. at a %ose o& / grams
t1ice %aily 1as not e>ecti)e in HIE patients &or
pre)enting 'ypersensiti)ity reactions to
trimet'oprim<sul&amet'oxa;ole -"M8<SMX.6 a
prop'ylactic treatment against 8neumocystis
carinii pneumonia. In a ran%omi;e% trial 1it' +3*
HIE<in&ecte% patients 1'o 1ere (eing treate%
1it' trimet'oprim *0 milligrams -mg. an%
sul&amet'oxa;ole G00 mg orally t1ice %aily6 3,
patients also recei)e% oral NA7 / grams -+=
milliliters o& a B0I solution. + 'our (e&ore eac'
%ose o& "M8<SMX &or B mont's. 8atients 1ere
&ollo1e% &or / a%%itional mont's 1'ile continuing
to ta:e "M8<SMX 1it'out NA7. "'e nee% to
%iscontinue "M8<SMX treatment (ecause o&
&e)er6 ras'6 or pruritus occurre% in B=I o& t'ose
recei)ing "M8<SMX alone an% in B+I o& t'ose
recei)ing "M8<SMX plus NA7 -pO0.,=.. "'ere
1ere statistically signi@cant %i>erences in
symptoms lea%ing to %iscontinuation (et1een t'e
B groups. NA7 1as not 1ell tolerate% in t'e
&ormulation use%6 e)en t'oug' it 1as
a%ministere% in cola or orange 4uice to ma:e it
more palata(le. Because o& t'e unpleasant taste
an% t'e si%e e>ects o& nausea an% )omiting6
compliance may 'a)e (een less t'an reporte%.
Mit' t'e %ose an% &ormulation use%6 NA7
cannot (e recommen%e% to pre)ent
HA8ERSENSI"IEI"A REA7"ION "O "M8<SMX
in HIE patients Malmsley et al6 +33*..
O. HEMORRHAGIC CYSTITIS PROPHYLAXIS
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# is #++#&tiv# in "%#v#ntin1 o%
%#du&in1 &/&lo"4os"4$3id#- o% i+os+$3id#-
indu&#d 4#3o%%4$1i& &/stitis
- )o3"$%$tiv# studi#s $%# li3it#d $ 1%#$t#%
u%o"%ot#&tiv# #++#&t 6$s o0t$in#d 6it4 3#sn$
4o6#v#% 3#sn$ 4$s not 0##n s4o6n to 0#
su"#%io% to non"4$%3$&olo1i& 3#t4ods o+
"%ot#&tion (4/"#%4/d%$tion)
/. AD$?"#
0. GENERAL INFORMATION
-+. ?imiting aspects o& t'e use o& t'e
c'emot'erapeutic al:ylating agents6 suc' as
cyclop'osp'ami%e an% i&os&ami%e6 'a)e
(een inNammation6 ulceration an% @(rosis
o& t'e urinary (la%%er. "'e inci%ence or
se)erity o& (la%%er %amage can (e re%uce%
(y lo1ering or &ractionating t'e %osage an%
a%eJuate 'y%ration2 'o1e)er6 t'is is not
suLcient to protect t'e (la%%er. N<
acetylcysteine -NA7. 'as (een use% to
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 -Matson6 +3*G..
-B. !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 +0I is excrete% in
t'e urine. -Sc'oeni:e F Dana6 +330..
7omparati)e stu%ies in%icate t'at mesna
-mercaptoet'ane sul&onate.6 anot'er t'iol
compoun% capa(le o& (in%ing 1it' acrolein6
is more e>ecti)e t'an acetylcysteine &or
'emorr'agic cystitis -Milliams 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<in%uce% 'emorr'agic
cystitis -Hasel(erger F Sc'1ing'ammer6
+33=..
3. USE WITH IFOSFAMIDE
-+. Oral acetylcysteine 1as e>ecti)e in
pre)enting i&os&ami%e<in%uce% 'ematuria in
a stu%y o& ten patients -Morgan et al6
+3*+.. 8atients recei)e% i&os&ami%e +.B
grams/sJuare meter/%ay intra)enously &or =
%ays e)ery B* %ays6 1'ile anot'er group
o& +0 patients recei)e% acetylcysteine +
gram orally &our times a %ay on t'e same
%ays i&os&ami%e 1as a%ministere%. O& t'e
+3 patients recei)ing i&os&ami%e alone6 D o&
+0 patients %emonstrate% 'ematuria 1'ile
only / o& +0 patients recei)ing (ot'
acetylcysteine an% i&os&ami%e %e)elope%
'ematuria. In t'ese / patients6 'ematuria
%e)elope% a&ter t'e patients (ecame
nauseate% an% re&use% t'e acetylcysteine
(ut continue% to recei)e i&os&ami%e.
-B. Ele)en o& +* patients 1'o %e)elope%
microscopic 'ematuria -G or greater re%
(loo% cells/'ig' po1er @el%.. 1it' t'e @rst
course o& i&os&ami%e -+B00
milligrams/sJuare meter/%ay &or = %ays6
repeate% e)ery B* %ays. recei)e% oral
acetylcysteine. Acetylcysteine 1as
a%ministere% G times a %ay -as a B0I
solution. &or = %ays along 1it' i&os&ami%e.
"'e @rst %ose 1as starte% B 'ours (e&ore
i&os&ami%e t'erapy. Doses o& /6 ,6 36 or +B
grams/%ay o& acetylcysteine 1ere assesse%.
I& lo1er %oses 1ere tolerate% (y t'e
patient6 t'e %ose 1as escalate% to t'e next
le)el 1it' su(seJuent courses o& treatment.
"'e num(er o& patients per oral %aily %ose
o& acetylcysteine 1as small6 (ut ,
milligrams/%ay appeare% to (e t'e optimum
uroprotecti)e %ose an% 1as tolerate%
1it'out signi@cant nausea or )omiting
-Sla)i: F Saiers6 +3*/..
P. HEPATORENAL SYNDROME
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# i3"%ov#d %#n$l +un&tion in
"$ti#nts 6it4 4#"$to%#n$l s/nd%o3#
- Liv#% +un&tion 6$s not $++#&t#d
/. AD$?"#
a. Renal &unction 1as impro)e% in patients 1it'
early 'epatorenal syn%rome (y treatment 1it' N<
acetylcysteine -NA7.. "1el)e patients meeting
t'e = ma4or %iagnostic criteria &or 'epatorenal
syn%rome 1ere treate% 1it' NA7 -+=0
milligrams/:ilogram -mg/:g. intra)enously &or B
'ours6 &ollo1e% (y continuous in&usion o& +00
mg/:g &or = %ays.. 7reatinine clearance
increase% -p less t'an 0.00+.6 serum creatinine
%ecrease% -p less t'an 0.0B.6 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 ,DI an% =*I6 respecti)ely
-inclu%ing B 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
+. OEEREIEM#
B. S$MMARA#
- -$/ d#&%#$s# tu3o% n#&%osis +$&to% l#v#ls
- -$/ d#&%#$s# $&tiv$t#d su""%#sso% &#lls
- Do#s not $""#$% to #n4$n&# 1lut$t4ion#
"%odu&tion
/. AD$?"#
a. M'en N<acetylcysteine -NA7. 1as teste% in
HIE<patients6 it 1as &oun% to increase plasma
concentrations o& cysteine (ut not to in'i(it &ree<
ra%ical pro%uction (y neutrop'ils2 7DGP cell loss
continue%6 (ut t'e rate o& loss mig't 'a)e (een
slo1e% -A:erlun% et al6 +33,.. "'e %ou(le<(lin%6
place(o<controlle% stu%y 1as complete% in /D
asymptomatic HIE<seropositi)e )olunteers6 1'o
1ere ran%omi;e% to recei)e acetylcysteine -*00
mg per %ay in B %i)i%e% %oses. or place(o &or G
mont's. 8retreatment e>ects s'o1e% t'at HIE<
seropositi)e participants 'a% lo1er plasma
cysteine concentrations6 'ig'er "N!<alp'a le)els6
an% 'ig'er &ree ra%ical acti)ity in neutrop'ils in
plasma t'an %i% non<HIE<seropositi)e controls2
no signi@cant %i>erences 1ere &oun% in
glutat'ione plasma le)els. At t'e en% o& t'e
stu%y6 t'e NA7 group 'a% signi@cantly 'ig'er
plasma cysteine le)els -pO0.00=. an% lo1er "N!<
alp'a le)els -p less t'an 0.0=. compare% 1it'
t'e place(o group6 (ut no %i>erence 1as
o(ser)e% in plasma<in%uce% ra%ical pro%uction (y
neutrop'ils. "1o people %i% not complete t'e
stu%y (ecause o& si%e e>ects.
(. "reatment o& symptom<&ree HIE -'uman
immuno%e@ciency )irus.<in&ecte% patients 1it'
acetylcysteine -A7. an% selenium resulte% in
(ene@cial c'anges in lymp'ocyte su(sets (ut %i%
not a>ect plasma glutat'ione -SH. or t'e
(alance o& oxi%i;e% an% re%uce% SH. In a
ran%omi;e%6 partial crosso)er trial6 +/ patients
1ere gi)en A7 +*00 milligrams/%ay an% so%ium
selenite =00 micrograms/%ay &or BG 1ee:s
-group A.. Anot'er similar ++ patients 1ere gi)en
no treatment &or +B 1ee:s an% t'e acti)e
treatment &or t'e next +B 1ee:s -group B.. At ,
an% +B 1ee:s6 group A s'o1e% a signi@cantly
re%uce% 7DG lymp'ocyte percentage6 7D*
lymp'ocyte count6 an% percentage o& acti)ate%
suppressor cells -7D*/7D/*. relati)e to group B.
Alt'oug' t'ere 1as no increase in 7DG
lymp'ocyte count6 t'e ratio o& 7DG to 7D*
lymp'ocytes rose. "'ese c'anges 1ere regar%e%
as a (ene@cial treatment e>ect. Baseline le)els
o& SH in t'e HIE<in&ecte% patients 1ere lo1er
t'an in 'ealt'y controls. "'e a(sence o& c'ange
in plasma SH concentration o)er BG 1ee:s o&
treatment suggests t'at lo1 cysteine a)aila(ility
is not t'e cause o& t'e SH %epletion in HIE<
in&ecte% patients. Because (aseline an% +B<1ee:
measures o& )iral loa% 1ere so near t'e limit o&
%etection6 t'e a(sence o& c'ange cannot (e
interprete% -?oo: et al6 +33*..
R. ICHTHYOSIS
+. OEEREIEM#
'FF()A)*! Adult #++#&tiv#
B. S$MMARA#
- .o"i&$l $""li&$tion #++#&tiv# in l$3#ll$%
i&4t4/osis in on# %#"o%t#d &$s#
/. AD$?"#
a. "opical application o& a 1ater<in<oil emulsion
containing +0I N<acetylcysteine -NA7.
signi@cantly impro)e% ?AME??AR I7H"HAOSIS
in a //<year<ol% 1oman 1'o 'a% (een treate%
&or B years 1it' acitretin /0 milligrams per %ay
an% urea lotions. "'e NA7<containing emulsion
1as applie% to one &orearm an% t'e )e'icle to
t'e ot'er &orearm. Outstan%ing impro)ement 1as
e)i%ent at = 1ee:s on t'e NA7<treate% arm6
1'ereas t'ere 1as no c'ange in place(o<treate%
areas. A culture o& :eratinocytes s'o1e% t'at
NA7 in'i(ite% cell gro1t' in a %ose< an% time<
%epen%ent manner -Re%on%o F Bau;a6 +333..
S. INHALATION IN%URY
+. OEEREIEM#
'FF()A)*: P#di$t%i& #++#&tiv#
DO),-'N.A.(ON: P#di$t%i& 1ood
B. S$MMARA#
- A#%osoliE#d 4#"$%in $nd $&#t/l&/st#in# to1#t4#%
%#du&#d 3o%t$lit/ in &4ild%#n 6it4 in4$l$tion
in9u%/
/. 8EDIA"RI7#
a. 8rogressi)e pulmonary &ailure an% mortality
1ere re%uce% in c'il%ren 1'o recei)e%
aerosoli;e% 'eparin an% acetylcysteine in
a%%ition to stan%ar% treatment &or (urns an%
smo:e in'alation compare% to c'il%ren 1'o
recei)e% stan%ar% t'erapy alone. !orty<se)en
c'il%ren 1it' (ronc'oscopically i%enti@e%
in'alation in4ury an% nee%ing mec'anical
)entilation recei)e% aerosoli;e% 'eparin =000
units6 alternating 1it' / milliliters o& a B0I
solution o& acetylcysteine6 e)ery B 'ours &or t'e
@rst D %ays a&ter in4ury. Anot'er G/ similar
c'il%ren ser)e% as controls. "'e inci%ences o&
reintu(ation &or progressi)e pulmonary &ailure6
atelectasis an% mortality 1ere all signi@cantly
lo1er in t'e treatment group t'an in t'e control
group -p less t'an 0.0=. -Desai et al6 +33*..
T. KERATOCON%UNCTIVITIS
+. OEEREIEM#
B. S$MMARA#
- 8o3# &$s#s o+ B#%$to&on9un&tivitis (DR* '*')
4$v#
%#s"ond#d to $&#t/l&/st#in# 64il# 3$n/ 4$v# not
- Pl$Gu#s $sso&i$t#d 6it4
IO8.'R -,)O,8 PLAJ,' F'RA.(.(8 4$v# 0##n
#++#&tiv#l/ t%#$t#d 6it4 $&#t/l&/st#in#
15D #/#d%o"s
/. AD$?"#
a. 8laJues associate% 1it' COS"ER M$7O$S
8?AQ$E 9ERA"I"IS 'a)e (een e>ecti)ely
treate% 1it' acetylcysteine +0I eye%rops -Mars'
F 7ooper6 +3*D..
(. Se)enteen patients 1it' :eratocon4uncti)itis
an% corneal mucus plaJues respon%e% 1ell to
ocular a%ministration o& acetylcysteine +0I &our
times %aily. M'en acetylcysteine treatment 1as
%iscontinue%6 plaJues generally %i% not recur
-!raun&el%er et al6 +3DD..
c. Acetylcysteine / to +0I eye%rops -%ilute%
1it' anti(iotic solution. 'as also (een reporte%
to (e success&ul in one patient 1it' 9ERA"I"IS
M$7OSA (ut 1it' normal tear secretion an% no
o)ert systemic %isease -S'a1 F asset6 +3DG..
"'e patient 1as also treate% 1it' a 'y%rop'ilic
contact lens.
%. Acetylcysteine B0I applie% to t'e eyes e)ery
B 'ours resulte% in mar:e% impro)ement in
)isual acuity6 relie& o& &oreign (o%y sensation an%
(lep'arospasm6 an% pre)ention o& mucus
accumulation in a patient 1it' :eratocon4uncti)itis
-Messner F ?ei(o1it;6 +3D+..
e. A %ou(le<(lin%6 cross<o)er6 ran%omi;e% stu%y
assesse% acetylcysteine5s use&ulness -Alsolon F
Bro1n6 +3,*.. In /0 patients 1it' 97S &or +.=
to B0 years6 acetylcysteine B0I an% arti@cial
tears6 applie% e)ery t1o 'ours6 1ere assesse%
&or t1o mont's eac'. "'e acetylcysteine<treate%
group experience% a signi@cant -pO0.0B*.
impro)ement (y o(4ecti)e assessment -slit lamp.6
(ut su(4ecti)e assessment s'o1e% no %i>erence
(et1een t'e t1o treatments.
U. LIPOPROTEIN REDUCTION
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# is not #++#&tiv# +o% %#du&in1
s#%u3 li"o"%ot#in &on&#nt%$tions
/. AD$?"#
a. One report in%icate% a =0I to D=I re%uction
in t'e plasma concentration o& lipoprotein -A.
-?p-A.. in t1o patients gi)en B an% G grams N<
acetylcysteine -NA7. -Stalen'oe&6 +33+..
Ho1e)er6 no c'ange in +B patients 1it' 'ig'
?p-A. an% D )olunteers 1it' normal ?p-A. 1as
note%. "'e +0I (ioa)aila(ility o& NA7 an% its
large )olume o& %istri(ution suggest t'at )ery
'ig' oral %oses 1oul% (e necessary to reac' a
serum concentration 'ig' enoug' -a(o)e *0
milligrams/liter. to %issociate apo-A. &rom t'e
lo1<%ensity lipoprotein particle.
(. A small (ut signi@cant %ecrease in ?p-A. -a
complex o& lo1 %ensity lipoproteins.
concentration -DI. 1as o(ser)e% a&ter t'e
a%ministration o& NA7 in %oses o& +.B g per %ay
&or , 1ee:s -9roon et al6 +33+.. "'e aut'or &elt
t'at t'is re%uction 1as not clinically signi@cant.
c. Acetylcysteine 'a% no e>ect on t'e
suscepti(ility o& lo1<%ensity lipoprotein -?D?. to
oxi%ation -9lein)el% et al6 +33B.. "'is stu%y %oes
not support t'e suppose% antioxi%ation action o&
N<acetylcysteine.
V. LIVER DISORDERS
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# 3$/ "%odu&# #n4$n&#d liv#%
&i%&ul$tion $nd +un&tion in "$ti#nts 6it4
4#"$ti& i3"$i%3#nt
/. AD$?"#
a. N<acetylcysteine -NA7. in%uce% signi@cant
increases in li)er (loo% No1
-HE8A"OS8?AN7HNI7. in%ex6 car%iac in%ex6
an% li)er &unction in patients experiencing t'e
early stage o& septic s'oc:. In a ran%omi;e%6
%ou(le<(lin% stu%y6 patients experiencing t'e
onset o& SE8"I7 SHO79 1it'in t'e past BG
'ours 1ere assigne% to recei)e eit'er place(o
-nO/0. or intra)enous NA7 +=0
milligrams/:ilogram -mg/:g. gi)en as a loa%ing
%ose6 &ollo1e% (y a continuous in&usion o& NA7
+B.= mg/:g/'our gi)en o)er 30 minutes -nO/0..
All patients 1ere 'emo%ynamically sta(le a&ter
con)entional resuscitation6 an% maintaine% on
mec'anical )entilation. Hepatosplanc'nic -HSp.
per&usion 1as measure% (y in%ocyanine green
%ye tec'niJue6 an% microsomal li)er &unction 1as
assesse% (y t'e %egree o& meta(olism impose%
upon lignocaine gi)en as a single + mg/:g
in&usion. 8atients recei)ing NA7 experience%
signi@cant increases in HSp (loo% No1 in%ex
an% car%iac in%ex6 compare% 1it' patients
recei)ing place(o -pO0.0+ an% 0.0B6
respecti)ely.. NA7<group patients also
experience% signi@cant increases in serum
concentrations o& monoet'ylglycinexyli%i%e
-MEX.6 t'e primary meta(olite o& lignocaine6
compare% 1it' t'e place(o group -pO0.0G.2 a
signi@cant correlation 1as &oun% (et1een MEX
an% t'e li)er (loo% No1 in%ex -p less t'an or
eJual to 0.0+.. A signi@cant %ecrease 1as seen
in t'e %i>erence (et1een arterial an% gastric
mucosal car(on %ioxi%e tension -pO0.0=.6
in%irectly reNecti)e o& t'e impro)ement in
splanc'nic per&usion sustaine% (y patients
recei)ing NA7. "'ere 1ere no serious a%)erse
e)ents o(ser)e% 1it' t'e in&usion o& NA72
'o1e)er6 patients recei)ing NA7 experience% a
signi@cant %ecline in pulmonary oxygenation a&ter
t'e NA7 in&usion -Ran: et al6 B000..
(. Acetylcysteine appears to impro)e 'epatic
circulation an% oxygen %eli)ery an% consumption
in patients 1it' se)ere li)er %ys&unction -li)er
&ailure6 alco'olic or autoimmune 'epatitis6 an%
li)er transplantation.. !i&teen 'emo%ynamically
sta(le patients 1it' 'epatic impairment an% ot'er
critical illness an% reJuiring mec'anical
)entilation 1ere in&use% 1it' acetylcysteine +=0
mg/:g in B=0 m? o& %extrose =I in 1ater
-D=M. o)er += minutes &ollo1e% (y =0 mg/:g in
D=M B=0 m? o)er G= minutes at an in&usion
rate o& ,B.= m?/'r. Impro)e% in%ocyanine green
clearance in +/ o& t'e += patients suggeste%
impro)e% 'epatic circulation. Also6 oxygen
%eli)ery -DoB. an% oxygen consumption -EoB.
1ere &oun% to increase signi@cantly in +/ o& +=
su(4ects. "'ese in)estigators conclu%e% t'at
circulatory an% 'emo%ynamic (ene@ts associate%
1it' acetylcysteine in&usion may (e use&ul in
patients 1it' li)er %isor%ers or ot'er critical
illnesses 1'ere systemic or regional circulation is
compromise% -De)lin et al6 +33D..
c. "'ree patients 1'o %e)elope% HE8A"I7
EENO<O77?$SIEE DISEASE a&ter allogeneic
stem cell transplantation -AS7". 1ere
success&ully treate% 1it' acetylcysteine. All t'ree
patients mani&este% ele)ate% (iliru(in (e&ore %ay
B+ a&ter AS7"6 'epatomegaly6 ascites6 an%
unexpecte% 1eig't gain o& more t'an =I.
Acetylcysteine 1as a%ministere% intra)enously6
typically as +00 to +=0 milligrams/:ilogram per
%ay &or +B to /+ %ays6 %epen%ing on t'e
se)erity o& t'e con%ition. Biliru(in6 serum li)er
en;ymes6 an% ele)ate% cyto:ines returne% to
normal Acetylcysteine may (e an e>ecti)e
treatment option &or t'is o&ten &atal %isease
-Ring%en et al6 B000..
%. In&usion o& acetylcysteine -A7. into sta(ili;e%
patients 1it' !$?MINAN" HE8A"I7 !AI?$RE
%i% NO" impro)e oxygen upta:e or tissue
oxygen extraction. Ele)en patients recei)e% a
loa%ing %ose o& A7 +=0 milligrams/:ilogram
-mg/:g. in B00 milliliters -m?. =I %extrose o)er
+= minutes6 &ollo1e% (y =0 mg/:g in =00 m?
=I %extrose o)er G 'ours6 an% t'en +00 mg/:g
in + ? o)er +, 'ours. Se)en patients recei)e%
)olume<matc'e% in&usions o& =I %extrose alone.
Oxygen consumption -EOB. an% oxygen %eli)ery
-DOB. 1ere measure% in%epen%ently. Mit'
respect to car%iac output6 t'ere 1ere respon%ers
an% nonrespon%ers6 (ut t'ere 1ere no signi@cant
%i>erences (et1een t'e B groups. In all (ut /
cases6 t'ere 1as no relations'ip (et1een EOB
an% DOB. "'ere also 1ere no correlations
(et1een A7 concentrations an% mean arterial
pressure6 car%iac output6 or systemic )ascular
resistance. "'ese results %i>er &rom t'ose o&
ot'er stu%ies6 per'aps (ecause o& t'e
in%epen%ent %eterminations o& EOB an% DOB
an% (ecause o& t'e %egree o& illness o& t'e
patients -Mals' et al6 +33*..
W. MALARIA
+. OEEREIEM#
'FF()A)*: Adult in&on&lusiv#
B. S$MMARA#
- L$%1#% t%i$ls 6it4 3o%t$lit/ $s $n #nd"oint $%#
n##d#d
- A "%o1nosti& indi&$to% l$&t$t# l#v#ls 6$s
i3"%ov#d 6it4 n-$&#t/l&/st#in# t4#%$"/
/. AD$?"#
a. Serum lactate le)els in su(4ects 1it' SEEERE
MA?ARIA returne% to normal t1ice as Juic:ly
a&ter N<acetylcysteine -NA7. a%ministration
compare% to place(o in a %ou(le<(lin%
prospecti)e stu%y. A%ult males -+* to =0 years6
nO/0. 1it' se)ere malaria (eing treate% 1it'
Juinine 1ere a%ministere% eit'er /00
milligrams/:ilogram -mg/:g. NA7 or place(o &or
B0 'ours. O)er += minutes6 a NA7 loa%ing %ose
-+=0 mg/:g. 1as intra)enously in&use% in B00
milliliters -m?. o& =I %extrose. "'is 1as &ollo1e%
(y a G<'our in&usion o& NA7 =0 mg/:g in =00
m? o& =I %extrose. O)er t'e next +, 'ours6
+00 mg/:g in one liter o& =I %extrose 1as
in&use%. 8lace(o 1as =I %extrose. In NA7<
treate% su(4ects6 lactate concentrations 1ere
restore% to normal t1ice as Juic:ly -me%ianOB+
'ours6 3=I con@%ence inter)al +B to /, 'ours.
compare% to place(o su(4ects -me%ianOGB 'ours6
3=I con@%ence inter)al /0 to *G 'ours2
pO0.00B.. In se)ere malaria6 ele)ate% (loo%
lactate is a signi@cant prognosticator o& outcome
-Matt et al6 B00B..
X. MECONIUM ILEUS
+. OEEREIEM#
DO),-'N.A.(ON: Adult 1ood! "#di$t%i& 1ood
B. S$MMARA#
- A&#t/l&/st#in# #n#3$s #++#&tiv# in %#3ovin1
3#&oniu3 "lu1s
/. AD$?"#
a. "'e use o& acetylcysteine enemas 'as (een
reporte% in connection 1it' meconium ileus6
meconium plugs6 an% meconium ileus eJui)alent
-Spiro6 +3DD.. Meconium ileus eJui)alent
%escri(es intestinal o(struction in cystic @(rosis
patients outsi%e t'e neonatal perio% -Spiro6
+3DD2 Ho%son et al6 +3D,.. Some a%ults 1it'
cystic @(rosis an% meconium ileus eJui)alent
'a)e (een success&ully treate% 1it'
acetylcysteine enemas -Ho%son et al6 +3D,..
G. 8EDIA"RI7#
a. Meconium ileus an% plugs6 generally seen in
ne1(orn in&ants6 are c'aracteri;e% (y (o1el
o(struction cause% (y inspissate%6 protein<ric'6
tenacious meconium -Spiro6 +3DD2 S'ir:ey6 +3D=2
9opel6 +3DB.. Meconium ileus is present in
a(out +0I to B0I o& in&ants 1it' cystic @(rosis6
1'ile meconium plugs are not relate% to t'e
%isease -Spiro6 +3DD2 9opel6 +3DB..
(. One report %escri(e% t'e success&ul treatment
o& a neonate 1it' acetylcysteine enemas
-Simpson et al6 +3,*.. A +0I acetylcysteine
solution -B0I acetylcysteine6 /0 milliliters2 normal
saline6 /0 milliliters. 1as a%ministere% as an
enema an% t'e (uttoc:s 1ere 'el% toget'er
manually &or @)e minutes. A &e1 minutes later a
+0<cm ri((on o& meconium 1as passe%. "'e
proce%ure 1as repeate% &our times 1it'in +G
'ours6 1it' goo% results. At t'at time B0
milliliters o& t'e +0I solution 1as gi)en )ia
nasogastric tu(e passe% into t'e upper 4e4unum2
six 'ours later a 'uge stool 1as passe%6
clearing t'e (o1el.
c. A 3<year<ol% girl 1it' cystic @(rosis an%
meconium ileus eJui)alent 1as treate%
success&ully 1it' GI acetylcysteine enemas
-%ilute% to /00 milliliters 1it' normal saline. at
t1el)e<'our inter)als -@)e enemas total. -Derman
et al6 +3D=..
Y. MULTISYSTEM ORGAN FAILURE PREVENTION
+. OEEREIEM#
B. S$MMARA#
- )ontinuous in+usion o+ $&#t/l&/st#in# to
&%iti&$ll/
ill "$ti#nts did not %#du&# 3o%t$lit/
/. AD$?"#
a. Mortality 1as NO" %ecrease% (y in&usion o&
N<acetylcysteine -NA7. into critically ill6
mec'anically )entilate% patients 1'o reJuire%
support o& t1o or more ma4or organ systems or
1'o 'a% mo%erate or se)ere organ &ailure o&
one system. $pon a%mission to t'e intensi)e
care unit -I7$.6 patients &ul@lling stu%y criteria
1ere ran%omly assigne% to recei)e NA7 as a
(olus o& +=0 milligrams/:ilogram -mg/:g. in B=0
milliliters -m?. o& =I %extrose6 &ollo1e% (y a
continuous in&usion o& +B mg/:g/'our in =00 m?
o& =I %extrose per BG 'ours -nOG+.6 or =I
%extrose -place(o2 nOG=.. "reatment continue%
&or a minimum o& / %ays an% a maximum o& =
%ays6 %epen%ing on multiple organ %ys&unction
scores. ?i)er &unction 1as signi@cantly impro)e%
in NA7<treate% patients -pO0.0+.6 (ut t'e &unction
o& no ot'er organ system 1as impro)e% (y
NA7. Among patients a%mitte% to t'e I7$ more
t'an BG 'ours a&ter 'ospital a%mission6 mortality
in t'e NA7 group 1as nearly t1ice t'at in t'e
place(o group6 suggesting t'at NA7 at t'e time
an% %oses gi)en may actually 'a)e 'a% 'arm&ul
e>ects -Molnar et al6 +333.
4. NITRATE TOLERANCE
+. OEEREIEM#
B. S$MMARA#
- .4# v$sodil$to% #++#&ts o+ int%$v#nous ((V)
nit%o1l/&#%in &$n 0# #n4$n&#d 6it4 &on&u%%#nt (V
$&#t/l&/st#in# (NA)) (7o%o6itE #t $l 1<83!
Ainni+o%d #t $l 1<8?)
- Nit%o1l/&#%in tol#%$n&# &$n 0# $tt#nu$t#d 0/
&on&u%%#nt NA) $d3inist%$tion (Bo#s1$$%d #t $l
1<<1)
- ,n&l#$% 64#t4#% t4#s# %#sults 4$v# $n/ &lini&$l
si1ni+i&$n&# in t4# 3$n$1#3#nt o+ 4#$%t dis#$s#
o% 4#$%t +$ilu%#
/. AD$?"#
a. 7oncurrent a%ministration o& NA7 attenuates
loss o& )aso%ilatory response to nitroglycerin in
some angina patients 1it' normal )entricular
&unction. In a controlle% stu%y -8i;;ulli et al6
+33D.6 patients 1it' angina pectoris an% normal
le&t )entricle &unction 1ere teste% &or response to
nitroglycerin 0.* milligram -mg. su(lingually
(e&ore an% a&ter a G*<'our continuous
nitroglycerin in&usion -+.= micrograms/:ilogram
-:g./minute.. !or +, patients6 a concomitant
in&usion o& NA7 -= mg/:g/'our. 1as a%ministere%
1it' t'e G*<'our nitroglycerin in&usion. A group
o& += matc'e% controls recei)e% no concurrent
NA7 %uring t'e G*<'our nitroglycerin in&usion.
Ele)en o& +, in t'e NA7 group respon%e% to
su(lingual nitroglycerin a&ter t'e G*<'our in&usion6
1'ile only + in t'e control group respon%e% to
t'e secon% %ose o& su(lingual nitroglycerin.
(. In contrast6 one stu%y reporte% t'at N<
acetylcysteine at +00 milligrams/:ilogram
intra)enously %i% not re)erse tolerance to t'e
'emo%ynamic an% antianginal e>ects o&
isosor(i%e %initrate in +B patients 1it' c'ronic
sta(le angina -8ar:er et al6 +3*D.. Ho1e)er6 in
++ 'ealt'y )olunteers6 N<acetylcysteine
potentiate% an% prolonge% t'e 'ea%ac'e
response an% nitroglycerin<in%uce% %ilation o& t'e
temporal artery at lo1 %oses o& nitroglycerin
-I)ersen6 +33B..
c. N<acetylcysteine -B00 milligrams/:ilogram
orally. 1as at least partially e>ecti)e in re)ersing
t'e tolerance o(ser)e% in HEAR" !AI?$RE
patients recei)ing continuous IE in&usions o&
nitroglycerin -8ac:er et al6 +3*D.. N<
acetylcysteine a%ministration resulte% in
restoration o& 'emo%ynamic (ene@ts6 approac'ing
t'ose o(ser)e% at t'e start o& t'e nitroglycerin
in&usion.
%. !or More In&ormation#
See Drug 7onsult re&erence# KNI"RA"E
"O?ERAN7EK
AA. OTITIS MEDIA
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# %#du&#d t4# n##d +o% %#ins#%tion
o+ v#ntil$tion tu0#s in &4ild%#n +o% %#&u%%#nt
otitis 3#di$ 6it4 #++usion
/. 8EDIA"RI7#
a. Instillation o& N<acetylcysteine -NA7. into t'e
ears o& c'il%ren un%ergoing insertion o&
)entilation tu(es -E". &or otitis me%ia 1it'
e>usion -OME. ten%e% to lengt'en t'e time until
E" extrusion an% signi@cantly re%uce% t'e rate
o& recurrence o& OME reJuiring reinsertion o&
E"s. In a ran%omi;e%6 %ou(le<(lin%6 place(o<
controlle% trial6 D= c'il%ren age% + to D years
un%ergoing (ilateral E" insertion &or OME 1ere
ran%omi;e% to recei)e eit'er NA7 -Mucomyst
solution B0 milligrams/milliliter. or place(o
-)e'icle only. in one ear -instille% t'roug' a
tu(e. at t'e time o& tu(e insertion. "'e
contralateral ear 1as treate% only 1it' E"
insertion. NA7 or place(o treatments 1ere
repeate% on t'e t'ir% an% se)ent' post<operati)e
%ays. "ime to E" extrusion ten%e% to (e longer
in t'e NA7<treate% ears t'an in place(o< treate%
ears -3 )s D mont's. (ut t'e %i>erence 1as not
signi@cant. Recurrence o& OME 1as also not
less in NA7< treate% t'an in place(o<treate%
ears. Ho1e)er6 persistent OME reJuiring re<
insertion o& E"s 1as signi@cantly less &reJuent in
NA7<treate% ears t'an in place(o<treate% ears
-+GI )s /DI6 p less t'an 0.0B=. an% also in
untreate% ears o& t'e NA7 group t'an in
untreate% ears o& t'e place(o group -+3I )s
G=I.. "'e total num(er o& episo%es o& mi%%le
ear pro(lems 1as signi@cantly lo1er in t'e NA7
group t'an in t'e place(o group -p less t'an
0.0B=.6 resulting in signi@cantly &e1er clinic )isits
(y c'il%ren in t'e NA7 group -pO0.0/*/. %uring
&ollo1< up -++ to /3 mont's. -O)esen et al6
B000..
AB. PSEUDOPORPHYRIA HEMODIALYSISINDUCED
1. OVERVIEW
2. SUMMARY
- 7$s "%o3ot#d 4#$lin1 o+ 0list#%s $nd #%osions
(2 &$s#s)
3. ADULT
a. S:in lesions resem(ling porp'yria cutanea
tar%a (ut not associate% 1it' ele)ate% plasma
porp'yrin le)els mani&este% in B 1omen 1'o
'a% (een un%ergoing 'emo%ialysis &or +0 an% D
years6 respecti)ely. "'e only a(normal la(oratory
test 1as 'ig'er<t'an<normal &erritin6 &or (ot'
1omen. A&ter elimination o& o()ious possi(le
causes6 t'e 1omen 1ere treate% 1it' N<
acetylcysteine -NA7.# B00 milligrams -mg. G
times per %ay &or one 1oman an% ,00 mg t1ice
%aily &or t'e ot'er. ?esions cleare% 1it'in B
mont's. In t'e @rst case6 %iscontinuing NA7
resulte% in a recurrence o& lesions6 1'ic' again
cleare% a&ter restarting NA7 treatment. "'ere
1ere no &urt'er recurrences , mont's later
-Ea%ou%<Seye%i et al6 B000..
AC. RENAL FUNCTION IMPAIRMENT CONTRAST
AGENTINDUCED
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# "%#v#nt#d %$dio1%$"4i& &ont%$st
$1#nt-indu&#d %#du&tions o+ %#n$l +un&tion in
%#n$ll/ i3"$i%#d "$ti#nts und#%1oin1 &o3"ut#d
to3o1%$"4i& i3$1in1 6it4 $ nonioni&
lo6-os3ol$lit/ %$dio1%$"4i& &ont%$st $1#nt
/. AD$?"#
a. 8rop'ylactic use o& acetylcysteine -A77.
signi@cantly re%uce% t'e ris: o& ra%iograp'ic
contrast agent<in%uce% re%uctions in renal
&unction6 in patients 1it' (aseline renal
insuLciency. In a ran%omi;e%6 %ou(le<(lin%6
clinical stu%y6 patients 1it' (aseline renal
insuLciency -mean serum creatinine
concentrations eJual to B.G milligrams/%eciliter
-mg/%?.. prior to un%ergoing computer
tomograp'y 1it' a ra%iograp'ic contrast agent
-R7A. 1ere assigne% to recei)e B %aily oral
%oses o& eit'er place(o -nOGB. or A77 ,00 mg
-nOG+.6 gi)en on t'e %ay (e&ore an% t'e %ay o&
contrast agent a%ministration. All patients
recei)e% concomitant intra)enous 'y%ration 1it'
+ m?/:ilogram 0.G=I saline6 &or +B 'ours prior
to6 an% +B 'ours a&ter t'e a%ministration o&
contrast agent -D= m? o& nonionic6 lo1<osmolality
iopromi%e 0.,B/ grams/m?.. An acute contrast
agent<in%uce% re%uction in renal &unction -7AIR!.
1as %e@ne% as an increase in serum creatinine
concentration o& 0.= mg/%? G* 'ours a&ter R7A
a%ministration. Mean serum creatinine
concentration increase% a&ter G* 'ours6 &rom B.G
to B., mg/%? in patients recei)ing place(o6
compare% 1it' a re%uction &rom B.= to B.+
mg/%? in t'e A77 group2 t'e a(solute c'ange in
serum creatinine concentration 1as signi@cantly
greater in t'e place(o group -p less t'an 0.00+..
8atients recei)ing place(o 'a% increases a&ter
G* 'ours in mean serum urea nitrogen
concentration -B$N2 &rom GG to GD mg/%?.6
1'ereas B$N signi@cantly %ecline% in t'e A77
group -&rom =+ to GG mg/%?2 p less t'an 0.00+..
7AIR! occurre% in 3 o& GB -B+I. patients
recei)ing place(o compare% 1it' + o& G+
patients -BI. recei)ing A77 -pO0.0+6 relati)e
ris:O0.+2 3=I con@%ence inter)al6 0.B to 0.3.. In
a su(<group o& patients 1it' (aseline serum
creatinine concentrations greater t'an B.= mg/%?6
= o& +B -GBI. place(o<group patients %e)elope%
7AIR! compare% 1it' none o& +/ patients
recei)ing A77 -pO0.0B.. "ransient %i;;iness an%
gastrointestinal %iscom&ort 1ere t'e only a%)erse
e)ents reporte% &or (ot' groups -"epel et al6
B000..
AD. RESPIRATORY DISTRESS SYNDROME ADULT
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# 4$s 4$d 0#n#+i&i$l #++#&ts in
ARD8
"$ti#nts
/. AD$?"#
a. Repletion o& glutat'ione (y a%ministration o&
acetylcysteine to patients 1it' a%ult respiratory
%istress syn%rome -ARDS. may re%uce t'e
%uration o& lung in4ury. In a ran%omi;e%6 %ou(le<
(lin% stu%y o& patients 1it' ARDS o& )arious
etiologies6 +G patients recei)e% N<acetylcysteine
-NA7. D0 milligrams/:ilogram (o%y 1eig't
-mg/:g.6 +D recei)e% anot'er cysteine precursor
-?<B<oxot'ia;oli%ine<G<car(oxylate6 O"C. ,/
mg/:g6 an% += recei)e% place(o6 intra)enously
e)ery * 'ours &or +0 %ays. Re% (loo% cell
glutat'ione increase% signi@cantly in t'e NA7
group -p less t'an 0.0=. %uring t'e +0 %ays. O&
t'e patients recei)ing NA7 or O"C6 /3I
%e)elope% a ne1 organ &ailure %uring treatment6
1'ile D/I o& t'e place(o group %e)elope% a
ne1 organ &ailure -pO0.0=D.. Mortality a&ter /0
%ays o& &ollo1<up 1as not %i>erent among
groups -Bernar% et al6 +33D..
(. Acetylcysteine 1as a%ministere% to a patient
1it' AD$?" RES8IRA"ORA DIS"RESS
SANDROME an% renal &ailure as a complication
o& acute pancreatitis -Bragan;a et al6 +3*,..
Acetylcysteine 1as gi)en at 'al& t'e %osage
recommen%e% &or acetaminop'en poisoning an%
gi)en o)er =, 'ours. "'e precise %ose an%
route 1ere not speci@e% in t'is report6 alt'oug'
t'e intra)enous route 1as implie%. Mit'in DB
'ours o& t'e start o& acetylcysteine6 inotropic an%
renal support 1ere no longer nee%e%6 an% t'e
nee% &or oxygen 1as re%uce% &rom +00I to
=0I.
AE. RESPIRATORY TRACT INFECTIONS
+. OEEREIEM#
DO),-'N.A.(ON: Adult 1ood! "#di$t%i& 1ood
B. S$MMARA#
- '++i&$&ious 64#n us#d in &o30in$tion 6it4
)'F,RO>(-' to t%#$t $dult $nd "#di$t%i&
%#s"i%$to%/
in+#&tions
- 8u&&#ss+ull/ us#d $s (NFL,'NIA PROP7*LA>(8 in
#ld#%l/ $nd d#0ilit$t#d "$ti#nts 64o 4$d not
%#&#iv#d in+lu#nE$ i33uniE$tion
/. AD$?"#
a. Se)eral reports %escri(e t'e e>ecti)eness o&
t'e com(ination o& A7E"A?7AS"EINE an%
7E!$ROXIME in t'e treatment o& respiratory
tract in&ections in in&ants -Rameng'i et al6 +3*3.6
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<@)e a%ult patients6 B= 1it' acute
(ronc'opulmonary respiratory tract %iseases an%
G0 1it' acute exacer(ations o& c'ronic
respiratory tract in&ections6 1ere treate% (y
means o& intramuscular in4ection o& a
com(ination o& + g ce&uroxime an% /00 mg
acetylcysteine. 8atients 1ere %i)i%e% into B
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 ,B o& t'e ,=
patients. O& a total o& =B 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 -nOB,B.6
oral N<A7E"A?7AS"EINE ,00 milligrams t1ice
%aily t'roug'out t'e col% an% Nu season -,<
mont' %uration. signi@cantly %ecrease% t'e
inci%ence o& symptomatic inNuen;a cases. None
o& t'e su(4ects 'a% respiratory %isease at
(aseline or recei)e% t'e inNuen;a )accine. In
t'e acti)e an% control groups6 inNuen;a occurre%
in B3I an% =+I o& su(4ects6 respecti)ely.
Alt'oug' t'e rate o& serocon)ersion 1as similar6
only B=I o& patients experience% clinical
symptoms 1'ile on acetylcysteine6 as compare%
to D3I o& t'ose on place(o. N<acetylcysteine
also en'ance% cell<me%iate% immunity 1it'
regar% to antigenic s:in testing. It is unclear
1'at (ene@t6 i& any6 acetylcysteine mig't o>er to
patients 1'o are appropriately immuni;e% against
inNuen;a -De !lora et al6 +33D..
%. A7E"A?7AS"EINE may (e (ene@cial as an
a%4unct to anti<inNammatory t'erapy in patients
1it' !IBROSIN A?EEO?I"IS -!A.. In an open<
la(el case series stu%y6 +* patients 1it' !A
1ere a%ministere% acetylcysteine ,00 milligrams
t'ree times %aily &or +B 1ee:s -Be'r et al6
+33D.. ?ung &unction parameters 1ere
signi@cantly impro)e% (y acetylcysteine in
patients on immunosuppressi)e t'erapy -p less
t'an 0.0+.. Bronc'oal)eolar la)age analysis
s'o1e% increases in glutat'ione an% %ecreases
in met'ionine sul&oxi%e6 in%icating an antioxi%ant
e>ect at t'e al)eolar sur&ace. "'e %rug 1as 1ell
tolerate%. It 1as recommen%e% t'at a place(o<
controlle% trial (e con%ucte% o& acetylcysteine as
a%4uncti)e t'erapy in @(rosing al)eolitis.
G. 8EDIA"RI7#
a. One stu%y reporte% t'e eLcacy o& com(ine%
ce&uroxime -,0 to +00 milligrams/:ilogram/%ay.
an% N<acetylcysteine -B0 to /0
milligrams/:ilogram/%ay. &or = to +0 %ays in t'e
treatment o& lo1er respiratory tract in&ection in
c'il%ren. Bot' %rugs 1ere gi)en intramuscularly
-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 B0 in&ants ranging in
age &rom +0 mont's to B 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/< /.B %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..
AF. S%OGREN&S SYNDROME
+. OEEREIEM#
B. S$MMARA#
- A&#t/l&/st#in# $""#$%s to l$&B #++i&$&/ in t4#
t%#$t3#nt o+ 89o1%#n:s s/nd%o3#
/. 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' N<
acetylcysteine &or +G %ays -Na'ir6 +3*3.. "'e
control group consiste% o& eig't patients 1it'
r'eumatoi% art'ritis (ut 1it'out xerostomia an%/or
:eratocon4ucti)itis sicca. Su(4ecti)e ocular an%
oral impro)ement 1as marginal2 no signi@cant
c'ange in o(4ecti)e parameters -op't'almic or
oral. 1as registere% except &or an increase in
en;yme concentration. No serious si%e e>ects
1ere reporte%.
(. Among B0 patients 1it' SHOREN5S
SANDROME 1'ose :eratocon4uncti)itis %i% not
respon% to replacement t'erapy 1it' arti@cial
tears6 , patients impro)e% 1it' +B mont's o&
topical treatment 1it' acetylcysteine =I6 +/
s'o1e% no c'ange6 an% one 1orsene%
-Milliamson et al6 +3DG..
AG. SURGERY CARDIOPULMONARY
+. OEEREIEM#
B. S$MMARA#
- On# stud/ s4o6#d "ositiv# #++#&ts o+
$&#t/l&/st#in# t%#$t3#nt 0#+o%# su%1#%/
/. AD$?"#
a. 8re<operati)e acetylcysteine -NA7. may (e
use&ul in maintaining respiratory &unction an%
%o1nregulating immune system responses to
7ARDIO8$?MONARA S$RERA an%
extracorporeal circulation. 8atients un%ergoing
car%iac surgery 1ere a%ministere% pre<surgery
acetylcysteine -loa%ing %ose6 DB
milligrams/:ilogram -mg/:g. intra)enously o)er +
'our2 continuous in&usion o& DB mg/:g o)er +B
'ours -)olume =00 milliliters -m?... A&ter surgery
t'e oxygenation in%ex -partial pressure o&
oxygen in arterial (loo%/&ractional inspire% oxygen
-8aOB/!IOB.. 1as more &a)ora(le in patients
1'o 'a% (een pre<treate% 1it' NA7. "'e
increase in plasma neutrop'il elastase acti)ity
1as mo%erate% in t'e NA7 group compare% 1it'
controls. Interleu:in<* an% myeloperoxi%ase
concentrations 1ere lo1er6 an% glutat'ione -SH.
le)els more sta(le in NA7<treate% patients -De
Bac:er et al6 +33,..
AH. UNVERRICHTLUNDBORG DISEASE
+. OEEREIEM#
B. S$MMARA#
- (n isol$t#d &$s#s $&#t/l&/st#in# t%#$t3#nt 4$s
%#sult#d in 3$%B#dl/ i3"%ov#d +un&tion in
"$ti#nts 6it4 ,nv#%%i&4t-Lund0o%1 dis#$s#
/. AD$?"#
a. A G0<year<ol% man 1it' a 'istory o& BD years
o& tonic<clonic sei;ures an% progressi)e
%eterioration o& speec' an% cognition %ue to
genetically con@rme% $n)erric't<?un%(org
%isease -an autosomal recessi)e %egenerati)e
%isor%er. s'o1e% %ramatic impro)ement 1'en
treate% 1it' N<acetylcysteine -NA7. / grams/%ay
an% antioxi%ant )itamins. 8rior to treatment 1it'
NA76 'e mani&este% se)ere action myoclonus6
1orsening 1it' sensory stimulation o& any type6
an% spo:e in one< to t'ree<1or% p'rases. He
coul% ta:e only one or t1o steps6 1it' support
(y atten%ants. One 1ee: a&ter (eginning NA7
treatment6 'e 1as 1al:ing all %ay in t'e
1or:s'op6 'is tremors 'a% %iminis'e%
signi@cantly6 an% 'e 1as tal:ing more. At a
meeting6 'e reporte%ly tal:e% &or + 'our6 Nuently.
A&ter G.= mont's o& sustaine% impro)ement6 'e
stoppe% ta:ing NA7 &or a 1ee: (ecause o& t'e
unappealing taste. Mit'in / %ays6 'is careta:ers
notice% re%uce% Nuency o& speec' an%
%eterioration o& 'is a(ility to 1al:. He restarte%
me%ication an% impro)ement 1as e)i%ent in B
%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 B atypical6 (rie& -=< to +0<secon%. spells
an% no generali;e% sei;ures -Sel1a6 +333..
AI. URINARY TRACT MUCOLYSIS
+. OEEREIEM#
B. S$MMARA#
- On# %#"o%t d#s&%i0#s su&&#ss+ul us# o+
$&#t/l&/st#in# in $&4i#vin1 u%in$%/ t%$&t
3u&ol/sis
/. AD$?"#
a. Acetylcysteine 1as e>ecti)ely use% &or relie&
o& mucinous o(struction o& t'e %istal ureter a&ter
a mi%<ureteral replacement 1it' ileum.
Acetylcysteine -/00 milliliters o& +I solution. 1as
instille% at lo1 pressure )ia nep'rostomy tu(e
&ollo1ing %ocumentation o& t'e o(struction 1it' a
nep'rostogram. 8atency o& t'e ureter 1as
ac'ie)e% 1it'in = minutes. Re<o(struction ensue%
(ut it resol)e% 1it' repeat percutaneous
instillation o& acetylcysteine. 8atency6 con@rme%
(y a &ollo1<up nuclear renogram at G mont's6
1as maintaine% 1it' D00 milligrams
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<acetylcysteine as a mucolytic in
/, pe%iatric patients 1it' cystic @(rosis -Rat4en
et al6 +3*=.. 8atients 1ere ran%omi;e% to
recei)e eit'er am(roxol /0 milligrams -mg.6 N<
acetylcysteine B00 mg6 or place(o / times a %ay
&or +B 1ee:s. "'irty<t1o patients complete% t'e
stu%y. All c'anges in pulmonary &unction test
parameters 1ere (elo1 t'e statistical %etection
limit -p greater t'an 0.0=.2 no signi@cant clinical
%i>erences 1ere &oun% (et1een t'e / groups.
Signi@cant impairment 1as note% in t'e place(o
group6 (ut 1as &elt to (e coinci%ental. None o&
t'e patients5 parents reporte% impro)ement an%
,,I o& t'e total &elt t'at t'eir c'il% 'a% recei)e%
place(o. A t'erapeutic e>ect 1it' eit'er %rug
1as not %emonstrate%6 t'us more stu%y is
nee%e%.
B. CYSTEAMINE
1. ACETAMINOPHEN OVERDOSE
a. Intra)enous N<acetylcysteine 1as consi%ere%
more e>ecti)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& N<acetylcysteine o)er
cysteamine inclu%e lesser toxicity an% a possi(ly
longer time inter)al o& eLcacy -+= )ersus +0
'ours &ollo1ing o)er%ose. -Da)is6 +3*,2 8rescott6
+3*+.. Oral or intra)enous N<acetylcysteine is
t'us pre&era(le to cysteamine in t'is setting.
C. SOBREROL
1. ADVERSE EFFECTS
a. So(rerol 1as reporte% to 'a)e &e1er si%e
e>ects6 *I6 t'an acetylcysteine6 B*I -Melica6
+3*D.. 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,.
B. AH!S# American Hospital !ormulary Ser)ice Drug In&ormation
+3*3. American Society o& Hospital 8'armacists6 Bet'es%a6 MD6
+3*3.
/. A:erlun% B6 Harstan% 76 ?in%e:e B et al# E>ect o& N<
acetylcysteine -NA7. treatment on HIE<+ in&ection# a %ou(le<(lin%
place(o<controlle% trial. Eur H 7lin 8'armacol +33,2 =0#G=D<G,+.
G. Alsolon MH F Bro1n 7A# Acetylcysteine in :eratocon4uncti)itis
sicca. Br H Op't'almol +3,*2 =B#/+0</+,.
=. Amir;a%e' A F Mc7otter 7# "'e intra)enous use o& oral
acetylcysteine -Mucomyst. &or t'e treatment o& acetaminop'en
o)er%ose. Arc' Intern Me% B00B2 +,B#3,<3D.
,. Anai;i NH6 S1enson 7! F Dentinger 8H# Sta(ility o&
acetylcysteine in an extemporaneously compoun%e% op't'almic
solution. Am H Healt'<Syst 8'arm +33D2 =G#=G3<==/.
D. Anon# Acetylcysteine6 Respaire an% Mucomyst. Me% ?ett Drugs
"'er +3D02 +B#B=.
*. Anon# Deat' a&ter N<acetylcysteine. ?ancet +3*G2 +#+GB+.
3. Anon# Oral N<acetylcysteine an% exacer(ation rates in patients
1it' c'ronic (ronc'itis an% se)ere air1ays o(struction. "'orax
+3*=2 G0#*/B<*/=.
+0. Ar%issino D6 Merlini 8A6 Sa)onitto S et al# E>ect o&
trans%ermal nitroglycerin or n<acetylcysteine6 or (ot'6 in t'e long<
term treatment o& unsta(le angina pectoris. H Am 7oll 7ar%iol
+33D2 B3#3G+<3GD.
++. Arstall MA6 Aang H6 Sta>or% I et al# N<acetylcysteine in
com(ination 1it' nitroglycerin an% strepto:inase &or t'e treatment
o& e)ol)ing acute myocar%ial in&arction# sa&ety an% (ioc'emical
e>ects. 7irculation +33=2 3B#B*==<B*,B.
+B. Aruoma OI6 Halli1ell B6 Hoey BM et al# "'e antioxi%ant
action o& N<acetylcysteine# its reaction 1it' 'y%rogen peroxi%e6
'y%roxyl ra%ical6 superoxi%e6 an% 'ypoc'lorous aci%. !ree Ra%ic
Biol Me% +3*32 ,#=3/<=3D.
+/. Bailey B F Mcuigan MA# Management o& anap'ylactoi%
reactions to intra)enous N<acetylcysteine. Ann Emerg Me% +33*2
/+-,.#D+0<D+=.
+G. Bailey DH F An%res HM# ?i)er in4ury a&ter oral an% rectal
a%ministration o& N<acetylcysteine &or meconium ileus eJui)alent
in a patient 1it' cystic @(rosis. 8e%iatrics +3*D2 D3#B*+<B*B.
+=. Ba::er H6 C'ang H6 Depierreux M et al# E>ects o& N<
acetycysteine in en%otoxic s'oc:. H 7rit 7are +33G2 3#B/,<BG/.
+,. Bar(ieri EH# Mucolytics. Am !am 8'ysician +3*/2 B*#+D=<+DD.
+D. Barte: MH6 ?aBu%%e HA F Mai(ac' HI# S:in permea(ility in
)i)o# comparison in rat6 ra((it6 pig an% man. H In)est Dermatol
+3DB2 =*#++G.
+*. Barton AD# Aerosoli;e% %etergents an% mucolytic agents in
t'e treatment o& sta(le c'ronic o(structi)e pulmonary %isease.
Am Re) Resp Dis +3DG2 ++0#+0G<++0.
+3. Bateman DN6 Moo%'ouse 9M F Ra1lins MD# A%)erse
reactions to N<acetylcysteine. Human "oxicology +3*G(2 /#/3/<
/3*.
B0. Bateman DN6 Moo%'ouse 9M F Ra1lins MD# A%)erse
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B30.
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Syn%rome. 7urr "'er Res +3*32 G,#+*D<+3B.
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Am H Hosp 8'arm +3*+2 /*#+0BB<+0BG.
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SJui(( F Sons6 8rinceton6 NH6 +33+.
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Dermatol B0002 +GB#=*0<=*+.
BG*. Eale H F M'eeler D# Anap'ylactoi% reactions to
acetylcysteine. ?ancet +3*B2 B#3**.
BG3. )an Can%1i4: N6 Dalesio O6 8astorino $ et al#
E$ROS7AN6 a ran%omi;e% trial o& )itamin A an% N<
acetylcysteine in patients 1it' 'ea% an% nec: cancer or
lung cancer. H Natl 7ancer Inst B0002 3B-+B.#3DD<3*,.
B=0. Eenturelli H F "ein I# Increase% intracranial pressure
associate% 1it' N<acetylcysteine in'alation t'erapy -letter..
7rit 7are Me% +3*G2 +B#3B,<3BD.
B=+. Eincent H6 9ongpatana:ul S6 Blasc':e "! et al#
Desensiti;ation o& nitrate<in%uce% )eno%ilation# re)ersal 1it'
oral N<acetylcysteine in 'umans. H 7ar%io)asc 8'armacol
+33B2 B0#30D<3+B.
B=B. Mactemat' 7? F Bergman NA# Increase% respiratory
resistance pro)o:e% (y en%otrac'eal a%ministration o&
aerosols. Am Re) Resp Dis +3D/2 +0*#=B0.
B=/. Malmsley S?6 9'oras'e' S6 Singer H et al# A
ran%omi;e% trial o& N<acetylcysteine &or pre)ention o&
trimet'oprim<sul&amet'oxa;ole 'ypersensiti)ity reactions in
8neumocystis carinii pneumonia prop'ylaxis -7"N 0=D.. H
AcJuir Immune De@c Syn%r Hum Retro)irol +33*2 +3#G3*<
=0=.
B=G. Mals' "S6 Hopton 86 8'ilips BH et al# "'e e>ect o&
N<acetylcysteine on oxygen transport an% upta:e in patients
1it' &ulminant 'epatic &ailure. Hepatology +33*2 BD#+//B<
+/G0.
B==. Malton N6 Mann "AN F S'a1 9M# Anap'ylactoi%
reaction to N<acetyleysteine. ?ancet +3D32 B#+B3*.
B=,. Matson RA# I&os&ami%e# c'emot'erapy 1it' ne1
promise an% ne1 pro(lems &or t'e urologist. $rology +3*G2
BG#G,=<G,*.
B=D. Matson MA F Mc9inney 8E# Acti)ate% c'arcoal an%
acetylcysteine a(sorption# issues in interpreting
p'armaco:inetic %ata. DI78 +33+2 B=#+0*+<+0*G.
B=*. Matt 6 Hongsa:ul 9 F Ruang)irayut' R# A pilot stu%y
o& N<acetylcysteine as a%4uncti)e t'erapy &or se)ere malaria.
QHM B00B2 3=-=.#B*=<B30.
B=3. Matt 6 Hongsa:ul 9 F Ruang)irayut' R# A pilot stu%y
o& N< acetylcysteine as a%4uncti)e t'erapy &or se)ere
malaria. Q H Me% B00B2 3=-=.#B*=<B30..
B,0. Me(( MR Hr# 7linical e)aluation o& a ne1 mucolytic
agent6 acetylcysteine. H "'or 7ar%io)asc Surg +3,B2
GG#//0.
B,+. Mel(ourn 7RB F Aoung A# En%otoxin6 septic s'oc:6
an% acute lung in4ury# neutrop'ils6 macrop'ages an%
inNammatory me%iators. Br H Surg +33B2 D3#33*<+00/.
B,B. Mestlin M F Mullane 9M# Does captopril attenuate
reper&usion<in%uce% myocar%ial %ys&unction (y sca)enging
&ree ra%icalsR 7irculation +3**2 DD-suppl I.#/0</3.
B,/. Mestman ?# N<acetylcysteine in t'e treatment o&
acetaminop'en o)er%ose. N Engl H Me% +3*32 /B0#+G+D<
+G+*.
B,G. Milliamson H6 Doig MM6 !orrester HE et al#
Management o& t'e %ry eye in S4ogrenRs syn%rome. Br H
Op't'almol +3DG2 =*#D3*<*0=.
B,=. Milliams SD6 Muns'i N6 Ein'orn ?H et al#
7yclop'osp'ami%e an% i&os&ami%e# role o& uroprotecti)e
agents. 7anc In)est +3302 *D#B,3.
B,,. Milpart M6 Mainguet 86 eeroms D et al#
Desmutagenic e>ects o& N<acetylcysteine on %irect an%
in%irect mutagens. Mutat Res +3*=2 +GB#+,3<+DD.
B,D. Minni&or% MD6 9enne%y 8?6 Mells 8H et al#
8otentiation o& nitroglycerin<in%uce% coronary %ilatation (y
N<acetylcysteine. 7irculation +3*,2 D/#+/*<+GB.
B,*. Moo O!6 Mueller 8D6 Olson 9R et al# S'orter %uration
o& oral N<acetylcysteine t'erapy &or acute acetaminop'en
o)er%ose. Ann Emerg Me% B0002 /=-G.#/,/</,*.
B,3. Aalcin E6 Altin !6 7in'useyinoglue ! et al# N<
acetylcysteine in c'ronic (lep'aritis. 7ornea B00B2
B+-+.#+,G<+,*.
BD0. Aar(ro HM6 Bornstein RS F Mastrangelo MH -e%s.# N<
acetylcysteine -NA7.# a signi@cant c'emoprotecti)e a%4u)ant.
8rocee%ings o& a symposium. Semin Oncol +3*/2 +0-suppl
+..
BD+. Aip ?6 Dart R7 F Hurl(ut 9M# Intra)enous
a%ministration o& oral N<acetylcysteine. 7rit 7are Me% +33*#
B,#G0<G/.
BDB. Aoung IS6 8ur)is HA6 ?ig't(o%y HH et al# ?ipi%
peroxi%ation an% antioxi%ant status &ollo1ing t'rom(olytic
t'erapy &or acute myocar%ial in&arction. Eur Heart H +33/2
+G#+0BD<+0//.
BD/. Aunis AA6 ?im ?O F Arimura 9# DNA %amage
in%uce% (y c'loramp'enicol an% nitrosoc'loramp'enicol#
protection (y N<acetylcysteine. Respiration +3*,2 =0-suppl
+.#=0.
BDG. Ciment I# Acetylcysteine# a %rug t'at is muc' more
t'an a muco:inetic. Biome% 8'armacot'er +3**2 GB#=+/<
=B0.
BD=. Ciment I# Acetylcysteine# a %rug 1it' an interesting
past an% &ascinating &uture. Respiration +3*,2 =0-suppl
+.#B,</0.
#.0 AUTHOR INFORMATION
O%i1in$l "u0li&$tion: 5<;1<78
-ost %#&#nt %#vision: 53;2553
List o+ &ont%i0uto%s:
1. )4#%/l Bun&4 P4$%3D
2. P$ul L Do#%in1 -8
3. K$3#s P Du++/ B8 RP4
4. Kuli$ F 'l#n0$$s P4$%3D
C. 7$ns-P#t#% 'lsn#% )lini&$l P4$%3$&ist =#%3$n/
?. K$3#s ' F$%lst%$nd -$9o% B8) ,8AF
7. P%o+ D% D% '%nst -uts&4l#% =#%3$n/
8. D$vid Aoods B8 -P4$%3 N#6 I#$l$nd
<. DR,=D'>(R) 'dito%i$l 8t$++
Fo% +u%t4#% in+o%3$tion on &ont%i0utin1 $ut4o%s
s## #dito%i$l 0o$%d listin1s.
-DE0+BD.
E'( )* D)+,-.'/

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