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SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
PHARMACAL PHARMACAL
SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
IMPRINTAREA
RESEALAREA
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPCherry Flavor
THIS PROOF IS NOT INTENDED FOR COLOR REPRESENTATION. PLEASE REVIEW FOR COPY AND POSITIONING OF GRAPHICS AND TEXT.
APPROVAL SIGNATURE
APPROVED
REVISE AND RE-PROOF
PLATINUM PRESS FAX - (469)733-1510
GRAPHICS PROOFSize:
Rev:
4.125” x 4.125” MC 10/07/11 Copy Position11
Co
py
#4
#4
920 Avenue R Bldg. #200Grand Prairie, TX 75050 (469)733-1506
Healthcare Packaging
BLACK PMS 321GREEN
PMS 485RED
Base Label
Cherry Flavor
Book Placement
Rx only
16 fl oz (473 mL)
Rev. 823:07 7/11
NDC 50383-823-16
50383-823-163 2
4.125"
4.125"
Cherry Flavor
SHAKE WELL BEFORE USING.
16 fl oz (473 mL)
HI-TECH PHARMACAL CO., INC.Amityville, NY 11701
Each teaspoonful (5 mL) contains:Sulfamethoxazole ............................. 200 mgTrimethoprim ..................................... 40 mgAlcohol .............................................. 0.26%
USUAL DOSAGE: See package insert for dosage and full prescribing information.
Dispense in a tight, light-resistant container as defined in the USP. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from light.
1.813" 2.000"
0.313"
Reference ID: 3057440
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPCherry Flavor
920 Avenue R Bldg. #200Grand Prairie, TX 75050 (469)733-1506
Healthcare Packaging
Front
Cover(Page #1)
Page #20 Page #21 Page #22 Page #23 Page #24 Page #25 Page #26 Page #27 Page #28Page #16 Page #17 Page #18 Page #19
THIS PROOF IS NOT INTENDED FOR COLOR REPRESENTATION. PLEASE REVIEW FOR COPY AND POSITIONING OF GRAPHICS AND TEXT.
APPROVAL SIGNATURE
APPROVED
REVISE AND RE-PROOF
PLATINUM PRESS FAX - (469)733-1510
GRAPHICS PROOFSize:
Rev:
4.125” x 4.125” Copy Position11
Co
py
#4
#4BLACK PMS 321
GREENPMS 485
RED
Info
rmat
ion
for P
atie
nts
Patie
nts
shou
ld b
e co
unse
led
that
ant
ibac
teria
l dru
gs in
clud
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
shou
ld
only
be
used
to tr
eat b
acte
rial i
nfec
tions
. The
y do
not
trea
t vira
l inf
ectio
ns (e
.g.,
the
com
mon
col
d). W
hen
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
is p
resc
ribed
to tr
eat a
bac
teria
l inf
ectio
n, p
atie
nts
shou
ld b
e to
ld th
at
alth
ough
it is
com
mon
to fe
el b
ette
r ear
ly in
the
cour
se o
f the
rapy
, the
med
icat
ion
shou
ld b
e ta
ken
exac
tly a
s di
rect
ed.
Skip
ping
dos
es o
r not
com
plet
ing
the
full
cour
se o
f the
rapy
may
(1) d
ecre
ase
the
effe
ctiv
enes
s of
the
imm
edia
te tr
eatm
ent
and
(2) i
ncre
ase
the
likel
ihoo
d th
at b
acte
ria w
ill d
evel
op re
sist
ance
and
will
not
be
treat
able
by
sulfa
met
hoxa
zole
and
tri
met
hopr
im o
ral s
uspe
nsio
n or
oth
er a
ntib
acte
rial d
rugs
in th
e fu
ture
.Pa
tient
s sh
ould
be
inst
ruct
ed to
mai
ntai
n an
ade
quat
e flu
id in
take
in o
rder
to p
reve
nt c
ryst
allu
ria a
nd s
tone
form
atio
n.Di
arrh
ea is
a c
omm
on p
robl
em c
ause
d by
ant
ibio
tics
whi
ch u
sual
ly e
nds
whe
n th
e an
tibio
tic is
dis
cont
inue
d. S
omet
imes
af
ter s
tarti
ng tr
eatm
ent w
ith a
ntib
iotic
s, p
atie
nts
can
deve
lop
wat
ery
and
bloo
dy s
tool
s (w
ith a
nd w
ithou
t sto
mac
h cr
amps
an
d fe
ver)
eve
n as
late
as
two
or m
ore
mon
ths
afte
r hav
ing
take
n th
e la
st d
ose
of th
e an
tibio
tic. I
f thi
s oc
curs
, pat
ient
s sh
ould
con
tact
thei
r phy
sici
an a
s so
on a
s po
ssib
le.
Labo
rato
ry T
ests
Com
plet
e bl
ood
coun
ts s
houl
d be
don
e fre
quen
tly in
pat
ient
s re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
; if a
sig
nific
ant
redu
ctio
n in
the
coun
t of a
ny fo
rmed
blo
od e
lem
ent i
s no
ted,
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im s
houl
d be
dis
cont
inue
d.
Urin
alys
is w
ith c
aref
ul m
icro
scop
ic e
xam
inat
ion
and
rena
l fun
ctio
n te
sts
shou
ld b
e pe
rform
ed d
urin
g th
erap
y, p
artic
ular
ly
for t
hose
pat
ient
s w
ith im
paire
d re
nal f
unct
ion.
Drug
Inte
ract
ions
In e
lder
ly p
atie
nts
conc
urre
ntly
rece
ivin
g ce
rtain
diu
retic
s, p
rimar
ily th
iazid
es, a
n in
crea
sed
inci
denc
e of
thro
mbo
cyto
peni
a w
ith p
urpu
ra h
as b
een
repo
rted.
It
has
been
repo
rted
that
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay p
rolo
ng th
e pr
othr
ombi
n tim
e in
pat
ient
s w
ho a
re
rece
ivin
g th
e an
ticoa
gula
nt w
arfa
rin. T
his
inte
ract
ion
shou
ld b
e ke
pt in
min
d w
hen
sulfa
met
hoxa
zole
and
trim
etho
prim
is
give
n to
pat
ient
s al
read
y on
ant
icoa
gula
nt th
erap
y, a
nd th
e co
agul
atio
n tim
e sh
ould
be
reas
sess
ed.
Sulfa
met
hoxa
zole
and
trim
etho
prim
may
inhi
bit t
he h
epat
ic m
etab
olis
m o
f phe
nyto
in. S
ulfa
met
hoxa
zole
and
trim
etho
prim
, gi
ven
at a
com
mon
clin
ical
dos
age,
incr
ease
d th
e ph
enyt
oin
half-
life
by 3
9% a
nd d
ecre
ased
the
phen
ytoi
n m
etab
olic
cle
aran
ce
rate
by
27%
. Whe
n ad
min
iste
ring
thes
e dr
ugs
conc
urre
ntly
, one
sho
uld
be a
lert
for p
ossi
ble
exce
ssiv
e ph
enyt
oin
effe
ct.
Sulfo
nam
ides
can
als
o di
spla
ce m
etho
trexa
te fr
om p
lasm
a pr
otei
n bi
ndin
g si
tes
and
can
com
pete
with
the
rena
l tra
nspo
rt of
met
hotre
xate
, thu
s in
crea
sing
free
met
hotre
xate
con
cent
ratio
ns.
Ther
e ha
ve b
een
repo
rts o
f mar
ked
but r
ever
sibl
e ne
phro
toxi
city
with
coa
dmin
istra
tion
of s
ulfa
met
hoxa
zole
and
tri
met
hopr
im a
nd c
yclo
spor
ine
in re
nal t
rans
plan
t rec
ipie
nts.
In
crea
sed
digo
xin
bloo
d le
vels
can
occ
ur w
ith c
onco
mita
nt s
ulfa
met
hoxa
zole
and
trim
etho
prim
ther
apy,
esp
ecia
lly in
el
derly
pat
ient
s. S
erum
dig
oxin
leve
ls s
houl
d be
mon
itore
d.
Incr
ease
d su
lfam
etho
xazo
le b
lood
leve
ls m
ay o
ccur
in p
atie
nts
who
are
als
o re
ceiv
ing
indo
met
haci
n.
Occa
sion
al re
ports
sug
gest
that
pat
ient
s re
ceiv
ing
pyrim
etha
min
e as
mal
aria
pro
phyl
axis
in d
oses
exc
eedi
ng 2
5 m
g w
eekl
y m
ay d
evel
op m
egal
obla
stic
ane
mia
if s
ulfa
met
hoxa
zole
and
trim
etho
prim
is p
resc
ribed
. Th
e ef
ficac
y of
tric
yclic
ant
idep
ress
ants
can
dec
reas
e w
hen
coad
min
iste
red
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im.
Like
oth
er s
ulfo
nam
ide-
cont
aini
ng d
rugs
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im p
oten
tiate
s th
e ef
fect
of o
ral h
ypog
lyce
mic
s.
In th
e lit
erat
ure,
a s
ingl
e ca
se o
f tox
ic d
eliri
um h
as b
een
repo
rted
afte
r con
com
itant
inta
ke o
f su
lfam
etho
xazo
le/tr
imet
hopr
im a
nd a
man
tadi
ne.
In th
e lit
erat
ure,
thre
e ca
ses
of h
yper
kale
mia
in e
lder
ly p
atie
nts
have
bee
n re
porte
d af
ter c
onco
mita
nt in
take
of
sulfa
met
hoxa
zole
/trim
etho
prim
and
an
angi
oten
sin
conv
ertin
g en
zym
e in
hibi
tor.7
,8
Drug
/Lab
orat
ory
Test
Inte
ract
ions
Sulfa
met
hoxa
zole
and
trim
etho
prim
, spe
cific
ally
the
trim
etho
prim
com
pone
nt, c
an in
terfe
re w
ith a
ser
um m
etho
trexa
te
assa
y as
det
erm
ined
by
the
com
petit
ive
bind
ing
prot
ein
tech
niqu
e (C
BPA)
whe
n a
bact
eria
l dih
ydro
fola
te re
duct
ase
is u
sed
as th
e bi
ndin
g pr
otei
n. N
o in
terfe
renc
e oc
curs
, how
ever
, if m
etho
trexa
te is
mea
sure
d by
a ra
dioi
mm
unoa
ssay
(RIA
).Th
e pr
esen
ce o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay a
lso
inte
rfere
with
the
Jaffé
alk
alin
e pi
crat
e re
actio
n as
say
for
crea
tinin
e, re
sulti
ng in
ove
rest
imat
ions
of a
bout
10%
in th
e ra
nge
of n
orm
al v
alue
s.Ca
rcin
ogen
esis
, Mut
agen
esis
, Im
pairm
ent o
f Fer
tility
Carc
inog
enes
is: L
ong-
term
stu
dies
in a
nim
als
to e
valu
ate
carc
inog
enic
pot
entia
l hav
e no
t bee
n co
nduc
ted
with
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im.
Mut
agen
esis
: Bac
teria
l mut
agen
ic s
tudi
es h
ave
not b
een
perfo
rmed
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im in
co
mbi
natio
n. T
rimet
hopr
im w
as d
emon
stra
ted
to b
e no
nmut
agen
ic in
the
Ames
ass
ay. N
o ch
rom
osom
al d
amag
e w
as
obse
rved
in h
uman
leuk
ocyt
es c
ultu
red
in v
itro
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
lone
or i
n co
mbi
natio
n; th
e co
ncen
tratio
ns u
sed
exce
eded
blo
od le
vels
of t
hese
com
poun
ds fo
llow
ing
ther
apy
with
sul
fam
etho
xazo
le a
nd
trim
etho
prim
. Obs
erva
tions
of l
euko
cyte
s ob
tain
ed fr
om p
atie
nts
treat
ed w
ith s
ulfa
met
hoxa
zole
and
trim
etho
prim
reve
aled
no
chr
omos
omal
abn
orm
aliti
es.
Impa
irmen
t of F
ertil
ity: N
o ad
vers
e ef
fect
s on
ferti
lity
or g
ener
al re
prod
uctiv
e pe
rform
ance
wer
e ob
serv
ed in
rats
giv
en
oral
dos
ages
as
high
as
350
mg/
kg/d
ay s
ulfa
met
hoxa
zole
plu
s 70
mg/
kg/d
ay tr
imet
hopr
im.
Preg
nanc
yTe
rato
geni
c Ef
fect
s: P
regn
ancy
Cat
egor
y C.
In ra
ts, o
ral d
oses
of 5
33 m
g/kg
or 2
00 m
g/kg
pro
duce
d te
rato
logi
c ef
fect
s m
anife
sted
mai
nly
as c
left
pala
tes.
Th
e hi
ghes
t dos
e w
hich
did
not
cau
se c
left
pala
tes
in ra
ts w
as 5
12 m
g/kg
sul
fam
etho
xazo
le o
r 192
mg/
kg tr
imet
hopr
im
whe
n ad
min
iste
red
sepa
rate
ly. I
n tw
o st
udie
s in
rats
, no
tera
tolo
gy w
as o
bser
ved
whe
n 51
2 m
g/kg
of s
ulfa
met
hoxa
zole
w
as u
sed
in c
ombi
natio
n w
ith 1
28 m
g/kg
of t
rimet
hopr
im. I
n on
e st
udy,
how
ever
, cle
ft pa
late
s w
ere
obse
rved
in o
ne li
tter
out o
f 9 w
hen
355
mg/
kg o
f sul
fam
etho
xazo
le w
as u
sed
in c
ombi
natio
n w
ith 8
8 m
g/kg
of t
rimet
hopr
im.
In s
ome
rabb
it st
udie
s, a
n ov
eral
l inc
reas
e in
feta
l los
s (d
ead
and
reso
rbed
and
mal
form
ed c
once
ptus
es) w
as a
ssoc
iate
d w
ith d
oses
of t
rimet
hopr
im 6
tim
es th
e hu
man
ther
apeu
tic d
ose.
Whi
le th
ere
are
no la
rge,
wel
l-con
trolle
d st
udie
s on
the
use
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
in p
regn
ant w
omen
, Br
umfit
t and
Pur
sell,
9 in
a re
trosp
ectiv
e st
udy,
repo
rted
the
outc
ome
of 1
86 p
regn
anci
es d
urin
g w
hich
the
mot
her r
ecei
ved
eith
er p
lace
bo o
r sul
fam
etho
xazo
le a
nd tr
imet
hopr
im. T
he in
cide
nce
of c
onge
nita
l abn
orm
aliti
es w
as 4
.5%
(3 o
f 66)
in
thos
e w
ho re
ceiv
ed p
lace
bo a
nd 3
.3%
(4 o
f 120
) in
thos
e re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
. The
re w
ere
no
abno
rmal
ities
in th
e 10
chi
ldre
n w
hose
mot
hers
rece
ived
the
drug
dur
ing
the
first
trim
este
r. In
a s
epar
ate
surv
ey, B
rum
fitt
and
Purs
ell a
lso
foun
d no
con
geni
tal a
bnor
mal
ities
in 3
5 ch
ildre
n w
hose
mot
hers
had
rece
ived
ora
l sul
fam
etho
xazo
le a
nd
trim
etho
prim
at t
he ti
me
of c
once
ptio
n or
sho
rtly
ther
eafte
r.Be
caus
e su
lfam
etho
xazo
le a
nd tr
imet
hopr
im m
ay in
terfe
re w
ith fo
lic a
cid
met
abol
ism
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
shou
ld b
e us
ed d
urin
g pr
egna
ncy
only
if th
e po
tent
ial b
enef
it ju
stifi
es th
e po
tent
ial r
isk
to th
e fe
tus.
Nont
erat
ogen
ic E
ffect
s: S
ee C
ONTR
AIND
ICAT
IONS
sec
tion.
Nurs
ing
Mot
hers
See
CONT
RAIN
DICA
TION
S se
ctio
n.Pe
diat
ric U
seSu
lfam
etho
xazo
le a
nd tr
imet
hopr
im is
not
reco
mm
ende
d fo
r inf
ants
you
nger
than
2 m
onth
s of
age
(see
INDI
CATI
ONS
AND
USAG
E an
d CO
NTRA
INDI
CATI
ONS
sect
ions
).Ge
riatri
c Us
eCl
inic
al s
tudi
es o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im d
id n
ot in
clud
e su
ffici
ent n
umbe
rs o
f sub
ject
s ag
ed 6
5 an
d ov
er to
de
term
ine
whe
ther
they
resp
ond
diffe
rent
ly fr
om y
oung
er s
ubje
cts.
Ther
e m
ay b
e an
incr
ease
d ris
k of
sev
ere
adve
rse
reac
tions
in e
lder
ly p
atie
nts,
par
ticul
arly
whe
n co
mpl
icat
ing
cond
ition
s ex
ist,
e.g.
, im
paire
d ki
dney
and
/or l
iver
func
tion,
pos
sibl
e fo
late
def
icie
ncy,
or c
onco
mita
nt u
se o
f oth
er d
rugs
. Sev
ere
skin
re
actio
ns, g
ener
alize
d bo
ne m
arro
w s
uppr
essi
on (s
ee W
ARNI
NGS
and
ADVE
RSE
REAC
TION
S se
ctio
ns),
a sp
ecifi
c de
crea
se in
pla
tele
ts (w
ith o
r with
out p
urpu
ra),
and
hype
rkal
emia
are
the
mos
t fre
quen
tly re
porte
d se
vere
adv
erse
re
actio
ns in
eld
erly
pat
ient
s. In
thos
e co
ncur
rent
ly re
ceiv
ing
certa
in d
iure
tics,
prim
arily
thia
zides
, an
incr
ease
d in
cide
nce
of
thro
mbo
cyto
peni
a w
ith p
urpu
ra h
as b
een
repo
rted.
Incr
ease
d di
goxi
n bl
ood
leve
ls c
an o
ccur
with
con
com
itant
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im th
erap
y, e
spec
ially
in e
lder
ly p
atie
nts.
Ser
um d
igox
in le
vels
sho
uld
be m
onito
red.
He
mat
olog
ical
cha
nges
indi
cativ
e of
folic
aci
d de
ficie
ncy
may
occ
ur in
eld
erly
pat
ient
s. T
hese
effe
cts
are
reve
rsib
le b
y fo
linic
aci
d th
erap
y. A
ppro
pria
te d
osag
e ad
just
men
ts s
houl
d be
mad
e fo
r pat
ient
s w
ith im
paire
d ki
dney
func
tion
and
dura
tion
of u
se s
houl
d be
as
shor
t as
poss
ible
to m
inim
ize ri
sks
of u
ndes
ired
reac
tions
(see
DOS
AGE
AND
ADM
INIS
TRAT
ION
sect
ion)
. The
trim
etho
prim
com
pone
nt o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay c
ause
hyp
erka
lem
ia
whe
n ad
min
iste
red
to p
atie
nts
with
und
erly
ing
diso
rder
s of
pot
assi
um m
etab
olis
m, w
ith re
nal i
nsuf
ficie
ncy
or w
hen
give
n co
ncom
itant
ly w
ith d
rugs
kno
wn
to in
duce
hyp
erka
lem
ia, s
uch
as a
ngio
tens
in c
onve
rting
enz
yme
inhi
bito
rs. C
lose
m
onito
ring
of s
erum
pot
assi
um is
war
rant
ed in
thes
e pa
tient
s. D
isco
ntin
uatio
n of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
treat
men
t is
reco
mm
ende
d to
hel
p lo
wer
pot
assi
um s
erum
leve
ls.
Phar
mac
okin
etic
s pa
ram
eter
s fo
r sul
fam
etho
xazo
le w
ere
sim
ilar f
or g
eria
tric
subj
ects
and
you
nger
adu
lt su
bjec
ts. T
he
mea
n m
axim
um s
erum
trim
etho
prim
con
cent
ratio
n w
as h
ighe
r and
mea
n re
nal c
lear
ance
of t
rimet
hopr
im w
as lo
wer
in
geria
tric
subj
ects
com
pare
d w
ith y
oung
er s
ubje
cts
(see
CLI
NICA
L PH
ARM
ACOL
OGY:
Ger
iatri
c Ph
arm
acok
inet
ics)
.AD
VERS
E RE
ACTI
ONS
The
mos
t com
mon
adv
erse
effe
cts
are
gast
roin
test
inal
dis
turb
ance
s (n
ause
a, v
omiti
ng, a
nore
xia)
and
alle
rgic
ski
n re
actio
ns (s
uch
as ra
sh a
nd u
rtica
ria).
FATA
LITI
ES A
SSOC
IATE
D W
ITH
THE
ADM
INIS
TRAT
ION
OF S
ULFO
NAM
IDES
, AL
THOU
GH R
ARE,
HAV
E OC
CURR
ED D
UE T
O SE
VERE
REA
CTIO
NS, I
NCLU
DING
STE
VENS
-JOH
NSON
SYN
DROM
E,
TOXI
C EP
IDER
MAL
NEC
ROLY
SIS,
FUL
MIN
ANT
HEPA
TIC
NECR
OSIS
, AGR
ANUL
OCYT
OSIS
, APL
ASTI
C AN
EMIA
AND
OT
HER
BLOO
D DY
SCRA
SIAS
(SEE
WAR
NING
S SE
CTIO
N).
Hem
atol
ogic
: Agr
anul
ocyt
osis
, apl
astic
ane
mia
, thr
ombo
cyto
peni
a, le
ukop
enia
, neu
trope
nia,
hem
olyt
ic a
nem
ia,
meg
alob
last
ic a
nem
ia, h
ypop
roth
rom
bine
mia
, met
hem
oglo
bine
mia
, eos
inop
hilia
.Al
lerg
ic R
eact
ions
: Ste
vens
-Joh
nson
syn
drom
e, to
xic
epid
erm
al n
ecro
lysi
s, a
naph
ylax
is, a
llerg
ic m
yoca
rditi
s, e
ryth
ema
mul
tifor
me,
exf
olia
tive
derm
atiti
s, a
ngio
edem
a, d
rug
feve
r, ch
ills,
Hen
och-
Schö
enle
in p
urpu
ra, s
erum
sic
knes
s-lik
e sy
ndro
me,
gen
eral
ized
alle
rgic
reac
tions
, gen
eral
ized
skin
eru
ptio
ns, p
hoto
sens
itivi
ty, c
onju
nctiv
al a
nd s
cler
al in
ject
ion,
pr
uritu
s, u
rtica
ria a
nd ra
sh. I
n ad
ditio
n, p
eria
rterit
is n
odos
a an
d sy
stem
ic lu
pus
eryt
hem
atos
us h
ave
been
repo
rted.
Gast
roin
test
inal
: Hep
atiti
s, (i
nclu
ding
cho
lest
atic
jaun
dice
and
hep
atic
nec
rosi
s), e
leva
tion
of s
erum
tran
sam
inas
e an
d bi
lirub
in,
pseu
dom
embr
anou
s en
tero
colit
is, p
ancr
eatit
is, s
tom
atiti
s, g
loss
itis,
nau
sea,
em
esis
, abd
omin
al p
ain,
dia
rrhe
a, a
nore
xia.
Geni
tour
inar
y: R
enal
failu
re, i
nter
stiti
al n
ephr
itis,
BUN
and
ser
um c
reat
inin
e el
evat
ion,
toxi
c ne
phro
sis
with
olig
uria
and
an
uria
, cry
stal
luria
and
nep
hrot
oxic
ity in
ass
ocia
tion
with
cyc
losp
orin
e.M
etab
olic
and
Nut
ritio
nal:
Hype
rkal
emia
(see
PRE
CAUT
IONS
: Use
in th
e Tr
eatm
ent o
f and
Pro
phyl
axis
for
Pneu
moc
ystis
Car
inii
Pneu
mon
ia in
Pat
ient
s w
ith A
cqui
red
Imm
unod
efic
ienc
y Sy
ndro
me
(AID
S).
Neur
olog
ic: A
sept
ic m
enin
gitis
, con
vuls
ions
, per
iphe
ral n
eurit
is, a
taxi
a, v
ertig
o, ti
nnitu
s, h
eada
che.
Psyc
hiat
ric: H
allu
cina
tions
, dep
ress
ion,
apa
thy,
ner
vous
ness
.En
docr
ine:
The
sul
fona
mid
es b
ear c
erta
in c
hem
ical
sim
ilarit
ies
to s
ome
goitr
ogen
s, d
iure
tics
(ace
tazo
lam
ide
and
the
thia
zides
) and
ora
l hyp
ogly
cem
ic a
gent
s. C
ross
-sen
sitiv
ity m
ay e
xist
with
thes
e ag
ents
. Diu
resi
s an
d hy
pogl
ycem
ia h
ave
occu
rred
rare
ly in
pat
ient
s re
ceiv
ing
sulfo
nam
ides
.M
uscu
losk
elet
al: A
rthra
lgia
and
mya
lgia
. Iso
late
d ca
ses
of rh
abdo
myo
lysi
s ha
ve b
een
repo
rted
with
sul
fam
etho
xazo
le a
nd
trim
etho
prim
, mai
nly
in A
IDS
patie
nts.
Resp
irato
ry: C
ough
, sho
rtnes
s of
bre
ath
and
pulm
onar
y in
filtra
tes
(see
WAR
NING
S).
Mis
cella
neou
s: W
eakn
ess,
fatig
ue, i
nsom
nia.
Post
mar
ketin
g Ex
perie
nce
The
follo
win
g ad
vers
e re
actio
ns h
ave
been
iden
tifie
d du
ring
post
-app
rova
l use
of t
rimet
hopr
im-s
ulfa
met
hoxa
zole
. Bec
ause
th
ese
reac
tions
wer
e re
porte
d vo
lunt
arily
from
a p
opul
atio
n of
unc
erta
in s
ize, i
t is
not p
ossi
ble
to re
liabl
y es
timat
e th
eir
frequ
ency
or e
stab
lish
a ca
usal
rela
tions
hip
to d
rug
expo
sure
:Σ
Thr
ombo
tic th
rom
bocy
tope
nia
purp
ura
Σ Id
iopa
thic
thro
mbo
cyto
peni
c pu
rpur
aOV
ERDO
SAGE
Acut
e: T
he a
mou
nt o
f a s
ingl
e do
se o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im th
at is
eith
er a
ssoc
iate
d w
ith s
ympt
oms
of
over
dosa
ge o
r is
likel
y to
be
life-
thre
aten
ing
has
not b
een
repo
rted.
Sig
ns a
nd s
ympt
oms
of o
verd
osag
e re
porte
d w
ith
sulfo
nam
ides
incl
ude
anor
exia
, col
ic, n
ause
a, v
omiti
ng, d
izzin
ess,
hea
dach
e, d
row
sine
ss a
nd u
ncon
scio
usne
ss. P
yrex
ia,
hem
atur
ia a
nd c
ryst
allu
ria m
ay b
e no
ted.
Blo
od d
yscr
asia
s an
d ja
undi
ce a
re p
oten
tial l
ate
man
ifest
atio
ns o
f ove
rdos
age.
Si
gns
of a
cute
ove
rdos
age
with
trim
etho
prim
incl
ude
naus
ea, v
omiti
ng, d
izzin
ess,
hea
dach
e, m
enta
l dep
ress
ion,
con
fusi
on
and
bone
mar
row
dep
ress
ion.
Ge
nera
l prin
cipl
es o
f tre
atm
ent i
nclu
de th
e in
stitu
tion
of g
astri
c la
vage
or e
mes
is, f
orci
ng o
ral f
luid
s, a
nd th
e ad
min
istra
tion
of in
trave
nous
flui
ds if
urin
e ou
tput
is lo
w a
nd re
nal f
unct
ion
is n
orm
al. A
cidi
ficat
ion
of th
e ur
ine
will
incr
ease
rena
l el
imin
atio
n of
trim
etho
prim
. The
pat
ient
sho
uld
be m
onito
red
with
blo
od c
ount
s an
d ap
prop
riate
blo
od c
hem
istri
es,
incl
udin
g el
ectro
lyte
s. If
a s
igni
fican
t blo
od d
yscr
asia
or j
aund
ice
occu
rs, s
peci
fic th
erap
y sh
ould
be
inst
itute
d fo
r the
se
com
plic
atio
ns. P
erito
neal
dia
lysi
s is
not
effe
ctiv
e an
d he
mod
ialy
sis
is o
nly
mod
erat
ely
effe
ctiv
e in
elim
inat
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
.Ch
roni
c: U
se o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
t hig
h do
ses
and/
or fo
r ext
ende
d pe
riods
of t
ime
may
cau
se b
one
mar
row
dep
ress
ion
man
ifest
ed a
s th
rom
bocy
tope
nia,
leuk
open
ia a
nd/o
r meg
alob
last
ic a
nem
ia. I
f sig
ns o
f bon
e m
arro
w
depr
essi
on o
ccur
, the
pat
ient
sho
uld
be g
iven
leuc
ovor
in 5
to 1
5 m
g da
ily u
ntil
norm
al h
emat
opoi
esis
is re
stor
ed.
DOSA
GE A
ND A
DMIN
ISTR
ATIO
NNo
t rec
omm
ende
d fo
r use
in p
edia
tric
patie
nts
less
than
2 m
onth
s of
age
.Ur
inar
y Tr
act I
nfec
tions
and
Shi
gello
sis
in A
dults
and
Ped
iatri
c Pa
tient
s, a
nd A
cute
Otit
is M
edia
in C
hild
ren:
Adul
ts: T
he u
sual
adu
lt do
sage
in th
e tre
atm
ent o
f urin
ary
tract
infe
ctio
ns is
four
teas
poon
fuls
(20
mL)
sul
fam
etho
xazo
le
and
trim
etho
prim
ora
l sus
pens
ion
ever
y 12
hou
rs fo
r 10
to 1
4 da
ys. A
n id
entic
al d
aily
dos
age
is u
sed
for 5
day
s in
the
treat
men
t of s
hige
llosi
s.Ch
ildre
n: T
he re
com
men
ded
dose
for c
hild
ren
with
urin
ary
tract
infe
ctio
ns o
r acu
te o
titis
med
ia is
40
mg/
kg
sulfa
met
hoxa
zole
and
8 m
g/kg
trim
etho
prim
per
24
hour
s, g
iven
in tw
o di
vide
d do
ses
ever
y 12
hou
rs fo
r 10
days
. An
iden
tical
dai
ly d
osag
e is
use
d fo
r 5 d
ays
in th
e tre
atm
ent o
f shi
gello
sis.
The
follo
win
g ta
ble
is a
gui
delin
e fo
r the
atta
inm
ent
of th
is d
osag
e:
Acut
e Ex
acer
batio
ns o
f Chr
onic
Bro
nchi
tis in
Adu
lts:
The
usua
l adu
lt do
sage
in th
e tre
atm
ent o
f acu
te e
xace
rbat
ions
of c
hron
ic b
ronc
hitis
is fo
ur te
aspo
onfu
ls (2
0 m
L)
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
ever
y 12
hou
rs fo
r 14
days
.Pn
eum
ocys
tis C
arin
ii Pn
eum
onia
:Tr
eatm
ent:
Adul
ts a
nd C
hild
ren:
The
reco
mm
ende
d do
sage
for t
reat
men
t of p
atie
nts
with
doc
umen
ted
Pneu
moc
ystis
ca
rinii
pneu
mon
ia is
75
to 1
00 m
g/kg
sul
fam
etho
xazo
le a
nd 1
5 to
20
mg/
kg tr
imet
hopr
im p
er 2
4 ho
urs
give
n in
equ
ally
di
vide
d do
ses
ever
y 6
hour
s fo
r 14
to 2
1 da
ys.1
0 T
he fo
llow
ing
tabl
e is
a g
uide
line
for t
he u
pper
lim
it of
this
dos
age:
For t
he lo
wer
lim
it do
se (7
5 m
g/kg
sul
fam
etho
xazo
le a
nd 1
5 m
g/kg
trim
etho
prim
per
24
hour
s) a
dmin
iste
r 75%
of t
he
dose
in th
e ab
ove
tabl
e.Pr
ophy
laxi
s:Ad
ults
: The
reco
mm
ende
d do
sage
for p
roph
ylax
is in
adu
lts is
four
teas
poon
fuls
(20
mL)
of t
he o
ral s
uspe
nsio
n da
ily.1
1Ch
ildre
n: F
or c
hild
ren,
the
reco
mm
ende
d do
se is
750
mg/
m2 /
day
sulfa
met
hoxa
zole
with
150
mg/
m2 /
day
trim
etho
prim
gi
ven
oral
ly in
equ
ally
div
ided
dos
es tw
ice
a da
y, o
n 3
cons
ecut
ive
days
per
wee
k. T
he to
tal d
aily
dos
e sh
ould
not
exc
eed
1600
mg
sulfa
met
hoxa
zole
and
320
mg
trim
etho
prim
.12
The
follo
win
g ta
ble
is a
gui
delin
e fo
r the
atta
inm
ent o
f thi
s do
sage
in c
hild
ren:
Trav
eler
's D
iarr
hea
in A
dults
: Fo
r the
trea
tmen
t of t
rave
ler's
dia
rrhe
a, th
e us
ual a
dult
dosa
ge is
four
teas
poon
fuls
(20
mL)
of s
ulfa
met
hoxa
zole
and
tri
met
hopr
im o
ral s
uspe
nsio
n ev
ery
12 h
ours
for 5
day
s.
HOW
SUP
PLIE
DSu
lfam
etho
xazo
le a
nd T
rimet
hopr
im O
ral S
uspe
nsio
n, U
SP is
sup
plie
d in
a p
urpl
e gr
ape-
flavo
red
susp
ensi
on a
nd in
a p
ink
cher
ry-fl
avor
ed s
uspe
nsio
n co
ntai
ning
200
mg
sulfa
met
hoxa
zole
and
40
mg
trim
etho
prim
per
5 m
L (te
aspo
onfu
l) bo
th
pack
aged
in 1
pin
t (47
3 m
L) b
ottle
s.St
ore
at 2
0°-2
5°C
(68°
-77°
F) [s
ee U
SP C
ontro
lled
Room
Tem
pera
ture
]. Pr
otec
t fro
m li
ght.
SHAK
E W
ELL
BEFO
RE U
SING
.Di
spen
se in
a ti
ght,
light
-res
ista
nt c
onta
iner
as
defin
ed in
the
USP,
with
a c
hild
-res
ista
nt c
losu
re (a
s re
quire
d).
To re
port
SUSP
ECTE
D AD
VERS
E RE
ACTI
ONS,
con
tact
Hi-T
ech
Phar
mac
al, C
o., I
nc. a
t 1-8
00-2
62-9
010
or F
DA a
t 1-
800-
FDA-
1088
or w
ww
.fda.
gov/
med
wat
ch.
Rx o
nly
REFE
RENC
ES1.
Kr
emer
s P,
Duv
ivie
r J, H
eusg
hem
C. P
harm
acok
inet
ic S
tudi
es o
f Co-
Trim
oxaz
ole
in M
an a
fter S
ingl
e an
d Re
peat
edDo
ses.
J C
lin P
harm
acol
. Feb
-Mar
197
4; 1
4:11
2–11
7.
2.
Kapl
an S
A, e
t al.
Phar
mac
okin
etic
Pro
file
of T
rimet
hopr
im-S
ulfa
met
hoxa
zole
in M
an. J
Infe
ct D
is. N
ov 1
973;
128
(Sup
pl):
S547
–S55
5.
3.
Varo
quau
x O,
et a
l. Ph
arm
acok
inet
ics
of th
e tri
met
hopr
im-s
ulfa
met
hoxa
zole
com
bina
tion
in th
e el
derly
.Br
J C
lin P
harm
acol
. 198
5;20
:575
–581
. 4.
Ru
doy
RC, N
elso
n JD
, Hal
talin
KC.
Ant
imic
robi
al A
gent
s Ch
emot
her.
May
197
4;5:
439–
443.
5.
Na
tiona
l Com
mitt
ee fo
r Clin
ical
Lab
orat
ory
Stan
dard
s. M
etho
ds fo
r Dilu
tion
Antim
icro
bial
Sus
cept
ibili
ty T
ests
for
Bact
eria
that
Gro
w A
erob
ical
ly; A
ppro
ved
Stan
dard
– F
ourth
Edi
tion.
NCC
LS D
ocum
ent M
7–A4
, Vol
.17,
No.
2, N
CCLS
, W
ayne
, PA,
Jan
uary
, 199
7.
6.
Hard
y DW
, et a
l. A
cont
rolle
d tri
al o
f trim
etho
prim
-sul
fam
etho
xazo
le o
r aer
osol
ized
pent
amid
ine
for s
econ
dary
prop
hyla
xis
of P
neum
ocys
tis c
arin
ii pn
eum
onia
in p
atie
nts
with
the
acqu
ired
imm
unod
efic
ienc
y sy
ndro
me.
N En
gl J
Med
. 199
2; 3
27: 1
842–
1848
. 7.
M
arin
ella
Mar
k A.
199
9. T
rimet
hopr
im-in
duce
d hy
perk
alem
ia: A
n an
alys
is o
f rep
orte
d ca
ses.
Ger
onto
l. 45
:209
–212
. 8.
M
arga
sser
y, S
. and
B. B
asta
ni. 2
002.
Life
thre
aten
ing
hype
rkal
emia
and
aci
dosi
s se
cond
ary
totri
met
hopr
im-s
ulfa
met
hoxa
zole
trea
tmen
t. J.
Nep
hrol
. 14:
410–
414.
9.
Br
umfit
t W, P
urse
ll R.
Trim
etho
prim
/Sul
fam
etho
xazo
le in
the
Trea
tmen
t of B
acte
riuria
in W
omen
. J In
fect
Dis
.No
v 19
73; 1
28 (S
uppl
):S65
7–S6
63.
10. M
asur
H. P
reve
ntio
n an
d tre
atm
ent o
f Pne
umoc
ystis
pne
umon
ia. N
Eng
l J M
ed. 1
992;
327
: 185
3–18
80.
11. R
ecom
men
datio
ns fo
r pro
phyl
axis
aga
inst
Pne
umoc
ystis
car
inii
pneu
mon
ia fo
r adu
lts a
nd a
dole
scen
ts in
fect
ed w
ithhu
man
imm
unod
efic
ienc
y vi
rus.
MM
WR.
199
2; 4
1(RR
-4):1
–11.
12
. CDC
Gui
delin
es fo
r pro
phyl
axis
aga
inst
Pne
umoc
ystis
car
inii
pneu
mon
ia fo
r chi
ldre
n in
fect
ed w
ith h
uman
imm
unod
efic
ienc
y vi
rus.
MM
WR.
199
1; 4
0(RR
-2):1
–13.
M
anuf
actu
red
by:
Hi-T
ech
Phar
mac
al C
o., I
nc.
Rev.
823
:07
7/11
Amity
ville
, New
Yor
k 11
701
PHARMACAL
SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
Cherry Flavor
SHAKE WELL BEFORE USING.
16 fl oz (473 mL)
HI-TECH PHARMACAL CO., INC.Amityville, NY 11701
Each teaspoonful (5 mL) contains:Sulfamethoxazole ............................. 200 mgTrimethoprim ..................................... 40 mgAlcohol .............................................. 0.26%
USUAL DOSAGE: See package insert for dosage and full prescribing information.
Dispense in a tight, light-resistant container as defined in the USP. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from light.
Lift Here
Child
ren
2 m
onth
s of
age
or o
lder
:
Dose
— e
very
12
hour
s
Dose
— e
very
6 h
ours
Dose
— e
very
12
hour
s
4.12
5"
24.625"
1.750" 1.813" 1.750" 1.688" 1.688" 1.750" 1.750" 1.750" 1.750" 1.688" 1.688" 1.750" 1.813" 2.000"
Reference ID: 3057440
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPCherry Flavor
920 Avenue R Bldg. #200Grand Prairie, TX 75050 (469)733-1506
Healthcare Packaging
Back
THIS PROOF IS NOT INTENDED FOR COLOR REPRESENTATION. PLEASE REVIEW FOR COPY AND POSITIONING OF GRAPHICS AND TEXT.
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#4
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Page #11 Page #12 Page #13 Page #14 Page #15
CH
3
HN 2
SO
NH
2
NO
N
N
NH
2
CH
2N
H2
CH
O3
OC
H3
OC
H3
SULF
AMET
HOXA
ZOLE
AND
TRI
MET
HOPR
IMOR
AL S
USPE
NSIO
N, U
SPTo
redu
ce th
e de
velo
pmen
t of d
rug-
resi
stan
t bac
teria
and
mai
ntai
n th
e ef
fect
iven
ess
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
or
al s
uspe
nsio
n an
d ot
her a
ntib
acte
rial d
rugs
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im o
ral s
uspe
nsio
n sh
ould
be
used
onl
y to
tre
at o
r pre
vent
infe
ctio
ns th
at a
re p
rove
n or
stro
ngly
sus
pect
ed to
be
caus
ed b
y ba
cter
ia.
DESC
RIPT
ION
Sulfa
met
hoxa
zole
and
trim
etho
prim
is a
syn
thet
ic a
ntib
acte
rial c
ombi
natio
n pr
oduc
t con
tain
ing
200
mg
sulfa
met
hoxa
zole
an
d 40
mg
trim
etho
prim
per
5 m
L fo
r ora
l adm
inis
tratio
n.
Sulfa
met
hoxa
zole
is N
1 -(5
-met
hyl-3
-isox
azol
yl)s
ulfa
nila
mid
e; th
e m
olec
ular
form
ula
is C
10H 1
1N3O
3S. I
t is
an a
lmos
t whi
te,
odor
less
, tas
tele
ss c
ompo
und
with
a m
olec
ular
wei
ght o
f 253
.28
and
the
follo
win
g st
ruct
ural
form
ula:
Trim
etho
prim
is 2
,4-d
iam
ino-
5-(3
,4,5
-trim
etho
xybe
nzyl
)pyr
imid
ine;
the
mol
ecul
ar fo
rmul
a is
C14
H 18N
4O3.
It is
a w
hite
to
light
yel
low
, odo
rless
, bitt
er c
ompo
und
with
a m
olec
ular
wei
ght o
f 290
.3 a
nd th
e fo
llow
ing
stru
ctur
al fo
rmul
a:
Inac
tive
ingr
edie
nts:
alc
ohol
0.2
6%, m
ethy
lpar
aben
0.1
% a
nd s
odiu
m b
enzo
ate
0.1%
(add
ed a
s pr
eser
vativ
es),
carb
oxym
ethy
lcel
lulo
se s
odiu
m, c
itric
aci
d (a
nhyd
rous
), gl
ycer
in, m
icro
crys
talli
ne c
ellu
lose
, pol
ysor
bate
80,
pur
ified
wat
er,
sacc
harin
sod
ium
, and
sor
bito
l. Th
e lig
ht p
urpl
e, g
rape
flav
ored
sus
pens
ion
cont
ains
the
follo
win
g ad
ditio
nal i
nact
ive
ingr
edie
nts:
FD&
C Re
d No
. 40,
FD&
C Bl
ue N
o. 1
and
nat
ural
and
arti
ficia
l gra
pe fl
avor
. The
pin
k, c
herr
y fla
vore
d su
spen
sion
co
ntai
ns th
e fo
llow
ing
addi
tiona
l ina
ctiv
e in
gred
ient
s: F
D&C
Red
No. 4
0, F
D&C
Yello
w N
o. 6
and
arti
ficia
l che
rry
flavo
r.CL
INIC
AL P
HARM
ACOL
OGY
Sulfa
met
hoxa
zole
and
trim
etho
prim
is ra
pidl
y ab
sorb
ed fo
llow
ing
oral
adm
inis
tratio
n. B
oth
sulfa
met
hoxa
zole
and
tri
met
hopr
im e
xist
in th
e bl
ood
as u
nbou
nd, p
rote
in-b
ound
and
met
abol
ized
form
s; s
ulfa
met
hoxa
zole
als
o ex
ists
as
the
conj
ugat
ed fo
rm. T
he m
etab
olis
m o
f sul
fam
etho
xazo
le o
ccur
s pr
edom
inat
ely
by N
4-ac
etyl
atio
n, a
lthou
gh th
e gl
ucur
onid
e co
njug
ate
has
been
iden
tifie
d. T
he p
rinci
pal m
etab
olite
s of
trim
etho
prim
are
the
1- a
nd 3
-oxi
des
and
the
3’- a
nd 4
’-hyd
roxy
de
rivat
ives
. The
free
form
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re c
onsi
dere
d to
be
the
ther
apeu
tical
ly a
ctiv
e fo
rms.
Ap
prox
imat
ely
70%
of s
ulfa
met
hoxa
zole
and
44%
of t
rimet
hopr
im a
re b
ound
to p
lasm
a pr
otei
ns. T
he p
rese
nce
of 1
0 m
g pe
rcen
t sul
fam
etho
xazo
le in
pla
sma
decr
ease
s th
e pr
otei
n bi
ndin
g of
trim
etho
prim
by
an in
sign
ifica
nt d
egre
e; tr
imet
hopr
im
does
not
influ
ence
the
prot
ein
bind
ing
of s
ulfa
met
hoxa
zole
.Pe
ak b
lood
leve
ls fo
r the
indi
vidu
al c
ompo
nent
s oc
cur 1
to 4
hou
rs a
fter o
ral a
dmin
istra
tion.
The
mea
n se
rum
hal
f-liv
es o
f su
lfam
etho
xazo
le a
nd tr
imet
hopr
im a
re 1
0 an
d 8
to 1
0 ho
urs,
resp
ectiv
ely.
How
ever
, pat
ient
s w
ith s
ever
ely
impa
ired
rena
l fu
nctio
n ex
hibi
t an
incr
ease
in th
e ha
lf-liv
es o
f bot
h co
mpo
nent
s, re
quiri
ng d
osag
e re
gim
en a
djus
tmen
t (se
e DO
SAGE
AND
AD
MIN
ISTR
ATIO
N se
ctio
n). D
etec
tabl
e am
ount
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re p
rese
nt in
the
bloo
d 24
hou
rs
afte
r dru
g ad
min
istra
tion.
Dur
ing
adm
inis
tratio
n of
800
mg
sulfa
met
hoxa
zole
and
160
mg
trim
etho
prim
b.i.
d., t
he m
ean
stea
dy-s
tate
pla
sma
conc
entra
tion
of tr
imet
hopr
im w
as 1
.72
μg/
mL.
The
ste
ady-
stat
e m
ean
plas
ma
leve
ls o
f fre
e an
d to
tal
sulfa
met
hoxa
zole
wer
e 57
.4 μ
g/m
L an
d 68
.0 μ
g/m
L, re
spec
tivel
y. T
hese
ste
ady-
stat
e le
vels
wer
e ac
hiev
ed a
fter t
hree
day
s of
dru
g ad
min
istra
tion.
1 Ex
cret
ion
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
is p
rimar
ily b
y th
e ki
dney
s th
roug
h bo
th
glom
erul
ar fi
ltrat
ion
and
tubu
lar s
ecre
tion.
Urin
e co
ncen
tratio
ns o
f bot
h su
lfam
etho
xazo
le a
nd tr
imet
hopr
im a
re
cons
ider
ably
hig
her t
han
are
the
conc
entra
tions
in th
e bl
ood.
The
ave
rage
per
cent
age
of th
e do
se re
cove
red
in u
rine
from
0
to 7
2 ho
urs
afte
r a s
ingl
e or
al d
ose
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
is 8
4.5%
for t
otal
sul
fona
mid
e an
d 66
.8%
for
free
trim
etho
prim
. Thi
rty p
erce
nt o
f the
tota
l sul
fona
mid
e is
exc
rete
d as
free
sul
fam
etho
xazo
le, w
ith th
e re
mai
ning
as
N 4-a
cety
late
d m
etab
olite
.2 W
hen
adm
inis
tere
d to
geth
er a
s su
lfam
etho
xazo
le a
nd tr
imet
hopr
im, n
eith
er s
ulfa
met
hoxa
zole
no
r trim
etho
prim
affe
cts
the
urin
ary
excr
etio
n pa
ttern
of t
he o
ther
.Bo
th s
ulfa
met
hoxa
zole
and
trim
etho
prim
dis
tribu
te to
spu
tum
, vag
inal
flui
d an
d m
iddl
e ea
r flu
id; t
rimet
hopr
im a
lso
dist
ribut
es to
bro
nchi
al s
ecre
tions
, and
bot
h pa
ss th
e pl
acen
tal b
arrie
r and
are
exc
rete
d in
hum
an m
ilk.
Geria
tric
Phar
mac
okin
etic
sTh
e ph
arm
acok
inet
ics
of s
ulfa
met
hoxa
zole
800
mg
and
trim
etho
prim
160
mg
wer
e st
udie
d in
6 g
eria
tric
subj
ects
(mea
n ag
e: 7
8.6
year
s) a
nd 6
you
ng h
ealth
y su
bjec
ts (m
ean
age:
29.
3 ye
ars)
usi
ng a
non
-U.S
. app
rove
d fo
rmul
atio
n.
Phar
mac
okin
etic
val
ues
for s
ulfa
met
hoxa
zole
in g
eria
tric
subj
ects
wer
e si
mila
r to
thos
e ob
serv
ed in
you
ng a
dult
subj
ects
. Th
e m
ean
rena
l cle
aran
ce o
f trim
etho
prim
was
sig
nific
antly
low
er in
ger
iatri
c su
bjec
ts c
ompa
red
with
you
ng a
dult
subj
ects
(1
9 m
L/h/
kg v
s. 5
5 m
L/h/
kg).
How
ever
, afte
r nor
mal
izing
by
body
wei
ght,
the
appa
rent
tota
l bod
y cl
eara
nce
of
trim
etho
prim
was
on
aver
age
19%
low
er in
ger
iatri
c su
bjec
ts c
ompa
red
with
you
ng a
dult
subj
ects
.3M
icro
biol
ogy
Sulfa
met
hoxa
zole
inhi
bits
bac
teria
l syn
thes
is o
f dih
ydro
folic
aci
d by
com
petin
g w
ith p
ara-
amin
oben
zoic
aci
d (P
ABA)
. Tr
imet
hopr
im b
lock
s th
e pr
oduc
tion
of te
trahy
drof
olic
aci
d fro
m d
ihyd
rofo
lic a
cid
by b
indi
ng to
and
reve
rsib
ly in
hibi
ting
the
requ
ired
enzy
me,
dih
ydro
fola
te re
duct
ase.
Thu
s, s
ulfa
met
hoxa
zole
and
trim
etho
prim
blo
cks
two
cons
ecut
ive
step
s in
th
e bi
osyn
thes
is o
f nuc
leic
aci
ds a
nd p
rote
ins
esse
ntia
l to
man
y ba
cter
ia.
In v
itro
stud
ies
have
sho
wn
that
bac
teria
l res
ista
nce
deve
lops
mor
e sl
owly
with
bot
h su
lfam
etho
xazo
le a
nd tr
imet
hopr
im in
co
mbi
natio
n th
an w
ith e
ither
sul
fam
etho
xazo
le o
r trim
etho
prim
alo
ne.
Sulfa
met
hoxa
zole
and
trim
etho
prim
hav
e be
en s
how
n to
be
activ
e ag
ains
t mos
t stra
ins
of th
e fo
llow
ing
mic
roor
gani
sms,
bo
th in
vitr
o an
d in
clin
ical
infe
ctio
ns a
s de
scrib
ed in
the
INDI
CATI
ONS
AND
USAG
E se
ctio
n.Ae
robi
c gr
am-p
ositi
ve m
icro
orga
nism
s:
Stre
ptoc
occu
s pn
eum
onia
e Ae
robi
c gr
am-n
egat
ive
mic
roor
gani
sms:
Es
cher
ichi
a co
li (in
clud
ing
susc
eptib
le e
nter
otox
igen
ic s
train
s im
plic
ated
in tr
avel
er's
dia
rrhe
a)Kl
ebsi
ella
spe
cies
Ente
roba
cter
spe
cies
Haem
ophi
lus
influ
enza
eM
orga
nella
mor
gani
iPr
oteu
s m
irabi
lisPr
oteu
s vu
lgar
isSh
igel
la fl
exne
riSh
igel
la s
onne
iOt
her O
rgan
ism
s:
Pneu
moc
ystis
car
inii
Susc
eptib
ility
Tes
ting
Met
hods
: Di
lutio
n Te
chni
ques
: Qu
antit
ativ
e m
etho
ds a
re u
sed
to d
eter
min
e an
timic
robi
al m
inim
um in
hibi
tory
con
cent
ratio
ns (M
ICs)
. The
se M
ICs
prov
ide
estim
ates
of t
he s
usce
ptib
ility
of b
acte
ria to
ant
imic
robi
al c
ompo
unds
. The
MIC
s sh
ould
be
dete
rmin
ed u
sing
a
stan
dard
ized
proc
edur
e. S
tand
ardi
zed
proc
edur
es a
re b
ased
on
a di
lutio
n m
etho
d4 (b
roth
or a
gar)
or e
quiv
alen
t with
st
anda
rdize
d in
ocul
um c
once
ntra
tions
and
sta
ndar
dize
d co
ncen
tratio
ns o
f sul
fam
etho
xazo
le/tr
imet
hopr
im p
owde
r. Th
e M
IC v
alue
s sh
ould
be
inte
rpre
ted
acco
rdin
g to
the
follo
win
g cr
iteria
: Fo
r tes
ting
Ente
roba
cter
iace
ae:
MIC
(μg/
mL)
In
terp
reta
tion
≤ 2/
38
Susc
eptib
le (S
)≥
4/76
Re
sist
ant (
R)W
hen
test
ing
eith
er H
aem
ophi
lus
influ
enza
ea o
r Stre
ptoc
occu
s pn
eum
onia
eb:
MIC
(μg/
mL)
In
terp
reta
tionb
≤ 0.
5/9.
5 Su
scep
tible
(S)
1/19
– 2
/38
Inte
rmed
iate
(I)
≥ 4/
76
Resi
stan
t (R)
a.Th
ese
inte
rpre
tativ
e st
anda
rds
are
appl
icab
le o
nly
to b
roth
mic
rodi
lutio
n su
scep
tibili
ty te
sts
with
Hae
mop
hilu
s in
fluen
zae
usin
g Ha
emop
hilu
s Te
st M
ediu
m (H
TM).4
b.
Thes
e in
terp
reta
tive
stan
dard
s ar
e ap
plic
able
onl
y to
bro
th m
icro
dilu
tion
susc
eptib
ility
test
s us
ing
catio
n-ad
just
edM
uelle
r-Hi
nton
bro
th w
ith 2
% to
5%
lyse
d ho
rse
bloo
d.4
A re
port
of "S
usce
ptib
le" i
ndic
ates
that
the
path
ogen
is li
kely
to b
e in
hibi
ted
if th
e an
timic
robi
al c
ompo
und
in th
e bl
ood
reac
hes
the
conc
entra
tions
usu
ally
ach
ieva
ble.
A re
port
of "I
nter
med
iate
" ind
icat
es th
at th
e re
sult
shou
ld b
e co
nsid
ered
eq
uivo
cal,
and,
if th
e m
icro
orga
nism
is n
ot fu
lly s
usce
ptib
le to
alte
rnat
ive,
clin
ical
ly fe
asib
le d
rugs
, the
test
sho
uld
be
repe
ated
. Thi
s ca
tego
ry im
plie
s po
ssib
le c
linic
al a
pplic
abili
ty in
bod
y si
tes
whe
re th
e dr
ug is
phy
siol
ogic
ally
con
cent
rate
d or
in s
ituat
ions
whe
re h
igh
dosa
ge o
f dru
g ca
n be
use
d. T
his
cate
gory
als
o pr
ovid
es a
buf
fer z
one
whi
ch p
reve
nts
smal
l un
cont
rolle
d te
chni
cal f
acto
rs fr
om c
ausi
ng m
ajor
dis
crep
anci
es in
inte
rpre
tatio
n. A
repo
rt of
"Res
ista
nt" i
ndic
ates
that
the
path
ogen
is n
ot li
kely
to b
e in
hibi
ted
if th
e an
timic
robi
al c
ompo
und
in th
e bl
ood
reac
hes
the
conc
entra
tions
usu
ally
ac
hiev
able
; oth
er th
erap
y sh
ould
be
sele
cted
. Qu
ality
Con
trol:
Stan
dard
ized
susc
eptib
ility
test
pro
cedu
res
requ
ire th
e us
e of
labo
rato
ry c
ontro
l mic
roor
gani
sms
to c
ontro
l the
tech
nica
l as
pect
s of
the
labo
rato
ry p
roce
dure
s. S
tand
ard
sulfa
met
hoxa
zole
/trim
etho
prim
pow
der s
houl
d pr
ovid
e th
e fo
llow
ing
rang
e of
val
ues:
M
icro
orga
nism
MIC
(μg/
mL)
Esch
eric
hia
coli
ATCC
259
22
≤ 0.
5/9.
5Ha
emop
hilu
s in
fluen
zaec
AT
CC 4
9247
0.
03/0
.59
– 0.
25/4
.75
Stre
ptoc
occu
s pn
eum
onia
ed
ATCC
496
19
0.12
/2.4
– 1
/19
c.Th
is q
ualit
y co
ntro
l ran
ge is
app
licab
le o
nly
to H
aem
ophi
lus
influ
enza
e AT
CC 4
9247
test
ed b
y br
oth
mic
rodi
lutio
npr
oced
ure
usin
g Ha
emop
hilu
s Te
st M
ediu
m (H
TM).4
d.Th
is q
ualit
y co
ntro
l ran
ge is
app
licab
le to
test
s pe
rform
ed b
y th
e br
oth
mic
rodi
lutio
n m
etho
d on
ly u
sing
cat
ion-
adju
sted
Mue
ller-
Hint
on b
roth
with
2%
to 5
% ly
sed
hors
e bl
ood.
4 Di
ffusi
on T
echn
ique
s:
Quan
titat
ive
met
hods
that
requ
ire m
easu
rem
ent o
f zon
e di
amet
ers
also
pro
vide
repr
oduc
ible
est
imat
es o
f the
sus
cept
ibili
ty
of b
acte
ria to
ant
imic
robi
al c
ompo
unds
. One
suc
h st
anda
rdize
d pr
oced
ure5
requ
ires
the
use
of s
tand
ardi
zed
inoc
ulum
co
ncen
tratio
ns. T
his
proc
edur
e us
es p
aper
dis
ks im
preg
nate
d w
ith 1
.25/
23.7
5 μ
g of
sul
fam
etho
xazo
le/tr
imet
hopr
im to
test
th
e su
scep
tibili
ty o
f mic
roor
gani
sms
to s
ulfa
met
hoxa
zole
/trim
etho
prim
. Re
ports
from
the
labo
rato
ry p
rovi
ding
resu
lts o
f the
sta
ndar
d si
ngle
-dis
k su
scep
tibili
ty te
st w
ith a
1.2
5/23
.75
μg
of
sulfa
met
hoxa
zole
/trim
etho
prim
dis
k sh
ould
be
inte
rpre
ted
acco
rdin
g to
the
follo
win
g cr
iteria
: Fo
r tes
ting
eith
er E
nter
obac
teria
ceae
or H
aem
ophi
lus
influ
enza
ee:
Zone
Dia
met
er (m
m)
Inte
rpre
tatio
n≥
16
Susc
eptib
le (S
)11
– 1
5 In
term
edia
te (I
)≤
10
Resi
stan
t (R)
e.Th
ese
zone
dia
met
er s
tand
ards
are
app
licab
le o
nly
for d
isk
diffu
sion
test
ing
with
Hae
mop
hilu
s in
fluen
zae
and
Haem
ophi
lus
Test
Med
ium
(HTM
).5
Whe
n te
stin
g St
rept
ococ
cus
pneu
mon
iaef
:Zo
ne D
iam
eter
(mm
) In
terp
reta
tion
≥ 19
Su
scep
tible
(S)
16 –
18
Inte
rmed
iate
(I)
≤ 15
Re
sist
ant (
R)f.
Thes
e zo
ne d
iam
eter
inte
rpre
tativ
e st
anda
rds
are
appl
icab
le o
nly
to te
sts
perfo
rmed
usi
ng M
uelle
r-Hi
nton
aga
rsu
pple
men
ted
with
5%
def
ibrin
ated
she
ep b
lood
whe
n in
cuba
ted
in 5
% C
O 2.5
In
terp
reta
tion
shou
ld b
e as
sta
ted
abov
e fo
r res
ults
usi
ng d
ilutio
n te
chni
ques
. Int
erpr
etat
ion
invo
lves
cor
rela
tion
of th
e di
amet
er o
btai
ned
in th
e di
sk te
st w
ith th
e M
IC fo
r sul
fam
etho
xazo
le/tr
imet
hopr
im.
Qual
ity C
ontro
l: As
with
sta
ndar
dize
d di
lutio
n te
chni
ques
, diff
usio
n m
etho
ds re
quire
the
use
of la
bora
tory
con
trol m
icro
orga
nism
s th
at a
re
used
to c
ontro
l the
tech
nica
l asp
ects
of t
he la
bora
tory
pro
cedu
res.
For
the
diffu
sion
tech
niqu
e, th
e 1.
25/2
3.75
μg
sulfa
met
hoxa
zole
/trim
etho
prim
dis
k* s
houl
d pr
ovid
e th
e fo
llow
ing
zone
dia
met
ers
in th
ese
labo
rato
ry te
st q
ualit
y co
ntro
l st
rain
s:M
icro
orga
nism
Zone
Dia
met
er R
ange
s (m
m)
Esch
eric
hia
coli
AT
CC 2
5922
23
–29
Haem
ophi
lus
influ
enza
eg
ATCC
492
47
24–3
2 St
rept
ococ
cus
pneu
mon
iaeh
AT
CC 4
9619
20
–28
* M
uelle
r-Hi
nton
aga
r sho
uld
be c
heck
ed fo
r exc
essi
ve le
vels
of t
hym
idin
e or
thym
ine.
To
dete
rmin
e w
heth
erM
uelle
r-Hi
nton
med
ium
has
suf
ficie
ntly
low
leve
ls o
f thy
mid
ine
and
thym
ine,
an
Ente
roco
ccus
faec
alis
(ATC
C 29
212
or
ATCC
331
86) m
ay b
e te
sted
with
sul
fam
etho
xazo
le/tr
imet
hopr
im d
isks
. A zo
ne o
f inh
ibiti
on ≥
20 m
m th
at is
ess
entia
lly
free
of fi
ne c
olon
ies
indi
cate
s a
suffi
cien
tly lo
w le
vel o
f thy
mid
ine
and
thym
ine.
g.
This
qua
lity
cont
rol r
ange
is a
pplic
able
onl
y to
Hae
mop
hilu
s in
fluen
zae
ATCC
492
47 te
sted
by
a di
sk d
iffus
ion
proc
edur
eus
ing
Haem
ophi
lus
Test
Med
ium
(HTM
).5h.
This
qua
lity
cont
rol r
ange
is a
pplic
able
onl
y to
test
s pe
rform
ed b
y di
sk d
iffus
ion
usin
g M
uelle
r-Hi
nton
aga
r sup
plem
ente
dw
ith 5
% d
efib
rinat
ed s
heep
blo
od w
hen
incu
bate
d in
5%
CO 2
.5IN
DICA
TION
S AN
D US
AGE
To re
duce
the
deve
lopm
ent o
f dru
g-re
sist
ant b
acte
ria a
nd m
aint
ain
the
effe
ctiv
enes
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
oral
sus
pens
ion
and
othe
r ant
ibac
teria
l dru
gs, s
ulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
shou
ld b
e us
ed o
nly
to
treat
or p
reve
nt in
fect
ions
that
are
pro
ven
or s
trong
ly s
uspe
cted
to b
e ca
used
by
susc
eptib
le b
acte
ria. W
hen
cultu
re a
nd
susc
eptib
ility
info
rmat
ion
are
avai
labl
e, th
ey s
houl
d be
con
side
red
in s
elec
ting
or m
odify
ing
antib
acte
rial t
hera
py. I
n th
e ab
senc
e of
suc
h da
ta, l
ocal
epi
dem
iolo
gy a
nd s
usce
ptib
ility
pat
tern
s m
ay c
ontri
bute
to e
mpi
ric s
elec
tion
of th
erap
y.Ur
inar
y Tr
act I
nfec
tions
: For
the
treat
men
t of u
rinar
y tra
ct in
fect
ions
due
to s
usce
ptib
le s
train
s of
the
follo
win
g or
gani
sms:
Es
cher
ichi
a co
li, K
lebs
iella
spe
cies
, Ent
erob
acte
r spe
cies
, Mor
gane
lla m
orga
nii,
Prot
eus
mira
bilis
and
Pro
teus
vul
garis
. It i
s re
com
men
ded
that
initi
al e
piso
des
of u
ncom
plic
ated
urin
ary
tract
infe
ctio
ns b
e tre
ated
with
a s
ingl
e ef
fect
ive
antib
acte
rial
agen
t rat
her t
han
the
com
bina
tion.
Acut
e Ot
itis
Med
ia: F
or th
e tre
atm
ent o
f acu
te o
titis
med
ia in
ped
iatri
c pa
tient
s du
e to
sus
cept
ible
stra
ins
of S
trept
ococ
cus
pneu
mon
iae
or H
aem
ophi
lus
influ
enza
e w
hen
in th
e ju
dgm
ent o
f the
phy
sici
an s
ulfa
met
hoxa
zole
and
trim
etho
prim
offe
rs
som
e ad
vant
age
over
the
use
of o
ther
ant
imic
robi
al a
gent
s. T
o da
te, t
here
are
lim
ited
data
on
the
safe
ty o
f rep
eate
d us
e of
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im in
ped
iatri
c pa
tient
s un
der t
wo
year
s of
age
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
not
in
dica
ted
for p
roph
ylac
tic o
r pro
long
ed a
dmin
istra
tion
in o
titis
med
ia a
t any
age
.Ac
ute
Exac
erba
tions
of C
hron
ic B
ronc
hitis
in A
dults
: For
the
treat
men
t of a
cute
exa
cerb
atio
ns o
f chr
onic
bro
nchi
tis d
ue to
su
scep
tible
stra
ins
of S
trept
ococ
cus
pneu
mon
iae
or H
aem
ophi
lus
influ
enza
e w
hen
in th
e ju
dgm
ent o
f the
phy
sici
an
sulfa
met
hoxa
zole
and
trim
etho
prim
offe
rs s
ome
adva
ntag
e ov
er th
e us
e of
a s
ingl
e an
timic
robi
al a
gent
.Sh
igel
losi
s: F
or th
e tre
atm
ent o
f ent
eriti
s ca
used
by
susc
eptib
le s
train
s of
Shi
gella
flex
neri
and
Shig
ella
son
nei w
hen
antib
acte
rial t
hera
py is
indi
cate
d.Pn
eum
ocys
tis C
arin
ii Pn
eum
onia
: For
the
treat
men
t of d
ocum
ente
d Pn
eum
ocys
tis c
arin
ii pn
eum
onia
and
for p
roph
ylax
is
agai
nst P
neum
ocys
tis c
arin
ii pn
eum
onia
in in
divi
dual
s w
ho a
re im
mun
osup
pres
sed
and
cons
ider
ed to
be
at a
n in
crea
sed
risk
of d
evel
opin
g Pn
eum
ocys
tis c
arin
ii pn
eum
onia
.Tr
avel
ers’
Dia
rrhe
a In
Adu
lts: F
or th
e tre
atm
ent o
f tra
vele
rs’ d
iarr
hea
due
to s
usce
ptib
le s
train
s of
ent
erot
oxig
enic
E. c
oli.
CONT
RAIN
DICA
TION
SSu
lfam
etho
xazo
le a
nd tr
imet
hopr
im is
con
train
dica
ted
in p
atie
nts
with
a k
now
n hy
pers
ensi
tivity
to tr
imet
hopr
im o
r su
lfona
mid
es, i
n pa
tient
s w
ith a
his
tory
of d
rug-
indu
ced
imm
une
thro
mbo
cyto
peni
a w
ith u
se o
f trim
etho
prim
and
/or
sulfo
nam
ides
, and
in p
atie
nts
with
doc
umen
ted
meg
alob
last
ic a
nem
ia d
ue to
fola
te d
efic
ienc
y. S
ulfa
met
hoxa
zole
and
tri
met
hopr
im is
als
o co
ntra
indi
cate
d in
pre
gnan
t pat
ient
s an
d nu
rsin
g m
othe
rs, b
ecau
se s
ulfo
nam
ides
pas
s th
e pl
acen
ta
and
are
excr
eted
in th
e m
ilk a
nd m
ay c
ause
ker
nict
erus
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
con
train
dica
ted
in p
edia
tric
patie
nts
less
than
2 m
onth
s of
age
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
als
o co
ntra
indi
cate
d in
pat
ient
s w
ith m
arke
d he
patic
dam
age
or w
ith s
ever
e re
nal i
nsuf
ficie
ncy
whe
n re
nal f
unct
ion
stat
us c
anno
t be
mon
itore
d.W
ARNI
NGS
FATA
LITI
ES A
SSOC
IATE
D W
ITH
THE
ADM
INIS
TRAT
ION
OF S
ULFO
NAM
IDES
, ALT
HOUG
H RA
RE, H
AVE
OCCU
RRED
DUE
TO
SEV
ERE
REAC
TION
S, IN
CLUD
ING
STEV
ENS-
JOHN
SON
SYND
ROM
E, T
OXIC
EPI
DERM
AL N
ECRO
LYSI
S, F
ULM
INAN
T HE
PATI
C NE
CROS
IS, A
GRAN
ULOC
YTOS
IS, A
PLAS
TIC
ANEM
IA A
ND O
THER
BLO
OD D
YSCR
ASIA
S.SU
LFON
AMID
ES, I
NCLU
DING
SUL
FONA
MID
E-CO
NTAI
NING
PRO
DUCT
S SU
CH A
S SU
LFAM
ETHO
XAZO
LE/T
RIM
ETHO
PRIM
, SH
OULD
BE
DISC
ONTI
NUED
AT
THE
FIRS
T AP
PEAR
ANCE
OF
SKIN
RAS
H OR
ANY
SIG
N OF
ADV
ERSE
REA
CTIO
N. In
rare
in
stan
ces,
a s
kin
rash
may
be
follo
wed
by
a m
ore
seve
re re
actio
n, s
uch
as S
teve
ns-J
ohns
on s
yndr
ome,
toxi
c ep
ider
mal
ne
crol
ysis
, hep
atic
nec
rosi
s, a
nd s
erio
us b
lood
dis
orde
rs (s
ee P
RECA
UTIO
NS).
Clin
ical
sig
ns, s
uch
as ra
sh, s
ore
thro
at,
feve
r, ar
thra
lgia
, pal
lor,
purp
ura
or ja
undi
ce m
ay b
e ea
rly in
dica
tions
of s
erio
us re
actio
ns.
Coug
h, s
hortn
ess
of b
reat
h, a
nd p
ulm
onar
y in
filtra
tes
are
hype
rsen
sitiv
ity re
actio
ns o
f the
resp
irato
ry tr
act t
hat h
ave
been
repo
rted
in a
ssoc
iatio
n w
ith s
ulfo
nam
ide
treat
men
t.Th
rom
bocy
tope
nia
Sulfa
met
hoxa
zole
/trim
etho
prim
-indu
ced
thro
mbo
cyto
peni
a m
ay b
e an
imm
une-
med
iate
d di
sord
er. S
ever
e ca
ses
of
thro
mbo
cyto
peni
a th
at a
re fa
tal o
r life
thre
aten
ing
have
bee
n re
porte
d. T
hrom
bocy
tope
nia
usua
lly re
solv
es w
ithin
a w
eek
upon
dis
cont
inua
tion
of s
ulfa
met
hoxa
zole
/trim
etho
prim
.Th
e su
lfona
mid
es s
houl
d no
t be
used
for t
he tr
eatm
ent o
f gro
up A
β-h
emol
ytic
stre
ptoc
occa
l inf
ectio
ns. I
n an
est
ablis
hed
infe
ctio
n, th
ey w
ill n
ot e
radi
cate
the
stre
ptoc
occu
s an
d, th
eref
ore,
will
not
pre
vent
seq
uela
e su
ch a
s rh
eum
atic
feve
r.Cl
ostri
dium
diff
icile
ass
ocia
ted
diar
rhea
(CDA
D) h
as b
een
repo
rted
with
use
of n
early
all
antib
acte
rial a
gent
s, in
clud
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
, and
may
rang
e in
sev
erity
from
mild
dia
rrhe
a to
fata
l col
itis.
Tre
atm
ent w
ith
antib
acte
rial a
gent
s al
ters
the
norm
al fl
ora
of th
e co
lon
lead
ing
to o
verg
row
th o
f C. d
iffic
ile.
C. d
iffic
ile p
rodu
ces
toxi
ns A
and
B w
hich
con
tribu
te to
the
deve
lopm
ent o
f CDA
D. H
yper
toxi
n pr
oduc
ing
stra
ins
of C
. di
ffici
le c
ause
incr
ease
d m
orbi
dity
and
mor
talit
y, a
s th
ese
infe
ctio
ns c
an b
e re
fract
ory
to a
ntim
icro
bial
ther
apy
and
may
re
quire
col
ecto
my.
CDA
D m
ust b
e co
nsid
ered
in a
ll pa
tient
s w
ho p
rese
nt w
ith d
iarr
hea
follo
win
g an
tibio
tic u
se. C
aref
ul
med
ical
his
tory
is n
eces
sary
sin
ce C
DAD
has
been
repo
rted
to o
ccur
ove
r tw
o m
onth
s af
ter t
he a
dmin
istra
tion
of
antib
acte
rial a
gent
s.If
CDAD
is s
uspe
cted
or c
onfir
med
, ong
oing
ant
ibio
tic u
se n
ot d
irect
ed a
gain
st C
. diff
icile
may
nee
d to
be
disc
ontin
ued.
Ap
prop
riate
flui
d an
d el
ectro
lyte
man
agem
ent,
prot
ein
supp
lem
enta
tion,
ant
ibio
tic tr
eatm
ent o
f C. d
iffic
ile, a
nd s
urgi
cal
eval
uatio
n sh
ould
be
inst
itute
d as
clin
ical
ly in
dica
ted.
PREC
AUTI
ONS
Gene
ral
Pres
crib
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
in th
e ab
senc
e of
a p
rove
n or
stro
ngly
sus
pect
ed b
acte
rial
infe
ctio
n or
a p
roph
ylac
tic in
dica
tion
is u
nlik
ely
to p
rovi
de b
enef
it to
the
patie
nt a
nd in
crea
ses
the
risk
of th
e de
velo
pmen
t of
dru
g-re
sist
ant b
acte
ria.
Sulfa
met
hoxa
zole
and
trim
etho
prim
sho
uld
be g
iven
with
cau
tion
to p
atie
nts
with
impa
ired
rena
l or h
epat
ic fu
nctio
n, to
th
ose
with
pos
sibl
e fo
late
def
icie
ncy
(e.g
., th
e el
derly
, chr
onic
alc
ohol
ics,
pat
ient
s re
ceiv
ing
antic
onvu
lsan
t the
rapy
, pa
tient
s w
ith m
alab
sorp
tion
synd
rom
e, a
nd p
atie
nts
in m
alnu
tritio
n st
ates
) and
to th
ose
with
sev
ere
alle
rgie
s or
bro
nchi
al
asth
ma.
In g
luco
se-6
-pho
spha
te d
ehyd
roge
nase
def
icie
nt in
divi
dual
s, h
emol
ysis
may
occ
ur. T
his
reac
tion
is fr
eque
ntly
do
se-r
elat
ed (s
ee C
LINI
CAL
PHAR
MAC
OLOG
Y an
d DO
SAGE
AND
ADM
INIS
TRAT
ION)
.Ca
ses
of h
ypog
lyce
mia
in n
on-d
iabe
tic p
atie
nts
treat
ed w
ith s
ulfa
met
hoxa
zole
and
trim
etho
prim
are
see
n ra
rely
, usu
ally
oc
curr
ing
afte
r a fe
w d
ays
of th
erap
y. P
atie
nts
with
rena
l dys
func
tion,
live
r dis
ease
, mal
nutri
tion
or th
ose
rece
ivin
g hi
gh
dose
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re p
artic
ular
ly a
t ris
k.
Hem
atol
ogic
al c
hang
es in
dica
tive
of fo
lic a
cid
defic
ienc
y m
ay o
ccur
in e
lder
ly p
atie
nts
or in
pat
ient
s w
ith p
reex
istin
g fo
lic
acid
def
icie
ncy
or k
idne
y fa
ilure
. The
se e
ffect
s ar
e re
vers
ible
by
folin
ic a
cid
ther
apy.
Tr
imet
hopr
im h
as b
een
note
d to
impa
ir ph
enyl
alan
ine
met
abol
ism
, but
this
is o
f no
sign
ifica
nce
in p
heny
lket
onur
ic p
atie
nts
on a
ppro
pria
te d
ieta
ry re
stric
tion.
As
with
all
drug
s co
ntai
ning
sul
fona
mid
es, c
autio
n is
adv
isab
le in
pat
ient
s w
ith p
orph
yria
or t
hyro
id d
ysfu
nctio
n.Us
e in
the
Trea
tmen
t of a
nd P
roph
ylax
is fo
r Pne
umoc
ystis
Car
inii
Pneu
mon
ia in
Pat
ient
s w
ith A
cqui
red
Imm
unod
efic
ienc
y Sy
ndro
me
(AID
S): A
IDS
patie
nts
may
not
tole
rate
or r
espo
nd to
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im in
th
e sa
me
man
ner a
s no
n-AI
DS p
atie
nts.
The
inci
denc
e of
sid
e ef
fect
s, p
artic
ular
ly ra
sh, f
ever
, leu
kope
nia
and
elev
ated
am
inot
rans
fera
se (t
rans
amin
ase)
val
ues,
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im th
erap
y in
AID
S pa
tient
s w
ho a
re b
eing
tre
ated
for P
neum
ocys
tis c
arin
ii pn
eum
onia
has
bee
n re
porte
d to
be
grea
tly in
crea
sed
com
pare
d w
ith th
e in
cide
nce
norm
ally
ass
ocia
ted
with
the
use
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
in n
on-A
IDS
patie
nts.
The
inci
denc
e of
hy
perk
alem
ia a
ppea
rs to
be
incr
ease
d in
AID
S pa
tient
s re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
. Adv
erse
effe
cts
are
gene
rally
less
sev
ere
in p
atie
nts
rece
ivin
g su
lfam
etho
xazo
le a
nd tr
imet
hopr
im fo
r pro
phyl
axis
. A h
isto
ry o
f mild
into
lera
nce
to s
ulfa
met
hoxa
zole
and
trim
etho
prim
in A
IDS
patie
nts
does
not
app
ear t
o pr
edic
t int
oler
ance
of s
ubse
quen
t sec
onda
ry
prop
hyla
xis.
6 Ho
wev
er, i
f a p
atie
nt d
evel
ops
skin
rash
or a
ny s
ign
of a
dver
se re
actio
n, th
erap
y w
ith s
ulfa
met
hoxa
zole
and
tri
met
hopr
im s
houl
d be
reev
alua
ted
(see
WAR
NING
S).
High
dos
age
of tr
imet
hopr
im, a
s us
ed in
pat
ient
s w
ith P
neum
ocys
tis c
arin
ii pn
eum
onia
, ind
uces
a p
rogr
essi
ve b
ut
reve
rsib
le in
crea
se o
f ser
um p
otas
sium
con
cent
ratio
ns in
a s
ubst
antia
l num
ber o
f pat
ient
s. E
ven
treat
men
t with
re
com
men
ded
dose
s m
ay c
ause
hyp
erka
lem
ia w
hen
trim
etho
prim
is a
dmin
iste
red
to p
atie
nts
with
und
erly
ing
diso
rder
s of
po
tass
ium
met
abol
ism
, with
rena
l ins
uffic
ienc
y, o
r if d
rugs
kno
wn
to in
duce
hyp
erka
lem
ia a
re g
iven
con
com
itant
ly. C
lose
m
onito
ring
of s
erum
pot
assi
um is
war
rant
ed in
thes
e pa
tient
s.
Durin
g tre
atm
ent,
adeq
uate
flui
d in
take
and
urin
ary
outp
ut s
houl
d be
ens
ured
to p
reve
nt c
ryst
allu
ria. P
atie
nts
who
are
"s
low
ace
tyla
tors
" may
be
mor
e pr
one
to id
iosy
ncra
tic re
actio
ns to
sul
fona
mid
es.
24.625"
2.000" 1.813" 1.750" 1.688" 1.688" 1.750" 1.750" 1.750" 1.750" 1.688" 1.688" 1.750" 1.813" 1.750"
4.12
5"
Reference ID: 3057440
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPGrape Flavor
920 Avenue R Bldg. #200Grand Prairie, TX 75050 (469)733-1506
Healthcare Packaging
IMPRINTAREA
RESEALAREABLACK PMS 321
GREENPMS 2613PURPLE
Base Label
50383-824-163 9
Grape Flavor
Grape Flavor
SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
Rx only
16 fl oz (473 mL)
Rev. 824:07 7/11
NDC 50383-824-16
4.125"
4.125"
SHAKE WELL BEFORE USING.
16 fl oz (473 mL)
HI-TECH PHARMACAL CO., INC.Amityville, NY 11701
Each teaspoonful (5 mL) contains:Sulfamethoxazole ............................. 200 mgTrimethoprim ..................................... 40 mgAlcohol .............................................. 0.26%
USUAL DOSAGE: See package insert for dosage and full prescribing information.
Dispense in a tight, light-resistant container as defined in the USP. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from light.
Book Placement1.813" 2.000"
0.313"
THIS PROOF IS NOT INTENDED FOR COLOR REPRESENTATION. PLEASE REVIEW FOR COPY AND POSITIONING OF GRAPHICS AND TEXT.
APPROVAL SIGNATURE/DATE:
APPROVED
REVISE AND RE-PROOF
PLATINUM PRESS FAX:(469)733-1510
GRAPHICS PROOFSize:
Rev:
4.125” x 4.125” CopyPosition
8
Co
py
#4
#4
5 09/15/11 TA6 09/23/11 TA7 09/29/11 TA8 10/17/11 MC
Rev.# Date Artist
PHARMACAL PHARMACAL
Reference ID: 3057440
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPGrape Flavor
920 Avenue R Bldg. #200Grand Prairie, TX 75050 (469)733-1506
Healthcare Packaging
Front
Cover(Page #1)
Page #20 Page #21 Page #22 Page #23 Page #24 Page #25 Page #26 Page #27 Page #28Page #16 Page #17 Page #18 Page #19
THIS PROOF IS NOT INTENDED FOR COLOR REPRESENTATION. PLEASE REVIEW FOR COPY AND POSITIONING OF GRAPHICS AND TEXT.
APPROVAL SIGNATURE
APPROVED
REVISE AND RE-PROOF
PLATINUM PRESS FAX - (469)733-1510
GRAPHICS PROOFSize:
Rev:
4.125” x 4.125” Copy Position8
Co
py
#4
#4BLACK PMS 321
GREENPMS 2613PURPLE
4.12
5"
24.625"
1.750" 1.813" 1.750" 1.688" 1.688" 1.750" 1.750" 1.750" 1.750" 1.688" 1.688" 1.750" 1.813" 2.000"
Grape Flavor
SULFAMETHOXAZOLEAND TRIMETHOPRIMORAL SUSPENSION, USP200 mg / 40 mg per 5 mL
SHAKE WELL BEFORE USING.
16 fl oz (473 mL)
HI-TECH PHARMACAL CO., INC.Amityville, NY 11701
Each teaspoonful (5 mL) contains:Sulfamethoxazole ............................. 200 mgTrimethoprim ..................................... 40 mgAlcohol .............................................. 0.26%
USUAL DOSAGE: See package insert for dosage and full prescribing information.
Dispense in a tight, light-resistant container as defined in the USP. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from light.
Lift HerePHARMACAL
Info
rmat
ion
for P
atie
nts
Patie
nts
shou
ld b
e co
unse
led
that
ant
ibac
teria
l dru
gs in
clud
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
shou
ld
only
be
used
to tr
eat b
acte
rial i
nfec
tions
. The
y do
not
trea
t vira
l inf
ectio
ns (e
.g.,
the
com
mon
col
d). W
hen
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
is p
resc
ribed
to tr
eat a
bac
teria
l inf
ectio
n, p
atie
nts
shou
ld b
e to
ld th
at
alth
ough
it is
com
mon
to fe
el b
ette
r ear
ly in
the
cour
se o
f the
rapy
, the
med
icat
ion
shou
ld b
e ta
ken
exac
tly a
s di
rect
ed.
Skip
ping
dos
es o
r not
com
plet
ing
the
full
cour
se o
f the
rapy
may
(1) d
ecre
ase
the
effe
ctiv
enes
s of
the
imm
edia
te tr
eatm
ent
and
(2) i
ncre
ase
the
likel
ihoo
d th
at b
acte
ria w
ill d
evel
op re
sist
ance
and
will
not
be
treat
able
by
sulfa
met
hoxa
zole
and
tri
met
hopr
im o
ral s
uspe
nsio
n or
oth
er a
ntib
acte
rial d
rugs
in th
e fu
ture
.Pa
tient
s sh
ould
be
inst
ruct
ed to
mai
ntai
n an
ade
quat
e flu
id in
take
in o
rder
to p
reve
nt c
ryst
allu
ria a
nd s
tone
form
atio
n.Di
arrh
ea is
a c
omm
on p
robl
em c
ause
d by
ant
ibio
tics
whi
ch u
sual
ly e
nds
whe
n th
e an
tibio
tic is
dis
cont
inue
d. S
omet
imes
af
ter s
tarti
ng tr
eatm
ent w
ith a
ntib
iotic
s, p
atie
nts
can
deve
lop
wat
ery
and
bloo
dy s
tool
s (w
ith a
nd w
ithou
t sto
mac
h cr
amps
an
d fe
ver)
eve
n as
late
as
two
or m
ore
mon
ths
afte
r hav
ing
take
n th
e la
st d
ose
of th
e an
tibio
tic. I
f thi
s oc
curs
, pat
ient
s sh
ould
con
tact
thei
r phy
sici
an a
s so
on a
s po
ssib
le.
Labo
rato
ry T
ests
Com
plet
e bl
ood
coun
ts s
houl
d be
don
e fre
quen
tly in
pat
ient
s re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
; if a
sig
nific
ant
redu
ctio
n in
the
coun
t of a
ny fo
rmed
blo
od e
lem
ent i
s no
ted,
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im s
houl
d be
dis
cont
inue
d.
Urin
alys
is w
ith c
aref
ul m
icro
scop
ic e
xam
inat
ion
and
rena
l fun
ctio
n te
sts
shou
ld b
e pe
rform
ed d
urin
g th
erap
y, p
artic
ular
ly
for t
hose
pat
ient
s w
ith im
paire
d re
nal f
unct
ion.
Drug
Inte
ract
ions
In e
lder
ly p
atie
nts
conc
urre
ntly
rece
ivin
g ce
rtain
diu
retic
s, p
rimar
ily th
iazid
es, a
n in
crea
sed
inci
denc
e of
thro
mbo
cyto
peni
a w
ith p
urpu
ra h
as b
een
repo
rted.
It
has
been
repo
rted
that
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay p
rolo
ng th
e pr
othr
ombi
n tim
e in
pat
ient
s w
ho a
re
rece
ivin
g th
e an
ticoa
gula
nt w
arfa
rin. T
his
inte
ract
ion
shou
ld b
e ke
pt in
min
d w
hen
sulfa
met
hoxa
zole
and
trim
etho
prim
is
give
n to
pat
ient
s al
read
y on
ant
icoa
gula
nt th
erap
y, a
nd th
e co
agul
atio
n tim
e sh
ould
be
reas
sess
ed.
Sulfa
met
hoxa
zole
and
trim
etho
prim
may
inhi
bit t
he h
epat
ic m
etab
olis
m o
f phe
nyto
in. S
ulfa
met
hoxa
zole
and
trim
etho
prim
, gi
ven
at a
com
mon
clin
ical
dos
age,
incr
ease
d th
e ph
enyt
oin
half-
life
by 3
9% a
nd d
ecre
ased
the
phen
ytoi
n m
etab
olic
cle
aran
ce
rate
by
27%
. Whe
n ad
min
iste
ring
thes
e dr
ugs
conc
urre
ntly
, one
sho
uld
be a
lert
for p
ossi
ble
exce
ssiv
e ph
enyt
oin
effe
ct.
Sulfo
nam
ides
can
als
o di
spla
ce m
etho
trexa
te fr
om p
lasm
a pr
otei
n bi
ndin
g si
tes
and
can
com
pete
with
the
rena
l tra
nspo
rt of
met
hotre
xate
, thu
s in
crea
sing
free
met
hotre
xate
con
cent
ratio
ns.
Ther
e ha
ve b
een
repo
rts o
f mar
ked
but r
ever
sibl
e ne
phro
toxi
city
with
coa
dmin
istra
tion
of s
ulfa
met
hoxa
zole
and
tri
met
hopr
im a
nd c
yclo
spor
ine
in re
nal t
rans
plan
t rec
ipie
nts.
In
crea
sed
digo
xin
bloo
d le
vels
can
occ
ur w
ith c
onco
mita
nt s
ulfa
met
hoxa
zole
and
trim
etho
prim
ther
apy,
esp
ecia
lly in
el
derly
pat
ient
s. S
erum
dig
oxin
leve
ls s
houl
d be
mon
itore
d.
Incr
ease
d su
lfam
etho
xazo
le b
lood
leve
ls m
ay o
ccur
in p
atie
nts
who
are
als
o re
ceiv
ing
indo
met
haci
n.
Occa
sion
al re
ports
sug
gest
that
pat
ient
s re
ceiv
ing
pyrim
etha
min
e as
mal
aria
pro
phyl
axis
in d
oses
exc
eedi
ng 2
5 m
g w
eekl
y m
ay d
evel
op m
egal
obla
stic
ane
mia
if s
ulfa
met
hoxa
zole
and
trim
etho
prim
is p
resc
ribed
. Th
e ef
ficac
y of
tric
yclic
ant
idep
ress
ants
can
dec
reas
e w
hen
coad
min
iste
red
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im.
Like
oth
er s
ulfo
nam
ide-
cont
aini
ng d
rugs
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im p
oten
tiate
s th
e ef
fect
of o
ral h
ypog
lyce
mic
s.
In th
e lit
erat
ure,
a s
ingl
e ca
se o
f tox
ic d
eliri
um h
as b
een
repo
rted
afte
r con
com
itant
inta
ke o
f su
lfam
etho
xazo
le/tr
imet
hopr
im a
nd a
man
tadi
ne.
In th
e lit
erat
ure,
thre
e ca
ses
of h
yper
kale
mia
in e
lder
ly p
atie
nts
have
bee
n re
porte
d af
ter c
onco
mita
nt in
take
of
sulfa
met
hoxa
zole
/trim
etho
prim
and
an
angi
oten
sin
conv
ertin
g en
zym
e in
hibi
tor.7
,8
Drug
/Lab
orat
ory
Test
Inte
ract
ions
Sulfa
met
hoxa
zole
and
trim
etho
prim
, spe
cific
ally
the
trim
etho
prim
com
pone
nt, c
an in
terfe
re w
ith a
ser
um m
etho
trexa
te
assa
y as
det
erm
ined
by
the
com
petit
ive
bind
ing
prot
ein
tech
niqu
e (C
BPA)
whe
n a
bact
eria
l dih
ydro
fola
te re
duct
ase
is u
sed
as th
e bi
ndin
g pr
otei
n. N
o in
terfe
renc
e oc
curs
, how
ever
, if m
etho
trexa
te is
mea
sure
d by
a ra
dioi
mm
unoa
ssay
(RIA
).Th
e pr
esen
ce o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay a
lso
inte
rfere
with
the
Jaffé
alk
alin
e pi
crat
e re
actio
n as
say
for
crea
tinin
e, re
sulti
ng in
ove
rest
imat
ions
of a
bout
10%
in th
e ra
nge
of n
orm
al v
alue
s.Ca
rcin
ogen
esis
, Mut
agen
esis
, Im
pairm
ent o
f Fer
tility
Carc
inog
enes
is: L
ong-
term
stu
dies
in a
nim
als
to e
valu
ate
carc
inog
enic
pot
entia
l hav
e no
t bee
n co
nduc
ted
with
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im.
Mut
agen
esis
: Bac
teria
l mut
agen
ic s
tudi
es h
ave
not b
een
perfo
rmed
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im in
co
mbi
natio
n. T
rimet
hopr
im w
as d
emon
stra
ted
to b
e no
nmut
agen
ic in
the
Ames
ass
ay. N
o ch
rom
osom
al d
amag
e w
as
obse
rved
in h
uman
leuk
ocyt
es c
ultu
red
in v
itro
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
lone
or i
n co
mbi
natio
n; th
e co
ncen
tratio
ns u
sed
exce
eded
blo
od le
vels
of t
hese
com
poun
ds fo
llow
ing
ther
apy
with
sul
fam
etho
xazo
le a
nd
trim
etho
prim
. Obs
erva
tions
of l
euko
cyte
s ob
tain
ed fr
om p
atie
nts
treat
ed w
ith s
ulfa
met
hoxa
zole
and
trim
etho
prim
reve
aled
no
chr
omos
omal
abn
orm
aliti
es.
Impa
irmen
t of F
ertil
ity: N
o ad
vers
e ef
fect
s on
ferti
lity
or g
ener
al re
prod
uctiv
e pe
rform
ance
wer
e ob
serv
ed in
rats
giv
en
oral
dos
ages
as
high
as
350
mg/
kg/d
ay s
ulfa
met
hoxa
zole
plu
s 70
mg/
kg/d
ay tr
imet
hopr
im.
Preg
nanc
yTe
rato
geni
c Ef
fect
s: P
regn
ancy
Cat
egor
y C.
In ra
ts, o
ral d
oses
of 5
33 m
g/kg
or 2
00 m
g/kg
pro
duce
d te
rato
logi
c ef
fect
s m
anife
sted
mai
nly
as c
left
pala
tes.
Th
e hi
ghes
t dos
e w
hich
did
not
cau
se c
left
pala
tes
in ra
ts w
as 5
12 m
g/kg
sul
fam
etho
xazo
le o
r 192
mg/
kg tr
imet
hopr
im
whe
n ad
min
iste
red
sepa
rate
ly. I
n tw
o st
udie
s in
rats
, no
tera
tolo
gy w
as o
bser
ved
whe
n 51
2 m
g/kg
of s
ulfa
met
hoxa
zole
w
as u
sed
in c
ombi
natio
n w
ith 1
28 m
g/kg
of t
rimet
hopr
im. I
n on
e st
udy,
how
ever
, cle
ft pa
late
s w
ere
obse
rved
in o
ne li
tter
out o
f 9 w
hen
355
mg/
kg o
f sul
fam
etho
xazo
le w
as u
sed
in c
ombi
natio
n w
ith 8
8 m
g/kg
of t
rimet
hopr
im.
In s
ome
rabb
it st
udie
s, a
n ov
eral
l inc
reas
e in
feta
l los
s (d
ead
and
reso
rbed
and
mal
form
ed c
once
ptus
es) w
as a
ssoc
iate
d w
ith d
oses
of t
rimet
hopr
im 6
tim
es th
e hu
man
ther
apeu
tic d
ose.
Whi
le th
ere
are
no la
rge,
wel
l-con
trolle
d st
udie
s on
the
use
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
in p
regn
ant w
omen
, Br
umfit
t and
Pur
sell,
9 in
a re
trosp
ectiv
e st
udy,
repo
rted
the
outc
ome
of 1
86 p
regn
anci
es d
urin
g w
hich
the
mot
her r
ecei
ved
eith
er p
lace
bo o
r sul
fam
etho
xazo
le a
nd tr
imet
hopr
im. T
he in
cide
nce
of c
onge
nita
l abn
orm
aliti
es w
as 4
.5%
(3 o
f 66)
in
thos
e w
ho re
ceiv
ed p
lace
bo a
nd 3
.3%
(4 o
f 120
) in
thos
e re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
. The
re w
ere
no
abno
rmal
ities
in th
e 10
chi
ldre
n w
hose
mot
hers
rece
ived
the
drug
dur
ing
the
first
trim
este
r. In
a s
epar
ate
surv
ey, B
rum
fitt
and
Purs
ell a
lso
foun
d no
con
geni
tal a
bnor
mal
ities
in 3
5 ch
ildre
n w
hose
mot
hers
had
rece
ived
ora
l sul
fam
etho
xazo
le a
nd
trim
etho
prim
at t
he ti
me
of c
once
ptio
n or
sho
rtly
ther
eafte
r.Be
caus
e su
lfam
etho
xazo
le a
nd tr
imet
hopr
im m
ay in
terfe
re w
ith fo
lic a
cid
met
abol
ism
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
shou
ld b
e us
ed d
urin
g pr
egna
ncy
only
if th
e po
tent
ial b
enef
it ju
stifi
es th
e po
tent
ial r
isk
to th
e fe
tus.
Nont
erat
ogen
ic E
ffect
s: S
ee C
ONTR
AIND
ICAT
IONS
sec
tion.
Nurs
ing
Mot
hers
See
CONT
RAIN
DICA
TION
S se
ctio
n.Pe
diat
ric U
seSu
lfam
etho
xazo
le a
nd tr
imet
hopr
im is
not
reco
mm
ende
d fo
r inf
ants
you
nger
than
2 m
onth
s of
age
(see
INDI
CATI
ONS
AND
USAG
E an
d CO
NTRA
INDI
CATI
ONS
sect
ions
).Ge
riatri
c Us
eCl
inic
al s
tudi
es o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im d
id n
ot in
clud
e su
ffici
ent n
umbe
rs o
f sub
ject
s ag
ed 6
5 an
d ov
er to
de
term
ine
whe
ther
they
resp
ond
diffe
rent
ly fr
om y
oung
er s
ubje
cts.
Ther
e m
ay b
e an
incr
ease
d ris
k of
sev
ere
adve
rse
reac
tions
in e
lder
ly p
atie
nts,
par
ticul
arly
whe
n co
mpl
icat
ing
cond
ition
s ex
ist,
e.g.
, im
paire
d ki
dney
and
/or l
iver
func
tion,
pos
sibl
e fo
late
def
icie
ncy,
or c
onco
mita
nt u
se o
f oth
er d
rugs
. Sev
ere
skin
re
actio
ns, g
ener
alize
d bo
ne m
arro
w s
uppr
essi
on (s
ee W
ARNI
NGS
and
ADVE
RSE
REAC
TION
S se
ctio
ns),
a sp
ecifi
c de
crea
se in
pla
tele
ts (w
ith o
r with
out p
urpu
ra),
and
hype
rkal
emia
are
the
mos
t fre
quen
tly re
porte
d se
vere
adv
erse
re
actio
ns in
eld
erly
pat
ient
s. In
thos
e co
ncur
rent
ly re
ceiv
ing
certa
in d
iure
tics,
prim
arily
thia
zides
, an
incr
ease
d in
cide
nce
of
thro
mbo
cyto
peni
a w
ith p
urpu
ra h
as b
een
repo
rted.
Incr
ease
d di
goxi
n bl
ood
leve
ls c
an o
ccur
with
con
com
itant
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im th
erap
y, e
spec
ially
in e
lder
ly p
atie
nts.
Ser
um d
igox
in le
vels
sho
uld
be m
onito
red.
He
mat
olog
ical
cha
nges
indi
cativ
e of
folic
aci
d de
ficie
ncy
may
occ
ur in
eld
erly
pat
ient
s. T
hese
effe
cts
are
reve
rsib
le b
y fo
linic
aci
d th
erap
y. A
ppro
pria
te d
osag
e ad
just
men
ts s
houl
d be
mad
e fo
r pat
ient
s w
ith im
paire
d ki
dney
func
tion
and
dura
tion
of u
se s
houl
d be
as
shor
t as
poss
ible
to m
inim
ize ri
sks
of u
ndes
ired
reac
tions
(see
DOS
AGE
AND
ADM
INIS
TRAT
ION
sect
ion)
. The
trim
etho
prim
com
pone
nt o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im m
ay c
ause
hyp
erka
lem
ia
whe
n ad
min
iste
red
to p
atie
nts
with
und
erly
ing
diso
rder
s of
pot
assi
um m
etab
olis
m, w
ith re
nal i
nsuf
ficie
ncy
or w
hen
give
n co
ncom
itant
ly w
ith d
rugs
kno
wn
to in
duce
hyp
erka
lem
ia, s
uch
as a
ngio
tens
in c
onve
rting
enz
yme
inhi
bito
rs. C
lose
m
onito
ring
of s
erum
pot
assi
um is
war
rant
ed in
thes
e pa
tient
s. D
isco
ntin
uatio
n of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
treat
men
t is
reco
mm
ende
d to
hel
p lo
wer
pot
assi
um s
erum
leve
ls.
Phar
mac
okin
etic
s pa
ram
eter
s fo
r sul
fam
etho
xazo
le w
ere
sim
ilar f
or g
eria
tric
subj
ects
and
you
nger
adu
lt su
bjec
ts. T
he
mea
n m
axim
um s
erum
trim
etho
prim
con
cent
ratio
n w
as h
ighe
r and
mea
n re
nal c
lear
ance
of t
rimet
hopr
im w
as lo
wer
in
geria
tric
subj
ects
com
pare
d w
ith y
oung
er s
ubje
cts
(see
CLI
NICA
L PH
ARM
ACOL
OGY:
Ger
iatri
c Ph
arm
acok
inet
ics)
.AD
VERS
E RE
ACTI
ONS
The
mos
t com
mon
adv
erse
effe
cts
are
gast
roin
test
inal
dis
turb
ance
s (n
ause
a, v
omiti
ng, a
nore
xia)
and
alle
rgic
ski
n re
actio
ns (s
uch
as ra
sh a
nd u
rtica
ria).
FATA
LITI
ES A
SSOC
IATE
D W
ITH
THE
ADM
INIS
TRAT
ION
OF S
ULFO
NAM
IDES
, AL
THOU
GH R
ARE,
HAV
E OC
CURR
ED D
UE T
O SE
VERE
REA
CTIO
NS, I
NCLU
DING
STE
VENS
-JOH
NSON
SYN
DROM
E,
TOXI
C EP
IDER
MAL
NEC
ROLY
SIS,
FUL
MIN
ANT
HEPA
TIC
NECR
OSIS
, AGR
ANUL
OCYT
OSIS
, APL
ASTI
C AN
EMIA
AND
OT
HER
BLOO
D DY
SCRA
SIAS
(SEE
WAR
NING
S SE
CTIO
N).
Hem
atol
ogic
: Agr
anul
ocyt
osis
, apl
astic
ane
mia
, thr
ombo
cyto
peni
a, le
ukop
enia
, neu
trope
nia,
hem
olyt
ic a
nem
ia,
meg
alob
last
ic a
nem
ia, h
ypop
roth
rom
bine
mia
, met
hem
oglo
bine
mia
, eos
inop
hilia
.Al
lerg
ic R
eact
ions
: Ste
vens
-Joh
nson
syn
drom
e, to
xic
epid
erm
al n
ecro
lysi
s, a
naph
ylax
is, a
llerg
ic m
yoca
rditi
s, e
ryth
ema
mul
tifor
me,
exf
olia
tive
derm
atiti
s, a
ngio
edem
a, d
rug
feve
r, ch
ills,
Hen
och-
Schö
enle
in p
urpu
ra, s
erum
sic
knes
s-lik
e sy
ndro
me,
gen
eral
ized
alle
rgic
reac
tions
, gen
eral
ized
skin
eru
ptio
ns, p
hoto
sens
itivi
ty, c
onju
nctiv
al a
nd s
cler
al in
ject
ion,
pr
uritu
s, u
rtica
ria a
nd ra
sh. I
n ad
ditio
n, p
eria
rterit
is n
odos
a an
d sy
stem
ic lu
pus
eryt
hem
atos
us h
ave
been
repo
rted.
Gast
roin
test
inal
: Hep
atiti
s, (i
nclu
ding
cho
lest
atic
jaun
dice
and
hep
atic
nec
rosi
s), e
leva
tion
of s
erum
tran
sam
inas
e an
d bi
lirub
in,
pseu
dom
embr
anou
s en
tero
colit
is, p
ancr
eatit
is, s
tom
atiti
s, g
loss
itis,
nau
sea,
em
esis
, abd
omin
al p
ain,
dia
rrhe
a, a
nore
xia.
Geni
tour
inar
y: R
enal
failu
re, i
nter
stiti
al n
ephr
itis,
BUN
and
ser
um c
reat
inin
e el
evat
ion,
toxi
c ne
phro
sis
with
olig
uria
and
an
uria
, cry
stal
luria
and
nep
hrot
oxic
ity in
ass
ocia
tion
with
cyc
losp
orin
e.M
etab
olic
and
Nut
ritio
nal:
Hype
rkal
emia
(see
PRE
CAUT
IONS
: Use
in th
e Tr
eatm
ent o
f and
Pro
phyl
axis
for
Pneu
moc
ystis
Car
inii
Pneu
mon
ia in
Pat
ient
s w
ith A
cqui
red
Imm
unod
efic
ienc
y Sy
ndro
me
(AID
S).
Neur
olog
ic: A
sept
ic m
enin
gitis
, con
vuls
ions
, per
iphe
ral n
eurit
is, a
taxi
a, v
ertig
o, ti
nnitu
s, h
eada
che.
Psyc
hiat
ric: H
allu
cina
tions
, dep
ress
ion,
apa
thy,
ner
vous
ness
.En
docr
ine:
The
sul
fona
mid
es b
ear c
erta
in c
hem
ical
sim
ilarit
ies
to s
ome
goitr
ogen
s, d
iure
tics
(ace
tazo
lam
ide
and
the
thia
zides
) and
ora
l hyp
ogly
cem
ic a
gent
s. C
ross
-sen
sitiv
ity m
ay e
xist
with
thes
e ag
ents
. Diu
resi
s an
d hy
pogl
ycem
ia h
ave
occu
rred
rare
ly in
pat
ient
s re
ceiv
ing
sulfo
nam
ides
.M
uscu
losk
elet
al: A
rthra
lgia
and
mya
lgia
. Iso
late
d ca
ses
of rh
abdo
myo
lysi
s ha
ve b
een
repo
rted
with
sul
fam
etho
xazo
le a
nd
trim
etho
prim
, mai
nly
in A
IDS
patie
nts.
Resp
irato
ry: C
ough
, sho
rtnes
s of
bre
ath
and
pulm
onar
y in
filtra
tes
(see
WAR
NING
S).
Mis
cella
neou
s: W
eakn
ess,
fatig
ue, i
nsom
nia.
Post
mar
ketin
g Ex
perie
nce
The
follo
win
g ad
vers
e re
actio
ns h
ave
been
iden
tifie
d du
ring
post
-app
rova
l use
of t
rimet
hopr
im-s
ulfa
met
hoxa
zole
. Bec
ause
th
ese
reac
tions
wer
e re
porte
d vo
lunt
arily
from
a p
opul
atio
n of
unc
erta
in s
ize, i
t is
not p
ossi
ble
to re
liabl
y es
timat
e th
eir
frequ
ency
or e
stab
lish
a ca
usal
rela
tions
hip
to d
rug
expo
sure
:Σ
Thr
ombo
tic th
rom
bocy
tope
nia
purp
ura
Σ Id
iopa
thic
thro
mbo
cyto
peni
c pu
rpur
aOV
ERDO
SAGE
Acut
e: T
he a
mou
nt o
f a s
ingl
e do
se o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im th
at is
eith
er a
ssoc
iate
d w
ith s
ympt
oms
of
over
dosa
ge o
r is
likel
y to
be
life-
thre
aten
ing
has
not b
een
repo
rted.
Sig
ns a
nd s
ympt
oms
of o
verd
osag
e re
porte
d w
ith
sulfo
nam
ides
incl
ude
anor
exia
, col
ic, n
ause
a, v
omiti
ng, d
izzin
ess,
hea
dach
e, d
row
sine
ss a
nd u
ncon
scio
usne
ss. P
yrex
ia,
hem
atur
ia a
nd c
ryst
allu
ria m
ay b
e no
ted.
Blo
od d
yscr
asia
s an
d ja
undi
ce a
re p
oten
tial l
ate
man
ifest
atio
ns o
f ove
rdos
age.
Si
gns
of a
cute
ove
rdos
age
with
trim
etho
prim
incl
ude
naus
ea, v
omiti
ng, d
izzin
ess,
hea
dach
e, m
enta
l dep
ress
ion,
con
fusi
on
and
bone
mar
row
dep
ress
ion.
Ge
nera
l prin
cipl
es o
f tre
atm
ent i
nclu
de th
e in
stitu
tion
of g
astri
c la
vage
or e
mes
is, f
orci
ng o
ral f
luid
s, a
nd th
e ad
min
istra
tion
of in
trave
nous
flui
ds if
urin
e ou
tput
is lo
w a
nd re
nal f
unct
ion
is n
orm
al. A
cidi
ficat
ion
of th
e ur
ine
will
incr
ease
rena
l el
imin
atio
n of
trim
etho
prim
. The
pat
ient
sho
uld
be m
onito
red
with
blo
od c
ount
s an
d ap
prop
riate
blo
od c
hem
istri
es,
incl
udin
g el
ectro
lyte
s. If
a s
igni
fican
t blo
od d
yscr
asia
or j
aund
ice
occu
rs, s
peci
fic th
erap
y sh
ould
be
inst
itute
d fo
r the
se
com
plic
atio
ns. P
erito
neal
dia
lysi
s is
not
effe
ctiv
e an
d he
mod
ialy
sis
is o
nly
mod
erat
ely
effe
ctiv
e in
elim
inat
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
.Ch
roni
c: U
se o
f sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
t hig
h do
ses
and/
or fo
r ext
ende
d pe
riods
of t
ime
may
cau
se b
one
mar
row
dep
ress
ion
man
ifest
ed a
s th
rom
bocy
tope
nia,
leuk
open
ia a
nd/o
r meg
alob
last
ic a
nem
ia. I
f sig
ns o
f bon
e m
arro
w
depr
essi
on o
ccur
, the
pat
ient
sho
uld
be g
iven
leuc
ovor
in 5
to 1
5 m
g da
ily u
ntil
norm
al h
emat
opoi
esis
is re
stor
ed.
DOSA
GE A
ND A
DMIN
ISTR
ATIO
NNo
t rec
omm
ende
d fo
r use
in p
edia
tric
patie
nts
less
than
2 m
onth
s of
age
.Ur
inar
y Tr
act I
nfec
tions
and
Shi
gello
sis
in A
dults
and
Ped
iatri
c Pa
tient
s, a
nd A
cute
Otit
is M
edia
in C
hild
ren:
Adul
ts: T
he u
sual
adu
lt do
sage
in th
e tre
atm
ent o
f urin
ary
tract
infe
ctio
ns is
four
teas
poon
fuls
(20
mL)
sul
fam
etho
xazo
le
and
trim
etho
prim
ora
l sus
pens
ion
ever
y 12
hou
rs fo
r 10
to 1
4 da
ys. A
n id
entic
al d
aily
dos
age
is u
sed
for 5
day
s in
the
treat
men
t of s
hige
llosi
s.Ch
ildre
n: T
he re
com
men
ded
dose
for c
hild
ren
with
urin
ary
tract
infe
ctio
ns o
r acu
te o
titis
med
ia is
40
mg/
kg
sulfa
met
hoxa
zole
and
8 m
g/kg
trim
etho
prim
per
24
hour
s, g
iven
in tw
o di
vide
d do
ses
ever
y 12
hou
rs fo
r 10
days
. An
iden
tical
dai
ly d
osag
e is
use
d fo
r 5 d
ays
in th
e tre
atm
ent o
f shi
gello
sis.
The
follo
win
g ta
ble
is a
gui
delin
e fo
r the
atta
inm
ent
of th
is d
osag
e:
Acut
e Ex
acer
batio
ns o
f Chr
onic
Bro
nchi
tis in
Adu
lts:
The
usua
l adu
lt do
sage
in th
e tre
atm
ent o
f acu
te e
xace
rbat
ions
of c
hron
ic b
ronc
hitis
is fo
ur te
aspo
onfu
ls (2
0 m
L)
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
ever
y 12
hou
rs fo
r 14
days
.Pn
eum
ocys
tis C
arin
ii Pn
eum
onia
:Tr
eatm
ent:
Adul
ts a
nd C
hild
ren:
The
reco
mm
ende
d do
sage
for t
reat
men
t of p
atie
nts
with
doc
umen
ted
Pneu
moc
ystis
ca
rinii
pneu
mon
ia is
75
to 1
00 m
g/kg
sul
fam
etho
xazo
le a
nd 1
5 to
20
mg/
kg tr
imet
hopr
im p
er 2
4 ho
urs
give
n in
equ
ally
di
vide
d do
ses
ever
y 6
hour
s fo
r 14
to 2
1 da
ys.1
0 T
he fo
llow
ing
tabl
e is
a g
uide
line
for t
he u
pper
lim
it of
this
dos
age:
For t
he lo
wer
lim
it do
se (7
5 m
g/kg
sul
fam
etho
xazo
le a
nd 1
5 m
g/kg
trim
etho
prim
per
24
hour
s) a
dmin
iste
r 75%
of t
he
dose
in th
e ab
ove
tabl
e.Pr
ophy
laxi
s:Ad
ults
: The
reco
mm
ende
d do
sage
for p
roph
ylax
is in
adu
lts is
four
teas
poon
fuls
(20
mL)
of t
he o
ral s
uspe
nsio
n da
ily.1
1Ch
ildre
n: F
or c
hild
ren,
the
reco
mm
ende
d do
se is
750
mg/
m2 /
day
sulfa
met
hoxa
zole
with
150
mg/
m2 /
day
trim
etho
prim
gi
ven
oral
ly in
equ
ally
div
ided
dos
es tw
ice
a da
y, o
n 3
cons
ecut
ive
days
per
wee
k. T
he to
tal d
aily
dos
e sh
ould
not
exc
eed
1600
mg
sulfa
met
hoxa
zole
and
320
mg
trim
etho
prim
.12
The
follo
win
g ta
ble
is a
gui
delin
e fo
r the
atta
inm
ent o
f thi
s do
sage
in c
hild
ren:
Trav
eler
's D
iarr
hea
in A
dults
: Fo
r the
trea
tmen
t of t
rave
ler's
dia
rrhe
a, th
e us
ual a
dult
dosa
ge is
four
teas
poon
fuls
(20
mL)
of s
ulfa
met
hoxa
zole
and
tri
met
hopr
im o
ral s
uspe
nsio
n ev
ery
12 h
ours
for 5
day
s.
HOW
SUP
PLIE
DSu
lfam
etho
xazo
le a
nd T
rimet
hopr
im O
ral S
uspe
nsio
n, U
SP is
sup
plie
d in
a p
urpl
e gr
ape-
flavo
red
susp
ensi
on a
nd in
a p
ink
cher
ry-fl
avor
ed s
uspe
nsio
n co
ntai
ning
200
mg
sulfa
met
hoxa
zole
and
40
mg
trim
etho
prim
per
5 m
L (te
aspo
onfu
l) bo
th
pack
aged
in 1
pin
t (47
3 m
L) b
ottle
s.St
ore
at 2
0°-2
5°C
(68°
-77°
F) [s
ee U
SP C
ontro
lled
Room
Tem
pera
ture
]. Pr
otec
t fro
m li
ght.
SHAK
E W
ELL
BEFO
RE U
SING
.Di
spen
se in
a ti
ght,
light
-res
ista
nt c
onta
iner
as
defin
ed in
the
USP,
with
a c
hild
-res
ista
nt c
losu
re (a
s re
quire
d).
To re
port
SUSP
ECTE
D AD
VERS
E RE
ACTI
ONS,
con
tact
Hi-T
ech
Phar
mac
al, C
o., I
nc. a
t 1-8
00-2
62-9
010
or F
DA a
t 1-
800-
FDA-
1088
or w
ww
.fda.
gov/
med
wat
ch.
Rx o
nly
REFE
RENC
ES1.
Kr
emer
s P,
Duv
ivie
r J, H
eusg
hem
C. P
harm
acok
inet
ic S
tudi
es o
f Co-
Trim
oxaz
ole
in M
an a
fter S
ingl
e an
d Re
peat
edDo
ses.
J C
lin P
harm
acol
. Feb
-Mar
197
4; 1
4:11
2–11
7.
2.
Kapl
an S
A, e
t al.
Phar
mac
okin
etic
Pro
file
of T
rimet
hopr
im-S
ulfa
met
hoxa
zole
in M
an. J
Infe
ct D
is. N
ov 1
973;
128
(Sup
pl):
S547
–S55
5.
3.
Varo
quau
x O,
et a
l. Ph
arm
acok
inet
ics
of th
e tri
met
hopr
im-s
ulfa
met
hoxa
zole
com
bina
tion
in th
e el
derly
.Br
J C
lin P
harm
acol
. 198
5;20
:575
–581
. 4.
Ru
doy
RC, N
elso
n JD
, Hal
talin
KC.
Ant
imic
robi
al A
gent
s Ch
emot
her.
May
197
4;5:
439–
443.
5.
Na
tiona
l Com
mitt
ee fo
r Clin
ical
Lab
orat
ory
Stan
dard
s. M
etho
ds fo
r Dilu
tion
Antim
icro
bial
Sus
cept
ibili
ty T
ests
for
Bact
eria
that
Gro
w A
erob
ical
ly; A
ppro
ved
Stan
dard
– F
ourth
Edi
tion.
NCC
LS D
ocum
ent M
7–A4
, Vol
.17,
No.
2, N
CCLS
, W
ayne
, PA,
Jan
uary
, 199
7.
6.
Hard
y DW
, et a
l. A
cont
rolle
d tri
al o
f trim
etho
prim
-sul
fam
etho
xazo
le o
r aer
osol
ized
pent
amid
ine
for s
econ
dary
prop
hyla
xis
of P
neum
ocys
tis c
arin
ii pn
eum
onia
in p
atie
nts
with
the
acqu
ired
imm
unod
efic
ienc
y sy
ndro
me.
N En
gl J
Med
. 199
2; 3
27: 1
842–
1848
. 7.
M
arin
ella
Mar
k A.
199
9. T
rimet
hopr
im-in
duce
d hy
perk
alem
ia: A
n an
alys
is o
f rep
orte
d ca
ses.
Ger
onto
l. 45
:209
–212
. 8.
M
arga
sser
y, S
. and
B. B
asta
ni. 2
002.
Life
thre
aten
ing
hype
rkal
emia
and
aci
dosi
s se
cond
ary
totri
met
hopr
im-s
ulfa
met
hoxa
zole
trea
tmen
t. J.
Nep
hrol
. 14:
410–
414.
9.
Br
umfit
t W, P
urse
ll R.
Trim
etho
prim
/Sul
fam
etho
xazo
le in
the
Trea
tmen
t of B
acte
riuria
in W
omen
. J In
fect
Dis
.No
v 19
73; 1
28 (S
uppl
):S65
7–S6
63.
10. M
asur
H. P
reve
ntio
n an
d tre
atm
ent o
f Pne
umoc
ystis
pne
umon
ia. N
Eng
l J M
ed. 1
992;
327
: 185
3–18
80.
11. R
ecom
men
datio
ns fo
r pro
phyl
axis
aga
inst
Pne
umoc
ystis
car
inii
pneu
mon
ia fo
r adu
lts a
nd a
dole
scen
ts in
fect
ed w
ithhu
man
imm
unod
efic
ienc
y vi
rus.
MM
WR.
199
2; 4
1(RR
-4):1
–11.
12
. CDC
Gui
delin
es fo
r pro
phyl
axis
aga
inst
Pne
umoc
ystis
car
inii
pneu
mon
ia fo
r chi
ldre
n in
fect
ed w
ith h
uman
imm
unod
efic
ienc
y vi
rus.
MM
WR.
199
1; 4
0(RR
-2):1
–13.
M
anuf
actu
red
by:
Hi-T
ech
Phar
mac
al C
o., I
nc.
Rev.
824:
07 7
/11
Amity
ville
, New
Yor
k 11
701
Child
ren
2 m
onth
s of
age
or o
lder
:
Dose
— e
very
12
hour
s
Dose
— e
very
6 h
ours
Dose
— e
very
12
hour
s
Reference ID: 3057440
Hi-Tech Pharmacal Co., Inc.16oz. Sulfamethoxazole and
Trimethoprim OS, USPGrape Flavor
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4.125” x 4.125” Copy Position7
Co
py
#4
#4BLACK
24.625"
2.000" 1.813" 1.750" 1.688" 1.688" 1.750" 1.750" 1.750" 1.750" 1.688" 1.688" 1.750" 1.813" 1.750"
4.12
5"
CH
3
HN 2
SO
NH
2
NO
N
N
NH
2
CH
2N
H2
CH
O3
OC
H3
OC
H3
SULF
AMET
HOXA
ZOLE
AND
TRI
MET
HOPR
IMOR
AL S
USPE
NSIO
N, U
SPTo
redu
ce th
e de
velo
pmen
t of d
rug-
resi
stan
t bac
teria
and
mai
ntai
n th
e ef
fect
iven
ess
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
or
al s
uspe
nsio
n an
d ot
her a
ntib
acte
rial d
rugs
, sul
fam
etho
xazo
le a
nd tr
imet
hopr
im o
ral s
uspe
nsio
n sh
ould
be
used
onl
y to
tre
at o
r pre
vent
infe
ctio
ns th
at a
re p
rove
n or
stro
ngly
sus
pect
ed to
be
caus
ed b
y ba
cter
ia.
DESC
RIPT
ION
Sulfa
met
hoxa
zole
and
trim
etho
prim
is a
syn
thet
ic a
ntib
acte
rial c
ombi
natio
n pr
oduc
t con
tain
ing
200
mg
sulfa
met
hoxa
zole
an
d 40
mg
trim
etho
prim
per
5 m
L fo
r ora
l adm
inis
tratio
n.
Sulfa
met
hoxa
zole
is N
1 -(5
-met
hyl-3
-isox
azol
yl)s
ulfa
nila
mid
e; th
e m
olec
ular
form
ula
is C
10H 1
1N3O
3S. I
t is
an a
lmos
t whi
te,
odor
less
, tas
tele
ss c
ompo
und
with
a m
olec
ular
wei
ght o
f 253
.28
and
the
follo
win
g st
ruct
ural
form
ula:
Trim
etho
prim
is 2
,4-d
iam
ino-
5-(3
,4,5
-trim
etho
xybe
nzyl
)pyr
imid
ine;
the
mol
ecul
ar fo
rmul
a is
C14
H 18N
4O3.
It is
a w
hite
to
light
yel
low
, odo
rless
, bitt
er c
ompo
und
with
a m
olec
ular
wei
ght o
f 290
.3 a
nd th
e fo
llow
ing
stru
ctur
al fo
rmul
a:
Inac
tive
ingr
edie
nts:
alc
ohol
0.2
6%, m
ethy
lpar
aben
0.1
% a
nd s
odiu
m b
enzo
ate
0.1%
(add
ed a
s pr
eser
vativ
es),
carb
oxym
ethy
lcel
lulo
se s
odiu
m, c
itric
aci
d (a
nhyd
rous
), gl
ycer
in, m
icro
crys
talli
ne c
ellu
lose
, pol
ysor
bate
80,
pur
ified
wat
er,
sacc
harin
sod
ium
, and
sor
bito
l. Th
e lig
ht p
urpl
e, g
rape
flav
ored
sus
pens
ion
cont
ains
the
follo
win
g ad
ditio
nal i
nact
ive
ingr
edie
nts:
FD&
C Re
d No
. 40,
FD&
C Bl
ue N
o. 1
and
nat
ural
and
arti
ficia
l gra
pe fl
avor
. The
pin
k, c
herr
y fla
vore
d su
spen
sion
co
ntai
ns th
e fo
llow
ing
addi
tiona
l ina
ctiv
e in
gred
ient
s: F
D&C
Red
No. 4
0, F
D&C
Yello
w N
o. 6
and
arti
ficia
l che
rry
flavo
r.CL
INIC
AL P
HARM
ACOL
OGY
Sulfa
met
hoxa
zole
and
trim
etho
prim
is ra
pidl
y ab
sorb
ed fo
llow
ing
oral
adm
inis
tratio
n. B
oth
sulfa
met
hoxa
zole
and
tri
met
hopr
im e
xist
in th
e bl
ood
as u
nbou
nd, p
rote
in-b
ound
and
met
abol
ized
form
s; s
ulfa
met
hoxa
zole
als
o ex
ists
as
the
conj
ugat
ed fo
rm. T
he m
etab
olis
m o
f sul
fam
etho
xazo
le o
ccur
s pr
edom
inat
ely
by N
4-ac
etyl
atio
n, a
lthou
gh th
e gl
ucur
onid
e co
njug
ate
has
been
iden
tifie
d. T
he p
rinci
pal m
etab
olite
s of
trim
etho
prim
are
the
1- a
nd 3
-oxi
des
and
the
3’- a
nd 4
’-hyd
roxy
de
rivat
ives
. The
free
form
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re c
onsi
dere
d to
be
the
ther
apeu
tical
ly a
ctiv
e fo
rms.
Ap
prox
imat
ely
70%
of s
ulfa
met
hoxa
zole
and
44%
of t
rimet
hopr
im a
re b
ound
to p
lasm
a pr
otei
ns. T
he p
rese
nce
of 1
0 m
g pe
rcen
t sul
fam
etho
xazo
le in
pla
sma
decr
ease
s th
e pr
otei
n bi
ndin
g of
trim
etho
prim
by
an in
sign
ifica
nt d
egre
e; tr
imet
hopr
im
does
not
influ
ence
the
prot
ein
bind
ing
of s
ulfa
met
hoxa
zole
.Pe
ak b
lood
leve
ls fo
r the
indi
vidu
al c
ompo
nent
s oc
cur 1
to 4
hou
rs a
fter o
ral a
dmin
istra
tion.
The
mea
n se
rum
hal
f-liv
es o
f su
lfam
etho
xazo
le a
nd tr
imet
hopr
im a
re 1
0 an
d 8
to 1
0 ho
urs,
resp
ectiv
ely.
How
ever
, pat
ient
s w
ith s
ever
ely
impa
ired
rena
l fu
nctio
n ex
hibi
t an
incr
ease
in th
e ha
lf-liv
es o
f bot
h co
mpo
nent
s, re
quiri
ng d
osag
e re
gim
en a
djus
tmen
t (se
e DO
SAGE
AND
AD
MIN
ISTR
ATIO
N se
ctio
n). D
etec
tabl
e am
ount
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re p
rese
nt in
the
bloo
d 24
hou
rs
afte
r dru
g ad
min
istra
tion.
Dur
ing
adm
inis
tratio
n of
800
mg
sulfa
met
hoxa
zole
and
160
mg
trim
etho
prim
b.i.
d., t
he m
ean
stea
dy-s
tate
pla
sma
conc
entra
tion
of tr
imet
hopr
im w
as 1
.72
μg/
mL.
The
ste
ady-
stat
e m
ean
plas
ma
leve
ls o
f fre
e an
d to
tal
sulfa
met
hoxa
zole
wer
e 57
.4 μ
g/m
L an
d 68
.0 μ
g/m
L, re
spec
tivel
y. T
hese
ste
ady-
stat
e le
vels
wer
e ac
hiev
ed a
fter t
hree
day
s of
dru
g ad
min
istra
tion.
1 Ex
cret
ion
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
is p
rimar
ily b
y th
e ki
dney
s th
roug
h bo
th
glom
erul
ar fi
ltrat
ion
and
tubu
lar s
ecre
tion.
Urin
e co
ncen
tratio
ns o
f bot
h su
lfam
etho
xazo
le a
nd tr
imet
hopr
im a
re
cons
ider
ably
hig
her t
han
are
the
conc
entra
tions
in th
e bl
ood.
The
ave
rage
per
cent
age
of th
e do
se re
cove
red
in u
rine
from
0
to 7
2 ho
urs
afte
r a s
ingl
e or
al d
ose
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
is 8
4.5%
for t
otal
sul
fona
mid
e an
d 66
.8%
for
free
trim
etho
prim
. Thi
rty p
erce
nt o
f the
tota
l sul
fona
mid
e is
exc
rete
d as
free
sul
fam
etho
xazo
le, w
ith th
e re
mai
ning
as
N 4-a
cety
late
d m
etab
olite
.2 W
hen
adm
inis
tere
d to
geth
er a
s su
lfam
etho
xazo
le a
nd tr
imet
hopr
im, n
eith
er s
ulfa
met
hoxa
zole
no
r trim
etho
prim
affe
cts
the
urin
ary
excr
etio
n pa
ttern
of t
he o
ther
.Bo
th s
ulfa
met
hoxa
zole
and
trim
etho
prim
dis
tribu
te to
spu
tum
, vag
inal
flui
d an
d m
iddl
e ea
r flu
id; t
rimet
hopr
im a
lso
dist
ribut
es to
bro
nchi
al s
ecre
tions
, and
bot
h pa
ss th
e pl
acen
tal b
arrie
r and
are
exc
rete
d in
hum
an m
ilk.
Geria
tric
Phar
mac
okin
etic
sTh
e ph
arm
acok
inet
ics
of s
ulfa
met
hoxa
zole
800
mg
and
trim
etho
prim
160
mg
wer
e st
udie
d in
6 g
eria
tric
subj
ects
(mea
n ag
e: 7
8.6
year
s) a
nd 6
you
ng h
ealth
y su
bjec
ts (m
ean
age:
29.
3 ye
ars)
usi
ng a
non
-U.S
. app
rove
d fo
rmul
atio
n.
Phar
mac
okin
etic
val
ues
for s
ulfa
met
hoxa
zole
in g
eria
tric
subj
ects
wer
e si
mila
r to
thos
e ob
serv
ed in
you
ng a
dult
subj
ects
. Th
e m
ean
rena
l cle
aran
ce o
f trim
etho
prim
was
sig
nific
antly
low
er in
ger
iatri
c su
bjec
ts c
ompa
red
with
you
ng a
dult
subj
ects
(1
9 m
L/h/
kg v
s. 5
5 m
L/h/
kg).
How
ever
, afte
r nor
mal
izing
by
body
wei
ght,
the
appa
rent
tota
l bod
y cl
eara
nce
of
trim
etho
prim
was
on
aver
age
19%
low
er in
ger
iatri
c su
bjec
ts c
ompa
red
with
you
ng a
dult
subj
ects
.3M
icro
biol
ogy
Sulfa
met
hoxa
zole
inhi
bits
bac
teria
l syn
thes
is o
f dih
ydro
folic
aci
d by
com
petin
g w
ith p
ara-
amin
oben
zoic
aci
d (P
ABA)
. Tr
imet
hopr
im b
lock
s th
e pr
oduc
tion
of te
trahy
drof
olic
aci
d fro
m d
ihyd
rofo
lic a
cid
by b
indi
ng to
and
reve
rsib
ly in
hibi
ting
the
requ
ired
enzy
me,
dih
ydro
fola
te re
duct
ase.
Thu
s, s
ulfa
met
hoxa
zole
and
trim
etho
prim
blo
cks
two
cons
ecut
ive
step
s in
th
e bi
osyn
thes
is o
f nuc
leic
aci
ds a
nd p
rote
ins
esse
ntia
l to
man
y ba
cter
ia.
In v
itro
stud
ies
have
sho
wn
that
bac
teria
l res
ista
nce
deve
lops
mor
e sl
owly
with
bot
h su
lfam
etho
xazo
le a
nd tr
imet
hopr
im in
co
mbi
natio
n th
an w
ith e
ither
sul
fam
etho
xazo
le o
r trim
etho
prim
alo
ne.
Sulfa
met
hoxa
zole
and
trim
etho
prim
hav
e be
en s
how
n to
be
activ
e ag
ains
t mos
t stra
ins
of th
e fo
llow
ing
mic
roor
gani
sms,
bo
th in
vitr
o an
d in
clin
ical
infe
ctio
ns a
s de
scrib
ed in
the
INDI
CATI
ONS
AND
USAG
E se
ctio
n.Ae
robi
c gr
am-p
ositi
ve m
icro
orga
nism
s:
Stre
ptoc
occu
s pn
eum
onia
e Ae
robi
c gr
am-n
egat
ive
mic
roor
gani
sms:
Es
cher
ichi
a co
li (in
clud
ing
susc
eptib
le e
nter
otox
igen
ic s
train
s im
plic
ated
in tr
avel
er's
dia
rrhe
a)Kl
ebsi
ella
spe
cies
Ente
roba
cter
spe
cies
Haem
ophi
lus
influ
enza
eM
orga
nella
mor
gani
iPr
oteu
s m
irabi
lisPr
oteu
s vu
lgar
isSh
igel
la fl
exne
riSh
igel
la s
onne
iOt
her O
rgan
ism
s:
Pneu
moc
ystis
car
inii
Susc
eptib
ility
Tes
ting
Met
hods
: Di
lutio
n Te
chni
ques
: Qu
antit
ativ
e m
etho
ds a
re u
sed
to d
eter
min
e an
timic
robi
al m
inim
um in
hibi
tory
con
cent
ratio
ns (M
ICs)
. The
se M
ICs
prov
ide
estim
ates
of t
he s
usce
ptib
ility
of b
acte
ria to
ant
imic
robi
al c
ompo
unds
. The
MIC
s sh
ould
be
dete
rmin
ed u
sing
a
stan
dard
ized
proc
edur
e. S
tand
ardi
zed
proc
edur
es a
re b
ased
on
a di
lutio
n m
etho
d4 (b
roth
or a
gar)
or e
quiv
alen
t with
st
anda
rdize
d in
ocul
um c
once
ntra
tions
and
sta
ndar
dize
d co
ncen
tratio
ns o
f sul
fam
etho
xazo
le/tr
imet
hopr
im p
owde
r. Th
e M
IC v
alue
s sh
ould
be
inte
rpre
ted
acco
rdin
g to
the
follo
win
g cr
iteria
: Fo
r tes
ting
Ente
roba
cter
iace
ae:
MIC
(μg/
mL)
In
terp
reta
tion
≤ 2/
38
Susc
eptib
le (S
)≥
4/76
Re
sist
ant (
R)W
hen
test
ing
eith
er H
aem
ophi
lus
influ
enza
ea o
r Stre
ptoc
occu
s pn
eum
onia
eb:
MIC
(μg/
mL)
In
terp
reta
tionb
≤ 0.
5/9.
5 Su
scep
tible
(S)
1/19
– 2
/38
Inte
rmed
iate
(I)
≥ 4/
76
Resi
stan
t (R)
a.Th
ese
inte
rpre
tativ
e st
anda
rds
are
appl
icab
le o
nly
to b
roth
mic
rodi
lutio
n su
scep
tibili
ty te
sts
with
Hae
mop
hilu
s in
fluen
zae
usin
g Ha
emop
hilu
s Te
st M
ediu
m (H
TM).4
b.
Thes
e in
terp
reta
tive
stan
dard
s ar
e ap
plic
able
onl
y to
bro
th m
icro
dilu
tion
susc
eptib
ility
test
s us
ing
catio
n-ad
just
edM
uelle
r-Hi
nton
bro
th w
ith 2
% to
5%
lyse
d ho
rse
bloo
d.4
A re
port
of "S
usce
ptib
le" i
ndic
ates
that
the
path
ogen
is li
kely
to b
e in
hibi
ted
if th
e an
timic
robi
al c
ompo
und
in th
e bl
ood
reac
hes
the
conc
entra
tions
usu
ally
ach
ieva
ble.
A re
port
of "I
nter
med
iate
" ind
icat
es th
at th
e re
sult
shou
ld b
e co
nsid
ered
eq
uivo
cal,
and,
if th
e m
icro
orga
nism
is n
ot fu
lly s
usce
ptib
le to
alte
rnat
ive,
clin
ical
ly fe
asib
le d
rugs
, the
test
sho
uld
be
repe
ated
. Thi
s ca
tego
ry im
plie
s po
ssib
le c
linic
al a
pplic
abili
ty in
bod
y si
tes
whe
re th
e dr
ug is
phy
siol
ogic
ally
con
cent
rate
d or
in s
ituat
ions
whe
re h
igh
dosa
ge o
f dru
g ca
n be
use
d. T
his
cate
gory
als
o pr
ovid
es a
buf
fer z
one
whi
ch p
reve
nts
smal
l un
cont
rolle
d te
chni
cal f
acto
rs fr
om c
ausi
ng m
ajor
dis
crep
anci
es in
inte
rpre
tatio
n. A
repo
rt of
"Res
ista
nt" i
ndic
ates
that
the
path
ogen
is n
ot li
kely
to b
e in
hibi
ted
if th
e an
timic
robi
al c
ompo
und
in th
e bl
ood
reac
hes
the
conc
entra
tions
usu
ally
ac
hiev
able
; oth
er th
erap
y sh
ould
be
sele
cted
. Qu
ality
Con
trol:
Stan
dard
ized
susc
eptib
ility
test
pro
cedu
res
requ
ire th
e us
e of
labo
rato
ry c
ontro
l mic
roor
gani
sms
to c
ontro
l the
tech
nica
l as
pect
s of
the
labo
rato
ry p
roce
dure
s. S
tand
ard
sulfa
met
hoxa
zole
/trim
etho
prim
pow
der s
houl
d pr
ovid
e th
e fo
llow
ing
rang
e of
val
ues:
M
icro
orga
nism
MIC
(μg/
mL)
Esch
eric
hia
coli
ATCC
259
22
≤ 0.
5/9.
5Ha
emop
hilu
s in
fluen
zaec
AT
CC 4
9247
0.
03/0
.59
– 0.
25/4
.75
Stre
ptoc
occu
s pn
eum
onia
ed
ATCC
496
19
0.12
/2.4
– 1
/19
c.Th
is q
ualit
y co
ntro
l ran
ge is
app
licab
le o
nly
to H
aem
ophi
lus
influ
enza
e AT
CC 4
9247
test
ed b
y br
oth
mic
rodi
lutio
npr
oced
ure
usin
g Ha
emop
hilu
s Te
st M
ediu
m (H
TM).4
d.Th
is q
ualit
y co
ntro
l ran
ge is
app
licab
le to
test
s pe
rform
ed b
y th
e br
oth
mic
rodi
lutio
n m
etho
d on
ly u
sing
cat
ion-
adju
sted
Mue
ller-
Hint
on b
roth
with
2%
to 5
% ly
sed
hors
e bl
ood.
4 Di
ffusi
on T
echn
ique
s:
Quan
titat
ive
met
hods
that
requ
ire m
easu
rem
ent o
f zon
e di
amet
ers
also
pro
vide
repr
oduc
ible
est
imat
es o
f the
sus
cept
ibili
ty
of b
acte
ria to
ant
imic
robi
al c
ompo
unds
. One
suc
h st
anda
rdize
d pr
oced
ure5
requ
ires
the
use
of s
tand
ardi
zed
inoc
ulum
co
ncen
tratio
ns. T
his
proc
edur
e us
es p
aper
dis
ks im
preg
nate
d w
ith 1
.25/
23.7
5 μ
g of
sul
fam
etho
xazo
le/tr
imet
hopr
im to
test
th
e su
scep
tibili
ty o
f mic
roor
gani
sms
to s
ulfa
met
hoxa
zole
/trim
etho
prim
. Re
ports
from
the
labo
rato
ry p
rovi
ding
resu
lts o
f the
sta
ndar
d si
ngle
-dis
k su
scep
tibili
ty te
st w
ith a
1.2
5/23
.75
μg
of
sulfa
met
hoxa
zole
/trim
etho
prim
dis
k sh
ould
be
inte
rpre
ted
acco
rdin
g to
the
follo
win
g cr
iteria
: Fo
r tes
ting
eith
er E
nter
obac
teria
ceae
or H
aem
ophi
lus
influ
enza
ee:
Zone
Dia
met
er (m
m)
Inte
rpre
tatio
n≥
16
Susc
eptib
le (S
)11
– 1
5 In
term
edia
te (I
)≤
10
Resi
stan
t (R)
e.Th
ese
zone
dia
met
er s
tand
ards
are
app
licab
le o
nly
for d
isk
diffu
sion
test
ing
with
Hae
mop
hilu
s in
fluen
zae
and
Haem
ophi
lus
Test
Med
ium
(HTM
).5
Whe
n te
stin
g St
rept
ococ
cus
pneu
mon
iaef
:Zo
ne D
iam
eter
(mm
) In
terp
reta
tion
≥ 19
Su
scep
tible
(S)
16 –
18
Inte
rmed
iate
(I)
≤ 15
Re
sist
ant (
R)f.
Thes
e zo
ne d
iam
eter
inte
rpre
tativ
e st
anda
rds
are
appl
icab
le o
nly
to te
sts
perfo
rmed
usi
ng M
uelle
r-Hi
nton
aga
rsu
pple
men
ted
with
5%
def
ibrin
ated
she
ep b
lood
whe
n in
cuba
ted
in 5
% C
O 2.5
In
terp
reta
tion
shou
ld b
e as
sta
ted
abov
e fo
r res
ults
usi
ng d
ilutio
n te
chni
ques
. Int
erpr
etat
ion
invo
lves
cor
rela
tion
of th
e di
amet
er o
btai
ned
in th
e di
sk te
st w
ith th
e M
IC fo
r sul
fam
etho
xazo
le/tr
imet
hopr
im.
Qual
ity C
ontro
l: As
with
sta
ndar
dize
d di
lutio
n te
chni
ques
, diff
usio
n m
etho
ds re
quire
the
use
of la
bora
tory
con
trol m
icro
orga
nism
s th
at a
re
used
to c
ontro
l the
tech
nica
l asp
ects
of t
he la
bora
tory
pro
cedu
res.
For
the
diffu
sion
tech
niqu
e, th
e 1.
25/2
3.75
μg
sulfa
met
hoxa
zole
/trim
etho
prim
dis
k* s
houl
d pr
ovid
e th
e fo
llow
ing
zone
dia
met
ers
in th
ese
labo
rato
ry te
st q
ualit
y co
ntro
l st
rain
s:M
icro
orga
nism
Zone
Dia
met
er R
ange
s (m
m)
Esch
eric
hia
coli
AT
CC 2
5922
23
–29
Haem
ophi
lus
influ
enza
eg
ATCC
492
47
24–3
2 St
rept
ococ
cus
pneu
mon
iaeh
AT
CC 4
9619
20
–28
* M
uelle
r-Hi
nton
aga
r sho
uld
be c
heck
ed fo
r exc
essi
ve le
vels
of t
hym
idin
e or
thym
ine.
To
dete
rmin
e w
heth
erM
uelle
r-Hi
nton
med
ium
has
suf
ficie
ntly
low
leve
ls o
f thy
mid
ine
and
thym
ine,
an
Ente
roco
ccus
faec
alis
(ATC
C 29
212
or
ATCC
331
86) m
ay b
e te
sted
with
sul
fam
etho
xazo
le/tr
imet
hopr
im d
isks
. A zo
ne o
f inh
ibiti
on ≥
20 m
m th
at is
ess
entia
lly
free
of fi
ne c
olon
ies
indi
cate
s a
suffi
cien
tly lo
w le
vel o
f thy
mid
ine
and
thym
ine.
g.
This
qua
lity
cont
rol r
ange
is a
pplic
able
onl
y to
Hae
mop
hilu
s in
fluen
zae
ATCC
492
47 te
sted
by
a di
sk d
iffus
ion
proc
edur
eus
ing
Haem
ophi
lus
Test
Med
ium
(HTM
).5h.
This
qua
lity
cont
rol r
ange
is a
pplic
able
onl
y to
test
s pe
rform
ed b
y di
sk d
iffus
ion
usin
g M
uelle
r-Hi
nton
aga
r sup
plem
ente
dw
ith 5
% d
efib
rinat
ed s
heep
blo
od w
hen
incu
bate
d in
5%
CO 2
.5IN
DICA
TION
S AN
D US
AGE
To re
duce
the
deve
lopm
ent o
f dru
g-re
sist
ant b
acte
ria a
nd m
aint
ain
the
effe
ctiv
enes
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im
oral
sus
pens
ion
and
othe
r ant
ibac
teria
l dru
gs, s
ulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
shou
ld b
e us
ed o
nly
to
treat
or p
reve
nt in
fect
ions
that
are
pro
ven
or s
trong
ly s
uspe
cted
to b
e ca
used
by
susc
eptib
le b
acte
ria. W
hen
cultu
re a
nd
susc
eptib
ility
info
rmat
ion
are
avai
labl
e, th
ey s
houl
d be
con
side
red
in s
elec
ting
or m
odify
ing
antib
acte
rial t
hera
py. I
n th
e ab
senc
e of
suc
h da
ta, l
ocal
epi
dem
iolo
gy a
nd s
usce
ptib
ility
pat
tern
s m
ay c
ontri
bute
to e
mpi
ric s
elec
tion
of th
erap
y.Ur
inar
y Tr
act I
nfec
tions
: For
the
treat
men
t of u
rinar
y tra
ct in
fect
ions
due
to s
usce
ptib
le s
train
s of
the
follo
win
g or
gani
sms:
Es
cher
ichi
a co
li, K
lebs
iella
spe
cies
, Ent
erob
acte
r spe
cies
, Mor
gane
lla m
orga
nii,
Prot
eus
mira
bilis
and
Pro
teus
vul
garis
. It i
s re
com
men
ded
that
initi
al e
piso
des
of u
ncom
plic
ated
urin
ary
tract
infe
ctio
ns b
e tre
ated
with
a s
ingl
e ef
fect
ive
antib
acte
rial
agen
t rat
her t
han
the
com
bina
tion.
Acut
e Ot
itis
Med
ia: F
or th
e tre
atm
ent o
f acu
te o
titis
med
ia in
ped
iatri
c pa
tient
s du
e to
sus
cept
ible
stra
ins
of S
trept
ococ
cus
pneu
mon
iae
or H
aem
ophi
lus
influ
enza
e w
hen
in th
e ju
dgm
ent o
f the
phy
sici
an s
ulfa
met
hoxa
zole
and
trim
etho
prim
offe
rs
som
e ad
vant
age
over
the
use
of o
ther
ant
imic
robi
al a
gent
s. T
o da
te, t
here
are
lim
ited
data
on
the
safe
ty o
f rep
eate
d us
e of
su
lfam
etho
xazo
le a
nd tr
imet
hopr
im in
ped
iatri
c pa
tient
s un
der t
wo
year
s of
age
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
not
in
dica
ted
for p
roph
ylac
tic o
r pro
long
ed a
dmin
istra
tion
in o
titis
med
ia a
t any
age
.Ac
ute
Exac
erba
tions
of C
hron
ic B
ronc
hitis
in A
dults
: For
the
treat
men
t of a
cute
exa
cerb
atio
ns o
f chr
onic
bro
nchi
tis d
ue to
su
scep
tible
stra
ins
of S
trept
ococ
cus
pneu
mon
iae
or H
aem
ophi
lus
influ
enza
e w
hen
in th
e ju
dgm
ent o
f the
phy
sici
an
sulfa
met
hoxa
zole
and
trim
etho
prim
offe
rs s
ome
adva
ntag
e ov
er th
e us
e of
a s
ingl
e an
timic
robi
al a
gent
.Sh
igel
losi
s: F
or th
e tre
atm
ent o
f ent
eriti
s ca
used
by
susc
eptib
le s
train
s of
Shi
gella
flex
neri
and
Shig
ella
son
nei w
hen
antib
acte
rial t
hera
py is
indi
cate
d.Pn
eum
ocys
tis C
arin
ii Pn
eum
onia
: For
the
treat
men
t of d
ocum
ente
d Pn
eum
ocys
tis c
arin
ii pn
eum
onia
and
for p
roph
ylax
is
agai
nst P
neum
ocys
tis c
arin
ii pn
eum
onia
in in
divi
dual
s w
ho a
re im
mun
osup
pres
sed
and
cons
ider
ed to
be
at a
n in
crea
sed
risk
of d
evel
opin
g Pn
eum
ocys
tis c
arin
ii pn
eum
onia
.Tr
avel
ers’
Dia
rrhe
a In
Adu
lts: F
or th
e tre
atm
ent o
f tra
vele
rs’ d
iarr
hea
due
to s
usce
ptib
le s
train
s of
ent
erot
oxig
enic
E. c
oli.
CONT
RAIN
DICA
TION
SSu
lfam
etho
xazo
le a
nd tr
imet
hopr
im is
con
train
dica
ted
in p
atie
nts
with
a k
now
n hy
pers
ensi
tivity
to tr
imet
hopr
im o
r su
lfona
mid
es, i
n pa
tient
s w
ith a
his
tory
of d
rug-
indu
ced
imm
une
thro
mbo
cyto
peni
a w
ith u
se o
f trim
etho
prim
and
/or
sulfo
nam
ides
, and
in p
atie
nts
with
doc
umen
ted
meg
alob
last
ic a
nem
ia d
ue to
fola
te d
efic
ienc
y. S
ulfa
met
hoxa
zole
and
tri
met
hopr
im is
als
o co
ntra
indi
cate
d in
pre
gnan
t pat
ient
s an
d nu
rsin
g m
othe
rs, b
ecau
se s
ulfo
nam
ides
pas
s th
e pl
acen
ta
and
are
excr
eted
in th
e m
ilk a
nd m
ay c
ause
ker
nict
erus
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
con
train
dica
ted
in p
edia
tric
patie
nts
less
than
2 m
onth
s of
age
. Sul
fam
etho
xazo
le a
nd tr
imet
hopr
im is
als
o co
ntra
indi
cate
d in
pat
ient
s w
ith m
arke
d he
patic
dam
age
or w
ith s
ever
e re
nal i
nsuf
ficie
ncy
whe
n re
nal f
unct
ion
stat
us c
anno
t be
mon
itore
d.W
ARNI
NGS
FATA
LITI
ES A
SSOC
IATE
D W
ITH
THE
ADM
INIS
TRAT
ION
OF S
ULFO
NAM
IDES
, ALT
HOUG
H RA
RE, H
AVE
OCCU
RRED
DUE
TO
SEV
ERE
REAC
TION
S, IN
CLUD
ING
STEV
ENS-
JOHN
SON
SYND
ROM
E, T
OXIC
EPI
DERM
AL N
ECRO
LYSI
S, F
ULM
INAN
T HE
PATI
C NE
CROS
IS, A
GRAN
ULOC
YTOS
IS, A
PLAS
TIC
ANEM
IA A
ND O
THER
BLO
OD D
YSCR
ASIA
S.SU
LFON
AMID
ES, I
NCLU
DING
SUL
FONA
MID
E-CO
NTAI
NING
PRO
DUCT
S SU
CH A
S SU
LFAM
ETHO
XAZO
LE/T
RIM
ETHO
PRIM
, SH
OULD
BE
DISC
ONTI
NUED
AT
THE
FIRS
T AP
PEAR
ANCE
OF
SKIN
RAS
H OR
ANY
SIG
N OF
ADV
ERSE
REA
CTIO
N. In
rare
in
stan
ces,
a s
kin
rash
may
be
follo
wed
by
a m
ore
seve
re re
actio
n, s
uch
as S
teve
ns-J
ohns
on s
yndr
ome,
toxi
c ep
ider
mal
ne
crol
ysis
, hep
atic
nec
rosi
s, a
nd s
erio
us b
lood
dis
orde
rs (s
ee P
RECA
UTIO
NS).
Clin
ical
sig
ns, s
uch
as ra
sh, s
ore
thro
at,
feve
r, ar
thra
lgia
, pal
lor,
purp
ura
or ja
undi
ce m
ay b
e ea
rly in
dica
tions
of s
erio
us re
actio
ns.
Coug
h, s
hortn
ess
of b
reat
h, a
nd p
ulm
onar
y in
filtra
tes
are
hype
rsen
sitiv
ity re
actio
ns o
f the
resp
irato
ry tr
act t
hat h
ave
been
repo
rted
in a
ssoc
iatio
n w
ith s
ulfo
nam
ide
treat
men
t.Th
rom
bocy
tope
nia
Sulfa
met
hoxa
zole
/trim
etho
prim
-indu
ced
thro
mbo
cyto
peni
a m
ay b
e an
imm
une-
med
iate
d di
sord
er. S
ever
e ca
ses
of
thro
mbo
cyto
peni
a th
at a
re fa
tal o
r life
thre
aten
ing
have
bee
n re
porte
d. T
hrom
bocy
tope
nia
usua
lly re
solv
es w
ithin
a w
eek
upon
dis
cont
inua
tion
of s
ulfa
met
hoxa
zole
/trim
etho
prim
.Th
e su
lfona
mid
es s
houl
d no
t be
used
for t
he tr
eatm
ent o
f gro
up A
β-h
emol
ytic
stre
ptoc
occa
l inf
ectio
ns. I
n an
est
ablis
hed
infe
ctio
n, th
ey w
ill n
ot e
radi
cate
the
stre
ptoc
occu
s an
d, th
eref
ore,
will
not
pre
vent
seq
uela
e su
ch a
s rh
eum
atic
feve
r.Cl
ostri
dium
diff
icile
ass
ocia
ted
diar
rhea
(CDA
D) h
as b
een
repo
rted
with
use
of n
early
all
antib
acte
rial a
gent
s, in
clud
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
, and
may
rang
e in
sev
erity
from
mild
dia
rrhe
a to
fata
l col
itis.
Tre
atm
ent w
ith
antib
acte
rial a
gent
s al
ters
the
norm
al fl
ora
of th
e co
lon
lead
ing
to o
verg
row
th o
f C. d
iffic
ile.
C. d
iffic
ile p
rodu
ces
toxi
ns A
and
B w
hich
con
tribu
te to
the
deve
lopm
ent o
f CDA
D. H
yper
toxi
n pr
oduc
ing
stra
ins
of C
. di
ffici
le c
ause
incr
ease
d m
orbi
dity
and
mor
talit
y, a
s th
ese
infe
ctio
ns c
an b
e re
fract
ory
to a
ntim
icro
bial
ther
apy
and
may
re
quire
col
ecto
my.
CDA
D m
ust b
e co
nsid
ered
in a
ll pa
tient
s w
ho p
rese
nt w
ith d
iarr
hea
follo
win
g an
tibio
tic u
se. C
aref
ul
med
ical
his
tory
is n
eces
sary
sin
ce C
DAD
has
been
repo
rted
to o
ccur
ove
r tw
o m
onth
s af
ter t
he a
dmin
istra
tion
of
antib
acte
rial a
gent
s.If
CDAD
is s
uspe
cted
or c
onfir
med
, ong
oing
ant
ibio
tic u
se n
ot d
irect
ed a
gain
st C
. diff
icile
may
nee
d to
be
disc
ontin
ued.
Ap
prop
riate
flui
d an
d el
ectro
lyte
man
agem
ent,
prot
ein
supp
lem
enta
tion,
ant
ibio
tic tr
eatm
ent o
f C. d
iffic
ile, a
nd s
urgi
cal
eval
uatio
n sh
ould
be
inst
itute
d as
clin
ical
ly in
dica
ted.
PREC
AUTI
ONS
Gene
ral
Pres
crib
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
ora
l sus
pens
ion
in th
e ab
senc
e of
a p
rove
n or
stro
ngly
sus
pect
ed b
acte
rial
infe
ctio
n or
a p
roph
ylac
tic in
dica
tion
is u
nlik
ely
to p
rovi
de b
enef
it to
the
patie
nt a
nd in
crea
ses
the
risk
of th
e de
velo
pmen
t of
dru
g-re
sist
ant b
acte
ria.
Sulfa
met
hoxa
zole
and
trim
etho
prim
sho
uld
be g
iven
with
cau
tion
to p
atie
nts
with
impa
ired
rena
l or h
epat
ic fu
nctio
n, to
th
ose
with
pos
sibl
e fo
late
def
icie
ncy
(e.g
., th
e el
derly
, chr
onic
alc
ohol
ics,
pat
ient
s re
ceiv
ing
antic
onvu
lsan
t the
rapy
, pa
tient
s w
ith m
alab
sorp
tion
synd
rom
e, a
nd p
atie
nts
in m
alnu
tritio
n st
ates
) and
to th
ose
with
sev
ere
alle
rgie
s or
bro
nchi
al
asth
ma.
In g
luco
se-6
-pho
spha
te d
ehyd
roge
nase
def
icie
nt in
divi
dual
s, h
emol
ysis
may
occ
ur. T
his
reac
tion
is fr
eque
ntly
do
se-r
elat
ed (s
ee C
LINI
CAL
PHAR
MAC
OLOG
Y an
d DO
SAGE
AND
ADM
INIS
TRAT
ION)
.Ca
ses
of h
ypog
lyce
mia
in n
on-d
iabe
tic p
atie
nts
treat
ed w
ith s
ulfa
met
hoxa
zole
and
trim
etho
prim
are
see
n ra
rely
, usu
ally
oc
curr
ing
afte
r a fe
w d
ays
of th
erap
y. P
atie
nts
with
rena
l dys
func
tion,
live
r dis
ease
, mal
nutri
tion
or th
ose
rece
ivin
g hi
gh
dose
s of
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im a
re p
artic
ular
ly a
t ris
k.
Hem
atol
ogic
al c
hang
es in
dica
tive
of fo
lic a
cid
defic
ienc
y m
ay o
ccur
in e
lder
ly p
atie
nts
or in
pat
ient
s w
ith p
reex
istin
g fo
lic
acid
def
icie
ncy
or k
idne
y fa
ilure
. The
se e
ffect
s ar
e re
vers
ible
by
folin
ic a
cid
ther
apy.
Tr
imet
hopr
im h
as b
een
note
d to
impa
ir ph
enyl
alan
ine
met
abol
ism
, but
this
is o
f no
sign
ifica
nce
in p
heny
lket
onur
ic p
atie
nts
on a
ppro
pria
te d
ieta
ry re
stric
tion.
As
with
all
drug
s co
ntai
ning
sul
fona
mid
es, c
autio
n is
adv
isab
le in
pat
ient
s w
ith p
orph
yria
or t
hyro
id d
ysfu
nctio
n.Us
e in
the
Trea
tmen
t of a
nd P
roph
ylax
is fo
r Pne
umoc
ystis
Car
inii
Pneu
mon
ia in
Pat
ient
s w
ith A
cqui
red
Imm
unod
efic
ienc
y Sy
ndro
me
(AID
S): A
IDS
patie
nts
may
not
tole
rate
or r
espo
nd to
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im in
th
e sa
me
man
ner a
s no
n-AI
DS p
atie
nts.
The
inci
denc
e of
sid
e ef
fect
s, p
artic
ular
ly ra
sh, f
ever
, leu
kope
nia
and
elev
ated
am
inot
rans
fera
se (t
rans
amin
ase)
val
ues,
with
sul
fam
etho
xazo
le a
nd tr
imet
hopr
im th
erap
y in
AID
S pa
tient
s w
ho a
re b
eing
tre
ated
for P
neum
ocys
tis c
arin
ii pn
eum
onia
has
bee
n re
porte
d to
be
grea
tly in
crea
sed
com
pare
d w
ith th
e in
cide
nce
norm
ally
ass
ocia
ted
with
the
use
of s
ulfa
met
hoxa
zole
and
trim
etho
prim
in n
on-A
IDS
patie
nts.
The
inci
denc
e of
hy
perk
alem
ia a
ppea
rs to
be
incr
ease
d in
AID
S pa
tient
s re
ceiv
ing
sulfa
met
hoxa
zole
and
trim
etho
prim
. Adv
erse
effe
cts
are
gene
rally
less
sev
ere
in p
atie
nts
rece
ivin
g su
lfam
etho
xazo
le a
nd tr
imet
hopr
im fo
r pro
phyl
axis
. A h
isto
ry o
f mild
into
lera
nce
to s
ulfa
met
hoxa
zole
and
trim
etho
prim
in A
IDS
patie
nts
does
not
app
ear t
o pr
edic
t int
oler
ance
of s
ubse
quen
t sec
onda
ry
prop
hyla
xis.
6 Ho
wev
er, i
f a p
atie
nt d
evel
ops
skin
rash
or a
ny s
ign
of a
dver
se re
actio
n, th
erap
y w
ith s
ulfa
met
hoxa
zole
and
tri
met
hopr
im s
houl
d be
reev
alua
ted
(see
WAR
NING
S).
High
dos
age
of tr
imet
hopr
im, a
s us
ed in
pat
ient
s w
ith P
neum
ocys
tis c
arin
ii pn
eum
onia
, ind
uces
a p
rogr
essi
ve b
ut
reve
rsib
le in
crea
se o
f ser
um p
otas
sium
con
cent
ratio
ns in
a s
ubst
antia
l num
ber o
f pat
ient
s. E
ven
treat
men
t with
re
com
men
ded
dose
s m
ay c
ause
hyp
erka
lem
ia w
hen
trim
etho
prim
is a
dmin
iste
red
to p
atie
nts
with
und
erly
ing
diso
rder
s of
po
tass
ium
met
abol
ism
, with
rena
l ins
uffic
ienc
y, o
r if d
rugs
kno
wn
to in
duce
hyp
erka
lem
ia a
re g
iven
con
com
itant
ly. C
lose
m
onito
ring
of s
erum
pot
assi
um is
war
rant
ed in
thes
e pa
tient
s.
Durin
g tre
atm
ent,
adeq
uate
flui
d in
take
and
urin
ary
outp
ut s
houl
d be
ens
ured
to p
reve
nt c
ryst
allu
ria. P
atie
nts
who
are
"s
low
ace
tyla
tors
" may
be
mor
e pr
one
to id
iosy
ncra
tic re
actio
ns to
sul
fona
mid
es.
Reference ID: 3057440