Butoconazole and miconazole in treating vaginal candidiasis


Bradbeer, C.S.; Mayhew, S.R.; Barlow, D.

Genitourinary Medicine 61(4): 270-272

1985


In a single blind trial, a three day course of butoconazole nitrate cream was compared with a seven day course of miconazole nitrate cream, both applied intravaginally, in treating vaginal candidiasis. They were equally effective. The cure rate for patients treated with butoconazole was 82.8% at the first follow up (a mean of 18.4 days from the beginning of the treatment) and 76.7% at second follow up (a mean of 40.4 days). Cure rates for patients treated with miconazole were 84.4% and 75.8% respectively. The differences between these cure rates were not significant.

Genitourin
Med
1985;61:270-2
Butoconazole
and
miconazole
in
treating
vaginal
candidiasis
C
S
BRADBEER,*
S
R
MAYHEW,t
AND
D
BARLOW*
From
the
*Department
of
Genitourinary
Medicine,
St
Thomas's
Hospital,
London,
and
the
-I-Eaton
Socon
Health
Centre,
Huntingdon
SUMMARY
In
a
single
blind
trial,
a
three
day
course
of
butoconazole
nitrate
cream
was
compared
with
a
seven
day
course
of
miconazole
nitrate
cream,
both
applied
intravaginally,
in
treating
vaginal
candidiasis.
They
were
equally
effective.
The
cure
rate
for
patients
treated
with
butoconazole
was
82.8%
at
the
first
follow
up
(a
mean
of
18.4
days
from
the
beginning
of
the
treatment)
and
76.7%
at
second
follow
up
(a
mean
of
40.4
days).
Cure
rates
for
patients
treated
with
miconazole
were
84.4%
and
75.8%
respectively.
The
differences
between
these
cure
rates
were
not
significant.
Introduction
Butoconazole
is
a
new
imidazole
antifungal
agent,
which
is
highly
active
in
vitro'
and
in
vivo
2
.
Its
use
in
treating
vaginal
candidiasis
in
laboratory
animals
has
suggested
that
it
is
more
active
than
miconazole
or
clotrimazole,
and
that
butoconazole
might
therefore
be
used
in
lower
doses
than
those
required
for
the
other
two
drugs,
3
with
improvement
in
patient
compliance.
45
Patients,
materials,
and
methods
MATERIALS
Both
drugs
were
made
up
as
intravaginal
creams
containing
2%
of
the
active
agent.
The
dose
of
butoconazole
prescribed
was
5
g
nightly
for
three
nights.
The
dose
of
miconazole
was
10
g
nightly
for
seven
nights.
The
drugs
were
packed
in
identical
boxes
and
coded,
using
a
random
number
table,
by
Syntex
Pharmaceuticals
(Maidenhead,
Berkshire,
England).
The
investigators
were
unaware
of
which
product
was
being
prescribed.
SELECTION
OF
PATIENTS
Patients
from
the
department
of
genitourinary
medicine
at
St
Thomas's
Hospital
and
the
Eaton
Socon
Health
Centre,
Huntingdon,
were
enrolled
in
the
trial
if
they
had
symptoms
of
vulvovaginal
candidiasis
and
a
positive
culture
for
yeasts
with
or
Address
for
reprints:
Dr
C
S
Bradbeer,
Department
of
Genitourinary
Medicine,
St
Thomas's
Hospital,
London
SE1
7EH
Accepted
for
publication
29
November
1984
without
initial
diagnosis
by
direct
microscopy.
They
were
required
to
give
informed
consent
and
to
be
over
18
years
of
age.
Patients
were
excluded
from
entry
if
they:
(1)
had
any
other
sexually
transmitted
disease
or
gynaeco-
logical
abnormality
requiring
treatment;
(2)
had
a
disease
known
to
predispose
to
candidiasis
such
as
diabetes
mellitus,
or
were
receiving
antibiotics
or
corticosteriods;
(3)
were
pregnant;
(4)
had
used
anti-
fungal
medication
in
the
week
before
entry;
or
(5)
were
expected
to
menstruate
within
seven
days
of
the
start
of
treatment.
Their
sexual
partners
were
not
seen
or
treated
and
no
restrictions
were
placed
on
sexual
intercourse.
Approval
for
this
trial
was
obtained
from
the
Ethical
Committee
at
St
Thomas's
Hospital.
INVESTIGATIONS
At
the
first
visit
each
patient
was
asked
the
duration
of
her
symptoms.
Discharge,
itching,
and
burning
were
each
graded
on
a
four
point
scale
(none
=
0,
mild
=
1,
moderate
=
2,
and
severe
=
3).
These
scores
were
added
to
give
an
arbitrary
index
of
severity.
A
vaginal
examination
was
performed
to
exclude
other
pelvic
disease
or
abnormality,
samples
of
vaginal
discharge
were
Gram
stained
for
immediate
microscopical
examination,
and
plates
were
set
up
for
yeast
culture.
Each
patient
was
instructed
in
the
application
of
vaginal
cream
and
given
a
14
day
diary
card
to
record
daily
symptom
changes
and
any
side
effects
under
the
headings
of
(a)
leakage
of
the
preparation,
(b)
staining,
(c)
odour,
and
(d)
others.
270
Butoconazole
and
miconazole
in
treating
vaginal
candidiasis
271
Patients
were
asked
to
return
at
14
and
35
days
to
be
seen
by
CSB
at
St
Thomas's
Hospital
and
SRM
at
Eaton
Socon
Health
Centre.
At
these
visits
further
Gram
stained
smears
and
cultures
were
obtained.
PATIENTS
We
studied
69
patients,
39
from
the
Eaton
Socon
Health
Centre
and
30
from
St
Thomas's
Hospital.
One
patient
was
withdrawn
after
yielding
a
negative
culture,
having
already
received
butoconazole
with
no
side
effects,
and
is
excluded
from
all
analyses.
Of
the
remaining
68
patients,
35
received
miconazole
nitrate
cream
and
33
butoconazole
nitrate
cream.
The
two
groups
of
patients
were
well
matched
(table
I)
for
age,
use
of
oral
contraceptives,
duration
of
symptoms
before
treatment,
and
the
index
of
their
severity.
A
higher
proportion
of
patients
treated
with
butoconazole,
however,
had
had
previous
episodes
of
candidiasis
(x
2
=
1.27,
not
significant).
Two
patients,
both
receiving
butoconazole,
lost
their
diary
cards.
Five
patients,
three
receiving
butoconazole
and
two
miconazole,
failed
to
use
the
products
exactly
as
instructed.
All
were
cured
and
are
included
in
the
analysis
of
results.
The
mean
number
of
days
to
the
resolution
of
itching
(table
II)
was
4.7
in
the
patients
receiving
miconazole
and
4.8
in
those
receiving
butoconazole.
The
mean
number
of
days
to
the
resolution
of
burning
was
3.7
in
both
groups.
The
patients'
assess-
ment
of
the
resolution
of
discharge
was
difficult
to
evaluate:
many
patients
-considered
that
they
always
had
a
discharge,
others
found
discharge
difficult
to
distinguish
from
leakage
of
cream.
TABLE
II
Resolution
of
symptoms
in
61
patients
with
candidiasis
Mean
No
of
days
to
resolution
in
patients
receiving:
TABLE
I
Characteristics
of
68
patients
with
candidiasis
Symptoms
Miconazole
Butoconazole
Patients
receiving
miconazole
(n
=
35)
Patients
receiving
butoconazole
(n
=
33)
Mean
age
(years)
29.9
29.1
No
(%)
using
oral
contraceptives
16
(45.7)
16
(48.5)
Mean
duration
of
attack
before
treatment
(days)
14.5
12.1
No
(%)
with
history
of
candidiasis
21
(60)
26
(78.8)
Mean
index*
of
severity
of
symptoms
4.8
5.0
*Sum
of
grades
of
discharge,
itching,
and
burning
on
four
point
scale
(0
=
none,
1=
mild,
2=
moderate,
3
=
severe).
Results
Sixty
one
patients
attended
for
the
first
follow
up
visit
after
a
mean
of
17.1
(range
7-28)
days,
and
51
attended
for
a
second
follow
up
visit
after
a
mean
of
40.4
(range
22-105)
days.
Those
with
positive
cultures
at
the
first
follow
up
were
not
asked
to
return
for
the
second.
Itching
4.7
(n=30)
4.8
(n
=
25)
Burning
3.7
(n=25)
3.7
(n=20)
The
microbiological
cure
rates
for
both
products
did
not
differ
appreciably
at
either
follow
up
visit,
and
over
75%
of
patients
were
free
from
infection
at
the
second
visit
(table
III).
No
serious
side
effects
were
experienced,
(table
IV)
but
both
creams
led
some
patients
to
complain
of
stinging
on
application,
and
one
patient
found
this
severe
enough
to
withdraw
from
the
trial.
Six
patients
receiving
butoconazole
compared
with
three
receiving
miconazole
complained
of
odour,
but
this
difference
was
not
significant.
The
complaint
of
odour
was
not
associated
with
anaerobic
vaginosis
in
either
group.
More
patients
receiving
miconazole
complained
of
the
preparation
leaking
(x
=
6.44;
0•025>p>0
01).
Discussion
The
symptomatic
and
mycological
cure
rates
achieved
with
the
two
preparations
did
not
differ
TABLE
III
Microbiological
cure
rate
in
63
patients
with
candidiasis
Mean
(range)
days
after
No
of
Treatment
Follow
up
visit
start
of
treatment
patients
attending
Positive
cultures
Cumulative
No
(%)
cured
Miconazole
(n
=
33)
1
15.9
(11-28)
32
5
27
(84.4)
2
40.9
(25-105)
27
3
25*
(75.8)
Butoconazole
(n
=
30)
1
18.4
(7-27)
29
5
24
(82.8)
2
40.0
(22-99)
24
2
23*
(76.7)
*Including
one
patient
whose
only
follow
up
was
later
than
28
days
after
start
of
treatment.
272
C
S
Bradbeer,
S
R
Mayhew,
and
D
Barlow
TABLE
IV
Incidence
of
side
effects
of
miconazole
and
butoconazole
in
62
patients
with
candidiasis
No
(%)
reporting
side
effects
receiving:
Side
effect
Miconazole
(n
=
33)
Butoconazole
(n
=
29)
Leakage
22
(66.7)
(31)
Staining
6
(18.2)
8
(27.6)
Odour
3
(9.1)
6
(20.7)
Stinging
6
(18.2)
6(20.7)
appreciably
and
our
results
are
comparable
with
those
achieved
using
other
imidazole
derivatives.
6
7
The
treatment
groups
were
well
matched
except
for
history
of
candidiasis,
which
was
more
common
in
those
receiving
butoconazole.
If
the
activity
of
both
drugs
were
equivalent,
increased
relapses
might
have
been
expected,
giving
a
lower
cure
rate
for
butoconazole;
but
this
was
not
seen.
Nine
patients
(five
receiving
butoconazole
and
four
miconazole)
received
antibiotic
treatment
during
follow-up,
and
one
of
them
(receiving
miconazole)
subsequently
relapsed.
The
incidence
of
side
effects
with
both
drugs
was
relatively
high,
which
may
have
been
a
result
of
the
direct
and
specific
questions
answered
at
the
time
of
application.
As
miconazole
was
prescribed
in
a
larger
volume
and
for
a
longer
period,
it
is
not
surprising
that
more
patients
receiving
this
preparation
complained
of
leakage.
Stinging
or
irritation
has
been
reported
with
other
imidazole
drugs,
but
our
complaint
rate
was
higher
than
usually
seen.
The
advantage
of
cream
preparations,
such
as
miconazole
or
butoconazole,
is
that
they
can
be
used
to
treat
both
vulval
and
vaginal
candidiasis.
This,
coupled
with
the
low
dose
and
short
treatment
period
necessary
for
cure
with
butoconazole,
makes
this
drug
ideal
for
patients
who
comply
poorly
with
treat-
ment.
We
thank
Drs
Williams
and
Newby
of
Eaton
Socon
Health
Centre
for
permission
to
study
patients
under
their
care;
the
Department
of
Microbiology,
St
Thomas's
Hospital,
for
mycological
studies;
and
Syntex
Pharmaceuticals
for
provision
of
the
antifungal
agents.
References
1.
Beggs
WH.
The
effect
of
antifungal
imidazoles
on
resting
cells
of
Candida
parapsilosis.
International
Research
Communications
System
Journal
of
Medical
Sciences
1983;
11:677.
2.
Jacobson
JB,
Hajman
AJ,
Gandrup
PB,
Wiese
J,
Forsstrom
S.
First
clinical
experience
with
a
new
vaginal
antifungal
agent,
butoconazole
nitrate:
a
double-blind
comparison
to
miconazole
nitrate.
Xth
World
Congress
of
Gynecology
and
Obstetrics,
October
17-22
1982.
San
Francisco,
USA.
New
York:
Academy
Professional
Information
Services,
1982:368.
3.
Walker
KAM,
Braemer
AC,
Hitt
S,
Jones
RE,
Matthews
TR.
144-(4-Chloropheny1)-2-(2,6-dichlorophenylthio)-n-buty11-1.
H-imidazole
nitrate,
a
new
potent
antifungal
agent.
J
Med
Chem
1978;
21:840-3.
4.
Hull
FM.
The
management
of
vaginal
discharge.
Prescriber's
Journal
1982;
22:91-6.
5.
Oriel
JD.
Non-specific
urethritis
and
vaginal
discharge.
Prescriber's
Journal
1976;
16
:
108-16.
6.
Eliot
BW,
Howat
RCL,
Mack
AE.
A
comparison
between
the
effects
of
nystatin,
clotrimazole
and
miconazole
on
vaginal
candidiasis.
Br
J
Obstet
Gynaecol
1979;
86:
572-7.
7.
Gabriel
G,
Thin
RNT.
Clotrimazole
and
econazole
in
the
treatment
of
vaginal
candidosis.
British
Journal
of
Venereal
Diseases
1983;
59:56-8.