Drugs 2009; 69 (3): 339-359

ADIS DRUG EVALUATION 0012-6667/09/0003-0339/$55.55/0

2009 Adis Data Information BV. All rights reserved.

Sertaconazole
A Review of Its Use in the Management of Superficial
Mycoses in Dermatology and Gynaecology
Jamie D. Croxtall and Greg L. Plosker
Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health,
Conshohocken, Pennsylvania, USA

Various sections of the manuscript reviewed by:

M. Bassetti, Infectious Diseases Division, San Martino University and University of Genoa, Genoa, Italy;
A.J. Carrillo-Munoz, Department of Microbiology, Asesoria Cientifica y de la Investigacion Aplicada Hospital
Vall dHebron, Barcelona, Spain; J. das Neves, Department of Pharmaceutical Technology, Faculty of Pharmacy,
University of Porto, Porto, Portugal; H.C. Korting, Klinik und Poliklinik fur Dermatologie und Allergologie,
Klinikum der Universitat Munchen, Munich, Germany; M.A. Pfaller, Department of Pathology, College of
Medicine, University of Iowa, Iowa City, Iowa, USA; S. Veraldi, Institute of Dermatological Sciences, University of
Milan, I.R.C.C.S. Foundation, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.

Data Selection
Sources: Medical literature published in any language since 1980 on sertaconazole, identified using MEDLINE and EMBASE,
supplemented by AdisBase (a proprietary database of Wolters Kluwer Health j Adis). Additional references were identified from the
reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the
company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were sertaconazole and mycoses. Searches were last updated
16 February 2009.
Selection: Studies in patients with superficial mycoses who received sertaconazole. Inclusion of studies was based mainly on the
methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant
pharmacodynamic and pharmacokinetic data are also included.
Index terms: Sertaconazole, mycoses, dermatology, gynaecology, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Contents
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
2. Pharmacodynamic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
2.1 Mechanism of Action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
2.2 Fungistatic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
2.3 Fungicidal Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
2.4 Other Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
2.5 Resistance Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
3. Pharmacokinetic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
4. Therapeutic Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
4.1 Dermatological Mycoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
4.1.1 Clinical Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
4.1.2 Mycological Efficacy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
4.1.3 Recurrence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
4.2 Gynaecological Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
4.2.1 Clinical Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
340 Croxtall & Plosker

4.2.2 Mycological Efficacy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351

4.2.3 Recurrence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
5. Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
5.1 Dermatological Mycoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
5.2 Gynaecological Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
6. Dosage and Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
7. Place of Sertaconazole in the Management of Superficial Mycoses in Dermatology
and Gynaecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353

Summary
Abstract Sertaconazole (Dermofix, Ertaczo, Ginedermofix, Monazol, Mykosert or
Zalain), an imidazole antifungal agent, inhibits the synthesis of ergosterol, an
essential cell wall component of fungi. It is indicated in the EU for the treatment
of superficial skin mycoses such as dermatophytosis (including tinea corporis,
tinea cruris, tinea manus, tinea barbae and tinea pedis), cutaneous candidiasis,
pityriasis versicolor and seborrhoeic dermatitis of the scalp, and in the US for
tinea pedis only.
Sertaconazole has broad-spectrum antifungal activity against dermatophytes
of the Trichophyton, Epidermophyton and Microsporum genera, and yeasts of the
genera Candida and Cryptococcus; additionally, it is effective against opportu-
nistic filamentous fungi and Gram-positive bacteria. Moreover, the antifungal
activity of sertaconazole is maintained in clinical isolates of dermatophytes that
show reduced susceptibility to other azoles. While the drug has good dermal
penetration, this is not associated with systemic absorption. In clinical trials in
patients with superficial mycoses, 2% sertaconazole cream applied twice daily was
effective in the eradication of a range of dermatophytoses, and a significantly
greater proportion of patients were cured compared with those receiving 2%
miconazole cream twice-daily treatment. In patients with vulvovaginal candi-
diasis, sertaconazole as a single-dose ovule or tablet was effective in the eradica-
tion of Candida spp., and achieved both a more rapid and a higher cure rate
compared with a triple dose of econazole. Both as a topical cream and suppository
preparation, sertaconazole was generally well tolerated. Sertaconazole is a well
established antifungal agent, which is now available in a variety of formulations,
and remains a useful treatment option particularly in patients with fungal infec-
tions resistant to other azoles.
Pharmacological Like other azoles, sertaconazole inhibits the synthesis of ergosterol, an essential
Properties component of fungal cell walls, resulting in disruption of mycelial growth and
replication. However, at higher concentrations, sertaconazole binds directly to
nonsterol lipids in the fungal cell wall, which leads to increased permeability and
subsequent lysis of the mycelium. Thus, depending on the concentration, serta-
conazole may exhibit both fungistatic and fungicidal activities.
Sertaconazole shows good in vitro fungistatic activity against a broad range of
dermatophytes of the Trichophyton, Epidermophyton and Microsporum genera,
and yeasts of the genera Candida and Cryptococcus. The geometric minimum
inhibitory concentration (MIC) of sertaconazole ranged from 0.06 to 1 mg/mL
against a variety of dermatophyte isolates (n = 456), which included 114 isolates
with reduced susceptibility to fluconazole (MICs 16 mg/mL). Similarly, against a
variety of Candida spp., MIC values at which 90% of cultures were inhibited
(MIC90) for sertaconazole were 0.14 mg/mL compared with MIC90 of 0.1 to
>100 mg/mL for fluconazole. Furthermore, fungicidal activity of sertaconazole

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
Sertaconazole: A Review 341

was apparent against a variety of Candida spp., with minimum fungicidal con-
centration values of 0.564 mg/mL.
Additionally, sertaconazole showed antibacterial activity with a geometric
MIC of 0.88 mg/mL against 21 isolates of Gram-positive bacteria. When applied
topically in experimental models of inflammation, sertaconazole showed some
evidence of anti-inflammatory action. Only 4% of 250 clinical isolates of derma-
tophytes and Scopulariopsis brevicaulis from Spanish hospitals showed resistance
to sertaconazole, and continuous culture of Candida spp. in sertaconazole-
containing media failed to induce resistance.
Following application of sertaconazole as a topical cream or vaginal supposi-
tory, plasma levels of the drug remained undetectable in healthy volunteers.
Therapeutic Efficacy In randomized, double-blind, multicentre trials of 36 weeks duration
(n = 127383), a significantly greater number of patients with tinea of the glabrous
skin and tinea pedis receiving topical 2% sertaconazole cream once or twice daily
achieved a successful mycological cure compared with recipients of a placebo
cream. Moreover, the clinical cure rate and the mycological cure rate of 2% ser-
taconazole cream twice daily was significantly higher than that of 2% miconazole
cream twice daily in patients with a range of cutaneous mycoses (n = 631) in a
randomized, double-blind, multicentre, phase III, comparator trial of 35 days
duration. Furthermore, a greater proportion of patients receiving sertaconazole
achieved the category of clinically cured at a significantly earlier timepoint than
recipients of miconazole. An open-label, noninferiority trial of 28 days duration
in 313 patients with tinea corporis, tinea pedis or a corresponding candidiasis
showed that sertaconazole as a 2% solution was as effective as treatment with a
2% cream preparation.
Sertaconazole as a single-dose 300 mg vaginal ovule or 500 mg tablet was suc-
cessful in the eradication of Candida spp. in 65100% of patients with vaginal
candidiasis in trials that evaluated clinical and mycological cure rates up to 1 year
after the last treatment application (n = 37327). Furthermore, the clinical cure
rate and the mycological cure rate of single-dose sertaconazole 500 mg tablet was
significantly greater than that of triple-dose econazole 150 mg in the eradication
of Candida albicans and also achieved a more rapid response rate in patients with
vaginal candidiasis (n = 37).
Tolerability Sertaconazole was generally well tolerated in patients with dermatological and
gynaecological mycoses. Adverse events associated with topical application
of sertaconazole cream were mostly cutaneous-related and included contact
dermatitis, dry or burning skin, application-site reaction, eczema, itch and skin
tenderness. However, the frequency of adverse events did not differ from that of
the placebo vehicle treatment arm. Furthermore, sertaconazole showed no evi-
dence of a sensitizing action in causing contact dermatitis in healthy volunteers.
Sertaconazole administered as a vaginal suppository was generally associated
with an absence of adverse events and, where reported, included only local irri-
tation after insertion.

1. Introduction only widespread, but underlie many common

causes of diseases of the skin and mucosal
Superficial fungal infections of dermatophy- membranes.[1-5] For example, up to 20% of the
toses, candidiasis and pityriasis versicolor are not population of the US may be affected by a

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
342
dermatophyte infection at any one time, with
tinea pedis the most common infection, occurring
in up to 70% of adults.[3] Moreover, nearly 75%
of women are affected by at least one vulvo-
vaginal infection of Candida spp. during their
lifetime and, as a consequence, this remains one
of the most common reasons for a gynaecological
consultation.[6,7] Additionally, Malassezia furfur
is widespread in tropical areas, and is responsible
for between 30% and 40% of the population
affected by pityriasis versicolor, which if left un-
treated progresses to a chronic invasive disease.[4]
Furthermore, dermatological infections are sig-
nificantly more prevalent in the elderly, where
tinea pedis, onychomycosis, candidiasis and
seborrhoeic dermatitis are particularly common as
a result of impaired host defence mechanisms.[8]
Increased frequencies of fungal infections have
been associated with high temperature and hu-
midity, and these infections are especially pre-
valent when combined with poor nutrition,
overcrowding and poverty.[9] Until recently, most
superficial fungal infections were considered to
be mild in intensity, respond well to treatment
and be rarely life threatening.[5,10] However, over
the past two decades, a growing global im-
munocompromised population has changed
perspectives on the significance of infectious dis-
eases.[5,11,12] As a result of an HIV pandemic and
an increasingly widespread use of immuno-
suppressive agents for the treatment of cancer,
transplantation and autoimmune diseases, there
has been (i) an increase in the incidence and se-
verity of fungal infections; (ii) a shift in Candida
spp. associated with candidiasis to species with
reduced susceptibility to antifungal treatment;
and (iii) an increased incidence of opportunistic
co-infections of filamentous fungi (e.g. Aspergil-
lus spp.) and Gram-positive bacteria.[2,5,7,11-15]
As a consequence, where fungal infections
may have previously been considered to affect
morbidity only, they may now be increasingly
associated with sepsis, organ failure and death
in this immunocompromised population.[5,11,15]
Indeed, mortality rates may be as high as
75100% in at-risk patient groups with systemic
infections, which clearly presents major health-
care challenges.[5]
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
However, the development of new broad-
spectrum antifungal agents has presented new
treatment options for the management of the
growing pathogenicity of superficial cutaneous
mycoses. This article focuses on the pharmaco-
logical profile and clinical efficacy of sertacona-
zole (Dermofix, Ertaczo, Ginedermofix,
Monazol, Mykosert or Zalain) as a cream or
suppository preparation in the treatment of der-
matological and gynaecological mycoses.[16-24]
2. Pharmacodynamic Properties
The pharmacodynamic properties of sertaco-
nazole have been evaluated in a wide range of
fully published in vitro studies against dermato-
phytes,[25-31] yeasts[25-27,29,32-36] and opportunistic
infections of filamentous fungi[25,26,29,31] and
Gram-positive bacteria.[25] In addition, the
anti-inflammatory and antipruritic properties
of sertaconazole have been evaluated in both
in vitro and animal studies that are also fully
published.[37,38]
The culture procedure and the evaluation
methods used in the determination of the mini-
mum inhibitory concentration (MIC) and the
minimum fungicidal concentration (MFC) of any
antifungal agent have a direct bearing on the
variation in apparent susceptibilities of the fungal
strains under investigation.[25] Current guidelines
for antifungal susceptibility testing from the
Clinical and Laboratory Standards Institute
(CLSI), formerly the National Committee for
Clinical and Laboratory Standards Institute
(NCCLS), provide a standardized culture meth-
odology for yeasts (M27-A3) and filamentous
fungi (M38-A2).[39,40] However, many of the
in vitro studies reported in this section were pub-
lished prior to the inclusion of a procedure for
susceptibility testing of dermatophytes, which
was only recently adopted.[41]
With this in mind, the fungistatic activity stu-
dies of sertaconazole against yeasts mostly used
methodology from earlier versions of CLSI
(NCCLS) guidelines M27-A,[25-27,29,32-36] and
susceptibility testing of sertaconazole against
dermatophytes used a variety of in vitro culture
methods.[25-31] Furthermore, across all studies,
Drugs 2009; 69 (3)
Sertaconazole: A Review
N of 14-a-methylated sterols, and this leads to a
CI
N which disrupts mycelial hyphae formation, cell
HNO3
*
S However, at higher concentrations, sertaco-
CI
O CI
Fig. 1. Chemical structure of sertaconazole nitrate.
MIC values were variously reported as arithmetic
or geometric means, the lowest concentration at
which growth was 50%, 90%, 95% or 100% of
control (MIC50, MIC90, MIC95 or MIC100, re-
spectively) or as a range over which growth
inhibition was observed, and these assessments
were made at a variety of timepoints (114 days,
where defined).[25-30,32-36] Similarly, MFC values
were variously defined as the minimum con-
centration of the antifungal agent to elicit a 90%
or total inhibition of cell growth of an inoculum
taken from yeast cultures in exponential growth
phase at reading times of 1, 24 and 48 hours
(where defined).[25,26,29,33,35]
2.1 Mechanism of Action
Sertaconazole has both fungistatic and fungi-
cidal activity depending on the concentration of
the drug and the specific organisms involved in
the infection.[33,34,42-44] These activities are
brought about through selective inhibition of er-
gosterol biosynthesis and direct binding to non-
sterol lipids in fungal cell membranes.[33,34,42-44]
Ergosterol is an essential component of fungal
cell membranes and serves a similar function
to that of cholesterol in eukaryotic cells.[45] In
fungal cells, ergosterol is derived by demethyl-
ation of the precursor lanosterol by the
cytochrome P450 (CYP)-dependent enzyme
14-a-demethylase.[43,46] Sertaconazole acts pri-
marily by inhibiting the activity of 14-a-
demethylase.[43,46] Demethylation is a key step in
sterol generation and, in human cells, this process
is much less sensitive to inhibition by azoles.[47]
Inhibition of 14-a-demethylase in fungi results
in a depletion of ergosterol and an accumulation
2009 Adis Data Information BV. All rights reserved.
343
decrease in the integrity of the cell membrane,
growth and replication.[1,44,48]
nazole has a further antifungal action that is
mediated via direct binding of nonsterol lipids in
the fungal membrane.[1,42,46,48,49] This affects
membrane permeability, resulting in rapid leak-
age of key intracellular constituents (e.g. adeno-
sine triphosphate) to such an extent that
immediate cell death ensues.[42,44,48,49]
In addition, the lipophilic benzothiophene
ether side chain of sertaconazole (figure 1) aids
dermal penetration[50] resulting in an enhanced
cutaneous retention time[51] without leading to an
increase in absorption into systemic circulation
(see section 3).
2.2 Fungistatic Activity
Sertaconazole demonstrated a broad range of
fungistatic activity against dermatophytes of the
Trichophyton, Epidermophyton and Microsporum
genera,[25-31] and yeasts of the genera Candida
and Cryptococcus.[25-27,29,32-36] Notably, this sen-
sitivity was maintained in isolates of dermato-
phytes and laboratory strains of Candida that
exhibited reduced susceptibility to other
azoles.[26,30]
The results of three studies evaluating the
fungistatic activity of sertaconazole against
a variety of clinical isolates of dermatophytes
(n = 456), including 114 cultures that exhibited
reduced sensitivity to fluconazole (defined as
MICs 16 mg/mL),[30] are shown in table I.[28-30]
Sertaconazole demonstrated good fungistatic
activity against all dermatophyte cultures tested,
with geometric MIC values of 0.061 mg/mL fol-
lowing a 4-day culture period (where defined).[28-30]
Furthermore, in one of these studies, isolates of
T. rubrum (n = 29) showed a higher sensitivity
to sertaconazole (geometric MIC 0.063 mg/mL)
than to bifonazole (0.267 mg/mL), fluconazole
(5.58 mg/mL) and cyclopyroxolamine (0.351 mg/mL)
but not to amorolfine (0.037 mg/mL) or terbinafine
(0.024 mg/mL).[29] A similar rank activity profile was
seen in another study of 53 varied dermatophyte
Drugs 2009; 69 (3)
344 Croxtall & Plosker

isolates (including Trichophyton, Epidermophyton Moreover, in comparator studies, sertaconazole

and Microsporum spp.) with arithmetic MIC100
values of 1.04, 0.41 and 0.05 mg/mL for bifonazole,
sertaconazole and terbinafine, respectively.[27]
The main comparator with sertaconazole in the
treatment of superficial mycoses in the clinical ef-
ficacy studies reported in section 4.1 was micona-
zole. Comparative in vitro studies using a range of
isolates of Trichophyton spp. and Microsporum
spp. (n = 23 in total), which were evaluated at a
reading time of 10 days revealed a geometric
MIC95 range of 0.242 for sertaconazole and
0.711.85 mg/mL for miconazole.[25] By contrast, in
another study of 21 dermatophyte isolates, MIC50
values ranged from 0.366.25 mg/mL for sertaco-
nazole and 0.186.25 mg/mL for miconazole.[26]
The results of four studies evaluating the fun-
gistatic activity of sertaconazole and fluconazole
against a range of Candida spp. are reported in
table II.[27,34-36] Sertaconazole demonstrated
good fungistatic activity against Candida spp.
in vitro with MIC100 values of 0.131.49 mg/mL at
reading times of 2448 hours (where de-
fined).[27,36] Two of these studies also showed
sertaconazole to exhibit good fungistatic activity
against Cryptococcus neoformans with an MIC100
range of 0.120.17 mg/mL at a reading time of
2448 hours (where defined).[27,36]
showed an MIC90 range of 0.14 mg/mL against a
range of Candida spp. versus 0.1 to >100 mg/mL for
fluconazole at reading times of 2448 hours.[34,35]
Similarly, lower MIC100 values for sertaconazole
(1.36 mg/mL) versus bifonazole and terbinafine (7.2
and 13.77 mg/mL) were reported against a range of
177 isolates of Candida spp. in one study (reading
time not defined)[27] and versus bifonazole and
naftifine (0.34 vs 13.2 and 16.3 mg/mL) in another
study of 151 yeast isolates at a reading time of
48 hours.[36] Sertaconazole also showed lower
MIC100 values compared with miconazole
(0.090.78 vs 1.5625 mg/mL) against eight strains
of C. albicans.[26] However, when evaluated across
a range of 32 varied yeast isolates, MIC95 values
were similar for sertaconazole and miconazole
(0.355.04 vs 0.245.66 mg/mL)[25] at a reading time
of 2 days for both studies.
In general, it appears that MIC values for
azole antifungal agents against Candida non-
albicans spp. are higher than those for C. albi-
cans.[34] In particular, C. glabrata, C. tropicalis
and C. krusei show a tendency for reduced anti-
fungal susceptibility to this class of agents.[34]
However, sertaconazole showed good activity
against a range of 64 isolates of Candida non-
albicans at a reading time of 2448 hours when

Table I. In vitro fungistatic activity of sertaconazole against clinical isolates of dermatophytes including 114 isolates with reduced suscept-
ibility to fluconazole (MICs of >16 mg/mL) from Spanish hospitals
Species G MIC MIC50 MIC90 References
(total no. of isolates) (mg/mL) (mg/mL) (mg/mL)
Trichophyton rubrum (141) 0.060.19 0.125 0.51.0 28,29a, 30
T. mentagrophytes (97) 0.490.62 0.5 1.02.0 28,29a, 30
T. interdigitale (32) 0.350.43 0.5 1.0 28,30
T. tonsurans (22) 0.130.35 0.125 1.0 28,30
T. violaceum (8) 0.330.5 NR NR 28,30
T. schoenleinii (4) 1.0 NR NR 28,30
T. verrucosum (2) 0.25 NR NR 28,30
Microsporum canis (80) 0.190.27 0.25 0.5 28,30
M. gypseum (30) 0.310.5 0.250.5 1.0 28,30
M. audounii (14) 0.590.89 NR NR 28,30
M. ferrugineum (1) 0.125 NR NR 30
Epidermophyton floccosum (25) 0.070.08 0.06 0.5 28,30
a Clinical isolates from onychomycosis-causing agents; culture period not defined.
G MIC = geometric mean minimum inhibitory concentration; MIC50 or 90 = minimum inhibitory concentration at which 50% or 90% of isolates
were inhibited following a 4-day culture period except where indicated otherwise; NR = not reported.

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
Sertaconazole: A Review 345

Table II. In vitro fungistatic activity against clinical isolates of Candida spp. from Spanish hospitalsa
Species Sertaconazole Fluconazole References
(total no. of isolates) MIC50 (mg/mL) MIC90 (mg/mL) MIC100 (mg/mL) MIC50 (mg/mL) MIC90 (mg/mL)
Candida albicans (239) 0.061 0.064 0.241.14 11.6 46.4 27b, 34-36
C. tropicalis (130) 0.312 1.254 0.441.49 3.264 64 to >100 27b, 34-36
C. parapsilosis (85) 0.070.25 0.251 0.260.3 0.44 3.28 27b, 34-36
C. glabrata (72) 0.10.31 0.10.25 0.40.66 <0.0532 0.164 27b, 34-36
C. krusei (48) 0.10.62 0.251 0.771.27 2532 5064 27b, 34-36
C. guilliermondii (13) 0.1 0.1 0.130.41 3.2 12.5 27b, 35,36
C. lustaniae (7) 0.1 0.25 NR <0.05 1.6 35
a A total of 12 laboratory reference strains of Candida spp. are included.
b Culture period not defined.
MIC50, 90 or 100 = minimum inhibitory concentration at which 50%, 90% or 100% of isolates were inhibited following a 24- to 48-hour culture
period except where indicated otherwise; NR = not reported.

compared with fluconazole, ketoconazole, fenti-
conazole, clotrimazole and itraconazole.[34] For
example, against C. glabrata (n = 11) sertacona-
zole was the most active agent with an MIC90 of
0.25 mg/mL versus 0.564 mg/mL for the other
antifungals.[34] Similarly, against C. tropicalis
(n = 20) the MIC90 for sertaconazole was 2 mg/mL
versus 264 mg/mL for the other agents.[34] On the
other hand, against C. krusei (n = 15) the MIC90
for sertaconazole was 1 mg/mL versus 64 mg/mL
for fluconazole and 8 mg/mL for fenticonazole,
while lower values were reported for both
clotrimazole and ketoconazole (0.5 mg/mL).[34]
Lipophilic yeasts such as M. furfur (the cau-
sative agent of pityriasis versicolor) show a much
lower sensitivity to imidazoles with a geometric
MIC100 of 19.84 mg/mL for sertaconazole and
25 mg/mL for miconazole at a reading time of
3 days (n = 3).[26]
When evaluated against a total of 13 isolates
of opportunistic filamentous fungi including
Scopulariopsis brevicaulis and species of Aspergil-
lus, Alternaria, Acremonium and Fusarium, serta-
conazole showed a geometric MIC100 range of
12.539.69 mg/mL versus 2570.71 mg/mL for mi-
conazole at a reading time of 48 hours,[26] whereas
a smaller study of six isolates of Aspergillus spp.
revealed geometric MIC95 ranges of 1.412 mg/mL
for sertaconazole versus 2.834 mg/mL for mico-
nazole at a reading time of 4 days.[25] Furthermore,
isolates of S. brevicaulis showed a higher sensitivity
to sertaconazole (geometric MIC 5.46 mg/mL) than
to bifonazole (10.55 mg/mL) and fluconazole
(78.8 mg/mL) but not to cyclopiroxolamine
(3.48 mg/mL), amorolfine (0.4 mg/mL) or terbina-
fine (0.97 mg/mL) [reading time not defined].[29]
Moreover, in a comparative study of susceptibil-
ity against 250 clinical isolates of dermatophytes
and S. brevicaulis collected from Spanish hospitals,
sertaconazole was shown to be one of the most
effective of ten antifungal agents evaluated.[31]
Breakpoints were defined by inhibition diameters
around a sertaconazole tablet (10 mg/mL) using an
agar diffusion method.[32] According to the man-
ufacturers criteria, strains classified as susceptible
showed inhibition diameters 20 mm, moderately
susceptible strains were 1219 mm and strains
classified as resistant were 11 mm.[32] The dis-
tribution of susceptibilities was terbinafine 94%,
sertaconazole 87.6%, clotrimazole 86.4%, tiocona-
zole 85.2%, econazole 81.6%, itraconazole 78.4%,
ketoconazole 74.4%, miconazole 73.3%, iso-
conazole 57.2% and fluconazole 42.8%.[31]
2.3 Fungicidal Activity
The in vitro fungicidal activity of sertaconazole
was demonstrated in studies with a limited num-
ber of Candida spp. and two isolates of T. menta-
grophytes.[25,26,33,35] Sertaconazole showed a
broad range of fungicidal activity (defined as a
total absence of growth) in one study of 194 iso-
lates of Candida spp. (0.54 mg/mL) after 48 hours
of culture (the profile of fungicidal action was

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
346
identical after 24 hours of culture).[35] Another
study of 77 isolates of three Candida spp. that
used an undefined culture period revealed fungi-
cidal activity for sertaconazole over a wider
concentration range of 0.564 mg/mL.[25] A com-
parator study against eight isolates of C. albicans
showed that sertaconazole had a greater degree of
fungicidal activity than miconazole after 48 hours
of culture (0.09 to 50 vs 25 to 50 mg/mL).[26]
Moreover, in a comparator study against one
strain of C. albicans from the American Type
Culture Collection, sertaconazole was the only
agent to achieve a 90% fungicidal effect at a
concentration of 8 mg/mL after 1 hour of culture,
with miconazole, clotrimazole, ketoconazole and
bifoconazole requiring higher concentrations.[33]
In contrast with the studies with Candida spp.,
two isolates of T. mentagrophytes required
50 mg/mL of either sertaconazole or miconazole
to achieve a fungicidal effect following 48 hours
of culture.[26]
2.4 Other Activities
Dermatological fungal infections are often ac-
companied by other opportunistic infections, which
may include Gram-positive bacteria.[25,44] Sertaco-
nazole demonstrated in vitro antibacterial activity
against 21 clinical isolates of Gram-positive bac-
teria from the Staphylococcus and Streptococcus
genera.[25] The geometric MIC value for sertaco-
nazole was 0.88 mg/mL versus 0.97 mg/mL for
miconazole and 1.44 mg/mL for clotrimazole fol-
lowing an undefined culture period.[25]
Fungal infections of the dermis may elicit a
local inflammatory response that results in irri-
tation and itching.[44] The anti-inflammatory
properties of sertaconazole have been evaluated
in both in vitro[38] and animal studies,[37,38] but
there are no data available in studies with healthy
volunteers. In human peripheral blood lympho-
cytes stimulated with phytohaemagglutinin, ser-
taconazole significantly (p < 0.05) reduced the
release of several proinflammatory cytokines
compared with a range of other antifungal agents
tested.[38]
Dermal application of 2% sertaconazole solu-
tion in an experimental model of inflammation
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
using the external ear of the rat (n = 63) resulted
in a 39.8% reduction of croton oil-induced
oedema.[37] Moreover, a comparison of the anti-
inflammatory effects of a range of antifungal
agents (all as 1% solutions) in a tetradecanoyl
phorbol acetate-induced murine model of der-
matitis (n = 56) revealed that only sertaconazole,
butoconazole and ketoconazole significantly
(p < 0.05) reduced inflammation versus vehicle,
whereas miconazole, fluconazole, terconazole and
tioconazole were without significant effect.[38]
Furthermore, 1% sertaconazole solution signifi-
cantly (p < 0.05) reduced substance P-induced
itch in mice (n = 21) compared with vehicle and
was not significantly different from a 1% solu-
tion of hydrocortisone.[38] These therapeutically
relevant concentrations indicate that sertacona-
zole may exert anti-inflammatory activity against
skin irritations associated with some dermatophyte
infections.[38,48]
2.5 Resistance Issues
Drug resistance is an increasing problem that
affects all antifungal agents, including the azoles.
However, data currently available regarding
fungal resistance to sertaconazole are limited.
Furthermore, at the present time there is no de-
fined correlation between MIC values for serta-
conazole and clinical outcomes.
Biochemical studies have revealed that the
underlying mechanisms of azole resistance are
diverse and may develop in a stepwise or con-
certed manner.[52] The adaptive changes of fungi
identified so far include either an over-expression
or reduced affinity of the cellular target (lanos-
terol 14a demethylase), increased expression of
mediators that control drug efflux and a shift to
other sterol biosynthetic pathways.[52]
Resistance testing of 250 clinical isolates of
dermatophytes and S. brevicaulis from Spanish
hospitals against a range of antifungal agents re-
vealed that only 4% of strains were resistant to
sertaconazole and terbinafine.[31] Numerically
higher rates were seen with tioconazole (4.8%),
econazole (6%), ketoconazole (10.8%), micona-
zole (15.6%), itraconazole (20%), isoconazole
(25.6%) and fluconazole (48.8%); only clotrimazole
Drugs 2009; 69 (3)
Sertaconazole: A Review
showed a numerically lower resistance rate of
3.6%.[31] More importantly perhaps, dermato-
phyte strains showing reduced susceptibility to
fluconazole retained sensitivity to sertaconazole
(table I).[30]
Continuous culture of 29 isolates of C. albi-
cans and one isolate of C. pseudotropicalis for up
to eight passages in media containing sub-
inhibitory concentrations of sertaconazole did
not induce resistance in either strain, since MIC
values were unchanged at the end of the culture
period.[25]
3. Pharmacokinetic Properties
This section focuses on pharmacokinetic data
in healthy volunteers receiving approved dosages
of 2% sertaconazole cream,[50,53,54] vaginal tablet
500 mg[53] or ovule 300 mg[55,56] (as discussed in
section 4) and from one study with a nail patch
formulation.[57] These data are supported by an
animal pharmacokinetic study using dermal ap-
plications of sertaconazole cream, solution,
powder and gel.[58]
Immediately following topical application of
100 mg single-dose 2% sertaconazole cream on
the skin of the back of 12 healthy volunteers, a
mean of 88.9% of the compound was recovered
on the skin surface.[50] This decreased linearly
over 48 hours to a mean of 52.4% of the originally
applied dose. Sertaconazole rapidly penetrated
the skin, with a mean of 5.3% of the applied dose
recovered in the stratum corneum 30 minutes
after administration. This plateaued to a mean of
6.9% after 3 hours and this level of penetration
was maintained for up to 48 hours.[50] Repeated
applications of 2% sertaconazole cream over
13 days on the forearm of seven healthy volun-
teers failed to show any detectable amount of the
drug in serum.[54]
In 16 healthy volunteers treated with nail pat-
ches containing 3.63 mg of sertaconazole, which
were replaced every week, the mean concentra-
tion of the compound exceeded 100 mg/g in nail
clippings recovered at 2, 4 and 6 weeks.[57] From
measurements of residual sertaconazole in the
nail patch, it was estimated that 1671% of the
drug had penetrated the nail.[57]
2009 Adis Data Information BV. All rights reserved.
347
Following treatment with single or repeated
vaginal applications of 2% sertaconazole cream,[53]
a single-dose vaginal tablet 500 mg[53] or a single-
dose 14C-radiolabelled sertaconazole vaginal ovule
300 mg,[55,56] high levels of the drug persisted in
vaginal fluids for 7296 hours.
In all studies, plasma concentrations of sertaco-
nazole remained undetectable following repeated
applications of either topical cream, nail patches or
vaginal suppository preparations.[53-57] Further-
more, dermal application of 14C-radiolabelled ser-
taconazole (10 mg/kg) to hairless Sprague-Dawley
rats revealed low systemic absorption of the drug
when applied as a cream (1.47% of the total dose in
plasma), solution (1.97%), gel (0.88%) or powder
(0.66%) formulation.[58]
No pharmacokinetic data are available re-
garding the use of sertaconazole in special popu-
lations such as the elderly, pregnant women or
nursing mothers. Similarly, no data are available
for interaction with other drugs.
4. Therapeutic Efficacy
The efficacy of sertaconazole has been eval-
uated in the treatment of dermatological my-
coses[59-66] and vaginal candidiasis,[67-70] and this
section reviews these therapeutic indications
separately.
4.1 Dermatological Mycoses
The efficacy of 2% sertaconazole cream as an
antimycotic agent has been evaluated in the
treatment of superficial mycoses in adults,[59-64,66]
adolescents[59] and children.[65] Fully published
trials were randomized, placebo- or active
comparator-controlled, double-blind or open-
label,[63] multicentre[59-61,63] (of which two were
phase III)[60,61] or single-centre[62,64,66] studies of
36 weeks duration (n = 20631). An open-label,
multicentre trial of 4 weeks duration evaluated
the efficacy of sertaconazole in children aged
216 years (n = 16).[65] Treatment durations were
for 2,[65] 3[60] or 4[59,61-64,66] weeks with efficacy
endpoints measured at the end of treatment,
except for two trials where relapses were eval-
uated either 1[61] or 2[59] weeks after treatment
Drugs 2009; 69 (3)
348
had stopped. One randomized, open-label,
multicentre trial evaluated the noninferiority
of 2% sertaconazole cream versus 2% solution
(n = 313).[63] The only active comparator used was
miconazole.[61]
Immunocompetent patients were eligible for
inclusion based on a clinical diagnosis of the signs
and symptoms of a range of cutaneous my-
coses,[59-63,65,66] which included, where defined,
tinea pedis,[59,60,63] tinea corporis,[60,61,63] tinea
manus,[60,61] tinea inguinalis,[60,61] tinea faciei[60]
or a candidiasis on corresponding parts of the
body.[63] Two trials included patients with a
clinical diagnosis of pityriasis versicolor (M. fur-
fur) confirmed by microscopic examination.[64,66]
Exclusion criteria included, where defined,
widespread dermatophytoses,[59] extremely se-
vere tinea pedis,[59] oral, vaginal or chronic mu-
cocutaneous candidiasis[59,63] or bacterial skin
infections.[59] Some trials excluded patients with
onychomycosis,[61,62,64] tinea capitis,[61-64] tinea
manus,[63] tinea faciei,[63] candidiasis[62,64] or
pityriasis versicolor.[61,62] Most trials excluded
patients with severe chronic diseases, prior treat-
ment with topical or systemic antifungal or im-
munosuppressive agents (14 weeks before trial
start) and pregnant or lactating women.[59-64]
Successful treatment outcomes were defined in
all trials by a clinical assessment of signs and
symptoms.[59-66] Most trials also included an as-
sessment of mycological recovery either by a
fluorescence examination,[64,66] microscopic ana-
lysis[61,62,64,66] or a culture test,[59-63] which was
defined as a primary endpoint in one trial.[60] Two
trials provided a dichotomous efficacy parameter
based on a combination of clinical assessment
and culture test, which was defined as a primary
efficacy endpoint.[59,63]
4.1.1 Clinical Efficacy
A significantly greater proportion of patients
with tinea pedis achieved both a successful clin-
ical and mycological cure following topical
treatment with 2% sertaconazole cream twice
daily for 4 weeks than with a placebo vehicle
cream (table III).[59]
Moreover, an active comparator trial of
35 days duration showed that the clinical cure
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
rate and the mycological cure rate of 2% sertacona-
zole cream twice daily was significantly greater
than that of 2% miconazole cream twice daily
in patients with a range of cutaneous mycoses
(table III).[61] Furthermore, a greater proportion
of patients achieved the category of clinically
cured at a significantly earlier timepoint (day 21;
p < 0.05 vs miconazole) following sertaconazole
treatment.[61]
Comparisons of 2% sertaconazole cream twice
daily with 1% sertaconazole cream twice daily for
the treatment of cutaneous dermatophytosis
(n = 20)[62] or pityriasis versicolor (n = 21)[64]
showed that all patients were cured (100% cure)
after 28 days,[62,64] albeit that patients achieved
the category of clinically cured at a significantly
earlier timepoint with the 2% cream (week 2;
p < 0.05 vs 1% cream) than with the 1% cream
(week 3; p < 0.05).[62] In contrast, the healing rate
of patients with pityriasis versicolor (n = 60) re-
ceiving 2% sertaconazole solution for 28 days was
100% versus 50% for recipients of placebo.[66]
Furthermore, in a noninferiority trial in patients
with tinea corporis, tinea pedis or a correspond-
ing candidiasis, sertaconazole twice daily as a
2% solution was shown to be as effective as 2%
sertaconazole cream twice daily in a combina-
tion of clinical and mycological efficacy para-
meters (primary endpoint), following 28 days
treatment (table III).[63]
In pediatric patients aged 216 years with cu-
taneous dermatophyte infections, 75% achieved
a clinical cure following 2 weeks treatment with
2% sertaconazole cream once daily and this
increased to 100% after a 2-week follow-up
period.[65]
4.1.2 Mycological Efficacy
2% Sertaconazole cream once or twice daily
effected a mycological cure in a significantly
greater number of patients with tinea pedis or
tinea of the glabrous skin than placebo vehicle
cream (table III).[59,60] Furthermore, following
28 days treatment, a significantly greater number
of patients achieved a mycological cure with
2% sertaconazole cream than with 2% micona-
zole cream (table III).[61] More importantly, a sig-
nificantly greater number of patients returned
Drugs 2009; 69 (3)
Sertaconazole: A Review 349

Table III. Efficacy of sertaconazole (SER) cream applied twice daily in the treatment of superficial mycoses.aResults of randomized, double-
blind, multicentre trials[59-61] (of which two were phase III studies)[60,61] and an open-label noninferiority trial[63] in adult and adolescent
patients (pts)
Study No. of pts Treatment Treatment success (% pts)
(timepoint of efficacy evaluation)b clinical cure mycological cure clinical and
mycological cure
PL-controlled
Savin and Jorizzo.[59]c 195 (mITT) SER 2% 64.6** 66.2** 46.7**d
(6 wk) 188 PL 37.8 22e 14.9d
Susilo et al.[60] 66 (PPP) SER 2% od 75f 81.8*g NR
(3 wk) 61 PL 66f 60.6g NR
Active comparator-controlled
Alomar et al.[61] 317 SER 2% 83.4* 98.3** NR
(4 wk) 314 MI 2% 77.1 90.3 NR
Cream versus solution
Borelli et al.[63] 153 (FAS) SER 2% 94 89.5 88.9h
(4 wk) 160 SER 2% solution 99 90.6 90.6h,i
[59] [60] [61]
a Pts with tinea pedis, tinea of the glabrous skin, cutaneous mycoses, or tinea corporis, tinea pedis or a corresponding
candidiasis.[63]
b Treatment durations were either 3[60] or 4[59,61,63] weeks.
c Combined results from two separate trials with pts aged 12 y.
d Primary endpoint: percentage of pts with a successful treatment outcome defined as a mycological cure in addition to either a
marked improvement of clinical signs and symptoms from baseline or normal appearance of the skin.
e Value read from graph.
f Global assessment of clinical signs and symptoms 1 week after the end of treatment.
g Primary endpoint.
h Primary endpoint: percentage of pts with successful eradication of pathogen in a culture test and a reduction of clinical score by 2 points
from baseline.
i Difference between success rates: solution minus cream Dp = 0.017. The one-sided 97.5% CI was a subset of the noninferiority region in
both analyses.
FAS = full analysis set; MI = miconazole cream; mITT = modified intent-to-treat; NR = not reported; od = once daily; PL = placebo;
PPP = per-protocol population; * p < 0.05, ** p < 0.0001 vs comparator.

negative culture tests at an earlier timepoint
(day 14) following sertaconazole treatment
(84.6% vs 71.4% miconazole; p < 0.001).[61]
The efficacy of 2% sertaconazole cream versus
1% cream was identical in terms of mycological
recoveries of both cutaneous dermatophytoses
and pityriasis versicolor.[62,64] All patients (100%)
returned negative culture tests after 28 days of
treatment; however, mycological assessments
were not recorded at earlier timepoints in these
studies and therefore it is not possible to ascertain
if the 2% cream showed a more rapid eradica-
tion.[62,64] Similarly, the frequency of negative
culture tests in patients treated with 2% sertaco-
nazole cream or 2% solution was not significantly
different (p = 0.631 by stratified analysis) after
28 days of treatment (table III).[63]
On day 15 of a 28 day trial in patients with
pityriasis versicolor, significantly fewer recipients
of 2% sertaconazole solution than recipients of
placebo had evidence of mycological infection as
revealed by both microscopic analysis (3.6% vs
36%; p < 0.003) and fluorescence examination
(3.6% vs 32%; p < 0.008).[66]
4.1.3 Recurrence
Relapse rates of tinea pedis, which were defined
as the number of patients initially cured at week 4
but who subsequently showed a recurrence of
clinical symptoms at week 6, were significantly

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
350
lower with 2% sertaconazole cream twice daily
than with placebo (29.5% vs 66.7%; p < 0.0001).[59]
The proportion of patients with an active in-
fection of cutaneous mycoses 1 week after 28 days
of twice-daily treatment with 2% sertaconazole
cream or 2% miconazole cream was significantly
higher in the miconazole treatment arm (4.4% vs
11.9%; p = 0.001).[61]
4.2 Gynaecological Mycoses
The therapeutic efficacy of sertaconazole
has been evaluated in the treatment of vaginal
mycoses as a topical cream[67] and/or supposi-
tory[67-70] in comparator trials of up to 1 years
duration (n = 37327).[67-70] All studies are fully
published and, where specified, were of a rando-
mized, double-blind[68] or open-label,[67,69] and
multicentre[67-69] or single-centre design;[70] one
was a phase III trial.[68] Active comparator drugs
included econazole[68,70] and fenticonazole.[69]
Immunocompetent women aged 1870 years
were eligible for inclusion if they exhibited clin-
ical signs and symptoms of vaginal candidiasis,
which was confirmed by a microscopic examina-
tion.[67-70] Most trials included patients with
C. albicans as the infective pathogen;[69,70] two
trials included patients with strains of Candida
spp. that were not defined.[67,68] Exclusion cri-
teria included women who were pregnant or lac-
tating, had vaginitis of a different aetiology or
other severe chronic diseases and prior treatment
with corticosteroids, immunosuppressive drugs
or other antimycotic agents 728 days before en-
rolment.[67-70] Furthermore, participants agreed
not to become pregnant or to use other vaginal
applications (e.g. contraceptives) and to avoid
sexual relations during the study period.[67-70]
All trials measured treatment outcomes by a
clinical assessment of signs and symptom[67-70]
and most also included an assessment of myco-
logical recovery either by microscopic analysis[70]
or a culture test.[67,68] Two trials evaluated re-
currence rates.[68,69] One trial defined primary
efficacy endpoints as the incidence of clinical
and mycological recoveries (no signs and symp-
toms and a negative culture test) at each visit
and the recurrence rates at the final visit in
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
women cured at 1 week after the last treatment
application.[68]
4.2.1 Clinical Efficacy
Sertaconazole as a vaginal tablet or ovule
formulation was successful in the eradication of
Candida spp. in 65100% of patients with vaginal
candidiasis in trials that evaluated clinical cure
rates up to 1 year after the last treatment appli-
cation.[67-70] Furthermore, its clinical efficacy
was shown to be significantly greater than econa-
zole, which was administered more frequently
(table IV).[70]
Sertaconazole treatment was at least as effec-
tive as econazole treatment.[68,70] A single dose
of sertaconazole 500 mg was significantly more
effective than three doses of econazole 150 mg
given over 3 days in a single-centre study (table
IV).[70] After 7 days of treatment, 95% of patients
receiving sertaconazole achieved complete or ad-
vanced healing compared with 39% of patients
receiving econazole (table IV). By day 14, the com-
plete healing response rates were 89.5% and 55.6%
and were no longer significantly different.[70]
In a multicentre study, 1 month after the last
application (of either one or two applications
1 week apart), the incidence of clinical recoveries
observed with a sertaconazole 300 mg ovule was
not significantly different from that of an econa-
zole 150 mg suppository (table IV).[68] A long-
term, prospective follow-up study of patients
(n = 327) who received a single vaginal tablet of
sertaconazole 500 mg revealed that 83.8% of pa-
tients had a clinical resolution 1 year after the
application compared with 84.6% of patients who
received a single vaginal pessary of fenticonazole
600 mg.[69]
Clinical cure rates were numerically higher in
patients receiving a combination of a once-daily
application of 2% sertaconazole cream for 7 days
together with a single vaginal ovule of sertaco-
nazole 300 mg than in patients treated with the
ovule formulation alone (table IV).[67] Further-
more, the cure rate increased to 100% with com-
bination treatment versus 80% for the ovule alone
after 14 days, although the differences were not
statistically significant at either timepoint.[67]
Drugs 2009; 69 (3)
Sertaconazole: A Review 351

Table IV. Efficacy of sertaconazole (SER) formulations in the treatment of vaginal candidiasis. Results of randomized, single-[70] or
multicentre[67,68] trials (of which one was a phase III study)[68] in adult patients (pts)
Study (timepoint of efficacy No. of pts Treatment Treatment success (% pts)
evaluation) clinical cure mycological clinical and
cure mycological cure
Comparisons with econazole (ECO)
Dellenbach et al.[68] 150 SER 300 mg ovulea 65.5 65.4 65.3b
(1 mo)
160 ECO 150 mg suppositorya 65.1 58.9 62b
[70] c ** *
Wang et al. 19 SER 500 mg vaginal tablet 95 100 NR
(7 d)
18 ECO 150 mg vaginal tabletd 39 72.2 NR
Comparisons with SER cream
Quereux et al.[67] 39 SER 300 mg ovulec 68 77 NR
(7 d)
38 SER 300 mg ovule + creame 76 77 NR
a One or two applications 1 week apart.
b Primary endpoint defined as the incidence of clinical and mycological recoveries (no signs and symptoms and a negative culture
test) at each visit, and the recurrence rates at the final visit in women cured at 1 week after the last treatment application.
c Single dose.
d Three doses over 3 days.
e Single-dose ovule + 2% cream once daily for 7 days.
NR = not reported; * p = 0.013, ** p = 0.004 vs comparator.

4.2.2 Mycological Efficacy Long-term follow-up (1 year) of patients

One hundred percent of recipients of a single
vaginal tablet of sertaconazole 500 mg achieved a
mycological cure (assessed by a microscopic
smear test) on day 7 compared with 72.2% of
patients receiving 3 days of treatment with three
vaginal tablets of econazole 150 mg (table IV).[70]
This mycological efficacy of sertaconazole was
maintained at day 14, with 100% of patients
showing a negative smear test compared with
77.8% of econazole recipients (p = 0.03).[70]
However, when administered as one or two
vaginal ovule preparations 1 week apart, the
mycological cure rate in patients 1 month after
the last application of sertaconazole 300 mg was
not significantly different from that in patients
treated with econazole 150 mg (table IV).[68]
Mycological cure rates of sertaconazole
300 mg administered as a single ovule or in com-
bination with a once-daily application of 2%
sertaconazole cream for 7 days were similar, with
a total of 77% of patients with candidiasis show-
ing a negative test (numbers in each treatment
arm and statistical analysis were not reported).[67]
with candidiasis after treatment with a single
vaginal tablet of sertaconazole 500 mg (n = 191)
showed that 11.5% returned a positive myco-
logical culture versus 5.9% of recipients of a
single vaginal pessary of fenticonazole 600 mg
(n = 136), but this difference was not statistically
significant.[69]
4.2.3 Recurrence
In patients cured 1 week after the last appli-
cation of either a vaginal ovule of sertaconazole
300 mg or econazole 150 mg suppository, the
mycological recurrence rate after 1 month was
significantly lower with sertaconazole (19.8% vs
32.7%; p = 0.035); however, clinical recurrence
rates were not significantly different (18.2% vs
22.8%) at the same timepoint.[68] A comparison
of single-dose sertaconazole 500 mg as a vaginal
tablet with single-dose fenticonazole 600 mg as a
vaginal pessary showed no significant difference
(16.2% vs 15.4%) in mycological recurrence
1 year after treatment.[69]

2009 Adis Data Information BV. All rights reserved. Drugs 2009; 69 (3)
352
5. Tolerability
Sertaconazole was generally well tolerated for
the treatment of dermatological and gynaeco-
logical mycoses.[59-64,67-70] A low incidence of
adverse events was observed in patients with
dermatological mycoses and these were mostly
cutaneous-related;[59,63] adverse events in patients
with vaginal candidiasis were largely absent and
haematological and biochemical parameters
did not deviate from normal.[67-70] This section
reviews tolerability profiles in these indications
separately.
5.1 Dermatological Mycoses
The tolerability of sertaconazole as either a
cream or solution preparation was evaluated in
the therapeutic efficacy trials reported in section
4.1 in patients with dermatological mycoses[59-63]
and pityriasis versicolor.[64] In addition, a small
(n = 8), placebo-controlled trial in healthy male
volunteers evaluated the tolerability of repeated
application of 2% sertaconazole cream once daily
over a 13-day period.[54] Furthermore, the sensi-
tizing capacity of sertaconazole in causing con-
tact dermatitis was evaluated in a randomized,
double-blind, placebo-controlled trial in 78 heal-
thy volunteers.[71]
Sertaconazole as a 1% or 2% cream or a 2%
solution was well tolerated in trials of up to
6 weeks duration.[59-64] Where reported, the most
common adverse events were cutaneous-related
and included contact dermatitis, dry or burning
skin, application site reaction, eczema, itch and
skin tenderness.[59,63] The frequency of cutaneous
adverse events did not differ between 2% serta-
conazole cream and placebo (2.4% each treat-
ment arm);[59] cutaneous adverse events were
considered to be severe in intensity in four pa-
tients (two in each treatment arm).[59]
A placebo-controlled trial in patients with
tinea of the glabrous skin showed 15.5% of 2%
sertaconazole cream recipients and 20% of pla-
cebo vehicle recipients experienced adverse events
but the nature and frequency of these events was
not described.[60] However, several other com-
parator trials reported no adverse events fol-
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
lowing treatment with 1% or 2% sertaconazole
cream for 2835 days in patients with dermato-
logical mycoses[61,62] or pityriasis versicolor.[64] In
contrast, 2% miconazole cream was associated
with a low incidence of contact dermatitis
(1.6%).[61]
The incidence of recipients of either 2% serta-
conazole solution or 2% sertaconazole cream
having at least one adverse event did not differ;
occurring with a frequency of 6.1% or 7.4%,
respectively.[63]
Repeated application of 2% sertaconazole
cream once daily for 13 days did not elicit any
local skin irritation or adverse events in healthy
volunteers.[54] Furthermore, blood pressure, vital
signs and haematological parameters remained
within the normal range and serum testosterone
levels were not changed from baseline.[54]
The sensitizing action of 2% sertaconazole
cream, five other antimycotic agents and a vehicle
excipient in causing contact dermatitis showed
that of the agents screened, only micona-
zole elicited a positive reaction.[71] Two out of
78 volunteers (2.6%) treated with miconazole
showed a sensitizing effect, whereas sertacona-
zole, ketoconazole, bifoconazole, clotrimazole
and the vehicle excipient showed no reaction
when evaluated at 48 and 96 hours after
application.[71]
5.2 Gynaecological Mycoses
The tolerability profiles of sertaconazole as a
cream and/or suppository in patients with vaginal
candidiasis reported in the clinical trials in section
4.2 were largely of a descriptive nature.[67-70]
However, the tolerability of 2% sertaconazole
cream (single- and repeated-dose over 7 days) and
a vaginal tablet 500 mg (single-dose only) was
evaluated more thoroughly in a randomized,
double-blind, placebo-controlled study in 12
healthy female volunteers.[53]
Most clinical trials of up to 28 days duration
showed that sertaconazole was well tolerated and
generally associated with an absence of adverse
events.[67,68,70] Where reported, adverse events
following one or two applications of a supposi-
tory formulation of sertaconazole or econazole
Drugs 2009; 69 (3)
Sertaconazole: A Review
were local itching and burning (8.7% vs 13.4%, no
significant difference).[68] Similarly, a long-term
(1 year), prospective, follow-up study showed
that following a single application of a sertaco-
nazole vaginal tablet or a fenticonazole pessary,
the only adverse event reported was irritation
after insertion (1.6% vs 1.5%, no significant dif-
ference).[69] There were no serious adverse events
reported in any trial.[67-70]
Sertaconazole in both cream and vaginal tab-
let formulations showed favourable tolerability
profile in healthy volunteers.[53] Blood pressure,
vital signs, biochemical and haematological
parameters and a gynaecological examination
(which included a smear test and colposcopy)
showed no difference between cream, tablet or
placebo and were all within physiologically nor-
mal ranges.[53]
6. Dosage and Administration
In the EU, sertaconazole as a 2% cream or
solution is indicated for the topical treatment of
superficial skin mycoses including dermatophytes
(tinea corporis, tinea cruris, tinea manus, tinea
barbae and tinea pedis), cutaneous candidiasis,
pityriasis versicolor and seborrhoeic dermatitis of
the scalp.[16,18,19,21,23,24] Sertaconazole is also
available in the EU as a 300 mg ovule, 500 mg
tablet and 2% cream for the treatment of vaginal
candidiasis.[20,22] In the US, sertaconazole is
available as a 2% cream formulation only and is
indicated for the treatment of tinea pedis in pa-
tients 12 years.[17]
For the treatment of superficial mycoses, ser-
taconazole may be applied as a cream or solution
once or twice daily to the affected region. While
the duration of treatment varies between
patients, generally 4 weeks of therapy is re-
commended to ensure a complete clinical re-
covery and microbiological elimination and to
reduce the likelihood of recurrence of infec-
tion.[16,17,19,21,23,24] Sertaconazole cream or
solution is not recommended for ophthalmic
treatments and its use in pregnant or lactating
women should only be when necessary and with
appropriate precautions.[16-19,21,23,24]
2009 Adis Data Information BV. All rights reserved.
353
For the treatment of vaginal candidiasis, either
a single application of sertaconazole as a 300 mg
ovule or 500 mg tablet (with a second applica-
tion 7 days later if required)[20,22] or a once-
daily application of 2% cream for 7 days is
recommended.[20]
Sertaconazole should not be used in patients
with known allergies to imidazoles or compo-
nents of the excipient.[16-19,21,23,24] Caution
should be exercised when using any antifungal
agent in combination with a topical fluorinated
corticosteroid (section 7).[72]
Local prescribing information should be con-
sulted for detailed information including contra-
indications, precautions, drug interactions and
use in special populations.
7. Place of Sertaconazole in the
Management of Superficial Mycoses in
Dermatology and Gynaecology
The overall aim of the management of all su-
perficial mycoses is (i) the rapid and complete
relief of clinical signs and symptoms; (ii) a nega-
tive mycological recovery; and (iii) the prevention
of further recurrences of infection.[2,12,73,74]
Where possible, the preferred management of
superficial dermatophytes is by topical treatment
because this avoids many of the adverse events
that are commonly associated with systemic
exposure to antifungal agents.[3] With this in
mind, the American Academy of Dermatology
(AAD) recommends topical treatment for non-
inflammatory tinea corporis, tinea cruris, tinea
faciei, tinea manuum and tinea pedis with anti-
fungal agents that include (but are not restricted
to) imidazoles, allylamines and ciclopirox ola-
mine.[72] However, topical treatment alone is not
recommended for inflammatory dermatophyto-
ses, onychomycosis, tinea capitis or invasive
fungal infections, as these may require additional
therapy.[47,72-74] In particular, superficial infec-
tions of some Trichophyton spp. and M. canis are
prone to elicit localized inflammatory reactions
and treatment with an antifungal agent in
combination with a topical corticosteroid may be
appropriate.[72,75]
Drugs 2009; 69 (3)
354
Guidelines for the treatment of candidiasis
published by the Infectious Disease Society of
America (IDSA) recommend topical azole agents
as first-line therapy.[2] However, vaginal candi-
diasis may be classified into complicated and
uncomplicated forms. Uncomplicated candi-
diasis is represented by 90% of patients and is
typified by a C. albicans infection of mild to
moderate severity, which responds well to topical
azole treatment.[2] In contrast, complicated
candidiasis is typified by severe infections of
Candida non-albicans species where topical azole
therapy is generally unreliable.[2] For this reason,
although most topical azole agents are available
over-the-counter, self-diagnosis of genital candi-
diasis is not recommended because it may result
in inappropriate treatment.[2] Furthermore, the
IDSA guidelines also indicate that candidial
onychomycosis is not particularly susceptible to
any topical treatment.[2]
Specific guidelines for the treatment of pity-
riasis versicolor are not formalized. However,
the British Association of Dermatologists re-
commends topical treatment with azoles or sele-
nium sulphide for superficial infections, whereas
widespread or invasive infections require oral
azole treatment.[76]
Sertaconazole is indicated in the EU for the
treatment of superficial skin mycoses such as
dermatophytosis (including tinea corporis, tinea
cruris, tinea manus, tinea barbae and tinea pedis),
cutaneous candidiasis, pityriasis versicolor and
seborrhoeic dermatitis of the scalp, and in the US
for tinea pedis only.[16-18,21,23,24] It is available
as a cream, solution, powder or gel for topical
application, or as a tablet, ovule or cream for
vaginal treatment.[19,20,22] Additionally, a nail
patch formulation of sertaconazole is available
for the treatment of onychodystrophy.
Approved dosages of 2% sertaconazole cream
in pharmacokinetic studies show good dermal
retention without accompanying systemic ex-
posure. Similarly, sertaconazole as a vaginal
tablet 500 mg or ovule 300 mg shows good re-
tention in vaginal fluids while plasma levels re-
main undetectable (section 3). In general, topical
agents show poor efficacy in the treatment of
onychomycosis as a result of poor penetration of
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
the nail bed;[2,3,74] however, sertaconazole as a
nail patch formulation shows good penetration
of the nail (section 3).
Sertaconazole not only shows good fungistatic
activity in vitro against a range of dermatophyte
cultures, but is one of the most active antifungal
agents available from the azole class (section 2.2).
In particular, sertaconazole shows better in vitro
activity than miconazole, the main comparator
used in clinical trials reported in section 4.1.
More importantly, the fungistatic activity of
sertaconazole is maintained in dermatophyte
cultures that exhibit reduced susceptibility to
fluconazole. Furthermore, isolates of T. rubrum,
a strain that is known to be recalcitrant to anti-
fungal treatment,[72] show a high susceptibility to
sertaconazole (section 2.2).
Similarly, sertaconazole shows good fungi-
static activity in vitro against yeasts including a
broad range of Candida spp. and C. neoformans
and, in general, shows better activity than com-
parative azoles (section 2.2). More importantly,
against isolates of Candida non-albicans, which
are known to exhibit reduced susceptibility to
azole agents,[34] sertaconazole also shows good
activity.
However, much lower fungistatic activity
of sertaconazole is seen against M. furfur com-
pared with other mycoses, and in vitro studies
with opportunistic filamentous fungi such as
Aspergillus spp. show considerable variation in
MIC values (section 2.2). This is probably due to
a lack of standardization of culture methodology
for these particular mycoses and the relatively
small number of fungal isolates used in these
studies.
Unlike many of the azole agents, sertacona-
zole has additional fungicidal activity (defined as
a total absence of cell growth) at higher con-
centrations against a limited number of Candida
spp. (section 2.3). Furthermore, sertaconazole
shows evidence of antibacterial activity in vitro
against some Gram-positive bacteria and de-
monstrates anti-inflammatory activity in experi-
mental models of inflammation (section 2.4);
however, data are again limited.
MIC values determined by in vitro testing have
not been correlated with clinical outcomes.
Drugs 2009; 69 (3)
Sertaconazole: A Review
However, resistance testing of sertaconazole
against a range of clinical isolates of dermato-
phytes revealed a low number of resistant strains
(4%) with most other azoles showing higher levels
(section 2.5). Furthermore, continuous culture of
two Candida spp. with sub-inhibitory levels of
sertaconazole-containing media failed to induce
resistance in either strain.
In randomized, double-blind, multicentre
trials of up to 6 weeks duration, a significantly
greater number of patients with tinea pedis or
tinea of the glabrous skin receiving 2% sertaco-
nazole cream achieved a successful mycological
cure than with a placebo cream (section 4.1).
Furthermore, the clinical cure rate and the my-
cological cure rate achieved with 2% sertacona-
zole cream were significantly higher than those of
2% miconazole cream, and significantly more
recipients of 2% sertaconazole cream returned a
negative culture test at an earlier time point.
Moreover, recurrence rates in patients with
cutaneous mycoses were significantly lower in
recipients of sertaconazole than in recipients of
miconazole. In addition, when evaluated in a
noninferiority trial, 2% sertaconazole solution
was shown to be as effective as 2% sertaconazole
cream in achieving a clinical and mycological
cure in patients with a range of cutaneous my-
coses. When evaluated in patients with pityriasis
versicolor, 1% or 2% sertaconazole cream
achieved a complete clinical and mycological cure
after 28 days of treatment.
When used as a vaginal ovule or tablet in trials
of up to 1 years duration, sertaconazole showed
good clinical and mycological efficacy in the
eradication of Candida spp. in patients with
vulvovaginal candidiasis (section 4.2). More impor-
tantly, when used as a single-dose vaginal tablet
formulation, sertaconazole 500 mg showed more
rapid eradication of candidiasis than with a
triple dose of econazole 150 mg tablet treatment
(section 4.2). Clinical recurrence of candidiasis
following sertaconazole treatment was apparent in
trials that evaluated recurrence rates up to 1
month and 1 year after treatment (section 4.2.3).
However, the incidence of mycological recurrence
was significantly different from that reported
with econazole but not with fenticonazole.
2009 Adis Data Information BV. All rights reserved.
355
Sertaconazole was generally well tolerated in
patients with dermatological and gynaecological
mycoses (section 5). Adverse events associated
with topical application of the cream were mostly
cutaneous related and did not differ from those
associated with placebo in trials of up to 6 weeks
duration. Furthermore, no sensitizing action of
sertaconazole was observed in causing contact
dermatitis in healthy volunteers. Suppository
treatments with sertaconazole were also well tol-
erated, with a notable absence of adverse events
in trials that evaluated outcomes for up to 1 year
after treatment.
The AAD recognizes that fungal infections
frequently require prolonged therapy for suc-
cessful eradication.[72] The recommended dosage
of 2% sertaconazole cream for the treatment of
superficial mycoses is once or twice daily for a
period of 4 weeks, whereas a single application of
sertaconazole 300 mg ovule or 500 mg tablet is
recommended for the treatment of vaginal can-
didiasis with a second application 7 days later
if required. One of the main considerations in
antifungal therapy concerns patient adherence to
treatment regimens.[44] A particular issue with
topical antimycotic therapies is that patients dis-
continue treatment when clinical signs and
symptoms disappear but infective fungal spores
still remain on the skin.[44,72] The main reason for
recurrence of infection stems from a failure to
successfully eradicate the original infection.[72]
Clearly, topical antifungal treatments that effect
rapid and complete eradication are more likely to
reduce the recurrence of infection.
Most azole drugs are fungistatic, which, al-
though limits fungal cell growth, does not prevent
the shedding of viable mycelial cells from the skin
surface.[77] Sertaconazole, however, has an addi-
tional fungicidal activity; in other words, the
fungal cells are killed. In general, fungicidal drugs
are preferred over fungistatic drugs for super-
ficial dermatophyte infections because higher
cure rates are achieved in shorter treatment
times,[77] thus increasing the likelihood of patient
adherence and decreasing the incidence of recur-
rence. Other antifungal agents available that
show fungicidal activity are the allylamines.[77]
However, these drugs are less effective against
Drugs 2009; 69 (3)
356
yeast infections such as C. albicans and, for this
reason, azole agents remain the preferred treat-
ment option.[77]
Superficial mycoses are often accompanied by
localized irritation and itching, and in particular,
some Trichophyton spp. and M. canis are prone
to elicit an inflammatory reaction requiring
additional treatment.[75] Topically applied corti-
costeroids are highly effective in controlling
superficial inflammatory reactions. However,
systemic corticosteroids suppress immune func-
tion and, for this reason, topically-applied fluori-
nated corticosteroids, which are highly lipophilic
and readily absorbed, should be used with caution
if coadministered with an antifungal agent.[72,75]
Any compromise in immune function could
potentially affect the severity of fungal infection.
Sertaconazole shows additional anti-inflammatory
activity in a limited number of experimental mod-
els of inflammation (section 2.4). Moreover, de-
spite good dermal penetration, the drug shows
little evidence of systemic exposure (section 3).
Therefore, sertaconazole has the potential to con-
trol local inflammatory responses associated with
dermal mycoses, but without impairing immune
function. Further clinical data are required to
support this.
Co-infections of Gram-positive bacteria are
often observed in patients with superficial my-
coses, which may require additional antibacterial
therapy. Sertaconazole shows antibacterial activity
against Gram-positive bacterial isolates in vitro
with MIC values that are therapeutically relevant
(section 2.4). There is therefore the potential to
control bacterial co-infections in patients with
superficial mycoses with sertaconazole treatment
alone without recourse to other treatments, thus
enhancing the likelihood of patient adherence.
Again, further clinical data are required to sup-
port this.
In conclusion, sertaconazole has broad-
spectrum antifungal activity against dermato-
phytes of the Trichophyton, Epidermophyton and
Microsporum genera, the yeasts of the genera
Candida and Cryptococcus, and, additionally, is
effective against opportunistic filamentous fungi
and Gram-positive bacteria. Moreover, the anti-
fungal activity of sertaconazole is maintained in
2009 Adis Data Information BV. All rights reserved.
Croxtall & Plosker
clinical isolates of dermatophytes that show
reduced susceptibility to other azoles. While the
drug has good dermal penetration, this is not
associated with systemic absorption. In clinical
trials in patients with superficial mycoses, 2%
sertaconazole cream applied twice-daily was ef-
fective in the eradication of a range of dermato-
phytoses and a significantly greater proportion
of patients were cured compared with those re-
ceiving 2% miconazole cream twice-daily treat-
ment. In patients with vulvovaginal candidiasis,
sertaconazole as a single-dose ovule or tablet was
effective in the eradication of Candida spp. and
achieved both a more rapid and a higher cure rate
than three doses of econazole tablet. Both as
a topical cream and suppository preparation,
sertaconazole was generally well tolerated. Ser-
taconazole is a well established antifungal agent,
which is now available in a variety of formula-
tions and remains a useful treatment option
particularly in patients with fungal infections
resistant to other azoles.
Disclosure
The preparation of this review was not supported by any
external funding. During the peer review process, the manu-
facturer of the agent under review was offered an opportunity
to comment on this article. Changes resulting from comments
received were made on the basis of scientific and editorial
merit.
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Correspondence: Jamie D. Croxtall, Wolters Kluwer
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