Ciclopirox Nail Lacquer 8% for the Treatment of Onychomycosis: A Canadian Perspective
A. K. Gupta MD, PhD, MBA/HCM, FRCPC1,2
J. R. Schouten, BSc2, L. E. Lynch, HBSc2
1Division of Dermatology, Department of Medicine, Sunnybrook and Women’s
College Health Sciences Centre (Sunnybrook site) and the University of Toronto,
2Mediprobe Research Inc., London, Ontario, Canada
Onychomycosis is prevalent in the Canadian population, and risk factors, such as old
age and diabetes, are increasing. This condition has traditionally been treated using oral
antifungal agents with varying degrees of success. Recently, ciclopirox nail lacquer 8%
solution became the first topical agent approved in Canada for onychomycosis. Ciclopirox
nail lacquer may be safe and effective for the treatment of onychomycosis, and certain
candidates may benefit from therapy. Ciclopirox may be implicated for prophylactic use in
order to prevent recurrent infection and may be used in combination with oral agents.
onychomycosis, ciclopirox nail lacquer
Demographic studies suggest that onychomycosis affects between 6.1% and
6.9% of the Canadian population.1 Several risk factors are associated with the
development of onychomycosis, including male gender, increasing age, diabetes,
peripheral vascular disease, and immunosuppression.2
With the increasing age
of the Canadian population and the high incidence of diabetes, a set of safe and
effective options for the treatment of this condition is needed.
Ciclopirox Nail Lacquer
Ciclopirox (Penlac™, Dermik) 8% solution is the only topical antifungal approved
for onychomycosis in Canada. This compound is fungicidal in vitro against
proliferating and dormant fungal cells,3 and has a broad spectrum of activity.4
Ciclopirox nail lacquer was recently approved in Canada (April 2004) as part of
a comprehensive nail management program, in which the lacquer is applied once
daily for 48 weeks and nail debridement is performed under the supervision of a
Mechanism of Action
Ciclopirox targets a variety of metabolic processes in the fungal cell. It chelates
polyvalent cations (Fe+3 and Al+3) that are involved in fungal enzymatic activity,
ultimately interrupting intracellular energy production and toxic peroxide
degradation.6 Ciclopirox may also inhibit fungal nutrient uptake, resulting in a
depletion of amino acids and nucleotides and a reduction in protein synthesis.6
Ciclopirox nail lacquer penetrates the nail plate via
a transungual delivery system. When the solvent
evaporates the concentration of ciclopirox increases
from 8% to 34.8%, providing a concentration gradient
that facilitates the transfer of the drug through the nail
plate.6 This mode of application permits distribution of
the active compound throughout the entire nail plate,
including the lateral margins and onycholytic portions
of the nail.7-9
In vitro penetration studies in pigskin,
cow horn, sheep hoof plates, and human nails6,10 using
radiolabelled ciclopirox demonstrated penetration of
the active ingredient as deep as 0.4mm into the
nail after one application.
demonstrate that ciclopirox nail lacquer, applied daily
for 7-14 days, penetrates the nail at concentrations that
exceed the in vitro minimum inhibitory concentrations
(MICs) for most fungal species.6
Ciclopirox has no reported interactions with other
Ciclopirox treatment-emergent adverse events
(TEAE) reported in US pivotal trials were localized to
the treatment area.12 Nine percent of patients treated
with ciclopirox nail lacquer and 7% of patients
treated with vehicle reported TEAEs considered by
the investigator to be related to the test material.5 The
most common TEAE was a mild rash at the application
site13 (5% ciclopirox, 1% vehicle).
TEAEs included nail disorders such as shape change,
irritation, ingrown toenail, and discolouration.
Low levels of ciclopirox are recovered systemically.5
The mean systemic absorption of ciclopirox is less
than 5% of the applied dose.10
The efficacy of ciclopirox has been demonstrated
in vitro against a broad spectrum of proliferating
and dormant fungal strains.3 The MIC (mean ±
SEM) for ciclopirox was 0.04±0.02mgml-1 against
dermatophytes, 0.05±0.02mgml-1 against yeasts, and
1.04±2.62mgml-1 against other nondermatophytes.4
Two double-blind, vehicle-controlled, multicenter
pivotal US clinical trials5,12 assessing the use
of ciclopirox nail lacquer for mild-to-moderate
onychomycosis (20%-65% surface area involvementof the target toenail) demonstrated significant
mycological efficacy of the active compound when
compared with the vehicle. The mycological cure
(negative KOH and culture) rate for ciclopirox nail
lacquer applied once daily for 48 weeks was 29%
(ciclopirox) vs. 11% (vehicle) in the first trial and
36% (ciclopirox) vs. 9% (vehicle) in the second
Data from a meta-analysis of 10 trials conducted
worldwide showed a mean (±SE) mycological cure rate
of 52.6%±4.2% (range: 46.7%-85.7%).12 Although
the parameters of these studies were different,
these results were consistent with the US results.
These studies and US pivotal trials establish the
efficacy of ciclopirox nail lacquer for the treatment
Successful treatment of onychomycosis caused by
nondermatophyte molds with ciclopirox nail lacquer
has been reported.13 These results demonstrate the
broad spectrum of activity of ciclopirox nail lacquer
Ciclopirox has demonstrated synergy in vitro
when combined with oral agents. Synergy between
ciclopirox and terbinafine was demonstrated in
vitro4 against 5 of 6 nondermatophyte species tested.
Synergy, additivism, and indifference were observed
between ciclopirox and itraconazole.4 No antagonism
was observed for either combination.
Mycological cure rates in patients receiving 8
weeks of terbinafine (250mg/day) plus ciclopirox
nail lacquer (once daily for 48 weeks) compared
with patients receiving 12 weeks of terbinafine
monotherapy (250mg/day) suggest that combination
therapy of ciclopirox nail lacquer with lower doses of
terbinafine may be effective. At the end of 48 weeks,
mycological cure was reported in 66.7% of patients
treated for 8 weeks with terbinafine and ciclopirox,
70.4% of patients receiving 12 weeks terbinafine and
ciclopirox, and 56.0% for those treated with 12 weeks
of terbinafine alone (p>0.05).14
Candidates for Treatment
Patients not eligible for systemic treatment due to
safety issues (i.e., the elderly and patients with hepatic
dysfunction), those using multiple medications, or
patients unwilling to use systemic treatment are
candidates for topical antifungal therapy using
ciclopirox nail lacquer.
In patients with onycholysis,
the lacquer may penetrate to onycholytic regions that
may not receive adequate drug from conventional oral
therapy. In cases of dermatophytoma, a subungual
mass of densely packed thick-walled fungal hyphae, a combined approach of oral/topical/mechanical
therapies may increase efficacy rates. In lateral
onychomycosis, the concentration of the oral
antifungal agent is lower in the lateral portion of
the nail plate, and combining it with ciclopirox nail
lacquer may help improve efficacy by providing drug
to this area of the nail.15
Patients may benefit from the use of ciclopirox
nail lacquer applied twice weekly7,11 as a means
of preventing recurrence. However, the benefit of
prophylactic treatment needs to be confirmed in
Pharmaco-economic analysis16 suggests that ciclopirox
nail lacquer may be a cost-effective option for the
management of dermatophyte onychomycosis.
wholesale price of the lacquer in Canada is $89.95/6g
bottle, which offers more than 1,000 applications.17
Ciclopirox nail lacquer is the only approved
topical agent for the treatment of mild-to-moderate
onychomycosis. The choice of antifungal therapy
depends on several factors: efficacy, spectrum of
activity, convenience, cost, and patient/physician
preference. Combination therapy using ciclopirox
nail lacquer and terbinafine may be a consideration in
moderate-to-severe cases of onychomycosis.
- Gupta AK, Jain HC, Lynde CW, Macdonald P,Cooper EA, Summerbell RC. Prevalence and epidemiology of onychomycosis in patients visiting physicians’ offices: a multicenter Canadian survey of 15,000 patients. J Am Acad Dermatol 43(2 Pt 1):244-8 (2000 Aug).
- Gupta AK, Konnikov N, Macdonald P, et al. Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey. Br J Dermatol 139(4):665-71 (1998 Oct).
- Seebacher C. Action mechanisms of modern antifungal agents and resulting problems in the management of onychomycosis. Mycoses 46(11- 12):506-10 (2003 Dec).
- Gupta AK, Kohli Y. In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation of combination antifungal activity. Br J Dermatol 149(2):296-305 (2003 Aug).
- Penlac® (Ciclopirox) topical solution 8% [Canadian prescribing information] (2004) Laval, Quebec.
- Bohn M, Kraemer K. The dermatopharmacologic profile of ciclopirox 8% nail lacquer. J Am Podiatr Med Assoc 90(10):491-4 (2000 Nov-Dec).
- Baran R, De Doncker P. Lateral edge nail involvement indicates poor prognosis for treating onychomycosis with the new systemic antifungals. Acta Derm Venereol 76(1):82-3 (1996 Jan).
- Gupta AK, Daniel CR. Onychomycosis: strategies to reduce failure and recurrence. Cutis 62(4):189- 91 (1998 Oct).
- Gupta AK, Lynch LE. Onychomycosis: review of recurrence rates, poor prognostic factors, and strategies to prevent disease recurrence. Cutis 74(1 Suppl):10-5 (2004 Jul).
- Gupta AK, Ryder JE, Baran R. The use of topical therapies to treat onychomycosis. Dermatol Clin 21(3):481-9 (2003 Jul).
- Gupta AK. Ciclopirox nail lacquer: a brush with onychomycosis. Cutis 68(2 Suppl):13-6 (2001 Aug).
- Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol 43(4 Suppl):S70-80 (2000 Oct).
- Tosti A, Piraccini BM, Lorenzi S. Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases. J Am Acad Dermatol 42(2 Pt 1):217-24 (2000 Feb).
- Gupta AK, and the Onychomycosis Combination Therapy Study Group. Ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized, evalutor-blinded study. J Drugs Dermatol 4(4):481-5 (2005 Aug).
- Gupta AK, Baran R. Ciclopirox nail lacquer solution 8% in the 21st century. J Am Acad Dermatol 43(4 Suppl):S96-102 (2000 Oct).
- Gupta AK. Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States. J Am Acad Dermatol 43(4 Suppl):S81-95 (2000 Oct).
- PPS Pharma Buyers Guide. Moncton, NB: Total Pricing Systems Inc. P.174 (2005 July).
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