Ciclopirox Olamine
Indications: Candidiasis; Tinea corporis; Tinea cruris; Tinea pedis; Tinea versicolor
CICLOPIROX OLAMINE
DESCRIPTION:
FOR DERMATOLOGIC USE ONLY. DO NOT USE IN EYES.
CLINICAL PHARMACOLOGY:
Ciclopirox olamine is a broad-spectrum, antifungal agent that inhibits the growth of pathogenic dermatophytes, yeasts, and Malassezia furfur . Ciclopirox olamine exhibits fungicidal activity in vitro against isolates of Trichophyton rubrum , Trichophyton mentagrophytes , Epidermophyton floccosum , Microsporum canis , and Candida albicans .
Pharmacokinetic studies in men with tagged 1% ciclopirox olamine solution in polyethylene glycol 400 showed an average of 1.3% absorption of the dose when it was applied topically to 750 cm2 on the back followed by occlusion for 6 hours. The biological half-life was 1.7 hours and excretion occurred via the kidney. Two days after application only 0.01% of the dose applied could be found in the urine. Fecal excretion was negligible.
Penetration studies in human cadaverous skin from the back, with ciclopirox olamine cream 1% with tagged ciclopirox olamine showed the presence of 0.8-1.6% of the dose in stratum corneum 1.5 to 6 hours after application. The levels in the dermis were still 10 to 15 times above the minimum inhibitory concentrations.
Autoradiographic studies with human cadaverous skin showed that ciclopirox olamine penetrates into the hair and through the epidermis and hair follicles into the sebaceous glands and dermis, while a portion of the drug remains in the stratum corneum.
Draize Human Sensitization Assay, 21-Day Cumulative Irritancy study, Phototoxicity study, and Photo-Draize study conducted in a total of 142 healthy male subjects showed no contact sensitization of the delayed hypersensitivity type, no irritation, no phototoxicity, and no photo-contact sensitization due to ciclopirox olamine cream 1%.
In vitro penetration studies in frozen or fresh excised human cadaver and pig skin indicated that the penetration of ciclopirox olamine lotion 1% is equivalent to that of ciclopirox olamine cream 1%. Therapeutic equivalence of cream and lotion formulations also was indicated by studies of experimentally induced guinea pig and human trichophytosis.
INDICATIONS AND USAGE:
Ciclopirox olamine cream 1% and lotion 1% are indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris and tinea corporis due to Trichophyton rubrum , Trichophyton mentagrophytes , Epidermophyton floccosum , and Microsporum canis ; cutaneous candidiasis (moniliasis) due to Candida albicans ; and tinea (pityriasis) versicolor due to Malassezia furfur .
CONTRAINDICATIONS:
Ciclopirox olamine cream 1% and lotion 1% are contraindicated in individuals who have shown hypersensitivity to any of its components.
WARNINGS:
General: Ciclopirox olamine cream 1% and lotion 1% are not for ophthalmic use.
PRECAUTIONS:
If a reaction suggesting sensitivity or chemical irritation should occur with the use of ciclopirox olamine cream 1% or lotion 1%, treatment should be discontinued and appropriate therapy instituted.
Information for the Patient
The patient Should Be Told to:
1. Use the medication for the full treatment time even though symptoms may have improved and notify the physician if there is no improvement after four weeks.
2. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing) indicative of possible sensitization.
3. Avoid the use of occlusive wrappings or dressings.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
A carcinogenicity study in female mice dosed cutaneously twice per week for 50 weeks followed by a 6-month drug-free observation period prior to necropsy revealed no evidence of tumors at the application site. The following in vitro and in vivo genotoxicity tests have been conducted with ciclopirox olamine: studies to evaluate gene mutation in the Ames Salmonella /Mammalian Microsome Assay (negative) and Yeast Saccharomyces Cerevisiae Assay (negative) and studies to evaluate chromosome aberrations in vivo in the Mouse Dominant Lethal Assay and in the Mouse Micronucleus Assay at 500 mg/kg (negative). The following battery of in vitro genotoxicity tests were conducted with ciclopirox: a chromosome aberration assay in V79 Chinese Hamster Cells, with and without metabolic activation (positive); a gene mutation assay in the HGPRT-test with V79 Chinese Hamster Cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA Synthesis Assay in A549 Human Cells (negative)). An in vitro Cell Transformation Assay in BALB/C3T3 Cells was negative for cell transformation. In an in vivo Chinese Hamster Bone Marrow Cytogenetic Assay, ciclopirox was negative for chromosome aberrations at 5000 mg/kg.
Pregnancy Category B
Reproduction studies have been performed in the mouse, rat, rabbit, and monkey (via various routes of administration) at doses 10 times or more the topical human dose and have revealed no significant evidence of impaired fertility or harm to the fetus due to ciclopirox olamine. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Loprox (ciclopirox olamine) Cream 1% or Lotion 1% is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 10 years have not been established.
ADVERSE REACTIONS:
In all controlled clinical studies with 514 patients using ciclopirox olamine cream 1% and in 296 patients using the vehicle cream, the incidence of adverse reactions was low. This included pruritus at the site of application in one patient and worsening of the clinical signs and symptoms in another patient using ciclopirox olamine cream 1% and burning in one patient and worsening of the clinical signs and symptoms in another patient using the vehicle cream.
In the controlled clinical trial with 89 patients using ciclopirox olamine lotion 1% and 89 patients using the vehicle, the incidence of adverse reactions was low. Those considered possibly related to treatment or occurring in more than one patient were pruritus, which occurred in two patients using ciclopirox olamine lotion 1% and one patient using the lotion vehicle, and burning, which occurred in one patient using ciclopirox olamine lotion 1%.
DOSAGE AND ADMINISTRATION:
Gently massage ciclopirox olamine cream 1% or lotion 1% into the affected and surrounding skin areas twice daily, in the morning and evening. Clinical improvement with relief of pruritus and other symptoms usually occurs within the first week of treatment. If a patient shows no clinical improvement after four weeks of treatment with ciclopirox olamine cream 1% or lotion 1%, the diagnosis should be redetermined. Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.
REFERENCES:
1. Hanel H, Raether W, Dittmar, W. Evaluation of fungicidal action in vitro and in a skin model considering the influence of penetration kinetics of various standard antimycotics. Ann NY Acad Sci. 1988;544:329-337.
2. Lassus A, Nolting KS, Savopoulos C. Comparison of ciclopirox olamine 1% cream with ciclopirox 1%-hydrocortisone acetate 1% cream in the treatment of inflamed superficial mycoses. Clin Ther. 1988;10(5):594-599.
3. Kligman AM, Bogaert H, Cordero C, et al. Evaluation of ciclopirox olamine cream for the treatment of tinea pedis: multicenter, double-blind comparative studies. Clin Ther. 1985;7(4):409-417.
4. Cullen SI, Frost P, Jacobson C, et al. Treatment of tinea versicolor with a new antifungal agent, ciclopirox olamine cream 1%. Clin Ther. 1985;7(5):574-583.
5. Bagatell FK, Bogaert H, Cullen SI, et al. Evaluation of a new antifungal cream, ciclopirox olamine 1% in the treatment of cutaneous candidosis. Clin Ther. 1985;8(1):41-48.
6. Bogaert H, Cordero C, Ollague W, Savin RC, Shalita AR, Zaias N. Multicentre double-blind clinical trials of ciclopirox olamine cream 1% in the treatment of tinea corporis and tinea cruris. J Int Med Res. 1986;14(4):210-216.