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ciclopirox 0.77% gel

Out of Stock Manufacturer ALVOGEN INC 47781053084
Out of Stock

Uses

Ciclopirox olamine cream or lotion is used topically for the treatment of certain dermatophytoses (i.e., tinea pedis, tinea cruris, tinea corporis) caused by Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum, or Microsporum canis; for the treatment of tinea (pityriasis) versicolor caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale); and for the treatment of cutaneous candidiasis (moniliasis) caused by Candida albicans. Ciclopirox gel is used topically for the treatment of tinea corporis and interdigital tinea pedis caused by T. rubrum, T. mentagrophytes, or E. floccosum and for the treatment of seborrheic dermatitis of the scalp. Ciclopirox shampoo is used topically for the treatment of seborrheic dermatitis of the scalp. Ciclopirox solution (nail lacquer) is used topically for the treatment of mild to moderate onychomycosis of fingernails and toenails, without lunula involvement, caused by T. rubrum in immunocompetent patients.

Dermatophytoses and Cutaneous Candidiasis

Ciclopirox olamine topical cream or lotion is used for the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidiasis. The gel is used topically for the treatment of tinea corporis and tinea pedis. Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; however, an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection is chronic or does not respond to topical therapy, or the patient is immunocompromised or has coexisting disease. Many clinicians consider topical imidazole-derivative azole antifungals (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole) or topical allylamine antifungals (e.g., naftifine, terbinafine) the drugs of first choice for the topical treatment of tinea corporis or tinea cruris, although other topical antifungal agents (e.g., ciclopirox olamine, butenafine hydrochloride, tolnafate, undecylenic acid) also can be effective in the treatment of these infections. While topical antifungals usually are effective for the treatment of uncomplicated tinea pedis, an oral antifungal usually is necessary for the treatment of hyperkeratotic areas on the palms and soles, for chronic moccasin-type (dry-type) tinea pedis, and for the treatment of tinea unguium (onychomycosis).

Clinical studies to date indicate that ciclopirox olamine 0.77% (expressed in terms of the base) cream or lotion is effective for the topical treatment of dermatophytoses and appears to be similar in efficacy and safety to topical clotrimazole 1% cream. Some studies reported by the manufacturer suggest a slight advantage over topical clotrimazole 1% cream for the treatment of tinea pedis or cutaneous candidiasis, but additional controlled, comparative studies are needed to establish the relative efficacy of ciclopirox olamine and other currently available topical antifungal agents. Like imidazole derivatives (e.g., clotrimazole, econazole, ketoconazole, miconazole, sulconazole), ciclopirox olamine has an advantage over some other topical antifungal agents (e.g., nystatin, tolnaftate) in the treatment of mixed infections or for empiric treatment pending identification of the causative organism since the drug is active against both dermatophytes and Candida.

Pityriasis (Tinea) Versicolor

Ciclopirox olamine topical cream or lotion is used for the treatment of pityriasis (tinea) versicolor, a superficial infection caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale). Pityriasis (tinea) versicolor generally can be treated topically with an imidazole-derivative azole antifungal (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole), an allylamine antifungal (e.g., terbinafine), ciclopirox olamine, or certain other topical therapies (e.g., selenium sulfide 2.5%). However, an oral antifungal (e.g., itraconazole, ketoconazole) may be indicated, with or without a topical agent, in patients who have extensive or severe infections or who fail to respond to or have frequent relapses with topical therapy.

Seborrheic Dermatitis

Ciclopirox gel or shampoo is used topically for the treatment of seborrheic dermatitis of the scalp. Efficacy of ciclopirox gel has not been studied in immunocompromised individuals or in patients with acne-, atopic dermatitis-, parkinsonian syndrome-, psoriasis-, or rosacea-associated seborrheic dermatitis. There is no clinical experience to date with use of ciclopirox shampoo in immunocompromised individuals such as those with extensive, persistent, or unusual distribution of dermatomycoses; recent or recurrent herpes zoster or persistent herpes simplex; human immunodeficiency virus (HIV) infection; transplantation; or diabetic neuropathy.

Efficacy of ciclopirox shampoo for the treatment of seborrheic dermatitis of the scalp has been established in 2 randomized, double-blind clinical studies of 4 weeks' duration in patients 16 years of age or older. Patients in these studies were evaluated at week 4 on the overall status of the seborrheic dermatitis, the presence and severity of erythema or inflammation, and scaling, using a scale of 0 (none) to 5 (severe). In these 2 studies, 26-58% of patients receiving ciclopirox shampoo twice weekly simultaneously achieved scores of 0 (or a score of 1 if the baseline score was 3 or greater) for status of the seborrheic dermatitis, erythema or inflammation, and scaling compared with 13-31% of those receiving vehicle twice weekly. These 2 studies did not include sufficient numbers of black patients to determine whether they respond differently to ciclopirox shampoo than patients of other races.

Onychomycosis

Overview

The management of onychomycosis may include no therapy, palliative treatment with mechanical or chemical debridement, oral and/or topical antifungal therapy, or a combination of several of these therapies. Many clinicians consider oral antifungals (e.g., itraconazole, terbinafine) first-line drugs for the management of onychomycosis of toenails because of their greater efficacy compared with that of topical antifungals. However, oral antifungals may be associated with potentially serious adverse systemic effects in some patients. Topical antifungals (e.g., ciclopirox solution, amorolfine solution [currently not commercially available in the US], bifonazole cream or ointment [currently not commercially available in the US]) usually do not cause serious adverse systemic effects; however, their relative efficacy is low. Response rate to topical antifungal therapy is dependent on the type and extent of infection. Failure to respond to topical antifungals is more likely to occur in patients with 5 or more infected toenails, infections involving more than 30-50% of the nail plate, and in those with thickly keratinized, dystrophic, already damaged nails. In cases of minor nail involvement (less than 30% of nail plate in distal subungual onychomycosis) topical therapy may be useful; however, oral therapy usually is preferred in patients with more extensive involvement.

Although there are no studies evaluating the concomitant use of oral antifungals with topical antifungals (i.e., ciclopirox topical solution [nail lacquer]), some clinicians suggest that such use may be beneficial in the management of onychomycosis since the topical solutions may quickly reach nail plate areas that are not touching the nail bed while oral agents may affect the nail bed and proximal areas. In addition, because, in some patients, therapy-resistant onychomycosis may be associated with the presence of persistent fungi packets in both the infected nail beds and nail plates, concomitant oral and topical therapy may be useful in such patients.

Use of Ciclopirox in Onychomycosis

Ciclopirox topical solution (Penlac nail lacquer) is used as a component of a comprehensive management program (e.g., monthly removal of unattached, infected nail(s) by a qualified clinician experienced in nail disorders) in the treatment of mild-to-moderate onychomycosis of fingernails and toenails, without lunula involvement, caused by T. rubrum, in immunocompetent patients. Efficacy and safety of ciclopirox topical solution (nail lacquer) have not been studied in immunocompromised individuals such as those with extensive, persistent, or unusual distribution of dermatomycoses; extensive seborrheic dermatitis; severe plantar/moccasin-type tinea pedis, recent or recurrent herpes zoster or persistent herpes simplex, HIV infection; solid organ transplantation, insulin-dependent diabetes, or diabetic neuropathy; and those with seizures requiring anticonvulsants.

Ciclopirox topical solution (nail lacquer) received FDA approval for onychomycosis based on 2 double-blind, placebo-controlled studies. Efficacy of ciclopirox topical solution (nail lacquer) has been established in patients with toenail onychomycosis. Patients were assessed for ''complete cure'' (mycologic and clinical [clear nail] cure), ''almost clear'' (mycologic cure and 10% or less nail involvement), and ''negative mycology alone'' (mycologic cure only). In these toenail studies, up to 48 weeks of continuous therapy with topical 8% ciclopirox topical solution (nail lacquer) (applied once daily in conjunction with monthly removal of unattached, infected toenail[s] by the clinical investigators) was more effective than placebo. In these studies, 5.5-8.5 or 0-0.9% of patients experienced ''complete cure'' receiving the drug or placebo, respectively, 6.5-12 or 0.9% experienced ''almost clear'' cure receiving the drug or placebo, respectively, and 29-36 or 9- 11% experienced a ''mycologic cure alone'' receiving the drug or placebo, respectively, when evaluated 48 weeks after initiating therapy. However, only 58% of those experiencing ''complete cure'' were still free of the infection 12 weeks after completion of therapy.

Although comparative data are lacking, oral antifungal agents (e.g., itraconazole, terbinafine) reportedly have greater efficacy in the treatment of onychomycosis of the toenails than topical antifungals (e.g., ciclopirox topical solution). Results of several placebo-controlled studies indicate that 14-38% of patients receiving 12 weeks of continuous therapy with oral itraconazole or terbinafine experienced both mycologic and clinical cure, while only 5.5-8.5% of patients receiving topical ciclopirox solution (nail lacquer) experienced ''complete cure'' (mycologic and clinical [clear nail] cure).

Some clinicians state that in patients with onychomycosis, combined use of an oral antifungal agent with a topical antifungal (e.g., ciclopirox solution) may result in improved efficacy relative to the use of an oral antifungal agent alone; however, further studies are needed to determine whether such combined therapy will be a feasible option in terms of efficacy, adverse effects profile, and cost. The manufacturer of ciclopirox topical solution (Penlac [nail lacquer]) states that since no studies have been conducted in patients with onychomycosis to determine whether topical ciclopirox solution might reduce efficacy of systemic antifungals, combined use of the topical solution with a systemic antifungal agent for the management of this condition currently is not recommended.

Other Uses

Ciclopirox olamine has been used with some success as a vaginal cream for the treatment of vulvovaginal candidiasis. The vaginal cream currently is not commercially available in the US.

Dosage and Administration

Administration

Ciclopirox olamine is applied topically to the skin as a cream or lotion while ciclopirox is applied topically to the skin as a gel or shampoo and to nails as a solution (nail lacquer). The ciclopirox olamine lotion, which should be shaken vigorously before each use, may be particularly useful for infections involving relatively large areas or areas where a less viscous formulation might be preferred. Occlusive dressings or wrappings should not be used. Ciclopirox and ciclopirox olamine preparations should not be applied to the eye nor administered orally or intravaginally.

Patients should remove any loose nail or nail material (using nail clippers or nail files) before initiating therapy with ciclopirox solution (nail lacquer). Removal of unattached, infected nail(s) as frequently as once monthly by a qualified clinician in nail disorders, weekly self-trimming of infected nail(s) by the patient, and daily application of the topical solution (nail lacquer) are all essential components of the topical management of onychomycosis.

Dosage

The labeled strengths of ciclopirox olamine creams and lotions are no longer expressed in terms of the olamine salt (i.e., 1% ciclopirox olamine), but instead are expressed in terms of the base, ciclopirox (i.e., 0.77% ciclopirox).

Dermatophytoses and Cutaneous Candidiasis

For the treatment of tinea pedis, tinea cruris, tinea corporis, or cutaneous candidiasis, a sufficient amount of ciclopirox olamine 0.77% (of ciclopirox) topical cream or lotion should be applied and rubbed gently into the affected and surrounding areas of skin twice daily, in the morning and evening.

For the treatment of interdigital tinea pedis and tinea corporis due to T. rubrum, T. mentagrophytes, or Epidermophyton floccosum, a sufficient amount of ciclopirox 0.77% topical gel should be applied and rubbed gently into the cleansed affected and surrounding areas of the skin twice daily, in the morning and evening.

Clinical improvement and relief of pruritus and other symptoms usually occur within the first week of therapy, but tinea pedis, tinea cruris, tinea corporis, and cutaneous candidiasis should generally be treated for 4 weeks. However, plantar tinea pedis infections may be particularly difficult to treat topically, possibly requiring more prolonged therapy and/or systemic antifungal agents. If clinical improvement does not occur after 4 weeks of treatment, the diagnosis should be reevaluated.

Pityriasis (Tinea) Versicolor

For the treatment of pityriasis (tinea) versicolor, a sufficient amount of ciclopirox olamine 0.77% (of ciclopirox) topical cream or lotion should be applied and rubbed gently into the affected and surrounding areas of skin twice daily, in the morning and evening. Patients with pityriasis (tinea) versicolor usually exhibit clinical and mycologic clearing after 2 weeks of treatment, at which time therapy may be discontinued if response is considered sufficient.

Seborrheic Dermatitis

For the treatment of seborrheic dermatitis of the scalp, a sufficient amount of ciclopirox 0.77% topical gel should be applied to the affected areas twice daily, in the morning and evening. Clinical improvement usually occurs within the first week of therapy; however, resolution of signs and symptoms continues through 4 weeks of treatment. If clinical improvement does not occur after 4 weeks of treatment, the diagnosis should be reevaluated.

Alternatively, approximately 5 mL (or up to 10 mL for long hair) of ciclopirox shampoo is applied to wet hair and scalp, lathered, and left on the hair and scalp for 3 minutes. A timer may be used. The hair should then be rinsed thoroughly. Ciclopirox shampoo should be used twice weekly for 4 weeks, with a minimum of 3 days between applications. If clinical improvement does not occur after 4 weeks of therapy, the diagnosis should be reevaluated.

Onychomycosis

Ciclopirox topical solution (nail lacquer) should be applied once daily to infected nail(s) (preferably at bedtime or 8 hours before bathing). The topical solution should be applied evenly over the entire nail plate and 5 mm of surrounding skin, using the applicator brush provided by the manufacturer. The topical solution (nail lacquer) should be applied, if possible, to the nail bed, hyponychium (the thickened epidermis underneath the free distal end of the nail), and the undersurface of the nail plate when it is free of the nail bed (e.g., onycholysis). Following application of the topical solution (nail lacquer), the nail(s) should be allowed to dry (about 30 seconds) before wearing socks or stockings. Nail polish or other cosmetic nail products should not be applied on treated nail(s).

The manufacturer of ciclopirox topical solution (nail lacquer) does not recommend daily removal of the solution. The drug should be reapplied daily over previous coats of the solution and be removed with alcohol every 7 days. These cycles should be repeated throughout the duration of therapy. The manufacturer states that generally 6 months of therapy may be required for initial improvement of symptoms of onychomycosis and up to 48 weeks of continuous comprehensive therapy is considered necessary to achieve clear or almost clear nail(s). Safety and efficacy of ciclopirox topical solution (nail lacquer) have not been established for therapy longer than 48 weeks.

Cautions

Ciclopirox and ciclopirox olamine preparations generally are well tolerated when applied topically. The most frequent adverse effects reported with topical ciclopirox and ciclopirox olamine preparations are local and dermatologic effects. However, these reactions rarely are severe enough to require discontinuance of the drugs.

Dermatologic and Sensitivity Reactions

Pruritus at the site of application occurred in 1-5% of patients receiving ciclopirox gel or shampoo and in a few patients receiving ciclopirox olamine cream or lotion. A transient burning sensation of the skin and pain may occur following topical application of preparations containing ciclopirox or ciclopirox olamine. Burning sensation upon application (especially in sensitive areas) was reported in about 34 and 7% of patients with seborrheic dermatitis (15-20% of patients had seborrheic dermatitis of the scalp) and tinea pedis, respectively, receiving ciclopirox gel and in 1% of patients receiving ciclopirox topical solution (nail lacquer) or shampoo.

In addition, the most frequent adverse dermatologic effects reported in patients receiving ciclopirox topical solution (nail lacquer) were periungual erythema and erythema of the proximal nail fold; these effects occurred in 5 and 1% of patients receiving the solution or placebo (vehicle alone), respectively. Nail disorders (e.g., ingrown toenails, irritation, discoloration, changes in shape) occurred in patients receiving ciclopirox topical solution (nail lacquer). Dry skin, acne, rash, and alopecia were reported in less than 1% of patients receiving ciclopirox gel. Worsening of clinical signs or symptoms may occur in some patients receiving topical application of the drug.

Results of several studies in healthy males did not reveal evidence of contact sensitization of the delayed hypersensitivity type, phototoxicity, or photocontact sensitization following topical application of ciclopirox topical cream. In addition, no evidence of allergic contact sensitization was reported in patients receiving ciclopirox topical solution (nail lacquer). However, in clinical studies, contact dermatitis was reported in 1-5% of individuals receiving ciclopirox gel.

Other Adverse Effects

Ocular pain and facial edema were reported in less than 1% of patients receiving ciclopirox gel.

Precautions and Contraindications

Patients receiving topical ciclopirox therapy should be instructed to use the drug for the full, prescribed treatment period, even if symptoms improve, and to contact their physician if their skin condition does not improve after 4 weeks of treatment. Patients should be advised that topical ciclopirox preparations should not be used for any disorder other than that for which they were prescribed.

Patients receiving ciclopirox shampoo should be advised to avoid contact of the shampoo with the eyes. If contact with the eye(s) occurs, the affected eye(s) should be rinsed thoroughly with water.

Because of the risk of adverse dermatologic reactions (e.g., mild, transient irritation [erythema]) associated with ciclopirox topical solution (nail lacquer) therapy, contact with skin other than that immediately surrounding the treated nail(s) should be avoided. Patients also should be instructed to avoid the use of occlusive dressings or wrappings and to contact their physician if signs of increased irritation (e.g., erythema, pruritus, burning, blistering, swelling, oozing) indicative of possible sensitization occur at the site of application. If a reaction suggesting sensitivity or chemical irritation occurs during treatment with ciclopirox or ciclopirox olamine preparations, the drugs should be discontinued and appropriate therapy initiated.

In addition, patients with onychomycosis should be given detailed instructions regarding the use of ciclopirox topical solution (nail lacquer) as a component of a comprehensive management program that includes daily applications of the topical solution for up to 48 weeks and removal of the unattached, infected nail(s) as frequently as once a month by a qualified clinician experienced in nail disorders in order to achieve a clear or almost clear nail (defined as 10% or less residual nail involvement). These patients should be informed that 6 months of therapy may be required for initial improvement in symptoms and they also should be notified that completely clear nail(s) may not be achieved with use of ciclopirox topical solution (nail lacquer). Because onychomycosis is an infectious disease, patients should be discouraged from sharing nail grooming instruments. The manufacturer of ciclopirox topical solution (nail lacquer) states that before prescribing the drug, clinicians should carefully consider the risks associated with the removal of unattached, infected nail(s) (by a qualified clinician experienced in nail disorders) and the risk of self-trimming infected nails in patients with insulin-dependent diabetes mellitus or those with diabetic neuropathy.

Topical ciclopirox or ciclopirox olamine preparations are contraindicated in patients who have shown hypersensitivity to the drug or any ingredient in the respective formulation.Commercially available ciclopirox and ciclopirox olamine preparations are intended for topical application to the skin only and should not be applied to the eyenor administered orally or intravaginally. Contact with mucous membranes also should be avoided.

Pediatric Precautions

Safety and efficacy of ciclopirox topical solution (nail lacquer) in pediatric patients have not been established. In addition, safety and efficacy of topical ciclopirox olamine preparations (i.e., cream, lotion) and topical ciclopirox gel in pediatric patients younger than 10 and 16 years of age, respectively, have not been established. Although seborrheic dermatitis may appear at puberty, clinical studies of ciclopirox shampoo have not been performed in patients younger than 16 years of age.

Geriatric Precautions

Clinical studies of ciclopirox topical solution (nail lacquer) have not included sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. In clinical studies of ciclopirox shampoo, safety and tolerability in geriatric patients were similar to those in younger adults. However, these clinical studies did not include sufficient numbers of patients 65 years of age and older to determine whether efficacy of the drug in geriatric patients is different from that in younger patients. Other clinical experience has not revealed age-related differences in response to the drug.

Mutagenicity and Carcinogenicity

Ciclopirox olamine was not mutagenic when tested in vitro in the Ames Salmonella mammalian microsome and the yeast Saccharomyces cerevisiae gene mutation assays. Ciclopirox olamine, at doses of 500 mg/kg, did not demonstrate any potential to induce chromosome aberrations in vivo in the mouse dominant lethal test and the mouse micronucleus test assay. In addition, ciclopirox was not mutagenic in several in vitro studies, including gene mutation assays (i.e., the Ames Salmonella and Escherichia coli microbial mutagen tests and the V-79/HGPRT assay in Chinese hamster cells), the DNA damage assays (i.e., unscheduled DNA synthesis in human A549 cells), and the cell transformation assays (using Balb/c 3T3 cell). However, in vitro, ciclopirox was mutagenic in the V-79 Chinese hamster chromosome aberration assay (with or without metabolic activation). Ciclopirox (5 g/kg) was not mutagenic in an in vivo cytogenetic assay using Chinese hamster bone marrow for chromosome aberration.

A study in female mice dosed cutaneously twice weekly for 50 weeks with the drug followed by a 6-month drug-free observation period prior to necropsy revealed no evidence of tumors at the application site.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in mice, rats, rabbits, and monkeys using ciclopirox olamine dosages (via various routes of administration) 10 or more times the topical human dosage have not revealed evidence of harm to the fetus. Reproduction studies in rats and rabbits using topical dosages of ciclopirox up to 120 and 100 mg/kg of body weight, respectively, (approximately 121 and 147 times the maximum recommended topical human dosage based on surface area, respectively), also have not revealed evidence of fetotoxicity. In addition, reproduction studies in mice, rats, rabbits, and monkeys using oral dosages of ciclopirox up to 100, 30, 30, and 50 mg/kg of body weight, respectively (approximately 37.5, 30, 44, and 77 times the maximum recommended topical human dosage based on surface area, respectively), have not revealed evidence of fetotoxicity. There are no adequate and controlled studies to date using topical ciclopirox or ciclopirox olamine in pregnant women; topical ciclopirox olamine cream and lotion and ciclopirox shampoo should be used during pregnancy only when clearly needed, while topical ciclopirox gel and solution (nail lacquer) should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.

Fertility

Reproduction studies in mice, rats, rabbits, and monkeys using ciclopirox olamine dosages (via various routes of administration) 10 or more times the topical human dosage have not revealed evidence of impaired fertility. In addition, reproduction studies in rats using oral dosages of ciclopirox up to 5 mg/kg of body weight (approximately 5 times the maximum recommended topical human dosage based on surface area) also have not revealed evidence of impaired fertility.

Lactation

It is not known whether ciclopirox or ciclopirox olamine is distributed in human milk. Because many drugs are distributed in human milk, ciclopirox or ciclopirox olamine preparations should be used with caution in nursing women.

Pharmacokinetics

Absorption

Percutaneous absorption of ciclopirox olamine appears to be rapid but minimal following topical application of the drug to intact skin. In one study in healthy males in which 3.6-3.7 g of ciclopirox olamine cream was applied to a 750-cm spinal skin area, rubbed in for 4 minutes, and then, after 1 hour, covered with an occlusive dressing for 5 hours, an average of 1.3% of the dose was recovered in urine. Serum concentrations of the drug could only be measured within the first several hours after application of the dose and were generally less than 0.01 mcg/mL. Systemic absorption of topically applied ciclopirox gel is higher than that of topically applied ciclopirox olamine cream. Following topical application of a 5-g dose of ciclopirox gel (as the base) or cream (as the olamine) in healthy men, total mean peak serum ciclopirox concentrations were about 25 or 19 ng/mL, respectively. In another study, following topical application of 15 g of ciclopirox gel daily for 14.5 days in 16 men with moderate to severe tinea cruris, total peak serum ciclopirox concentrations were 100 and 238 ng/mL on day 1 and 15 of therapy, respectively. In one study in patients with seborrheic dermatitis of the scalp, topical application of 5.2 g (5 mL) of ciclopirox shampoo twice weekly for 4 weeks (exposure time: 3 minutes per application) produced detectable serum concentrations of ciclopirox in approximately 33% of patients. In this study, serum concentrations of the drug ranged from 10.3-13.2 ng/mL on day 1 and 29 of therapy.

Systemic absorption of topically applied ciclopirox solution (nail lacquer) also appears to be low. Following topical application of ciclopirox 8% solution (nail lacquer) to all 20 digits and adjacent 5 mm of skin once daily for 6 months in a limited number of patients with dermatophytic onychomycosis, the mean systemic absorption was less than 5% of the applied dose and serum concentrations of the drug ranged from 12-80 ng/mL. One month after discontinuance of the solution, serum and urine concentrations of ciclopirox were undetectable.

Distribution

Following topical application of ciclopirox olamine cream to human cadaverous skin from the back, 0.8-1.6% of the applied dose was present in the stratum corneum 1.5-6 hours after application. Although the highest drug concentrations, averaging 2300-4500 mcg/cm, were present in the stratum corneum, concentrations in the dermis ranged from 20-30 mcg/cm, which exceeded the usual MIC for most susceptible fungi. Autoradiographic studies have shown that following topical application of ciclopirox olamine cream to human cadaverous skin, the drug penetrates into hair and is absorbed through the epidermis and hair follicles into sebaceous glands and dermis, while a portion remains in the stratum corneum. In vitro, ciclopirox olamine has been shown to penetrate both average and thick horny layers of the skin as well as compact horny material such as fingernails following topical application as a cream; in one in vitro study using bovine horn plate, application of ciclopirox olamine cream to one side of the plate resulted in growth inhibition of Trichophyton mentagrophytes on the opposing side of the plate, indicating penetration of the drug. In vitro studies also indicate that following topical administration of the 8% ciclopirox solution, (nail lacquer) the drug penetrates into compact horny material (e.g., avulsed onychomycotic toenails) up to a depth of about 0.4 mm. In general, penetration of ciclopirox appeared to be dependent on the structure and thickness of the nail; penetration appears to increase with extent of mycotic infection (i.e., in nails with rougher and more fissured surfaces). However, the clinical importance of these findings is not known.

In vitro studies in human cadaverous and pig skin indicate that penetration of the drug following topical application of the commercially available ciclopirox olamine lotion is equivalent to that of the cream. In addition, studies of trichophytoses in guinea pigs and humans indicates that these 2 preparations are therapeutically equivalent in the topical treatment of these infections.

It is not known if ciclopirox olamine is distributed into milk. In rats, the drug crosses the placenta in very small amounts.

At concentrations of 0.01-11 mcg/mL in vitro, ciclopirox olamine is approximately 94-98% bound to serum proteins.

Elimination

Following percutaneous absorption, ciclopirox olamine has an elimination half-life of about 1.7 hours in healthy individuals. Following percutaneous absorption, ciclopirox (administered as a gel) has an elimination half-life of about 5.5 hours.

The metabolic fate of ciclopirox olamine has not been fully elucidated. Ciclopirox appears to be almost completely conjugated with glucuronic acid; about 1-2% of the drug appears to be metabolized to N-desoxyciclopirox and another unidentified metabolite. Preliminary evidence suggests that the drug undergoes tautomerization in vivo and that the tautomer is extensively glucuronidated.

Ciclopirox and its metabolites are excreted rapidly and almost completely in urine; fecal excretion of the drug is negligible. Following topical application of ciclopirox olamine cream to the back of healthy males in one study, most of the systemically absorbed fraction of the dose was excreted in urine within 8 hours after application; after 48 hours, less than 0.01% of the dose was excreted in urine. In another study in healthy men, about 3% of a 5-g dose of ciclopirox gel was excreted in urine within 48 hours after topical application. Following topical application of a 15-g dose of ciclopirox gel in a limited number of men with moderate to severe tinea cruris, about 10% of the dose was excreted in urine within 10 hours after dosing. In addition, the total urinary excretion of ciclopirox following topical application of a 5.2-g (5 mL) dose of ciclopirox shampoo in patients with seborrheic dermatitis of the scalp was less than 0.5% of the administered dose.

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