Ciclopirox topical solution, 8% is contraindicated in individuals who have shown hypersensitivity to any of its components.
Ciclopirox topical solution, 8% is not for ophthalmic, oral, or intravaginal use. For use on nails and immediately adjacent skin only.
If a reaction suggesting sensitivity or chemical irritation should occur with the use of ciclopirox topical solution, 8% treatment should be discontinued and appropriate therapy instituted.
So far there is no relevant clinical experience with patients with insulin dependent diabetes or who have diabetic neuropathy. The risk of removal of the unattached, infected nail, by the health care professional and trimming by the patient, should be carefully considered before prescribing to patients with a history of insulin dependent diabetes mellitus or diabetic neuropathy.
Information for Patients
Patients should have detailed instructions regarding the use of ciclopirox topical solution, 8% as a component of a comprehensive management program for onychomycosis in order to achieve maximum benefit with the use of this product.
The patient should be told to:
- Use ciclopirox topical solution, 8% as directed by a health care professional. Avoid contact with the eyes and mucous membranes. Contact with skin other than skin immediately surrounding the treated nail(s) should be avoided. Ciclopirox topical solution, 8% is for external use only.
- Ciclopirox topical solution, 8% should be applied evenly over the entire nail plate and 5 mm of surrounding skin. If possible, ciclopirox topical solution, 8% should be applied to the nail bed, hyponychium, and the under surface of the nail plate when it is free of the nail bed (e.g., onycholysis). Contact with the surrounding skin may produce mild, transient irritation (redness).
- Removal of the unattached, infected nail, as frequently as monthly, by a health care professional is needed with use of this medication. Inform a health care professional if they have diabetes or problems with numbness in their toes or fingers for consideration of the appropriate nail management program.
- Inform a health care professional if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing).
- Up to 48 weeks of daily applications with ciclopirox topical solution, 8% and professional removal of the unattached, infected nail, as frequently as monthly, are considered the full treatment needed to achieve a clear or almost clear nail (defined as 10% or less residual nail involvement).
- Six months of therapy with professional removal of the unattached, infected nail may be required before initial improvement of symptoms is noticed.
- A completely clear nail may not be achieved with use of this medication. In clinical studies less than 12% of patients were able to achieve either a completely clear or almost clear toenail.
- Do not use the medication for any disorder other than that for which it is prescribed.
- Do not use nail polish or other nail cosmetic products on the treated nails.
- Avoid use near heat or open flame, because product is flammable.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity study was conducted with ciclopirox topical solution, 8% formulation. A carcinogenicity study of ciclopirox (1% and 5% solutions in polyethylene glycol 400) in female mice dosed topically 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 sites.
In human systemic tolerability studies following daily application (~340 mg of ciclopirox topical solution, 8%) in subjects with distal subungual onychomycosis, the average maximal serum level of ciclopirox was 31 ± 28 ng/mL after two months of once daily applications. This level was 159 times lower than the lowest toxic dose and 115 times lower than the highest nontoxic dose in rats and dogs fed 7.7 and 23.1 mg ciclopirox (as ciclopirox olamine)/kg/day.
The following in vitro genotoxicity tests have been conducted with ciclopirox: evaluation of gene mutation in Ames Salmonella and E. coli assays (negative); chromosome aberration assays in V79 Chinese hamster lung fibroblasts, with and without metabolic activation (positive); gene mutation assay in the HGPRT-test with V79 Chinese hamster lung fibroblasts (negative); unscheduled DNA synthesis in human A549 cells (negative); and BALB/c3T3 cell transformation assay (negative). In an in vivo Chinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at 5,000 mg/kg.
The following in vitro genotoxicity tests were conducted with ciclopirox topical solution, 8%: Ames Salmonella test (negative); unscheduled DNA synthesis in the rat hepatocytes (negative); cell transformation assay in BALB/c3T3 cell assay (positive). The positive response of the lacquer formulation in the BALB/c3T3 test was attributed to its monobutylester of poly[methyl vinyl ether/maleic acid] resin component (Gantrez® ES-435), which also tested positive in this test. The cell transformation assay may have been confounded because of the film-forming nature of the resin. Gantrez® ES-435 tested nonmutagenic in both the in vitro mouse lymphoma forward mutation assay with or without activation and unscheduled DNA synthesis assay in rat hepatocytes.
Oral reproduction studies in rats at doses up to 3.85 mg ciclopirox (as ciclopirox olamine)/kg/ day [equivalent to approximately 1.4 times the potential exposure at the maximum recommended human topical dose (MRHTD)] did not reveal any specific effects on fertility or other reproductive parameters. MRHTD (mg/m2) is based on the assumption of 100% systemic absorption of 27.12 mg ciclopirox (~340 mg ciclopirox topical solution, 8%) that will cover all the fingernails and toenails including 5 mm proximal and lateral fold area plus onycholysis to a maximal extent of 50%.
Teratogenic Effects: Pregnancy Category B
Teratology studies in mice, rats, rabbits, and monkeys at oral doses of up to 77, 23, 23, or 38.5 mg, respectively, of ciclopirox as ciclopirox olamine/kg/day (14, 8, 17, and 28 times MRHTD), or in rats and rabbits receiving topical doses of up to 92.4 and 77 mg/kg/day, respectively (33 and 55 times MRHTD), did not indicate any significant fetal malformations.
There are no adequate or well-controlled studies of topically applied ciclopirox in pregnant women. Ciclopirox topical solution, 8% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether this drug is excreted in human milk. Since many drugs are excreted in human milk, caution should be exercised when ciclopirox topical solution, 8% is administered to a nursing woman.
Based on the safety profile in adults, ciclopirox topical solution, 8% is considered safe for use in children twelve years and older. No clinical trials have been conducted in the pediatric population.
Clinical studies of ciclopirox topical solution, 8% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients.
In the vehicle-controlled clinical trials conducted in the US, 9% (30/327) of patients treated with ciclopirox topical solution, 8% and 7% (23/328) of patients treated with vehicle reported treatment-emergent adverse events (TEAE) considered by the investigator to be causally related to the test material.
The incidence of these adverse events, within each body system, was similar between the treatment groups except for Skin and Appendages: 8% (27/327) and 4% (14/328) of subjects in the ciclopirox and vehicle groups reported at least one adverse event, respectively. The most common were rash-related adverse events: periungual erythema and erythema of the proximal nail fold were reported more frequently in patients treated with ciclopirox topical solution, 8%, (5% [16/327]) than in patients treated with vehicle (1% [3/328]). Other TEAEs thought to be causally related included nail disorders such as shape change, irritation, ingrown toenail, and discoloration.
The incidence of nail disorders was similar between the treatment groups (2% [6/327] in the ciclopirox topical solution, 8% group and 2% [7/328] in the vehicle group). Moreover, application site reactions and/or burning of the skin occurred in 1% of patients treated with ciclopirox topical solution, 8% (3/327) and vehicle (4/328).
A 21-Day Cumulative Irritancy study was conducted under conditions of semi-occlusion. Mild reactions were seen in 46% of patients with the ciclopirox topical solution, 8%, 32% with the vehicle and 2% with the negative control, but all were reactions of mild transient erythema. There was no evidence of allergic contact sensitization for either the ciclopirox topical solution, 8% or the vehicle base. In a separate study of the photosensitization potential of ciclopirox topical solution, 8% in a maximized test design that included the occluded application of sodium lauryl sulfate, no photoallergic reactions were noted. In four subjects localized allergic contact reactions were observed. In the vehicle-controlled studies, one patient treated with ciclopirox topical solution, 8% discontinued treatment due to a rash, localized to the palm (causal relation to test material undetermined).
Use of ciclopirox topical solution, 8% for 48 additional weeks was evaluated in an open-label extension study conducted in patients previously treated in the vehicle-controlled studies. Three percent (9/281) of subjects treated with ciclopirox topical solution, 8% experienced at least one TEAE that the investigator thought was causally related to the test material. Mild rash in the form of periungual erythema (1% [2/281]) and nail disorders (1% [4/281]) were the most frequently reported. Four patients discontinued because of TEAEs. Two of the four had events considered to be related to test material: one patient’s great toenail “broke away” and another had an elevated creatine phosphokinase level on Day 1 (after 48 weeks of treatment with vehicle in the previous vehicle-controlled study).
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