lacquer) should be used only under medical supervision as described above. the effectiveness and safety of ciclopirox topical solution, 8% (nail lacquer) in the following populations has not been studied. the clinical trials with use of ciclopirox topical solution, 8% (nail lacquer) excluded patients who: were pregnant or nursing, planned to become pregnant, had a history of immunosuppression (e.g., extensive, persistent, or unusual distribution of dermatomycoses, extensive seborrheic dermatitis, recent or recurring herpes zoster, or persistent herpes simplex), were hiv seropositive, received organ transplant, required medication to control epilepsy, were insulin dependent diabetics or had diabetic neuropathy. patients with severe plantar (moccasin) tinea pedis were also excluded. the safety and efficacy of using ciclopirox topical solution, 8% (nail lacquer) daily for greater than 48 weeks have not been established.

and discoloration. the incidence of nail disorders was similar between the treatment groups (2% [6/327] in the ciclopirox topical solution, 8% (nail lacquer) 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% (nail lacquer) (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% (nail lacquer), 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% (nail lacquer), or the vehicle base. in a separate study of the photosensitization potential of ciclopirox topical solution, 8% (nail lacquer) 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% (nail lacquer) discontinued treatment due to a rash, localized to the palm (causal relation to test material undetermined). use of ciclopirox topical solution, 8% (nail lacquer) 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% (nail lacquer) 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).

initiation of treatment and 4 weeks post-treatment. in this study, ciclopirox serum levels ranged from 12-80 ng/ml. based on urinary data, mean absorption of ciclopirox from the dosage form was <5% of the applied dose. one month after cessation of treatment, serum and urine levels of ciclopirox were below the limit of detection. in two vehicle-controlled trials, patients applied ciclopirox topical solution, 8% (nail lacquer) to all toenails and affected fingernails. out of a total of 66 randomly selected patients on active treatment, 24 had detectable serum ciclopirox concentrations at some point during the dosing interval (range 10.0-24.6 ng/ml). it should be noted that eleven of these 24 patients took concomitant medication containing ciclopirox as ciclopirox olamine cream 0.77%. the penetration of the ciclopirox topical solution, 8% (nail lacquer) was evaluated in an in vitro investigation. radiolabeled ciclopirox applied once to onychomycotic toenails that were avulsed demonstrated penetration up to a depth of approximately 0.4 mm. as expected, nail plate concentrations decreased as a function of nail depth. the clinical significance of these findings in nail plates is unknown. nail bed concentrations were not determined.

ene 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 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% (nail lacquer): 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 butyl monoester of poly[methylvinyl 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/m 2 ) is based on the assumption of 100% systemic absorption of 27.12 mg ciclopirox (~340 mg ciclopirox topical solution, 8% ((nail lacquer)) that will cover all the fingernails and toenails including 5 mm proximal and lateral fold area plus onycholysis to a maximal extent of 50%.

sient 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 you have diabetes or problems with numbness in your 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% (nail lacquer) 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.