CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`
`21-022
`
`FINAL PRINTED LABELING
`
`Page 1 of 16
`
`ACRUX DDS PTY LTD. et al.
`
`EXHIBIT 1521
`
`IPR Petition for
`
`U.S. Patent No. 7,214,506
`
`

`

`PENLACTM NAIL LACQUER (CICLOPIROX) TOPICAL SOLUTION, 8%
`
`FOR USE ON FINGERNAILS AND TOENAILS AND IMMEDIATELY
`ADJACENT SKIN ONLY
`
`NOT FOR USE IN EYES
`
`CAUTION
`Federal Law Prohibits Dispensing Without Prescription
`
`DESCRIPTION
`
`PENLAC™ NAIL LACQUER ( ciclopirox) Topical Solution, 8%, contains a synthetic
`antifungal agent, ciclopirox. It is intended for topical use on fingernails and toenails and
`immediately adjacent skin.
`
`Each gram of PENLAC™ NAIL LACQUER ( ciclopirox) Topical Solution, 8%, contains
`80 mg ciclopirox in a solution base consisting of ethyl acetate, NF; isopropyl alcohol,
`USP; and butyl monoester of poly[ methylvinyl ether/maleic acid] in isopropyl alcohol.
`Ethyl acetate and isopropyl alcohol are solvents that vaporize after application.
`
`PENLAC™ NAIL LACQUER (ciclopirox) Topical Solution, 8%, is a clear, colorless to
`slightly yellowish solution.
`
`The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)(cid:173)
`pyridinone, with the empirical formula C12H17N02 and a molecular weight of207.27.
`The CAS Registry Number is [29342-05-0]. The chemical structure is:
`
`~0
`
`Page 2 of 16
`
`

`

`CLINICAL PHARMACOLOGY
`
`Microbiology
`
`Mechanism of Action
`The mechanism of action of ciclopirox has been investigated using various in vitro and in
`vivo infection models. One in vitro study suggested that ciclopirox acts by chelation of
`polyvalent cations (fe+3 or Al+3) resulting in the inhibition of the metal-dependent
`enzymes that are responsible for the degradation of peroxides within the fungal cell. The
`clinical significance of this observation is not known.
`
`Activity in vitro and ex vivo
`
`In vitro methodologies employing various broth or solid media with and without
`additional nutrients have been utilized to determine ciclopirox minimum inhibitory
`concentration (MIC) values for the dermatophytic molds (1-2). As a consequence, a
`broad range of MIC values, 1-20 uglmL, were obtained for Trichophyton rub rum and
`Trichophyton mentagrophytes species. Correlation between in vitro MIC results and
`clinical outcome has yet to be established for ciclopirox.
`
`One ex vivo study was conducted evaluating 8% ciclopirox against new and established
`Trichophyton rubrum and Trichophyton mentagrophytes infections in ovine hoof
`material(3). After 10 days of treatment the growth ofT. rubrum and T. mentagrophytes
`in the established infection model was very minimally affected. Elimination of the molds
`from hoof material was not achieved in either the new or established infection models.
`
`Susceptibility testing for Trichophyton rubrum species
`
`In vitro susceptibility testing methods for determining ciclopirox MIC values against the
`dermatophytic molds, including Trichophyton rubrum species, have not been
`standardized or validated. Ciclopirox MIC values will vary depending on the
`susceptibility testing method employed, composition and pH of media and the utilization
`of nutritional supplements. Breakpoints to determine whether clinical isolates of_
`Trichophyton rubrum are susceptible or resistant to ciclopirox have not been established.
`
`Resistance
`
`Studies have not been conducted to evaluate drug resistance development in T. rubrum
`species exposed to 8% ciclopirox topical solution. Studies assessing cross-resistance to
`ciclopirox and other known antifungal agents have not been performed.
`
`Antifungal Drug Interactions
`
`No studies have been conducted to determine whether ciclopirox might reduce the
`effectiveness of systemic antifungal agents for ony~:1omycosis.
`
`2
`
`Page 3 of 16
`
`

`

`Therefore, the concomitant use of 8% ciclopirox topical solution and systemic antifungal
`agents for onychomycosis, is not recommended.
`
`Pharmacokinetics
`
`As demonstrated in pharmacokinetic studies in animals and man, ciclopirox olamine is
`rapidly absorbed after oral administration and completely eliminated in all species via
`feces and urine. Most of the compound is excreted either unchanged or as glucuronide.
`After oral administration of 10 mg of radiolabeled drug (14C-ciclopirox) to healthy
`volunteers, approximately 96% of the radioactivity was excreted renally within 12 hours
`of administration. Ninety-four percent ofthe renally excreted radioactivity was in the
`form of glucuronides. Thus, glucuronidation is the main metabolic pathway of this
`compound.
`
`Systemic absorption of ciclopirox was determined in 5 patients with dermatophytic
`onychomycoses, after application ofPENLAC™ NAIL LACQUER Topical Solution,
`8%, to all 20 digits and adjacent 5 mm of skin once daily for six months. Random serum
`concentrations and 24 hour urinary excretion of ciclopirox were determined at two weeks
`and at 1, 2, 4 and 6 months after initiation oftreatment 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 PENLAC™ NAIL LACQUER Topical
`Solution, 8%, 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 (Loprox® Cream, 0.77%).
`
`The penetration of the PENLAC™ NAIL LACQUER Topical Solution, 8%, 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 ofthese findings in nail plates is unknown. Nail bed
`concentrations were not determined.
`
`INDICATIONS AND USAGE
`
`(To understand fully the indication for this product, please read the entire
`INDICATION AND USAGE section of the labeling.)
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, as a component of a
`comprehensive management program, is indicated as topical treatment in
`immunocompetent patients with mild to moderate onychomycosis of fingernails and
`
`3
`
`Page 4 of 16
`
`

`

`toenails without lunula involvement, due to Trichophyton rubrum. The comprehensive
`management program includes removal of the unattached, infected nails as frequently as
`monthly, by a health care professional who has special competence in the diagnosis and
`treatment of nail disorders, including minor nail procedures.
`
`• No studies have been conducted to determine whether ciclopirox might reduce the
`effectiveness of systemic antifungal agents for onychomycosis. Therefore, the
`concomitant use of 8% ciclopirox topical solution and systemic antifungal agents for
`onychomycosis, is not recommended.
`·
`
`• PENLAC™ NAIL LACQUER Topical Solution, 8%, should be used only under
`medical supervision as described above.
`
`• The effectiveness and safety ofPENLAC™ NAIL LACQUER Topical Solution, 8%,
`in the following populations has not been studied. The clinical trials with use of
`PENLAC™ NAIL LACQUER Topical Solution, 8%, 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 PENLAC™ NAIL LACQUER Topical Solution,
`8%, daily for greater than 48 weeks have not been established.
`
`Clinical Trials Data:
`
`The results of use of PENLAC™ NAIL LACQUER Topical Solution, 8%, in treatment
`of onychomycosis of the toenail without lunula involvement were obtained from two
`double-blind, placebo-controlled studies conducted in the US. In these studies, patients
`with onychomycosis of the great toenails without lunula involvement were treated with
`ciclopirox topical solution, 8%, in conjunction with monthly removal of the unattached,
`infected toenail by the investigator. PENLAC™ NAIL LACQUER Topical Solm:ion,
`8%, was applied for 48 weeks. At baseline, patients had 20-65% involvement of the
`target great toenail plate. Statistical significance was demonstrated in one of two studies
`for the endpoint "complete cure" (clear nail and negative mycology), and in two studies
`for the endpoint "almost clear" (slO% nail involvement and negative mycology) at the
`end of study. These results are presented below.
`
`4
`
`Page 5 of 16
`
`

`

`At Week 48 (olus Last Observation Carried Forward) for the Intent-to-Treat (ITT) Population
`Study 312
`Study 313
`
`Active
`
`Vehicle
`
`Active
`
`Vehicle
`
`Complete Cure*
`61110 (5.5%)
`Almost Clear**
`71107 (6.5%)
`Negative Mycology
`30/I05 (29%)
`AI owe•••
`* Clear nail and negative mycology
`•• Sl 0% nail involvement and negative mycology
`••• Negative KOH and negative culture
`
`1/109 (0.9%)
`1/108 (0.9%)
`121106 (11%)
`
`10/118 _(8.5o/o}
`14/116 _(12%_}_
`41/115 (36%)
`
`0/117 (0%)
`IIII5 (0.9%_}_
`10/114 (9%)
`
`The summary of reported patient outcomes for the ITT population at 12 weeks following
`the end of treatment are presented below. Note that post-treatment efficacy assessments
`were scheduled only for patients who achieved a complete cure.
`
`Post-treatment Week 12 Data for Patients Who Achieved Complete Cure at Week 48
`Study 3I2
`Study 313
`Active
`Active
`
`Vehicle
`
`Vehicle
`
`Number of Treated Patients
`Complete Cure at Week 48
`Post-treatment Week I2 Outcomes:
`Patients Missing All Week I2 Assessments
`Patients with Week 12 Assessments
`Complete Cure
`Almost Clear
`Negative Mycology
`
`112
`6
`
`2
`4
`3
`2*
`3
`
`Ill
`I
`
`0
`I
`I
`I
`1
`
`119
`10
`
`2
`8
`4
`t•
`5
`
`118
`0
`
`0
`0
`0
`0
`0
`
`*Four patients (from studies 312 and 313) who were completely cured did not have post(cid:173)
`treatment Week 12 planimetry data.
`
`CONTRAINDICATIONS
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, is contraindicated in individuals
`who have shown hypersensitivity to any of its components.
`
`WARNINGS
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, is not for ophthalmic, oral, or
`intravaginal use. For use on nails and immediately adjacent skin only.
`
`5
`
`Page 6 of 16
`
`

`

`PRECAUTIONS
`
`If a reaction suggesting sensitivity or chemical irritation should occur with the use of
`PENLACTM NAIL LACQUER 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 PENLAC"M NAIL
`LACQUER 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:
`
`1. Use PENLAC™ NAIL LACQUER Topical Solution, 8%, as directed by a health
`care professional. A void contact with the eyes and mucous membranes. Contact
`with skin other than skin immediately surrounding the treated nail(s) should be
`avoided. PENLAC™ NAIL LACQUER Topical Solution, 8%, is for external use
`only.
`
`2.
`
`3.
`
`4.
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, should be applied evenly
`over the entire nail plate and 5 mm of surrounding skin. If possible, PENLAC™
`NAIL LACQUER 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 the area of application shows signs of increased
`irritation (redness, itching, burning, blistering, swelling, oozing).
`
`5. Up to 48 weeks of daily applications with PENLAC™ NAIL LACQUER 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).
`
`6
`
`Page 7 of 16
`
`

`

`6.
`
`Six months of therapy with professional removal of the unattached, infected nail
`may be required before initial improvement of symptoms is noticed.
`
`7. 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.
`
`8. Do not use the medication for any disorder other than that for which it is prescribed.
`
`9. Do not use nail polish or other nail cosmetic products on the treated nails.
`
`10. Avoid use near heat or open flame, because product is flammable.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`
`No carcinogenicity study was conducted with PENLAC™ NAIL LACQUER 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
`PENLAC™ NAIL LACQUER Topical Solution, 8%) in subjects with distal subungual
`onychomycosis, the average maximal serum level of ciclopirox was 31±28 nglmL 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)/kglday.
`
`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 a5say (negative). In an in vivo Chinese hamster bone
`marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at 5,000
`mglkg.
`
`The following in vitro genotoxicity tests were conducted with PENLAC™ NAIL
`LACQUER 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 butyl monoester ofpoly[methylvinyl ether/maleic acid] resin
`component (Gantrez~S-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
`
`7
`
`Page 8 of 16
`
`

`

`forward mutation assay with or without activation and unscheduled DNA .synthesis assay
`in rnt hepatocytes.
`
`Oral reproduction studies in rats at doses up to 3.85 mg ciclopirox (as ciclopirox
`olamine)lkg/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!rrl} is based on the
`assumption of 100% systemic absorption of 27.12 mg ciclopirox (-340 mg PENLAC™
`NAIL LACQUER 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%.
`
`Pregnancy:
`
`Teratogenic effects: Pregnancy Category B
`
`Terntology studies in mice, rats, rabbits, and monkeys at ornl doses of up to 77, 23, 23, or
`38.5 mg, respectively, of ciclopirox as ciclopirox olaminelkg/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. PENLACTM NAIL LACQUER Topical Solution, 8%, should be used
`during pregnancy only if the potential benefit justifies the potential risk to the fetus.
`
`Nursing Mothers:
`
`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 PENLAC™ NAIL
`LACQUER Topical Solution, 8%, is administered to a nursing woman.
`
`Pediatric Use:
`
`Safety and effectiveness in pediatric patients have not been established.
`
`Geriatric Use:
`
`Clinical studies of PENLACTM NAIL LACQUER 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.
`
`8
`
`Page 9 of 16
`
`

`

`ADVERSE REACTIONS
`
`In the vehicle-controlled clinical trials conducted in the US, 9% (30/327) of patients
`treated with PENLAC™ NAIL LACQUER Topical Solution and 7% (23/328) ofpatients
`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 rasl:rrelated adverse events: periungual erythema
`and erythema of the proximal nail fold were reported more frequently in patients treated
`with PENLAC™ NAIL LACQUER Topical Solution (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 PENLAC™ NAIL LACQUER Topical Solution 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 PENLAC™ NAIL LACQUER Topical Solution (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 PENLAC™ NAIL LACQUER
`Topical Solution, 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 PENLAC™ NAIL LACQUER Topical Solution, 8%, or the
`vehicle base. In the vehicle-controlled studies, one patient treated with PENLAC™
`NAIL LACQUER Topical Solution, 8%, discontinued treatment due to a rash, localized
`to the palm (causal relation to test material undetermined).
`
`Use of PENLAC™ NAIL LACQUER 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 PENbA.C™
`NAIL LACQUER 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 ofTEAEs. 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).
`
`DOSAGE AND ADMINISTRATION
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, should be used as a component of a
`comprehensive management program for onychomycosis. Removal of the unattached,
`
`9
`
`Page 10 of 16
`
`

`

`infected nail, as frequently as monthly, by a health care professional, wee~y trimming by
`the patient, and daily application of the medication are all integral parts of this therapy.
`
`Nail Care By Health Care Professionals:
`
`Removal of the unattached, infected nail, as frequently as monthly, trimming of
`onycholytic nail, and filing of excess horny material should be performed by
`professionals trained in treatment of nail disorders.
`
`Nail Care By Patient:
`
`Patients should file away (with emery board) loose nail material and trim nails, as
`required, every seven days after PENLAC™ NAIL LACQUER Topical Solution, 8%, is
`removed with alcohol.
`
`PENLAC™ NAIL LACQUER Topical Solution, 8%, should be applied once daily
`(preferably at bedtime or eight hours before washing) to all affected nails with the
`applicator brush provided. The PENLAC™ NAIL LACQUER Topical Solution, 8%,
`should be applied evenly over the entire nail plate.
`
`If possible, PENLAC™ NAIL LACQUER 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).
`
`The PENLAC™ NAIL LACQUER Topical Solution, 8%, should not be removed on a
`daily basis. Daily applications should be made over the previous coat and removed with
`alcohol every seven days. This cycle should be repeated throughout the duration of
`therapy.
`
`HOW SUPPLIED
`
`PENLAC™ NAIL LACQUER (ciclopirox) Topical Solution, 8%, is supplied in 3.3 mL
`(NDC 0088-2200-13) glass bottles with screw caps which are fitted with brushes.
`
`Protect from light (e.g., store the bottle in the carton after every use).
`
`PENLAC™ NAIL LACQUER ( ciclopirox) Topical Solution, 8%, should be stored at
`room temperature between 59° and 86° F (15° and 30°C).
`
`CAUTION: Flammable. Keep away from heat and flame.
`
`RxONLY
`
`References:
`1. Dittmar W., Lohaus G. 1973. HOE296, A new antimycotic compound with a broad
`antimicrobial spectrum. Arzneim-Forsch/Drug Res. 23:670-674.
`
`10
`
`Page 11 of 16
`
`

`

`2. Niewerth et. a/., 1998. Antimicrobial susceptibility testing of dermatophytes:
`Comparison of the agar macrodilution and broth micro dilution tests. Chemotherapy.
`44:31-35.
`
`3. Yang et. a/. 1997. A new simulation model for studying in vitro topical penetration of
`antifungal drugs into hard keratin. J. Mycol. Med. 7:195-98.
`
`---X--------------------------------------------------------------------------------~----------------------------------
`
`PENLACTM NAIL LACQUER (ciclopirox)
`Topical Solution, 8%
`
`Patient Information and Instructions
`
`Patients should have detailed instructions regarding the use of PENLACTM NAIL
`LACQUER 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. Discuss your treatment plan with your health care professional for
`regular removal of the unattached, infected nail.
`
`Before using this medication, tell your doctor if you:
`
`• Are pregnant or nursing
`• Are an insulin dependent diabetic or have diabetic neuropathy
`• Have a history of immunosuppression
`• Are immunocompromised (e.g., received an organ transplant, etc.)
`• Require medication to control epilepsy
`• Use or require topical corticosteroids on a repeated monthly basis
`• Use steroid inhalers on a regular basis
`
`Patient Information:
`
`• Use PENLAC™ NAIL LACQUER Topical Solution, 8%, as directed by your
`health care professional.
`• PENLAC™ NAIL LACQUER Topical Solution, 8%, is for external use only.
`• Contact with skin other than skin immediately surrounding the treated nail(s)
`should be avoided.
`• A void contact with the eyes and mucous membranes.
`• Removal of the unattached, infected nail, as frequently as monthly, by your health
`care professional-is needed with use of this medication to obtain maximal benefit
`with use of this product.
`Inform your health ca:re professional if the area of application shows signs of
`increased irritation (redness, itching, burning, blistering, swelling, oozing).
`
`•
`
`11
`
`Page 12 of 16
`
`

`

`• Up to 48 weeks of daily applications with PENLAC™ NAIL LAC.QUER Topical
`Solution, 8%, and professional removal, as frequently as monthly, of the
`unattached, infected nail are considered the full treatment time to achieve a clear
`or almost clear nail (defmed 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 clear or
`almost clear toenail.
`• Do not use nail polish or other nail cosmetic products on the treated nails.
`• A void use near heat or open flame, because product is flammable.
`
`Patient Instructions
`
`1.
`
`Before starting treatment, remove
`any loose nail or nail material
`using nail clippers or nail files.
`
`2. Apply PENLAC™ NAIL
`LACQUER Topical Solution, 8%,
`once daily (preferably at bedtime)
`to all affected nails with the
`.applicator brush provided. Apply
`the lacquer evenly over the entire
`nail. Where possible, nail lacquer
`should also be applied to the
`underside of the nail and to the
`skin beneath it. Allow lacquer to
`dry (approximately 30 seconds)
`before putting on socks or
`stockings. After applying
`medication, wait 8 hours before
`taking a bath or shower.
`
`3.
`
`. Apply PENLAC™ NAIL
`LACQUER Topical Solution, 8%,
`daily over the previous coat.
`
`12
`
`Page 13 of 16
`
`

`

`4. Once a week, remoye the
`PENLAC™ NAIL LACQUER
`Topical Solution, 8%, with alcohol.
`Remove as much as possible of the
`damaged nail using nail clippers,
`or nail files.
`
`5.
`
`Repeat process (steps 2 through 4).
`
`Please Note:
`
`1. To prevent screw cap from sticking to
`the bottle, do not allow solution to get
`into the bottle threads.
`
`2. To prevent the solution from drying
`out, bottle should be closed tightly after
`every use.
`
`3. To protect from light, replace bottle
`into carton after each use.
`
`Mfdby:
`A ventis Pharma Deutschland GmbH
`D-65926 Frankfurt am Main
`Germany
`
`Mfd. for:
`A ventis Pharmaceuticals, Inc.
`10236 Marion Park Drive
`Kansas City, MO 64137
`
`Made in Germany
`
`Marketed by:
`DERMIK LABORATORIES, INC,
`Collegeville, P A 19426
`
`Prescribing Informatio~ as of December 1999
`
`13
`
`Page 14 of 16
`
`

`

`dlr3
`
`..,
`%8 'DO!lDJOS p:>!dO.L
`XOJidOj:JI:I
`
`.J~DOOlrJ fi8N
`IWe·e "':1qu~d
`
`£L~:KIN
`
`Penlac"' Nail Lacquer
`cicloplrox
`
`Each ...... of Pen!M:"' lUI
`L8cquer (ctcloplroll) Topical
`Sc*ltlon, 8%, contalna:
`80 mg clcloptnlx In • aolutlon
`11.- con.l8llng of ethyl
`
`- · NF; iaopnlpyl
`alcohol, USP; and butJI
`_ . . .o f poly[melhyl(cid:173)
`....,. ...... ,llllllelc ackl[ In
`Isopropyl McohoL
`uau.l Douge: Apply to the
`affected nails once daly. See
`Insert for lui pnoscribing infor(cid:173)
`mation.
`WARNING: Keep this and al
`medication out of the reac11 of
`cllldren.
`
`~ This pac.._ is
`
`not ell*! rwsistant.
`Storeatnoom._,.....
`'--'!Ill" anciiii"F (15"
`anci30"C).
`Protect bottle from lghl
`cautlon:~.Keep
`away from heat and .......
`
`Mid. by: Aventls Phanna
`DeutscNand GmbH
`D-65926 Frankfurt am Main
`Gennany
`Mid. lor:
`Aventis Pharmaceuticals Inc.
`10236 Marion Park Drill8
`Kanlas City, MO 64137
`Made in Germany
`Marketed by:
`DERMIK LABORAlORJES. INC.
`Collegeyile, PA 19426
`
`NDC 0088-2200-13
`
`Penlac™
`Nail Lacquer
`ciclopirox
`Topical Solution, 8%
`
`NDC 0088-2200-13
`
`Penlac™
`Nail Lacquer
`ciclopirox
`Topical Solution, 8%
`
`3.3ml
`
`3.3ml
`
`For dermatologic
`.... only
`Not for use in ev•
`Rxonly
`
`1Botle
`
`1aollle
`
`Q)
`"0
`0
`(.)
`
`uo
`a.. a..
`:::>u..
`
`Penla.C 3.3ml
`Nail Lacquer
`ciclopirox
`Topiool Sol ....... I%
`
`Pmlloc:"' Nllll Uo:iquer
`
`tidopirol TDplclol--
`
`lot
`
`Exp.
`
`Mtd.by.-(cid:173)
`-GmbH
`Mid. fer.
`~.---h:.
`KoMu Cily, MO 84137
`
`Page 15 of 16
`
`

`

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`
`-
`
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`·- . -.. ~-
`
`•• •. ·'":-o.-: •• ....,._
`
`..
`
`..
`
`.
`
`_B_ Page(s) Redacted
`
`-
`
`-- .-
`
`-.... -
`
`--
`
`rf-\ft
`
`.· - .
`.. -- .
`
`-
`
`-
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`..
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`Page 16 of 16
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