Prescription Drug Information: CNL8 (Page 2 of 2)

CARCINOGENESIS, MUTAGENESIS and IMPAIRMENT OF FERTILITY

No carcinogenicity study was conducted with CNL8 (ciclopirox topical solution, 8%) nail lacquer 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 CNL8 (ciclopirox topical solution, 8%) nail lacquer) 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 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.

PREGNANCY

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. CNL8 (ciclopirox topical solution, 8%) nail lacquer should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

NURSING MONTHERS

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 CNL8

PEDIATRIC USE

Based on the safety profile in adults, CNL8 (ciclopirox topical solution, 8%) nail lacquer is considered safe for use in children twelve years and older. No clinical trials have been conducted in the pediatric population.

GERIATRIC USE

Based on the safety profile in adults, CNL8 (ciclopirox topical solution, 8%) nail lacquer is considered safe for use in children twelve years and older. No clinical trials have been conducted in the pediatric population.

ADVERSE REATIONS

In the vehicle-controlled clinical trials conducted in the US, 9% (30/327) of patients treated with CNL8 (ciclopirox topical solution, 8%) nail lacquer 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 CNL8 (ciclopirox topical solution, 8%) nail lacquer (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.


four subjects localized allergic contact reactions were observed. In the vehicle-controlled studies, one patient treated with CNL8 (ciclopirox topical solution, 8%) nail lacquer discontinued treatment due to a rash, localized to the palm (causal relation to test material undetermined).
Use of CNL8 (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. Threecpercent (9/281) of subjects treated with CNL8 (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).
To report SUSPECTED ADVERSE REACTIONS contact JSJ Pharmaceuticals at 800-499-4468.

DOSAGE and ADMINISTRATION

CNL8 (ciclopirox topical solution, 8%) nail lacquer should be used as a component of a comprehensive management program for onychomycosis. Removal of the unattached, infected nail, as frequently as monthly, by a health care professional, weekly trimming by the patient, and daily application of the medication are all integral parts of this therapy. Careful consideration of the appropriate nail management program should be given to patients with diabetes (see PRECAUTIONS).

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, or as directed by the health care professional, every seven days after CNL8 (ciclopirox topical solution, 8%) nail lacquer is removed with alcohol. CNL8 (ciclopirox topical solution, 8%) nail lacquer should be applied once daily (preferably at bedtime or eight hours before washing) to all affected nails with the applicator brush provided. CNL8 (ciclopirox topical solution, 8%) nail lacquer should be applied evenly over the entire nail plate.

If possible, CNL8 (ciclopirox topical solution, 8%) nail lacquer 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).

CNL8 (ciclopirox topical solution, 8%) nail lacquer 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

CNL8 nail kit (ciclopirox topical solution, 8%), Swabplus nail lacquer remover, emery board – which contains 3 — 5 ml bottles of CNL8 (ciclopirox topical solution, 8%) nail lacquer (glass bottles with screw caps which are fitted with brushes), 25 — 0.15 ml nail lacquer remover swabs and 1 emery board (NDC 68712-027-01).

CNL8 (ciclopirox topical solution, 8%) nail lacquer, single count 5 ml bottle (NDC 68712-027-03).

Protect from light (e.g., store the bottle in the carton after every use).

CNL8 (ciclopirox topical solution, 8%) nail lacquer should be stored at room temperature between 59° and 86° F (15° and 30° C).

INFORMATION FOR PATIENTS

Patients should have detailed instruction regarding the use of CNL8 (ciclopirox topical solution, 8%) nail lacquer 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 CNL8 (ciclopirox topical solution, 8%) nail lacquer as directed by a health care professional. Avoid contact with eyes and mucous membranes. Contact with skin other than skin immediately surrounding the treated nail(s) should be avoided. CNL8 (ciclopirox topical solution, 8%) nail lacquer is for external use only.

2. CNL8 (ciclopirox topical solution, 8%) nail lacquer should be applied evenly over the entire nail plate and 5 mm of surrounding skin. If possible, CNL8 (ciclopirox topical solution, 8%) nail lacquer 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).

3. Removal of the unattached, infected nail, as frequently as monthly, by a health care professional is needed with the 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.

4. 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 CNL8 (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).

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 productson the treated nails.

10. Avoid use near heat or open flame, because product is flammable.

Manufactured for:

Innocutis Holdings LLC

Charleston, SC 29401

1-800-499-4468

CNL8nails.com

REFERENCES

References:

1. Dittmar W., Lohaus G. 1973. HOE296, A new antimycotic compound with a broad antimicrobial spectrum. Arzneim- Forsch./Drug Res. 23:670-674.

2. Niewerth et al., 1998. Antimicrobial susceptibility testing of dermatophytes: Comparison of the agar macrodilution and broth micro dilution tests. Chemotherapy. 44:31-35.

3. Yang et al., 1997. A new simulation model for studying in vitro topical penetration of antifungaldrugs into hard keratin. J. Mycol. Med. 7:195-98. Gantrez is a registered trademark of GAF Corporation

Rev. 419:00 12/07

Image of outer carton
(click image for full-size original)
CNL8 ciclopirox solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68712-027
Route of Administration TOPICAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CICLOPIROX (CICLOPIROX) CICLOPIROX 2.28 g in 1 mL
Inactive Ingredients
Ingredient Name Strength
ETHYL ACETATE
ISOPROPYL ALCOHOL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:68712-027-01 3 BOTTLE, GLASS (BOTTLE) in 1 CARTON contains a BOTTLE, GLASS (68712-027-03)
1 NDC:68712-027-03 5 mL in 1 BOTTLE, GLASS This package is contained within the CARTON (68712-027-01)
2 NDC:68712-027-03 5 mL in 1 BOTTLE, GLASS None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078270 10/31/2008
Labeler — Innocutis Holdings LLC (071501252)

Revised: 12/2011 Innocutis Holdings LLC

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