Penlac

Yes

PENLAC® NAIL LACQUER
(ciclopirox) Topical Solution, 8%

Patient Information and Instructions

Patients should have detailed instructions regarding the use of PENLAC® NAIL LACQUER (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. 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 (ciclopirox) Topical Solution, 8%, as directed by your health care professional.
• PENLAC ®NAIL LACQUER (ciclopirox) Topical Solution, 8%, is for external use only.
• Contact with skin other than skin immediately surrounding the treated nail(s) should be avoided.
• Avoid 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. If you have diabetes or problems with numbness in your toes or fingers, talk to your health care provider before trimming your nails or removing any nail material.
• Inform your 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 PENLAC® NAIL LACQUER (ciclopirox) 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 (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 clear or almost clear toenail.
• 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.

Patient Instructions

1. Before starting treatment, remove any loose nail or nail material using nail clippers or nail files. If you have diabetes or problems with numbness in your toes or fingers, talk to your health care provider before trimming your nails or removing any nail material.

2. Apply PENLAC® NAIL LACQUER (ciclopirox) 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 (ciclopirox) Topical Solution, 8%, daily over the previous coat.

4. Once a week, remove the PENLAC® NAIL LACQUER (ciclopirox) Topical Solution, 8%, with alcohol. Remove as much as possible of the damaged nail using scissors, 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.

• Fungal Nails

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Irritation where Penlac is used.
• Swelling.
• Blisters or sores.
• Oozing or bleeding.
• Burning.
• Redness.

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)-pyridone, with the empirical formula C12H17NO2 and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0]. The chemical structure is:

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 mcg/mL, were obtained for Trichophyton rubrum 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 of T. 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 onychomycosis. 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 of the 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 of Penlac® Nail Lacquer (ciclopirox) 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 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 Penlac® Nail Lacquer (ciclopirox) 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 (ciclopirox) 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 of these findings in nail plates is unknown. Nail bed concentrations were not determined.

Penlac® Nail Lacquer (ciclopirox) Topical Solution, 8%, is contraindicated in individuals who have shown hypersensitivity to any of its components.

Penlac® Nail Lacquer (ciclopirox) Topical Solution, 8%, is not for ophthalmic, oral, or intravaginal use. For use on nails and immediately adjacent skin only.

Patient Information and Instructions

Patients should have detailed instructions regarding the use of Penlac® Nail Lacquer (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. 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 (ciclopirox) Topical Solution, 8%, as directed by your health care professional. • Penlac® Nail Lacquer (ciclopirox) Topical Solution, 8%, is for external use only. • Contact with skin other than skin immediately surrounding the treated nail(s) should be avoided. • Avoid 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 the product. If you have diabetes or problems with numbness in your toes or fingers, talk to your health care provider before trimming your nails or removing any nail material. • Inform your 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 Penlac® Nail Lacquer (ciclopirox) 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 (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 clear or almost clear toenail. • 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.

Patient Instructions

1. Before starting treatment, remove any loose nail or nail material using nail clippers or nail files. If you have diabetes or problems with numbness in your toes or fingers, talk to your health care provider before trimming your nails or removing any nail material. 1. Apply Penlac® Nail Lacquer (ciclopirox) 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. 2. Apply Penlac® Nail Lacquer (ciclopirox) Topical Solution, 8%, daily over the previous coat.

	1. Once a week, remove the Penlac® Nail Lacquer (ciclopirox) Topical Solution, 8%, with alcohol. Remove as much as possible of the damaged nail using scissors, nail clippers, or nail files. 2. 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.

Manufactured for:

Valeant Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA

by:
Sanofi-Aventis Deutschland GmbH

65926 Frankfurt am Main, Germany

Penlac is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©2016 Valeant Pharmaceuticals North America LLC

Rev. 06/2016

9542701

NDC 0187-5180-06
Rx only

Penlac®

Nail

Lacquer

ciclopirox

Topical

Solution, 8%

FOR DERMATOLOGIC USE ONLY
NOT FOR USE IN EYES

One 6.6 mL Bottle

VALEANT

Penlac  ciclopirox solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0187-5180 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ciclopirox (ciclopirox) ciclopirox 80 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength ethyl acetate   isopropyl alcohol   BUTYL ESTER OF METHYL VINYL ETHER/MALEIC ANHYDRIDE COPOLYMER (125000 MW)

Packaging # Item Code Package Description 1 NDC:0187-5180-06 6.6 mL in 1 BOTTLE, WITH APPLICATOR

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021022 05/01/2013

Labeler - Valeant Pharmaceuticals North America LLC (042230623)

Establishment
Name	Address	ID/FEI	Operations
sanofi-aventis Deutschland GmbH		313218430	MANUFACTURE(0187-5180)

Revised: 06/2016   Valeant Pharmaceuticals North America LLC