CICLOPIROX gel

1. No Title 1572549769
2. Ciclopirox Gel 0.77%
3. Description:
4. Clinical Pharmacology:
5. Indications And Usage:
6. Contraindications:
7. Warnings:
8. Precautions:
9. Adverse Reactions:
10. Dosage And Administration:
11. How Supplied:
12. Package Label Principal Display Panel 30 Gram Container
13. Package Label Principal Display Panel 30 Gram Carton
14. For Dermatologic Use Only.
15. Clinical Pharmacology
16. Indications And Usage
17. Contraindications
18. Warnings
19. Precautions
20. Adverse Reactions
21. Dosage And Administration
22. How Supplied
23. Package/label Display Panel
24. Ciclopirox Gel, 0.77%
25. Description
26. Clinical Pharmacology
27. Indications And Usage
28. Contraindications
29. Warnings
30. Precautions
31. Adverse Reactions
32. Dosage And Administration
33. How Supplied
34. Principal Display Panel - Carton

No Title 1572549769 ⮝

NDC 47781-530-84

Ciclopirox Gel

0.77%

45 g
Rx Only

CICLOPIROX ciclopirox gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:47781-530 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Ciclopirox (UNII: 19W019ZDRJ) (Ciclopirox - UNII:19W019ZDRJ) Ciclopirox 7.7 mg in 1 g

Inactive Ingredients Ingredient Name Strength Water (UNII: 059QF0KO0R) Isopropyl Alcohol (UNII: ND2M416302) Octyldodecanol (UNII: 461N1O614Y) Peg/Ppg-18/18 Dimethicone (UNII: 9H0AO7T794) Carbomer Homopolymer Type C (Allyl Pentaerythritol Crosslinked) (UNII: 4Q93RCW27E) Sodium Hydroxide (UNII: 55X04QC32I) Docusate Sodium (UNII: F05Q2T2JA0)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47781-530-73 1 in 1 CARTON 02/14/2017 09/01/2021 1 30 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:47781-530-84 1 in 1 CARTON 02/14/2017 09/01/2021 2 45 g in 1 TUBE; Type 0: Not a Combination Product 3 NDC:47781-530-85 1 in 1 CARTON 02/14/2017 09/01/2021 3 100 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020519 02/14/2017 09/01/2021

Labeler - Alvogen Inc. (008057330)

Registrant - Alvogen Group Inc. (963294397)

Revised: 6/2019 Document Id: ae057112-f3cd-aee4-e64e-c8b24bc7957a 34391-3 Set id: b145e01c-2760-8665-41a8-aedbfa7a39e6 Version: 6 Effective Time: 20190630 Alvogen Inc.

Ciclopirox Gel 0.77%  ⮝

FOR DERMATOLOGIC USE ONLY.
Rx only
NOT FOR USE IN EYES.

Description:  ⮝

Ciclopirox Gel 0.77% contains a synthetic antifungal agent, ciclopirox. It is intended for topical dermatologic use only.

Each gram of ciclopirox gel 0.77% contains 7.70 mg of ciclopirox in a gel consisting of purified water, isopropyl alcohol, octyldodecanol, dimethicone copolyol 190, carbomer 980, sodium hydroxide, and docusate sodium.

Ciclopirox gel 0.77% is a white, slightly fluid gel.

The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone, with the empirical formula C12H17NO2 and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0].The chemical structure is:

Clinical Pharmacology:  ⮝

Mechanism of Action: Ciclopirox acts by chelation of polyvalent cations (Fe3+ or Al3+) resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell. In vitro studies showed that ciclopirox inhibited the formation of 5-lipoxygenase inflammatory mediators (5-HETE and LTB4) and also inhibited PGE2 release in a cell culture model. In vivo, ciclopirox inhibited inflammation in an arachidonic acid-induced murine ear edema model. The clinical significance of these findings is unknown.

Pharmacokinetics: A comparative study of the pharmacokinetics of ciclopirox gel and ciclopirox cream (ciclopirox olamine) 0.77% in 18 healthy males indicated that systemic absorption of ciclopirox from ciclopirox gel was higher than that of ciclopirox cream. A 5 gm dose of ciclopirox gel produced a mean ( SD) peak serum concentration of 25.02 ( 20.6) ng/mL total ciclopirox and 5 gm of ciclopirox cream produced 18.62 ( 13.56) ng/mL total ciclopirox. Approximately 3% of the applied ciclopirox was excreted in the urine within 48 hours after application, with a renal elimination half-life of about 5.5 hours. In a study of ciclopirox gel, 16 men with moderate to severe tinea cruris applied approximately 15 grams/day of the gel for 14.5 days. The mean ( SD) dose-normalized values of Cmax for total ciclopirox in serum were 100 ( 42) ng/mL on day 1 and 238 ( 144) ng/mL on Day 15. During the 10 hours after dosing on Day 1, approximately 10% of the administered dose was excreted in the urine.

Microbiology: Ciclopirox is a hydroxypyridinone antifungal agent that inhibits the growth of pathogenic dermatophytes. Ciclopirox has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

Indications And Usage:  ⮝

Superficial Dermotophyte Infections - Ciclopirox gel 0.77% is indicated for the topical treatment of interdigital tinea pedis and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum. Seborrheic Dermatitis - Ciclopirox gel 0.77% is indicated for the topical treatment of seborrheic dermatitis of the scalp.

Contraindications:  ⮝

Ciclopirox gel 0.77% is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings:  ⮝

Ciclopirox gel 0.77% is not for ophthalmic, oral, or intravaginal use. Keep out of reach of children.

Precautions:  ⮝

If a reaction suggesting sensitivity or chemical irritation should occur with the use of ciclopirox gel 0.77%, treatment should be discontinued and appropriate therapy instituted. A transient burning sensation may occur, especially after application to sensitive areas. Avoid contact with eyes. Efficacy of ciclopirox gel 0.77% in immunosuppressed individuals has not been studied. Seborrheic dermatitis in association with acne, atopic dermatitis, Parkinsonism, psoriasis and rosacea has not been studied with ciclopirox gel 0.77%. Efficacy in the treatment of plantar and vesicular types of tinea pedis has not been established.

Information for Patients

The patient should be told the following:

1.

Use ciclopirox gel 0.77% as directed by the physician. Avoid contact with the eyes and mucous membranes. Ciclopirox gel 0.77% is for external use only.

2.

Use the medication for fungal infections for the full treatment time even though symptoms may have improved, and notify the physician if there is no improvement after four weeks.

3.

A transient burning/stinging sensation may be felt. This may occur in approximately 15% to 20% of cases, when ciclopirox gel 0.77% is used to treat seborrheic dermatitis of the scalp.

4.

Inform the physician if the area of application shows signs of increased irritation or possible sensitization (redness with itching, burning, blistering, swelling and/or oozing).

5.

Avoid the use of occlusive dressings.

6.

Do not use this medication for any disorder other than that for which it is prescribed.

Carcinogenesis, Mutagenesis, Impairment of Fertility: A carcinogenicity study of ciclopirox (1% and 5% solutions in polyethylene glycol 400) in female mice dosed cutaneously 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 site. The following battery of in vitro genotoxicity tests was conducted with ciclopirox: evaluation of gene mutation in the Ames Salmonella and E. coli assays (negative); chromosome aberration assays in V79 Chinese hamster cells, with and without metabolic activation (positive); gene mutation assays in the in the HGPRT-test with V79 Chinese hamster cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA synthesis assay in A549 human cells) (negative). An in vitro cell transformation assay in BALB/c 3T3 cells was negative for cell transformation. In an in vivo Chinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at 5000 mg/kg.

Pregnancy - Teratogenic effects: Pregnancy Category B. Reproduction studies of ciclopirox revealed no significant evidence of impaired fertility in rats exposed orally up to 5 mg/kg body weight (approximately 5 times the maximum recommended topical human dose based on surface area). No fetotoxicity was shown due to ciclopirox in the mouse, rat, rabbit, and monkey at oral doses up to 100, 30, 30, and 50 mg/kg body weight, respectively (approximately 37.5, 30, 44, and 77 times the maximum recommended topical human dose based on surface area). By the dermal route of administration, no fetotoxicity was shown due to ciclopirox in the rat and rabbit at doses up to 120 and 100 mg/kg body weight, respectively (approximately 121 and 147 times, respectively, the maximum recommended topical human dose based on surface area). There are no adequate or well-controlled studies of topically applied ciclopirox in pregnant women. Ciclopirox gel 0.77% 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 ciclopirox gel 0.77% is administered to a nursing woman.

Pediatric Use: The efficacy and safety of ciclopirox gel 0.77% in pediatric patients below the age of 16 years have not been established.

Adverse Reactions:  ⮝

In clinical trials, 140 (39%) of 359 subjects treated with ciclopirox gel 0.77% reported adverse experiences, irrespective of relationship to test materials, which resulted in 8 subjects discontinuing treatment. The most frequent experience reported was skin burning sensation upon application, which occurred in approximately 34% of seborrheic dermatitis patients and 7% of tinea pedis patients. Adverse experiences occurring between 1% to 5% were contact dermatitis and pruritus. Other reactions that occurred in less than 1% included dry skin, acne, rash, alopecia, pain upon application, eye pain, and facial edema.

Dosage And Administration:  ⮝

Superficial Dermotophyte Infections - Gently massage ciclopirox gel 0.77% into the affected areas and surrounding skin twice daily, in the morning and evening immediately after cleaning or washing the areas to be treated. Interdigital tinea pedis and tinea corporis should be treated for four weeks. If a patient shows no clinical improvement after four weeks of treatment, the diagnosis should be reviewed. Seborrheic Dermatitis of the Scalp -Apply ciclopirox gel 0.77% to affected scalp areas twice daily, in the morning and evening for four weeks. Clinical improvement usually occurs within the first week with continuing resolution of signs and symptoms through the fourth week of treatment. If a patient shows no clinical improvement after four weeks of treatment, the diagnosis should be reviewed.

How Supplied:  ⮝

Ciclopirox Gel 0.77% is supplied in:

NDC 0168-0407-30 30 gram tube

NDC 0168-0407-46 45 gram tube

NDC 0168-0407-99 100 gram tube

Store between 15 -30 C (59 -86 F).

Fougera
PHARMACEUTICALS INC.
E. FOUGERA & CO.
A division of Fougera Pharmaceuticals Inc.
Melville, New York 11747

I2407D
R10/13
#150

Package Label Principal Display Panel 30 Gram Container  ⮝

NDC 0168-0407-30

Fougera

CICLOPIROX GEL 0.77%

FOR DERMATOLOGIC USE ONLY.

NOT FOR USE IN EYES.

Rx only

NET WT 30 grams

Package Label Principal Display Panel 30 Gram Carton  ⮝

NDC 0168-0407-30

Fougera

Rx only

CICLOPIROX GEL 0.77%

FOR DERMATOLOGIC USE ONLY. NOT FOR USE IN EYES.

NET WT 30 grams

CICLOPIROX ciclopirox gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0168-0407 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CICLOPIROX (UNII: 19W019ZDRJ) (CICLOPIROX - UNII:19W019ZDRJ) CICLOPIROX 7.70 mg in 1 g

Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R) ISOPROPYL ALCOHOL (UNII: ND2M416302) OCTYLDODECANOL (UNII: 461N1O614Y) PEG/PPG-18/18 DIMETHICONE (UNII: 9H0AO7T794) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E) SODIUM HYDROXIDE (UNII: 55X04QC32I) DOCUSATE SODIUM (UNII: F05Q2T2JA0)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0168-0407-30 30 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:0168-0407-46 45 g in 1 TUBE; Type 0: Not a Combination Product 3 NDC:0168-0407-99 100 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077896 06/10/2008

Labeler - E. Fougera & Co. a division of Fougera Pharmaceuticals Inc. (043838424)

Revised: 10/2013 Document Id: 0c2acee6-0de3-4a80-9483-c45c8506e504 34391-3 Set id: 88324009-d5cc-4982-be3e-058e0436f608 Version: 6 Effective Time: 20131015 E. Fougera & Co. a division of Fougera Pharmaceuticals Inc.

For Dermatologic Use Only.  ⮝

NOT FOR USE IN EYES.

Rx Only

Clinical Pharmacology  ⮝

Mechanism of Action

Ciclopirox is a hydroxypyridone antifungal agent although the relevance of this property for the indication of seborrheic dermatitis is not known. Ciclopirox acts by chelation of polyvalent cations (Fe3+ or Al3+), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

Pharmacokinetics

A comparative study of the pharmacokinetics of ciclopirox gel and ciclopirox cream (ciclopirox olamine) 0.77% in 18 healthy males indicated that systemic absorption of ciclopirox from ciclopirox gel was higher than that of ciclopirox cream. A 5 gm dose of ciclopirox gel produced a mean ( SD) peak serum concentration of 25.02 ( 20.6) ng/mL total ciclopirox and 5 gm of ciclopirox cream produced 18.62 ( 13.56) ng/mL total ciclopirox. Approximately 3% of the applied ciclopirox was excreted in the urine within 48 hours after application, with a renal elimination half-life of about 5.5 hours.

In a study of ciclopirox gel, 16 men with moderate to severe tinea cruris applied approximately 15 grams/day of the gel for 14.5 days. The mean ( SD) dose- normalized values of Cmax for total ciclopirox in serum were 100 ( 42) ng/mL on Day 1 and 238 ( 144) ng/mL on Day 15. During the 10 hours after dosing on Day 1, approximately 10% of the administered dose was excreted in the urine.

Microbiology

Ciclopirox is a hydroxypyridinone antifungal agent that inhibits the growth of pathogenic dermatophytes. Ciclopirox has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum

Indications And Usage  ⮝

Superficial Dermatophyte Infections

Ciclopirox gel is indicated for the topical treatment of interdigital tinea pedis and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum.

Seborrheic Dermatitis

Ciclopirox gel is indicated for the topical treatment of seborrheic dermatitis of the scalp.

Contraindications  ⮝

Ciclopirox gel is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings  ⮝

Ciclopirox gel is not for ophthalmic, oral, or intravaginal use.

Keep out of reach of children.

Precautions  ⮝

If a reaction suggesting sensitivity or chemical irritation should occur with the use of ciclopirox gel, treatment should be discontinued and appropriate therapy instituted. A transient burning sensation may occur, especially after application to sensitive areas. Avoid contact with eyes. Efficacy of ciclopirox gel in immunosuppressed individuals has not been studied. Seborrheic dermatitis in association with acne, atopic dermatitis, Parkinsonism, psoriasis and rosacea has not been studied with ciclopirox gel. Efficacy in the treatment of plantar and vesicular types of tinea pedis has not been established.

Information for Patients

The patient should be told the following:

1.

Use ciclopirox gel as directed by the physician. Avoid contact with the eyes and mucous membranes. Ciclopirox gel is for external use only.

2.

Use the medication for fungal infections for the full treatment time even though symptoms may have improved, and notify the physician if there is no improvement after 4 weeks.

3.

A transient burning/stinging sensation may be felt. This may occur in approximately 15% to 20% of cases, when ciclopirox gel is used to treat seborrheic dermatitis of the scalp.

4.

Inform the physician if the area of application shows signs of increased irritation or possible sensitization (redness with itching, burning, blistering, swelling, and/or oozing).

5.

Avoid the use of occlusive dressings.

6.

Do not use this medication for any disorder other than that for which it is prescribed.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 104-week dermal carcinogenicity study in mice was conducted with ciclopirox cream formulation applied at doses up to 1.93% (100 mg/kg/day or 300 mg/m2/day). No increase in drug related neopalsms was noted when compared to control.

The following in vitro genotoxicity tests have been conducted with ciclopirox: evaluation of gene mutation in the Ames Salmonella and E. coli assays (negative); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells, with and without metabolic activation (positive); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells in the presence of supplemental Fe3+, with and without metabolic activation (negative); gene mutation assays in the HGPRT-test with V79 Chinese hamster lung fibroblast cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA synthesis assay in A549 human cells) (negative). An in vitro cell transformation assay in BALB/c 3T3 cells was negative for cell transformation. In an in vivo Chinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at a dosage of 5000 mg/kg body weight.

A combined oral fertility and embryofetal developmental study was conducted in rats with ciclopirox olamine. No effect on fertility or reproductive performance was noted at the highest dose tested of 3.85 mg/kg/day ciclopirox (approximately 1.2 times the maximum recommended human dose based on body surface area comparisons).

Pregnancy

Teratogenic effects: Pregnancy Category B

There are no adequate or well-controlled studies in pregnant women. Therefore, ciclopirox gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Oral embryofetal developmental studies were conducted in mice, rats, rabbits and monkeys. Ciclopirox or ciclopirox olamine was orally administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 77, 125, 80 and 38.5 mg/kg/day ciclopirox in mice, rats, rabbits and monkeys, respectively (approximately 11, 37, 51 and 24 times the maximum recommended human dose based on body surface area comparisons, respectively).

Dermal embryofetal developmental studies were conducted in rats and rabbits with ciclopirox olamine dissolved in PEG 400. Ciclopirox olamine was topically administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 92 mg/kg/day and 77 mg/kg/day ciclopirox in rats and rabbits, respectively (approximately 27 and 49 times the maximum recommended human dose based on body surface area comparisons, respectively).

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 ciclopirox gel is administered to a nursing woman.

Pediatric Use

The efficacy and safety of ciclopirox gel in pediatric patients below the age of 16 years have not been established.

Adverse Reactions  ⮝

In clinical trials, 140 (39%) of 359 subjects treated with ciclopirox gel reported adverse experiences, irrespective of relationship to test materials, which resulted in 8 subjects discontinuing treatment. The most frequent experience reported was skin burning sensation upon application, which occurred in approximately 34% of seborrheic dermatitis patients and 7% of tinea pedis patients. Adverse experiences occurring between 1% to 5% were contact dermatitis and pruritus. Other reactions that occurred in less than 1% included dry skin, acne, rash, alopecia, pain upon application, eye pain, and facial edema.

Dosage And Administration  ⮝

Superficial Dermatophyte Infections

Gently massage ciclopirox gel into the affected areas and surrounding skin twice daily, in the morning and evening immediately after cleaning or washing the areas to be treated. Interdigital tinea pedis and tinea corporis should be treated for 4 weeks. If a patient shows no clinical improvement after 4 weeks of treatment, the diagnosis should be reviewed.

Seborrheic Dermatitis of the Scalp

Apply ciclopirox gel to affected scalp areas twice daily, in the morning and evening for 4 weeks. Clinical improvement usually occurs within the first week with continuing resolution of signs and symptoms through the fourth week of treatment. If a patient shows no clinical improvement after 4 weeks of treatment, the diagnosis should be reviewed.

How Supplied  ⮝

Ciclopirox gel 0.77% is supplied in aluminium tubes and LDPE tubes.

30 g tubes (NDC 68462-455-35), 45 g tubes (NDC 68462-455-47) and 100 g tubes (NDC 68462-455-94).

Store at 20 to 25 C (68 to 77 F) [See USP Controlled Room Temperature].

Manufactured by:

Glenmark Pharmaceuticals Limited

Colvale-Bardez, Goa 403 513, India

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888)721-7115

www.glenmarkpharma.com/usa

January 2017

Package/label Display Panel  ⮝

CICLOPIROX ciclopirox gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68462-455 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CICLOPIROX (UNII: 19W019ZDRJ) (CICLOPIROX - UNII:19W019ZDRJ) CICLOPIROX 7.7 mg in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E) ISOPROPYL ALCOHOL (UNII: ND2M416302) MEDIUM-CHAIN TRIGLYCERIDES (UNII: C9H2L21V7U) SODIUM HYDROXIDE (UNII: 55X04QC32I) SODIUM LAURYL SULFATE (UNII: 368GB5141J) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68462-455-35 30 g in 1 TUBE; Type 0: Not a Combination Product 02/29/2012 2 NDC:68462-455-47 45 g in 1 TUBE; Type 0: Not a Combination Product 02/29/2012 3 NDC:68462-455-94 100 g in 1 TUBE; Type 0: Not a Combination Product 02/29/2012

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091595 02/29/2012

Labeler - Glenmark Pharmaceuticals Inc., USA (130597813)

Establishment
Name	Address	ID/FEI	Business Operations
Glenmark Pharmaceuticals Limited		677318665	MANUFACTURE(68462-455) , ANALYSIS(68462-455)

Revised: 1/2017 Document Id: f4188436-4d86-48c2-89a9-7c73862bb8fe 34391-3 Set id: 3c22416e-4293-4ba5-a983-137cbc6022db Version: 5 Effective Time: 20170113 Glenmark Pharmaceuticals Inc., USA

Ciclopirox Gel, 0.77% ⮝

FOR DERMATOLOGIC USE ONLY.

NOT FOR USE IN EYES.

Rx Only

Description ⮝

Ciclopirox Gel, 0.77% contains a synthetic antifungal agent, ciclopirox. It is intended for topical dermatologic use only.

Each gram of Ciclopirox Gel contains 7.70 mg of ciclopirox in a gel consisting of purified water USP, isopropyl alcohol USP, octyldodecanol NF, dimethicone copolyol 190, carbomer 980, sodium hydroxide NF, and docusate sodium USP.

Ciclopirox Gel is a white, slightly fluid gel.

The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl- 2(1H)-pyridinone, with the empirical formula C12H17NO2 and a molecular weight of 207.27. The CAS Registry Number is [29342 05 0]. The chemical structure is:

Clinical Pharmacology ⮝

Mechanism of Action

Ciclopirox is a hydroxypyridone antifungal agent although the relevance of this property for the indication of seborrheic dermatitis is not known. Ciclopirox acts by chelation of polyvalent cations (Fe3+ or Al3+), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

Pharmacokinetics

A comparative study of the pharmacokinetics of Ciclopirox Gel, and ciclopirox olamine cream, 0.77% in 18 healthy males indicated that systemic absorption of ciclopirox from Ciclopirox Gel was higher than that of ciclopirox olamine cream. A 5 gm dose of Ciclopirox Gel produced a mean ( SD) peak serum concentration of 25.02 ( 20.6) ng/mL total ciclopirox and 5 gm of ciclopirox olamine cream produced 18.62 ( 13.56) ng/mL total ciclopirox. Approximately 3% of the applied ciclopirox was excreted in the urine within 48 hours after application, with a renal elimination half life of about 5.5 hours.

In a study of Ciclopirox Gel, 16 men with moderate to severe tinea cruris applied approximately 15 grams/day of the gel for 14.5 days. The mean ( SD) dose-normalized values of Cmax for total ciclopirox in serum were 100 ( 42) ng/mL on Day 1 and 238 ( 144) ng/mL on Day 15. During the 10 hours after dosing on Day 1, approximately 10% of the administered dose was excreted in the urine.

Microbiology

Ciclopirox is a hydroxypyridinone antifungal agent that inhibits the growth of pathogenic dermatophytes. Ciclopirox has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum

Indications And Usage ⮝

Superficial Dermatophyte Infections

Ciclopirox Gel is indicated for the topical treatment of interdigital tinea pedis and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum.

Seborrheic Dermatitis

Ciclopirox Gel is indicated for the topical treatment of seborrheic dermatitis of the scalp.

Contraindications ⮝

Ciclopirox Gel is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings ⮝

Ciclopirox Gel is not for ophthalmic, oral, or intravaginal use.

Keep out of reach of children.

Precautions ⮝

If a reaction suggesting sensitivity or chemical irritation should occur with the use of Ciclopirox Gel, treatment should be discontinued and appropriate therapy instituted. A transient burning sensation may occur, especially after application to sensitive areas. Avoid contact with eyes. Efficacy of Ciclopirox Gel in immunosuppressed individuals has not been studied. Seborrheic dermatitis in association with acne, atopic dermatitis, Parkinsonism, psoriasis and rosacea has not been studied with Ciclopirox Gel. Efficacy in the treatment of plantar and vesicular types of tinea pedis has not been established.

Information for Patients

The patient should be told the following:

1. Use Ciclopirox Gel as directed by the physician. Avoid contact with the eyes and mucous membranes. Ciclopirox Gel is for external use only.
2. Use the medication for fungal infections for the full treatment time even though symptoms may have improved, and notify the physician if there is no improvement after 4 weeks.
3. A transient burning/stinging sensation may be felt. This may occur in approximately 15% to 20% of cases, when Ciclopirox Gel is used to treat seborrheic dermatitis of the scalp.
4. Inform the physician if the area of application shows signs of increased irritation or possible sensitization (redness with itching, burning, blistering, swelling, and/or oozing).
5. Avoid the use of occlusive dressings.
6. Do not use this medication for any disorder other than that for which it is prescribed.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 104-week dermal carcinogenicity study in mice was conducted with ciclopirox cream formulation applied at doses up to 1.93% (100 mg/kg/day or 300 mg/m2/day). No increase in drug related neoplasms was noted when compared to control.

The following in vitro genotoxicity tests have been conducted with ciclopirox: evaluation of gene mutation in the Ames Salmonella and E. coli assays (negative); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells, with and without metabolic activation (positive); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells in the presence of supplemental Fe3+, with and without metabolic activation (negative); gene mutation assays in the HGPRT-test with V79 Chinese hamster lung fibroblast cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA synthesis assay in A549 human cells) (negative). An in vitro cell transformation assay in BALB/c 3T3 cells was negative for cell transformation. In an in vivo Chinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at a dosage of 5000 mg/kg body weight.

A combined oral fertility and embryofetal developmental study was conducted in rats with ciclopirox olamine. No effect on fertility or reproductive performance was noted at the highest dose tested of 3.85 mg/kg/day ciclopirox (approximately 1.2 times the maximum recommended human dose based on body surface area comparisons).

Pregnancy

Teratogenic effects: Pregnancy Category B

There are no adequate or well-controlled studies in pregnant women. Therefore, Ciclopirox Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Oral embryofetal developmental studies were conducted in mice, rats, rabbits and monkeys. Ciclopirox or ciclopirox olamine was orally administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 77, 125, 80 and 38.5 mg/kg/day ciclopirox in mice, rats, rabbits and monkeys, respectively (approximately 11, 37, 51 and 24 times the maximum recommended human dose based on body surface area comparisons, respectively).

Dermal embryofetal developmental studies were conducted in rats and rabbits with ciclopirox olamine dissolved in PEG 400. Ciclopirox olamine was topically administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 92 mg/kg/day and 77 mg/kg/day ciclopirox in rats and rabbits, respectively (approximately 27 and 49 times the maximum recommended human dose based on body surface area comparisons, respectively).

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 Ciclopirox Gel is administered to a nursing woman.

Pediatric Use

The efficacy and safety of Ciclopirox Gel in pediatric patients below the age of 16 years have not been established.

Adverse Reactions ⮝

In clinical trials, 140 (39%) of 359 subjects treated with Ciclopirox Gel reported adverse experiences, irrespective of relationship to test materials, which resulted in 8 subjects discontinuing treatment. The most frequent experience reported was skin burning sensation upon application, which occurred in approximately 34% of seborrheic dermatitis patients and 7% of tinea pedis patients. Adverse experiences occurring between 1% to 5% were contact dermatitis and pruritus. Other reactions that occurred in less than 1% included dry skin, acne, rash, alopecia, pain upon application, eye pain, and facial edema.

To report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dosage And Administration ⮝

Superficial Dermatophyte Infections

Gently massage Ciclopirox Gel into the affected areas and surrounding skin twice daily, in the morning and evening immediately after cleaning or washing the areas to be treated. Interdigital tinea pedis and tinea corporis should be treated for 4 weeks. If a patient shows no clinical improvement after 4 weeks of treatment, the diagnosis should be reviewed.

Seborrheic Dermatitis of the Scalp

Apply Ciclopirox Gel to affected scalp areas twice daily, in the morning and evening for 4 weeks. Clinical improvement usually occurs within the first week with continuing resolution of signs and symptoms through the fourth week of treatment. If a patient shows no clinical improvement after 4 weeks of treatment, the diagnosis should be reviewed.

How Supplied ⮝

Ciclopirox Gel, 0.77% is supplied in
30 g tubes (NDC 47781-530-73),
45 g tubes (NDC 47781-530-84), and
100 g tubes (NDC 47781-530-85).

Store at 15 -30 C (59 -86 F).

Principal Display Panel - Carton ⮝

Rx Only

NDC 0574-2061-01

Ciclopirox Gel, 0.77%

For Dermatologic Use Only. Not for Use in Eyes.

100 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

CICLOPIROX ciclopirox gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0574-2061 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CICLOPIROX (UNII: 19W019ZDRJ) (CICLOPIROX - UNII:19W019ZDRJ) CICLOPIROX 7.7 mg in 1 g

Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R) ISOPROPYL ALCOHOL (UNII: ND2M416302) OCTYLDODECANOL (UNII: 461N1O614Y) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E) SODIUM HYDROXIDE (UNII: 55X04QC32I) DOCUSATE SODIUM (UNII: F05Q2T2JA0) PEG/PPG-18/18 DIMETHICONE (UNII: 9H0AO7T794)

Product Characteristics Color WHITE Score Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0574-2061-30 1 in 1 CARTON 01/07/2009 1 30 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:0574-2061-45 1 in 1 CARTON 01/07/2009 2 45 g in 1 TUBE; Type 0: Not a Combination Product 3 NDC:0574-2061-01 1 in 1 CARTON 01/07/2009 3 100 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078266 01/07/2009

Labeler - Paddock Laboratories, LLC (967694121)

Registrant - L. Perrigo Company (006013346)

Revised: 11/2018 Document Id: 47417670-39e7-4c06-8638-cb8984aed47e 34391-3 Set id: b6a02568-867b-4c7b-890f-5d28bf0b363d Version: 5 Effective Time: 20181113 Paddock Laboratories, LLC