These Highlights Do Not Include All The Information Needed To Use

Limitations of Use

Safety and efficacy of Ketodan^® Foam, 2% for treatment of fungal infections have not been established.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not store under refrigerated conditions.

Contents are flammable. Do not expose containers to heat and/or store at temperatures above 49°C (120°F). Do not store in direct sunlight.

Contents under pressure. Do not puncture and/or incinerate container.

Keep out of reach of children.

Instructions for Use

Ketodan^® Foam, 2%

Important Information: Ketodan^® Foam, 2% is for use on the skin only. Do not use Ketodan^® Foam, 2% in your eyes, mouth or vagina.

Ketodan^® Foam, 2% contains 2% ketoconazole USP, an antifungal agent, in a thermolabile hydroethanolic foam for topical application.

The chemical name for ketoconazole is piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis- with the molecular formula C₂₆H₂₈Cl₂N₄O₄ and a molecular weight of 531.43. The following is the chemical structure:

Ketodan^® Foam, 2% contains 20 mg ketoconazole per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, citric acid, ethanol 58%, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

Ketoconazole is an antifungal agent which inhibits the in vitro synthesis of ergosterol, a key sterol in the cell membrane of Malassezia furfur. The clinical significance of antifungal activity in the treatment of seborrheic dermatitis is not known.

The safety and effectiveness of ketoconazole foam, 2% in pediatric patients less than 12 years of age have not been established.

Of the 672 subjects treated with ketoconazole foam, 2% in the clinical trials, 44 (7%) were from 12 to 17 years of age. [See Clinical Studies (14)].

Of the 672 subjects treated with ketoconazole foam, 2% in the clinical trials, 107 (16%) were 65 years and over.

Clinical trials of ketoconazole foam, 2% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

The safety and efficacy of ketoconazole foam, 2% were evaluated in a randomized, double-blind, vehicle-controlled trial in subjects 12 years and older with mild to severe seborrheic dermatitis. In the trial, 427 subjects received ketoconazole foam, 2% and 420 subjects received vehicle foam. Subjects applied ketoconazole foam, 2% or vehicle foam twice daily for 4 weeks to affected areas on the face, scalp, and/or chest. The overall disease severity in terms of erythema, scaling, and induration was assessed at Baseline and week 4 on a 5-point Investigator's Static Global Assessment (ISGA) scale.

Treatment success was defined as achieving a Week 4 (end of treatment) ISGA score of 0 (clear) or 1 (majority of lesions have individual scores for scaling, erythema, and induration that averages 1 [minimal or faint]) and at least two grades of improvement from baseline. The results are presented in Table 2. The database was not large enough to assess whether there were differences in effects in age, gender, or race subgroups.

None.

Hepatitis has been seen with orally administered ketoconazole (1:10,000 reported incidence). Lowered testosterone and ACTH–induced corticosteroid serum levels have been seen with high doses of orally administered ketoconazole. These effects have not been seen with topical ketoconazole.

The most common adverse reactions observed in clinical studies (incidence >1%) were application site burning and application site reaction (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Medimetriks at 1-973-882-7512 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The pharmacodynamics of Ketodan^® Foam, 2% has not been established.

In a bioavailability study, 12 subjects with moderate to severe seborrheic dermatitis applied 3 g of ketoconazole foam, 2% twice daily for 4 weeks. Circulating plasma levels of ketoconazole were < 6 ng/mL for a majority of subjects (75%), with a maximum level of 11 ng/mL observed in one subject.

The contents of Ketodan^® Foam, 2% include alcohol and propane/butane, which are flammable. Avoid fire, flame and/or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

Ketodan^® Foam, 2% is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older.

The mechanism of action of ketoconazole in the treatment of seborrheic dermatitis is not known.

Ketodan^® Foam, 2% may result in contact sensitization, including photoallergenicity [see Adverse Reactions (6.2)].

In a photoallergenicity study, 9 of 53 subjects (17%) had reactions during the challenge period at both the irradiated and non-irradiated sites treated with ketoconazole foam, 2%. Ketodan^® Foam, 2% may cause contact sensitization.

• Ketodan^® Foam, 2% may result in contact sensitization, including photoallergenicity (5.1, 6.2).
• The contents of Ketodan^® Foam, 2% are flammable. Avoid fire, flame, or smoking during and immediately following application. (5.2).

Ketodan^® Foam, 2% should be applied to the affected area(s) twice daily for four weeks.

Hold the container upright, and dispense Ketodan^® Foam, 2% into the cap of the can or other cool surface in an amount sufficient to cover the affected area(s). Dispensing directly onto hands is not recommended, as the foam will begin to melt immediately upon contact with warm skin. Pick up small amounts of Ketodan^® Foam, 2% with the fingertips, and gently massage into the affected area(s) until the foam disappears. For hair-bearing areas, part the hair, so that Ketodan^® Foam, 2% may be applied directly to the skin (rather than on the hair).

Avoid contact with the eyes and other mucous membranes. Ketodan^® Foam, 2% is not for ophthalmic, oral or intravaginal use.

The following adverse events have been identified during postmarketing use of ketoconazole foam, 2%:

Gastrointestinal disorders: Cheilitis

General disorders and administration site conditions: Application site pain and application site burn Skin and subcutaneous tissue disorders: Skin burning sensation and erythema

Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Ketodan^® Foam, 2% contains 20 mg of ketoconazole, USP per gram, supplied in 100 g containers.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use and for approximating rates.

The safety data presented in Table 1 reflect exposure to ketoconazole foam, 2% in 672 subjects, 12 years and older with seborrheic dermatitis. Subjects applied ketoconazole foam, 2% or vehicle foam twice daily for 4 weeks to affected areas on the face, scalp, and/or chest. Adverse reactions occurring in > 1% of subjects are presented in Table 1.

Application site reactions that were reported in <1% of subjects were dryness, erythema, irritation, paresthesia, pruritus, rash and warmth.

See FDA-approved patient labeling (Patient Package Insert).

Instruct patients on a proper use of Ketodan^® Foam, 2%

• Avoid fire, flame and/or smoking during and immediately following application.
• Do not apply Ketodan^® Foam, 2% directly to hands. Dispense onto a cool surface, and apply to the affected areas using the fingertips.
• Wash their hands after application
• Ketodan^® Foam, 2% may cause skin irritation (application site burning and/or reactions)
• Instruct a patient to contact a health care provider if the area of application shows signs of increased irritation and report any signs of adverse reactions.

Ketodan^® Foam, 2% contains 20 mg of ketoconazole, USP per gram. The thermolabile hydroethanolic foam is available as follows:

•  
  NDC 43538-530-10
  
  100 g aluminum can

NDC 43538-530-10

R_x Only

Ketodan^®

Ketoconazole Foam, 2%

For Topical Use Only.

Not For Ophthalmic, Oral,

or Intravaginal Use.

Net wt. 100 g

MEDIMETRIKS

PHARMACEUTICALS, INC.

Long-term animal studies have not been performed to evaluate the carcinogenic or photo-carcinogenic potential of ketoconazole foam, 2%.

In oral carcinogenicity studies in mice (18-months) and rats (24-months) at dose levels of 5, 20 and 80 mg/kg/day ketoconazole was not carcinogenic. The high dose in these studies was approximately 2.4 to 4.8 times the MRHD based on BSA comparisons. In a bacterial reverse mutation assay, ketoconazole did not express any mutagenic potential. In three in vivo assays (sister chromatid exchange in humans, dominant lethal and micronucleus tests in mice), ketoconazole did not exhibit any genotoxic potential.

In animal fertility studies, oral ketoconazole impaired both male and female fertility in rats in a dose and duration dependent manner. In females, oral doses up to 40 mg/kg (2.4 times the MRHD based on BSA comparisons) had no effect on fertility, while doses of 75 mg/kg (4.5 times the MRHD based on BSA comparisons) and higher decreased the pregnancy rate and number of implantation sites. In male rats, oral dosing at 200 mg/kg/day (12 times the MRHD based on BSA comparisons) for three days decreased fertility and 400 mg/kg/day (24 times the MRHD based on BSA comparisons) for three days resulted in a complete loss of fertility. When administered for longer durations (up to 3 months), decreased fertility in male rats was observed at doses as low as 24 mg/kg/day (1.4 times the MRHD based on BSA comparisons). In male beagle dogs, an oral dose of 25 mg/kg/day ketoconazole for up to 4 weeks (5.2 times the MRHD based on BSA comparisons) resulted in decreased sperm motility, decreased sperm count, increased abnormal sperm and atrophy of the testes. These effects were reversed subsequent to withdrawal of treatment.

Limitations of Use

Safety and efficacy of Ketodan^® Foam, 2% for treatment of fungal infections have not been established.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not store under refrigerated conditions.

Contents are flammable. Do not expose containers to heat and/or store at temperatures above 49°C (120°F). Do not store in direct sunlight.

Contents under pressure. Do not puncture and/or incinerate container.

Keep out of reach of children.

Instructions for Use

Ketodan^® Foam, 2%

Important Information: Ketodan^® Foam, 2% is for use on the skin only. Do not use Ketodan^® Foam, 2% in your eyes, mouth or vagina.

Ketodan^® Foam, 2% contains 2% ketoconazole USP, an antifungal agent, in a thermolabile hydroethanolic foam for topical application.

The chemical name for ketoconazole is piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis- with the molecular formula C₂₆H₂₈Cl₂N₄O₄ and a molecular weight of 531.43. The following is the chemical structure:

Ketodan^® Foam, 2% contains 20 mg ketoconazole per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, citric acid, ethanol 58%, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

Ketoconazole is an antifungal agent which inhibits the in vitro synthesis of ergosterol, a key sterol in the cell membrane of Malassezia furfur. The clinical significance of antifungal activity in the treatment of seborrheic dermatitis is not known.

The safety and effectiveness of ketoconazole foam, 2% in pediatric patients less than 12 years of age have not been established.

Of the 672 subjects treated with ketoconazole foam, 2% in the clinical trials, 44 (7%) were from 12 to 17 years of age. [See Clinical Studies (14)].

Of the 672 subjects treated with ketoconazole foam, 2% in the clinical trials, 107 (16%) were 65 years and over.

Clinical trials of ketoconazole foam, 2% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

The safety and efficacy of ketoconazole foam, 2% were evaluated in a randomized, double-blind, vehicle-controlled trial in subjects 12 years and older with mild to severe seborrheic dermatitis. In the trial, 427 subjects received ketoconazole foam, 2% and 420 subjects received vehicle foam. Subjects applied ketoconazole foam, 2% or vehicle foam twice daily for 4 weeks to affected areas on the face, scalp, and/or chest. The overall disease severity in terms of erythema, scaling, and induration was assessed at Baseline and week 4 on a 5-point Investigator's Static Global Assessment (ISGA) scale.

Treatment success was defined as achieving a Week 4 (end of treatment) ISGA score of 0 (clear) or 1 (majority of lesions have individual scores for scaling, erythema, and induration that averages 1 [minimal or faint]) and at least two grades of improvement from baseline. The results are presented in Table 2. The database was not large enough to assess whether there were differences in effects in age, gender, or race subgroups.

None.

Hepatitis has been seen with orally administered ketoconazole (1:10,000 reported incidence). Lowered testosterone and ACTH–induced corticosteroid serum levels have been seen with high doses of orally administered ketoconazole. These effects have not been seen with topical ketoconazole.

The most common adverse reactions observed in clinical studies (incidence >1%) were application site burning and application site reaction (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Medimetriks at 1-973-882-7512 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The pharmacodynamics of Ketodan^® Foam, 2% has not been established.

In a bioavailability study, 12 subjects with moderate to severe seborrheic dermatitis applied 3 g of ketoconazole foam, 2% twice daily for 4 weeks. Circulating plasma levels of ketoconazole were < 6 ng/mL for a majority of subjects (75%), with a maximum level of 11 ng/mL observed in one subject.

The contents of Ketodan^® Foam, 2% include alcohol and propane/butane, which are flammable. Avoid fire, flame and/or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

Ketodan^® Foam, 2% is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older.

The mechanism of action of ketoconazole in the treatment of seborrheic dermatitis is not known.

Ketodan^® Foam, 2% may result in contact sensitization, including photoallergenicity [see Adverse Reactions (6.2)].

In a photoallergenicity study, 9 of 53 subjects (17%) had reactions during the challenge period at both the irradiated and non-irradiated sites treated with ketoconazole foam, 2%. Ketodan^® Foam, 2% may cause contact sensitization.

• Ketodan^® Foam, 2% may result in contact sensitization, including photoallergenicity (5.1, 6.2).
• The contents of Ketodan^® Foam, 2% are flammable. Avoid fire, flame, or smoking during and immediately following application. (5.2).

Ketodan^® Foam, 2% should be applied to the affected area(s) twice daily for four weeks.

Hold the container upright, and dispense Ketodan^® Foam, 2% into the cap of the can or other cool surface in an amount sufficient to cover the affected area(s). Dispensing directly onto hands is not recommended, as the foam will begin to melt immediately upon contact with warm skin. Pick up small amounts of Ketodan^® Foam, 2% with the fingertips, and gently massage into the affected area(s) until the foam disappears. For hair-bearing areas, part the hair, so that Ketodan^® Foam, 2% may be applied directly to the skin (rather than on the hair).

Avoid contact with the eyes and other mucous membranes. Ketodan^® Foam, 2% is not for ophthalmic, oral or intravaginal use.

The following adverse events have been identified during postmarketing use of ketoconazole foam, 2%:

Gastrointestinal disorders: Cheilitis

General disorders and administration site conditions: Application site pain and application site burn Skin and subcutaneous tissue disorders: Skin burning sensation and erythema

Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Ketodan^® Foam, 2% contains 20 mg of ketoconazole, USP per gram, supplied in 100 g containers.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use and for approximating rates.

The safety data presented in Table 1 reflect exposure to ketoconazole foam, 2% in 672 subjects, 12 years and older with seborrheic dermatitis. Subjects applied ketoconazole foam, 2% or vehicle foam twice daily for 4 weeks to affected areas on the face, scalp, and/or chest. Adverse reactions occurring in > 1% of subjects are presented in Table 1.

Application site reactions that were reported in <1% of subjects were dryness, erythema, irritation, paresthesia, pruritus, rash and warmth.

See FDA-approved patient labeling (Patient Package Insert).

Instruct patients on a proper use of Ketodan^® Foam, 2%

• Avoid fire, flame and/or smoking during and immediately following application.
• Do not apply Ketodan^® Foam, 2% directly to hands. Dispense onto a cool surface, and apply to the affected areas using the fingertips.
• Wash their hands after application
• Ketodan^® Foam, 2% may cause skin irritation (application site burning and/or reactions)
• Instruct a patient to contact a health care provider if the area of application shows signs of increased irritation and report any signs of adverse reactions.

Ketodan^® Foam, 2% contains 20 mg of ketoconazole, USP per gram. The thermolabile hydroethanolic foam is available as follows:

•  
  NDC 43538-530-10
  
  100 g aluminum can

NDC 43538-530-10

R_x Only

Ketodan^®

Ketoconazole Foam, 2%

For Topical Use Only.

Not For Ophthalmic, Oral,

or Intravaginal Use.

Net wt. 100 g

MEDIMETRIKS

PHARMACEUTICALS, INC.

Long-term animal studies have not been performed to evaluate the carcinogenic or photo-carcinogenic potential of ketoconazole foam, 2%.

In oral carcinogenicity studies in mice (18-months) and rats (24-months) at dose levels of 5, 20 and 80 mg/kg/day ketoconazole was not carcinogenic. The high dose in these studies was approximately 2.4 to 4.8 times the MRHD based on BSA comparisons. In a bacterial reverse mutation assay, ketoconazole did not express any mutagenic potential. In three in vivo assays (sister chromatid exchange in humans, dominant lethal and micronucleus tests in mice), ketoconazole did not exhibit any genotoxic potential.

In animal fertility studies, oral ketoconazole impaired both male and female fertility in rats in a dose and duration dependent manner. In females, oral doses up to 40 mg/kg (2.4 times the MRHD based on BSA comparisons) had no effect on fertility, while doses of 75 mg/kg (4.5 times the MRHD based on BSA comparisons) and higher decreased the pregnancy rate and number of implantation sites. In male rats, oral dosing at 200 mg/kg/day (12 times the MRHD based on BSA comparisons) for three days decreased fertility and 400 mg/kg/day (24 times the MRHD based on BSA comparisons) for three days resulted in a complete loss of fertility. When administered for longer durations (up to 3 months), decreased fertility in male rats was observed at doses as low as 24 mg/kg/day (1.4 times the MRHD based on BSA comparisons). In male beagle dogs, an oral dose of 25 mg/kg/day ketoconazole for up to 4 weeks (5.2 times the MRHD based on BSA comparisons) resulted in decreased sperm motility, decreased sperm count, increased abnormal sperm and atrophy of the testes. These effects were reversed subsequent to withdrawal of treatment.