Limitations of Use

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

5.1 Contact Sensitization

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

5.2 Flammable Contents

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).

5.3 Systemic Effects

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.

6.1 Clinical Trials Experience

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.

6.2 Dermal Safety Studies

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.

6.3 Postmarketing Experience

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.

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

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)].

8.5 Geriatric Use

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.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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.

12.4 Microbiology

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.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

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.