ADVERSE REACTIONS SECTION.

6. ADVERSE REACTIONS. 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.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 basis for identifying the adverse reactions that appear to be related to drug use and for approximating rates.The safety data presented in Table 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 weeks to affected areas on the face, scalp, and/or chest. Adverse reactions occurring in 1% of subjects are presented in Table 1.Table 1: Adverse Reactions Reported by 1% Subjects in Clinical TrialsAdverse ReactionsKetoconazole Foam, 2%N 672n (%)Vehicle FoamN 497n (%)Subjects with an Adverse Reaction188 (28%)122 (25%)Application site burning67 (10%)49 (10%)Application site reaction41 (6%)24 (5%)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 photoallergenicity study, of 53 subjects (17%) had reactions during the challenge period at both the irradiated and non-irradiated sites treated with ketoconazole foam, 2%. Ketodan(R) 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: CheilitisGeneral disorders and administration site conditions: Application site pain and application site burn Skin and subcutaneous tissue disorders: Skin burning sensation and erythemaBecause these events are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.

HOW SUPPLIED SECTION.

16. HOW SUPPLIED/STORAGE AND HANDLING. Ketodan(R) Foam, 2% contains 20 mg of ketoconazole, USP per gram. The thermolabile hydroethanolic foam is available as follows: NDC 43538-530-10100 aluminum can. NDC 43538-530-10100 aluminum can. Store at 20 to 25C (68 to 77F). [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 49C (120F). Do not store in direct sunlight.Contents under pressure. Do not puncture and/or incinerate container.Keep out of reach of children.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 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 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 complete loss of fertility. When administered for longer durations (up to 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 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.

CLINICAL PHARMACOLOGY SECTION.

12. CLINICAL PHARMACOLOGY. 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(R) Foam, 2% has not been established.. 12.3 Pharmacokinetics. In bioavailability study, 12 subjects with moderate to severe seborrheic dermatitis applied g of ketoconazole foam, 2% twice daily for weeks. Circulating plasma levels of ketoconazole were 6 ng/mL for majority of subjects (75%), with 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, key sterol in the cell membrane of Malassezia furfur. The clinical significance of antifungal activity in the treatment of seborrheic dermatitis is not known.

CLINICAL STUDIES SECTION.

14. CLINICAL STUDIES. The safety and efficacy of ketoconazole foam, 2% were evaluated in 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 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 on 5-point Investigators Static Global Assessment (ISGA) scale.Treatment success was defined as achieving Week (end of treatment) ISGA score of (clear) or (majority of lesions have individual scores for scaling, erythema, and induration that averages [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.Table 2: Efficacy ResultsNumber of SubjectsKetoconazole Foam, 2%N 427n (%)Vehicle FoamN 420n (%)Subjects Achieving Treatment Success239 (56%)176 (42%).

CONTRAINDICATIONS SECTION.

4. CONTRAINDICATIONS. None.. None.

DESCRIPTION SECTION.

11. DESCRIPTION. Ketodan(R) Foam, 2% contains 2% ketoconazole USP, an antifungal agent, in 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 molecular weight of 531.43. The following is the chemical structure:Ketodan(R) Foam, 2% contains 20 mg ketoconazole per gram in thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, citric acid, ethanol (denatured with tert-butyl alcohol and brucine sulfate) 58%, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with hydrocarbon (propane/butane) propellant.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2. DOSAGE AND ADMINISTRATION. Ketodan(R) Foam, 2% should be applied to the affected area(s) twice daily for four weeks.Hold the container upright, and dispense Ketodan(R) 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(R) 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(R) Foam, 2% may be applied directly to the skin (rather than on the hair).Avoid contact with the eyes and other mucous membranes. Ketodan(R) Foam, 2% is not for ophthalmic, oral or intravaginal use.. Ketodan(R) Foam, 2% should be applied to the affected area(s) twice daily for four weeks (2).Ketodan(R) Foam, 2% is not for ophthalmic, oral, or intravaginal use (2).. Ketodan(R) Foam, 2% should be applied to the affected area(s) twice daily for four weeks (2).. Ketodan(R) Foam, 2% is not for ophthalmic, oral, or intravaginal use (2).

DOSAGE FORMS & STRENGTHS SECTION.

3. DOSAGE FORMS AND STRENGTHS. Ketodan(R) Foam, 2% contains 20 mg of ketoconazole, USP per gram, supplied in 100 containers.. Foam: 2% ketoconazole in 100 containers (3).

FEMALES & MALES OF REPRODUCTIVE POTENTIAL SECTION.

8.3 Females and Males of Reproductive Potential. InfertilityIn animal fertility studies in rats and dogs, administration of oral doses of ketoconazole between 3-day and 3-month periods resulted in infertility that was reversible [see Nonclinical Toxicology (13.1)].

GERIATRIC USE SECTION.

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.

INDICATIONS & USAGE SECTION.

1. INDICATIONS AND USAGE. Ketodan(R) Foam, 2% is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older.. Ketodan(R) Foam, 2% is indicated for topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older (1).Limitations of UseSafety and efficacy of Ketodan(R) Foam, 2% for treatment of fungal infections have not been established.. Limitations of UseSafety and efficacy of Ketodan(R) Foam, 2% for treatment of fungal infections have not been established.

INFORMATION FOR PATIENTS SECTION.

17. PATIENT COUNSELING INFORMATION. See FDA-approved patient labeling (Patient Package Insert).Instruct patients on proper use of Ketodan(R) Foam, 2%Avoid fire, flame and/or smoking during and immediately following application.Do not apply Ketodan(R) Foam, 2% directly to hands. Dispense onto cool surface, and apply to the affected areas using the fingertips.Wash their hands after applicationKetodan(R) Foam, 2% may cause skin irritation (application site burning and/or reactions)Instruct patient to contact health care provider if the area of application shows signs of increased irritation and report any signs of adverse reactions.. Avoid fire, flame and/or smoking during and immediately following application.. Do not apply Ketodan(R) Foam, 2% directly to hands. Dispense onto cool surface, and apply to the affected areas using the fingertips.. Wash their hands after application. Ketodan(R) Foam, 2% may cause skin irritation (application site burning and/or reactions). Instruct patient to contact health care provider if the area of application shows signs of increased irritation and report any signs of adverse reactions.

INSTRUCTIONS FOR USE SECTION.

Instructions for Use Ketodan(R) Foam, 2%Important Information: Ketodan(R) Foam, 2% is for use on the skin only. Do not use Ketodan(R) Foam, 2% in your eyes, mouth or vagina.Step 1: Remove the clear cap from the Ketodan(R) Foam, 2% can.Step 2: Hold the can upright and firmly press the nozzle to dispense Ketodan(R) Foam, 2% into the clear cap. Dispense enough Ketodan(R) Foam, 2% to cover the entire affected area(s). If the can seems warm or the foam seems runny, run the can under cold water.Step 3: Pick up small amounts of Ketodan(R) Foam, 2% with your fingertips and gently rub the foam into the affected area(s) until the foam disappears.If you are treating areas such as your scalp, part the hair so that Ketodan(R) Foam, 2% may be applied directly to the skin.Step 4: Wash your hands after applying Ketodan(R) Foam, 2%. Throw away any of the unused medicine that is left in the cap. How should store Ketodan(R) Foam, 2% Store Ketodan(R) Foam, 2% at room temperature between 68F to 77F (20C to 25C).Do not store the Ketodan(R) Foam, 2% can in the refrigerator or freezer.Keep Ketodan(R) Foam, 2% away from heat. Never throw the can into fire, even if the can is empty.Do not store Ketodan(R) Foam, 2% at temperatures above 120F (49C).Do not break through (puncture) the Ketodan(R) Foam, 2% can. Keep Ketodan(R) Foam, 2% and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Dispense enough Ketodan(R) Foam, 2% to cover the entire affected area(s).. If the can seems warm or the foam seems runny, run the can under cold water.. If you are treating areas such as your scalp, part the hair so that Ketodan(R) Foam, 2% may be applied directly to the skin.. Throw away any of the unused medicine that is left in the cap.. Store Ketodan(R) Foam, 2% at room temperature between 68F to 77F (20C to 25C).. Do not store the Ketodan(R) Foam, 2% can in the refrigerator or freezer.. Keep Ketodan(R) Foam, 2% away from heat. Never throw the can into fire, even if the can is empty.. Do not store Ketodan(R) Foam, 2% at temperatures above 120F (49C).. Do not break through (puncture) the Ketodan(R) Foam, 2% can.. Image. Image. Image. Image. Image. Image. Image.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere is no information available on the presence of ketoconazole in human milk, or the effects on the breastfed child, or the effects on milk production after topical application of ketoconazole foam, 2% to women who are breastfeeding. In animal studies ketoconazole was found in milk following oral administration. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Ketodan(R) Foam, 2% and any potential adverse effects on the breastfed infant from Ketodan(R) Foam, 2% or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

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

MICROBIOLOGY SECTION.

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

NONCLINICAL TOXICOLOGY SECTION.

13. NONCLINICAL TOXICOLOGY. 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 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 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 complete loss of fertility. When administered for longer durations (up to 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 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 100 Can Carton. NDC 43538-530-10Rx OnlyKetodan(R) Ketoconazole Foam, 2%For Topical Use Only.Not For Ophthalmic, Oral,or Intravaginal Use.Net wt. 100 gMEDIMETRIKSPHARMACEUTICALS, INC.. PRINCIPAL DISPLAY PANEL 100 Can Carton.

PEDIATRIC USE SECTION.

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)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. The pharmacodynamics of Ketodan(R) Foam, 2% has not been established.

PHARMACOKINETICS SECTION.

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

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere are no available data on ketoconazole foam, 2% use in pregnant women to identify drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. No reproductive studies in animals have been performed with ketoconazole foam, 2%. In animal reproduction studies with pregnant mice, rats and rabbits both embryotoxic and developmental effects (structural abnormalities) were observed following oral dosing of ketoconazole during organogenesis. Assuming equivalent systemic absorption of topical and oral ketoconazole doses and ketoconazole foam, 2% maximum recommended human dose (MRHD) of grams (equivalent to 160 mg ketoconazole), embryotoxic effects were observed at 0.8 to 2.4 times the MRHD and developmental effects were observed at 4.8 times the MRHD [see Data].The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.. Data. Animal DataThe animal multiples of human exposure calculations are based on body surface area (BSA) comparisons of oral doses administered to animals and ketoconazole foam, 2% maximum recommended human dose (MRHD) of grams (equivalent to 2.67 mg ketoconazole/kg/day for 60 kg individual or 98.8 mg ketoconazole/m2/day).Embryofetal development studies have been conducted in mice, rats and rabbits with orally administered ketoconazole. When orally administered to mice on gestational days through 18 (covering the period of organogenesis), ketoconazole was embryotoxic (25 mg/kg and higher; 0.8 times the MRHD based on BSA comparisons) with high incidence of resorptions, increased number of stillbirths and delayed parturition. Delays in maturation were also observed. There was no evidence of maternal toxicity or malformations at up to 50 mg/kg (1.5 times the MRHD based on BSA comparisons). No treatment related developmental effects were observed at 10 mg/kg (0.3 times the MRHD based on BSA comparisons).In the presence of maternal toxicity in rats, orally administered ketoconazole was both embryotoxic (40 mg/kg and higher; 2.4 times the MRHD based on BSA comparisons), including increased resorbed fetuses and stillbirths, and teratogenic (80 mg/kg and higher; 4.8 times the MRHD based on BSA comparisons), including syndactylia, oligodactylia, waved ribs and cleft palate. Additionally, 100 mg/kg (6 times the MRHD based on BSA comparisons) ketoconazole orally administered on single day during gestation (gestational days through 12) was embryotoxic (increased resorptions). This same oral dose given on gestation day 12, 13, 14 or 15 induced external malformations including cleft palate, micromelia and digital anomalies (brachydactyly, ectrodactyly, syndactyly).In pregnant rabbits orally administered ketoconazole, evidence of embryotoxicity (increased resorptions) was observed at 10 mg/kg (1.2 times the MRHD based on BSA comparisons) and higher and an increased incidence of skeletal abnormalities was observed at 40 mg/kg (4.8 times the MRHD based on BSA comparisons).

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATIONKetodan(R) Foam, 2%Important Information: Ketodan(R) Foam, 2% is for use on the skin only. Do not use Ketodan(R) Foam, 2% in your eyes, mouth or vagina.What is Ketodan(R) Foam, 2%Ketodan(R) Foam, 2% is prescription medicine used on the skin (topical) to treat seborrheic dermatitis in people 12 years of age and older with normal immune system.It is not known if Ketodan(R) Foam, 2% is safe and effective when used to treat fungal infections.It is not known if Ketodan(R) Foam, 2% is safe and effective in children less than 12 years of age.Before using Ketodan(R) Foam, 2%, tell your healthcare provider about all of your medical conditions, including if you:are pregnant or plan to become pregnant. It is not known if Ketodan(R) Foam, 2% will harm your unborn baby.are breastfeeding or plan to breastfeed. It is not known if Ketodan(R) Foam, 2% passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Ketodan(R) Foam, 2%.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How should use Ketodan(R) Foam, 2%Use Ketodan(R) Foam, 2% exactly as your healthcare provider tells you to use it. See the detailed Instructions for Use at the end of this leaflet for directions about how to apply Ketodan(R) Foam, 2% the right way.Apply Ketodan(R) Foam, 2% to the affected skin area(s) times each day for weeks. You should apply enough Ketodan(R) Foam, 2% to cover the entire affected area(s).Talk to your healthcare provider if your skin does not improve after weeks of treatment with Ketodan(R) Foam, 2%.Dispense Ketodan(R) Foam, 2% directly into the cap. Do not dispense Ketodan(R) Foam, 2% directly onto your hands, because the foam will begin to melt on contact with warm skin.Wash your hands after applying Ketodan(R) Foam, 2%.What should avoid while using Ketodan(R) Foam, 2%Ketodan(R) Foam, 2% is flammable. Avoid fire, flames, or smoking during and right after you apply Ketodan(R) Foam, 2% to your skin.Avoid getting Ketodan(R) Foam, 2% in or near your eyes, mouth, lips or vagina. If you get Ketodan(R) Foam, 2% on your lips or in your eyes, mouth or vagina, rinse well with water.What are the possible side effects of Ketodan(R) Foam, 2%Ketodan(R) Foam, 2% may cause serious side effects, including:Skin irritation at the application area(s), including skin reactions caused by exposure to light. Tell your healthcare provider if you develop skin irritation during treatment with Ketodan(R) Foam, 2%.The most common side effects of Ketodan(R) Foam, 2% include, burning, dryness, redness, irritation, numbness, itching, rash and warmth at the application site.These are not all of the possible side effects of Ketodan(R) Foam, 2%.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store Ketodan(R) Foam, 2%Store Ketodan(R) Foam, 2% at room temperature between 68F to 77F (20C to 25C).Do not store the Ketodan(R) Foam, 2% can in the refrigerator or freezer.Keep Ketodan(R) Foam, 2% away from heat. Never throw the Ketodan(R) Foam, 2% can into fire, even if the can is empty.Do not store Ketodan(R) Foam, 2% at temperatures above 120F (49C).Do not break through (puncture) the Ketodan(R) Foam, 2% can.Keep Ketodan(R) Foam, 2% and all medicines out of the reach of children.General information about the safe and effective use of Ketodan(R) Foam, 2%.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use Ketodan(R) Foam, 2% for condition for which it was not prescribed. Do not give Ketodan(R) Foam, 2% to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Ketodan(R) Foam, 2% that is written for health professionals.What are the ingredients in Ketodan(R) Foam, 2%Active ingredient: ketoconazole Inactive Ingredients: cetyl alcohol, citric acid, ethanol (denatured with tert-butyl alcohol and brucine sulfate) 58%, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with hydrocarbon (propane/butane) propellantFor more information, call Medimetriks at 1-973-882-7512This Patient Information leaflet has been approved by the U.S. Food and Drug Administration.. are pregnant or plan to become pregnant. It is not known if Ketodan(R) Foam, 2% will harm your unborn baby.. are breastfeeding or plan to breastfeed. It is not known if Ketodan(R) Foam, 2% passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Ketodan(R) Foam, 2%.. Use Ketodan(R) Foam, 2% exactly as your healthcare provider tells you to use it. See the detailed Instructions for Use at the end of this leaflet for directions about how to apply Ketodan(R) Foam, 2% the right way.. Apply Ketodan(R) Foam, 2% to the affected skin area(s) times each day for weeks. You should apply enough Ketodan(R) Foam, 2% to cover the entire affected area(s).. Talk to your healthcare provider if your skin does not improve after weeks of treatment with Ketodan(R) Foam, 2%.. Dispense Ketodan(R) Foam, 2% directly into the cap. Do not dispense Ketodan(R) Foam, 2% directly onto your hands, because the foam will begin to melt on contact with warm skin.. Wash your hands after applying Ketodan(R) Foam, 2%.. Ketodan(R) Foam, 2% is flammable. Avoid fire, flames, or smoking during and right after you apply Ketodan(R) Foam, 2% to your skin.. Avoid getting Ketodan(R) Foam, 2% in or near your eyes, mouth, lips or vagina. If you get Ketodan(R) Foam, 2% on your lips or in your eyes, mouth or vagina, rinse well with water.. Skin irritation at the application area(s), including skin reactions caused by exposure to light. Tell your healthcare provider if you develop skin irritation during treatment with Ketodan(R) Foam, 2%.. Store Ketodan(R) Foam, 2% at room temperature between 68F to 77F (20C to 25C).. Do not store the Ketodan(R) Foam, 2% can in the refrigerator or freezer.. Keep Ketodan(R) Foam, 2% away from heat. Never throw the Ketodan(R) Foam, 2% can into fire, even if the can is empty.. Do not store Ketodan(R) Foam, 2% at temperatures above 120F (49C).. Do not break through (puncture) the Ketodan(R) Foam, 2% can.

SPL UNCLASSIFIED SECTION.

Limitations of UseSafety and efficacy of Ketodan(R) Foam, 2% for treatment of fungal infections have not been established.

STORAGE AND HANDLING SECTION.

Store at 20 to 25C (68 to 77F). [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 49C (120F). Do not store in direct sunlight.Contents under pressure. Do not puncture and/or incinerate container.Keep out of reach of children.

USE IN SPECIFIC POPULATIONS SECTION.

8. USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThere are no available data on ketoconazole foam, 2% use in pregnant women to identify drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. No reproductive studies in animals have been performed with ketoconazole foam, 2%. In animal reproduction studies with pregnant mice, rats and rabbits both embryotoxic and developmental effects (structural abnormalities) were observed following oral dosing of ketoconazole during organogenesis. Assuming equivalent systemic absorption of topical and oral ketoconazole doses and ketoconazole foam, 2% maximum recommended human dose (MRHD) of grams (equivalent to 160 mg ketoconazole), embryotoxic effects were observed at 0.8 to 2.4 times the MRHD and developmental effects were observed at 4.8 times the MRHD [see Data].The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.. Data. Animal DataThe animal multiples of human exposure calculations are based on body surface area (BSA) comparisons of oral doses administered to animals and ketoconazole foam, 2% maximum recommended human dose (MRHD) of grams (equivalent to 2.67 mg ketoconazole/kg/day for 60 kg individual or 98.8 mg ketoconazole/m2/day).Embryofetal development studies have been conducted in mice, rats and rabbits with orally administered ketoconazole. When orally administered to mice on gestational days through 18 (covering the period of organogenesis), ketoconazole was embryotoxic (25 mg/kg and higher; 0.8 times the MRHD based on BSA comparisons) with high incidence of resorptions, increased number of stillbirths and delayed parturition. Delays in maturation were also observed. There was no evidence of maternal toxicity or malformations at up to 50 mg/kg (1.5 times the MRHD based on BSA comparisons). No treatment related developmental effects were observed at 10 mg/kg (0.3 times the MRHD based on BSA comparisons).In the presence of maternal toxicity in rats, orally administered ketoconazole was both embryotoxic (40 mg/kg and higher; 2.4 times the MRHD based on BSA comparisons), including increased resorbed fetuses and stillbirths, and teratogenic (80 mg/kg and higher; 4.8 times the MRHD based on BSA comparisons), including syndactylia, oligodactylia, waved ribs and cleft palate. Additionally, 100 mg/kg (6 times the MRHD based on BSA comparisons) ketoconazole orally administered on single day during gestation (gestational days through 12) was embryotoxic (increased resorptions). This same oral dose given on gestation day 12, 13, 14 or 15 induced external malformations including cleft palate, micromelia and digital anomalies (brachydactyly, ectrodactyly, syndactyly).In pregnant rabbits orally administered ketoconazole, evidence of embryotoxicity (increased resorptions) was observed at 10 mg/kg (1.2 times the MRHD based on BSA comparisons) and higher and an increased incidence of skeletal abnormalities was observed at 40 mg/kg (4.8 times the MRHD based on BSA comparisons).. 8.2 Lactation. Risk SummaryThere is no information available on the presence of ketoconazole in human milk, or the effects on the breastfed child, or the effects on milk production after topical application of ketoconazole foam, 2% to women who are breastfeeding. In animal studies ketoconazole was found in milk following oral administration. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Ketodan(R) Foam, 2% and any potential adverse effects on the breastfed infant from Ketodan(R) Foam, 2% or from the underlying maternal condition.. 8.3 Females and Males of Reproductive Potential. InfertilityIn animal fertility studies in rats and dogs, administration of oral doses of ketoconazole between 3-day and 3-month periods resulted in infertility that was reversible [see Nonclinical Toxicology (13.1)]. 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.

WARNINGS AND PRECAUTIONS SECTION.

5. WARNINGS AND PRECAUTIONS. Ketodan(R) Foam, 2% may result in contact sensitization, including photoallergenicity (5.1, 6.2).The contents of Ketodan(R) Foam, 2% are flammable. Avoid fire, flame, or smoking during and immediately following application. (5.2).. Ketodan(R) Foam, 2% may result in contact sensitization, including photoallergenicity (5.1, 6.2).. The contents of Ketodan(R) Foam, 2% are flammable. Avoid fire, flame, or smoking during and immediately following application. (5.2).. 5.1 Contact Sensitization. Ketodan(R) Foam, 2% may result in contact sensitization, including photoallergenicity [see Adverse Reactions (6.2)]. 5.2 Flammable Contents. The contents of Ketodan(R) 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 120F (49C).. 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.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 basis for identifying the adverse reactions that appear to be related to drug use and for approximating rates.The safety data presented in Table 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 weeks to affected areas on the face, scalp, and/or chest. Adverse reactions occurring in 1% of subjects are presented in Table 1.Table 1: Adverse Reactions Reported by 1% Subjects in Clinical TrialsAdverse ReactionsKetoconazole Foam, 2%N 672n (%)Vehicle FoamN 497n (%)Subjects with an Adverse Reaction188 (28%)122 (25%)Application site burning67 (10%)49 (10%)Application site reaction41 (6%)24 (5%)Application site reactions that were reported in <1% of subjects were dryness, erythema, irritation, paresthesia, pruritus, rash and warmth.

IMMUNOGENICITY.

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

POSTMARKETING EXPERIENCE SECTION.

6.3 Postmarketing Experience. The following adverse events have been identified during postmarketing use of ketoconazole foam, 2%:Gastrointestinal disorders: CheilitisGeneral disorders and administration site conditions: Application site pain and application site burn Skin and subcutaneous tissue disorders: Skin burning sensation and erythemaBecause these events are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.