FDA Label for Ketoconazole

1 Indications And Usage

Ketoconazole Foam, 2% is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older. Safety and efficacy of Ketoconazole Foam, 2% for treatment of fungal infections have not been established.

2 Dosage And Administration

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

Hold the container upright, and dispense Ketoconazole 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 Ketoconazole 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 Ketoconazole Foam, 2% may be applied directly to the skin (rather than on the hair).

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

3 Dosage Forms And Strengths

Ketoconazole Foam, 2% contains 2% ketoconazole in a thermolabile hydroethanolic foam, and is provided in 50 g and 100 g aluminum containers.

4 Contraindications

None

5.1 Contact Sensitization

Ketoconazole Foam, 2% may result in contact sensitization, including photoallergenicity. [See Adverse Reactions (6.2)]

5.2 Flammable Contents

The contents of Ketoconazole 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 corticosteroidserum levels have been seen with high doses of orally administered ketoconazole. These effects have not been seen with topical ketoconazole.

6.1 Adverse Reactions In Clinical Trials

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 (below) 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.

Table 1: Adverse Reactions Reported by >1% Subjects in Clinical Trials

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%. Ketoconazole Foam, 2% may cause contact sensitization.

Pregnancy Category C:

Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day (4.8 times the maximum expected human topical dose based on a mg/m² comparison, assuming 100% absorption from 8 g of foam). However, these effects may be partly related to maternal toxicity, which was also observed at this dose level. [See Pharmacokinetics (12.3)] No reproductive studies in animals have been performed with Ketoconazole Foam, 2%.

There are no adequate and well-controlled studies of Ketoconazole Foam, 2% in pregnant women. Ketoconazole Foam, 2% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

It is not known whether Ketoconazole Foam, 2% administered topically could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when Ketoconazole Foam, 2% is administered to women who are breastfeeding.

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.

11 Description

Ketoconazole 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 C₂₆H₂₈CI₂N₄O₄ and a molecular weight of 531.43.

The following is the chemical structure:

Ketoconazole Foam, 2% contains 20 mg ketoconazole USP per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol NF, citric acid USP, ethanol (denatured with tert-butyl alcohol and brucine sulfate) 58%, polysorbate 60 NF, potassium citrate USP, propylene glycol USP, purified water USP, and stearyl alcohol NF pressurized with a hydrocarbon (propane/butane) propellant.

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 Ketoconazole 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 expected topical dose in humans based on a mg/m² comparison. 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.

At oral dose levels of 75 mg/kg/day (4.5 times the expected topical human dose in mg/m²), ketoconazole impaired reproductive performance and fertility when administered to male rats (increased abnormal sperm, decreased sperm mobility and decreased pregnancy in mated females).

14 Clinical Studies

The safety and efficacy of ketoconazole foam, 2% were evaluated in a randomized, double-blind, vehicle-controlled study in subjects 12 years and older with mild to severe seborrheic dermatitis. In the study, 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.

Table 2: Efficacy Results

16 How Supplied/Storage And Handling

Ketoconazole Foam, 2% is supplied in 50 g (NDC 45802-532-32) and 100 g (NDC 45802-532-33) aluminum containers.

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

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

Contents are flammable.

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

Keep out of reach of children.

17 Patient Counseling Information

See FDA-approved patient labeling. (17.3)

17.1 Instructions For Use

• •Avoid fire, flame and/or smoking during and immediately following application.
• •Do not apply Ketoconazole Foam, 2% directly to hands. Dispense onto a cool surface, and apply to the affected areas using the fingertips.

17.2 Local Reactions

• •Ketoconazole Foam, 2% may cause skin irritation (application site burning and/or reactions)
• •Ketoconazole Foam, 2% may cause contact sensitization.
• •As with any topical medication, patients should wash their hands after application.
• •Inform a physician if the area of application shows signs of increased irritation and report any signs of adverse reactions.

17.3 Patient Package Insert

- See attached –

Patient Information

Ketoconazole Foam, 2%

IMPORTANT: For skin use only. Do not use in the eyes, mouth or vagina.

Read the Patient Information that comes with Ketoconazole Foam, 2% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or treatment.

What is Ketoconazole Foam, 2%?

Ketoconazole Foam, 2% is used on the skin (topical) to treat a skin condition called seborrheic dermatitis in patients 12 years and older. Seborrheic dermatitis can cause areas of flaky skin (scales) on the scalp, face, ears, chest or upper back.

Ketoconazole Foam, 2% has not been studied in children less than 12 years old.

What should I tell my doctor before using Ketoconazole Foam, 2%?

For female patients, tell your doctor if you:

• •are pregnant or become pregnant. It is not known if Ketoconazole Foam, 2% can harm a fetus (unborn baby).
• •breastfeeding. It is not known if Ketoconazole Foam, 2% passes into breast milk.

How should I use Ketoconazole Foam, 2%?

• • •Apply Ketoconazole Foam, 2% exactly as prescribed. Ketoconazole Foam, 2% is usually applied to the affected skin areas two times a day (once in the morning and once at night) for 4 weeks. Talk to your doctor if your skin does not improve after 4 weeks of treatment with Ketoconazole Foam, 2%.
  • • •Keep the Ketoconazole Foam, 2% can away from and do not spray it near fire, open flame, or direct heat. Ketoconazole Foam, 2% is flammable. Never throw the Ketoconazole Foam, 2% can into a fire, even if the can is empty.

    Instructions for applying Ketoconazole Foam, 2%

    • 1.Hold the can at an upright angle.
    • 2.Push the button to spray Ketoconazole Foam, 2% directly into the cap of the can or other cool surface. Spray only the amount of Ketoconazole Foam, 2% that you will need to cover your affected skin.

      Do not spray Ketoconazole Foam, 2% directly onto your affected skin or your hands because the foam will begin to melt right away when it touches your skin.

    • 3.If your fingers are warm, rinse them in cold water first. Be sure to dry them well before handling the Ketoconazole Foam, 2%. If the Ketoconazole Foam, 2% can seems warm or the foam seems runny, place the can under cool running water for a few minutes.
    • 4.Using your fingertips, gently massage Ketoconazole Foam, 2% into the affected areas until the foam disappears.
    • 5.If you are treating skin areas with hair such as your scalp, move any hair away so that the foam can be applied to the affected skin.
    • 6.Do not get Ketoconazole Foam, 2% in your eyes, mouth or vagina. If any Ketoconazole Foam, 2% gets in your eyes, mouth or vagina, rinse areas well with water.
    • 7.Wash your hands well after applying Ketoconazole Foam, 2%.

    What are the possible side effects of Ketoconazole Foam, 2%?

    The most common side effects of Ketoconazole Foam, 2% are reaction or burning on treated skin areas. Tell your doctor if you have any reaction on your treated skin such as redness, itching, or a rash. These are not all the side effects of Ketoconazole Foam, 2%. Ask your doctor or pharmacist for more information.

    How should I store Ketoconazole Foam, 2%?

    • •Ketoconazole Foam, 2% is flammable.
    • •Do not spray Ketoconazole Foam, 2% near fire or direct heat. Never throw the can into a fire, even if the can is empty.
    • •Store the can of Ketoconazole Foam, 2% at room temperature, 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Do not place the Ketoconazole Foam, 2% can in the refrigerator or freezer.
    • •Keep the Ketoconazole Foam, 2% can away from all sources of fire and heat. Do not leave the Ketoconazole Foam, 2% can in direct sunlight.
    • •Do not smoke while holding the Ketoconazole Foam, 2% can or while spraying or applying the foam.
    • •Do not pierce or burn the Ketoconazole Foam, 2% can.
    • •Keep Ketoconazole Foam, 2% and all medicines out of the reach of children.

    General information about Ketoconazole Foam, 2%

    Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use Ketoconazole Foam, 2% for any other condition for which it was not prescribed. Do not give Ketoconazole Foam, 2% to other people, even if they have the same condition that you have. It may harm them.

    This leaflet summarizes the most important information about Ketoconazole Foam, 2%. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Ketoconazole Foam, 2% that is written for health professionals.

    What are the ingredients in Ketoconazole Foam, 2%?

    Active ingredient: ketoconazole, USP

    Inactive Ingredients: cetyl alcohol NF, citric acid USP, ethanol (denatured with tert-butyl alcohol and brucine sulfate) 58%, polysorbate 60 NF, potassium citrate USP, propylene glycol USP, purified water USP, and stearyl alcohol NF pressurized with a hydrocarbon (propane/butane) propellant.

    This Patient Information leaflet has been approved by the U.S. Food and Drug Administration.

    The Patient Information leaflet was last revised: March 2015

    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Rx Only

    Made in Israel

    Manufactured By Perrigo

    Yeruham 80500, Israel

    Distributed By

    Perrigo®

    Allegan, MI 49010

    www.perrigo.com

    Rev 03-15

    : 5K200 RC J2

    
    

Package/Label Principal Display Panel - Carton

Rx Only

45802-532-32

Ketoconazole Foam, 2%

For Topical Use Only.

Not For Ophthalmic, Oral, or Intravaginal Use.

50 g