Prescription Drug Information: Ketoconazole (Page 2 of 3)

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 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 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 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.

14 CLINICAL STUDIES

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.

Table 2: Efficacy Results

Number of Subjects

Ketoconazole Foam, 2%

N = 427

n (%)

Vehicle Foam

N = 420

n (%)

Subjects Achieving Treatment Success

239 (56%)

176 (42%)

16 HOW SUPPLIED/STORAGE AND HANDLING

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

NDC 45802-532-32

50 g aluminum can

NDC 45802-532-33

100 g aluminum can

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.

17 PATIENT COUNSELING INFORMATION

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

Instruct patients on a proper use of ketoconazole foam, 2%.

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.
Wash their hands after application
Ketoconazole 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.

Made in Israel

Manufactured By Padagis

Yeruham, Israel

Distributed By

Padagis

Allegan, MI 49010

www.padagis.com

Rev 09-21

5K200 RC J5

PATIENT INFORMATION

Ketoconazole Foam, 2%

Important Information: Ketoconazole foam, 2% is for use on the skin only. Do not use ketoconazole foam, 2% in your eyes, mouth or vagina.

What is ketoconazole foam, 2%?

Ketoconazole foam, 2% is a prescription medicine used on the skin (topical) to treat seborrheic dermatitis in people 12 years of age and older with a normal immune system.

It is not known if ketoconazole foam, 2% is safe and effective when used to treat fungal infections.

It is not known if ketoconazole foam, 2% is safe and effective in children less than 12 years of age.

Before using ketoconazole 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 ketoconazole foam, 2% will harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if ketoconazole passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with ketoconazole 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 I use ketoconazole foam, 2%?

Use ketoconazole 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 ketoconazole foam, 2% the right way.
Apply ketoconazole foam, 2% to the affected skin area(s) 2 times each day for 4 weeks. You should apply enough ketoconazole foam, 2% to cover the entire affected area(s).
Talk to your healthcare provider if your skin does not improve after 4 weeks of treatment with ketoconazole foam, 2%.
Dispense ketoconazole foam, 2% directly into the cap. Do not dispense ketoconazole foam, 2% directly onto your hands, because the foam will begin to melt on contact with warm skin.
Wash your hands after applying ketoconazole foam, 2%.

What should I avoid while using ketoconazole foam, 2%?

Ketoconazole foam, 2% is flammable. Avoid fire, flames, or smoking during and right after you apply ketoconazole foam, 2% to your skin.
Avoid getting ketoconazole foam, 2% in or near your eyes, mouth, lips or vagina. If you get ketoconazole foam, 2% on your lips or in your eyes, mouth or vagina, rinse well with water.

What are the possible side effects of ketoconazole foam, 2%?

Ketoconazole 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 ketoconazole foam, 2%.

The most common side effects of ketoconazole 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 ketoconazole 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 I store ketoconazole foam, 2%?

Store ketoconazole foam, 2% at room temperature between 68°F to 77°F (20°C to 25°C).
Do not store the ketoconazole foam, 2% can in the refrigerator or freezer.
Keep ketoconazole foam, 2% away from heat. Never throw the ketoconazole foam, 2% can into a fire, even if the can is empty.
Do not store ketoconazole foam, 2% at temperatures above 120°F (49°C).
Do not break through (puncture) the ketoconazole foam, 2% can.
Keep ketoconazole foam, 2% and all medicines out of the reach of children.

General information about the safe and effective use of ketoconazole foam, 2%.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ketoconazole foam, 2% for a condition for which it was not prescribed. Do not give ketoconazole 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 ketoconazole foam, 2% that is written for health professionals.

What are the ingredients in ketoconazole foam, 2%?

Active ingredient: ketoconazole

Inactive Ingredients: cetyl alcohol, citric acid, ethanol 58%, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant

For more information, call Padagis at 1-866-634-9120

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

Instructions for Use

Ketoconazole Foam, 2%

Important Information: Ketoconazole foam, 2% is for use on the skin only. Do not use ketoconazole foam, 2% in your eyes, mouth or vagina.

Step 1: Remove the clear cap from the ketoconazole foam, 2% can.
step-1.jpg
Step 2: Hold the can upright and firmly press the nozzle to dispense ketoconazole foam, 2% into the clear cap.
Dispense enough ketoconazole foam, 2% to cover the entire affected area(s).
step-2.jpg
If the can seems warm or the foam seems runny, run the can under cold water.
step-2.1.jpg
Step 3: Pick up small amounts of ketoconazole foam, 2% with your fingertips and gently rub the foam into the affected area(s) until the foam disappears.
step-3.jpg
(click image for full-size original)
If you are treating areas such as your scalp, part the hair so that ketoconazole foam, 2% may be applied directly to the skin.
step-3.1.jpg
Step 4: Wash your hands after applying ketoconazole foam, 2%.
Throw away any of the unused medicine that is left in the cap.
step-4.jpg

How should I store ketoconazole foam, 2%?

Store ketoconazole foam, 2% at room temperature between 68°F to 77°F (20°C to 25°C).
Do not store the ketoconazole foam, 2% can in the refrigerator or freezer.
Keep ketoconazole foam, 2% away from heat. Never throw the can into a fire, even if the can is empty.
Do not store ketoconazole foam, 2% at temperatures above 120°F (49°C).
Do not break through (puncture) the ketoconazole foam, 2% can.

Keep ketoconazole 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.

Rx Only

Made in Israel

Manufactured By Padagis

Yeruham, Israel

Distributed By

Padagis

Allegan, MI 49010

www.padagis.com

Rev 09-21

5K200 RC J5

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