Adapalene and Benzoyl Peroxide Gel

Name: Adapalene and Benzoyl Peroxide Gel

Indications and Usage for Adapalene and Benzoyl Peroxide Gel


 Adapalene and Benzoyl Peroxide gel is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

Adapalene and Benzoyl Peroxide Gel Dosage and Administration

For topical use only; Adapalene and Benzoyl Peroxide gel is not for oral, ophthalmic, or intravaginal use.

Apply a thin film of Adapalene and Benzoyl Peroxide gel to affected areas of the face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes.

Dosage Forms and Strengths

Each gram of Adapalene and Benzoyl Peroxide gel contains 1 mg (0.1%) adapalene and 25 mg (2.5%) benzoyl peroxide in a white to very pale yellow, opaque, aqueous based gel.

Contraindications

None

Drug Interactions

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents.

No formal drug-drug interaction studies were conducted with Adapalene and Benzoyl Peroxide gel.

Adapalene and Benzoyl Peroxide Gel - Clinical Pharmacology

Mechanism of Action

Adapalene

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl peroxide

Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects.

Pharmacodynamics

Pharmacodynamics of  Adapalene and Benzoyl Peroxide gel is unknown.

Pharmacokinetics

A pharmacokinetic study was conducted in 10 adult subjects with acne vulgaris who were treated once daily for 30 days with 2 grams/day of Adapalene and Benzoyl Peroxide gel applied to 1000 cm2 of acne involved skin, (face, chest, and upper back).

Two subjects (20%) had quantifiable adapalene plasma concentrations above the limit of quantification (LOQ = 0.1ng/mL). The highest adapalene Cmax and AUC0-24h was 0.21 ng/mL and 1.99 ng•h/mL, respectively. Excretion of adapalene appears to be primarily by the biliary route. Pharmacokinetics of  Adapalene and Benzoyl Peroxide gel in pediatric subjects have not been evaluated.

Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, photocarcinogenicity, genotoxicity, or fertility studies were conducted with  Adapalene and Benzoyl Peroxide gel.

Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m2/day), and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3.0, and 9.0 mg/m2/day).  In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of 2 grams of Adapalene and Benzoyl Peroxide gel. In the rat study, an increased incidence of benign and malignant pheochromocytomas in the adrenal medulla of male rats was observed.

No significant increase in tumor formation was observed in rodents topically treated with 15-25% benzoyl peroxide carbopol gel (6-10 times the concentration of benzoyl peroxide in  Adapalene and Benzoyl Peroxide gel) for two years. Rats received maximum daily applications of 138 (males) and 205 (females) mg benzoyl peroxide/kg. In terms of body surface area, these levels are 27-40 times the MRHD. Similar results were obtained in mice topically treated with 25% benzoyl peroxide carbopol gel for 56 weeks followed by intermittent treatment with 15% benzoyl peroxide carbopol gel for the rest of the 2 year study period, and in mice topically treated with 5% benzoyl peroxide carbopol gel for two years.

The role of benzoyl peroxide as a tumor promoter has been well established in several animal species. However, the significance of this finding in humans is unknown.

In a photocarcinogenicity study conducted with 5% benzoyl peroxide carbopol gel, no increase in UV-induced tumor formation was observed in hairless mice topically treated for 40 weeks.

No photocarcinogenicity studies were conducted with adapalene. However, animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g., retinoids) when exposed to UV irradiation in the laboratory or sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources.

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test).

Bacterial mutagenicity assays (Ames test) with benzoyl peroxide has provided mixed results, mutagenic potential was observed in a few but not in a majority of investigations. Benzoyl peroxide has been shown to produce single-strand DNA breaks in human bronchial epithelial and mouse epidermal cells, it has caused DNA-protein cross-links in the human cells, and has also induced a dose-dependent increase in sister chromatid exchanges in Chinese hamster ovary cells.

In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

No fertility studies were conducted with benzoyl peroxide.

Patient Counseling Information

[See FDA approved Patient Labeling (Patient Information)]

Information for Patients

- Advise patients to cleanse the area to be treated with a mild or soapless cleanser; pat dry. Apply Adapalene and Benzoyl Peroxide gel as a thin layer, avoiding the eyes, lips and mucous membranes.

- Advise patients not to use more than the recommended amount and not to apply more than once daily as this will not produce faster results, but may increase irritation.

- Adapalene and Benzoyl Peroxide gel may cause irritation such as erythema, scaling, dryness, stinging or burning.

- Advise patients to minimize exposure to sunlight, including sunlamps.

- Recommend the use of sunscreen products and protective apparel, (e.g., hat) when exposure cannot be avoided.

- Adapalene and Benzoyl Peroxide gel may bleach hair and colored fabric.

Patient Information


Adapalene and Benzoyl Peroxide gel
0.1%/2.5%

Important: For use on the skin only (topical). Do not use Adapalene and Benzoyl Peroxide gel in or on your mouth, eyes, or vagina.

Read this Patient Information leaflet about Adapalene and Benzoyl Peroxide gel 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 treatment or your medical condition. If you have any questions about Adapalene and Benzoyl Peroxide gel, talk with your doctor or pharmacist.

What is Adapalene and Benzoyl Peroxide gel?
Adapalene and Benzoyl Peroxide gel is a prescription medicine for skin use only (topical) used to treat acne vulgaris in people 9 years of age and older.

Acne vulgaris is a condition in which the skin has blackheads, whiteheads and pimples.

It is not known if Adapalene and Benzoyl Peroxide gel is safe and effective in children younger than 9 years old.

What should I tell my doctor before using Adapalene and Benzoyl Peroxide gel?
Before you use Adapalene and Benzoyl Peroxide gel, tell your doctor if you:

  • have other skin problems, including cuts or sunburn
  • have any other medical conditions
  • are pregnant or planning to become pregnant. It is not known if Adapalene and Benzoyl Peroxide gel can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed. It is not known if Adapalene and Benzoyl Peroxide gel passes into your breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you use Adapalene and Benzoyl Peroxide gel.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.

Especially tell your doctor if you use any other medicine for acne. Using Adapalene and Benzoyl Peroxide gel with topical medicines that contain sulfur, resorcinol or salicylic acid may cause skin irritation.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I use Adapalene and Benzoyl Peroxide gel?

  • Use Adapalene and Benzoyl Peroxide gel exactly as your doctor tells you to use it. Adapalene and Benzoyl Peroxide gel is for skin use only. Do not use Adapalene and Benzoyl Peroxide gel in or on your mouth, eyes, or vagina.
  • Apply Adapalene and Benzoyl Peroxide gel 1 time a day.
  • Do not use more Adapalene and Benzoyl Peroxide gel than you need to cover the treatment area. Using too much Adapalene and Benzoyl Peroxide gel or using it more than 1 time a day may increase your chance of skin irritation.

Applying Adapalene and Benzoyl Peroxide gel:

  • Wash the area where the gel will be applied with a mild cleanser and pat dry.
  • Adapalene and Benzoyl Peroxide gel comes in a pump. If you have been prescribed the:
    • Pump: Depress the pump to dispense a small amount (about the size of a pea) of Adapalene and Benzoyl Peroxide gel and spread a thin layer over the affected area.

What should I avoid while using Adapalene and Benzoyl Peroxide gel?

  • You should avoid spending time in sunlight or artificial sunlight, such as tanning beds or sunlamps. Adapalene and Benzoyl Peroxide gel can make your skin sensitive to sun and the light from tanning beds and sunlamps. You should wear sunscreen and wear a hat and clothes that cover the areas treated with Adapalene and Benzoyl Peroxide gel if you have to be in sunlight.
  • You should avoid weather extremes such as wind and cold as this may cause irritation to your skin.
  • You should avoid applying Adapalene and Benzoyl Peroxide gel to cuts, abrasions and sunburned skin.
  • You should avoid skin products that may dry or irritate your skin such as harsh soaps, astringents, cosmetics that have strong skin- drying effects and products containing high levels of alcohol.
  • You should avoid the use of “waxing” as a hair removal method on skin treated with Adapalene and Benzoyl Peroxide gel.
  • Adapalene and Benzoyl Peroxide gel may bleach your clothes or hair. Allow Adapalene and Benzoyl Peroxide gel to dry completely before dressing to prevent bleaching of your clothes.

What are the possible side effects of Adapalene and Benzoyl Peroxide gel?

Adapalene and Benzoyl Peroxide gel may cause serious side effects including:

  • Local skin reactions. Local skin reactions are most likely to happen during the first 4 weeks of treatment and usually lessen with continued use of Adapalene and Benzoyl Peroxide gel. Signs and symptoms of local skin reaction include:
    • Redness
    • Dryness
    • Swelling
    • Scaling
    • Stinging or burning

Tell your doctor right away if these side effects continue for longer than 4 weeks or get worse, you may have to stop using Adapalene and Benzoyl Peroxide gel.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Adapalene and Benzoyl Peroxide gel. For more information, ask your doctor or pharmacist.

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

You may also report side effects to Prasco Laboratories at 1-866-525-0688.

How should I store Adapalene and Benzoyl Peroxide gel?

  • Store Adapalene and Benzoyl Peroxide gel at room temperature, 68° - 77° F (20° - 25° C).
  • Keep Adapalene and Benzoyl Peroxide gel inside container and out of light and away from heat.

Keep Adapalene and Benzoyl Peroxide gel and all medicines out of the reach of children.

General information about Adapalene and Benzoyl Peroxide gel

 Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Adapalene and Benzoyl Peroxide gel for a condition for which it was not prescribed. Do not give Adapalene and Benzoyl Peroxide gel to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Adapalene and Benzoyl Peroxide gel . If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about Adapalene and Benzoyl Peroxide gel that is written for health professionals.

What are the ingredients in Adapalene and Benzoyl Peroxide gel?
Active ingredient: adapalene and benzoyl peroxide
Inactive ingredients: acrylamide/sodium acryloydimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water and sorbitan oleate

Revised: February 2017

Marketed by:
Prasco Laboratories, Mason, OH 45040 USA
Manufactured by:
G Production Inc., Baie d’Urfé, QC, H9X 3S4 Canada
Made in Canada.

P53525-0

 

 

NDC 66993-869-48

Prasco

Adapalene and Benzoyl Peroxide Gel
0.1% / 2.5%

PUMP

FOR TOPICAL USE ONLY

P53623-0

Rx only

NET WT. 45 g

For topical use only. Not for ophthalmic, oral or intravaginal use.

Usual dosage: Apply a thin film once a day to affected areas.

See package insert for complete prescribing information.

Each gram contains Active: adapalene 0.1% and benzoyl peroxide 2.5% in an aqueous gel consisting of Inactive: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

Storage: Store at controlled room temperature 68° to 77°F (20° to 25°C) with excursions permitted between 59° and 86°F (15° and 30°C).

Marketed by:
Prasco Laboratories, Mason, OH 45040 USA
Manufactured by:
G Production Inc.
Baie d’Urfé, QC, H9X 3S4 Canada


Made in Canada.

See lot number and expiration date below.

ADAPALENE AND BENZOYL PEROXIDE 
Adapalene and Benzoyl Peroxide Gel
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:66993-869
Route of Administration TOPICAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ADAPALENE (ADAPALENE) ADAPALENE 1 mg  in 1 g
BENZOYL PEROXIDE (BENZOYL PEROXIDE) BENZOYL PEROXIDE 25 mg  in 1 g
Inactive Ingredients
Ingredient Name Strength
DOCUSATE SODIUM  
EDETATE DISODIUM  
GLYCERIN  
ISOHEXADECANE  
POLOXAMER 124  
POLYSORBATE 80  
PROPYLENE GLYCOL  
WATER  
SORBITAN MONOOLEATE  
Packaging
# Item Code Package Description
1 NDC:66993-869-48 45 g in 1 BOTTLE, PUMP
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA AUTHORIZED GENERIC NDA022320 08/03/2017
Labeler - Prasco Laboratories (065969375)
Revised: 08/2017   Prasco Laboratories
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