Adapalene Gel Usp, 0.3%

Prescription

Brand names: Adapalene Gel USP, 0.3%

Dosage Form

Topical

Route

TOPICAL

Manufacturer

Encube Ethicals, Inc.

About This Medication

11 DESCRIPTION Adapalene Gel USP, 0.3% contains adapalene 0.3% (3 mg/g) in a topical aqueous gel for use in the treatment of acne vulgaris, consisting of carbomer 980, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water, and sodium hydroxide. May contain hydrochloric acid for pH adjustment. The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. It is a white to off-white powder, which is soluble in tetrahydrofuran, very slightly soluble in ethanol, and practically insoluble in water. The molecular formula is C 28 H 28 O 3 and molecular weight is 412.53. Adapalene is represented by the following structural formula. adap-str

Active Ingredients

Ingredient	Strength
Adapalene	-

Indications & Usage

1 INDICATIONS AND USAGE ADAPALENE Gel, 0.3% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. ADAPALENE Gel, 0.3% is a retinoid, indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

How It Works

12.1 Mechanism of Action 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.

Dosage & Administration

2 DOSAGE AND ADMINISTRATION Wash affected areas gently with a non-medicated soap. Apply a thin film of adapalene gel, 0.3% to the entire face and any other affected areas of the skin once daily in the evening. Avoid application to the areas of skin around eyes, lips, and mucous membranes. A mild transitory sensation of warmth or slight stinging may occur shortly after the application of adapalene gel,0.3%. Instruct patients to minimize sun exposure and to use moisturizers for relief of dry skin or irritation. If therapeutic results are not noticed after 12 weeks of treatment, therapy should be re-evaluated. For topical use only. Not for ophthalmic, oral or intravaginal use. • Wash affected areas gently with a non-medicated soap. ( 2 ) • Apply a thin film of adapalene gel, to the entire face and other affected areas of the skin once daily in the evening. ( 2 ) For topical use only. Not for ophthalmic, oral or intravaginal use. ( 2 )

Side Effects Overview

6 ADVERSE REACTIONS The most frequently reported (≥1%) adverse reactions were erythema,scaling, dryness, and/or burning/stinging. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 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 reactions 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. In the multi-center, controlled clinical trial, signs and symptoms of local cutaneous irritation were monitored in 258 acne subjects who used Adapalene gel, 0.3% once daily for 12 weeks. Of the subjects who experienced cutaneous irritation (erythema, scaling, dryness, and/or burning/stinging), the majority of cases were mild to moderate in severity, occurred early in treatment and decreased thereafter. The incidence of local cutaneous irritation with Adapalene gel, 0.3% from the controlled clinical trial is provided in the following table: Table 1: Physician assessed local cutaneous irritation with Adapalene gel Incidence of Local Cutaneous Irritation with Adapalene gel, 0.3% (N = 253*) Maximum Severity Scores Higher Than Mild Moderate Severe Erythema 66 (26.1%) 33 (13.0%) 1 (0.4%) Scaling 110 (43.5%) 47 (18.6%) 3 (1.2%) Dryness 113 (44.7%) 43 (17.0%) 2 (0.8%) Burning / Stinging 72 (28.5%) 36 (14.2%) 9 (3.6%) * Total number of subjects with local cutaneous data for at least one post-Baseline evaluation. Table 2: Patient reported local cutaneous adverse reactions with Adapalene Gel Adapalene Gel, 0.3% Vehicle Gel N = 258 N = 134 Related* Adverse Reactions Dry Skin Skin Discomfort 57 (22.1%) 36 (14%) 15 (5.8%) 4 (1.6%) 6 (4.5%) 2 (1.5%) 0 (0.0%) 0 (0.0%) * Selected adverse reactions defined by investigator as Possibly, Probably or Definitely Related The following adverse reactions occurred in less than 1 % of subjects: acne flare, contact dermatitis, eyelid edema, conjunctivitis, erythema, pruritus, skin discoloration, rash, and eczema. In a one-year, open-label safety trial of 551 subjects with acne who received Adapalene gel, 0.3%, the pattern of adverse reactions was similar to the 12-week controlled study. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of adapalene: Immune system disorders: angioedema, face edema, lip swelling Skin disorders: application site pain Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Warnings & Precautions

5 WARNINGS AND PRECAUTIONS • Allergic/ Hypersensitivity Reactions: Allergy/hypersensitivity reactions include anaphylaxis, angioedema, face edema, eyelid edema, lip swelling, and pruritis. Discontinue adapalene gel in the event of an allergic/hypersensitivity reaction. ( 5.1 ) • Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided ( 5.2 ). • Local Cutaneous Reactions: Erythema, scaling, dryness. and stinging/burning were reported with use of adapalene gel. Concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution. ( 5.3 ). 5.1 Allergic/ Hypersensitivity Reactions Adverse reactions including anaphylaxis angioedema, face edema, eyelid edema, lip swelling, and pruritus that sometimes required medical treatment have been reported during postmarketing use of adapalene. Advise a patient to stop using Adapalene gel, 0.3% and seek medical attention if experiencing allergic or anaphylactoid/ anaphylactic reactions during treatment. 5.2 Ultraviolet Light and Environmental Exposure Exposure to sunlight, including sunlamps, should be minimized during use of adapalene gel, 0.3%. Patients who normally experience high levels of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with adapalene gel, 0.3%. 5.3 Local Cutaneous Reactions Cutaneous signs and symptoms such as erythema, scaling, dryness, and stinging/ burning were reported with use of adapalene gel, 0.3%. These were most likely to occur during the first four weeks of treatment, were mostly mild to moderate in intensity, and usually lessened with continued use of the medication. Depending upon the severity of these side effects, patients should be instructed to either use a moisturizer, reduce the frequency of application of adapalene gel, 0.3% or discontinue use. Avoid application to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of "waxing" as a depilatory method should be avoided on skin treated with adapalene. As adapalene gel, 0.3% has the potential to induce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution.

Contraindications

4 CONTRAINDICATIONS Adapalene gel, 0.3% is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel, 0.3% [see WARNINGS AND PRECAUTIONS (5.1) ]. Contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel,0.3%

Pharmacokinetics

12.3 Pharmacokinetics Systemic exposure of adapalene following topical application of adapalene gel was evaluated in a clinical trial. Sixteen acne subjects were treated once daily for 10 days with 2 grams of adapalene gel, 0.3% applied to the face, chest and back, corresponding to approximately 2 mg/cm 2 . Fifteen subjects had quantifiable (LOQ = 0.1 ng/mL) adapalene levels resulting in a mean C max , of 0.553 ± 0.466 ng/mL on Day 10 of treatment. The mean AUC 0-24hr was 8.37 ± 8.46 ng.h/mL as determined in 15 of the 16 subjects on Day 10. The terminal apparent half-life, determined in 15 of 16 subjects, ranged from 7 to 51 hours, with a mean of 17.2 ± 10.2 hours. Adapalene was rapidly cleared from plasma and was not detected 72 hours after the last application for all but one subject. Exposure of potential circulating metabolites of adapalene was not measured. Excretion of adapalene appears to be primarily by the biliary route. In another clinical trial in subjects with moderate to moderately severe acne, Adapalene gel, 0.3% or Adapalene Gel, 0.1% was applied to the face and optionally to the trunk, once daily for 12 weeks. Seventy-eight (78) subjects had plasma adapalene levels evaluated at Weeks 2, 8, and 12. Of the 209 plasma samples analyzed, adapalene concentrations were below the limit of detection (LOD = 0.15 ng/mL) of the method in all samples but three. For the three samples, traces of adapalene below the limit of quantification (LOQ= 0.25 ng/mL) of the method were found. One of these samples was taken at Week 12 from a male subject treated with adapalene gel, 0.3% who treated the face and the trunk for eight weeks (thereafter, only the face was treated). The second and third samples were from the Week 2 and 12 visits of a female subject treated with Adapalene Gel, 0.1% who treated only the face for 12 weeks. In this study, the average daily usage of product was 1 g/day.

Frequently Asked Questions

1 INDICATIONS AND USAGE ADAPALENE Gel, 0.3% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. ADAPALENE Gel, 0.3% is a retinoid, indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

2 DOSAGE AND ADMINISTRATION Wash affected areas gently with a non-medicated soap. Apply a thin film of adapalene gel, 0.3% to the entire face and any other affected areas of the skin once daily in the evening. Avoid application to the areas of skin around eyes, lips, and mucous membranes. A mild transitory sensation of warmth or slight stinging may occur shortly after the application of adapalene gel,0.3%. Instruct patients to minimize sun exposure and to use moisturizers for relief …

5 WARNINGS AND PRECAUTIONS • Allergic/ Hypersensitivity Reactions: Allergy/hypersensitivity reactions include anaphylaxis, angioedema, face edema, eyelid edema, lip swelling, and pruritis. Discontinue adapalene gel in the event of an allergic/hypersensitivity reaction. ( 5.1 ) • Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided ( 5.2 ). • Local Cutaneous Reactions: Erythema, scaling, dryness. and stinging/burning were reported with use of adapalene gel. Concomitant use of other potentially irritating topical …

4 CONTRAINDICATIONS Adapalene gel, 0.3% is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel, 0.3% [see WARNINGS AND PRECAUTIONS (5.1) ]. Contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel,0.3%

Adapalene Gel Usp, 0.3% is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

References & Data Sources

• DailyMed — Adapalene Gel Usp, 0.3% drug label (National Library of Medicine)
• openFDA — Adapalene Gel Usp, 0.3% label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 722111 (NLM Normalized Drug Names)
• NDC Directory — Adapalene Gel Usp, 0.3% (FDA National Drug Code)

Medical Disclaimer

The information on this page is intended for educational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment.

Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication.

Data sources: DailyMed (NLM), openFDA, MFDS