DIFFERIN® Gel, containing adapalene, is used for the topical treatment of acne vulgaris. Each gram of DIFFERIN® Gel contains adapalene 0.1% (1 mg) in a vehicle consisting of carbomer 940, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water and sodium hydroxide. May contain hydrochloric acid to adjust pH.

The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. Adapalene is a white to off-white powder which is soluble in tetrahydrofuran, sparingly soluble in ethanol, and practically insoluble in water. The molecular formula is C₂₈H₂₈O₃ and molecular weight is 412.52. Adapalene is represented by the following structural formula:

Last updated on RxList: 9/19/2007

DIFFERIN® Gel is indicated for the topical treatment of acne vulgaris.

DIFFERIN® Gel should be applied once a day to affected areas after washing in the evening before retiring. A thin film of the gel should be applied, avoiding eyes, lips, and mucous membranes.

During the early weeks of therapy, an apparent exacerbation of acne may occur. This is due to the action of the medication on previously unseen lesions and should not be considered a reason to discontinue therapy. Therapeutic results should be noticed after eight to twelve weeks of treatment.

DIFFERIN® (adapalene gel) Gel, 0.1% is supplied in the following sizes:

45g laminate tube NDC 0299-5910-45

75g laminate tube NDC 0299-5910-75

Storage: Store at controlled room temperature 68° - 77°F (20° - 25°C), excursions permitted between 59° and 86°F (15° - 30°C). Protect from freezing.

Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, Texas 76177, USA. Mfd. by: Galderma Production Canada Inc. Baie d'Urfe, QC, H9X 3S4 Canada. Made in Canada. GALDERMA is a registered trademark. www.differin.com P51101-0. Revised: April 2007. FDA Rev date: 9/5/2007

Last updated on RxList: 9/19/2007

Some adverse effects such as erythema, scaling, dryness, pruritus, and burning will occur in 10-40% of patients. Pruritus or burning immediately after application also occurs in approximately 20% of patients. The following additional adverse experiences were reported in approximately 1% or less of patients: skin irritation, burning/stinging, erythema, sunburn, and acne flares. These are most commonly seen during the first month of therapy and decrease in frequency and severity thereafter. All adverse effects with use of DIFFERIN® Gel during clinical trials were reversible upon discontinuation of therapy.

As DIFFERIN® Gel has the potential to produce 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. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid in combination with DIFFERIN® Gel. If these preparations have been used, it is advisable not to start therapy with DIFFERIN® Gel until the effects of such preparations in the skin have subsided.

Last updated on RxList: 9/19/2007

Use of DIFFERIN® Gel should be discontinued if hypersensitivity to any of the ingredients is noted. Patients with sunburn should be advised not to use the product until fully recovered.

General

If a reaction suggesting sensitivity or chemical irritation occurs, use of the medication should be discontinued. Exposure to sunlight, including sunlamps, should be minimized during the use of adapalene. 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. Avoid contact with the eyes, lips, angles of the nose, and mucous membranes. The product should not be applied to cuts, abrasions, eczematous skin, or sunburned skin.

Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may be experienced during treatment. These are most likely to occur during the first two to four weeks and will usually lessen with continued use of the medication. Depending upon the severity of adverse events, patients should be instructed to reduce the frequency of application or discontinue use.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.3, 0.9, and 2.6 mg/kg/day and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day, approximately 4-75 times the maximal daily human topical dose. In the oral study, positive linear trends were observed in the incidence of follicular cell adenomas and carcinomas in the thyroid glands of female rats, and in the incidence of benign and malignant pheochromocytomas in the adrenal medullas of male rats.

No photocarcinogenicity studies were conducted. 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 to sunlight. Although the significance of these studies to human use is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial UV irradiation sources.

In a series of in vivo and in vitro studies, adapalene did not exhibit mutagenic or genotoxic activities.

Pregnancy: Teratogenic effects. Pregnancy Category C. No teratogenic effects were seen in rats at oral doses of adapalene 0.15 to 5.0 mg/kg/day, up to 120 times the maximal daily human topical dose. Cutaneous route teratology studies conducted in rats and rabbits at doses of 0.6, 2.0, and 6.0 mg/kg/day, up to 150 times the maximal daily human topical dose exhibited no fetotoxicity and only minimal increases in supernumerary ribs in rats. There are no adequate and well-controlled studies in pregnant women. Adapalene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DIFFERIN® Gel is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Last updated on RxList: 9/19/2007

DIFFERIN® Gel is intended for cutaneous use only. If the medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. The acute oral toxicity of DIFFERIN® Gel in mice and rats is greater than 10 mL/kg. Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.

DIFFERIN® Gel should not be administered to individuals who are hypersensitive to adapalene or any of the components in the vehicle gel.

Last updated on RxList: 9/19/2007

Adapalene is a chemically stable, retinoid-like compound. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris.

Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Pharmacokinetics: Absorption of adapalene through human skin is low. Only trace amounts (<0.25 ng/mL) of parent substance have been found in the plasma of acne patients following chronic topical application of adapalene in controlled clinical trials. Excretion appears to be primarily by the biliary route.

Last updated on RxList: 9/19/2007

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 9/19/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ADAPALENE - TOPICAL

(a-DAP-a-leen)

COMMON BRAND NAME(S): Differin

USES: This medication is used to treat acne. It may decrease the number and severity of acne pimples and promote quick healing of pimples that do develop. Adapalene belongs to a class of medications called retinoids. It works by affecting the growth of cells and decreasing swelling and inflammation.

HOW TO USE: Wash your hands before applying this medication. Gently clean the affected skin with a mild or soapless cleanser and pat dry. Use your fingertips to apply a small amount of medication (about the size of a pea) in a thin layer, usually once daily at bedtime, or as directed by your doctor. A gauze pad or cotton swab can be used to apply the solution.

Use this medication on the skin only. Do not apply to the inner lip area or inside the nose/mouth. Do not apply to cut, scraped, sunburned, or eczema-affected skin.

Avoid getting this medication in your eyes. If this medication gets into your eyes, flush with large amounts of water. Call your doctor if eye irritation develops. Wash your hands after using the medication to avoid accidentally getting it in your eyes.

During the first few weeks of using adapalene, your acne might appear worse because the medication is working on pimples forming inside the skin. It may take up to 8-12 weeks to notice results from this medication.

Use it regularly in order to get the most benefit from it. To help you remember, use it at the same time each day. Do not use a larger amount or use it more frequently than recommended. Your skin will not improve any faster, and it will increase the risk of developing redness, peeling and pain.

This medication is available in different strengths and forms (e.g., gel, cream, solution). The best type of medication for you to use will depend on the condition of your skin and your response to therapy. Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: A brief sensation of warmth or stinging may occur immediately after applying the medication. Skin redness, dryness, itching, scaling, mild burning, or worsening of acne may occur during the first 2-4 weeks of using the medication. These effects usually decrease with continued use. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Your doctor may want you to decrease how often you use adapalene, change the strength, or have you stop using it.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: very red/irritated skin, an intense burning sensation, eye redness and watering (conjunctivitis), eyelid swelling, skin discoloration.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using adapalene, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eczema.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Weather extremes such as wind or cold may also be irritating to the skin. Use a sunscreen daily and wear protective clothing when outdoors. Wait until your skin has completely recovered from a sunburn before using adapalene.

Avoid electrolysis, waxing and chemical depilatories for hair removal on the treated areas while using this product.

If you have recently used products containing sulfur, resorcinol or salicylic acid, use adapalene with caution. Wait until the effects of such products on the skin have decreased before using adapalene.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also Precautions section.

Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: products containing alpha hydroxy acids, products containing glycolic acid.

If you are currently using medications containing the ingredients listed above, tell your doctor or pharmacist before starting adapalene.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: hair perming solutions, alcohol/lime/menthol-containing products (such as astringents, toners, shaving lotions), medicated or abrasive soaps and cleansers, products containing sulfur, resorcinol or salicylic acid, soaps and cosmetics with a strong drying effect, other drugs that may increase your sensitivity to sunlight (e.g., fluoroquinolones such as ciprofloxacin, tetracyclines, thiazide water pills such as hydrochlorothiazide, sulfa drugs such as sulfamethoxazole, phenothiazines such as chlorpromazine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medication may be harmful if swallowed.

NOTES: Do not share this medication with others.

Cosmetics may be used, but clean skin thoroughly before applying the medication.

Some cosmetics and soaps may worsen your acne. Moisturizers may be safe to use. When buying cosmetics, moisturizers or other skin care products, check the label for "non-comedogenic" or "non-acnegenic." These products are unlikely to worsen your acne. Ask your doctor or pharmacist which products are safe to use. Remember, acne is not caused by dirt. Cleaning your skin too often or too vigorously can irritate your skin and worsen acne.

MISSED DOSE: If you forget to use this medication, use it as soon as you remember if you remember the same day. If you don't remember until morning, wait until your next dose is scheduled.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Gel preparations are flammable. Do not expose to heat or fire sources. Do not smoke during use. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.