Clinical data
Trade names Differin, Pimpal, Gallet, Adelene, Adeferin
AHFS/ Monograph
MedlinePlus a604001
License data
  • AU: D
  • US: C (Risk not ruled out)
    Routes of
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability Very low
    Excretion Biliary
    CAS Number
    PubChem CID
    ECHA InfoCard 100.149.379
    Chemical and physical data
    Formula C28H28O3
    Molar mass 412.52 g/mol
    3D model (JSmol)

    Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions.[1] It is effective against acne conditions where comedones are predominant.

    Medical uses

    It is used for the treatment of acne.[2]

    Off-label uses

    Adapalene has the unique ability to inhibit keratinocyte differentiation and decrease keratin deposition. This property makes adapalene an effective treatment for keratosis pilaris and callus. It may be used by men undergoing foreskin restoration to reduce excess keratin that forms a layer on the exterior of the human penis after circumcision.

    Side effects

    It is common (between 1% and 10% of users)[3] to experience a brief sensation of warmth or stinging, as well as skin redness and dryness during the first 2-4 weeks of using the medication.[4] These effects generally decrease over time.[4] Any serious allergic reaction is rare.[4]

    In pregnancy

    This use has not been well studied. Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy. Use is at the consumer’s own risk.[2]


    Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased.[5] Application of adapalene gel to the skin 3–5 minutes before application of clindamycin enhances penetration of clindamycin into the skin, which may enhance the overall efficacy of the treatment as compared to clindamycin alone.[6]


    Unlike the retinoid tretinoin (Retin-A), adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure.[7]


    Absorption of adapalene through the skin is low. A study with six acne patients treated once daily for five days with two grams of adapalene cream applied to 1000 cm² of skin found no quantifiable amounts, or less than 0.35 ng/mL of the drug, in the patients' blood plasma.[8]


    Unlike tretinoin, adapalene inhibits keratinocyte differentiation. This inhibition of keratinocyte differentiation and proliferation is responsible for adapalene’s comedolytic effect. It has both exfoliating and anti-inflammatory effects. In an in vivo study, adapalene’s ability to reduce comedo formation was demonstrated by a 50–60% reduction in comedo counts compared with vehicle.[9]

    Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those that constitute skin.[10] Its agonism of the gamma subtype is largely responsible for adapalene's observed effects. In fact, when adapalene is applied in conjuction with a retinoic acid receptor gamma antagonist, adapalene loses clinical efficacy.[11]


    Adapalene is a research product of Galderma Laboratories, France.[12] Adapalene was approved in 1996 by the U.S. Food and Drug Administration (FDA) for use in the treatment of acne.[13]

    Available forms

    In the United States, adapalene is available under the brand name Differin in three preparations: 0.1% cream, 0.1% gel, and 0.3% gel.[14] The 0.1% gel is available as a generic made by Teva.[15][16] It is also available combined with benzoyl peroxide under the brand name Epiduo.[17] In Europe, only the 0.1% cream and 0.1% gel are available. Adapalene is currently marketed by Galderma under the trade names Differin in some countries, and Adaferin in India.[18] It is mostly available in 0.1% w/w gel form.

    As of July 8, 2016, Galderma received approval from the U.S. Food and Drug Administration (FDA) for Differin Gel (adapalene gel 0.1%) as an over-the-counter (OTC) treatment for acne.[2]

    The Proactiv Company also sells the adapalene gel 0.1% under its brand name Proactiv MD Adapalene 0.1%.


    1. Rolewski SL (October 2003). "Clinical review: topical retinoids". Dermatology Nursing. 15 (5): 447–50, 459–65. PMID 14619325.
    2. 1 2 3 "FDA approves Differin Gel 0.1% for over-the-counter use to treat acne". July 8, 2016. Retrieved 14 July 2016.
    3. "Differin". Swedish Drug Formulary. Retrieved 2017-12-11.
    4. 1 2 3 "Adapalene Gel". WebMD. Retrieved 2017-12-11.
    5. Wolf JE, Kaplan D, Kraus SJ, Loven KH, Rist T, Swinyer LJ, Baker MD, Liu YS, Czernielewski J (September 2003). "Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study". Journal of the American Academy of Dermatology. 49 (3 Suppl): S211–7. doi:10.1067/S0190-9622(03)01152-6. PMID 12963897.
    6. Jain GK, Ahmed FJ (2007). "Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies". Indian Journal of Dermatology, Venereology and Leprology. 73 (5): 326–9. doi:10.4103/0378-6323.34010. PMID 17921613.
    7. Martin B, Meunier C, Montels D, Watts O (October 1998). "Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation". The British Journal of Dermatology. 139 Suppl 52: 8–11. doi:10.1046/j.1365-2133.1998.1390s2008.x. PMID 9990414.
    8. "DIFFERIN® (adapalene) Cream, 0.1% Label" (PDF). FDA. May 25, 2000. Retrieved 4 Oct 2011.
    9. Czernielewski J, Michel S, Bouclier M, Baker M, Hensby JC (December 2001). "Adapalene biochemistry and the evolution of a new topical retinoid for treatment of acne". Journal of the European Academy of Dermatology and Venereology. 15 Suppl 3 (s3): 5–12. doi:10.1046/j.0926-9959.2001.00006.x. PMID 11843234.
    10. Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G (2006). "Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety". Clinical Interventions in Aging. 1 (4): 327–48. PMC 2699641. PMID 18046911.
    11. Michel S, Jomard A, Démarchez M (October 1998). "Pharmacology of adapalene". The British Journal of Dermatology. 139 Suppl 52: 3–7. doi:10.1046/j.1365-2133.1998.1390s2003.x. PMID 9990413.
    12. US Patent 4717720A, Shroot B, Eustache J, Bernardon J-M, "Benzonaphthalene derivatives and compositions", published 1988-01-05, issued 1988-01-05, assigned to Galderma Research and Development SNC
    13. "FDA approval of DIFFERIN® (adapalene) Solution, 0.1%". FDA. May 31, 1996. Retrieved 29 May 2017.
    14. About Differin Archived May 9, 2008, at the Wayback Machine.
    15. "Teva Introduces Adapalene Gel, 0.1%". PharmQD. 4 June 2010. Retrieved 30 Aug 2011.
    16. Webber K (2 June 2010). "FDA Approval Letter" (PDF). Department of Health and Human Services. Retrieved 30 August 2011.
    17. "EPIDUO® (adapalene and benzoyl peroxide) Gel 0.1%/2.5% Approval Letter" (PDF). FDA. Dec 8, 2008. Retrieved 29 May 2017.
    18. "Deriva-CMS from Glenmark (Gracewill) [ADAPALENE]".
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