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Adapalene structure.svg
Clinical data
Trade namesDifferin, Pimpal, Gallet, Adelene, Adeferin
License data
  • AU: D
  • US: C (Risk not ruled out)
Routes of
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityVery low
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.149.379 Edit this at Wikidata
Chemical and physical data
Molar mass412.52 g/mol g·mol−1
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.[citation needed]

Medical uses[edit]

Per the recommendations of the Global Alliance on Improving Outcomes of Acne, retinoids such as adapalene are considered first line therapy in acne treatment and are to be used either independently or in conjunction with benzoyl peroxide and/or an antimicrobial agent for maximum efficacy.[2][3]  Furthermore, adapalene, like other retinoids, increases the efficacy and penetration of other topical acne medications that are used in conjunction with topical retinoids as well as hastens the improvement of the post-inflammatory hyperpigmentation caused by acne.[2] In the long term, it can be used as maintenance therapy.[2]

While adapalene is often thought to be the least efficacious of the retinoid medications, two multicenter randomized double-blinded studies showed that the use of adapalene 0.1% lotion for 12 weeks improved inflammatory and noninflammatory acne as well as reduced the total lesion count from baseline in those patients in the treatment group.[2]

Off-label uses[edit]

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. Other non-FDA approved indications that have been reported in the literature include treatment of verruca vulgaris, molluscum contagiosum, Darier disease, photoaging, pigmentary disorders, actinic keratoses and alopecia areata.[4]

A study has concluded that adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.[5]

Side effects[edit]

It is common (between 1% and 10% of users)[6] to experience a brief sensation of warmth or stinging, as well as dry skin, peeling and redness during the first 2–4 weeks of using the medication.[2][7] These effects are considered mild and generally decrease over time.[2][7] Any serious allergic reaction is rare.[7] Furthermore, of the three topical retinoids, adapalene is often regarded as the most tolerable.[4]

In pregnancy[edit]

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.[8]

According to the Drugs and Lactation Database, topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) despite long term use, suggesting that there is low risk of harm for a nursing infant.[9] However, it is recommended that the topical medication not be applied to the nipple or any other area that may come into direct contact of the infant's skin.[9]


Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased.[10][non-primary source needed] 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.[11]


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.[12] Furthermore, due to adapalene's more stable chemical structure the concern for photodegeneration of the molecule is less of a concern in comparison to tretinoin and tazarotene.[4]


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.[13]


Topical adapalene first penetrates the hair follicle and binds to nuclear retinoic acid receptors.[3]  These complexes then bind to DNA and lead to normalization of keratinocyte differentiation allowing for decreased microcomedone formation, decreases clogging in pores, and gives adapalene its exfoliative properties by increasing cell turnover.[4][14]  Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of Cutibacterium acnes.[4]

Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those that constitute skin.[15] Its agonism of the gamma subtype is largely responsible for adapalene's observed effects. In fact, when adapalene is applied in conjunction with a retinoic acid receptor gamma antagonist, adapalene loses clinical efficacy.[16]

Retinization is a common temporary phenomenon reported by patients when the initiate treatment of retinols.[17] Within the initial period of treatment, skin can become red, irritated, dry and may burn or itch from retinol application; however, this tends to resolve within four weeks with once a day use.[17]


Adapalene is a research product of Galderma Laboratories, France.[18] Adapalene was approved in 1996 by the U.S. Food and Drug Administration (FDA) for use in the treatment of acne.[19]

Available forms[edit]

Tube of generic adapalene

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.[20] The 0.1% gel is available as a generic made by Teva.[21][22] It is also available combined with benzoyl peroxide under the brand names Epiduo and Tactupump.[23] 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.[24] 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.[8]

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

See also[edit]


  1. ^ Rolewski SL (October 2003). "Clinical review: topical retinoids". Dermatology Nursing. 15 (5): 447–50, 459–65. PMID 14619325.
  2. ^ a b c d e f Kolli, Sree S.; Pecone, Danielle; Pona, Adrian; Cline, Abigail; Feldman, Steven R. (2019-01-23). "Topical Retinoids in Acne Vulgaris: A Systematic Review". American Journal of Clinical Dermatology. 20 (3): 345–365. doi:10.1007/s40257-019-00423-z. ISSN 1179-1888. PMID 30674002.
  3. ^ a b Xiang, Leihong Flora; Troielli, Patricia; Lozada, Vicente Torres; Tan, Jerry; Suh, Dae Hun; See, Jo-Ann; Piquero-Martin, Jaime; Perez, Montserrat; Orozco, Beatriz (2018-02-01). "Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne". Journal of the American Academy of Dermatology. 78 (2): S1–S23.e1. doi:10.1016/j.jaad.2017.09.078. ISSN 0190-9622. PMID 29127053.
  4. ^ a b c d e Tolaymat, Leila; Zito, Patrick M. (2018), "Adapalene", StatPearls, StatPearls Publishing, PMID 29494115, retrieved 2019-03-13
  5. ^ Gupta, Ramji; Gupta, Sarthak (2015). "Topical Adapalene in the Treatment of Plantar Warts; Randomized Comparative Open Trial in Comparison with Cryo-Therapy". Indian Journal of Dermatology. 60 (1): 102. doi:10.4103/0019-5154.147835. ISSN 0019-5154. PMC 4318023. PMID 25657417.
  6. ^ "Differin". Swedish Drug Formulary. Retrieved 2017-12-11.
  7. ^ a b c "Adapalene Gel". WebMD. Retrieved 2017-12-11.
  8. ^ a b "FDA approves Differin Gel 0.1% for over-the-counter use to treat acne". July 8, 2016. Retrieved 14 July 2016.
  9. ^ a b "Adapalene", Drugs and Lactation Database (LactMed), National Library of Medicine (US), 2006, PMID 30000483, retrieved 2019-03-13
  10. ^ 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.
  11. ^ Jain GK, Ahmed FJ (2007). "Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies" (PDF). Indian Journal of Dermatology, Venereology and Leprology. 73 (5): 326–9. doi:10.4103/0378-6323.34010. PMID 17921613.
  12. ^ 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.
  13. ^ "DIFFERIN® (adapalene) Cream, 0.1% Label" (PDF). FDA. May 25, 2000. Retrieved 4 Oct 2011.
  14. ^ "DIFFERIN® (adapalene) Gel, 0.3%" (PDF). Retrieved March 12, 2019.
  15. ^ 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. doi:10.2147/ciia.2006.1.4.327. PMC 2699641. PMID 18046911.
  16. ^ 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.
  17. ^ a b "Differin Gel: An Over-the-Counter Retinoid for Acne". Retrieved 2019-03-25.
  18. ^ 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 
  19. ^ "FDA approval of DIFFERIN® (adapalene) Solution, 0.1%". FDA. May 31, 1996. Retrieved 29 May 2017.
  20. ^ About Differin Archived May 9, 2008, at the Wayback Machine
  21. ^ "Teva Introduces Adapalene Gel, 0.1%". PharmQD. 4 June 2010. Retrieved 30 Aug 2011.
  22. ^ Webber K (2 June 2010). "FDA Approval Letter" (PDF). Department of Health and Human Services. Retrieved 30 August 2011.[permanent dead link]
  23. ^ "EPIDUO® (adapalene and benzoyl peroxide) Gel 0.1%/2.5% Approval Letter" (PDF). FDA. Dec 8, 2008. Retrieved 29 May 2017.
  24. ^ "Deriva-CMS from Glenmark (Gracewill) [ADAPALENE]".

External links[edit]