adapalene

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, like clindamycin, for maximum efficacy.{{Cite journal |vauthors=Kolli SS, Pecone D, Pona A, Cline A, Feldman SR |date=June 2019 |title=Topical Retinoids in Acne Vulgaris: A Systematic Review |journal=American Journal of Clinical Dermatology |volume=20 |issue=3 |pages=345–365 |doi=10.1007/s40257-019-00423-z |pmid=30674002 |s2cid=59225325}}{{Cite journal |vauthors=Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI, Bettoli V, Casintahan F, Chow S, da Costa A, El Ouazzani T, Goh CL, Gollnick HP, Gomez M, Hayashi N, Herane MI, Honeyman J, Kang S, Kemeny L, Kubba R, Lambert J, Layton AM, Leyden JJ, López-Estebaranz JL, Noppakun N, Ochsendorf F, Oprica C, Orozco B, Perez M, Piquero-Martin J, See JA, Suh DH, Tan J, Lozada VT, Troielli P, Xiang LF |date=February 2018 |title=Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne |url=https://repository.uantwerpen.be/docman/irua/9af1f1/149272_2019_02_01.pdf |journal=Journal of the American Academy of Dermatology |volume=78 |issue=2 Suppl 1 |pages=S1–S23.e1 |doi=10.1016/j.jaad.2017.09.078 |pmid=29127053 |s2cid=31654121 |hdl-access=free |hdl=10067/1492720151162165141}} An adapalene/benzoyl peroxide combination medication is also available. 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 postinflammatory hyperpigmentation caused by acne. In the long term, it can be used as maintenance therapy.

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. Other non-FDA approved indications that have been reported in the literature include treatment of warts, molluscum contagiosum, Darier's disease, photoaging, pigmentary disorders, actinic keratoses and alopecia areata.

While adapalene is sold at 0.1% in over-the-counter topical products for treatment of acne{{cite journal | vauthors = Fix W, Desai S, Nussbaum D, Friedman A | title = Rx -to- OTC switch increased access and lowered cost of topical adapalene | journal = Archives of Dermatological Research | volume = 316 | issue = 5 | pages = 155 | date = May 2024 | pmid = 38734769 | doi = 10.1007/s00403-024-02890-9 }}, its availability is otherwise restricted to prescription drugs. A version of adapalene, oleyl adapalenate, is available for broader skincare and cosmetic usage.

Of the three topical retinoids, adapalene is often regarded as the best tolerated. It can cause mild adverse effects such as photosensitivity, irritation, redness, dryness, itching, and burning, and 1% to 10% of users{{Cite web |title=Differin |url=http://www.fass.se/LIF/product?11-1.ILinkListener-documentTabPanel-tabs-tabs~container-tabs-1-link&userType=0&nplId=19960830000022 |access-date=11 December 2017 |website=Swedish Drug Formulary}} experience a brief sensation of warmth or stinging, as well as dry skin, peeling and redness during the first two to four weeks using the medication.{{Cite web |title=Adapalene Gel |url=https://www.webmd.com/drugs/2/drug-6442/adapalene-topical/details |access-date=11 December 2017 |website=WebMD}} These effects are considered mild and usually decrease over time. Serious allergic reactions are rare.

Use of topical adapalene in pregnancy has not been well studied but has a theoretical risk of retinoid embryopathy.{{Cite journal |vauthors=Piskin S, Uzunali E |date=August 2007 |title=A review of the use of adapalene for the treatment of acne vulgaris |journal=Therapeutics and Clinical Risk Management |volume=3 |issue=4 |pages=621–624 |pmc=2374937 |pmid=18472984}} Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy.{{Cite press release |title=FDA approves Differin Gel 0.1% for over-the-counter use to treat acne |date=8 July 2016 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-differin-gel-01-over-counter-use-treat-acne |archive-url=https://web.archive.org/web/20191016102926/https://www.fda.gov/news-events/press-announcements/fda-approves-differin-gel-01-over-counter-use-treat-acne |url-status=dead |archive-date=16 October 2019 |access-date=14 July 2016 |website=Food and Drug Administration}}

Topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) even after long term use, suggesting that there is low risk of harm for a nursing infant.{{Citation |title=Adapalene |date=2006 |work=Drugs and Lactation Database (LactMed) |url=http://www.ncbi.nlm.nih.gov/books/NBK501423/ |access-date=13 March 2019 |publisher=National Library of Medicine (US) |pmid=30000483}}

Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased.{{Cite journal |vauthors=Wolf JE, Kaplan D, Kraus SJ, Loven KH, Rist T, Swinyer LJ, Baker MD, Liu YS, Czernielewski J |date=September 2003 |title=Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study |journal=Journal of the American Academy of Dermatology |volume=49 |issue=3 Suppl |pages=S211–S217 |doi=10.1067/S0190-9622(03)01152-6 |pmid=12963897}}{{Cite journal |vauthors=Jain GK, Ahmed FJ |date=2007 |title=Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies |journal=Indian Journal of Dermatology, Venereology and Leprology |volume=73 |issue=5 |pages=326–329 |doi=10.4103/0378-6323.34010 |pmid=17921613 |doi-access=free |title-link=doi}} 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.{{Cite journal |vauthors=Jain GK, Ahmed FJ |year=2007 |title=Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies |journal=Indian Journal of Dermatology, Venereology and Leprology |volume=73 |issue=5 |pages=326–329 |doi=10.4103/0378-6323.34010 |pmid=17921613 |doi-access=free |title-link=doi}}

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.{{Cite journal |vauthors=Martin B, Meunier C, Montels D, Watts O |date=October 1998 |title=Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation |journal=The British Journal of Dermatology |volume=139 |issue=Suppl 52 |pages=8–11 |doi=10.1046/j.1365-2133.1998.1390s2008.x |pmid=9990414 |s2cid=43287596}} Furthermore, photodegradation of the molecule is less of a concern in comparison to tretinoin and tazarotene.

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 {{Convert|1000|cm2||abbr=on}} of skin found no quantifiable amounts, or less than 0.35 ng/mL of the drug, in the patients' blood plasma. Controlled trials of chronic users of adapalene have found drug levels in the patients' plasma to be 0.25 ng/mL.

Adapalene is highly lipophilic. When applied topically, it readily penetrates hair follicles and absorption occurs five minutes after topical application. After penetration into the follicle, adapalene binds to nuclear retinoic acid receptors (namely retinoic acid receptor beta and gamma). These complexes then bind to the retinoid X receptor which induces gene transcription by binding to specific DNA sites, thus modulating downstream keratinocyte proliferation and differentiation. This results in normalization of keratinocyte differentiation, allowing for decreased microcomedone formation, decreased clogging of pores, and increased exfoliation by increasing cell turnover.{{Cite web |title=DIFFERIN® (adapalene) Gel, 0.3% |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021753lbl.pdf |access-date=12 March 2019}} Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of Cutibacterium acnes, and inhibits both lipoxygenase activity and the oxidative metabolism of arachidonic acid into prostaglandins.

Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those found in the skin.{{Cite journal |vauthors=Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G |date=2006 |title=Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety |journal=Clinical Interventions in Aging |volume=1 |issue=4 |pages=327–348 |doi=10.2147/ciia.2006.1.4.327 |pmc=2699641 |pmid=18046911 |doi-access=free |title-link=doi}} 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.{{Cite journal |vauthors=Michel S, Jomard A, Démarchez M |date=October 1998 |title=Pharmacology of adapalene |journal=The British Journal of Dermatology |volume=139 |issue=Suppl 52 |pages=3–7 |doi=10.1046/j.1365-2133.1998.1390s2003.x |pmid=9990413 |s2cid=23084886}}

Retinization is a common temporary phenomenon reported by patients when initiating use of retinoids.{{Cite web |title=Differin Gel: An Over-the-Counter Retinoid for Acne |url=https://www.differin.com/learn/faqs |access-date=25 March 2019 |website=www.differin.com}} Within the initial period of treatment, skin can become red, irritated, dry and may burn or itch from retinoid application; however, this tends to resolve within four weeks with once a day use.

Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as the parent drug.{{cite web | vauthors = Mainigi KD | title = DIFFERINTM (adapalene) Lotion 0.1% | date = 2 July 2009 | work = Pharmacology/Toxicology Review and Evaluation | publisher = Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration | id = Application Number: 22-502 | url = https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022502s000PharmR.pdf | archive-url = https://web.archive.org/web/20170211030502/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022502s000PharmR.pdf | url-status = dead | archive-date = 11 February 2017 }}

Adapalene was a research product of the Swiss company Galderma.{{cite patent | country= US | number= 4717720A | status= Patent | title= Benzonaphthalene derivatives and compositions | pubdate= 5 January 1988 | gdate = 5 January 1988 | fdate= 1986-04-10 | pridate= 1985-04-11 | inventor= Shroot B, Eustache J, Bernardon J-M | invent1= | invent2= | assign1= Galderma Research and Development SNC | assign2= | class = | url= https://patents.google.com/patent/US4717720}} Adapalene was approved in 1996 by the US Food and Drug Administration (FDA) for use in the treatment of acne.{{Cite web |date=31 May 1996 |title=FDA approval of Differin (adapalene) Solution, 0.1% |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020338 |archive-url=https://web.archive.org/web/20170216035729/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020338 |url-status=dead |archive-date=16 February 2017 |access-date=29 May 2017 |publisher=FDA}}

A study has concluded that adapalene can be used to treat plantar warts and may help clear lesions faster than cryotherapy.{{Cite journal |vauthors=Gupta R, Gupta S |date=2015 |title=Topical adapalene in the treatment of plantar warts; randomized comparative open trial in comparison with cryo-therapy |journal=Indian Journal of Dermatology |volume=60 |issue=1 |pages=102 |doi=10.4103/0019-5154.147835 |pmc=4318023 |pmid=25657417 |doi-access=free |title-link=doi}} A computational study claims that adapalene can be used as a potential entry inhibitor for Omicron variant of SARS-CoV-2.{{Cite journal |vauthors=Fidan O, Mujwar S, Kciuk M |date=February 2023 |title=Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing |journal=Molecular Diversity |volume=27 |issue=1 |pages=463–475 |doi=10.1007/s11030-022-10440-6 |pmc=9066996 |pmid=35507211}}

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Category:Anti-acne preparations

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