Adapalene

Last updated

Adapalene
Adapalene structure.svg
Adapalene-3D-balls.png
Clinical data
Trade names Differin, others
AHFS/Drugs.com Monograph
MedlinePlus a604001
License data
Pregnancy
category
  • AU:D
Routes of
administration 		Topical
Drug class Retinoids
ATC code
Physiological data
Receptors Retinoic acid receptor (RAR)
Metabolism 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 parent drug
Legal status
Legal status
Pharmacokinetic data
Bioavailability Very low[ medical citation needed ]
Metabolism 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 parent drug
Metabolites Glucuronides
Elimination half-life between 7 and 51 hours
Excretion Bile duct
Identifiers
  • 6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.149.379 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C28H28O3
Molar mass 412.529 g·mol−1
3D model (JSmol)
Melting point 300 °C (572 °F)
Boiling point 606.3 °C (1,123.3 °F)
  • COC1=C(C=C(C=C1)C2=CC3=C(C=C2)C=C(C=C3)C(=O)O)C45CC6CC(C4)CC(C6)C5
  • InChI=InChI=1S/C28H28O3/c1-31-26-7-6-23(21-2-3-22-12-24(27(29)30)5-4-20(22)11-21)13-25(26)28-14-17-8-18(15-28)10-19(9-17)16-28/h2-7,11-13,17-19H,8-10,14-16H2,1H3,(H,29,30) Yes check.svgY
  • Key:LZCDAPDĜCYOEH-UHFFFAOYSA-N Yes check.svgY
   (verify)
Adapalene Gel, sold in trade name Differin in China Adapalene Gel (Differin) in China.jpg
Adapalene Gel, sold in trade name Differin in China

Adapalene, sold under the brand name Differin among others, 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. [6] Studies have found adapalene is as effective as other retinoids, while causing less irritation. [7] It also has several advantages over other retinoids. The adapalene molecule is more stable compared to tretinoin and tazarotene, which leads to less concern for photodegradation. [7] It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with benzoyl peroxide. [7] Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. [8] The Swiss company Galderma developed adapalene.

Contents

Medical uses

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. [9] [10] 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. [9] In the long term, it can be used as maintenance therapy. [9]

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. 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. [7]

Side effects

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, [7] and 1% to 10% of users [11] 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. [9] [12] These effects are considered mild and usually decrease over time. [9] [12] Serious allergic reactions are rare. [12]

Pregnancy & lactation

Use of topical adapalene in pregnancy has not been well studied but has a theoretical risk of retinoid embryopathy. [13] Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy. [14]

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. [15]

Interactions

Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased. [16] [17] 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. [18]

Pharmacology

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. [19] Furthermore, photodegradation of the molecule is less of a concern in comparison to tretinoin and tazarotene. [7]

Pharmacokinetics

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 1,000 cm2 (160 sq in) of skin found no quantifiable amounts, or less than 0.35 ng/mL of the drug, in the patients' blood plasma. [3] Controlled trials of chronic users of adapalene have found drug levels in the patients' plasma to be 0.25 ng/mL. [13]

Pharmacodynamics

Adapalene is highly lipophilic. When applied topically, it readily penetrates hair follicles and absorption occurs five minutes after topical application. [7] After penetration into the follicle, adapalene binds to nuclear retinoic acid receptors (namely retinoic acid receptor beta and gamma). [10] [13] 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. [7] [13] This results in normalization of keratinocyte differentiation, allowing for decreased microcomedone formation, decreased clogging of pores, and increased exfoliation by increasing cell turnover. [7] [13] [20] Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of Cutibacterium acnes , [7] and inhibits both lipoxygenase activity and the oxidative metabolism of arachidonic acid into prostaglandins. [13]

Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those found in the skin. [21] 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. [22]

Retinization is a common temporary phenomenon reported by patients when initiating use of retinoids. [23] 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. [23]

Metabolism

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 parent drug [24]

History

Adapalene was a research product of the Swiss company Galderma. [25] Adapalene was approved in 1996 by the US Food and Drug Administration (FDA) for use in the treatment of acne. [26]

Research

A study has concluded that adapalene can be used to treat plantar warts and may help clear lesions faster than cryotherapy. [27] A computational study claims that adapalene can be used as a potential entry inhibitor for Omicron variant of SARS-CoV-2. [28]

Related Research Articles

<span class="mw-page-title-main">Acne</span> Skin condition characterized by pimples

Acne, also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back. The resulting appearance can lead to lack of confidence, anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.

<span class="mw-page-title-main">Isotretinoin</span> Medication primarily used to treat severe acne

Isotretinoin, also known as 13-cis-retinoic acid and sold under the brand name Accutane among others, is a medication used to treat skin diseases like harlequin-type ichthyosis, and lamellar ichthyosis, and severe cystic acne or moderate acne that is unresponsive to antibiotics. Isotretinoin is used off-label to treat basal cell carcinoma and squamous cell carcinoma, although clinical evidence suggests it is not effective in this setting. It is a retinoid, meaning it is related to vitamin A, and is found in small quantities naturally in the body. Its isomer, tretinoin, is also an acne drug.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.

<span class="mw-page-title-main">Tretinoin</span> Medication

Tretinoin, also known as all-trans retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For acute promyelocytic leukemia, it is effective only when the RARA-PML fusion mutation is present and is taken by mouth for up to three months. Topical tretinoin is also the most extensively investigated retinoid therapy for photoaging.

ATC code D10Anti-acne preparations is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup D10 is part of the anatomical group D Dermatologicals.

<span class="mw-page-title-main">Benzoyl peroxide</span> Chemical compound with uses in industry and acne treatment

Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula (C6H5−C(=O)O−)2, often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (C6H5−C(=O)−, Bz) groups connected by a peroxide (−O−O−). It is a white granular solid with a faint odour of benzaldehyde, poorly soluble in water but soluble in acetone, ethanol, and many other organic solvents. Benzoyl peroxide is an oxidizer, which is principally used in the production of polymers.

<span class="mw-page-title-main">Retinoid</span> Group of tetraterpenes

The retinoids are a class of chemical compounds that are natural derivatives of vitamin A or are chemically related to it. Synthetic retinoids are used in medicine where they regulate skin health, immunity and bone disorders.

<span class="mw-page-title-main">Tazarotene</span> Topical retinoid medication

Tazarotene, sold under the brand name Tazorac, among others, is a third-generation prescription topical retinoid. It is primarily used for the treatment of plaque psoriasis and acne. Tazarotene is also used as a therapeutic for photoaged and photodamaged skin. It is a member of the acetylenic class of retinoids.

<span class="mw-page-title-main">Proactiv</span> Acne focused skincare products

Proactiv is an American brand of skin-care products developed by two American dermatologists, Katie Rodan and Kathy A. Fields, and launched in 1995 by Guthy-Renker, a California-based direct marketing company, that was endorsed by famous celebrities The range includes moisturizers, body washes and treatment products, but the brand is known for its three-step anti-acne Solutions 3-step routine consisting of a BPO cleanser, glycolic toner and treatment lotion. Proactiv+, a reformulation of the three-step kit, was introduced in 2013, and in 2017, ProactivMD launches powered by Adapalene.

<span class="mw-page-title-main">Azelaic acid</span> Organic chemical compound

Azelaic acid (AzA) is an organic compound with the formula HOOC(CH2)7COOH. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of a number of hair and skin conditioners. AzA inhibits tyrosinase.

<span class="mw-page-title-main">Clindamycin/benzoyl peroxide</span> Type of medication

Clindamycin/benzoyl peroxide, sold under the brand name Benzaclin among others, is a topical gel used for the treatment of acne. It is a fixed-dose combination of clindamycin, as the phosphate, an antibiotic; and benzoyl peroxide, an antiseptic.

<span class="mw-page-title-main">Nadifloxacin</span> Chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

Clindamycin/tretinoin is a topical gel used in the treatment of acne. The two active ingredients are the antibiotic clindamycin phosphate (1.2%) and tretinoin (0.025%), a retinoid. The two active ingredients perform different functions, the clindamycin is active against gram-positive bacteria, including streptococci and penicillin-resistant staphylococci. The Tretinoin element acts to reduce the amount of oil released by oil glands in skin, as well as encouraging skin cell replenishment. The topical treatment is stored in 2, 30, and 60 gram tubes and should be stored at 25°C (77°F), with the tube tightly shut away from light. Side effects may include peeling, redness, dryness, itching and photosensitivity. Also, topical clindamycin may rarely cause diarrhea or colitis. Sun exposure while using this preparation can cause skin irritation.

<span class="mw-page-title-main">Neonatal acne</span> Medical condition

Neonatal acne, also known as acne neonatorum, is a type of acne that develops in newborns, typically within the first six weeks of life. It presents with open and closed comedones on the cheeks, chin and forehead.

<span class="mw-page-title-main">Pimple</span> Type of comedo

A pimple or zit is a kind of comedo that results from excess sebum and dead skin cells getting trapped in the pores of the skin. In its aggravated state, it may evolve into a pustule or papule. Pimples can be treated by acne medications, antibiotics, and anti-inflammatories prescribed by a physician, or various over the counter remedies purchased at a pharmacy.

<span class="mw-page-title-main">Photoaging</span> Ultraviolet light-induced biological development over time

Photoaging or photoageing is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging.

<span class="mw-page-title-main">Adapalene/benzoyl peroxide</span> Pharmaceutical combination

Adapalene/benzoyl peroxide, sold under the brand name Epiduo among others, is a fixed-dose combination medication for the treatment of acne vulgaris. It is a combination of adapalene, a retinoid; and benzoyl peroxide.

Infantile acne is a form of acne that begins in very young children. Typical symptoms include inflammatory and noninflammatory lesions, papules and pustules most commonly present on the face. No cause of infantile acne has been established but it may be caused by increased sebaceous gland secretions due to elevated androgens, genetics and the fetal adrenal gland causing increased sebum production. Infantile acne can resolve by itself by age 1 or 2. However, treatment options include topical benzyl peroxide, topical retinoids and topical antibiotics in most cases.

Tretinoin/benzoyl peroxide, sold under the brand name Twyneo, is a fixed-dose combination medication used for the treatment of acne. It contains tretinoin, a vitamin A derivative, and benzoyl peroxide, an oxidizing agent.

Clindamycin/adapalene/benzoyl peroxide, sold under the brand name Cabtreo, is a fixed-dose combination medication used for the treatment of acne. It contains clindamycin, as the phosphate, a lincosamide antibacterial; adapalene, a synthetic retinoid; and benzoyl peroxide, an oxidizing agent. It is applied to the skin.

References

  1. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 15 August 2023.
  2. ↑ "Differin- adapalene gel". DailyMed. 7 December 2022. Retrieved 15 May 2024.
  3. 1 2 "Differin- adapalene cream". DailyMed. 31 October 2022. Retrieved 15 May 2024.
  4. ↑ "Differin- adapalene gel". DailyMed. 27 December 2023. Retrieved 15 May 2024.
  5. ↑ "Differin- adapalene lotion". DailyMed. 19 April 2023. Retrieved 15 May 2024.
  6. ↑ Rolewski SL (October 2003). "Clinical review: topical retinoids". Dermatology Nursing. 15 (5): 447–50, 459–65. PMID   14619325.
  7. 1 2 3 4 5 6 7 8 9 10 Tolaymat L, Dearborn H, Zito PM (June 2023). "Adapalene". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   29494115.
  8. ↑ Asai Y, Baibergenova A, Dutil M, Humphrey S, Hull P, Lynde C, et al. (February 2016). "Management of acne: Canadian clinical practice guideline". CMAJ. 188 (2): 118–126. doi: 10.1503/cmaj.140665 . PMC   4732962 . PMID   26573753.
  9. 1 2 3 4 5 Kolli SS, Pecone D, Pona A, Cline A, Feldman SR (June 2019). "Topical Retinoids in Acne Vulgaris: A Systematic Review". American Journal of Clinical Dermatology. 20 (3): 345–365. doi:10.1007/s40257-019-00423-z. PMID   30674002. S2CID   59225325.
  10. 1 2 Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI, et al. (February 2018). "Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne" (PDF). Journal of the American Academy of Dermatology. 78 (2 Suppl 1): S1–S23.e1. doi:10.1016/j.jaad.2017.09.078. hdl: 10067/1492720151162165141 . PMID   29127053. S2CID   31654121.
  11. ↑ "Differin". Swedish Drug Formulary . Retrieved 11 December 2017.
  12. 1 2 3 "Adapalene Gel". WebMD . Retrieved 11 December 2017.
  13. 1 2 3 4 5 6 Piskin S, Uzunali E (August 2007). "A review of the use of adapalene for the treatment of acne vulgaris". Therapeutics and Clinical Risk Management. 3 (4): 621–624. PMC   2374937 . PMID   18472984.
  14. ↑ "FDA approves Differin Gel 0.1% for over-the-counter use to treat acne". Food and Drug Administration (Press release). 8 July 2016. Retrieved 14 July 2016.
  15. ↑ "Adapalene", Drugs and Lactation Database (LactMed), National Library of Medicine (US), 2006, PMID   30000483 , retrieved 13 March 2019
  16. ↑ Wolf JE, Kaplan D, Kraus SJ, Loven KH, Rist T, Swinyer LJ, et al. (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–S217. doi:10.1067/S0190-9622(03)01152-6. PMID   12963897.
  17. ↑ 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): 326–329. doi: 10.4103/0378-6323.34010 . PMID   17921613.
  18. ↑ 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): 326–329. doi: 10.4103/0378-6323.34010 . PMID   17921613.
  19. ↑ 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. S2CID   43287596.
  20. ↑ "DIFFERIN® (adapalene) Gel, 0.3%" (PDF). Retrieved 12 March 2019.
  21. ↑ 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): 327–348. doi: 10.2147/ciia.2006.1.4.327 . PMC   2699641 . PMID   18046911.
  22. ↑ 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. S2CID   23084886.
  23. 1 2 "Differin Gel: An Over-the-Counter Retinoid for Acne". www.differin.com. Retrieved 25 March 2019.
  24. ↑ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022502s000PharmR.pdf
  25. ↑ USPatent 4717720A,Shroot B, Eustache J, Bernardon J-M,"Benzonaphthalene derivatives and compositions",published 5 January 1988,issued 5 January 1988, assigned to Galderma Research and Development SNC
  26. ↑ "FDA approval of Differin (adapalene) Solution, 0.1%". FDA. 31 May 1996. Retrieved 29 May 2017.
  27. ↑ Gupta R, Gupta S (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 . PMC   4318023 . PMID   25657417.
  28. ↑ Fidan O, Mujwar S, Kciuk M (February 2023). "Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing". Molecular Diversity. 27 (1): 463–475. doi:10.1007/s11030-022-10440-6. PMC   9066996 . PMID   35507211.
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