|Trade names||Differin, Pimpal, Gallet, Adelene, Adeferin|
|Chemical and physical data|
|Molar mass||412.52 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. It is effective against acne conditions where comedones are predominant.
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. 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. In the long term, it can be used as maintenance therapy.
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. 
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, molluscum contagiosum, Darier disease, photoaging, pigmentary disorders, actinic keratoses and alopecia areata.
It is common (between 1% and 10% of users) 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. These effects are considered mild and generally decrease over time. Any serious allergic reaction is rare. Furthermore, of the three topical retinoids, adapalene is often regarded as the most tolerable. 
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.
According to the Drugs and Lactation Database, topical adapalene is 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. 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.
Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased. 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.
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. 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.
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.
Topical adapalene first penetrates the hair follicle and binds to nuclear retinoic acid receptors. These complexes then bind to DNA and lead to normalization of keratinocyte differentiation allowing for decreased microcomedone formation and gives adapalene its exfoliative properties. Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of Propionibacterium acnes.
Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those that constitute skin. 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.
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. The 0.1% gel is available as a generic made by Teva. It is also available combined with benzoyl peroxide under the brand names Epiduo and Tactupump. 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. 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.
The Proactiv Company also sells the adapalene gel 0.1% under its brand name Proactiv MD Adapalene 0.1%.
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