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How does adapalene work?

Retinoids are derivatives of vitamin A, and they can be used for a variety of things in medicine. 

Adapalene is one of the newer retinoids, and it is used to treat acne and other skin concerns. 

How does adapalene work, what is it used for, and what are some common side effects?

What is adapalene?

Adapalene, also known as Differin, is a prescription retinoid that is applied topically to the skin. It was approved by the FDA in 1996 to treat acne vulgaris in patients 12 years of age and older.1 

It may also be prescribed off-label to treat a variety of other skin concerns, such as photoaging, actinic keratoses, and more. Adapalene is available in a 0.1% concentration as a cream or gel, and a 0.3% concentration as a gel.1 

It may also be combined with other active ingredients to deliver optimal results for different skin types.

It may be less irritating than other prescription retinoids

Some evidence suggests that it may be less irritating than other prescription retinoids, such as tretinoin and tazarotene; this makes adapalene unique because skin dryness and irritation are common side effects of topical retinoid therapy.2,3 

Adapalene is also more chemically stable than tretinoin, as, unlike tretinoin, it can be used with benzoyl peroxide, which is an antimicrobial agent used to target acne-causing bacteria, and it is less easily degraded by UV exposure.3

Another difference between adapalene and tretinoin is that tretinoin is approved by the FDA as a treatment for the signs of photoaging, whereas adapalene is not. 

There is some research that suggests that adapalene could be beneficial for this, as one study found that participants using 0.3% adapalene gel displayed similar improvements in symptoms of photoaging to those using 0.05% tretinoin cream; however, more research is needed to determine whether or not this could be a clinical indication.4 

How does adapalene work?

Acne development is related to four key factors: hyperkeratinization, which refers to a decreased ability of the skin to naturally shed dead skin cells, resultant blockages of the sebaceous follicles, increased sebaceous gland secretion, and inflammation related to the presence of Cutibacterium acnes in the follicles.5 

Adapalene works to reduce acne development and severity by targeting some of these pathways

Firstly, adapalene regulates the replication of keratinocytes, as this rate can often be abnormal in patients with acne vulgaris. 

This can help reduce the buildup of keratin in the skin’s pores and helps prevent the formation of comedones, which lead to acne lesions.1 

There is also some evidence that adapalene may have anti-inflammatory properties; one study suggests that adapalene can inhibit the signals that Cutibacterium acnes sends to recruit pro-inflammatory cytokines, which are immune system molecules that cause inflammation in response to an invading pathogen.6 

Inflammation plays an important role in some forms of acne, and this suggests that adapalene could potentially be beneficial in these cases.

Side effects of adapalene

Some common side effects of adapalene may include excessive skin dryness, redness, irritation, and flaking.1 

This is usually most prominent in the first few weeks of using adapalene, and it often subsides as someone uses it for an extended period of time. 

These side effects are usually associated with using topical retinoids, but adapalene is thought to be less irritating than some other commonly prescribed retinoids.1 

Increased sensitivity to the sun

Using adapalene may also be associated with increased sensitivity to the sun, so it is especially important to limit sun exposure and use broad-spectrum sunscreens that protect against both UVA and UVB radiation.1

You should always report any side effects of concern to your doctor or pharmacist

It is important to tell your doctor or pharmacist about any side effects that you are concerned about; they may alter the strength of the medication or seek an alternate therapy. 

Allergic reactions

Additionally, seek medical help immediately if you experience signs of an allergic reaction after using adapalene, such as hives, chest tightness, and swelling of the face, mouth, or throat.

Orally-taken retinoids, such as isotretinoin (Accutane) are teratogens, which means that they can impact the development of a growing fetus. 

However, the research is fairly limited regarding the potential teratogenicity of topical retinoids such as adapalene and tretinoin.7 

Although there is minimal evidence suggesting that topical retinoids can be detrimental during pregnancy, there is not enough evidence to recommend the use of adapalene during pregnancy.7

Increased sun sensitivity

While adapalene is a relatively stable retinoid, it can be drying and lead to increased sun sensitivity. For this reason, your healthcare provider may not recommend using other drying or photosensitizing skincare ingredients when you begin treatment with topical adapalene. 

There is also a possibility of adapalene interacting with certain oral medications, so it is important to tell your doctor about any medications, vitamins, or supplements that you may be taking.

This article is not medical advice, and it is not intended to prescribe, diagnose, or promote specific treatments for any condition. Consult your doctor or another qualified healthcare provider for your unique skin needs.


  1. Tolaymat, L., Zito, P.M. (2020, September 29). Adapalene. StatPearls [Internet]. Accessed 2021, May 17, from
  2. Kolli, S., Pecone, D., Pona, A., et al (2019, June). Topical retinoids in acne vulgaris: a systematic review. Am J Clin Dermatol 20(3): 345-365. Doi: 10.1007/s40257-019-00423-z.
  3. Irby, C.E., Yentzer, B.A., Feldman, S.R. (2008, November). A review of adapalene in the treatment of acne vulgaris. Journal of Adolescent Health 43(5): 421-424. Doi: 10.1016/j.jadohealth.2008.06.005
  4. Bagatin, E., de Sa Goncalves, H., Sato, M., et al (2018, June). Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as a treatment for cutaneous photoaging. European Journal Dermatol 28(3): 343-350. Doi: 10.1684/ejd.2018.3320.
  5. Toyoda, M., Morohashi, M. (2001, March). Pathogenesis of acne. Med Electron Microsc 34(1): 29-40. Doi: 10.1007/s007950100002.
  6. Zuliani, T., Khammari, A., Chaussy, H., et al (2011, July). Ex vivo demonstration of a synergistic effect of Adapalene and benzoyl peroxide on inflammatory acne lesions. Experimental Dermatology 20(10): 850-853. Doi: 10.1111/j.1600-0625.2011.01339.x
  7. Panchaud, A., Csajka, C., Merlob, P., et al (2013, March). Pregnancy Outcome Following Exposure to Topical Retinoids: A Multicenter Prospective Study. Journal of Clinical Pharmacology 52(12): 1844-1851. Doi: 10.1177/0091270011429566
  8. Image by Joseph Mucira from Pixabay 

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