Topical Retinoid Medications: Tretinoin, Adapalene, Tazarotene, and Alitretinoin

What Are Topical Retinoids?

Retinoids are a family of compounds that are related to vitamin A and are used in both cosmetic and medical treatments.

The most commonly used prescription-based topical retinoids are tretinoin, adapalene, and tazarotene, but there are others that are used less often including alitretinoin. 

Table 1 – Common Retinoids and Their Brand Names

*All 2^nd generation retinoids are oral medications, and there are no 2^nd generation topical retinoids. 

Retinoids can be used as either oral medications or as topical preparations. Topical retinoids are typically formulated as creams, gels, or foams.  

How Do Retinoids Work?

Retinoids work by entering our cells and docking with receptors that are known as retinoid acid receptors. There are several different forms of retinoic acid receptors, and the skin is rich in these receptors.^[1] After the retinoid docks with the receptor, it then connects with the cell’s DNA to adjust the way that the DNA is read within the cell. This can either turn on or off different genes to allow the retinoid to have its effect. Sebaceous glands (oil producing cells of the skin) and epidermal skin cells, known as keratinocytes, are sensitive to the effects of retinoids. Their production can be increased or inhibited based on cellular retinoid levels.

In the skin, retinoids can cause the following reactions:

• Regulate how skin cells divide to promote skin cell turnover^[2,3]
• Stimulate the production of collagen^[4-6] to help with aging and reduce the formation of wrinkles
• Reduce hyperpigmentation (skin darkening)^[3,6]
• Reduce inflammation in acne^[7]

What Conditions Do Retinoids Treat? 

Table 2 – FDA Approved Treatments

*Alitretinoin is approved for chronic hand eczema in Europe, Canada, and Asia under the brand name Toctino.

Physicians may use topical retinoids, such as tretinoin, to prepare the face before a chemical peel or to help reduce thickened and scaly skin that prevents topical medications or products from penetrating the skin effectively. Please discuss whether this should be done and if so how to best use retinoids on your skin with a physician.

How Are Topical Retinoids Used? 

Retinoids are typically prescribed as a topical cream or a nighttime gel. It is not applied during the day as the compounds are not typically stable in sunlight and can cause sun sensitivity and irritation. One exception is that adapalene appears to be stable under visible light,^[8] but it is not known whether it is stable under UV light. For this reason, adapalene is typically applied at night as well.

What Are the Potential Side Effects of Topical Retinoids? 

All of the retinoids can cause skin peeling, flaking, redness, stinging sensations, and sun sensitivity. This tends to occur when the medication is first being used and can improve with use. A common way to alleviate its side effects is to start the topical retinoid (such as tretinoin) several times a week and slowly increase it towards nightly use as the skin becomes more used to the medication. Another option is to apply moisturizers prior to applying topical retinoids.  

Use in pregnancy

Table 3 – Topical Retinoid Use in Pregnancy

Care when using with benzoyl peroxide

Tretinoin may break down when used in combination with benzoyl peroxide (for those with acne) and adapalene (a synthetic retinoid). Adapalene is a more stable compound that does not break down.^[8] There are newer stabilized formulations of tretinoin that may not break down when used together with benzoyl peroxide.^[9] Consult with your physician to help select the best variant of tretinoin for you.

Benzoyl peroxide can also irritate the face, and the combination of the two may irritate the face further. For this reason, some physicians and prescribers may have you use benzoyl peroxide in the morning and a retinoid (such as tretinoin or adapalene) in the evening. 

1. Fisher GJ, Voorhees JJ. Molecular mechanisms of retinoid actions in skin. FASEB J.1996;10(9):1002-1013; PMID: 8801161.
2. Jetten AM. Multi-stage program of differentiation in human epidermal keratinocytes: regulation by retinoids. J Invest Dermatol.1990;95(5):44S-46S; PMID: 2230209.
3. Ortonne JP. Retinoid therapy of pigmentary disorders. Dermatol Ther.2006;19(5):280-288; PMID: 17014483.
4. Randhawa M, Rossetti D, Leyden JJ, et al. One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial. J Drugs Dermatol.2015;14(3):271-280; PMID: 25738849.
5. Lateef H, Stevens MJ, Varani J. All-trans-retinoic acid suppresses matrix metalloproteinase activity and increases collagen synthesis in diabetic human skin in organ culture. Am J Pathol.2004;165(1):167-174; PMID: 15215172.
6. Bhawan J. Short- and long-term histologic effects of topical tretinoin on photodamaged skin. Int J Dermatol.1998;37(4):286-292; PMID: 9585903.
7. Yeh L, Bonati LM, Silverberg NB. Topical retinoids for acne. Semin Cutan Med Surg.2016;35(2):50-56; PMID: 27416308.
8. Martin B, Meunier C, Montels D, et al. Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation. Br J Dermatol.1998;139 Suppl 52:8-11; PMID: 9990414.
9. Del Rosso JQ, Pillai R, Moore R. Absence of Degradation of Tretinoin When Benzoyl Peroxide is Combined with an Optimized Formulation of Tretinoin Gel (0.05%). J Clin Aesthet Dermatol.2010;3(10):26-28; PMID: 20967192.