What is adapalene? Understanding the Topical Retinoid

October 7, 2025 •

4 min read

In 2016, the FDA approved adapalene 0.1% gel for over-the-counter (OTC) use, making it the first topical retinoid available without a prescription. This third-generation synthetic retinoid is a powerful medication designed to treat and prevent acne vulgaris, working deep within the skin to regulate cell turnover and reduce inflammation.

Quick Summary

Adapalene is a topical retinoid medication primarily used to treat acne vulgaris by normalizing skin cell turnover and providing anti-inflammatory benefits. It is known for its effectiveness and is generally better tolerated than many older retinoids.

Key Points

Synthetic Retinoid: Adapalene is a third-generation, synthetic retinoid derived from vitamin A.
FDA Approved for OTC: The 0.1% gel formulation was approved for over-the-counter use in 2016 for treating acne vulgaris.
Acne Mechanism: It works by normalizing skin cell differentiation and turnover to prevent clogged pores and microcomedone formation.
Less Irritating: Adapalene is generally better tolerated and causes less irritation than older retinoids like tretinoin.
Photostable: Its stable chemical structure means it is less susceptible to photodegradation and can be used in combination with benzoyl peroxide.
Proper Use: Apply a thin layer once daily to clean, dry skin, and always use sunscreen to mitigate photosensitivity.
Initial Purging: Users may experience a temporary worsening of acne during the first few weeks, a normal process known as retinization.
For Long-Term Use: Adapalene is a suitable option for long-term acne maintenance therapy due to its favorable side effect profile.

What is Adapalene?

Adapalene is a synthetic third-generation retinoid, a derivative of vitamin A, used topically to treat acne vulgaris. It was initially available only by prescription but received FDA approval for an over-the-counter (OTC) version in 2016. This made the 0.1% adapalene gel (commonly known by the brand name Differin) widely accessible for adults and teenagers aged 12 and older. The OTC 0.1% concentration addresses mild to moderate acne, while higher 0.3% concentrations and other formulations like creams and lotions remain prescription-only options. The development of adapalene marked an advancement in acne treatment due to its selective action and improved tolerability profile compared to earlier retinoids.

The Mechanism of Action

Unlike traditional retinoids that bind to multiple retinoid receptors, adapalene selectively targets specific nuclear retinoic acid receptors (RAR-beta and RAR-gamma). This selective binding is key to its efficacy and tolerability. By binding to these receptors, adapalene influences gene transcription, which in turn normalizes the differentiation and turnover of follicular epithelial cells. In acne-prone skin, these cells tend to build up and clump together, leading to the formation of a microcomedone—the precursor to all acne lesions, including blackheads, whiteheads, and pimples. Adapalene prevents this process, effectively clearing existing comedones and preventing future breakouts.

In addition to its role in regulating cell turnover, adapalene possesses powerful anti-inflammatory properties. It works by suppressing the inflammatory response triggered by Propionibacterium acnes, the bacteria associated with acne breakouts. This dual-action approach of targeting both the cellular and inflammatory components of acne makes adapalene a comprehensive treatment for many acne types.

Benefits of Adapalene for Acne

Adapalene offers several advantages that make it a highly regarded treatment for acne:

Effective on Multiple Lesions: It is effective in treating both inflammatory acne (pimples, pustules) and non-inflammatory acne (blackheads, whiteheads).
Improved Tolerability: Compared to first-generation retinoids like tretinoin, adapalene is generally much less irritating, leading to better patient compliance and making it suitable for those with sensitive skin.
Photostable: Adapalene is a stable molecule that does not break down with sun exposure. This stability allows it to be used during the day and makes it suitable for combination therapy with other potentially unstable ingredients like benzoyl peroxide.
Long-Term Maintenance: Because of its favorable tolerability profile, adapalene is an excellent choice for long-term maintenance therapy to prevent acne from returning after an initial course of treatment.
Versatile Formulations: While the 0.1% gel is OTC, prescription options like lotions, creams, and the 0.3% gel provide dermatologists with flexibility in customizing treatment plans.

Adapalene vs. Tretinoin: A Comparative Look

Both adapalene and tretinoin are topical retinoids used to treat acne, but they have distinct differences in their properties and tolerability profiles. Tretinoin, a first-generation retinoid, has broader receptor binding, while adapalene's selective binding contributes to its improved tolerability. The following table compares some key characteristics of the two compounds:


Feature	Adapalene	Tretinoin
Availability	OTC (0.1% gel) and Prescription (0.1% cream/lotion, 0.3% gel)	Prescription only
Tolerability	Generally better tolerated with less initial redness, dryness, and irritation	Higher potential for initial irritation, dryness, and peeling
Chemical Stability	Photostable; can be used in the morning and with benzoyl peroxide	Photolabile; degrades in sunlight and with oxidizing agents
Acne Efficacy	Highly effective for inflammatory and non-inflammatory acne; comparable efficacy to tretinoin in some studies	Very potent and highly effective for acne
Other Uses	Primarily for acne; sometimes used off-label for other conditions	Also used for anti-aging and hyperpigmentation

How to Use Adapalene Safely

To ensure the best results and minimize potential irritation, proper application of adapalene is essential. Following a simple routine can help manage the initial acclimation period, often referred to as "retinization".

Application Steps:

Cleanse: Wash the affected skin gently with a mild cleanser and pat it dry completely.
Apply: Apply a pea-sized amount of adapalene gel as a thin layer over the entire affected area, not just on individual blemishes.
Frequency: Use the product only once per day, typically in the evening. Increasing frequency will not speed up results and may worsen irritation.
Moisturize: After the gel has absorbed for about 30 minutes, you can apply an oil-free, non-comedogenic moisturizer to help counteract dryness.
Wash Hands: Always wash your hands after application to avoid spreading the product to sensitive areas.

Key Precautions:

Avoid Sensitive Areas: Do not apply adapalene to sensitive skin around the eyes, lips, inside the nose, or on areas with cuts, abrasions, or sunburn.
Use Sunscreen: Adapalene increases skin's sensitivity to the sun. Use a broad-spectrum sunscreen with an SPF of 15 or higher every day, and minimize prolonged sun exposure.
Avoid Harsh Products: During treatment, avoid using other topical products that can cause dryness or irritation, such as products containing sulfur, salicylic acid, or a high alcohol content.
Hair Removal: Do not use waxing on treated skin, as it can cause irritation.

Common Side Effects

While adapalene is known for its improved tolerability, users may still experience temporary side effects, especially during the first few weeks of treatment. These are typically mild and often subside as the skin adjusts. Common side effects include:

Dryness and peeling of the skin
Redness
A burning or stinging sensation
Itching
Increased sensitivity to sunlight

If irritation becomes severe or if you experience symptoms of an allergic reaction (e.g., facial swelling, hives, shortness of breath), discontinue use and seek immediate medical attention.

Conclusion

Adapalene is a highly effective and well-tolerated topical retinoid that has revolutionized the approach to treating acne vulgaris. Its availability over-the-counter has provided a powerful tool for individuals managing acne at home. By normalizing skin cell turnover and reducing inflammation, it addresses key root causes of acne. While patience is required for optimal results, consistent and proper application, along with a protective skincare regimen, can lead to significantly clearer and healthier skin.

For additional authoritative information on adapalene and other dermatological medications, you can visit the NCBI Bookshelf.

Frequently Asked Questions

Yes, adapalene is photostable and chemically compatible with benzoyl peroxide, unlike some other retinoids. Many combination products containing both ingredients are available by prescription. When using separate products, it is often recommended to apply them at different times of the day to reduce the risk of skin irritation.

Individuals who are pregnant or breastfeeding should consult a doctor before using adapalene. While studies indicate minimal systemic absorption and no teratogenic risk has been identified with topical use, it is always recommended to seek medical advice.

It can take several weeks to begin seeing improvements, with full results often appearing after 12 weeks of consistent, once-daily use. A temporary worsening of acne may occur during the first few weeks before improvement is noticed.

No, a prescription is not needed for the 0.1% adapalene gel, which is available over-the-counter. However, stronger 0.3% gels and other formulations like creams and lotions require a prescription.

Skin purging is a temporary initial worsening of acne that some users experience. It occurs as the medication speeds up skin cell turnover, causing underlying comedones to surface all at once. This phase is normal and should not be a reason to stop treatment unless irritation becomes severe.

While adapalene's mechanism of action involves increasing cell turnover and improving skin texture, it is FDA-approved only for treating acne. Some healthcare professionals may recommend it off-label for photoaging, but other retinoids are more commonly used for this purpose.

Common side effects include dryness, redness, scaling, burning, and itching, particularly during the first month of use. These effects are generally mild and tend to decrease over time as the skin adjusts to the medication.