If you’ve been exploring acne treatments or prescription skincare, there’s a good chance you’ve come across adapalene. It is one of the most common topical retinoids for acne as it can deliver results with less irritation. Better known by its brand name Differin, adapalene is available over the counter and by prescription depending on the strength in countries like the United States. However, it remains a prescription-only medicine in the UK. In this article, we explain what adapalene is, how it works and what it can treat beyond acne. We’ll also review adapalene’s side effects and how it compares with the mot famous retinoid tretinoin.
What is Adapalene?
Adapalene is a synthetic third-generation retinoid. It is a man-made compound and is a derivative of vitamin A. Adapalene got approval from the FDA in 1996 for the topical treatment of acne vulgaris under the brand name Differin. It is manufactured by the pharmaceutical company Galderma. Unlike first-generation retinoids such as tretinoin, adapalene was designed from the ground up with a specific clinical goal in mind. The aim was to create a retinoid that kept the pore-clearing and anti-inflammatory benefits of tretinoin but with fewer side effects.
In the UK, adapalene is available by prescription in two strengths (0.1% and 0.3%). Adapalene comes as a cream or gel. It is also available in a combination formula (Epiduo) that contains either 0.1 or 0.3% adapalene and 2.5% benzoyl peroxide. Whilst Differin is available over the counter at 0.1% strength in the USA, all forms of adapalene require a prescription in the UK.
How Does it Work?
Like all retinoids, adapalene works by binding to retinoic acid receptors (RARs) in the skin which then influence gene expression in skin cells. However, what sets adapalene apart from tretinoin is the way it interacts with these receptors. Tretinoin binds broadly to RAR-α, RAR-β and RAR-γ subtypes of RAR receptor as well as to cytosolic retinoic acid binding proteins (CRABPs). Adapalene, on the other hand, mainly targets the RAR-β and RAR-γ receptors and does not bind the CRABPs at all. Since skin cells predominantly express RAR-γ, this selective binding is likely the main reason why adapalene causes less irritation whilst still being effective on the skin. The mechanism of action as well as structure of adapelene imparts a number clinical effects:
- Normalises turnover: Adapalene regulates how skin cells develop and shed within the hair follicle. This prevents the formation of microcomedones which are the microscopic precursors to blackheads, whiteheads and inflammatory acne.
- Comedolytic activity: It directly breaks down existing comedones (blocked pores). This helping to clear both open and closed pores that are already present on the skin.
- Anti-inflammatory action: Adapalene limits the migration of white blood cells to the skin, reduces the release of pro-inflammatory agents. This is why it works well for inflammatory acne.
- Excellent follicular penetration: Adapalene is highly lipophilic (fat-soluble) which means it concentrates well within the pilosebaceous unit (the oil gland and hair follicle). Fluorescence microscopy studies have shown that adapalene microcrystals penetrate into follicular openings to the level of the sebaceous gland within minutes of application.
- Stable: Many retinoids degrade with light exposure or become inactivate in the presence of benzoyl peroxide. Adapalene remains stable in both situations.
What Does Adapalene Treat?
Adapalene is only licensed for the treatment of acne vulgaris. However, it also has a number of additional off-label uses that reflect its broader effects on the skin. The main uses of adapalene include:
- Acne Vulgaris: This is adapalene’s primary indication. It is effective for both comedonal acne (blackheads and whiteheads) and inflammatory acne (papules and pustules). It works particularly well for mild to moderate acne. Epiduo (adapalene 0.1% or 0.3% with benzoyl peroxide 2.5%) is one of the most commonly prescribed topical acne treatments in the UK. This is because it combines the comedolytic activity of adapalene with the antibacterial effects of benzoyl peroxide. For moderate to severe acne, adapalene often requires pairing with oral antibiotics like doxycycline.
- Post-Inflammatory Hyperpigmentation: Adapalene can help fade the mild dark marks left behind after acne lesions heal. By increasing cell turnover, it helps the skin shed pigmented cells more quickly. This makes it a useful adjunct for people with acne-prone skin who are also dealing with post-inflammatory hyperpigmentation. This is particularly helpful in skin of colour where PIH is more common and more persistent. It may however require pairing with pigment suppressors like hydroquinone for best results.
- Photoageing: There is emerging evidence that adapalene, particularly at the 0.3% strength, can improve some signs of photoageing including fine lines and rough skin texture. However, the evidence for adapalene in skin ageing is considerably less robust than for tretinoin which has decades of clinical data to support its use for wrinkles, collagen stimulation and sun damage repair. If anti-ageing is a primary goal, tretinoin remains the most effective choice.
In addition to the above, adapalene may also have off-label uses for conditions including keratosis pilaris, warts, Darier disease and some pigmentary disorders. These uses are less common and require management by a specialist dermatologist.
How to Use Adapalene
In general, you apply adapalene once daily in the evening to clean, dry skin. A pea-sized amount is usually sufficient for the entire face and application should be as a thin layer. Avoid the eyes, lips and any broken or irritated skin. If you are using it alongside other actives, your prescriber will advise on the order and timing of these.
As with all retinoids, the general rule is to start low and go slow. If your skin is sensitive or you are new to retinoids, your prescriber may recommend starting with application every other night for the first 2 to 4 weeks before moving to nightly use. It typically takes at least 8 to 12 weeks to start seeing improvement. However, you will need to be consistent!. Prematurely stopping or using at low frequency often due to initial purging, dryness or irritation are often the main reasons people do not see results. You will also need to maintain your results once your acne clears and protect your skin from UV exposure.
Side Effects & Risks
One of adapalene’s main selling points is that it tends to be gentler than strong retinoids like tretinoin. However, it is still a retinoid and can cause side effects especially when you first start using it. The most common side effects of adapalene include:
- Dryness and peeling: This is the most frequently reported side effect. The skin may become noticeably dry, flakey or tight, particularly in the first few weeks. Using a good moisturiser and supporting the skin barrier can help manage this.
- Redness and irritation: Some redness, sensitivity or burning is common when starting adapalene. This usually goes away as the skin adjusts over 2 to 4 weeks. Starting with a lower frequency or sandwiching with moisturiser can minimise this.
- Skin purging: Like all retinoids, adapalene can cause an initial worsening of acne known as skin purging. This happens because adapalene speeds up cell turnover, bringing existing microcomedones to the surface more quickly. It is temporary and usually resolves within 4 to 8 weeks.
- Photosensitivity: Adapalene can increase the skin’s sensitivity to sunlight. Daily use of a broad-spectrum sunscreen with at least SPF30 is essential when using adapalene or any retinoid.
- Pregnancy risk: Like all retinoids, adapalene should not be used during pregnancy or breastfeeding due to the potential risk to the developing baby.
How Does Adapalene Compare with Tretinoin?
This is one of the most common questions we get and we’ve written a detailed comparison of tretinoin vs adapalene. However, in brief, adapalene is the gentler option. It causes less irritation and dryness, particularly in the initial weeks of use. This makes it a good choice for people who are new to retinoids, have sensitive skin or who have struggled with retinoid dermatitis in the past. Clinical studies have consistently shown that adapalene causes less irritation than tretinoin but with similar effects for mild to moderate acne.
Tretinoin is the more versatile and potent option though like adapalene it is also only licensed for use in acne vulgaris. It has over 50 years of clinical evidence and works across a much broader range of skin concerns because it binds to more retinoid receptors on skin cells. However, this broader activity also means it can be more irritating, particularly at higher strengths. The key advantages of tretinoin over adapalene include:
- More versatile for acne: Tretinoin has a longer track record for acne and is available in higher strengths for more stubborn cases. At equivalent strengths, both produce good results for mild to moderate acne but tretinoin offers more room to escalate if needed.
- Treats uneven skin tone: Tretinoin actively reduces excess pigmentation by speeding up cell turnover and suppressing melanin transfer. Adapalene does not have as much evidence for treating hyperpigmentation or melasma.
- Gold standard for skin ageing: Tretinoin has the most evidence backing as a topical treatment for photoageing. It boosts collagen production, improves fine lines and wrinkles and reverses sun damage at the cell level. Adapalene has not been approved or widely studied for anti-ageing.
- Improves scars & texture: Tretinoin can help improve superficial scars, texture and early stretch marks through its effects on cell turnover and collagen remodelling. This is an area where adapalene has limited evidence.
- Works well in combination formulations: Tretinoin is chemically compatible with a wide range of other prescription actives including hydroquinone, azelaic acid and niacinamide. This makes it ideal for compounded formulations that target multiple concerns in a single product.
For a deeper look at how different retinoids compare in terms of potency and how to convert between them, see our guide to retinoid equivalent strengths.
How to Get Adapalene in the UK
In the UK, adapalene is a prescription-only medicine in all its forms. To access adapalene, you will need a prescription from a GP, dermatologist or other registered prescriber. It is available on the NHS for the treatment of acne, which means your GP can prescribe it if they feel it is appropriate for you. The most common formulas are adapalene 0.1% gel and Epiduo gel (adapalene 0.1% with benzoyl peroxide 2.5%). The higher strength 0.3% adapalene gel is also available but is less commonly prescribed in general practice. If your GP has not been able to help or if you would like a more tailored approach to your skin, there are a number of private dermatology and online skin clinics that can assess your skin and prescribe retinoid treatments for acne.
Adapalene hits a sweet spot between effectiveness and tolerance. It is a truly good treatment for acne, particularly for those who find traditional retinoids like tretinoin too irritating. Its chemical stability, selective receptor binding and anti-inflammatory properties give it real advantages as a retinoid for acne. However, for addressing more stubborn acne, dark spots, fine lines or melasma, tretinoin still offers the broadest range of benefits. The right retinoid for you ultimately depends on your skin type, your concerns and your tolerance. Your medical provider can help guide that decision and boost your treatment protocol.
At City Skin Clinic, we are devoted to personalised skincare and provide safe effective custom skin treatments through our virtual clinic. Whilst we do not use adapalene, our doctors tailor treatments to each and every patient’s unique needs using ingredients like Tretinoin, Azelaic acid and Hydroquinone where appropriate. We treat conditions like acne, hyperpigmentation, melasma and skin ageing. To start your personalised skincare protocol, book a virtual video consultation or use our online consultation form. The journey towards great skin starts here.
This article is intended for general informational purposes only and is not a substitute for medical advice, diagnosis or treatment. Always consult a qualified medical professional with any concerns about your skin or treatment options.
