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, because it can deliver results with less irritation. Better known by its brand name Differin, adapalene is sold over the counter in some countries, such as the United States. Whether you need a prescription depends on the strength. However, it remains a prescription-only medicine in the UK. In this guide, we explain what adapalene is, how it works and what it can treat beyond acne. We also look at its side effects and how it compares with the most famous Retinoid, tretinoin.
What is Adapalene?
Adapalene is a synthetic third-generation Retinoid. It is a man-made compound and 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. The pharmaceutical company Galderma makes it. Unlike first-generation Retinoids such as tretinoin, adapalene had a specific clinical goal from the very start. The aim was to keep 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%), as a cream or gel. It also comes in a combination formula (Epiduo) that pairs 0.1% or 0.3% adapalene with 2.5% benzoyl peroxide. So, whilst Differin is sold over the counter at 0.1% in the USA, all forms of adapalene need 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 the RAR-α, RAR-β and RAR-γ subtypes, 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 mostly express RAR-γ, this selective binding is likely why adapalene causes less irritation whilst still working well. In practice, its structure and mechanism give it a number of clinical effects:
- Normalises turnover: Adapalene regulates how skin cells develop and shed within the hair follicle. This prevents the microcomedones that are the microscopic precursors to blackheads, whiteheads and inflammatory acne.
- Comedolytic activity: It directly breaks down existing comedones (blocked pores). This helps clear both the open and closed pores already present on the skin.
- Anti-inflammatory action: Adapalene limits the migration of white blood cells to the skin and reduces the release of pro-inflammatory agents. So, it works well for inflammatory acne.
- Excellent follicular penetration: Adapalene is highly lipophilic (fat-soluble), so it concentrates well within the pilosebaceous unit (the oil gland and hair follicle). In fact, fluorescence microscopy studies show that adapalene microcrystals reach follicular openings down to the sebaceous gland within minutes of application.
- Stable: Many Retinoids degrade in light or become inactive with benzoyl peroxide. Adapalene, however, stays stable in both situations.
What Does Adapalene Treat?
In the UK, adapalene’s licence covers only acne vulgaris. However, it also has several off-label uses that reflect its broader effects on the skin. The main uses of adapalene include:
- Acne vulgaris: This is adapalene’s main use. It is effective for both comedonal acne (blackheads and whiteheads) and inflammatory acne (papules and pustules). It also 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, because it combines the comedolytic action of adapalene with the antibacterial effect of benzoyl peroxide. For moderate to severe acne, adapalene often needs pairing with oral antibiotics like doxycycline.
- Post-inflammatory hyperpigmentation: Adapalene can help fade the mild dark marks left after acne heals. By speeding up cell turnover, it helps the skin shed pigmented cells faster. So, it is a useful add-on for acne-prone skin that is also dealing with post-inflammatory hyperpigmentation. This is particularly helpful in skin of colour, where PIH is more common and more stubborn. That said, it may need pairing with pigment suppressors like hydroquinone for the best results.
- Photoageing: There is emerging evidence that adapalene, particularly at 0.3%, can improve some signs of photoageing, including fine lines and rough texture. However, the evidence in skin ageing is far less robust than for tretinoin, which has decades of data behind wrinkles, collagen stimulation and sun damage repair. So, if anti-ageing is your main goal, tretinoin remains the more effective choice.
In addition, adapalene may have off-label uses for conditions like keratosis pilaris, warts, Darier disease and some pigmentary disorders. These are less common and need management by a specialist dermatologist.
How to Use Adapalene
In general, you apply adapalene once a day in the evening to clean, dry skin. A pea-sized amount is usually enough for the whole face, applied 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.
As with all Retinoids, the rule is to start low and go slow. If your skin is sensitive, or you are new to Retinoids, your prescriber may suggest applying it 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 see improvement, so consistency is key. In fact, stopping early, or using it too infrequently because of initial purging, dryness or irritation, is one of 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 stronger Retinoids like tretinoin. However, it is still a Retinoid, so it can cause side effects, especially when you first start. The most common side effects of adapalene include:
- Dryness and peeling: This is the most common side effect. Your skin may feel dry, flaky or tight, particularly in the first few weeks. A good moisturiser and support for the skin barrier help manage it.
- Redness and irritation: Some redness, sensitivity or burning is common early on. This usually settles as your skin adjusts over 2 to 4 weeks. Starting at a lower frequency, or sandwiching with moisturiser, can reduce it.
- Skin purging: Like all Retinoids, adapalene can cause an initial flare of acne known as skin purging. This happens because it speeds up cell turnover, which brings existing microcomedones to the surface faster. It is temporary and usually settles within 4 to 8 weeks.
- Photosensitivity: Adapalene can make your skin more sensitive to sunlight. So, daily use of a broad-spectrum sunscreen of at least SPF 30 is essential with adapalene or any Retinoid.
- Pregnancy risk: Like all Retinoids, adapalene is not safe during pregnancy or breastfeeding, because of the potential risk to the developing baby.
How Does Adapalene Compare with Tretinoin?
This is one of the most common questions we get, so we have written a detailed comparison of tretinoin and adapalene. In brief though, adapalene is the gentler option. It causes less irritation and dryness, particularly in the first few weeks, which makes it a good choice if you are new to Retinoids, have sensitive skin or have struggled with retinoid dermatitis before. Clinical studies consistently show that adapalene irritates less than tretinoin, but with similar results for mild to moderate acne.
Tretinoin is the more versatile and potent option, though, like adapalene, its licence covers only acne vulgaris. It has over 50 years of clinical evidence and works across a much broader range of concerns, because it binds to more Retinoid receptors. However, that broader activity also means it can be more irritating, particularly at higher strengths. The main advantages of tretinoin over adapalene include:
- More versatile for acne: Tretinoin has a longer track record for acne and comes in higher strengths for more stubborn cases. At equivalent strengths, both work well for mild to moderate acne, but tretinoin leaves more room to escalate.
- Treats uneven tone: Tretinoin actively reduces excess pigment by speeding up cell turnover and curbing melanin transfer. Adapalene has far less evidence for hyperpigmentation or melasma.
- Gold standard for skin ageing: Tretinoin has the most evidence as a topical treatment for photoageing. It boosts collagen, softens fine lines and wrinkles and repairs sun damage at the cell level. Adapalene has no approval for anti-ageing and little research behind it.
- Improves scars and texture: Tretinoin can improve superficial scars, texture and early stretch marks through its effects on cell turnover and collagen. Adapalene has limited evidence here.
- Works well in combinations: Tretinoin is chemically compatible with many other prescription actives, including hydroquinone, azelaic acid and niacinamide. So, it is ideal for compounded formulas that target several concerns at once.
| Adapalene | Tretinoin | |
|---|---|---|
| Tolerance | gentler, less irritating | stronger, more irritating |
| Acne | effective for mild to moderate | effective, with more room to escalate |
| Hyperpigmentation | limited evidence | actively fades pigment |
| Skin ageing | little evidence | gold standard for lines and collagen |
| Stability | stable in light and with benzoyl peroxide | degrades in light, inactivated by benzoyl peroxide |
| UK access | prescription only | prescription only |
For a deeper look at how Retinoids compare in 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. So, to get it, you will need a prescription from a GP, dermatologist or other registered prescriber. It is available on the NHS for acne, which means your GP can prescribe it if they feel it is appropriate. 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 doctors prescribe it less often in general practice. If your GP has not been able to help, or you would like a more tailored approach, a number of private dermatology and online skin clinics can assess your skin and prescribe Retinoid treatments for acne.
Adapalene hits a sweet spot between effectiveness and tolerance. It is a genuinely good treatment for acne, particularly for anyone who finds traditional Retinoids like tretinoin too irritating. Its chemical stability, selective receptor binding and anti-inflammatory action give it real advantages as a Retinoid for acne. However, for more stubborn acne, dark spots, fine lines or melasma, tretinoin still offers the broadest range of benefits. Ultimately, the right Retinoid for you depends on your skin type, your concerns and your tolerance, and your medical provider can help guide that decision.
At City Skin Clinic, we are passionate about personalised skin care. Whilst we do not use adapalene, our doctors tailor treatments to each patient using ingredients like tretinoin, azelaic acid and hydroquinone where appropriate through our online clinic. Our doctors treat acne, hyperpigmentation, melasma and skin ageing through bespoke compounded treatments designed around you. To start your personalised plan, 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 provider for any health concerns or questions you might have.
