Adapalene

BRAND NAMES

Common brands of adapalene include Differin, Epiduo—which combines adapalene with benzoyl peroxide—and Adaferin. Additional brand names vary by region and may include Deriva-CMS, Adaclin, and Acnovate.

• Differin: A well-known brand name for adapalene.

• Epiduo: A brand that combines adapalene with benzoyl peroxide.

• Adaferin: Another available brand name for adapalene.

MECHANISM OF ACTION

Adapalene is used to treat and maintain mild to severe acne (acne vulgaris). Acne is a complex condition influenced by multiple factors, and adapalene is believed to work through several mechanisms. It binds to retinoic acid receptors (RAR-beta and RAR-gamma), which then form a complex with one of three retinoid X receptors (RXRs). This receptor complex can bind to DNA and regulate gene transcription. Although the full scope of this transcriptional regulation is not completely understood, retinoid activation is generally known to influence cell proliferation and differentiation.

PHARMACOKINETICS:

Absorption

Adapalene is applied topically and absorbed through the skin. In a clinical study where patients applied 2 grams of 0.3% gel once daily over an area of 2 mg/cm², adapalene was detectable in the blood plasma of 15 patients at levels of 0.1 ng/ml. On day 10, the average maximum concentration (Cmax) reached 0.553 ± 0.466 ng/ml, and the average area under the curve (AUC) was 8.37 ± 8.46 ng·h/ml.

Distribution

After topical application, adapalene distributes throughout the epidermis and dermis, quickly penetrating the pilosebaceous units. It tends to accumulate around hair follicles, where it likely dissolves in the sebum. Although adapalene is present in the skin layers, systemic absorption is very low—only about 0.01% of the applied dose passes through the skin—with minimal amounts detected in the bloodstream or liver.

Metabolism

The metabolism of adapalene, a topical retinoid, is not fully characterized in humans, but what is known indicates minimal systemic processing. The drug is primarily used topically, and its very low systemic absorption minimizes the need for extensive metabolism throughout the body.

Excretion

Adapalene is mainly eliminated through the biliary system, with around 75% of the drug excreted unchanged. About 25% of adapalene undergoes metabolism into glucuronide conjugates prior to excretion.

PHARMACODYNAMICS

Adapalene exerts its pharmacodynamic effects as a retinoid-like agent that helps regulate skin cell differentiation, thereby preventing the development of microcomedones. It selectively binds to retinoic acid receptors (RAR-β and RAR-γ) within the cell nucleus, influencing gene transcription involved in cell proliferation, differentiation, and inflammation. These actions result in comedolytic (pore-clearing) and anti-inflammatory effects, making adapalene effective in the treatment of acne.

ADMINISTRATION

Topical adapalene is typically applied once daily as a thin layer to clean, dry skin—most often in the evening. For best results, consistent use is essential. It's also important to be mindful of possible side effects and follow recommended precautions to enhance effectiveness and reduce skin irritation.

DOSAGE AND STRENGTH

Adapalene is a topical retinoid available in different strengths and formulations, most commonly as a 0.1% strength available over-the-counter and a stronger 0.3% strength available by prescription. It is typically applied once daily, in the evening.

DRUG INTERACTIONS

Although adapalene is a topical medication with minimal systemic absorption, it can still interact with other products applied to the skin. One of the most common concerns is combining adapalene with other topical acne treatments such as benzoyl peroxide, salicylic acid, sulfur, resorcinol, or alpha hydroxy acids. While these ingredients are effective individually, using them together with adapalene may lead to increased skin irritation, dryness, and peeling. However, certain combination products like Epiduo (which contains both adapalene and benzoyl peroxide) are specifically formulated to minimize such effects and are safe when used as directed.

FOOD INTERACTIONS

There are no known interactions between adapalene (the active ingredient in Differin) and food or alcohol. Because it is a topical treatment, it is not ingested and is not affected by what you eat or drink.

CONTRAINDICATIONS

The contraindications for adapalene are primarily related to hypersensitivity to the drug and its use on compromised skin. Caution is also advised regarding its use during pregnancy and for children under 12.

SIDE EFFECTS

Common Side Effects:

• Skin dryness and peeling

• Redness with mild burning or irritation

• Flaky or shedding skin

• Increased sensitivity to sunlight (photosensitivity)

Less Common Side Effects:

• Itching and localized swelling

• Rashes or allergic hives

OVER DOSE

• Rare with topical use, but can occur with excessive application.

• Symptoms: Skin irritation, redness, dryness, peeling, or burning.

• Systemic effects: Unlikely due to low absorption.

• No specific antidote: Treatment is supportive.

• What to do: Stop use, moisturize irritated skin, and consult a doctor if needed.

• Prevention: Apply only a thin layer as directed—more is not better.

TOXICITY

Adapalene is a topical retinoid with a favorable safety profile and minimal systemic toxicity due to very low skin absorption. The primary toxicities are local and manageable skin irritations, with systemic effects only occurring from accidental chronic ingestion at high doses.