Adapalene

MECHANISM OF ACTION

Adapalene acts by binding to retinoic acid receptors (RARs) in skin cells, regulating keratinization to prevent clogged pores (microcomedones) and promote the exfoliation of existing ones. It also reduces inflammation by modulating inflammatory pathways and bacterial signals. By combining normalization of follicular cell turnover with anti-inflammatory effects, adapalene effectively targets the underlying causes of acne.

PHARMACOKINETICS

Absorption

Adapalene is minimally absorbed through the skin when applied topically, with only a small fraction reaching the systemic circulation. This limited absorption contributes to its localized effect on acne and a low risk of systemic side effects.

Distribution

The volume of distribution for topically applied adapalene is not typically expressed in liters, as systemic absorption is minimal. It mainly remains localized within the skin layers epidermis and dermis at the site of application.

Metabolism

After topical application, adapalene undergoes minimal metabolism, with most of the drug remaining in the skin (epidermis and dermis) where it binds to retinoic acid receptors (RARs) to regulate skin cell growth. Systemic absorption is very low, and the small amount that enters circulation is mainly metabolized in the liver to glucuronides and excreted primarily in the bile. Its stability and low water solubility help it stay localized, minimizing systemic side effects.

Excretion

When applied topically, adapalene is absorbed into the bloodstream at very low levels (less than 0.01% of the dose) and is mainly eliminated via the bile.

PHARMACODYNAMICS

Adapalene’s pharmacodynamics involve binding to nuclear retinoic acid receptors (RAR-β and RAR-γ) to regulate gene expression, promoting normal keratinocyte differentiation and proliferation. This prevents clogged pores (comedones) and reduces inflammation. Its strong anti-inflammatory activity, combined with improved skin tolerability compared to older retinoids, makes adapalene effective for acne by addressing both comedonal and inflammatory lesions through enhanced cell turnover and anti-inflammatory effects.

DOSAGE AND ADMINISTRATION

Formulations: Available as topical gel, cream, or lotion, commonly in 0.1% or 0.3% concentrations.

Indication: Primarily for acne vulgaris (comedonal and inflammatory lesions).

Dosage: Apply a thin layer once daily to the affected skin, usually in the evening.

Administration:

• Wash and gently dry the area before application.

• Avoid applying to eyes, lips, or mucous membranes.

• Use a pea-sized amount for the entire face to reduce irritation.

Duration: Improvement is typically seen within 8–12 weeks, but treatment may continue longer under medical guidance.

Precautions: May cause mild redness, dryness, or irritation initially; moisturizers can help. Sun protection is recommended due to increased photosensitivity.

DRUG INTERACTIONS

Adapalene has minimal systemic drug interactions due to low absorption, but combining it with other topical retinoids, acne treatments, or photosensitizing agents may increase skin irritation or sensitivity to sunlight.

FOOD INTERACTIONS

Topical adapalene has no known interactions with foods or drinks, so its use is not affected by meal times, and you can maintain your usual diet unless advised otherwise by your healthcare provider. However, there may be interactions with other topical products applied to the skin.

CONTRAINDICATIONS

Adapalene is mainly contraindicated in individuals with a known allergy to adapalene or any of its components. It should also be avoided on certain skin conditions or sensitive areas, and its use is generally not recommended during pregnancy.

SIDE EFFECTS

• Dryness and peeling.

• Redness.

• Burning/stinging.

• Itching.

• Sun sensitivity.

• Acne flares.

• Swelling of the face, lips, tongue, or throat.

• Difficulty breathing or wheezing.

• Severe dizziness or fainting.

OVERDOSE 

Symptoms of applying too much adapalene to the skin can include: 

• Marked skin redness or discoloration.

• Severe dryness and scaling/peeling skin.

• Intense burning or stinging sensation.

• Increased skin discomfort and irritation.

• Swollen or cracked skin.

• Increased sensitivity to sunlight.

TOXICITY

When used topically as directed, adapalene has low systemic toxicity due to minimal skin absorption. The main adverse effect is localized skin irritation such as redness, dryness, scaling, burning, or itching which is typically mild to moderate and temporary.