DERIVA 0.1% AQUEOUS GEL

Indications

• Acne vulgaris
• Mild to severe acne

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Apply a thin layer of adapalene to the affected areas once daily, preferably in the evening.

Mechanism of action

Adapalene binds to retinoic acid receptors RAR-beta and RAR-gamma, forming a complex that interacts with retinoid X receptors (RXRs) to modulate transcriptional activity. This action promotes cellular differentiation and inhibits proliferation, which is essential for its comedolytic and anticomedogenic effects. Additionally, adapalene down-regulates toll-like receptor 2 (TLR-2) expression and inhibits activator protein 1 (AP-1), reducing inflammation associated with acne by modulating the immune response.

Pharmacodynamics

Adapalene is anticomedogenic, preventing new comedone and inflammatory lesion formation, while also reducing inflammation through modulation of the innate immune response. Common adverse effects include minor skin irritations such as erythema, scaling, dryness, and stinging or burning sensations. Due to its photosensitivity, the use of sunscreen is recommended during treatment.

Pharmacokinetics

Adapalene has a molecular formula of C28H28O3. It is absorbed through the skin, with its pharmacokinetic profile characterized by local action at the site of application. Systemic absorption is minimal, limiting the risk of systemic side effects. The topical application leads to localized therapeutic concentrations, which contribute to its efficacy in treating acne.

Adverse effects

• Erythema
• Scaling
• Dryness
• Stinging
• Burning

Precautions

• Use with sunscreen due to photosensitivity
• Monitor for minor skin irritations

Pregnancy

Adapalene is classified as a category C drug. Use during pregnancy should only be if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data suggest that adapalene is excreted in breast milk, caution is advised when used during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Topical gel
• Topical cream

Mechanism of action

Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity. Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. These effects primarily account for adapalene's comedolytic and anticomedogenic properties. In addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes _Cutibacterium acnes_ (formerly _Propionibacterium acnes_), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms. When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.

Pharmacodynamics

Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.