Apalene

• Approved Indications:

  • Acne Vulgaris: Treatment of acne vulgaris (mild to moderate) in patients aged 12 years and older. Effective for both inflammatory papules/pustules and non-inflammatory comedones (blackheads, whiteheads).

  Important Off-Label (Clinically Accepted) Uses:

  • Photoaging: Off-label use for reducing signs of photoaging, including fine wrinkles and hyperpigmentation.
  • Keratosis Pilaris: Sometimes used topically to reduce hyperkeratosis.
  • Other Hyperkeratotic Conditions: Occasionally prescribed for off-label treatment of conditions with abnormal keratinization, such as pityriasis rubra pilaris or plane warts (less common).

Route: Topical use only. For external use on affected skin areas. Avoid contact with eyes, lips, and mucous membranes.

Typical Dosage:

• Adults & Adolescents (≥12 years): Apply a thin film of adapalene 0.1% or 0.3% gel, cream, or lotion once daily at bedtime to clean, dry skin.
• Pediatrics (<12 years): Safety and efficacy not established for acne in children under 12 years.
• Photoaging (off-label): Usually applied similarly at night, but safety data for long-term use in photoaging are limited.

Special Instructions:

• Wash hands before and after application.
• Use a mild cleanser; avoid harsh soaps or astringents.
• If irritation occurs, reduce frequency to every other night.
• Sunscreen use during the day is strongly advised, as adapalene can increase photosensitivity.

Renal/Hepatic Impairment:

• No dose adjustment required; negligible systemic absorption.

Elderly:

• No specific dosing guidelines; usually not prescribed for acne in older adults except for off-label photoaging.

Adapalene is a synthetic, third-generation topical retinoid. It binds specifically to nuclear retinoic acid receptors (RAR-β and RAR-γ) in the skin, modifying gene expression to normalize the differentiation of follicular epithelial cells. This leads to decreased microcomedone formation, enhanced keratinocyte turnover, and anti-inflammatory effects by inhibiting chemotactic and inflammatory mediators. The combined actions help clear existing acne lesions, prevent new ones, and improve overall skin texture.

Absorption:
Minimal percutaneous absorption; about 0.5% to 0.9% of the applied dose is absorbed systemically.

Distribution:
Once absorbed, adapalene is highly protein bound (>99%).

Metabolism:
Metabolized primarily in the liver by standard hepatic oxidative pathways.

Excretion:
Eliminated mainly via biliary excretion; urinary excretion is negligible. Systemic half-life is not clinically relevant due to minimal absorption.

Pregnancy:
Previously classified as FDA Pregnancy Category C. Human data are limited; animal studies show teratogenic effects at high systemic doses but negligible systemic absorption is expected from topical use. Use only if potential benefit justifies the potential risk.

Lactation:
Minimal systemic absorption suggests negligible excretion into breast milk. If needed, apply after breastfeeding and avoid application on the breast or nipple area to prevent infant ingestion.

• Primary Class: Topical Retinoid
• Subclass: Third-generation synthetic retinoid (naphthoic acid derivative)

• Hypersensitivity to adapalene or any excipients in the formulation
• Eczema or severe skin irritation on the intended treatment area
• Pregnancy is a precaution — generally not recommended without clear benefit

• Photosensitivity: Increased risk of sunburn; daily sunscreen use is strongly recommended.
• Skin Irritation: Erythema, dryness, scaling, and burning/stinging may occur, especially during the first few weeks.
• Concurrent Skin Products: Avoid other potentially irritating products (abrasive soaps, astringents, peeling agents, alcohol-based cleansers).
• Avoid Use on Damaged Skin: Do not apply to cuts, abrasions, or sunburned skin.
• Severe Irritation: Discontinue use if severe irritation or allergic contact dermatitis develops.

Common:

• Local skin irritation: erythema, dryness, scaling, burning, or stinging sensation
• Initial worsening of acne in first 2–4 weeks (transient “purge” effect)

Serious/Rare:

• Severe contact dermatitis
• Severe photosensitivity reaction
• Hypersensitivity reactions (rare)

Severity is usually mild to moderate and self-limiting.

• Other Topical Agents: Use caution with other topical retinoids, benzoyl peroxide, salicylic acid, or sulfur-based products; combined use may increase irritation.
• Photosensitizing Agents: Caution when using with photosensitizing drugs (e.g., tetracyclines) due to increased risk of sunburn.
• Astringents/Exfoliants: Avoid co-use with harsh cleansers or scrubs that may exacerbate dryness and peeling.

Enzyme interactions are clinically irrelevant due to minimal systemic absorption.

• FDA: No recent major updates; remains approved as first-line topical retinoid for mild to moderate acne.
• NICE & Other Guidelines: Continue to recommend adapalene as a preferred topical retinoid for acne, often in combination with benzoyl peroxide for enhanced efficacy.
• Recent Evidence: Supports once-daily application; combination products with benzoyl peroxide widely endorsed to reduce bacterial resistance.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep tube or container tightly closed.
• Protect from excessive heat and direct light.
• Do not freeze.