Nomark

Approved Indications:

• Acne Vulgaris: Approved for the topical treatment of acne vulgaris in patients ≥9 years old (depending on the brand and formulation). Indicated for mild to moderate acne presenting with both inflammatory lesions (papules, pustules) and non-inflammatory lesions (open and closed comedones). Combination therapy is recommended when monotherapy with a topical retinoid or benzoyl peroxide alone is insufficient.

Important Off-Label (Clinically Accepted) Uses:

• Acne Maintenance Therapy: Often used off-label as part of long-term acne maintenance to prevent recurrence once active breakouts are under control.
• Mild Acne Resistant to Monotherapy: When acne does not adequately respond to adapalene or benzoyl peroxide alone, this fixed-dose combination is an evidence-based escalation step.

Typical Dosage:

• Standard Regimen: Apply a thin layer of the combination gel (e.g., adapalene 0.1% or 0.3% + benzoyl peroxide 2.5%) once daily in the evening to the entire affected area of clean, dry skin.
• Initial Use: Some patients may tolerate every-other-night application during the first 1–2 weeks to minimize irritation.
• Children <9 Years: Safety and efficacy not established.
• Renal/Hepatic Impairment: No adjustments necessary — negligible systemic absorption.
• Elderly: Rarely used in elderly patients except in atypical cases of adult acne.

Special Instructions:

• Wash hands before and after use.
• Use a gentle cleanser; avoid abrasive or drying soaps.
• Use oil-free, non-comedogenic moisturizers to reduce dryness and irritation.
• Daily broad-spectrum sunscreen is essential due to increased photosensitivity.

This fixed-dose combination works through dual complementary mechanisms:

• Adapalene: A third-generation retinoid that binds to nuclear retinoic acid receptors (RAR-β, RAR-γ) in skin cells, promoting normal keratinocyte differentiation, decreasing microcomedone formation, and providing anti-inflammatory effects by inhibiting chemotactic and inflammatory mediators.
• Benzoyl Peroxide: An antibacterial and mild keratolytic agent that releases free radical oxygen to kill Cutibacterium acnes (formerly Propionibacterium acnes), the key acne-causing bacteria. It also helps to shed excess dead skin cells and unclog pores.
  Together, they reduce both comedonal and inflammatory acne lesions more effectively than either agent alone.

Absorption:

• Adapalene: Less than 0.1–0.3% is absorbed systemically through the skin.
• Benzoyl Peroxide: Rapidly absorbed into the skin and converted to benzoic acid, which is absorbed and excreted unchanged in the urine.

Distribution:

• Adapalene: >99% protein bound when systemically absorbed.
• Benzoic Acid: Widely distributed, but systemic levels are negligible at therapeutic doses.

Metabolism:

• Adapalene: Metabolized hepatically by oxidation and conjugation.
• Benzoyl Peroxide: Metabolized locally in the skin to benzoic acid.

Excretion:

• Adapalene: Mainly eliminated via biliary excretion.
• Benzoic Acid: Rapidly excreted in urine.

Pregnancy:

• Previously FDA Pregnancy Category C for adapalene. Limited human data; animal studies show teratogenicity at high systemic doses. Systemic absorption from topical use is very low, but avoid extensive use during pregnancy unless clearly needed.
• Benzoyl peroxide has minimal systemic absorption and is generally considered low risk.

Lactation:

• Systemic exposure is negligible for both components. Risk to nursing infants is considered very low when used as directed. Avoid application on the chest or areas that may come in direct contact with the infant’s mouth.

• Primary Class: Topical Combination Acne Agent
• Subclasses:
• Third-generation synthetic retinoid (adapalene)
• Antibacterial / keratolytic (benzoyl peroxide)

• Hypersensitivity to adapalene, benzoyl peroxide, or any product excipients
• Presence of eczema, severe sunburn, or damaged skin at application sites
• Not recommended during pregnancy unless benefit outweighs potential risk

• Photosensitivity: Increases risk of sunburn. Daily sunscreen use is essential.
• Skin Irritation: Erythema, scaling, dryness, burning, or stinging are common, especially in the first 2–4 weeks.
• Bleaching Effect: Benzoyl peroxide can bleach hair and colored fabrics.
• Avoid Harsh Products: Do not use with other irritant topical agents (alcohol, astringents, abrasives).
• Severe Irritation: If severe irritation or contact dermatitis occurs, discontinue use and consult a physician.

Common:

• Local skin irritation: dryness, redness, peeling, burning or stinging
• Mild sun sensitivity
• Initial acne flare (“purging”) during early weeks

Serious/Rare:

• Severe allergic contact dermatitis
• Severe photosensitivity reaction
• Hypersensitivity reactions

Most side effects are mild to moderate and decrease with continued use.

• Other Topical Retinoids: Avoid concurrent use to prevent additive irritation.
• Other Keratolytics: Avoid combining with strong exfoliants or chemical peels.
• Photosensitizing Drugs: Use caution with oral antibiotics like tetracyclines, which may increase sun sensitivity.
• No significant enzyme-mediated systemic drug interactions due to minimal absorption.

• FDA: No recent major label changes; fixed-dose adapalene + benzoyl peroxide remains a recommended first-line topical combination for mild to moderate acne.
• NICE & Other Guidelines: Widely recommended in national and international acne treatment guidelines as a preferred topical combination to reduce bacterial resistance and improve treatment adherence.
• Recent Research: Confirms combination therapy achieves faster and greater acne clearance than monotherapy with either agent alone.

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