What are the effects and uses of azelaic acid?

What Azelaic Acid Does

Azelaic acid is a topical medication with multiple mechanisms of action including anti-inflammatory, antimicrobial, comedolytic (pore-unclogging), and depigmenting properties, making it effective for treating acne vulgaris, rosacea, and hyperpigmentation disorders. 1, 2

Primary Mechanisms of Action

Azelaic acid works through several distinct pathways:

• Anti-inflammatory effects: Reduces inflammation by inhibiting the cathelicidin pathway, which is upregulated in rosacea-affected skin 1
• Antimicrobial activity: Inhibits cellular protein synthesis in Propionibacterium acnes and Staphylococcus epidermidis, the bacteria responsible for acne 3, 4
• Comedolytic action: Normalizes keratinization by reducing stratum corneum thickness, decreasing keratohyalin granules, and reducing filaggrin distribution, which prevents microcomedo formation 3
• Depigmenting effect: Inhibits tyrosinase enzyme activity, reducing melanin production in hyperactive melanocytes 4, 5
• Antioxidant properties: Scavenges harmful free radicals and inhibits reactive oxygen species production by neutrophils 4

FDA-Approved Clinical Uses

Acne Vulgaris

• Available as 20% cream formulation for treating mild to moderate inflammatory acne 1, 2
• In clinical trials, 28% more patients achieved 50-100% reduction in total lesion count compared to vehicle at 3 months 1, 2
• Demonstrated comparable efficacy to tretinoin, benzoyl peroxide, erythromycin, and oral tetracycline 5

Rosacea (Papulopustular Type)

• FDA-approved as 15% gel since 2002 for inflammatory papules and pustules of rosacea 1, 6
• In two pivotal trials with 664 subjects, inflammatory lesions decreased from baseline means of 17.5-17.8 to 6.8-8.9 at 12 weeks 1
• Achieved 51% marked improvement or complete remission rates in study 1 1
• More effective than metronidazole 0.75% for erythema severity, overall improvement, and inflammatory lesion reduction 7

Additional Dermatologic Applications

Hyperpigmentation Disorders

• Particularly beneficial for patients with darker skin types (Fitzpatrick IV or greater) due to lightening effect on post-inflammatory hyperpigmentation 1, 2, 8
• For melasma, azelaic acid 20% demonstrated significantly better results than hydroquinone 2% for global improvement 7
• Also used for perioral dermatitis and lentigo maligna 9, 5

Dosing and Administration

• Apply as a thin film twice daily (morning and evening), gently massaged into affected areas 2
• Available concentrations: 15% gel (rosacea) and 20% cream (acne) 1, 2, 6
• Avoid occlusive dressings and contact with eyes, mouth, and mucous membranes 3

Safety Profile

Common Side Effects

• Temporary skin irritation including pruritus, burning, stinging, tingling, erythema, dryness, rash, peeling, and contact dermatitis 2, 3
• Irritation typically occurs at treatment start and commonly subsides with continued use 3
• If irritation persists, reduce to once-daily application or discontinue temporarily 3

Special Populations

• Pregnancy Category B: Risk of fetal harm not expected based on limited systemic absorption (only 4% absorbed systemically) 1, 2, 8, 3
• Safe for nursing mothers as milk/plasma distribution coefficient is 0.7, with minimal expected uptake into breast milk 3
• Not established for pediatric patients under 12 years 3

Pharmacokinetics

• Approximately 3-5% penetrates stratum corneum, up to 10% reaches epidermis and dermis 3
• Only 4% systemically absorbed with negligible cutaneous metabolism 3
• Half-life: 45 minutes after oral dosing, 12 hours after topical dosing (indicating absorption rate-limited kinetics) 3
• Mainly excreted unchanged in urine with some β-oxidation to shorter chain dicarboxylic acids 3

Clinical Advantages

• Well-tolerated with adverse effects limited to mild, transient local irritation 5, 6
• Suitable for all skin types, especially sensitive skin 2, 6
• Can be used during pregnancy unlike many other acne/rosacea treatments 1, 2
• No antibiotic resistance concerns unlike topical antibiotics 1
• Addresses multiple pathogenic factors simultaneously (inflammation, bacteria, keratinization, pigmentation) 4, 5