What is the mechanism of action of azelaic acid in treating rosacea?

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From the Guidelines

Azelaic acid is effective for rosacea due to its anti-inflammatory activity on the cathelicidin pathway, which is upregulated in rosacea-affected skin. This is supported by a study published in 2024, which found that azelaic acid 15% gel improved rosacea by exerting anti-inflammatory activity on the cathelicidin pathway 1. The study also reported that azelaic acid 20% cream was studied in a split-face, 9-week study of 33 subjects, and at 9 weeks, complete remission or marked improvement occurred in 78.2% of the treated sides compared with 31.2% with placebo.

Some key points about azelaic acid for rosacea treatment include:

  • It is typically used as a 15% gel or 20% cream, applied twice daily to clean, dry skin
  • Patients should expect to use it consistently for at least 8-12 weeks to see significant improvement
  • Common side effects include temporary stinging, burning, or itching upon application, which usually diminishes with continued use
  • Azelaic acid is generally well-tolerated and can be used alongside other rosacea treatments like topical metronidazole or oral antibiotics for enhanced effectiveness

According to a 2017 study, azelaic acid is considered a first-line treatment for mild to moderate rosacea, and is recommended as a topical treatment for inflammatory papules and pustules 1. The study also notes that azelaic acid can be used in combination with other treatments, such as oral antibiotics, for enhanced effectiveness. Overall, azelaic acid is a effective and well-tolerated treatment for rosacea, and should be considered as a first-line treatment for patients with mild to moderate symptoms.

From the FDA Drug Label

The exact mechanism of action of azelaic acid is not known. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity.

The antimicrobial activity and anticomedonal effect of azelaic acid may contribute to its effectiveness in treating rosacea, although the exact mechanism of action is unknown 2.

  • Antimicrobial activity against certain bacteria, such as Propionibacterium acnes and Staphylococcus epidermidis, may help reduce inflammation and prevent infection.
  • Normalization of keratinization may help reduce the formation of microcomedones, which can contribute to the development of rosacea symptoms.

From the Research

Mechanism of Action

  • Azelaic acid has multiple modes of action in rosacea, with its anti-inflammatory effect achieved by reducing reactive oxygen species being the main pharmacological action 3
  • Azelaic acid also has anti-microbial and anti-oxidant properties, which contribute to its effectiveness in treating rosacea 4

Efficacy in Rosacea Treatment

  • Topical azelaic acid 15% gel has been shown to be an effective and safe first-line topical therapeutic option in patients with mild-to-moderate papulopustular rosacea 3
  • Azelaic acid has been demonstrated to significantly improve erythema severity, inflammatory lesion counts, overall improvement, and treatment success in rosacea patients 5
  • Combination therapy with azelaic acid and other topical or oral agents may have a synergistic effect in treating rosacea 6, 7

Clinical Evidence

  • A multicentre, prospective clinical trial found that a novel formulation cream containing 15% azelaic acid and 1% dihydroavenanthramide D significantly decreased inflammatory lesions and erythema in patients with mild/moderate inflammatory rosacea 4
  • A systematic review of 43 RCTs found that azelaic acid was more effective than vehicle in improving erythema severity, inflammatory lesion counts, and overall improvement in rosacea patients 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Azelaic acid 15% gel in the treatment of rosacea.

Expert opinion on pharmacotherapy, 2008

Research

Rosacea: a review of current topical, systemic and light-based therapies.

Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, 2009

Research

Treatment options for acne rosacea.

American family physician, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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