A Comprehensive Monograph on Azelaic Acid (DB00548): Mechanisms, Clinical Utility, and Regulatory Landscape

1.0 Executive Summary

Azelaic acid is a naturally occurring, saturated nine-carbon dicarboxylic acid that has emerged as a uniquely versatile and indispensable therapeutic agent in modern dermatology. Initially identified for its effects on skin pigmentation, its clinical utility has expanded significantly, driven by a growing understanding of its pleiotropic pharmacological activities. This monograph provides an exhaustive analysis of Azelaic acid, synthesizing data from pharmacological databases, clinical trials, and global regulatory documents to present a definitive, evidence-based report on its properties, mechanisms, and clinical applications.

The primary FDA-approved indications for Azelaic acid are the topical treatment of mild-to-moderate inflammatory acne vulgaris and the inflammatory papules and pustules of mild-to-moderate rosacea. Its efficacy in these conditions is underpinned by a multifaceted mechanism of action that simultaneously targets the core pathophysiological pillars of these diseases. Azelaic acid exerts potent anti-infective effects against key cutaneous microorganisms such as Propionibacterium acnes, notable for the absence of observed bacterial resistance. It possesses significant anti-inflammatory properties, scavenging reactive oxygen species and modulating critical inflammatory pathways, including the kallikrein-5/cathelicidin cascade central to rosacea. Furthermore, its anti-keratinizing activity normalizes follicular differentiation, preventing the formation of comedones in acne, while its inhibition of tyrosinase and selective cytotoxicity towards hyperactive melanocytes make it an effective agent for a growing number of off-label applications in disorders of hyperpigmentation, such as melasma and post-inflammatory hyperpigmentation.