Azelaic Acid

What it is

Azelaic acid is a compound applied to the skin as a 15% gel or foam or a 20% cream [1][2][3]. It is approved as a 15% gel for rosacea [2].

What the research says

Rosacea. A 2023 systematic review of 43 randomized trials found that in 20 rosacea trials azelaic acid improved erythema (redness), inflammatory lesion counts, overall improvement and treatment success versus vehicle after 12 weeks, and was more effective than metronidazole 0.75% for redness, overall improvement and lesion counts [3]. A Cochrane review rated the evidence for azelaic acid high quality, with patients more likely to report improvement than on placebo (risk ratio 1.46, 95% CI 1.30 to 1.63; 4 trials) [4]. A 2019 systematic review also found high-certainty evidence for topical azelaic acid in reducing papules and pustules [5]. A 2025 meta-analysis of 21 trials found ivermectin more effective than azelaic acid, and azelaic acid better than metronidazole [6]. Once-daily 15% gel was no different from twice-daily in a 12-week trial of 72 patients [1], and a phase 3 trial of 15% foam beat vehicle [2].

Acne. The 2023 review found 16 acne trials in which azelaic acid beat vehicle on global assessments and acne severity, and 20% cream reduced more lesions than erythromycin gel [3]. A Cochrane review judged azelaic acid probably less effective than benzoyl peroxide (risk ratio 0.82, 95% CI 0.72 to 0.95; 1 study, 351 participants) and probably about as effective as tretinoin (0.94, 0.78 to 1.14; 1 study, 289 participants), both moderate-quality evidence, with other comparisons low or very low quality [7]. The 2024 US acne guideline makes a conditional recommendation for azelaic acid, and strong recommendations for benzoyl peroxide and topical retinoids [8].

Melasma and hyperpigmentation. In seven melasma trials 20% azelaic acid was significantly better than vehicle for severity and global improvement, and better than 2% hydroquinone for global improvement [3]. A meta-analysis of 45 studies (2,359 patients) found azelaic acid (standardised mean difference -1.3, 95% CI -1.7 to -1.0) comparable to hydroquinone (-1.3, -1.6 to -1.0), cysteamine and tranexamic acid [9]. A network meta-analysis of 59 melasma trials ranked azelaic acid mid-table among 14 therapies versus placebo [10].

Skin aging and other uses. No eligible randomized trials evaluated azelaic acid for skin aging [3]. In perioral dermatitis, azelaic acid gel may result in no change in severity after 6 weeks (low-certainty evidence) [11].

Doses used in studies

Rosacea trials used 15% gel, once or twice daily for 12 weeks [1], 15% foam twice daily [2], and 20% cream and 15% gel formulations [12]. Melasma and acne trials in the 2023 review used 20% azelaic acid [3].

Safety and interactions

Common side effects. Drug-related adverse events were mainly mild to moderate, cutaneous and local in the foam trial [2]. Very few significant differences from comparators were seen for commonly reported adverse events [3]. In melasma trials, skin irritation was reported in 18.7% of azelaic acid users versus 50.9% for hydroquinone-containing combinations [9]. Application site reactions such as scaling were reported in comparisons with tretinoin [7].

Upper limits and toxic doses. No upper limits were established in the studies reviewed.

Interactions. No data on interactions with medicines were found in the studies reviewed.

Pregnancy and breastfeeding. Narrative reviews state that topical azelaic acid can be used for mild-to-moderate acne in pregnancy and lactation, but these are expert reviews, not trials [13][14].

Relevant conditions. No data on specific conditions were found in the studies reviewed.

Caveats and open questions

The strongest evidence is for rosacea; many acne comparisons are low or very low quality, with risk of bias and imprecision [7]. Ivermectin appears more effective than azelaic acid for rosacea bumps [6]. Meta-analyses of melasma pool different study designs and concentrations [9]. Randomized evidence is needed for skin aging [3].