Azelex
(azelaic acid)Azelex Prescribing Information
AZELEX® cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.
After the skin is thoroughly washed and patted dry, a thin film of AZELEX® cream should be gently but thoroughly massaged into the affected areas twice daily, in the morning and evening. The hands should be washed following application. The duration of use of AZELEX® cream can vary from person to person and depends on the severity of the acne. Improvement of the condition occurs in the majority of patients with inflammatory lesions within four weeks.
AZELEX® cream is contraindicated in individuals who have shown hypersensitivity to any of its components.
During U.S. clinical trials with AZELEX® cream, adverse reactions were generally mild and transient in nature. The most common adverse reactions occurring in approximately 1-5% of patients were pruritus, burning, stinging and tingling. Other adverse reactions such as erythema, dryness, rash, peeling, irritation, dermatitis, and contact dermatitis were reported in less than 1% of subjects. There is the potential for experiencing allergic reactions with use of AZELEX® cream.
In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.
AZELEX® (azelaic acid cream) 20% contains azelaic acid, a naturally occurring saturated dicarboxylic acid.
Structural Formula: HOOC-(CH2)7-COOH
Chemical Name: 1,7-heptanedicarboxylic acid
Empirical Formula: C9H16O4
Molecular Weight: 188.22
Active Ingredient: Each gram of AZELEX® contains azelaic acid......... 0.2 g (20% w/w).
Inactive Ingredients: cetearyl octanoate; cetostearyl alcohol; glycerin; glyceryl mono and dipalmitostearate; glyceryl monostearate; isopropyl myristate; PEG-30 stearate; propylene glycol; and purified water. Benzoic acid is present as a preservative.
The exact mechanism of action of azelaic acid is not known. The following in vitro data are available, but their clinical significance is unknown. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.
A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with AZELEX® cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.
Pharmacokinetics
Following a single application of AZELEX® cream to human skin in vitro, azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical application. Approximately 4% of the topically applied azelaic acid is systemically absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes some β-oxidation to shorter chain dicarboxylic acids. The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.
Azelaic acid is a dietary constituent (whole grain cereals and animal products), and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and ψ-oxidation of monocarboxylic acids. Endogenous plasma concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic acid are highly dependent on dietary intake. After topical treatment with AZELEX® cream in humans, plasma concentration and urinary excretion of azelaic acid are not significantly different from baseline levels.
AZELEX® cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:
30 g - NDC 16110-869-30
50 g - NDC 16110-869-50
Storage: Protect from freezing. Store product on its side. Store at 15°-30° C (59°-86° F).
Revised: 02/2024
Distributed by Almirall, LLC, Malvern, PA 19355, U.S.A.
© 2019 Almirall. All right reserved.
® marks owned by Almirall, LLC.
Made in Italy by LEO Pharma Manufacturing Italy S.r.l., Segrate (Milan), Italy
AZELEX® cream is for dermatologic use only and not for ophthalmic use.
There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexions, these patients should be monitored for early signs of hypopigmentation.