Allergan
AZELEX®
(azelaic acid cream) 20%

For Dermatologic Use Only
Not for Ophthalmic Use

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

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.

AZELEX^® Cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.

AZELEX^® Cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

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.

If sensitivity or severe irritation develop with the use of AZELEX^® Cream, treatment should be discontinued and appropriate therapy instituted.

Patients should be told:

• To use AZELEX^® Cream for the full prescribed treatment period.
• To avoid the use of occlusive dressings or wrappings.
• To keep AZELEX^®Cream away from the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, they should wash their eyes with large amounts of water and consult a physician if eye irritation persists.
• If they have dark complexions, to report abnormal changes in skin color to their physician.
• Due in part to the low pH of azelaic acid, temporary skin irritation (pruritus, burning, or stinging) may occur when AZELEX^® Cream is applied to broken or inflamed skin, usually at the start of treatment. However, this irritation commonly subsides if treatment is continued. If it continues, AZELEX^® Cream should be applied only once-a-day, or the treatment should be stopped until these effects have subsided. If troublesome irritation persists, use should be discontinued, and patients should consult their physician.

Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential, and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, animal studies to evaluate carcinogenic potential with AZELEX^® Cream were not deemed necessary. In a battery of tests (Ames assay, HGPRT test in Chinese hamster ovary cells, human lymphocyte test, dominant lethal assay in mice), azelaic acid was found to be nonmutagenic. Animal studies have shown no adverse effects on fertility.

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 μg/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when AZELEX^® Cream is administered to a nursing mother.

Safety and effectiveness in pediatric patients under 12 years of age have not been established.

Clinical studies of AZELEX^® Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

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.

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 supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:

30 g - NDC 0023-8694-30
50 g - NDC 0023-8694-50

Note: Protect from freezing. Store product on its side.

Store between 15° - 30°C (59° - 86°F).

Rx Only.

Distributed by ALLERGAN

Irvine, California 92612, U.S.A.

©2004 Allergan, Inc.

Made in Italy

8466X

Distributed under license.

^® Mark of Allergan, Inc.

Rev May 2004

70896US15P