Azelaic Acid

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.

General If sensitivity or severe irritation develop with the use of AZELEX ® cream, treatment should be discontinued and appropriate therapy instituted. Information for Patients 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 Carcinogenesis, Mutagenesis, Impairment of Fertility 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. Pregnancy Teratogenic Effects Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers Equilibrium dialysis was used to assess human milk partitioning in vitro . At an azelaic acid concentration of 25 mcg/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. Pediatric Use Safety and effectiveness in pediatric patients under 12 years of age have not been established. Geriatric Use 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.

Teratogenic Effects Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Equilibrium dialysis was used to assess human milk partitioning in vitro . At an azelaic acid concentration of 25 mcg/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.