Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: LEO Laboratories Limited, Horizon, Honey Lane, Hurley, Maidenhead, Berkshire, SL6 6RJ, UK
Pharmacotherapeutic group: other anti-acne preparations for topical use.
ATC Code: D10AX03
The antimicrobial action and a direct influence on follicular hyperkeratosis are assumed to be the basis for the therapeutic efficacy of Skinoren in acne.
Clinically, a significant reduction of the colonization density of Propionibacterium acnes and a significant reduction of the fraction of free fatty acids in the skin surface lipids is observed.
In vitro and in vivo, azelaic acid inhibits the proliferation of keratinocytes and normalizes the disturbed terminal epidermal differentiation processes in acne. In the rabbit ear model, azelaic acid accelerates the comedolysis of tetradecane-induced comedones.
There is clinical experience for a continuous application time period of up to one year.
After dermal administration of the cream, azelaic acid penetrates into all layers of human skin. The penetration is more rapid into damaged skin than into intact skin. A total of 3.6% of the administered dose was absorbed percutaneously after a single topical administration of 1 g azelaic acid (5 g cream).
A portion of the azelaic acid which is absorbed through the skin is eliminated unchanged with the urine. The remaining portion is metabolized through beta- oxidation into short-chained dicarboxylic acids (C7, C5 carboxylic acids) which have likewise been found in the urine.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, contact hypersensitivity, genotoxicity and toxicity to reproduction and development.
Embryofetal developmental studies with oral administration of azelaic acid to rats, rabbits, and cynomolgus monkeys during the period of organogenesis revealed embryotoxicity at doses where some maternal toxicity was noted. No teratogenic effects were observed. The embryofetal NOAEL was 32 times the MRHD based on BSA in rats, 6.5 times the MRHD based on BSA in rabbits and 19 times the MRHD based on BSA in monkeys (see section 4.6 Fertility, pregnancy and lactation).
In a peri- and post-natal developmental study in rats where azelaic acid was administered orally from gestational day 15 to through day 21 postpartum slight disturbances in the post-natal development of fetuses were noted at oral doses that generated some maternal toxicity. The NOAEL was 3 times the MRHD based on BSA. No effects on sexual maturation of the fetuses were noted in this study.
Studies on impairment of fertility in animals have not produced any evidence for such a risk during therapeutic use of Skinoren.
If azelaic acid came into contact with the eyes of monkeys and rabbits, signs of moderate to severe irritation became evident. Therefore, contact with the eyes should be avoided.
Azelaic acid administered once intravenously had no effects on the nervous system (Irwin test), cardiovascular function, intermediary metabolism, smooth muscles and liver and kidney function.
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