Azelaic acid

Pharmacological properties

azelaic acid, the active substance acnestop, is a straight-chain dicarboxylic acid, which is found in nature, is free from toxicity, teratogenicity and mutagenicity.

It is believed that the therapeutic efficacy of Acnestop cream in the treatment of acne is determined by its antimicrobial effect and direct effect on follicular hyperkeratosis.

Clinically, there is a significant decrease in the density of colonization of Propionibacterium acnes and a significant decrease in the fraction of free fatty acids in the lipids of the skin surface.

Azelaic acid in vitro and in vivo inhibits the proliferation of keratinocytes, normalizes the violation of the processes of terminal differentiation of the epidermis during the formation of acne. In a rabbit ear model, azelaic acid accelerates the comedolysis of tetradecane-induced comedones.

At a concentration of 0.31–2.5%, a biocidal effect appears after prolonged contact for 30–120 min against gram-positive and gram-negative aerobic bacteria, anaerobic bacteria and fungi.

In vitro studies have not demonstrated the presence of mutant forms resistant to azelaic acid in either Staphylococcus epidermidis or Propionibacterium acnes.

Pharmacokinetics After applying the cream, azelaic acid penetrates into all layers of the human skin. Penetration occurs at a faster rate through the affected skin than through intact skin. After a single application of 1 g of azelaic acid (5 g of cream) to the skin surface, 3.6% of the applied dose is adsorbed subcutaneously.

Part of the azelaic acid adsorbed through the skin is excreted unchanged in the urine. The other part is broken down by β-oxidation to dicarboxylic acids with a short chain length (C7, C5), which were also found in urine.

A study of systemic tolerance after repeated administration and external use of azelaic acid showed no signs that even in extreme conditions, for example, when applied to a large area and / or with occlusion, side effects can be expected to develop.

Indications

Treatment of acne (acne vulgaris), characterized by the presence of comedones, papules, pustules and small nodules.

Application

Apply acnestop cream 2 times a day (morning and evening) on ​​the affected skin and gently rub. approximately 0.5 g = 2.5 cm cream, which is sufficient for the entire surface of the face. Before applying the cream, you should thoroughly rinse the skin with water and dry it. You can also use a mild cosmetic cleanser.

Regular use of the cream throughout the course of treatment is important.

The duration of the course of treatment may vary depending on the individual course of the disease and is determined by its severity.

In patients with acne, significant improvement is noted, usually after about 4 weeks. However, to achieve an optimal result, it is recommended to use the drug continuously for several months. There is clinical experience with the continuous use of a topical azelaic acid preparation for up to 1 year.

In case of excessive skin irritation (see ADVERSE EFFECTS), the amount of cream for application or the frequency of application of Acnestop cream should be reduced to 1 time per day until the irritation disappears. If necessary, therapy can be interrupted for several days. After a short period of treatment without noticeable results, a second medical evaluation is necessary.

Contraindications

Hypersensitivity to the active substance or any of the excipients of the drug.

Side effects

The frequency of adverse reactions was determined according to meddra: very often (≥1 / 10); often (from ≥1 / 100 to 1/10); infrequently (from ≥1 / 1000 to 1/100); rarely (from ≥1 / 10,000 to 1/1000), very rarely (1/10 000), the frequency is unknown (cannot be estimated based on available data).

On the part of the skin and subcutaneous tissue: infrequently - seborrhea, acne, skin depigmentation; rarely - cheilitis (inflammation of the lips), rashes.

Local disorders: very often - burning, itching and erythema; often - peeling, pain, dryness, discoloration of the skin and irritation at the site of application; infrequently - paresthesia, dermatitis, discomfort and swelling at the place of use; single - urticaria, ulcer at the site of application; rarely - vesicles, eczema, a feeling of warmth and an ulcer at the site of application. Typically, local skin irritations disappear during treatment.

On the part of the immune system: rarely - hypersensitivity.

There have been cases of exacerbation of AD symptoms in patients using azelaic acid (frequency unknown).

The occurrence of any unwanted effects, including those not listed in the instructions, should be reported to the doctor.

Tolerance with topical administration of the drug in children aged 12 years and older is similar to that in adults.

special instructions

Designed exclusively for external use. The cream is not allowed to get into the eyes, mouth or mucous membranes. in case of accidental contact with eyes, oral cavity and other mucous membranes, they should be immediately rinsed with plenty of water. If eye irritation persists, consult a doctor. After each application of the cream, wash your hands.

The simultaneous use of cosmetic products, alcoholic or aggressive detergents, tinctures, astringents or abrasives or exfoliating agents should be limited during treatment as much as possible.

Benzoic acid can cause mild irritation of the skin, eyes and mucous membranes. Propylene glycol can also cause skin irritation.

In rare cases, post-registration observation has reported an exacerbation of AD in patients using azelaic acid.

Use during pregnancy and lactation. Pregnancy. Appropriate and well-controlled studies of azelaic acid preparations for external use involving pregnant women have not been conducted. Animal studies do not indicate a direct or indirect harmful effect on the course of pregnancy, development of the embryo / fetus, childbirth or postnatal development. In pregnant women, the drug should be used with caution.

Lactation. It is not known whether azelaic acid is excreted in breast milk in vivo. However, an in vitro experiment has shown that the active substance can pass into breast milk. It is expected that the distribution of azelaic acid in breast milk cannot lead to significant changes in relation to its base level, since it does not concentrate in breast milk and less than 4% of topically applied azelaic acid is absorbed systemically (without increasing the endogenous exposure of the substance above the physiological level ) However, in women who are breastfeeding, the drug should be used with caution.

Contact should be avoided with the skin / breast treated with the drug.

Children. Used in adolescents from 12 years. When using Acnestop cream in children aged 12 years and older, dose adjustment is not required. The safety and effectiveness of the use of Acnestop cream in children under 12 years of age have not been established.

The ability to influence the reaction rate when driving vehicles and working with other mechanisms. Does not affect.

Interactions

No interaction studies were performed.

No controlled drug interactions were observed during controlled clinical trials.

Azelaic acid is chemically incompatible with alkalis, strong oxidizing agents and reducing agents.

Given the composition of the cream, no undesirable interactions of the individual components are expected that could adversely affect the safety of the drug.

Overdose

The results of acute toxicity studies do not indicate that there is any risk of acute intoxication with a single overdose (applying the cream on a large surface of the skin under conditions favorable for adsorption) or with unintentional ingestion.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C. do not freeze!