Acnestop®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACNESTOP® (ACNESTOP)

Composition:

Active ingredient: 1 g of cream contains 0.2 g of micronized azelaic acid;

Excipients: benzoic acid (E 210), glycerol monostearate 40-55, macrogol stearate, «CUTINA CBS», octyldodecanol, propylene glycol, glycerin, purified water.

Pharmaceutical form. Cream.

Main physico-chemical properties: white opaque cream.

Pharmacotherapeutic group. Topical agents for treatment of acne.

ATC code D10AX03.

Pharmacological properties.

Pharmacodynamics.

Azelaic acid, the active ingredient of Aknestop® cream, is a naturally occurring straight-chain dicarboxylic acid that is non-toxic, non-teratogenic, and non-mutagenic.

The therapeutic efficacy of Aknestop® cream in the treatment of acne is believed to result from its antimicrobial activity and direct effect on follicular hyperkeratosis.

Clinically, a significant reduction in the colonization density of Propionibacterium acnes and a marked decrease in the fraction of free fatty acids in skin surface lipids are observed.

Azelaic acid inhibits keratinocyte proliferation in vitro and in vivo and normalizes impaired terminal differentiation processes of the epidermis in acne. In a rabbit ear model, azelaic acid accelerates the comedolytic breakdown of tetradecane-induced comedones.

At concentrations of 0.31–2.5%, after prolonged contact for 30–120 minutes, it exhibits biocidal activity 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, either in Staphylococcus epidermidis or in Propionibacterium acnes.

Pharmacokinetics.

After topical application, azelaic acid penetrates all layers of human skin. Penetration occurs more rapidly through affected skin than through intact skin. After a single application of azelaic acid (in the form of 5 g of cream) to the skin surface, 3.6% of the applied dose is absorbed into the subcutaneous tissue. The metabolism of azelaic acid has been studied after oral administration in doses up to 5 g.

Part of the azelaic acid absorbed through the skin is excreted unchanged in urine. The remainder undergoes β-oxidation, breaking down into dicarboxylic acids with shorter carbon chains (C7, C5), which have also been detected in urine.

Studies on systemic tolerance after repeated oral and topical administration of azelaic acid have not revealed any signs indicating that even under extreme conditions, such as application over a large skin area and/or under occlusion, adverse reactions could be expected.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Special precautions for use

For external use only.

Avoid contact of the cream with the eyes, oral cavity, or mucous membranes. If accidental contact occurs, rinse immediately with plenty of water. If eye irritation persists, medical advice should be sought. Hands should be washed after each application of Acnestop® cream.

Concomitant use of cosmetic products, alcohol-based or aggressive skin-cleansing agents, tinctures, astringents, abrasive substances, or exfoliating products should be minimized during treatment, if possible.

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

In rare cases, post-marketing surveillance has reported exacerbation of bronchial asthma in patients receiving azelaic acid (see section "Adverse reactions").

Use during pregnancy or breastfeeding

Pregnancy

There have been no adequate and well-controlled studies of topically applied azelaic acid in pregnant women.

Animal studies suggest a potential effect on pregnancy, embryonic/fetal development, parturition, or postnatal development. However, in animal studies using doses 3–32 times higher than the maximum recommended human dose adjusted for body surface area, no adverse effects were observed.

Acnestop® cream should be used with caution in pregnant women.

Breastfeeding

It is not known whether azelaic acid is excreted in human breast milk in vivo. However, an in vitro study using equilibrium dialysis demonstrated that the active substance may pass into breast milk. Distribution of azelaic acid into breast milk is not expected to result in significant changes above its baseline level already present in milk, as it does not concentrate in breast milk and less than 4% of topically applied azelaic acid is systemically absorbed, without increasing endogenous exposure to the substance above physiological levels. Nevertheless, Acnestop® cream should be used with caution in breastfeeding women.

Contact between the infant and treated skin/breast should be avoided.

Fertility

There are no data available on the effects of Acnestop® cream on human fertility. Animal studies did not reveal any effects on fertility in male or female rats.

Ability to affect reaction speed when driving or operating machinery. Azelaic acid has no influence on the ability to drive or operate machinery.

Method of Administration and Dosage

For topical use.

Apply Acnestop® cream twice daily (in the morning and evening) to affected skin areas and gently rub in with massaging motions. Approximately 2.5 cm of cream is sufficient for the entire facial surface. Before applying Acnestop® cream, thoroughly wash the skin with water and dry it. A mild cosmetic skin cleanser may also be used.

Regular application of Acnestop® cream throughout the entire treatment course is essential.

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

To achieve optimal results, Acnestop® should be used continuously for several months. There is clinical experience of continuous use of azelaic acid for periods of up to 1 year. In acne patients, noticeable improvement is usually observed after approximately 4 weeks.

In case of excessive skin irritation (see section "Adverse Reactions"), reduce the amount of cream applied or decrease the frequency of application to once daily until irritation subsides. If necessary, treatment may be temporarily interrupted for several days. If no noticeable improvement occurs after a short treatment period, a medical re-evaluation is required.

Elderly patients

Specific studies on the use of the medicinal product in patients aged 65 years and older have not been conducted.

Patients with hepatic impairment

Specific studies on the use of the medicinal product in patients with hepatic impairment have not been conducted.

Patients with renal impairment

Specific studies on the use of the medicinal product in patients with renal impairment have not been conducted.

Children — For use in adolescents aged 12 years and older. No dose adjustment is required when prescribing Acnestop® cream to adolescents aged 12 years and older. The safety and efficacy of Acnestop® cream in children under 12 years of age have not been established.

Overdose

Due to the very low local and systemic toxicity of azelaic acid, intoxication with this substance is unlikely.

Adverse reactions

In clinical studies and during post-marketing surveillance, the most frequently observed adverse reactions included burning, itching, and erythema at the application site.

Adverse reactions observed during clinical studies are listed in the table below by frequency of occurrence according to MedDRA classification:

very common (≥1/10);

common (≥1/100 to <1/10);

uncommon (≥1/1000 to <1/100);

rare (≥1/10000 to <1/1000);

very rare (<1/10000);

frequency not known (cannot be estimated based on available data).

1These additional adverse reactions were identified during post-marketing use of Acnestop® cream.

Local skin irritations usually resolve during the course of treatment.

Children

In clinical trials involving children and adolescents aged 12 to 18 years (454/1336; 34%), local tolerability was similar to that in adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25°C. Do not freeze. Keep out of reach of children.

Packaging. 30 g in tubes, 1 tube per pack.

Dispensing category. Over-the-counter.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine