Skinoren gel 15% tube 30 g

Instructions Skinoren gel 15% tube 30 g

Composition

active ingredient: azelaic acid;

1 g of gel contains 0.15 g of azelaic acid;

Excipients: propylene glycol, polysorbate 80, lecithin, carbomer 980, medium chain triglycerides, sodium hydroxide, disodium edetate, benzoic acid, purified water.

Dosage form

Gel.

Main physicochemical properties: white to yellowish-white opaque gel.

Pharmacotherapeutic group

Topical acne treatments. Azelaic acid. ATX code D10A X03.

Pharmacological properties

Pharmacodynamics.

Acne

The therapeutic efficacy of Skinoren® gel in the treatment of acne is believed to be due to its antimicrobial action and direct effect on follicular hyperkeratosis.

In vitro and in vivo, azelaic acid inhibits keratinocyte proliferation and normalizes the terminal processes of epidermal differentiation that are disrupted in acne.

Clinically, a significant decrease in the density of Propionibacterium acnes colonies and a significant decrease in the proportion of free fatty acids in lipids on the skin surface are observed.

In two double-blind, randomized clinical trials, Skinoren® gel was significantly more effective than placebo in assessing the median reduction in total papule and pustule volume and 6% less effective than benzoyl peroxide 5% (p=0.056).

In these studies, the efficacy of Skinoren® gel in the treatment of comedones was evaluated as a secondary endpoint. Skinoren® gel was more effective than placebo in the assessment of median comedone reduction and less effective than benzoyl peroxide 5%.

Rosacea

Although the pathophysiology of rosacea is not yet fully understood, experts agree that inflammation involves an increase in various effector molecules (such as kallikrein-5 and cathelicidin) as well as reactive oxygen species (ROS) that participate in pro-inflammatory responses, which is a central process in this disease.

Azelaic acid has been shown to modulate the inflammatory response in normal human keratinocytes by: activating peroxisome proliferator-activated receptor γ (PPARγ); inhibiting nuclear factor kB (NF-kB) transactivation; inhibiting the production of pro-inflammatory cytokines and inhibiting the release of reactive oxygen species (ROS) by neutrophils, as well as the effect of scavenging existing ROS.

Furthermore, azelaic acid has been observed to directly inhibit the expression of kallikrein-5 and cathelicidin in three models: in vitro (human keratinocytes), on mouse skin, and on facial skin from patients with rosacea.

These anti-inflammatory properties of azelaic acid may be important in the treatment of rosacea.

While the clinical relevance of this evidence regarding kallikrein-5 and cathelicidin and their impact on the pathophysiology of rosacea has not yet been fully demonstrated in a single large clinical trial, it is expected that initial studies in human facial skin will confirm the findings obtained in vitro and in mice.

In two placebo-controlled clinical trials of papulopustular rosacea lasting 12 weeks, Skinoren® gel demonstrated a statistically significant advantage over placebo in reducing inflammation according to the investigator's global assessment and a comprehensive assessment of the reduction in erythema intensity.

In a clinical study of papulopustular rosacea, Skinoren® gel showed a statistically significant advantage over metronidazole gel 0.75% in terms of reduction in the number of lesions (72.7% vs. 55.8%) and in terms of reduction in the intensity of erythema (56% vs. 42%) compared to the active ingredient metronidazole gel 0.75%. The incidence of adverse skin reactions, which were mostly mild or moderate, was 25.8% with Skinoren® gel and 7.1% with metronidazole gel 0.75%.

No effect on telangiectasia was observed during these three clinical studies.

Pharmacokinetics.

After topical application of the gel, azelaic acid penetrates all layers of human skin. Penetration occurs faster in damaged skin than in intact skin. In general, after a single topical application of 1 g of azelaic acid (5 g of 20% cream), 3.6% of the dose is absorbed through the skin. Clinical studies in patients with acne have shown the same rate of absorption of azelaic acid for Skinoren® gel and cream.

Part of the azelaic acid absorbed through the skin is excreted unchanged in the urine. The remainder is broken down by ß-oxidation into shorter chain dicarboxylic acids (C7, C5), which are also excreted in the urine.

Steady-state plasma concentrations of azelaic acid in rosacea patients after 8 weeks of treatment with Skinoren® gel twice daily were within the range observed in healthy volunteers and acne patients on a normal diet. This suggests that the extent of transdermal absorption of azelaic acid after twice daily application of Skinoren® gel does not alter the systemic exposure to azelaic acid from food and endogenous sources.

Indication

Treatment of mild and/or moderate papulopustular forms of facial acne, papulopustular form of rosacea.

Contraindication

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

Interaction with other medicinal products and other types of interactions

Interaction studies have not been conducted. The composition of Skinoren® gel does not suggest any undesirable interaction for individual components that could have a negative impact on the safety of the drug. No pharmacospecific interactions were observed during controlled clinical trials.

Application features

For external use only.

Skinoren® gel contains benzoic acid, which causes mild irritation of the skin, eyes and mucous membranes, and propylene glycol, which may cause skin irritation. Skinoren® gel should not be allowed to come into contact with the eyes, mouth or mucous membranes. If the gel accidentally gets into the eyes, mouth or mucous membranes, rinse them immediately with plenty of water. If eye irritation persists, it is recommended to consult a doctor. Wash your hands after each application of Skinoren®.

When treating papulopustular rosacea with Skinoren® gel, it is advisable not to use detergents containing alcohol, alcohol solutions, dyes and astringents, abrasives or exfoliants (for peeling).

In rare cases, exacerbation of bronchial asthma has been reported in patients receiving azelaic acid during post-marketing surveillance.

No specific studies have been conducted in patients with liver or kidney disease or in patients over 65 years of age.

Use during pregnancy or breastfeeding

Pregnancy

There are no adequate and well-controlled studies of topical azelaic acid preparations in pregnant women.

Animal studies indicate possible effects on pregnancy, embryonal/fetal development, parturition or postnatal development. However, no adverse effects were observed in animal studies at doses 3-32 times the maximum recommended human dose based on body surface area. Skinoren® gel should be used with caution in pregnant women.

Breast-feeding

Newborns should not come into contact with the skin/mammary gland to which Skinoren® gel has been applied.

It is not known whether azelaic acid is excreted in human milk in vivo. However, an in vitro experiment using the equilibrium dialysis technique has shown that the active substance may be excreted in human milk. The distribution of azelaic acid does not suggest significant changes in the levels of azelaic acid in human milk, as azelaic acid does not concentrate in human milk and less than 4% of topically applied azelaic acid is absorbed systemically (without increasing the endogenous exposure of the substance above physiological levels).

However, women who are breastfeeding should use Skinoren® gel with caution.

Fertility

There are no data available on the effect of Skinoren® gel on human fertility. Results from animal studies have not shown any effect on fertility.

Ability to influence reaction speed when driving vehicles or other mechanisms

Skinoren® gel has no effect on the reaction speed when driving or working with other mechanisms.

Method of administration and doses

Skinoren® gel is intended for application to the skin only.

The drug should be applied 2 times a day (morning and evening) to the affected areas of the skin and rubbed in lightly. The amount of the drug sufficient for the entire facial area is a strip approximately 2.5 cm long, which corresponds to 0.5 g of gel. Before using Skinoren® gel, the skin should be thoroughly washed with water or a mild cosmetic cleanser. Then the skin should be completely dried and the gel should be applied to it.

It is necessary to avoid using clothing and occlusive dressings at the site of application of the drug, and hands should also be washed thoroughly after applying the gel.

If skin irritation occurs, reduce the amount of gel used per application or reduce the frequency of application of Skinoren® gel to once a day until symptoms of irritation disappear. If necessary, discontinue treatment for a few days.

It is very important to use Skinoren® gel continuously throughout the entire treatment period.

The duration of treatment may be individual for each patient and depends, among other things, on the severity of the skin pathology.

Acne

Noticeable improvement is usually observed after about 4 weeks. However, to achieve optimal results, it is recommended to use Skinoren® gel regularly for several months, depending on the clinical outcome. If there is no improvement after 1 month or if acne worsens, Skinoren® gel should be discontinued and alternative treatment methods should be prescribed.

Noticeable improvement is usually observed after about 4 weeks. However, for optimal results, it is recommended to use Skinoren® gel regularly for several months, depending on the clinical outcome. If there is no improvement after 2 months or if rosacea worsens, Skinoren® gel should be discontinued and alternative treatments should be considered.

Children

Use for the treatment of acne in children aged 12–18 years does not require dose adjustment.

The safety and efficacy of Skinoren® gel for the treatment of acne in children under 12 years of age have not been established.

The safety and efficacy of Skinoren® gel for the treatment of papulopustular rosacea in children (under 18 years of age) have not been established.

Overdose

Due to the low toxicity of azelaic acid at the local and systemic levels, the occurrence of intoxication is unlikely.

Side effects

During clinical trials, only local side effects related to treatment were reported. In most cases, the symptoms were mild to moderate; the frequency of irritation symptoms gradually decreased with continued therapy.

In clinical studies, the most commonly reported side effects included itching, burning, and pain at the application site.

The frequency of adverse reactions observed during clinical studies and listed in the table is determined according to MedDRA: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100), rare (≥1/10,000, <1/1000).

Acne

Rosacea

During post-marketing studies, rare reports of immune system disorders were reported: hypersensitivity reactions, which may manifest as one or more of the following adverse reactions: angioedema, eye swelling, facial swelling, shortness of breath, exacerbation of bronchial asthma symptoms in patients using azelaic acid.

Adverse reactions such as seborrhea, cheilitis, skin depigmentation, irritation at the application site, eczema at the application site, and ulceration at the application site were also observed.

Use in children

Treatment of acne in children aged 12–18 years.

In 4 phase II and II/III clinical studies involving children aged 12 to 17 years (120 out of 383; 31%), the overall incidence of adverse reactions with Skinoren® gel was similar to that in the 12–17 year age group (40%), the 18 year age group (37%), and the overall patient population (38%). This similarity also applied to the 12–20 year age group (40%).

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 25 °C out of the reach of children.

Packaging

5 g or 30 g of gel in a tube; 1 tube in a cardboard pack.

Vacation category

Without a prescription.

Producer

LEO Pharma Manufacturing Italy SRL

Location of the manufacturer and its business address

Via E. Schering, 21, 20054 Segrate (MI), Italy.