Effezel Forte gel container 30g

Instructions Effezel Forte gel container 30g

Composition

active ingredients: adapalene, benzoyl peroxide;

1 g of gel contains adapalene 3 mg and benzoyl peroxide 25 mg;

excipients: Simulgel 600 RNA (copolymer of acrylamide and sodium acryloyldimethyltaurate, isohexadecane, polysorbate 80, sorbitan oleate), docusate sodium, disodium edetate, glycerin, poloxamer, propylene glycol, purified water.

Dosage form

Gel.

Main physicochemical properties: opaque gel from white to light yellow.

Pharmacotherapeutic group

Preparations for topical treatment of acne. Retinoids for topical treatment of acne. Adapalene, combinations. ATX code D10A D53.

Pharmacological properties

Pharmacodynamics.

The drug contains two active ingredients with different but complementary mechanisms of action.

Adapalene is a chemically stable derivative of naphthoic acid with retinoid-like activity. In studies of the biochemical and pharmacological profile, the effect of adapalene in the disease caused by Acne vulgaris has been shown: it is a potent modulator of cell differentiation and keratinization, and also has anti-inflammatory properties. The mechanism of action of adapalene is based on the binding of the compound to specific nuclear receptors for retinoic acid. Current data suggest that when applied topically, adapalene normalizes the differentiation of follicular epithelial cells, thereby reducing the formation of microcomedones. In in vitro models, adapalene inhibits the chemotactic (directed) and chemokinetic (random) responses of human polymorphonuclear leukocytes; it also inhibits the conversion of arachidonic acid to inflammatory mediators. According to in vitro studies, adapalene inhibits AP-1 factors, as well as the expression of toll-like receptors 2. This profile indicates that adapalene reduces the cell-mediated inflammatory component of acne.

Benzoyl peroxide has an antimicrobial effect, particularly against Propionibacterium acnes, which are present in excessive amounts in the affected sebaceous-hair complex.

The mechanism of action of benzoyl peroxide is explained by its high lipophilic activity, which occurs when it penetrates through the epidermis into the cell membranes of bacteria and keratinocytes in the sebaceous-hair complex. Benzoyl peroxide is considered a very effective broad-spectrum antibacterial agent in the treatment of acne vulgaris. It has been shown to exert a bactericidal effect by generating free radicals that oxidize proteins and other essential cell components in the bacterial wall. The minimum inhibitory concentration of benzoyl peroxide has bactericidal properties and is effective against susceptible and antibiotic-resistant strains of Propionibacterium acnes.

In addition, benzoyl peroxide has exfoliating and keratolytic properties.

Pharmacokinetics.

Absorption

A pharmacokinetic study was conducted in 26 adult and adolescent participants (aged 12 to 33 years) with severe acne vulgaris treated with Effezel Forte. Participants received treatment once daily to all potentially affected areas for 4 weeks, with a mean dose of 2.3 g/day (range: 1.6–3.1 g/day). Effezel Forte was applied as a thin layer to the face, shoulders, upper chest and upper back. After 4 weeks of treatment, 16 participants (62%) had plasma concentrations of adapalene above the limit of quantification (MIC of 0.1 ng/mL); the mean Cmax was 0.16 ± 0.08 ng/mL and the mean AUC0-24h was 2.49 ± 1.21 ng.h/mL. In the most exposed participant, the Cmax and AUC0-24h values of adapalene were 0.35 ng/mL and 6.41 ng.h/mL, respectively.

Pharmacokinetic studies of Effezel and Effezel Forte have confirmed that transdermal absorption of adapalene does not affect the absorption of benzoyl peroxide.

The penetration of benzoyl peroxide through the skin is low; when applied to the skin, it is completely converted to benzoic acid, which is rapidly eliminated.

Preclinical safety data.

The results of standard non-clinical safety pharmacology studies, repeated dose toxicity studies, genotoxicity, phototoxicity or carcinogenicity do not indicate any special hazards for humans.

Animal studies conducted with Effezel and Effezel Forte included local tolerability studies and repeated-dose dermal toxicity studies in rats, dogs and/or minipigs for up to 13 weeks and demonstrated local irritation and potential for sensitization, as predicted for a substance containing benzoyl peroxide. Systemic exposure to adapalene after repeated topical application in a fixed combination in animals was very low, consistent with clinical pharmacokinetic data. Benzoyl peroxide was rapidly and completely converted to benzoic acid in the skin and then absorbed and excreted in the urine, with limited systemic exposure.

Indication

Treatment of common acne (acne vulgaris) with comedones, papules and pustules.

Contraindication

• Pregnancy.
• Pregnancy planning.
• Hypersensitivity to the active substances or to any of the excipients.

Interaction with other medicinal products and other types of interactions

Drug interaction studies with Effezel Forte have not been conducted.

Based on previous experience with adapalene and benzoyl peroxide, no interactions with other medicinal products that may be applied to the skin simultaneously with Effezel Forte have been identified. However, other retinoids or benzoyl peroxide, or products with a similar mechanism of action, should not be used simultaneously. Caution should be exercised when using cosmetics that exhibit exfoliating, irritating or drying properties, as this may cause an additive irritant effect when using the product.

Absorption of adapalene through human skin is low, so interactions with systemic drugs are unlikely.

The penetration of benzoyl peroxide through the skin is low, it is completely metabolized to benzoic acid, which is rapidly excreted from the body. Thus, the interaction of benzoic acid with systemic drugs is unlikely.

Application features

Effezel Forte gel should not be applied to damaged, injured (cuts or abrasions) or eczematous skin.

Avoid contact of the gel with the eyes, mouth, nostrils or mucous membranes. If the drug gets into the eyes, they should be rinsed immediately with warm water.

The product contains propylene glycol (E1520), which may cause skin irritation.

If a reaction develops indicating sensitivity to any component of the drug, the use of Effezel Forte gel should be discontinued.

Hypersensitivity reactions, including anaphylaxis, angioedema and urticaria, have been reported with the use of benzoyl peroxide products. If a serious hypersensitivity reaction occurs, Effezel Forte gel should be discontinued immediately and appropriate therapy should be initiated.

Exposure to sunlight, including sunlamps, should be avoided while using Effezel Forte Gel. Particular caution should be exercised in patients with high levels of sun exposure and those with sun sensitivity. The use of broad-spectrum sunscreens and protective clothing (e.g., hats) is recommended when exposure cannot be avoided. Extreme weather conditions, such as wind or cold, may be irritating to patients using Effezel Forte Gel.

Avoid contact of the product with any colored material, including hair and dyed fabrics, as this may result in discoloration or discoloration.

The efficacy and safety of Effezel Forte gel in patients with severe nodular or deep nodular-cystic acne have not been studied. Since patients with severe nodular or deep nodular-cystic acne have an increased risk of secondary permanent scarring after acne lesions, the use of Effezel Forte in such patients is not recommended due to the risk of insufficient therapeutic response.

Use during pregnancy or breastfeeding.

Oral use of retinoids has been associated with congenital anomalies. As a general rule, when used topically as approved, retinoids are expected to have minimal systemic effects due to minimal absorption through the skin. However, there are individual factors (e.g., skin damage, overuse) that may contribute to increased systemic effects.

Pregnancy

Effezel Forte is contraindicated in pregnant women and women planning a pregnancy.

Clinical experience with topical adapalene and benzoyl peroxide in pregnant women is limited. Available pharmacovigilance data from the use of Effezel Forte gel in pregnant women are insufficient to establish a drug-related risk of serious birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with Effezel Forte gel.

Studies in animals treated with oral adapalene have shown reproductive toxicity at high systemic exposures. Oral administration of adapalene to pregnant rats and rabbits during organogenesis resulted in skeletal and visceral fetal malformations (see section 5.3).

The systemic effects of benzoyl peroxide are unknown. According to published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance) which is excreted in the urine. Therefore, maternal use of the drug is not expected to result in fetal exposure. The background risk of serious birth defects and miscarriage in this population is unknown.

If the drug is used during pregnancy or if the patient becomes pregnant while taking this drug, treatment should be discontinued.

Breast-feeding

No studies have been conducted on the penetration of the drug into animal or human breast milk after application of Effezel Forte gel (adapalene and benzoyl peroxide) to the skin.

Available pharmacokinetic data obtained in rats indicate that adapalene is excreted in breast milk after oral or intravenous administration of adapalene.

A risk to the breast-fed child cannot be excluded.

A decision on whether to discontinue breast-feeding or to discontinue/abstain from Effezel Forte therapy should be made taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

To minimize potential exposure to the infant via breast milk, Effezel Forte gel should be applied to the smallest area of skin and for the shortest period of time during breastfeeding. Do not apply directly to the nipple and areola to avoid direct exposure to the infant.

Fertility

No studies have been conducted on the effects of Effezel Forte gel on human fertility.

However, animal reproduction studies have not shown any effect of adapalene or benzoyl peroxide on fertility.

The ability to influence the reaction speed when driving vehicles or other mechanisms.

The effect of the drug Effezel Forte on the ability to drive or operate other mechanisms is absent or insignificant.

Method of administration and doses

Dosage

Effezel Forte is recommended to be applied once a day in the evening to all areas of the face and body affected by acne, the skin should be clean and dry.

The duration of treatment should be determined by the physician, taking into account the patient's general condition and therapeutic response to treatment. Early signs of clinical improvement usually appear after 1–4 weeks of treatment. If no improvement is observed after 4–8 weeks of treatment, the appropriateness of further use of the drug should be reconsidered.

A lower-dosage drug is available, Effezel, and the drug in this concentration is recommended for patients with moderate acne vulgaris.

If the entire facial skin is affected by numerous papulopustules, a better clinical outcome was observed in patients receiving Effezel Forte than in those receiving the comparator drug (Effezel). Physicians choose one of the two concentrations, taking into account the actual clinical condition of the patient and the severity of the disease.

Certain patient groups

Old age

The safety and effectiveness of Effezel Forte in geriatric patients over 65 years of age have not been established.

Renal and hepatic failure

The use of Effezel Forte gel in patients with renal and hepatic insufficiency has not been studied.

Method of application

For cutaneous use only.

Apply a thin layer of Effezel Forte gel to the affected areas of the face and/or body once a day after washing. Apply a pea-sized amount of gel to each area of the face (e.g. forehead, chin, each cheek), avoiding contact with the eyes and lips.

Patients should be instructed to wash their hands after applying the medication.

You can use cosmetics only after the medicine has completely dried.

If irritation occurs, the patient should be advised to use non-comedogenic moisturizers, reduce the frequency of use of the product (e.g., to once every two days), or temporarily or completely discontinue use.

Children

The safety and efficacy of Effezel Forte in children under 12 years of age have not been studied.

Overdose

The drug is intended for application to the skin only once a day.

Excessive use of Effezel Forte gel may cause severe irritation. In this case, you should stop using the medicine and wait until the skin recovers.

In case of accidental ingestion, appropriate symptomatic therapy should be administered.

Side effects

About 10% of patients may experience adverse skin reactions. Adverse reactions associated with the use of Effezel Forte include mild to moderate application site reactions, including skin irritation, usually characterized by peeling, dryness, erythema, and burning/pain. It is recommended to use a moisturizer, temporarily reduce the frequency of application to once every two days, or temporarily discontinue use of the drug until daily application can be resumed.

Such reactions usually occur at the beginning of treatment and gradually decrease over time.

Summary of adverse reactions

Adverse reactions are classified by system organ class and frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to 1 < 100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency unknown (cannot be estimated from the available data), they were reported during a clinical trial.

* Post-registration observation data.

** In most cases, burns were superficial, but cases of second-degree burns or severe burn reactions have also been reported.

Skin side effects occurred more frequently with Effezel Forte gel than with adapalene 0.1%/benzoyl peroxide 2.5% gel (Effezel).

In addition to those listed above, other adverse reactions have been reported associated with the use of adapalene 0.1%/benzoyl peroxide 2.5% gel (Effezel), a previously approved fixed combination of adapalene and benzoyl peroxide.

Clinical trials.

Other adverse reactions associated with the use of Effezel reported in clinical studies included hypersensitivity, irritant contact dermatitis and sunburn (see section Special warnings and precautions for use).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions during the post-marketing period of a medicinal product is important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Expiration date

2 years. After first opening the package, the drug is suitable for use for 3 months.

Storage conditions

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

Packaging

30 g of gel in a container; 1 container in a cardboard box.

Vacation category

According to the recipe.

Producer

HALDERMA LABORATORIES.

Location of the manufacturer and address of its place of business.

ZI Mondesir 74540 ALBI-SUR-CHERAN, France.