Cream for external use 1% 15 g in an aluminum tube.
1 tube with instructions for use in a cardboard box.
Anti-inflammatory agent for topical application.
Pharmacodynamics: Pimecrolimus is a derivative of ascomycin macrolactam and has an anti-inflammatory effect. Pimecrolimus selectively inhibits the production and release of cytokines and inflammatory mediators from T-lymphocytes and mast cells. Pimecrolimus specifically binds to the macrophilin-12 cytosolic receptor and inhibits calcium-dependent phosphatase – calcineurin. Inhibition of calcineurin inhibits the proliferation of T-lymphocytes and prevents transcription and production of early cytokines in type 1 and 2 helper T cells, such as interleukin-2, interferon-Î², interleukin-4, interleukin-5, interleukin-10, tumor necrosis factor – and granulocyte macrophage colony stimulating factor. Pimecrolimus and tacrolimus equally suppress the secondary immune response in isolated cell colonies of skin T-helper cells obtained in patients with atopic dermatitis. In vitro pimecrolimus also prevents antigen / IgE-mediated release of cytokines and inflammatory mediators from mast cells. Pimecrolimus does not affect the growth of keratinocytes, fibroblasts and endothelial cells and, unlike corticosteroids, has a selective effect on the cells of the immune system and does not cause impaired function, viability, differentiation processes, maturation of Langerhans cells of mice and dendritic cells of monocytic origin in humans. The drug does not affect the differentiation of ânaiveâ T-lymphocytes into T-effector cells under the action of Langerhans cells and dendritic cells, which is one of the main mechanisms of a specific immune response.
Experimental models of skin inflammation have demonstrated high anti-inflammatory activity of pimecrolimus after topical and systemic administration. When applied topically in experimental models of allergic contact dermatitis (AKD), pimecrolimus is comparable in effectiveness to highly active corticosteroids: clobetasol – 17-propionate and fluticasone, inhibits the inflammatory response in response to skin irritants, without causing changes in the consistency, compaction and atrophy of the skin.
In addition, with local and oral administration of acute currents in experimental AKD models, pimecrolimus effectively reduces skin inflammation, itching, and the severity of histopathological changes. When applied topically, the degree of penetration of tacrolimus and pimecrolimus into the skin is equally good. However, the ability of pimecrolimus to penetrate the skin is less than that of tacrolimus and glucocorticosteroids. Thus, pimecrolimus has a selective effect on the skin.
The uniqueness of the mechanism of action of pimecrolimus lies in the combination of selective anti-inflammatory effects on the skin with a slight effect on the systemic immune response.
When used for 6 weeks in children from 3 months to 17 years, pimecrolimus effectively reduces itching and skin inflammation (erythema, infiltration, excoriation and lichenization). With prolonged use for 12 months, pimecrolimus effectively reduces the incidence of sudden exacerbations of AKD, without causing atrophy, irritation and increased skin hypersensitivity and without having a phototoxic or photosensitizing effect.
The concentration of pimecrolimus in the blood was determined in 12 adult patients with atopic dermatitis (eczema) with lesions of 15-59% of the body surface area treated with 1% Elidel cream 2 times a day for 3 weeks. In 77.5% of cases, the concentration of pimecrolimus in the blood was below 0.5 ng / ml (the minimum detectable concentration), and in 99.8% it was below 1 ng / ml. The maximum value of the concentration of pimecrolimus in the blood recorded in one patient was 1.4 ng / ml. In 98% of 40 adult patients with an initial lesion of 14-62% of the body surface area after 1 year of treatment with Elidel, the concentration of pimecrolimus in the blood remained low and in most cases were below the minimum detectable concentration. The maximum concentration value of 0.8 ng / ml was recorded after 6 weeks of treatment in only two patients. None of the patients showed an increase in concentration over 12 months of treatment. For a 3-week period of treatment with Elidel 2 times a day in 13 adult patients with dermatitis of the hands (when applying the cream on the palm and back of the hands and bandaging overnight), the maximum recorded value of the concentration of pimecrolimus in the blood was 0.91 ng / ml. In 8 patients with pimecrolimus in the blood above the minimum detectable concentration, the AUC value ranged from 2.5-11.4 ng / ml.
Pharmacokinetic studies of pimecrolimus were performed in 58 children aged 3 to 14 years with atopic dermatitis (eczema) with lesions of 10-92% of body surface area treated with 1% Elidel cream 2 times a day for 3 weeks. Five children received treatment for 1 year as needed. Blood pimecrolimus concentrations were stably low regardless of the area of ââskin lesions and the duration of therapy, and were in the same range of values ââas in adult patients who received Elidel therapy in the same doses. In 97% of cases, the concentration of pimecrolimus in the blood was below 2 ng / ml, and in 60% below 0.5 ng / ml (the minimum detectable concentration). The maximum pimecrolimus concentration recorded in two patients aged 8 months and 14 years was 2.0 ng / ml. Among the youngest children (from 3 to 23 months), the maximum value of pimecrolimus concentration recorded in one patient was 2.6 ng / ml. In five children treated with Elidel for 1 year, pimecrolimus concentrations were stably low. The maximum value recorded in one child was 1.94 ng / ml. Throughout the treatment period, no increase in drug concentrations was observed in any of the patients. In 8 children aged 2 to 14 years with pimecrolimus in the blood above the minimum detectable concentration, the AUC value ranged from 5.4-18.8 ng / ml three times. The AUC values ââin patients with skin lesions of less than 40% and more than 40% were comparable. In in vitro studies, the binding of pimecrolimus to plasma proteins (mainly with various lipoproteins) was 99.6%. Since local concentration of pimecrolimus in the blood is very low, determination of metabolic parameters is not possible.
Use in elderly patients
Atopic dermatitis (eczema) is rarely observed in patients aged 65 years and older. The number of patients of this age in clinical studies of Elidel cream was insufficient to reveal any differences in treatment efficacy compared to younger patients.
Use in children
Dosage recommendations for infants (3-23 months), children (2-11 years) and adolescents (12-17 years) do not differ from recommendations for adult patients.
Atopic dermatitis (eczema). The drug is indicated for short-term and long-term treatment of atopic dermatitis in adults, adolescents and children (from 3 months).
Hypersensitivity to pimecrolimus or any components of the drug.
Children under 3 months of age (because the safety and effectiveness of Elidel cream in children under 3 months of age has not been studied).
Elidel cream should not be applied to areas of the skin affected by an acute viral, bacterial or fungal infection.
There is no data on the safety of using Elidel cream in patients with Netherton’s syndrome and generalized erythroderma. Given the possible risk of increased systemic absorption of the drug, Elidel cream is not recommended for use in patients with Netherton’s syndrome or in severe forms of inflammation or skin damage (for example, with erythroderma).
Since the effectiveness and safety of using Elidel cream in immunocompromised patients has not been studied, the drug is not recommended for use in this category of patients.
Safety data for prolonged use of Elidel cream is not available.
Since the effect of prolonged use of the drug on the immune defense of the skin and the incidence of malignant neoplasms has not been studied, Elidel cream should not be applied to damaged areas of the skin with possible malignancy or dysplastic changes.
In the case of bacterial or fungal skin lesions, the use of Elidel cream in the affected areas is possible only after the infection has been cured.
Use during pregnancy and lactation
Pregnancy. There are no data on the use of 1% Elidel cream in pregnant women. In experimental studies with topical use of the drug, the direct or indirect damaging effect of Elidel on pregnancy, the development of the embryo / fetus, the course of childbirth and the postnatal development of offspring was not detected. Caution should be exercised when prescribing 1% Elidel Cream for pregnant women. However, given the minimal degree of absorption of pimecrolimus when applied topically, the potential risk in humans is considered negligible.
Lactation. Isolation of the drug with breast milk after topical application in experimental models has not been studied. There are no data on the content of pimecrolimus in breast milk in nursing women. Since many drugs are excreted in breast milk, caution should be exercised when prescribing 1% Elidel cream to lactating women. However, given the minimal degree of systemic absorption of pimecrolimus when applied topically, the potential risk to humans is considered negligible.
Nursing women should not apply 1% Elidel cream to the area of ââthe mammary glands.
The effect of Elidel cream on fertility in men and women has not been established.
In the treatment of topical calcineurin inhibitors, including Elidel, the development of malignant neoplasms (for example, skin tumors and lymphomas) has been noted in rare cases. A causal relationship between these adverse events and the use of the drug has not been established.
In clinical trials with the use of Elidel cream, 0.9% of patients (14 of 1544) showed the development of lymphadenopathy. Typically, lymphadenopathy was caused by infectious diseases and disappeared after a course of appropriate antibiotic therapy. In all patients, either it was possible to identify the cause of the development of lymphadenopathy or the disappearance of this undesirable phenomenon was noted. In patients receiving treatment with Elidel, with the development of lymphadenopathy, it is necessary to establish the etiology of the process and ensure that patients are monitored until this undesirable phenomenon completely disappears. If the etiology of lymphadenopathy is unknown or if the patient has acute mononucleosis, the drug should be discontinued.
When treating with Elidel Cream, patients are advised to minimize artificial or natural insolation of the skin or to completely avoid ultraviolet radiation. The possible effect of the use of the drug in skin lesions caused by ultraviolet radiation is unknown.
Effect on the ability to drive vehicles or work with mechanisms: The effect of using Elidel cream on the ability to drive vehicles or work with mechanisms has not been established.
Homogeneous cream from white to almost white.
1 g of cream contains 10 mg of pimecrolimus, as well as excipients: sodium hydroxide 0.20 mg, anhydrous citric acid 0.50 mg, benzyl alcohol 10.00 mg, sodium cetostearyl sulfate 10.00 mg, mono and diglycerides 20.00 mg , cetyl alcohol 40.00 mg, stearyl alcohol 40.00 mg, propylene glycol 50.00 mg, oleyl alcohol 100.00 mg, medium chain triglycerides 150.00 mg, purified water 569.30 mg.
Dosage and administration of
Treatment should be started at the first manifestations of the disease to prevent a sharp development of its exacerbation.
1% Elidel cream 2 times a day is applied in a thin layer on the affected surface and gently rubbed until completely absorbed.
1% Elidel cream can be applied to the skin of any part of the body, including the head, face, neck, as well as in the area of ââdiaper rash.
Elidel cream should be used 2 times a day, until the symptoms disappear completely. While maintaining the severity of symptoms after 6 weeks of use of the drug, it is necessary to re-examine the patient to confirm the diagnosis of atopic dermatitis. After stopping treatment, in order to avoid subsequent exacerbations, at the first signs of a relapse of atopic dermatitis, therapy should be resumed.
Emollients can be used immediately after applying 1% Elidel cream. However, after water procedures, emollients should be used before applying Elidel cream.
Given the very slight systemic absorption of pimecrolimus, there are no restrictions on the total daily dose of the drug applied, the area of ââthe treated surface of the skin, or the duration of treatment.
If Elidel gets into the eyes, mucous membranes (oral or nasal cavity), immediately remove the cream and rinse the eyes and mucous membranes with running water.
Application of 1% Elidel cream may cause minor transient reactions at the application site, such as a feeling of warmth and / or burning. With a significant severity of these reactions, patients should consult a doctor.
The most common adverse events – reactions at the site of application of the drug were observed in 19% of patients treated with 1% Elidel cream, and in 16% of patients from the control group. These reactions mainly occurred at an early stage of treatment, were insignificant / moderate and short-lived. The following adverse events are listed in frequency, starting with the most common. The frequency of occurrence of adverse reactions was evaluated as follows: occurring âvery oftenâ -? 1/10, âoftenâ -? 1/100 <1/10, âsometimesâ -? 1/1000 <1/100, ârarelyâ -? 1/10 000 <1/1000, âVery rareâ - <1/10 000, including individual messages. Very often: a burning sensation at the place of application of the cream. Often: local reactions (irritation, itching and redness of the skin), skin infections (folliculitis). Sometimes: suppuration worsening of the disease herpes simplex dermatitis due to herpes simplex virus (herpes eczema) molluscum contagiosum, local reactions such as rash, pain, paresthesia, desquamation, dryness, swelling, skin papillomas, boils. The following adverse reactions were noted with post-marketing use of the drug (an estimate of the frequency of the number of cases of AE in an unidentified population). From the side of the immune system: very rarely – anaphylactic reactions. From the side of metabolism (metabolic disorders): rarely – intolerance to alcohol. From the skin and its appendages: rarely allergic reactions (rash, urticaria, angioedema) changes in skin color (hypopigmentation, hyperpigmentation). In most cases, redness of the face, rash, burning, itching, or swelling developed immediately after taking alcohol. When applying Elidel cream in rare cases, the development of malignant neoplasms was noted, including skin and other types of lymphomas, skin cancer. A causal relationship between these adverse events and the use of the drug has not been established. Drug Interactions Potential interactions of 1% Elidel Cream with other drugs have not been studied. Given that the systemic absorption of pimecrolimus is very small, any interactions of Elidel cream with drugs for systemic use are unlikely. When using Elidel cream in children aged 2 years and older, the drug did not affect the effectiveness of vaccination. It is not recommended to apply the cream to the vaccine administration area until the local manifestations of the post-vaccination reaction completely disappear. Incompatibility. Since compatibility studies have not been conducted, it is not recommended to use the drug in conjunction with other local drugs. Overdose There were no cases of overdose or accidental use of 1% Elidel cream. Storage Conditions Do not store above 25 ° C, do not freeze. The drug should be stored out of the reach of children. Shelf life 2 years. The drug should not be used after the expiration date. After the first opening, use within 1 year. Deystvuyushtee substance pimecrolimus Terms and conditions prescription i form cream Appointment Appointment adults prescribed by a doctor, Children older than 3 months For pregnant women prescribed by a doctor, For children prescribed by a doctor, Nursing mothers Meda Pharma GmbH & Co. KG, Germany