Elidel

General characteristics. Structure:

Active agent: 1 g of cream contains 10 mg of a pimekrolimus, and also excipients: sodium hydroxide of 0,20 mg, citric acid of anhydrous 0,50 mg, benzyl alcohol of 10,00 mg, sodium цетостеарилсульфат 10,00 mg, mono and diglycerides of 20,00 mg, cetyl alcohol of 40,00 mg, stearyl alcohol of 40,00 mg, propylene glycol of 50,00 mg, oleyl alcohol of 100,00 mg, triglycerides srednetsepochechny 150,00 mg, the water purified 569,30 mg.

Pharmacological properties:

Pharmacodynamics. Pimekrolimus is derivative a macrolactam of an askomitsin and possesses antiinflammatory action. Pimekrolimus selectively inhibits products and release of cytokines and mediators of an inflammation from T lymphocytes and mast cells. Pimekrolimus it is specific contacts a cytosolic receptor a macroeagle owl-12 and inhibits kaltsiyzavisimy phosphatase - кальциневрин. The inhibition of a kaltsinevrin leads to suppression of proliferation of T lymphocytes and prevents a transcription and development in T-helperakh 1 and 2 types of early cytokines, such as interleykin-2, интерферон-γ, interleykin-.4, interleykin-5, interleykin-10, a necrosis factor опухоли-α and a granulotsitarno-macrophagic colony stimulating factor. Pimekrolimus and такролимус equally suppress a secondary immune response in the isolated cellular colonies T-helperov of skin received at patients with atopic dermatitis. In vitro пимекролимус also prevents the antigen/IGE-mediated release of cytokines and mediators of an inflammation from mast cells. Pimekrolimus does not influence growth of keratinotsit, fibroblasts and endothelial cells and, unlike corticosteroids, has the selection effect on cells of immune system and does not cause dysfunctions, viability, processes of differentiation, maturing of cells of Langergans of mice and dendritic cells of a monocytic origin in the person. Drug does not exert impact on the differentiation of "naive" T lymphocytes in T-effector cells under the influence of Langergans's cells and dendritic cells which is one of the main mechanisms of a specific immune response. On experimental models of a skin inflammation high antiinflammatory activity of a pimekrolimus after its topical and system administration was shown. At topical administration on experimental models of the allergic contact dermatitis (ACD) пимекролимус it is comparable by efficiency to highly active corticosteroids: klobetazolom-17 propionate and flutikazony, inhibits inflammatory reaction in response to influence of skin irritants, without causing change of a consistence, consolidation and an atrophy of skin. Besides, at topical and oral administration on the AKD experimental models of an acute current пимекролимус effectively reduces a skin inflammation, an itch and expressiveness of histopathological changes. At topical administration extent of penetration into skin of a takrolimus and a pimekrolimus equally good. However ability of a pimekrolimus to get through skin is less, than at a takrolimus and glucocorticosteroids. Thus, пимекролимус possesses the selection action on skin.
Uniqueness of the mechanism of action of a pimekrolimus consists in a combination of the selection antiinflammatory action on skin with insignificant influence on a system immune response.
At use within weeks for children from 3 months to 17 years пимекролимус effectively would reduce an itch and a skin inflammation (an erythema, infiltration, excoriation and a likhenization). At prolonged use within 12 months пимекролимус effectively reduces the frequency of emergence of sudden aggravations of AKD, without causing an atrophy, irritation and increase in hypersensitivity of skin and without possessing the phototoxic or photosensitizing action.

Pharmacokinetics. Adults
Concentration of a pimekrolimus in blood determined at 12 adult patients with atopic dermatitis (eczema) at defeat 15-59% of surface area of a body receiving treatment of 1% cream Elidel 2 times a day for 3 weeks. In 77,5% of observations concentration of a pimekrolimus in blood was lower than 0,5 ng/ml (the minimum defined concentration), and in 99,8% — it is lower than 1 ng/ml. The maximum value of concentration of a pimekrolimus in blood registered at one patient made 1,4 ng/ml.
With initial defeat of 14-62% of surface area of a body after 1 year of treatment of concentration of a pimekrolimus by Elidel in blood remained with 98% from 40 adults of patients at a low level and in most cases were below the minimum defined concentration. The maximum value of concentration which made 0,8 ng/ml was registered after 6 weeks of treatment only at two patients. At one of patients increase of concentration for 12 months of treatment was not noted. For the 3 weeks period of treatment by Elidel 2 times a day at 13 adult patients with dermatitis of brushes (at use of cream on area of palms and the back of brushes and bandaging for the night) the maximum registered value of concentration of a pimekrolimus in blood made 0,91 ng/ml.
At 8 patients with the maintenance of a pimekrolimus in blood above the minimum defined concentration AUC value made from 2,5-11,4 ng/ml.
Children
Pharmacokinetic researches of a pimekrolimus were conducted at 58 children aged from 3 up to 14 years with atopic dermatitis (eczema) at defeat of 10-92% of surface area of a body receiving treatment of 1% cream Elidel 2 times a day for 3 weeks. Five children received treatment during 1 year as required.
Concentration of a pimekrolimus in blood were at steadily low level, irrespective of the area of defeat of integuments and duration of therapy, and were in the same range of values, as at the adult patients receiving therapy by Elidel in the same doses. In 97% of cases of concentration of a pimekrolimus in blood there were lower than 2 ng/ml, and in 60% - it is lower than 0,5 ng/ml (the minimum defined concentration). The maximum value of concentration of a pimekrolimus registered at two patients at the age of 8 months and 14 years made 2,0 ng/ml.
Among children of the youngest age (from 3 to 23 months) the maximum value of concentration of a pimekrolimus registered at one patient made 2,6 ng/ml.
At five children receiving treatment by Elidel during 1 year, concentration of a pimekrolimus were at steadily low level. The maximum value registered at one child made 1,94 ng/ml. Throughout the entire period of treatment growth of concentration of drug was not observed at one of patients.
At 8 children aged from 2 up to 14 years with the maintenance of a pimekrolimus in blood above the minimum defined concentration at triple measurement AUC value made from 5,4-18,8 ng/ml. AUC values at patients less than 40% and more than 40% were comparable to the area of defeat of integuments.
In the researches in vitro linkng of a pimekrolimus with proteins of plasma (generally with various lipoproteins) made 99,6%.
As at topical administration of concentration of a pimekrolimus in blood very low, determination of parameters of metabolism is not possible.
Use for elderly patients
Atopic dermatitis (eczema) is seldom observed at patients aged from 65 years and is more senior. The number of patients of such age in clinical trials of cream Elidel was insufficient to reveal any distinctions in efficiency of treatment in comparison with young patients.
Use for children
Recommendations about dosing for babies (3-23 months), children (2-11 years) and teenagers (12-17 years) do not differ from recommendations for adult patients.

Indications to use:

Atopic dermatitis (eczema).
Drug is shown for short-term and prolonged treatment of atopic dermatitis at adults, teenagers and children (of 3 months).

Route of administration and doses:

Treatment should be begun at the first displays of a disease for prevention of sharp development of its aggravation.
1% Elidel 2 times a day apply cream with a thin layer on the struck surface and carefully rub before full absorption.
1% Elidel can apply cream on skin of any parts of a body, including the head, a face, a neck, and also on areas of an intertrigo.
Elidel it is necessary to apply cream 2 times a day, before total disappearance of symptoms of a disease. At preservation of expressiveness of symptoms in 6 weeks of use of drug it is necessary to conduct repeated examination of the patient for confirmation of the diagnosis of atopic dermatitis. After the treatment termination, in order to avoid the subsequent aggravations, at the first signs of a recurrence of atopic dermatitis therapy should be resumed.
Emollients it is possible to apply right after drawing 1% of cream Elidel. However after hydrotherapeutic procedures emollients should be applied before putting cream Elidel.
Considering very insignificant system absorption of a pimekrolimus, restrictions of the general daily dose of the applied drug, the area of the processed surface of skin or duration of treatment does not exist.
At Elidel's hit in eyes, on mucous membranes (an oral or nasal cavity) it is necessary to remove immediately cream and to wash out eyes and mucous flowing water.

Features of use:

At treatment inhibitors of a kaltsinevrin of topical administration, including Elidel, in rare instances noted development of malignant new growths (for example, skin tumors and lymphoma). Relationship of cause and effect between these undesirable phenomena and use of drug is not established.
In clinical trials at cream use Elidel at 0,9% of patients (14 of 1544) development of a limfoadenopatiya was noted. Usually the limfoadenopatiya was caused by infectious diseases and disappeared after carrying out a course of the corresponding antibioticotherapia. At all patients or it was possible to establish the reason of development of a limfoadenopatiya or disappearance of this undesirable phenomenon was noted. At the patients receiving treatment by Elidel at development of a limfoadenopatiya it is necessary to establish an etiology of process and to provide observation of patients before total disappearance of this undesirable phenomenon. At an unspecified etiology of a limfoadenopatiya or existence at the patient of an acute mononukleozny inflammation drug should be cancelled.
At treatment by cream Elidel to patients is recommended to reduce artificial or natural insolation of skin to a minimum or to completely avoid ultra-violet radiation. Possible influence of use of drug at the damages of skin caused by ultra-violet radiation is unknown.
Influence on ability to manage motor transport or to work with mechanisms
Cream use influence Elidel on ability to manage motor transport or to work with mechanisms is not established.

Side effects:

Use of 1% of cream Elidel can cause insignificant passing reactions in a site of application, such as feeling of heat and/or burning. At considerable expressiveness of these reactions patients should consult at the doctor.
The most frequent undesirable phenomena - reactions in a site of application of drug were noted at 19% of the patients receiving treatment of 1% cream Elidel and at 16% of patients from control group. These reactions generally arose at an early stage of treatment, were insignificant/moderate and short.
The undesirable phenomena given below are listed on frequency, starting with the most frequent. Frequency of occurrence of undesirable reactions was estimated as follows: arising "it is very frequent" - ≥1/10, is "frequent" - ≥1/100 <1/10," sometimes" - ≥1/1000 <1/100,       is "rare" - ≥1/10 000 <1/1000, "it is very rare" - <1/10 000, including separate messages.
Very often: burning in a cream site of application. Often: local reactions (irritation, itch and erubescence), skin infections (folliculitis). Sometimes: suppuration; deterioration in a disease; herpes simplex; the dermatitis caused by a herpes simplex virus (herpetic eczema); contagious mollusk, local reactions, such as rash, pain, paresthesias, peeling, dryness, puffiness, skin papillomas, furuncles.
The undesirable reactions given below were noted at post-marketing use of drug (frequency assessment in quantity of cases of development of NYa in unspecified population).
From immune system: very seldom — anaphylactic reactions.
From a metabolism (metaball ichesky disturbances): seldom - intolerance of alcohol.
From skin and its appendages: seldom - allergic reactions (rash, urticaria, a Quincke's disease); skin discolorations (hypopigmentation, hyperpegmentation).
In most cases at once after alcohol intake face reddening, rash, burning, an itch or a swelling developed.
At cream use Elidel development of malignant new growths, including skin and other types of lymphoma, a carcinoma cutaneum was in rare instances noted. Relationship of cause and effect between these undesirable phenomena and use of drug is not established.

Interaction with other medicines:

Potential interactions of 1% of cream Elidel with other drugs were not studied. Considering that system absorption of a pimekrolimus is very insignificant, any interactions of cream Elidel with drugs for system use are improbable.
At cream use Elidel at children at the age of 2 years is also more senior drug did not exert impact on efficiency of vaccination.
Putting cream on area of introduction of a vaccine before total disappearance of local manifestations of postvaccinal reaction is not recommended.
Incompatibility
As researches of compatibility were not conducted, it is not recommended to use drug together with other local means.

Contraindications:

Hypersensitivity to a pimekrolimus or any components of drug.
Children's age up to 3 months (since safety and efficiency of use of cream Elidel at children is younger than 3 months it was not studied).
Cream Elidel should not be applied on the sites of skin affected with an acute viral, bacterial or fungal infection.
With care
Patients with Neterton's syndrome and a generalized erythrosis have data on safety of use of cream no Elidel. Considering possible risk of increase in system absorption of drug, cream Elidel is not recommended to apply at patients with Neterton's syndrome or at severe forms of an inflammation or damage of skin (for example, at an erythrosis).
As efficiency and safety of use of cream Elidel at patients with the weakened immunity were not studied, drug is not recommended to be used at this category of patients.
Data on safety of prolonged use of cream Elidel are absent.
As influence of prolonged use of drug on a host defense of skin and frequency of development of malignant new growths it is not studied, cream Elidel should not be applied on the damaged sites of an integument with a possible ozlokachestvleniye or dysplastic changes.
In case of a bacterial or fungal infection of skin cream use Elidel on affected areas is possible only after treatment of an infection.
Use during the periods of pregnancy and a lactation
Pregnancy. Pregnant women have data on use of 1% of cream no Elidel. In pilot studies at topical administration of drug of the direct or mediated damaging Elidel's action on the course of pregnancy, development of an embryo/fruit, the course of childbirth and post-natal development of posterity it is not revealed. It is necessary to be careful at purpose of 1% of cream Elidel to pregnant women. However, considering the minimum extent of absorption of a pimekrolimus at topical administration, the potential risk at the person is considered insignificant.
Lactation. Release of drug with breast milk after topical administration on experimental models was not studied. In breast milk the feeding women have no data on the maintenance of a pimekrolimus. As many drugs are emitted with breast milk, it is necessary to be careful at purpose of 1% of cream Elidel to the feeding women. However considering the minimum extent of system absorption of a pimekrolimus at topical administration, the potential risk for the person is considered insignificant.
The feeding women should not apply to 1% cream Elidel on area of mammary glands.
Cream influence Elidel on fertility at men and women is not established.

Overdose:

Cases of overdose or accidental use of 1% of cream Elidel inside were not observed.

Storage conditions:

To store at a temperature not above 25ºС, not to freeze. Drug should be stored in the place, unavailable to children. Period of validity 2 years. Drug should not be used after expiry date. After the first opening to use during 1 year.

Issue conditions:

According to the recipe

Packaging:

Cream for external use of 1% 15 g, 30 g and 100 g in an aluminum tuba. 1 tuba with the application instruction in a cardboard pack.