Tacropic 0.03% 15 g,

Per 100 g:

tacrolimus 30 mg.

Excipients: 

macrogol 400 - 10 g, 

liquid paraffin - 20 g, 

white soft petroleum jelly - 5 g, 

emulsion wax - 10 g, 

disodium edetate - 0.05 g, 

preservative Euxyl PE 9010 (phenoxyethanol 90%, ethylhexylglycerol 10%) in terms of phenoxyethanol - 0.45 mg, 

purified water - up to 100 g.

Tacrolimus belongs to the group of calcineurin inhibitors. It binds to a specific cytoplasmic protein immunophilin (FKBP12), which is the cytosolic receptor for calcineurin (FK506). As a result, a complex is formed that includes tacrolimus, FKBPI2, calcium, calmodulin and calcineurin. which leads to inhibition of the phosphatase activity of calcineurin. This makes it impossible for dephosphorylation and translocation of the nuclear factor of activated T cells (NFAT), which is necessary for the initiation of transcription of genes encoding the production of cytokines, key for the T cell immune response (IL-2 and interferon-gamma). 

In addition, tacrolimus inhibits the transcription of genes encoding the production of cytokines such as IL-3, IL-4, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF-α). which take part in the initial stages of T-lymphocyte activation. In addition, under the influence of tacrolimus, the release of inflammatory mediators from mast cells, basofluids and eosinophils is inhibited, as well as a decrease in the expression of FcɛRI (high-affinity surface receptor for immunoglobulin E) on Langerhans cells, which leads to a decrease in their activity and antigen presentation to T-lymphocytes.

Tacrolimus ointment does not affect collagen synthesis and thus does not cause skin atrophy.

Pharmacokinetics:

Absorption . The absorption of tacrolimus into the systemic circulation when applied topically is minimal. In most patients with atopic dermatitis (in adults and children), both with a single application and with repeated use of 0.03% and 0.1% tacrolimus ointment, its concentration in blood plasma was <1.0 ng / ml. Systemic absorption depends on the area of ​​the lesion and decreases as the clinical manifestations of atopic dermatitis disappear. Cumulation of the drug with prolonged use (up to 1 year) in children and adults was not observed.

Distribution. Due to the fact that the systemic absorption of tacrolimus ointment is low, a high ability to bind to plasma proteins (more than 98.8%) is considered clinically insignificant.

Metabolism.  Tacrolimus is not metabolized in the skin. When it enters the systemic circulation, tacrolimus is largely metabolized in the liver through the CYP3A4 isoenzyme.

Excretion.  With repeated topical application of tacrolimus ointment, the half-life is 75 hours in adults and 65 hours in children.

For systemic use: prevention and treatment of liver and kidney allograft rejection in adult patients. Treatment of allograft rejection resistant to standard immunosuppressive therapy in adult patients.

For external use: treatment of atopic dermatitis (moderate and severe) in case of insufficient patient response to traditional methods of treatment or the presence of contraindications to them.

- serious violations of the epidermal barrier, in particular, Netherton's syndrome, lamellar ichthyosis, skin manifestations of the graft-versus-host reaction, as well as generalized erythroderma (due to the risk of increased systemic absorption of tacrolimus);

- children's age up to 2 years (for 0.03% ointment);

- children and adolescents up to 16 years old (for 0.1% ointment);

- pregnancy;

- period of breastfeeding;

- hypersensitivity to tacrolimus, auxiliary components of the drug, macrolides.

Carefully

Tacrolimus is extensively metabolized in the liver, and although its concentration in the blood is very low when applied externally, the ointment should be used with caution in patients with decompensated liver failure.

Care must be taken when using Tacropic® ointment  in patients with extensive skin lesions, long courses, especially in children.

The most common adverse reactions are symptoms of skin irritation (burning and itching sensations, redness, pain, paresthesias and rashes) at the site of application. As a rule, they are moderately expressed and disappear within the first week after starting treatment.

Alcohol intolerance (redness of the face or symptoms of skin irritation after drinking alcohol) is common.

Patients using Tacropic® have an increased risk of developing folliculitis, acne, and herpes infection.

By the frequency of occurrence, adverse reactions are distributed as follows: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (? 1/10 000, <1/1000), very rarely (<1/10 000), the frequency is unknown (there is not enough data to estimate the frequency of development). Within each group, adverse reactions are presented in decreasing order of importance.

Infectious diseases:  often - local skin infections, regardless of etiology (in particular, but not limited to those listed, Kaposi's herpetic eczema, folliculitis, infection caused by the Herpes simplex virus, other infections caused by viruses of the Herpes viridae family).

From the side of metabolism and nutrition:  often - alcohol intolerance (flushing of the face or symptoms of skin irritation after drinking alcohol).

From the nervous system:  often - paresthesia, hyperesthesia.

From the skin and subcutaneous tissues:  often - folliculitis, itching; infrequently - acne.

General disorders and disorders at the injection site:  very often - burning and itching in the area of ​​application; often - a feeling of warmth, redness, pain, irritation, rash in the area of ​​application; frequency unknown - edema in the area of ​​application.

Over the entire period of observation of the drug, isolated cases of rosacea, malignancy (skin and other types of lymphomas, skin cancer) were registered.

Tacrolimus is not metabolized in the skin, which eliminates the risk of drug interactions in the skin that could affect its metabolism. Because systemic absorption of tacrolimus when used in the form of an ointment is minimal, interaction with inhibitors of the isoenzyme CYP3A4 (including erythromycin, itraconazole, ketoconazole, diltiazem) when used simultaneously with Tacropic® is  unlikely, but cannot be completely excluded in patients with extensive lesions and / or erythroderma.

The effect of Tacropic®  on the effectiveness of vaccination has not been studied. However, due to the potential risk of reduced efficacy, vaccination should be carried out before starting to use the ointment or 14 days after the last use of Tacropic® . If a live attenuated vaccine is used, this period should be extended to 28 days, otherwise alternative vaccines should be considered.

The simultaneous use of tacrolimus with a conjugated vaccine against Neisseria meningitidis serotype C in children from 2 to 11 years old does not affect the primary response to vaccination, the formation of immune memory, as well as the humoral and cellular immune response.

The possibility of joint use of Tacropic®  with other external drugs, systemic corticosteroids and immunosuppressants has not been studied.

For adults and children over 2 years of age, Tacropic®  is applied in a thin layer to the affected skin. The drug can be used on any part of the body, including the face and neck, in the area of ​​skin folds. Do not apply the drug to mucous membranes and under occlusive dressings.

Use in children (2 years old and older) and adolescents under 16 years old

Treatment should start with the application of 0.03% Tacropic®  ointment 2 times / day. The duration of treatment for this scheme should not exceed 3 weeks. In the future, the frequency of use is reduced to 1 time / day, the treatment continues until the lesions are completely cleared.

Use in adults and adolescents 16 years of age and older

Treatment should begin with the use of 0.1% Tacropic® ointment  2 times / day and continue until the lesions are completely cleared . As you improve, you can reduce the frequency of applying 0.1% ointment or switch to using 0.03% Tacropic® ointment . In case of recurrence of symptoms of the disease, treatment with 0.1% Tacropic® ointment should be resumed  2 times / day. If the clinical picture allows, an attempt should be made to reduce the frequency of drug use, or use a lower dosage - 0.03% Tacropic® ointment .

Use in the elderly (65 years and older)

There are no peculiarities of use in elderly people. Usually, improvement is observed within 1 week from the start of therapy. If there are no signs of improvement with therapy within 2 weeks, a change in therapeutic tactics should be considered.

Treatment of exacerbations

The drug Takropic®  can be used short-term or long-term in the form of periodically repeated courses of therapy. Treatment of affected skin areas is carried out until the clinical manifestations of atopic dermatitis completely disappear. Typically, improvement is seen within the first week of treatment. If signs of improvement are not observed within two weeks of starting using the ointment, other options for further treatment should be considered. Treatment should be resumed at the first signs of exacerbation of atopic dermatitis.

Prevention of exacerbations

To prevent exacerbations and increase the duration of remission in patients with frequent (more than 4 times a year) exacerbations of the disease in history, maintenance therapy with Tacropic® is recommended . The feasibility of prescribing maintenance therapy is determined by the effectiveness of previous treatment according to the standard scheme (2 times / day) for no more than 6 weeks. 

With maintenance therapy, Tacropic® ointment  should be applied 2 times a week (for example, on Monday and Thursday) on the skin areas usually affected by exacerbations. The time interval between the application of the drug should be at least 2-3 days.

In adults and adolescents 16 years of age and older, 0.1% Tacropic® ointment is used , in children (2 years of age and older) - 0.03% Tacropic® ointment. If signs of exacerbation appear, you should switch to the usual regimen of therapy with Tacropic® ointment  .

After 12 months of maintenance therapy, it is necessary to assess the clinical dynamics and decide whether to continue the prophylactic use of Tacropic® . In children, to assess clinical dynamics, the drug should be temporarily discontinued and then the need to continue maintenance therapy should be considered.

When applied topically, there were no cases of overdose. If ingested, it is necessary to take generally accepted measures, which include monitoring the vital functions of the body and monitoring the general condition. Induction of vomiting or gastric lavage is not recommended.

The drug Takropik®  can not be used in patients with congenital or acquired immunodeficiencies or in patients who are taking immunosuppressive drugs.

When using Tacropic® ointment  , avoid sun exposure, tanning beds, ultraviolet B or A therapy in combination with psoralen (PUVA therapy).

The drug Takropik®  should not be used to treat the affected areas, which are considered to be potentially malignant or pre-malignant.

Do not use emollients on the skin areas where Tacropic® has been applied for 2 hours .

The efficacy and safety of Tacropic®  in the treatment of infected atopic dermatitis has not been evaluated. If there are signs of infection  , appropriate therapy should be carried out prior to the appointment of Tacropic® . The use of Tacropic®  may be associated with an increased risk of developing herpes infection. In the presence of signs of herpes infection, the ratio of benefits and risks of using Tacropic® should be individually assessed .

In the presence of lymphadenopathy, it is necessary to examine the patient before starting therapy and monitor him during the period of drug use. In the absence of an obvious cause of lymphadenopathy or in the presence of symptoms of acute infectious mononucleosis, the use of Tacropic® should be discontinued .

It is necessary to avoid getting the drug in the eyes and on the mucous membranes (in case of accidental contact with the ointment, carefully remove and / or rinse with water).

It is not recommended to apply Tacropic® ointment  under occlusive dressings and wear tight, airtight clothing.

As with any topical medication, patients should wash their hands after applying the ointment, except when the ointment is applied to the hand area for therapeutic purposes.

It has been shown that in children aged 2 to 11 years, treatment with 0.03% tacrolimus ointment against the background of vaccination with a conjugated vaccine against Neisseria meningitidis serotype C does not affect the primary response to vaccination, induction of the T-cell immune response and the formation of immune memory.

Influence on the ability to drive vehicles and use mechanisms

Studies on the effect of the drug on the ability to drive a car and on the speed of reaction when working with complex equipment requiring increased attention have not been conducted. The drug Takropic®  is used externally and there is no reason to believe that it may affect the ability to drive and operate machinery.