Composition, form of production and packaging
Ointment for external use 0.03% from white to almost white, homogeneous; a slight specific odor is allowed.
100 g
tacrolimus 30 mg
[PRING] macrogol 400 - 10 g, paraffin liquid - 20 g, white soft vaseline - 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.
15 g - aluminum tubes (1) - cardboard packs.
Ointment for external use 0.1% of white to almost white, homogeneous; a slight specific odor is allowed.
100 g
tacrolimus 100 mg
[PRING] macrogol 400 - 15 g, paraffin liquid - 20 g, white soft vaseline - 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.
15 g - aluminum tubes (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Tacrolimus belongs to the group of calcineurin inhibitors. It binds to a specific cytoplasmic protein called immunophilin (FKBP12), which is a cytosolic receptor for calcineurin (FK506). As a result, a complex is formed, including tacrolimus, FKBPI2, calcium, calmodulin and calcineurin, which leads to inhibition of the phosphatase activity of calcineurin. This makes it impossible to dephosphorylate and translocate the nuclear factor of activated T-cells (NFAT), which is necessary for the initiation of transcription of genes encoding the production of key cytokines (IL-2 and interferon-gamma) for the T-cell immune response. In addition, tacrolimus inhibits the transcription of genes encoding the production of such cytokines as IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GMPCS) and tumor necrosis factor (TNF?), Which participate in the initial stages of activation T-lymphocytes. In addition, under the influence of tacrolimus, the release of inflammatory mediators from mast cells, basophils and eosinophils, as well as a decrease in the expression of Fc? RI (a high affinity surface receptor for immunoglobulin E), on the cells of Langerhans, leads to a decrease in their activity and presentation of the antigen to T lymphocytes .
Ointment tacrolimus does not affect the synthesis of collagen and, thus, does not cause skin atrophy.
PHARMACOKINETICS
Suction
Absorption of tacrolimus in the systemic blood stream with topical application is minimal. In most patients with atopic dermatitis (in adults and children), both with single application and repeated application of 0.03% and 0.1% of tacrolimus ointment, its plasma concentration was <1.0 ng / ml. Systemic absorption depends on the area of ​​the lesion and decreases with the disappearance of clinical manifestations of atopic dermatitis. Cumulation of the drug with prolonged use (up to 1 year) in children and adults was not noted.
Distribution
Due to the fact that systemic absorption of the tacrolimus ointment is low, the 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 by means of the CYP3A4 isoenzyme.
Excretion
With repeated topical application of tacrolimus ointment T 1/2 is 75 h in adults and 65 h in children.
INDICATIONS
- treatment of atopic dermatitis (moderate severity and severe forms) in case of its resistance to other external therapy or contraindications to such.
In adults and adolescents older than 16 years, the preparation Tacropic В® is used in the form of 0.03% ointment and 0.1% ointment; in children from 2 to 16 years only in the form of 0.03% ointment.
DOSING MODE
Adults and children over 2 years of preparation Tacropic ® are applied a thin layer on 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 the mucous membranes and under occlusive dressings.
Use in children (2 years and older) and adolescents under 16 years
Treatment should begin with the application of 0.03% Tacropic В® ointment 2 times / day. The duration of treatment under this scheme should not exceed 3 weeks. In the future, the frequency of application is reduced to 1 time / day, treatment is continued until the foci of lesion are completely cleared.
Application in adults and adolescents 16 years and older
Treatment should be started with the application of 0.1% Tacropic В® ointment 2 times / day and continue until complete clearance of lesions. As you improve, you can reduce the frequency of applying 0.1% of the ointment or switch to using 0.03% of Tacropic В® 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 application of the drug, or use a lower dosage of 0.03% Tacropic В® ointment.
Use in elderly people (65 years and older)
There are no special applications for elderly people. Usually, improvement is observed within 1 week from the start of therapy. If signs of improvement in the background of therapy are absent within 2 weeks, consideration should be given to changing therapeutic tactics.
Treatment of exacerbations
The drug Tacropic В® can be used for a short time or for a long time in the form of periodically repeated courses of therapy. Treatment of affected areas of the skin is carried out until the disappearance of clinical manifestations of atopic dermatitis. As a rule, improvement is observed during the first week of treatment. If signs of improvement are not observed within two weeks of starting the use of the ointment, other options for further treatment should be considered. Treatment should be resumed with the appearance of 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) exacerbation of the disease in history, supportive therapy with Tacropic В® is recommended.
The expediency of prescribing maintenance therapy is determined by the effectiveness of the previous treatment according to the standard schedule (2 times / day) for no more than 6 weeks.
With maintenance therapy, Tacropic В® ointment should be applied 2 times a week (for example, on Monday and Thursday) on skin areas, usually affected by exacerbations.
The time between application of the drug should be at least 2-3 days.
Adults and adolescents 16 years and older use 0.1% Tacropic В® ointment, in children (2 years and older) - 0.03% Tacropic В® ointment. When signs of exacerbation should move to the usual regimen of therapy with the ointment Tacropic В® .
After 12 months of maintenance therapy, it is necessary to assess the clinical dynamics and decide whether to continue the prophylactic use of Tacropic В® . Children should be temporarily discontinued to assess clinical dynamics and then consider whether to continue supporting therapy.
SIDE EFFECT
The most frequent adverse reactions are symptoms of skin irritation (burning sensation and itching, redness, pain, paresthesia and rash) at the application site.
As a rule, they are moderately expressed and pass within the first week after the start of treatment.
Often there is intolerance to alcohol (redness of the face or symptoms of skin irritation after drinking alcohol).
In patients using Tacropic В® , there is an increased risk of developing folliculitis, acne and herpetic infection.
The frequency of occurrence of unwanted 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 (insufficient data to estimate the frequency of development). Within each group, undesirable reactions are presented in descending order of significance.
Infectious diseases: often - local skin infections, regardless of the etiology (in particular, but not limited to, herpes zoster Kaposi, folliculitis, infection caused by the Herpes simplex virus, other infections caused by the viruses of the Herpes viridae family).
From the side of metabolism and nutrition: often - alcohol intolerance (face hyperemia or symptoms of skin irritation after drinking).
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 field of application.
During the entire period of observation of the drug, single cases of rosacea, malignization (cutaneous and other types of lymphomas, skin cancer) were recorded.
CONTRAINDICATIONS
- Serious disturbances of the epidermal barrier, in particular, the Netherton syndrome, lamellar ichthyosis, cutaneous manifestations of the "graft versus host" reaction, and generalized erythroderma (due to the risk of increased systemic absorption of tacrolimus);
- Children's age to 2 years (for 0.03% of ointment);
- Children's and adolescence under 16 years (for 0.1% of ointment);
- Pregnancy;
- the period of breastfeeding;
- Hypersensitivity to tacrolimus, auxiliary components of the drug, macrolides.
Carefully
Tacrolimus is largely metabolized in the liver, and although its concentration in the blood with external application is very low, in patients with decompensated hepatic insufficiency ointment should be used with caution.
Care should be taken when using Tacropic В® ointment in patients with extensive skin lesions, long courses, especially in children.
PREGNANCY AND LACTATION
Contraindicated use of the drug during pregnancy and lactation.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Tacrolimus is largely metabolized in the liver, and although its concentration in the blood with external application is very low, in patients with decompensated hepatic insufficiency ointment should be used with caution.
APPLICATION FOR CHILDREN
Contraindicated in children under 2 years. Children from 2 to 16 years of age use 0.03% Tacropic В® ointment.
APPLICATION IN ELDERLY PATIENTS
There are no special applications for elderly people. Usually, improvement is observed within 1 week from the start of therapy. If signs of improvement in the background of therapy are absent within 2 weeks, consideration should be given to changing the therapeutic tactics.
SPECIAL INSTRUCTIONS
Tacropic В® can not be used in patients with congenital or acquired immunodeficiencies or in patients who take immunosuppressive drugs.
During the application of the Tacropic В® ointment, sun rays should be avoided on the skin, a visit to the solarium, ultraviolet B or A therapy in combination with psvalenum (PUVA therapy).
Tacropic В® should not be used to treat lesions that are considered to be potentially malignant or pre-malignant.
For 2 hours on the skin areas on which the drug Tacropic В® was applied, you can not use emollients.
The efficacy and safety of Tacropic В® in the treatment of infected atopic dermatitis was not assessed. If signs of infection are present prior to the administration of Tacropic В® , appropriate therapy is necessary. The use of Tacropic В® may be associated with an increased risk of developing a herpetic infection. In the presence of signs of herpetic infection, one should individually evaluate the relationship between the benefits and risks of using Tacropic В® .
In the presence of lymphadenopathy, the patient should be examined before starting therapy and observed during the period of application of the drug. In the absence of an obvious cause of lymphadenopathy or in the presence of symptoms of acute infectious mononucleosis, Tacropic В® should be discontinued.
Avoid contact with eyes and mucous membranes (if accidentally ingested, the ointment should be carefully removed and / or rinsed with water).
It is not recommended to apply Tacropic В® ointment under occlusive dressings and wear tight, airtight clothing.
Also, as with any other topical drug, patients should wash their hands after applying the ointment, except when the ointment is applied to the area of ​​the hands for therapeutic purposes.
It has been shown that treatment of tacrolimus ointment 0.03% in children aged 2-11 years against vaccination with Neisseria meningitidis serotype C conjugate vaccine has no effect on the primary response to vaccination, the induction of the T-cell immune response, and the formation of immune memory.
Impact on the ability to drive vehicles and manage mechanisms
Studies on the effect of the drug on the ability to drive a car and the speed of response when working with complex equipment requiring increased attention were not conducted. Tacropic В® is used externally and there is no reason to believe that it can affect the ability to drive and work with machinery.
OVERDOSE
When topical application of cases of overdose was not noted.
When ingested, it is necessary to take common measures, which include monitoring of vital body functions and monitoring the general condition.
Stimulation of vomiting or gastric lavage is not recommended.
DRUG INTERACTION
Tacrolimus is not metabolized in the skin, which eliminates the risk of drug interaction in the skin, which can 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) with simultaneous use with the drug Tacropic В® is unlikely, but can not be completely ruled out in patients with extensive lesions and / or erythroderma.
The effect of Tacropic В® on the effectiveness of vaccination has not been studied. However, due to the potential risk of impairment, vaccination should be given prior to the application of the ointment or 14 days after the last use of Tacropic В® . If a live attenuated vaccine is used, this period should be increased to 28 days, otherwise alternative vaccines should be considered.
The simultaneous use of tacrolimus with a conjugate vaccine against Neisseria meningitidis serotype C in children 2 to 11 years of age does not affect the primary response to vaccination, the formation of immune memory, and also the humoral and cellular immune response.
The possibility of using Tacropic В® together with other external drugs, systemic SCS and immunosuppressants has not been studied.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years.
