Tacropic, ointment 0.03 g+0.03 g % 15 g

Tacrolimus belongs to the group of calcineurin inhibitors. It binds to the specific cytoplasmic protein immunophilin (FKBP12), which is a cytosolic receptor for calcineurin (FK506).

This results in the formation of a complex including tacrolimus, FKBPI2, calcium, calmodulin and calcineurin. which leads to inhibition of the phosphatase activity of calcineurin. This prevents dephosphorylation and translocation of nuclear factor of activated T cells (NFAT), which is essential for the initiation of transcription of genes encoding the production of cytokines key to the T-cell immune response (IL-2 and interferon gamma).

In addition, tacrolimus inhibits transcription of genes encoding production of cytokines such as IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GMSF) and tumor necrosis factor (TNF-α), which are involved in the initial stages of T cell activation.

In addition tacrolimus inhibits release of inflammatory mediators from mast cells, basophils and eosinophils and decreases expression of FcɛRI (high-affinity surface receptor for immunoglobulin E) on Langerhans cells, which leads to decrease of their activity and antigen presenting to T-lymphocytes.

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

Pharmacokinetics:

Absorption. Absorption of tacrolimus into the systemic bloodstream when used topically is minimal. In most patients with atopic dermatitis (adults and children), both single application and multiple applications of 0.03% and 0.1% tacrolimus ointment had plasma concentrations of < 1.0 ng/mL. Systemic absorption depends on the lesion area and decreases as the clinical manifestations of atopic dermatitis disappear. No cumulation of the drug was noted with long-term use (up to 1 year) in children and adults.

Distribution. Because systemic absorption of tacrolimus ointment is low, the high ability to bind to plasma proteins (over 98.8%) is considered clinically insignificant.

Metabolism. Tacrolimus is not metabolized in the skin. When entering the systemic bloodstream, tacrolimus is largely metabolized in the liver via the CYP3A4 isoenzyme.

Elimation. With multiple topical applications of tacrolimus ointment, the elimination half-life is 75 h in adults and 65 h in children.

Indications

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

For external use:the treatment of atopic dermatitis (moderate and severe forms) in patients with insufficient response to conventional methods of treatment or with contraindications to such methods.

Active ingredient

Composition

On 100 g:

Tacrolimus 30 mg.

Auxiliary substances:

macrogol 400 – 10 g,

liquid paraffin – 20 g,

White soft petroleum jelly – 5 g,

Emulsion wax – 10 g,

Dinatrium 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.

How to take, the dosage

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

Application in children (2 years and older) and adolescents under 16 years

The treatment should be started by applying 0.03% ointment Tacropic® twice a day. The duration of treatment according to this scheme should not exceed 3 weeks. Later the frequency of application is reduced to 1 time/day and treatment is continued until complete clearing of lesions.

Application in adults and adolescents 16 years and older

The treatment should be started with 0.1% ointment Tacropic® 2 times a day and continued until the lesions are completely clear. As symptoms improve, the frequency of application of the 0.1% ointment may be decreased or the 0.03% ointment may be switched to 0.03%. In case of recurrence of symptoms, treatment with Tacropic® 0.1% ointment should be resumed twice daily. If the clinical picture allows, an attempt should be made to reduce the frequency of use, or a lower dosage of 0.03% Tacropic® ointment should be used.

Application in the elderly (65 years and older)

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

Treatment of exacerbations

Tacropic® may be used for short-term or long-term repeated courses of therapy. Treatment of the affected skin areas is carried out until the clinical manifestations of atopic dermatitis have completely disappeared. As a rule, improvement is observed during the first week of treatment. If signs of improvement are not observed within two weeks of starting to use the ointment, other options for further treatment must be considered. Treatment should be resumed at the first signs of an exacerbation of atopic dermatitis.

Prophylaxis of exacerbations

In order to prevent exacerbations and increase the duration of remission in patients with a history of frequent (more than 4 times per year) exacerbations, maintenance therapy with Tacropic® is recommended. The appropriateness of prescription of maintenance therapy is determined by the effectiveness of previous therapy according to the standard regimen (2 times per day) for not more than 6 weeks.

In maintenance treatment, apply Tacropic® ointment twice weekly (e.g., on Monday and Thursday) to skin areas usually affected by an exacerbation. The interval between applications 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 is used. If signs of exacerbation occur, switch to the normal treatment regimen with Tacropic® ointment.

After 12 months of maintenance therapy, the clinical course should be evaluated and the continuation of prophylactic use of Tacropic® should be considered. In children, the drug should be temporarily discontinued to evaluate clinical progress and then consider whether continuation of maintenance therapy is warranted.

Interaction

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

The effect of Tacropic® on vaccine efficacy has not been studied. However, because of the potential risk of reduced efficacy, vaccination should be carried out before starting 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 concomitant use of tacrolimus with Neisseria meningitidis serotype C conjugate vaccine in children from 2 to 11 years of age has no effect on the initial vaccination response, immune memory formation, or the humoral and cellular immune response.

The possibility of co-administration of Tacropic® with other external agents, systemic GCS and immunosuppressants has not been studied.

Special Instructions

Tacropic® should not be used in patients with congenital or acquired immunodeficiencies or in patients taking immunosuppressive drugs.

You should avoid exposing the skin to sunlight, visiting a tanning bed, and UVB or A light therapy in combination with psoralen (PUVA therapy) during the use of Tacropic® ointment.

The drug Tacropic® should not be used to treat lesions that are considered to be potentially malignant or precancerous.

The areas of skin where Tacropic® was applied must not be treated with emollients 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 before prescribing Tacropic®, appropriate therapy is necessary. Use of Tacropic® may be associated with an increased risk of herpetic infection. If there are signs of herpetic infection, the benefit-risk ratio of Tacropic® should be individually evaluated.

If lymphoadenopathy is present, the patient should be evaluated before initiating therapy and monitored during use. If there is no apparent cause of lymphadenopathy or if symptoms of acute infectious mononucleosis are present, Tacropic® should be discontinued.

Contacting the drug in the eyes and on the mucous membranes should be avoided (if the ointment is accidentally touched, it should be carefully removed and/or washed with water).

The application of Tacropic® ointment under occlusive dressings and wearing tight, airtight clothing is not recommended.

As with any topical medication, patients should wash their hands after applying the ointment unless the ointment is applied to the hand area for a therapeutic purpose.

In children between 2 and 11 years of age, treatment with 0.03% tacrolimus ointment against Neisseria meningitidis serotype C conjugate vaccine has not been shown to affect the initial vaccine response, induction of the T-cell immune response, or formation of immune memory.

Influence on ability to drive and operate machinery

There have been no studies on the effect of the drug on the ability to drive and on the reaction time when operating complex machinery requiring increased attention. The drug Tacropic® is used topically, and there is no reason to believe that it may affect the ability to drive and operate machinery.

Contraindications

– Serious epidermal barrier disorders, particularly Netherton’s syndrome, lamellar ichthyosis, cutaneous manifestations of graft versus host reaction, and generalized erythroderma (due to the risk of increased systemic absorption of tacrolimus);

– Child age less than 2 years (for 0.03% ointment);

– childhood and adolescence under 16 years of age (for 0.1% ointment);

– pregnancy;

– period of breastfeeding;

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

Cautions

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

Caution should be exercised when using Tacropic® ointment in patients with extensive skin lesions, long-term courses, especially in children.

Side effects

The most common adverse reactions are skin irritation symptoms (burning and itching sensation, redness, pain, paraesthesia and rash) at the application site. As a rule, they are moderate and disappear within the first week of treatment.

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

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

In terms of frequency, adverse reactions are categorized as follows: very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10 000, < 1/1000), very rare (< 1/10 000), frequency unknown (not enough data to estimate frequency of development). Within each group, adverse reactions are presented in descending order of significance.

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

Metabolism and nutrition:often, alcohol intolerance (facial hyperemia or skin irritation symptoms after drinking alcohol).

Nervous system disorders:often – paresthesias, hyperaesthesia.

Skin and subcutaneous tissue: frequent – folliculitis, itching; infrequent – acne.

General disorders and disorders at the site of administration:very frequently – burning and itching in the area of application; frequently – feeling of heat, redness, pain, irritation, rash in the area of application; frequently unknown – edema in the area of application.

A solitary cases of rosacea and malignization (cutaneous and other types of lymphoma, skin cancer) have been reported during the entire period of drug monitoring.

Overdose

No cases of overdose have been reported with topical administration. If ingested, common measures should be taken, which include control of vital body functions and observation of the general condition. Induction of vomiting or gastric lavage is not recommended.

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