Tacropic (Ointment) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

AKRIKHIN JSC (Russia)

ATC Code

D11AH01 (Tacrolimus)

Active Substance

Tacrolimus (Rec.INN registered by WHO)

Dosage Forms

	Tacropic	Ointment for external use 0.1%: 15 g tube
		Ointment for external use 0.03%: 15 g tube

Dosage Form, Packaging, and Composition

Ointment for external use white or almost white, homogeneous; a slight specific odor is allowed.

* calculated as 100% substance.

Excipients: macrogol-400 – 10 g, liquid paraffin – 20 g, white soft paraffin – 5 g, emulsifying wax – 10 g, disodium edetate – 0.05 g, preservative Euxyl PE 9010 (phenoxyethanol 90%, ethylhexylglycerin 10%) calculated as phenoxyethanol – 0.45 g, purified water – up to 100 g.

15 g – aluminum tubes (1) – cardboard packs.

Ointment for external use white or almost white, homogeneous; a slight specific odor is allowed.

* calculated as 100% substance.

Excipients: macrogol-400 – 15 g, liquid paraffin – 20 g, white soft paraffin – 5 g, emulsifying wax – 10 g, disodium edetate – 0.05 g, preservative Euxyl PE 9010 (phenoxyethanol 90%, ethylhexylglycerin 10%) calculated as phenoxyethanol – 0.45 g, purified water – up to 100 g.

15 g – aluminum tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Topical anti-inflammatory drug. Selective inhibitor of the synthesis and release of inflammatory mediators

Pharmacotherapeutic Group

Other drugs used in dermatology; agents for the treatment of dermatitis, excluding corticosteroids

Pharmacological Action

Tacrolimus belongs to the group of calcineurin inhibitors. It binds to a specific cytoplasmic protein immunophilin (FKBP12), which is a 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 to dephosphorylate and translocate the nuclear factor of activated T-cells (NFAT), which is necessary for initiating the transcription of genes encoding the production of key cytokines for the T-cell immune response (IL-2 and interferon-gamma). Furthermore, 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 (TNFα), which are involved in the initial stages of T-lymphocyte activation. In addition, under the influence of tacrolimus, the release of inflammatory mediators from mast cells, basophils, and eosinophils is inhibited, and the expression of FcεRI (high-affinity surface receptor for immunoglobulin E) on Langerhans cells is reduced, leading 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 with topical application is minimal. In most patients with atopic dermatitis (adults and children), both after single application and after 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 affected area and decreases as the clinical manifestations of atopic dermatitis disappear. No accumulation of the drug was observed with long-term use (up to 1 year) in children and adults.

Distribution

Since the systemic absorption of tacrolimus ointment is low, its high ability to bind to plasma proteins (more than 98.8%) is considered clinically insignificant.

Metabolism

Tacrolimus is not metabolized in the skin. Upon entering the systemic circulation, Tacrolimus is largely metabolized in the liver via the CYP3A4 isoenzyme.

Excretion

With repeated topical application of tacrolimus ointment, T_1/2 is 75 hours in adults and 65 hours in children.

Indications

• Treatment of atopic dermatitis (moderate and severe forms) in case of its resistance to other topical therapies or the presence of contraindications to them.

In adults and adolescents over 16 years of age, the drug Tacropic is used as 0.03% ointment and 0.1% ointment; in children from 2 to 16 years only as 0.03% ointment.

ICD codes

Dosage Regimen

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

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

Treatment should be started by applying 0.03% Tacropic ointment 2 times/day. The duration of treatment according to this scheme should not exceed 3 weeks. Subsequently, the frequency of application is reduced to 1 time/day, treatment continues until the lesions are completely cleared.

Use in adults and adolescents 16 years and older

Treatment should be started by using 0.1% Tacropic ointment 2 times/day and continued until the lesions are completely cleared. As improvement occurs, the frequency of application of 0.1% ointment can be reduced or a switch can be made to using 0.03% Tacropic ointment. In case of recurrence of disease symptoms, treatment with 0.1% Tacropic ointment 2 times/day should be resumed. If the clinical picture allows, an attempt should be made to reduce the frequency of drug application or use a lower dosage – 0.03% Tacropic ointment.

Use in elderly people (65 years and older)

There are no specific features of use in elderly people. Usually, improvement is observed within 1 week from the start of therapy. If there are no signs of improvement during therapy within 2 weeks, the issue of changing the therapeutic tactics should be considered.

Treatment of exacerbations

Tacropic 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 complete disappearance of clinical manifestations of atopic dermatitis. As a rule, improvement is observed within the first week of treatment. If signs of improvement are not observed within two weeks from the start of 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 the anamnesis, maintenance therapy with Tacropic is recommended.

The advisability of prescribing maintenance therapy is determined by the effectiveness of previous treatment according to the standard regimen (2 times/day) for no more than 6 weeks.

During maintenance therapy, Tacropic ointment should be applied 2 times a week (for example, on Monday and Thursday) to areas of the skin that are usually affected during exacerbations.

The time interval between applications of the drug should be at least 2-3 days.

In adults and adolescents 16 years and older, 0.1% Tacropic ointment is used, in children (2 years and older) – 0.03% Tacropic ointment. When signs of exacerbation appear, one 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 on the advisability of continuing the prophylactic use of Tacropic. In children, to assess clinical dynamics, the drug should be temporarily discontinued and then the need for continuation of maintenance therapy should be considered.

Adverse Reactions

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 moderate and disappear within the first week after starting treatment.

Alcohol intolerance (facial redness or skin irritation symptoms after drinking alcoholic beverages) is common.

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

By frequency of occurrence, adverse reactions are distributed as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000), very rare (<1/10,000), frequency unknown (insufficient data to estimate frequency). Within each group, adverse reactions are presented in descending order of significance.

Infections and infestations: common – local skin infections regardless of etiology (in particular, but not limited to those listed, Kaposi’s varicelliform eruption, folliculitis, infection caused by Herpes simplex virus, other infections caused by viruses of the Herpes viridae family).

Metabolism and nutrition disorders: common – alcohol intolerance (facial flushing or skin irritation symptoms after drinking alcoholic beverages).

Nervous system disorders: common – paresthesia, hyperesthesia.

Skin and subcutaneous tissue disorders: common – folliculitis, pruritus; uncommon – acne.

General disorders and administration site conditions: very common – burning and itching at the application site; common – sensation of warmth, redness, pain, irritation, rash at the application site; frequency unknown – swelling at the application site.

Throughout the entire period of drug monitoring, isolated cases of rosacea, malignancy (skin and other types of lymphoma, skin cancer) have been recorded.

Contraindications

• Serious disorders of the epidermal barrier, in particular, Netherton’s syndrome, lamellar ichthyosis, skin manifestations of graft-versus-host disease, as well as generalized erythroderma (due to the risk of increased systemic absorption of tacrolimus);
• Children under 2 years of age (for 0.03% ointment);
• Children and adolescents under 16 years of age (for 0.1% ointment);
• Pregnancy;
• Breastfeeding period;
• Hypersensitivity to tacrolimus, excipients of the drug, macrolides.

With caution

Tacrolimus is largely metabolized in the liver, and although its concentration in the blood with external use is very low, the ointment should be used with caution in patients with decompensated hepatic insufficiency.

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

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Tacrolimus is largely metabolized in the liver, and although its concentration in the blood with external use is very low, the ointment should be used with caution in patients with decompensated hepatic insufficiency.

Pediatric Use

The use of the drug is contraindicated in children under 2 years of age. In children aged 2 to 16 years, 0.03% Tacropic ointment is used.

Geriatric Use

There are no specific features of use in elderly people. Usually, improvement is observed within 1 week from the start of therapy. If there are no signs of improvement during therapy within 2 weeks, the issue of changing the therapeutic tactics should be considered.

Special Precautions

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

During the use of Tacropic ointment, it is necessary to avoid exposure of the skin to sunlight, visiting a solarium, therapy with ultraviolet rays B or A in combination with psoralen (PUVA therapy).

Tacropic should not be used to treat lesions that are considered potentially malignant or premalignant.

Within 2 hours on areas of the skin where Tacropic was applied, emollients should not be used.

The efficacy and safety of using Tacropic in the treatment of infected atopic dermatitis have not been evaluated. If there are signs of infection, appropriate therapy should be carried out before prescribing Tacropic. The use of Tacropic may be associated with an increased risk of developing herpes infection. If there are signs of herpes infection, the benefit-risk ratio of using Tacropic should be assessed individually.

In the presence of lymphadenopathy, the patient should be examined before starting therapy and monitored during the period of drug use. If there is no obvious cause of lymphadenopathy or if there are symptoms of acute infectious mononucleosis, the use of Tacropic should be discontinued.

Avoid getting the drug into the eyes and on mucous membranes (if the ointment accidentally gets in, it must be carefully removed and/or rinsed with water).

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

Also, as with the use of any other topical medication, patients should wash their hands after applying the ointment, except in cases where the ointment is applied to the hands 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, the induction of T-cell immune response, and the formation of immune memory.

Effect on ability to drive vehicles and operate machinery

Studies on the effect of the drug on the ability to drive a car and the speed of reaction when working with complex machinery requiring increased attention have not been conducted. Tacropic is applied externally, and there is no reason to believe that it could affect the ability to drive a car and operate machinery.

Overdose

No cases of overdose have been reported with topical use.

If ingested, generally accepted measures should be taken, which include monitoring vital body functions and observing the general condition.

Induction of vomiting or gastric lavage is not recommended.

Drug Interactions

Tacrolimus is not metabolized in the skin, which eliminates the risk of drug interaction in the skin that could affect its metabolism. Since the systemic absorption of tacrolimus when used in the form of an ointment is minimal, interaction with inhibitors of the CYP3A4 isoenzyme (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 effectiveness, vaccination should be carried out before starting the use of the ointment or 14 days after the last use of Tacropic. In the case of using a live attenuated vaccine, this period should be increased to 28 days, otherwise, the possibility of using alternative vaccines should be considered.

Concomitant use of tacrolimus with a conjugated vaccine against Neisseria meningitidis serotype C in children from 2 to 11 years 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 concomitant use of Tacropic with other topical drugs, systemic corticosteroids, and immunosuppressants has not been studied.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.