TIMODEPRESSIN

Active material: c-D-глутамил-D-триптофана динатрия
When ATH: L04AA
CCF: Immunosuppressive drugs
ICD-10 codes (testimony): C84, D59.1, D69.3, D70, L10, L20.8, L28.0, L40, L94.0, M05, Z29.8, Z94
At KFU: 14.02
Manufacturer: CENTER PEPTOS Company (Russia)

Pharmaceutical form, composition and packaging

The solution for the / m colorless, clear; tolerance characteristic odor.

Excipients: sodium chloride, Sodium hydroxide 1 M (to pH 6.0-8.5), water d / and.

1 ml – ampoule (5) – packings Valium planimetric (1) – packs cardboard.

Nasal drops 0.1% Colorless, clear; tolerance characteristic odor.

Excipients: sodium chloride, Sodium hydroxide 1 M (to pH 6.0-8.5), water d / and.

5 ml – bottles (1) complete with plug-pipette – packs cardboard.
5 ml – bottles (1) complete with a cover-dropper – packs cardboard.

Spray nazalynыy dozirovannыy 0.25 mg / 1 dose as a colorless, a transparent liquid; tolerance characteristic odor.

Excipients: sodium chloride, benzalkonium chloride, sodium hydroxide solution 1 M (to pH 6.0-8.5), water d / and.

3 ml – bottles with a dosing device (1) – packs cardboard.
5 ml – bottles with a dosing device (1) – packs cardboard.
10 ml – bottles with a dosing device (1) – packs cardboard.

Spray nazalynыy dozirovannыy 0.5 mg / 1 dose as a colorless, a transparent liquid; tolerance characteristic odor.

Excipients: sodium chloride, benzalkonium chloride, Sodium hydroxide 1 M (to pH 6.0-8.5), water d / and.

3 ml – bottles with a dosing device (1) – packs cardboard.
5 ml – bottles with a dosing device (1) – packs cardboard.
10 ml – bottles with a dosing device (1) – packs cardboard.

Pharmacological action

Immunosuppressant. Synthetic peptide, consisting of D-amino acids (Glutamic acid and Tryptophan), γ-connected by a peptide bond. It inhibits the reaction of the humoral and cellular immunity. Reversibly reduces the total number of lymphocytes in peripheral blood, It causes a proportional reduction, as a helper, and suppressors. It suppresses colony formation and entry of stem cells - the precursors of blood formation in the S-phase.

Reduces the number of activation markers on lymphocytes, suppresses T cell proliferation.

Timodepressin^® inhibits spontaneous production of tumor necrosis factor α (FNOα), It increases the production of interleukin 7, It does not affect the production of interleukin 1.

Timodepressin^® reduces the overreaction “graft-versus-host disease” (GVHD), and 90% reduces chronic GVHD when administered thymodepressin^® donors and recipients, It promotes faster and cooperative exit healthy precursor cells in the proliferative phase and recovery leykopoeza.

Timodepressin^® non-toxic, effective in low doses and is characterized by wide therapeutic dose range.

Pharmacokinetics

Absorption

At intranasal absorption occurs with the use of the nasal mucous membranes. For parenteral administration the absorption of the drug from the injection site occurs. For parenteral administration, the systemic circulation gets about 90% product. When administered intranasally thymodepressin^® bioavailability is at least as 90%. FROM_max in the systemic circulation is achieved through 5 min after parenteral administration.

Distribution

FROM_max in organs and tissues is achieved through 15 minutes after administration. In bone marrow and liver C._max higher than that in the blood 9.5 and 3.45 fold, respectively. The plasma concentration thymodepressin^® above 1.5 times, ie mainly the drug accumulates in the plasma, rather than hemocytes. Through 24 h after administration of the drug concentration thymodepressin^® in the bone marrow and spleen reached 16% of that of the C_max in the brain - 41.6%, indicating a slower elimination of the drug from these organs.

Metabolism and excretion

The drug is metabolized in the 70% liver. Excretion thymodepressin^® It occurs in the urine (55- 59%), as well as in the faeces (13 – 19%). T_1/2 is about 14 no. The drug is completely eliminated within 24 hours and does not accumulate in the body.

Testimony

Treatment and prevention of recurrence of various autoimmune diseases both as monotherapy, and as part of combination therapy in adults and children 2 and older:

- Chronic recurrent dermatoses: psoriasis, pemphigus, atopic dermatitis, eczema, symptomatic treatment of T-cell lymphomas skin, Limited scleroderma;

- Autoimmune connective tissue disease: incl. rheumatoid arthritis; syndrome secondary to rheumatoid background lymph and other tumors;

- Hematologic diseases: autoimmunnaya gemoliticheskaya anemia, idiopaticheskaya trombotsitopenicheskaya purpura, two- and trehrostkovye cytopenia, incl. secondary to lymphocytic lymphoma and chronic lymphocytic leukemia.

Other indications:

- In cytostatic chemotherapy- and radiation therapy for the protection and preservation of the stem cells and accelerate the release of granulocytopenia;

- For the prevention of graft rejection in the transplantation of organs and tissues;

- For the prevention of graft rejection during transplantation of bone marrow.

Dosage regimen

Solution for i / m administration and nasal drops

Psoriasis

Timodepressin^® injected i / m 1-2 ml daily for 7-10 days, followed by a 2-day break, Further re-spend 7-10 day cycle of administration. Depending on the clinical situation can be carried out by 3 to 5 cycles. Repeated cycles can be carried out before 5 time.

Intranasal thymodepressin^® appointed adult predominantly as maintenance therapy and prevention of relapse, and children treatment. Preparation in the form of nasal drops are administered 1-2 ml in each nostril for 10-14 days.

At generalized erythrodermic psoriasis Timodepressin^® appoint / m 2 ml daily for 14 days, then 14 days intranasally with simultaneous addition of GCS in moderate doses (40-60 mg prednisolone).

Atopic dermatitis

Timodepressin^® injected i / m 1-2 ml daily for 7-14 days, treatment may be extended after a 2-day break. The duration of the courses and their number is determined by the clinical and morphological characteristics of the disease.

Intranasal drug prescribed adult predominantly as maintenance therapy and prevention of relapse or children treatment. Babies appoint 1-2 ml nasal drops in each nostril for 7 days, followed by a 2-day break and repeat the 7-day course

Eczema

Timodepressin^® injected i / m 1-2 ml daily for 10 days followed by a break for 2-5 days, Further re-conducted 10-day course.

Intranasal drug prescribed adult predominantly as maintenance therapy and prevention of relapse or children to treatment. Babies appoint 1-2 ml nasal drops in each nostril for 10 days, followed by 2-5 day break and repeat the 10-day course.

T-cell lymphoma of the skin

The drug is introduced into / m 2 ml solution every three 7-day course with a 5-day break on the background of corticosteroids in high doses (30-40 mg prednisolone).

Pemphigus

The drug is used for different varieties of pemphigus in treatment with corticosteroids. Timodepressin^® appoint / m 1 ml daily for 2 weeks in combination with prednisolone (60-80 mg / day). Through 7-10 days after start of treatment the daily dosage of prednisolone is reduced by 1/3 followed by gradual reduction of the dose of prednisolone (on 5 mg every 4-5 days). If necessary, keep a maintenance dose of prednisolone (5 mg / day).

Rheumatoid arthritis

Timodepressin^® injected i / m 1-3 ml daily for 7-14 days, then 2 times a week. Course of treatment 16 weeks.

Intranasal thymodepressin^® administered mostly as maintenance therapy and prevention of relapse – by 1-2 ml nasal drops in each nostril for 5-10 days, then 2 times a week.

Hematologic Disorders

The treatment regimen selected individually.

Application after cytostatic therapy

To reduce myelotoxic action of cytostatic therapy Timodepressin^® injected i / m 1-2 ml daily for 5-7 days. The introduction of the drug is started 24-48 hours before the first course of cytotoxic chemotherapy – 1-It is 2-e vvedenie; 3-ie the introduction of produce 12 hours before chemotherapy. Further, depending on the duration of the course of chemotherapy, the drug continues to be administered daily to / m 1-2 ml 1 time / day. Key Performance Indicator – the number of white blood cells and granulocytes for 3 the day before the start of the next course of cytostatic therapy. The drug can be administered intranasally 1-2 ml nasal drops in each nostril, or fractional – by 0.5 ml in each nostril 2-3 times / day, starting over 24-48 hours prior to the first course of chemotherapy.

Timodepressin^® indicated for use prior courses of chemotherapy, having a duration of not more than 2 weeks and breaks at least 2 weeks. During long-term continuous administration of cytostatic schemes its use impractical.

When recurrent course of primary and secondary autoimmune cytopenias Timodepressin^® It recommended as a first injection 2 exchange rate, then at the positive effect a transition for course use of the drug intranasally for a few months to stabilize the process.

With little effect from the first courses of the drug is recommended to increase the daily dose 2-3 times and to reduce the break between courses to 7 days. After reaching effect it is necessary to carry out supporting exchange treatment, during which the dose can be reduced, a break between courses to increase.

In severe recurrent course Timodepressin^® administered in combination with cytostatic immunosuppressive, dose which decreases 2 times, and when the effect of cytotoxic immunosuppressants canceled.

Dosage regimen in pediatric patients. Children aged 2 to 12 years Timodepressin^® appoint / m 0.5-1 ml solution for i / m administration or intranasally 0.5-1 ml nasal drops in each nostril 1 times / day for 7-10 days, then make a break 2 day and, if necessary, repeat rate. Carrying out of 1 to 5 rates.

Children over 12 years Timodepressin^® appoint / m 1-2 ml solution for i / m administration or intranasally 1-2 ml nasal drops each nozdryu1 times / day for 7-10 days, then make a break 2 day and then spend more 1-2 Course on 7-10 days.

Spray nazalynыy dozirovannыy

Psoriasis

Intranasal thymodepressin^® appointed adult predominantly as maintenance therapy and prevention of relapse, and children treatment. The drug is administered by 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril daily for 7-10 days, treatment may be extended after 2- day break.

At generalized erythrodermic psoriasis Timodepressin^® appoint / m 2 ml daily for 14 days, then for 14 days intranasally with simultaneous addition of GCS in moderate doses.

Atopic dermatitis

Timodepressin^® administered intranasally 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril daily for 7-14 days, treatment may be extended after a 2-day break. The duration of the courses and their number is determined by the clinical and morphological characteristics of the disease.

Eczema

The drug is prescribed for 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril daily for 10 days followed by a break for 2-5 days, then re-conducted 10-day course.

Rheumatoid arthritis

The drug is mostly used intranasally as maintenance therapy and prevention of relapse – by 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril daily for 7-14 days, then 2 times a week 1-2 dose, treatment of 16 weeks.

Hematologic Disorders

The treatment regimen selected individually.

Application after cytostatic therapy

To reduce myelotoxic action of cytostatic therapy Timodepressin^® intranasally administered daily for 5-7 days 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril or by fractional 1 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in one nostril 2-3 times / day.

The introduction of the drug is started 24-48 hours before the first course of cytotoxic chemotherapy – 1-It is 2-e vvedenie; 3-ie the introduction of produce 12 hours before chemotherapy. Further, depending on the duration of the course of chemotherapy, drug use 1 times / day for 2-5 days. Key Performance Indicator – the number of white blood cells and granulocytes for 3 the day before the start of the next course of cytostatic therapy.

Timodepressin^® indicated for use prior courses of chemotherapy, having a duration of not more than 2 weeks and breaks at least 2 weeks. During long-term continuous administration of cytostatic schemes its use impractical.

When recurrent course of primary and secondary autoimmune cytopenias Timodepressin^® It recommended as a first injection 2 exchange rate, then at the positive effect a transition for course use of the drug intranasally for a few months to stabilize the process.

With little effect from the first courses of the drug is recommended to increase the daily dose 2-3 times and to reduce the break between courses to 7 days. After reaching effect it is necessary to carry out supporting exchange treatment, during which the dose can be reduced, a break between courses to increase.

In severe recurrent course Timodepressin^® administered in combination with cytostatic immunosuppressive, dose which decreases 2 times, and when the effect of cytotoxic immunosuppressants canceled.

Dosage regimen in pediatric patients. Children aged 2 to 12 years Timodepressin^® administered intranasally 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril 1 times / day for 7-10 days, then make a break 2 day and, if necessary, repeat rate. Carrying out of 1 to 5 rates.

Children over 12 years Timodepressin^® administered intranasally 1-2 dose (0.25 mg / dose or 0.5 mg / dose) nasal spray in each nostril 1 times / day for 7-10 days, then make a break 2 day and then spend more 1-2 Course on 7-10 days.

Side effect

From the hematopoietic system: after the second course of treatment thymodepressin^® possible transient reduction in the number of white blood cells with preservation of peripheral blood leukocyte.

Other: allergic reactions.

Contraindications

- Uncontrolled hypertension;

- Infectious diseases in the acute stage;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

Pregnancy and lactation

Timodepressin^® contraindicated during pregnancy and lactation (breast-feeding).

Cautions

The drug thymodepressin^®, the results of clinical trials, It can be recommended for use in the treatment of autoimmune thyroiditis – 3 the introduction of cycle 1 ml / m daily for 5 days; cycles are repeated after a two-week break.

Application thymodepressin^®, as well as other immunosuppressants, predisposes to bacterial exacerbation of latent, fungal, parasitic and viral infections. At the first clinical signs of infection, you must assign the appropriate pathogenetic therapy.

Do not appoint thymodepressin^® simultaneously with drugs, providing immunostimulatory effects.

If you notice an unexpected effect of the drug the patient should seek medical advice.

Overdose

Data on drug overdose missing.

Drug Interactions

In a joint application thymodepressin^® It does not reduce the antitumor effect of cytostatics.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, protected from light, at a temperature of from 2 ° to 15 ° C.. Shelf life drift nazalynogo - 2 year; solution for i / m administration and nasal drops – 3 year.