Methotrexate - Teva solution for injection 25mg / ml, 2 ml No. 1 bottle

Trophoblastic tumors;

acute leukemias (especially lymphoblastic and myeloblastic variants);

neuroleukemia;

non-Hodgkin's lymphomas (including lymphosarcoma);

breast cancer, squamous cell carcinoma of the head and neck, lung cancer, skin cancer, cervical cancer, vulvar cancer, esophageal cancer, bladder cancer, testicular cancer, ovarian cancer, penile cancer, retinoblastoma, medulloblastoma;

osteosarcoma and soft tissue sarcoma;

fungal mycosis (advanced stages);

Severe psoriasis

psoriatic arthritis,

rheumatoid arthritis,

juvenile chronic arthritis,

dermatomyositis,

systemic lupus erythematosus,

ankylosing spondylitis (with the ineffectiveness of standard therapy).

Methotrexate for injection can be administered intramuscularly, intravenously, intraarterially, or intrathecally.

Set individually, depending on the indications and stage of the disease, the state of the hematopoietic system, the scheme of anticancer therapy.

The following dosage regimens are used:

Trophoblastic tumors: 15-30 mg intramuscularly, daily for 5 days at intervals of one or more weeks (depending on signs of toxicity). Or 50 mg once every 5 days with an interval of at least 1 month. The courses of treatment are usually repeated 3 to 5 times up to a total dose of 300-400 mg.

Solid tumors: in combination with other anticancer drugs 30-40 mg / m2 intravenously, once a week.

Leukemias and lymphomas: 200-500 mg / m2 by intravenous infusion every 2-4 weeks. Neuroleukemia: 12 mg / m2 intrathecally for 15-30 seconds 1 or 2 times a week. When treating children, the dose is selected depending on the age of the child: children under the age of 1 year are prescribed 6 mg, children aged 1 year - 8 mg, children aged 2 - 10 mg, children aged 3 and older - 12 mg. Before administration, cerebrospinal fluid should be removed in a volume approximately equal to the volume of the drug to be administered.

High-dose therapy: from 2 to 15 g / m2 as a 4-6 hour intravenous infusion with an interval of 1-5 weeks, with the obligatory subsequent administration of calcium folinate, which usually begins 24 hours after the start of the methotrexate infusion and is administered every 6 hours at a dose of 3 -40 mg / m2 (usually 15 mg / m2) and more depending on the concentration of methotrexate in the blood serum for 48-72 hours (see instructions for use of calcium folinate).

Rheumatoid arthritis: The starting dose is usually 7.5 mg once a week, which is given simultaneously intravenously or intramuscularly, or 2.5 mg every 12 hours (3 doses in total). To achieve optimal effect, the weekly dose can be increased, while it should not exceed 20 mg. When the optimal clinical effect is achieved, dose reduction should be started until the lowest effective dose is reached. The optimal duration of therapy is not known.

Psoriasis : intramuscular or intravenous injection in doses of 10-25 mg per week. The dose is usually increased gradually, when the optimal clinical effect is achieved, the dose is reduced until the lowest effective dose is reached.

Fungal mycosis : intramuscular injection of 50 mg 1 time per week or 25 mg 2 times a week for several weeks or months. Reducing the dose or canceling the administration of the drug is determined by the patient's response and hematological parameters.

1 ml solution for injection contains:

active substance:

methotrexate 2.50 mg / 25.0 mg;

Excipients:

sodium chloride 8.5 mg / 6.0 mg,

sodium hydroxide about 0.44 mg / about 4.4 mg,

water for injection up to 1 ml / up to 1 ml.

Hypersensitivity to methotrexate;

severe renal failure;

severe liver failure;

alcohol abuse;

a history of disorders of the hematopoietic system (in particular, bone marrow hypoplasia, leukopenia, thrombocytopenia, or clinically significant anemia);

immunodeficiency;

severe acute and chronic infectious diseases such as tuberculosis and HIV infection;

concomitant vaccination with live vaccines;

oral ulcers, gastrointestinal ulcers in the active phase;

simultaneous use of methotrexate at a dose of 15 mg / week. with acetylsalicylic acid;

pregnancy;

period of breastfeeding.

Carefully:if patients have impaired liver and kidney function, diabetes mellitus, obesity, previous therapy with hepatotoxic drugs, dehydration, ascites, inhibition of bone marrow hematopoiesis, pleural or peritoneal effusion, parasitic and infectious diseases of a viral, fungal or bacterial nature - the risk of developing a severe generalized disease ( currently or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amebiasis, strongyloidosis (established or suspected), gout (including history) or urate nephrourolithiasis (including history), infections and inflammation of the oral mucosa, vomiting, diarrhea, gastric ulcer and duodenal ulcer, ulcerative colitis, obstructive gastrointestinal diseases,previous chemotherapy or radiation therapy, asthenia, aciduria (urine pH less than 7), in children and elderly patients.

Latin name:

METHOTREXATE-TEVA

Description:

Transparent, yellow or orange to brown solution.

Composition:

1 ml solution for injection contains:

active substance:

methotrexate 2.50 mg / 25.0 mg;

Excipients:

sodium chloride 8.5 mg / 6.0 mg,

sodium hydroxide about 0.44 mg / about 4.4 mg,

water for injection up to 1 ml / up to 1 ml.

Pharmachologic effect:

Antineoplastic, cytostatic agent of the group of antimetabolites - analogs of folic acid.

Inhibits dihydrofolate reductase, which is involved in the reduction of dihydrofolic acid to tetrahydrofolic acid (carrier of carbon fragments necessary for the synthesis of purine nucleotides and their derivatives).

Inhibits synthesis, DNA repair and cellular mitosis (in the S-phase). Tissues with high cell proliferation are especially sensitive to the action of methotrexate: tumor tissue, bone marrow, epithelial cells of the mucous membranes, embryonic cells.

The mechanism of action in rheumatoid arthritis is associated with the immunomodulatory and anti-inflammatory action of the drug and is due to the induction of apoptosis of rapidly proliferating cells (activated T-lymphocytes, fibroblasts, synoviocytes), inhibition of the synthesis of anti-inflammatory cytokines (interleukin (IL) -1, tumor necrosis factor alpha cytokines IL-4, IL-10 and suppression of the activity of metalloproteinases.

In patients with rheumatoid arthritis, the use of methotrexate reduces the symptoms of inflammation (pain, swelling, stiffness), but there is limited research with long-term use (regarding the ability to maintain remission in rheumatoid arthritis).

In psoriasis, the growth rate of keratinocytes in psoriatic plaques increases compared to normal proliferation of skin cells. This difference in cell proliferation is the basis for the use of methotrexate for the treatment of psoriasis.

Pharmacokinetics:

With intramuscular administration, Cmax of methotrexate in blood plasma is achieved after 30-60 minutes. The systemic absorption of methotrexate after administration under the skin of the abdomen and thigh is the same. After intravenous administration, it is rapidly distributed within a volume equivalent to the total volume of body fluids. The initial Vd is 0.18 l / kg (18% of body weight), the equilibrium volume of distribution is 0.4-0.8 l / kg (40-80% of body weight). 50-60% of methotrexate circulating in the vascular bed is associated with proteins (mainly albumin). Competitive displacement is possible with simultaneous use with sulfonamides, salicylates, tetracyclines, chloramphenicol, phenytoin. Methotrexate does not penetrate the BBB when used in therapeutic doses. A high concentration of methotrexate in the central nervous system can be achieved with intrathecal administration.Methotrexate undergoes hepatic and intracellular metabolism with the formation of a pharmacologically active polyglutamine form, which also inhibits dihydrofolate reductase and thymidine synthesis. Small amounts of polyglutamate methotrexate can remain in tissues for a long period of time. The retention and prolongation of the action of the active metabolites of methotrexate differ depending on the type of cells, tissues and tumors. Average T1 / 2 values ??when using methotrexate at a dose of less than 30 mg / m2 are 6-7 hours. In patients receiving high doses of methotrexate, T1 / 2 is 8-17 hours. In chronic renal failure, both phases of methotrexate elimination can be significantly prolonged ...It is excreted mainly by the kidneys unchanged by glomerular filtration and tubular secretion (with intravenous administration, 80-90% is excreted within 24 hours), up to 10% is excreted with bile (with subsequent reabsorption in the intestine). Methotrexate accumulates in the liver, kidneys and organs over several weeks or months. With repeated administrations, it accumulates in tissues in the form of polyglutamates.

Indications:

Trophoblastic tumors;

acute leukemias (especially lymphoblastic and myeloblastic variants);

neuroleukemia;

non-Hodgkin's lymphomas (including lymphosarcoma);

breast cancer, squamous cell carcinoma of the head and neck, lung cancer, skin cancer, cervical cancer, vulvar cancer, esophageal cancer, bladder cancer, testicular cancer, ovarian cancer, penile cancer, retinoblastoma, medulloblastoma;

osteosarcoma and soft tissue sarcoma;

fungal mycosis (advanced stages);

Severe psoriasis

psoriatic arthritis,

rheumatoid arthritis,

juvenile chronic arthritis,

dermatomyositis,

systemic lupus erythematosus,

ankylosing spondylitis (with the ineffectiveness of standard therapy).

Contraindications:

Hypersensitivity to methotrexate;

severe renal failure;

severe liver failure;

alcohol abuse;

a history of disorders of the hematopoietic system (in particular, bone marrow hypoplasia, leukopenia, thrombocytopenia, or clinically significant anemia);

immunodeficiency;

severe acute and chronic infectious diseases such as tuberculosis and HIV infection;

concomitant vaccination with live vaccines;

oral ulcers, gastrointestinal ulcers in the active phase;

simultaneous use of methotrexate at a dose of 15 mg / week. with acetylsalicylic acid;

pregnancy;

period of breastfeeding.

Carefully:if patients have impaired liver and kidney function, diabetes mellitus, obesity, previous therapy with hepatotoxic drugs, dehydration, ascites, inhibition of bone marrow hematopoiesis, pleural or peritoneal effusion, parasitic and infectious diseases of a viral, fungal or bacterial nature - the risk of developing a severe generalized disease ( currently or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amebiasis, strongyloidosis (established or suspected), gout (including history) or urate nephrourolithiasis (including history), infections and inflammation of the oral mucosa, vomiting, diarrhea, gastric ulcer and duodenal ulcer, ulcerative colitis, obstructive gastrointestinal diseases,previous chemotherapy or radiation therapy, asthenia, aciduria (urine pH less than 7), in children and elderly patients.

Method of administration and dosage:

Methotrexate for injection can be administered intramuscularly, intravenously, intraarterially, or intrathecally.

Set individually, depending on the indications and stage of the disease, the state of the hematopoietic system, the scheme of anticancer therapy.

The following dosage regimens are used:

Trophoblastic tumors: 15-30 mg intramuscularly, daily for 5 days at intervals of one or more weeks (depending on signs of toxicity). Or 50 mg once every 5 days with an interval of at least 1 month. The courses of treatment are usually repeated 3 to 5 times up to a total dose of 300-400 mg.

Solid tumors: in combination with other anticancer drugs 30-40 mg / m2 intravenously, once a week.

Leukemias and lymphomas: 200-500 mg / m2 by intravenous infusion every 2-4 weeks. Neuroleukemia: 12 mg / m2 intrathecally for 15-30 seconds 1 or 2 times a week. When treating children, the dose is selected depending on the age of the child: children under the age of 1 year are prescribed 6 mg, children aged 1 year - 8 mg, children aged 2 - 10 mg, children aged 3 and older - 12 mg. Before administration, cerebrospinal fluid should be removed in a volume approximately equal to the volume of the drug to be administered.

High-dose therapy: from 2 to 15 g / m2 as a 4-6 hour intravenous infusion with an interval of 1-5 weeks, with the obligatory subsequent administration of calcium folinate, which usually begins 24 hours after the start of the methotrexate infusion and is administered every 6 hours at a dose of 3 -40 mg / m2 (usually 15 mg / m2) and more depending on the concentration of methotrexate in the blood serum for 48-72 hours (see instructions for use of calcium folinate).

Rheumatoid arthritis: The starting dose is usually 7.5 mg once a week, which is given simultaneously intravenously or intramuscularly, or 2.5 mg every 12 hours (3 doses in total). To achieve optimal effect, the weekly dose can be increased, while it should not exceed 20 mg. When the optimal clinical effect is achieved, dose reduction should be started until the lowest effective dose is reached. The optimal duration of therapy is not known.

Psoriasis : intramuscular or intravenous injection in doses of 10-25 mg per week. The dose is usually increased gradually, when the optimal clinical effect is achieved, the dose is reduced until the lowest effective dose is reached.

Fungal mycosis : intramuscular injection of 50 mg 1 time per week or 25 mg 2 times a week for several weeks or months. Reducing the dose or canceling the administration of the drug is determined by the patient's response and hematological parameters.

Side effects:

From the digestive system: ulcerative stomatitis, anorexia, gingivitis, pharyngitis, nausea are possible; rarely - diarrhea, melena, enteritis, pancreatitis; in some cases (with prolonged daily use) - liver necrosis, cirrhosis, fatty atrophy, periportal liver fibrosis.

From the hematopoietic system: leukopenia, anemia, thrombocytopenia.

From the side of the central nervous system: feeling tired, dizziness; rarely - headache, aphasia, drowsiness, convulsions.

On the part of the reproductive system: disorders of oogenesis and spermatogenesis, oligospermia, menstrual irregularities, decreased libido, impotence.

From the urinary system: hematuria, cystitis, severe renal dysfunction.

Allergic reactions: chills, decreased resistance to infection; rarely - urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Dermatological reactions: skin rash, photosensitivity, pigmentation disorders, telangiectasia, acne, furunculosis.

Drug interactions:

With simultaneous use with vitamin preparations containing folic acid or its derivatives, the effectiveness of methotrexate may decrease.

ќдновременное применение Ќѕ¬— в высоких дозах может привести к увеличению концентрации метотрексата в плазме и к удлинению периода его выведени¤, а также к увеличению концентрации метотрексата, не св¤занного с альбуминами плазмы, что в свою очередь усиливает токсические эффекты метотрексата (прежде всего на ? “ и систему кроветворени¤).

ѕри одновременном применении с пенициллинами метотрексата (даже в низких дозах) возможно усиление его токсических эффектов.

ѕри одновременном применении с сульфаниламидами, особенно с ко-тримоксазолом, существует риск усилени¤ миелодепрессивного действи¤.

ѕри применении азота закиси у пациентов, получающих метотрексат, возможно развитие т¤желой непредсказуемой миелодепрессии, стоматита.

ѕри одновременном применении с метотрексатом вальпроевой кислоты возможно уменьшение ее концентрации в плазме крови.

 олестирамин св¤зывает метотрексат, уменьшает его энтерогепатическую рециркул¤цию, что приводит к снижению его концентрации в плазме крови.

ѕри одновременном применении с меркаптопурином возможно повышение его биодоступности вследствие нарушени¤ метаболизма при 'первом прохождении' через печень.

Ќеомицин и паромомицин уменьшают абсорбцию метотрексата из ? “.

” пациентов, получающих омепразол, возможно повышение концентрации метотрексата в плазме крови.

ѕри одновременном применении с пробенецидом возможно 3-4 кратное увеличение концентрации метотрексата в плазме крови вследствие уменьшени¤ его почечной экскреции.

ѕри одновременном применении метотрексата с ретиноидами возможно повышение риска гепатотоксического действи¤.

—алицилаты потенцируют действие метотрексата вследствие уменьшени¤ его почечной экскреции.

ѕосле курса лечени¤ тетрациклином метотрексат, примен¤емый даже в низких дозах, может оказывать токсическое действие.

ѕри последовательном введении метотрексата и фторурацила возможен синергизм действи¤; фторурацил, введенный перед метотрексатом, может уменьшать его токсичность.

?исплатин оказывает нефротоксическое действие и поэтому может уменьшать почечную экскрецию метотрексата, что приводит к усилению его токсичности.

¬озможно повышение токсичности при применении циклоспорина у пациентов, получавших метотрексат.

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

Ќекоторые побочные действи¤ препарата могут отрицательно вли¤ть на способность управлени¤ автомобилем и выполнени¤ потенциально опасных видов де¤тельности, требующих повышенной концентрации внимани¤ и быстроты психомоторных реакций.

‘орма выпуска:

–аствор дл¤ инъекций.

”паковка:

In a bottle 2 ml of solution. The package contains 1 bottle.

Storage conditions:

Store in a dark place at a temperature not exceeding 25 ? C.

Shelf life:

2 years.

Terms of dispensing from pharmacies:

On prescription