Methotrexate | Methotrexate-Ebeve concentrate for solution for infusions 5000 mg / 50 ml vials 50 ml 1 pc.

Release form

Injection.

Packaging

In a bottle of 5 ml of solution. In the package 1 bottle.

Pharmacological action

Antitumor drug from the group of antimetabolites - analogues of folic acid. Along with antitumor, it has an immunosuppressive effect.

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

Slows down synthesis, DNA repair and cell mitosis (in S-phase). Particularly sensitive to the action of methotrexate are tissues with high cell proliferation: tumor tissue, bone marrow, epithelial cells of the mucous membranes, embryonic cells. When the cell proliferation of malignant tissues is greater than in most normal tissues, methotrexate can lead to impaired growth of malignant tumors without irreversible damage to normal tissue.

The mechanism of action in rheumatoid arthritis is associated with the immunomodulatory and anti-inflammatory effect of the drug and is caused by the induction of apoptosis of rapidly proliferating cells (activated T-lymphocytes, fibroblasts, synoviocytes), inhibition of the synthesis of anti-inflammatory cytokines (IL-1, FNO-anti-inflammatory inflammatory cytokines), 4, IK-10 and inhibition of metalloproteinase activity.

In patients with rheumatoid arthritis, the use of methotrexate reduces the symptoms of inflammation (pain, swelling, stiffness), however, there is a limited number of studies with prolonged use of methotrexate (regarding the ability to maintain remission in rheumatoid arthritis).

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

Indications

trophoblastic tumors

acute lymphoblastic and myeloid leukemia

neuroleukemia

non-Hodgkin lkmfoma, including lymphosarcoma

breast cancer, lung carcinoma, squamous cell carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, carcinoma of the lung, cervical cancer, renal carcinoma, pulmonary carcinoma, pulmonary carcinoma, renal carcinoma, lung cancer bladder cancer, testicular cancer, ovarian cancer, penile cancer, retinoblastoma, medulloblastoma

osteogenic sarcoma and soft tissue sarcoma

fungal mycosis (advanced stages)

severe forms of psoriasis, psoriatic arthritis, rheumatoid arthritis, dermatomyositis, SLE, ankylosing spondylitis (with standard therapy ineffective).

Contraindications

Severe anemia, leukopenia, neutropenia, thrombocytopenia

renal failure

liver failure

pregnancy

breastfeeding period

hypersensitivity to or to any other drug.

Caution: the drug should be used for ascites, effusions in the pleural cavity, gastric ulcer and duodenal ulcer, ulcerative colitis, dehydration, gout or nephrolithiasis in the anamnesis, previous radiation therapy or chemotherapy, infectious diseases of a viral, fungal or bacterial nature.

Use during pregnancy and lactation

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

Men and women of childbearing age should be treated with reliable methods of contraception during treatment with methotrexate and for at least 3 months after.

Composition of

1 vial contains:

Active substance: methotrexate 5000 mg.

Excipients: sodium hydroxide - 880.9 mg, water d / i - 46469.1 mg.

Dosage and administration of

methotrexate is part of many chemotherapeutic regimens, and therefore, when choosing the route of administration, regimen and doses in each individual case should be guided by the data of special literature.

Methotrexate-Ebeve for injection may be given i.v., i.v., i.v. or intrathecal. Methotrexate-Ebeve tablets should be taken orally before meals, without chewing.

In trophoblastic tumors - 15-30 mg orally or IM daily for 5 days with an interval of? 1 week (depending on signs of toxicity). Or 50 mg once every 5 days with an interval of? 1 month. Treatment courses are usually repeated 3 to 5 times to a total dose of 300-400 mg.

For solid tumors in combination with other antitumor drugs - 30-40 mg / m2 iv in a jet once a week.

With leukemia or lymphoma - 200-500 mg / m2 by iv infusion once every 2-4 weeks.

In case of neuroleukemia - 12 mg / m2 intrathecal for 15-30 seconds 1 or 2 times a week.

In the treatment of children, the dose is selected depending on age:

for children under 1 year of age is prescribed 6 mg

for children under 1 year of age - 8 mg

for children under 2 years of age - 10 mg

for children over 3 years of age - 12 mg.

Before administration, cerebrospinal fluid should be removed in a volume approximately equal to the volume of the drug that is to be administered.

When using high-dose therapy - from 2 to 15 g / m2 in the form of a 4-6-hour intravenous infusion with an interval of 1-5 weeks with mandatory subsequent administration of calcium folinate, which usually begins 24 hours after the start of methotrexate infusion and is administered every 6 hours at a dose of 3-40 mg / m2 (usually 15 mg / m2) and higher depending on the concentration of methotrexate in serum for 48-72 hours.

With rheumatoid arthritis, the initial dose is usually 7.5 mg once a week, which is administered at the same time in / in, / m or inside - 2.5 mg every 12 hours (3 doses in total). The day the optimum effect is achieved, the weekly dose can be increased, but it should not exceed 20 mg. When an optimal clinical effect is achieved, a dose reduction should be started until the lowest effective dose is achieved. The optimal duration of therapy is not known.

For psoriasis by mouth, intramuscularly or intravenously in doses of 10 to 25 mg per week. The dose is usually increased gradually, when the optimal clinical effect is achieved, a dose reduction is started until the lowest effective dose is reached.

With mushroom mycosis i / m 50 mg once a week or 25 mg 2 times a week or orally 2.5 mg / day for several weeks or months. Dose reduction or withdrawal of the drug is determined by the patient's response and hematological parameters.

Side effects of

From the hemopoietic system: leukopenia, neutropenia, lymphopenia (especially T-lymphocytes), thrombocytopenia, anemia.

From the digestive system: anorexia, nausea, vomiting, stomatitis, gingivitis, glossitis, pharyngitis rarely - enteritis, diarrhea, ulcerative gastrointestinal lesions, gastrointestinal bleeding in some cases (with prolonged daily use) - impaired liver function, increased activity of hepatic transaminases, periportal fibrosis and cirrhosis of the liver, liver necrosis, fatty degeneration of the liver, pancreatitis.

From the side of the central nervous system and peripheral nervous system: encephalopathy (with the introduction of multiple doses intrathecal, radiotherapy in the skull area), fatigue, weakness, confusion, ataxia, tremor, irritation, cramps, coma with intrathecal methotrexate - dizziness, blurred vision, headache, back pain, stiff neck, cramps, paralysis, hemiparesis.

From the respiratory system: rarely - interstitial pneumonitis, pulmonary fibrosis, exacerbation of pulmonary infections.

From the urinary system: cystitis, nephropathy, impaired renal function (increased creatinine, hematuria).

From the reproductive system: violation of the process of oogenesis, spermatogenesis, decreased libido / impotence, a change in fertility, teratogenic effects.

From the sensory organs: conjunctivitis, excessive lacrimation, cataracts, photophobia, cortical blindness (when used in high doses), impaired vision.

Dermatological reactions: skin erythema and / or rash, pruritus, telangiectasia, furunculosis, depigmentation or hyperpigmentation, ointment, peeling of the skin, folliculitis, alopecia (rarely), exacerbation of radiation dermatitis.

Allergic reactions: fever, chills, rash, urticaria, anaphylaxis, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), photosensitivity.

Other: immunosuppression (decreased resistance to infectious diseases), malaise, osteoporosis, hyperuricemia, vasculitis, arthralgia / myalgia.

Drug Interaction

When co-administered with high doses of methotrexate with various NSAIDs (including aspirin and other salicylates, azaproxone, dichlofenac, indomethacin, and ketoprofen), methotrexate toxicity may be increased. In some cases, severe toxic effects, sometimes even fatal, are possible. The use of methotrexate in low doses (7.5-15 mg per week), in particular in the treatment of rheumatoid arthritis, in combination with NSAIDs is not contraindicated, subject to special precautions and appropriate monitoring. srdl sr srl at the same time as sulfanilamide, sulfonylurea, phenytoin, phenylbutazone, aminobenzoic acid, probimetric, trimethoprim, chlorophyll, Antibiotics poorly absorbed from the gastrointestinal tract (including tetracyclines, chloramphenicol), reduce the absorption of methotrexate and impair its metabolism due to the suppression of normal intestinal microflora.

When used with methotrexate, retinoids, azathioprine, and sulfasalazine increase the risk of hepatotoxicity. Parenteral use of acyclovir against the background of intrathecal administration of methotrexate increases the risk of neurological disorders.

With the simultaneous use of methotrexate with multivitamin preparations containing folic acid or its derivatives, the effectiveness of methotrexate therapy may be reduced.

L-asparaginase is a methotrexate antagonist.

Anesthesia with dinitrogen oxide on methotrexate therapy can lead to the development of unpredictable severe myelosuppression and stomatitis.

When used with methotrexate, amiodarone may promote skin ulceration.

Methotrexate reduces the clearance of theophylline.

Several patients with psoriasis or fungal mycosis receiving methotrexate in combination with PUVA therapy (methoxalene and UFO) have been diagnosed with skin cancer.

Caution should be exercised when administering erythrocyte mass and methotrexate.

Combination of methotrexate therapy with radiotherapy may increase the risk of soft tissue necrosis.

Methotrexate may reduce the immunological response to vaccination while co-administration with a live vaccine may produce severe antigenic reactions.

overdose

Treatment: Immediately, preferably within the first hour, the introduction of a specific antidote - folinate calcium at a dose equal to or greater than methotrexate should be given, subsequent doses should be administered as needed, depending on the serum methotrexate concentration. To prevent the precipitation of methotrexate and / or its metabolites in the renal tubules, hydration and alkalinity of the urine are performed.

In case of overdose with intrathecal administration, repeated lumbar punctures should be performed immediately to ensure rapid drainage of cerebrospinal fluid. Neurosurgical intervention with ventriculolumbar perfusion is possible. All of these procedures should be performed against the background of intensive maintenance therapy and systemic administration of high-dose folinate calcium.

Storage conditions

Keep out of the reach of children, protected from light at a temperature not exceeding 25 РC.

Expiration

3 years.

Active ingredient

Methotrexate

Conditions of supply of

Pharmacy Prescription

dosage form

dosage form

infusion solution