Methotrexate - instructions for use, analogs, testimonials and release forms (tablets 2.5 mg, 5 mg and 10 mg, injections in ampoules for Ebewe injection) of a medicament for the treatment of rheumatoid arthritis, psoriasis in adults, children and pregnancy

In this article, you can read the instructions for using the drug Methotrexate. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of physicians specialists on the use of Methotrexate in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Methotrexate in the presence of existing structural analogues.Use for the treatment of rheumatoid arthritis, psoriasis, lymphoblastic leukemia in adults, children, as well as during pregnancy and lactation.

Methotrexate - antitumor, cytostatic agent of the group of antimetabolites, inhibits dihydrofolate reductase, which participates in the reduction of dihydrofolic acid into tetrahydrofolic acid (the carrier of carbon fragments necessary for the synthesis of purine nucleotides and their derivatives).

It inhibits synthesis, DNA repair and cellular mitosis. Especially sensitive to the action of rapidly proliferating tissues: cells of malignant tumors, bone marrow, embryonic cells, epithelial cells of the intestinal mucosa, urinary bladder, oral cavity. Along with the antitumor has an immunosuppressive effect.

Composition

Methotrexate + excipients.

Pharmacokinetics

Absorption from the digestive tract during ingestion depends on the dose: when taken 30 mg / m2 absorbed well, the average bioavailability is 50%. Absorption decreases when taken in doses> 80 mg / m2 (probably due to saturation). Food slows the absorption of methotrexate.When taken at therapeutic doses, regardless of the route of administration, methotrexate practically does not penetrate the blood-brain barrier (BBB) ​​(after intrathecal injection in the cerebrospinal fluid, high concentrations are achieved). Excreted in breast milk. After ingestion, methotrexate is partially metabolized by intestinal flora, the bulk - in the liver (regardless of the route of administration) to form a pharmacologically active polyglutamine form, inhibiting dihydrofolate reductase and thymidine synthesis. It is excreted unchanged mainly with urine by glomerular filtration and tubular secretion (with intravenous administration 80-90% is excreted within 24 hours), with bile is excreted up to 10% (followed by reabsorption in the intestine). With repeated administration, it accumulates in tissues in the form of metabolites.

Indications

• trophoblastic tumors;
• acute lymphoblastic and myeloblastic leukemia;
• Neuroleukemia;
• Non-Hodgkin's lymphoma, including lymphosarcomas;
• cancer of the breast, squamous cell carcinoma of the head and neck, lung cancer, skin cancer, cervical cancer, vulvar cancer, esophageal cancer, kidney cancer, bladder cancer, testicular cancer, ovarian cancer, penile cancer, retinoblastoma, medulloblastoma;
• osteogenic sarcoma and soft tissue sarcomas;
• mushroom mycosis (far advanced stages);
• severe forms of psoriasis, psoriatic arthritis, rheumatoid arthritis, dermatomyositis, SLE, ankylosing spondylitis (if standard therapy is ineffective).

Forms of release

Tablets 2.5 mg, 5 mg and 10 mg.

Solution for injection 10 mg (injections in ampoules for injection).

Concentrate for the preparation of a solution for infusions (imported by Ebwe Austria).

Instructions for use and dosage

Methotrexate is part of many chemotherapy regimens, therefore, when choosing the route of administration, regimen and dosage in each individual case, one should be guided by the literature data.

Methotrexate for injection can be administered intramuscularly, intravenously, intra-arterially or intrathecally. Tablets Methotrexate should be taken orally before eating, without chewing.

When trophoblastic tumors - 15-30 mg orally, / im, daily for 5 days with an interval of more than 1 week (depending on the signs of toxicity). Either 50 mg once every 5 days with an interval of more than 1 month. Treatment rates are usually repeated 3 to 5 times to a total dose of 300-400 mg.

With solid tumors in combination with other antitumor drugs - 30-40 mg / m2 iv in struyno 1 time per week.

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

With neiroleukemii - 12 mg / m2 intrathecally for 15-30 seconds 1 or 2 times a week.

In the treatment of children, the dose is selected depending on the age: children under the age of 1 year are prescribed 6 mg, children aged 1 year 8 mg, children 2 years 10 mg, children over 3 years 12 mg.

Before administration, it is necessary to remove cerebrospinal fluid in a volume approximately equal to the volume of the drug to be injected.

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

In rheumatoid arthritis, the initial dose is usually 7.5 mg once a week, which is administered concomitantly iv, in / m or inside - 2.5 mg every 12 hours (3 doses in total).The day of achieving the optimal effect, a weekly dose can be increased, but it should not exceed 20 mg. When the optimal clinical effect is achieved, the dose should be reduced before reaching the lowest effective dose. The optimal duration of therapy is not known.

With psoriasis inside, intramuscularly or intravenously strontaneously at doses of 10 to 25 mg per week. The dose is usually increased gradually, when the optimal clinical effect is achieved, a dose reduction begins before the lowest effective dose is reached.

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

Side effect

• leukopenia, neutropenia, lymphopenia (especially T-lymphocytes), thrombocytopenia, anemia;
• anorexia;
• nausea, vomiting;
• stomatitis;
• gingivitis;
• glossitis;
• pharyngitis;
• enteritis;
• diarrhea;
• izrozivno-ulcerative lesions of the gastrointestinal tract;
• gastrointestinal bleeding;
• periportal fibrosis and cirrhosis;
• necrosis of the liver;
• fatty degeneration of the liver;
• encephalopathy (with the introduction of multiple doses intrathecally, the conduct of radiation therapy in the skull);
• fatigue;
• weakness;
• confusion of consciousness;
• tremor;
• irritability;
• convulsions;
• coma;
• pain in the back;
• stiff neck;
• paralysis;
• interstitial pneumonitis;
• fibrosis of the lungs;
• exacerbation of pulmonary infections;
• cystitis;
• nephropathy;
• violation of the process of oogenesis, spermatogenesis;
• decreased libido;
• impotence;
• change in fertility;
• teratogenic effects;
• conjunctivitis;
• excessive lacrimation;
• cataract;
• photophobia;
• cutaneous erythema and / or rash;
• itching;
• furunculosis;
• depigmentation or hyperpigmentation;
• acne (pimples);
• skin peeling;
• folliculitis;
• alopecia (rarely);
• rash;
• hives;
• anaphylaxis;
• malignant exudative erythema (Stevens-Johnson syndrome);
• toxic epidermal necrolysis (Lyell's syndrome);
• photosensitization;
• immunosuppression (reduction of resistance to infectious diseases);
• osteoporosis;
• vasculitis.

Contraindications

• severe anemia, leukopenia, neutropenia, thrombocytopenia.
• kidney failure;
• liver failure;
• pregnancy;
• the period of breastfeeding;
• increased sensitivity to methotrexate and / or any other component of the drug.

Application in pregnancy and lactation

Contraindicated use of the drug during pregnancy and during breastfeeding.

Men and women of childbearing age should be treated with methotrexate and at least 3 months afterwards, reliable methods of contraception should be used.

special instructions

Caution should be exercised when using methotrexate.

Dosage forms containing preservatives (benzyl alcohol), can not be used for intrathecal administration and for high-dosage therapy.

When high doses of methotrexate are administered, careful monitoring of the patient is required to detect early signs of toxic reactions early.

High-dose therapy should be performed only by experienced chemotherapists who can monitor the concentration of methotrexate in blood plasma under steady conditions under the cover of calcium folinate.

During therapy with methotrexate in elevated and high doses, the pH of the patient's urine should be monitored: on the day of administration and for the next 2-3 days, the urine reaction should be alkaline.This is achieved by / in the drip introduction of a mixture consisting of 40 ml of 4.2% sodium hydrogen carbonate solution and 400-800 ml isotonic sodium chloride solution, on the day before, on the day of treatment and in the next 2-3 days.

Treatment of methotrexate in high and high doses should be combined with increased hydration - up to 2 liters per day.

The administration of methotrexate in a dose greater than 2 g / m3 should be carried out under the control of its concentration in serum. Normal decrease in the content of methotrexate in the blood serum after 22 hours after the introduction of 2 times compared with the baseline. Increasing the level of creatinine by more than 50% of the original content and / or increasing the level of bilirubin requires intensive detoxification therapy.

For the treatment of psoriasis, methotrexate is prescribed only to patients with severe disease that does not respond to other therapies.

To prevent toxicity during treatment with methotrexate, a blood test (once a week) should be performed periodically, leukocyte and platelet counts determined, and liver and kidney functional tests performed.

With the development of diarrhea and ulcerative stomatitis, methotrexate therapy should be interrupted to avoid the development of hemorrhagic enteritis and the death of the patient due to perforation of the intestine.

In patients with impaired liver function, the period of excretion of methotrexate is increased, so the drug should be treated with extreme caution, with lower doses.

Impaired renal function is dose dependent. The risk of impairment is elevated in patients with reduced renal function or dehydration, as well as in patients taking other nephrotoxic drugs.

Impact on the ability to drive vehicles and manage mechanisms

Some of the side effects of the drug may adversely affect the ability to drive and perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

With the simultaneous use of high doses of methotrexate with various non-steroidal anti-inflammatory drugs (NSAIDs) (including Aspirin and other salicylates, azaprene, diclofenac, Indomethacin and ketoprofen), the toxicity of methotrexate may be increased. In some cases, a potentially toxic effect is possible, sometimes even with a fatal outcome. With special precautions and appropriate monitoring, 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.

When used simultaneously with sulfonamides, sulfonylurea derivatives, phenytoin, phenylbutazone, aminobenzoic acid, probenecid, pyrimethamine or trimethoprim, a number of antibiotics (including penicillin, tetracycline, chloramphenicol), indirect anticoagulants and lipid lowering drugs (colestyramine) increase the toxicity of methotrexate. Antibiotics, poorly absorbed from the digestive tract (including tetracyclines, chloramphenicol), reduce the absorption of methotrexate and disrupt its metabolism due to suppression of normal intestinal microflora.

With simultaneous use with methotrexate, retinoids, azathioprine, Sulfasalazine increase the risk of hepatotoxicity. Parenteral use of Acyclovir against the background of intrathecal administration of methotrexate increases the risk of developing 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.

Conduction of anesthesia with the use of dinitrogen oxide on the background of methotrexate therapy can lead to the development of unpredictable severe myelosuppression and stomatitis.

When used simultaneously with methotrexate, Amiodarone may promote skin ulceration.

Methotrexate reduces the clearance of theophylline.

Several patients with psoriasis or fungal mycosis who were treated with methotrexate in combination with PUVA therapy (metoxalen and UFD) were diagnosed with skin cancer.

Caution should be exercised with the simultaneous use of erythrocyte mass and methotrexate.

The combination of methotrexate therapy with radiotherapy can increase the risk of soft tissue necrosis.

Methotrexate may reduce the immunological response to vaccination; With simultaneous administration of the drug with live vaccine, severe antigenic reactions can develop.

Analogues of the drug Methotrexate

Structural analogs for the active substance:

• Vero Methotrexate;
• Zexate;
• The methodical;
• Methotrexate (Emtexate);
• Methotrexate for injection;
• Lathema Methotrexate;
• Methotrexate sodium;
• Methotrexate LENS;
• Methotrexate Teva;
• Methotrexate Ebewe;
• Treksan;
• Evetrex.

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