Methotrexate
Methotrexate: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Drug interactions
- 11. Analogs
- 12. Terms and conditions of storage
- 13. Terms of dispensing from pharmacies
- 14. Reviews
- 15. Price in pharmacies
Latin name: Methotrexate
ATX code: L01BA01
Active ingredient: methotrexate (methotrexate)
Producer: Ebewe Pharma (Austria)
Description and photo update: 2019-16-08
Prices in pharmacies: from 21 rubles.
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Methotrexate is an antineoplastic agent.
Release form and composition
Dosage form - coated tablets (50 pcs. In polymer cans, 1 can in a cardboard box).
The active ingredient is methotrexate, in 1 tablet - 2.5 mg.
Pharmacological properties
Pharmacodynamics
Methotrexate is an antitumor, cytostatic agent belonging to the group of antimetabolites. It inhibits dihydrofolate reductase, which is responsible for the reduction of dihydrofolic acid to tetrahydrofolic acid (a carrier of carbon fragments necessary for the production of purine nucleotides and their derivatives).
Methotrexate slows down cellular mitosis and DNA synthesis and repair. Tissues prone to rapid proliferation are hypersensitive to its action: epithelial cells of the mucous membrane of the oral cavity, bladder, intestines, cells of malignant tumor formations, embryonic cells, bone marrow cells. Besides antitumor, the drug is also characterized by immunosuppressive action.
Pharmacokinetics
When administered orally, the absorption of methotrexate is determined by the size of the dose: when the drug is taken at a dose of 30 mg / m 2, it is absorbed well, and its bioavailability averages 60%.
In pediatric patients diagnosed with leukemia, the absorption of the substance varies from 23% to 95%. The maximum concentration of methotrexate is achieved over a period of time ranging from 40 minutes to 4 hours. Its combination with food intake leads to a decrease in the rate of absorption and a decrease in maximum concentration. The degree of binding to plasma proteins (mainly albumin) reaches approximately 50%.
After distribution in tissues, methotrexate is found in significant concentrations in the kidneys, liver and especially the spleen, passing into the form of polyglutamates. In these organs, the drug can accumulate over several weeks or even months.
When taking methotrexate in the recommended doses, it practically does not penetrate the blood-brain barrier. Found in breast milk.
After oral administration, the drug is partially metabolized with the participation of the intestinal flora, mainly in the liver (regardless of the route of administration). This forms the polyglutamine form of methotrexate, which has pharmacological activity and is an inhibitor of dihydrofolate reductase and thymidine synthesis. In patients receiving methotrexate at a dose of less than 30 mg / m 2, the half-life in the initial phase is 2-4 hours, and in the final phase, which is longer, - 3-10 hours when using small doses and 8-15 hours - when using significant doses of the drug. In patients with chronic renal failure, both phases of methotrexate excretion can be significantly prolonged.
Methotrexate is excreted mainly in the urine unchanged by tubular secretion and glomerular filtration. Up to 10% of the substance is excreted with bile, which is subsequently reabsorbed in the intestine. The elimination of methotrexate in patients with renal dysfunction, severe transudate or ascites is significantly slowed down. With repeated administration, the drug is accumulated in the tissues in the form of polyglutamates.
Indications for use
- Trophoblastic neoplasms;
- Non-Hodgkin's lymphoma, acute lymphoblastic leukemia;
- Severe psoriasis;
- Far advanced stages of fungal mycosis;
- Rheumatoid arthritis (in the absence of the effect of other treatments).
Contraindications
- Severe renal and / or liver dysfunction;
- Hematologic disorders, including bone marrow hypoplasia, leukopenia, thrombocytopenia, anemia;
- Acute form of infectious diseases;
- Immunodeficiency syndrome;
- The period of pregnancy and breastfeeding;
- Age up to 3 years;
- Hypersensitivity to drug components.
According to the instructions, it is recommended to prescribe methotrexate with caution to patients with gastric ulcer and duodenal ulcer, ulcerative colitis, infectious diseases of bacterial, viral or fungal genesis, with pleural effusion, ascites, dehydration, nephrolithiasis or gout in history; against the background of previous radiation or chemotherapy.
Instructions for the use of Methotrexate: method and dosage
Methotrexate tablets are taken orally.
The doctor prescribes the dose and period of treatment based on clinical indications individually, taking into account the chemotherapy regimen.
Recommended dosage:
- Trophoblastic tumors: 15-30 mg once a day for 5 days. The course of treatment is repeated 3 to 5 times with an interval of one or more weeks (taking into account signs of toxicity). In addition, an alternative appointment of 50 mg 1 time in 5 days with a break of 1 month or more is possible, the course provides for the intake of 300-400 mg of the drug;
- Non-Hodgkin's lymphomas (as part of complex therapy): 15-20 mg per 1 m 2 of the patient's body surface once a day, 2 times a week, or 7.5 mg per 1 m 2 1 time per day for 5 days;
- Acute lymphoblastic leukemia (as part of complex therapy): at the rate of 3.3 mg per 1 m 2 in combination with prednisolone. After achieving remission, the dosage regimen can be 15 mg per 1 m 2 2 times a week or 2.5 mg per 1 kg of patient weight every 14 days;
- Psoriasis: 10-25 mg per week, the dose should be increased gradually, after reaching the optimal clinical effect, it begins to be reduced to the level of the lowest effective dose;
- Fungal mycosis: initial dose - 25 mg 2 times a week, depending on the patient's response and hematological parameters, the dose is reduced or the drug is canceled;
- Rheumatoid arthritis: the initial dose is 7.5 mg once a week once or in 3 divided doses with an interval of 12 hours. In order to achieve an optimal clinical effect, an increase in the weekly dose to 20 mg is allowed. After achieving the desired result, it is recommended to gradually reduce the dose to the level of the lowest effective dose. The duration of therapy is determined individually. For children with juvenile chronic arthritis, the dose is determined at the rate of 10-30 mg per 1 m 2 of the child's body surface once a week or 0.3-1 mg per 1 kg of body weight.
Side effects
- Hematopoietic system: thrombocytopenia, anemia (including aplastic), leukopenia, agranulocytosis, neutropenia, eosinophilia, lymphoproliferative diseases, lymphadenopathy, pancytopenia, hypogammaglobulinemia;
- Cardiovascular system: pericardial effusion, pericarditis, decreased blood pressure, thromboembolism (cerebral thrombosis, arterial thrombosis, deep vein thrombosis, thrombophlebitis, retinal vein thrombosis, pulmonary embolism);
- Digestive system: nausea, vomiting, anorexia, stomatitis, pharyngitis, gingivitis, enteritis, erosive and ulcerative lesions and bleeding from the gastrointestinal tract (including melena, haematemesis), pancreatitis, hepatotoxicity (increased activity of liver enzymes, hepatic insufficiency, acute cirrhosis and liver fibrosis, hypoalbuminemia);
- Nervous system: drowsiness, dizziness, headache, hemiparesis, dysarthria, paresis, aphasia, convulsions; against the background of high doses - emotional lability, transient disorder of cognitive functions, encephalopathy (including leukoencephalopathy), unusual cranial sensitivity;
- Organ of vision: visual impairment (including transient blindness), conjunctivitis;
- Respiratory system: rarely - respiratory failure, pulmonary fibrosis, alveolitis, chronic obstructive pulmonary disease (COPD), interstitial pneumonitis (including fatal), symptoms of interstitial pneumonia (potentially dangerous) - shortness of breath, dry cough, fever;
- Skin: itching of the skin, erythematous rash, urticaria, pigmentation disorders, photosensitivity, alopecia, telangiectasia, ecchymosis, exfoliative dermatitis, furunculosis, acne, erythema multiforme (Stevens-Johnson syndrome), skin necrosis and ulceration, toxic epidermal necrolysis with psoriasis - burning of the skin, painful erosive plaques on the skin;
- Urogenital system: cystitis, renal failure or severe nephropathy, proteinuria, azotemia, hematuria, impaired ovo- and spermatogenesis, decreased libido, transient oligospermia, impotence, vaginal discharge, dysmenorrhea, gynecomastia, miscarriage, fetal defects, fetal death, infertility;
- Musculoskeletal system: myalgia, arthralgia, osteoporosis, fractures, osteonecrosis;
- Neoplasms: lymphoma, including reversible;
- Others: excessive sweating, diabetes mellitus, allergic reactions (including anaphylactic shock), allergic vasculitis, soft tissue necrosis, tumor lysis syndrome, sudden death, life-threatening opportunistic infections (including Pneumocystis pneumonia), cytomegalovirus (CMV) infection (including CMV pneumonia), histoplasmosis, nocardiosis, cryptococcosis, sepsis (including fatal), herpes zoster, simple and disseminated herpes.
Overdose
For an overdose of Methotrexate, specific symptoms are not characteristic, therefore it is determined by the level of the active substance of the drug in the blood plasma.
As a treatment, it is recommended to administer a specific antidote - calcium folinate - as soon as possible after taking the drug in high doses, preferably within the first hour. Its dose should be equal to or higher than the corresponding dose of methotrexate. Subsequent doses are given as needed, depending on serum methotrexate levels. In order to avoid precipitation of methotrexate and / or its metabolites in the renal tubules, urine alkalinization and hydration of the body should be carried out, leading to an accelerated excretion of the drug. To minimize the risk of developing nephropathy due to the formation of a precipitate of methotrexate or its metabolites in the urine, it is recommended to additionally determine the pH of the urine before each administration and every 6 hours during the entire period of application of calcium folinate, which is used as an antidote. The introduction of the latter should be continued until the concentration of methotrexate in the plasma decreases to a value not exceeding 0.05 μmol / L and the pH rises to values greater than 7.
special instructions
The cytotoxicity of the drug requires careful handling. The appointment of the drug can only be performed by an experienced specialist. Taking into account the properties and features of the action of Methotrexate, the doctor should inform the patient about the ability of the drug to cause severe and sometimes fatal side effects and the need to comply with a strict treatment regimen to minimize them.
The use of the drug should be accompanied by careful medical supervision for the timely detection of signs of toxic effects, their assessment, and adequate measures.
The appointment should be made on the basis of a complete general blood test with the determination of platelets, a biochemical blood test with the establishment of the activity of liver enzymes, serum albumin, bilirubin, renal function tests, chest X-ray, if necessary, tests for hepatitis and tuberculosis.
Reception of methotrexate should take place under conditions of regular monitoring of the state of the peripheral blood for the content of the number of leukocytes and platelets. During the first month of therapy, the analysis is carried out first every other day, then with an interval of 3-5 days. In the subsequent period - once every 7-10 days, with remission - once every 1-2 weeks. Before each intake of the drug, the mucous surface of the mouth and pharynx is examined for ulceration. It should be checked: systematically - the activity of hepatic transaminases, renal function (creatinine clearance, urea nitrogen), the level of concentration of uric acid in the blood; periodically - fluoroscopic examination of the chest organs. The state of bone marrow hematopoiesis is checked three times (before the start of therapy, during the treatment period, after the completion of the course).
The action of the drug can cause acute or chronic hepatotoxicity, including fibrosis and cirrhosis of the liver. Chronic hepatotoxicity can result from taking a total cumulative dose of 1.5 g or prolonged (2 or more years) methotrexate therapy, and lead to a fatal outcome.
Given the toxic effects of methotrexate on the patient's body, concomitant administration of other hepatotoxic agents should be avoided, except in cases of obvious need.
The degree of the toxic effect of the drug may be due to aggravating concomitant factors, such as obesity, alcoholism, diabetes mellitus and the patient's advanced age.
For an objective assessment of liver function, in addition to biochemical parameters, it is recommended to use liver biopsy data obtained before or after 2-4 months of treatment.
In the case of moderate liver fibrosis or signs of cirrhosis, methotrexate should be discontinued, and when a mild form of fibrosis is diagnosed, it is recommended to repeat the biopsy after 6 months. With minor histological changes in the liver (mild portal inflammation, fatty changes), special care should be taken with further use of the drug.
With ulcerative stomatitis and diarrhea, it is necessary to interrupt therapy with methotrexate because of the high risk of developing hemorrhagic enteritis and perforation of the intestinal wall.
Patients should avoid exposure to direct sunlight and ultraviolet radiation to prevent the development of photosensitivity reactions.
Consideration should be given to the effect of the drug on the immune system during immunological tests and the possible deterioration of the response to vaccination. Therefore, in the period 3-12 months after discontinuation of the drug, the patient is not shown immunization (except for the cases recommended by the doctor), persons living with the patient should cancel the immunization against poliomyelitis. The patient must wear a mask to avoid contact with people who have received the polio vaccine.
During the period of treatment, patients of childbearing age need to use reliable methods of contraception, as well as after the end of therapy - for men for 3 months, for women - for at least one ovulation cycle.
To reduce the toxicity of high doses of methotrexate after a course of treatment, the patient is shown taking calcium folinate.
Due to the effect of the drug on the central nervous system (dizziness, fatigue), patients should refrain from driving vehicles or machinery during the period of therapy.
Application during pregnancy and lactation
Methotrexate has a teratogenic effect: it can cause congenital malformations or intrauterine fetal death. If pregnancy occurs during drug treatment, abortion is recommended due to the high risk of negative effects on the fetus. Methotrexate passes into breast milk, therefore, during the course of therapy, it is necessary to stop breastfeeding.
Drug interactions
Since the drug is cytotoxic, the simultaneous administration of any drugs must be agreed with the attending physician. Considering the properties and characteristics of Methotrexate, the patient's condition and drug interactions of drugs, the doctor will give recommendations to avoid the appearance of severe side effects.
Analogs
Methotrexate analogs are: Vero-Methotrexate, Methotrexate Teva, Methotrexat-Ebeve, Methodject, Metotab.
Terms and conditions of storage
Store in a dark place at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Methotrexate
Currently, there are numerous reviews of Methotrexate. Sometimes it is used to interrupt an ectopic pregnancy, but women often report adverse reactions of its intake, expressed in pain in the abdomen and liver, severe nausea. It is imperative to monitor the effectiveness of terminating an ectopic pregnancy by the level of hCG.
Most patients do not recommend methotrexate tablets for psoriasis and do not approve of the treatment of this disease with its help. With an exacerbation of psoriasis, the drug significantly alleviates the condition, but its cancellation provokes a deterioration. There are reports of cases of toxic hepatitis.
The effectiveness of methotrexate in the treatment of rheumatoid arthritis and cancer is considered to be quite high. Patients report the onset of stable remission, but side reactions in the form of nausea are common. However, it is important to gradually increase the dose of the drug at the beginning of treatment. When methotrexate is discontinued, the patient's condition in this case usually worsens. There are also isolated mentions of the lack of effectiveness of the drug.
Price for Methotrexate in pharmacies
In pharmacy chains in Russia, the approximate price for Methotrexate with a dosage of 2.5 mg is about 183-228 rubles (the package includes 50 tablets).
Methotrexate: prices in online pharmacies
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Drug name Price Pharmacy |
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Methotrexate 2.5 mg film-coated tablets 50 pcs. RUB 21 Buy |
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Methotrexate 2.5 mg film-coated tablets 50 pcs. RUB 98 Buy |
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Methotrexate 2.5 mg film-coated tablets 50 pcs. 161 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
