Methotrexate is an antitumor drug.
Release form and composition
Methotrexate is produced in the form of coated tablets: from dark pink to pink, two layers are visible in the transverse section: the white core with a yellowish tinge and from dark pink to pink (10 or 50 pieces in blister packs , on 1-6, 8, 10 packings in a cardboard pack; on 20, 30, 40, 100 pieces in planimetric cell packings, on 1 packing in a cardboard pack, on 50 pieces in a polymeric or dark glass jar, on 1 jar in a carton box).
The composition of 1 tablet includes:
- Active ingredient: methotrexate - 2.5 mg;
- Auxiliary components: sucrose (sugar) - 43.97 mg; talc - 0.68 mg; potato starch - 21.82 mg; Crospovidone - 0.34 mg; calcium stearate - 0.34 mg; Povidone - 0.35 mg.
The composition of the shell: wheat flour - 16,144 mg; sucrose (sugar) - 32.5865 mg; magnesium hydroxycarbonate hydrate - 20.457 mg; gelatin - 0.138 mg; Povidone - 0.166 mg; dye azorubine (E122) (dye acid red 2C, carmoosin) - 0.0166 mg; wax - 0.0279 mg; titanium dioxide - 0.45 mg; talc - 0.014 mg.
Indications for use
- Severe psoriasis;
- Non-Hodgkin lymphomas and acute lymphoblastic leukemia;
- Mushroom mycosis in advanced stages;
- Rheumatoid arthritis (with the failure of other therapies);
- Trophoblastic tumors.
- Hematological disorders (anemia, leukopenia, bone marrow hypoplasia, thrombocytopenia);
- Pronounced changes in liver and kidney function;
- Immunodeficiency Syndrome;
- Infectious diseases of the eastern stage;
- Age up to 3 years;
- Pregnancy and during breastfeeding;
- Hypersensitivity to the drug.
Methotrexate should be used with caution with prior chemotherapy or radiotherapy, as well as patients with ascites, pleural effusion, gastric ulcer and duodenal ulcer, ulcerative colitis, dehydration, gout or nephrolithiasis in the history of infectious diseases of viral, bacterial or fungal etiology .
Dosing and Administration
Methotrexate is taken orally.
The doctor establishes the terms of treatment and the dose individually, depending on the chemotherapy regimen.
When trophoblastic tumors are usually prescribed:
- Daily 15-30 mg for 5 days with an interval of one or more weeks (depending on signs of toxicity). Courses of therapy are usually repeated 3-5 times;
- At 50 mg 1 time in 5 days with a break of at least 1 month. In the course of therapy - 300-400 mg.
In the treatment of acute lymphoblastic leukemia (simultaneously with other drugs) Methotrexate is used at 3.3 mg / m² at the same time as prednisone until remission is reached, then 15 mg / m² once a week or every 14 days at 2.5 mg / kg.
In the treatment of non-Hodgkin's lymphomas (simultaneously with other drugs) Methotrexate is prescribed:
- 2 times a week for 15-20 mg / m² per reception;
- Daily for 5 days at 7.5 mg / m².
The initial dose for rheumatoid arthritis is usually 7.5 mg 1 time per week. It is taken once or divided into three doses with a break of 12 hours. To achieve the optimal effect, the weekly dose can be increased, and it should not exceed 20 mg. After reaching the optimal clinical effect, one should start lowering the dose until the lowest effective dose is reached. The optimal duration of therapy is not known. For children with juvenile chronic arthritis, a dose of 10–30 mg / m² per week (0.3–1 mg / kg) is effective.
Therapy with methotrexate in psoriasis is carried out in doses of 10-25 mg per week. The dose should be increased gradually, when the optimum clinical effect is reached, a lowering of the dose begins until the minimum effective dose is reached.
When fungal mycosis is usually prescribed 2 times a week for 25 mg. Reducing the dose or cancellation of Methotrexate is determined by the patient's response and hematological parameters.
During the use of Methotrexate, the following side effects may occur:
- Cardiovascular system: pericarditis, pericardial effusion, lowering blood pressure, thromboembolism (including thrombophlebitis, arterial thrombosis, pulmonary embolism, thrombosis of cerebral vessels, deep veins and veins of the retina);
- Urogenital system: azotemia, renal failure or severe nephropathy, cystitis, transient oligospermia, hematuria, impaired sperm and ovogenesis, proteinuria, decreased libido, dysmenorrhea, impotence, vaginal discharge, infertility, gynecomastia, fetal death, miscarriage, defective, abdominal disfunctions, vaginal discharge, infertility, gynecomastia, fetal death, miscarriage, defective
- Respiratory system: rarely - respiratory failure, pulmonary fibrosis, interstitial pneumonitis (including fatal), alveolitis, chronic obstructive pulmonary disease, signs of potentially serious interstitial pneumonia - shortness of breath, dry non-productive cough, fever;
- Nervous system: dizziness, headache, drowsiness, aphasia, dysarthria, paresis, hemiparesis, convulsions; when using high doses - emotional lability, transient impairment of cognitive functions; encephalopathy (including leukoencephalopathy), unusual cranial sensitivity;
- Digestive system: nausea, anorexia, vomiting, pharyngitis, gingivitis, stomatitis, enteritis, erosive and ulcerative lesions, and bleeding from the gastrointestinal tract (including melena, hematemesis), hepatotoxicity (cirrhosis and liver fibrosis, acute hepatitis, hypoalmic, and hepatitis, as well as syme mare, and hepatotoxicity (hepatic cirrhosis and liver fibrosis, acute hepatitis, hypoalmic, and hepatomyceroma). failure, increased activity of "liver" transaminases);
- The hematopoietic system: pancytopenia, anemia (including aplastic), leukopenia, thrombocytopenia, agranulocytosis, neutropenia, eosinophilia, hypogammaglobulinemia, lymphoproliferative diseases, lymphadenopathy;
- Musculoskeletal system: myalgia, arthralgia, osteonecrosis, osteoporosis, fractures;
- Organ of vision: visual impairment (including transient blindness), conjunctivitis;
- Skin: skin itching, erythematous rash, photosensitivity, urticaria, disturbed pigmentation of the skin, furunculosis, ecchymosis, alopecia, acne, telangiectasia, erythema multiforme (including Stevens-Johnson syndrome), necrosis and skin ulceration, toxic epiderm, including toxic erythema, toxic erythema, necrosis and Stevens-Johnson syndrome, necrosis and alopecia, toxic erythema, erythema multiforme In the treatment of psoriasis - painful erosive plaques on the skin, burning sensation of the skin;
- Neoplasms: lymphoma (including reversible);
- General reactions: sepsis (including fatal), tumor lysis syndrome, allergic reactions up to anaphylactic shock, soft tissue necrosis, allergic vasculitis, sudden death, life-threatening opportunistic infections (including PCV), nocardiosis, cytomegalovirus (CMV) infections (including CMV-pneumonia), cryptococcosis, histoplasmosis, diabetes mellitus, infections caused by Herpes zoster and Herpes simplex (including disseminated herpes), increased sweating.
Methotrexate is a cytotoxic drug, so care should be taken when handling it.
The regimen should be prescribed by a physician experienced in the use of Methotrexate and familiar with its properties and action features. Due to the possible development of severe and even fatal side effects, patients should have complete information about possible risks and recommended safety measures.
Before starting therapy or when resuming it, a study of the kidney function, an X-ray examination of the chest should be performed, a complete general blood test should be performed to determine the level of platelets, a biochemical blood test (determination of liver enzymes, bilirubin, serum albumin), if necessary, tests for hepatitis and tuberculosis.
In order to identify the symptoms of intoxication in time, it is necessary to monitor the state of peripheral blood (the number of platelets and leukocytes: first every other day, then during the first month every 3-5 days, then 1 time in 7-10 days; during remission - 1 time in 7-14 days), the concentration of uric acid in the blood serum, kidney function, activity of “liver” transaminases, before each use, to examine the oral mucosa and pharynx for the presence of ulceration, periodically fluoroscopy of the chest organs. To monitor the state of bone marrow hematopoiesis should be before treatment, 1 time during the period of therapy and after the course.
Potentially, methotrexate can lead to signs of chronic or acute hepatotoxicity (including cirrhosis and liver fibrosis). As a rule, chronic hepatotoxicity develops after prolonged use of the drug (usually for 2 or more years) or reaching a total cumulative dose of not less than 1.5 g and may lead to adverse effects. Hepatotoxic effect may also be due to senile age and the burdened concomitant history (obesity, alcoholism, diabetes). Due to the toxic effects of methotrexate on the liver during therapy, it is necessary to refrain from prescribing other hepatotoxic drugs to patients except in cases of obvious need. Patients taking other hepatotoxic drugs (eg, leflunomide) should be carefully monitored.
With the development of ulcerative stomatitis and diarrhea, Methotrexate should be discontinued, which is associated with a high risk of perforation of the intestinal wall and hemorrhagic enteritis, which can be fatal.
After treatment with high doses of methotrexate, it is recommended to take calcium folinate to reduce its toxicity.
It is not recommended to expose unprotected skin to very prolonged sun exposure or to abuse the lamp of the UFO (due to the risk of a photosensitization reaction). Methotrexate, due to effects on the immune system, can worsen the response to vaccination and affect the results of immunological tests. In the period from 3 to 12 months after taking the drug, it is necessary to refuse immunization (if it is not approved by the doctor); other members of the patient’s family who live with him should not be given immunization with oral poliomyelitis vaccine. It is also recommended to avoid contact with people who have received a polio vaccine or wear a protective mask covering the mouth and nose. Patients of childbearing age of both sexes and their partners during therapy and after completing the course for at least 3 months should use reliable contraceptive measures.
During therapy, it is recommended to refrain from driving and performing work that requires quick psychomotor reactions (due to possible side effects, manifested as dizziness, feeling tired).
With the simultaneous use of methotrexate with certain drugs, undesirable effects may occur:
- Derivatives of coumarin or indandione: an increase in anti-coagulant activity, an increase in the risk of bleeding;
- Neomycin: reduced absorption of methotrexate;
- Anti-gouty medicines (colchicine, allopurinol, sulfinpyrazon): an increase in the concentration of uric acid in the blood;
- Non-steroidal anti-inflammatory drugs: an increase in the concentration and delayed elimination of methotrexate, which can lead to gastrointestinal intoxication and death from severe hematological (in the background of high doses of methotrexate);
- Urikozurichesky anti-gout remedies: an increased risk of nephropathy;
- Theophylline: reduced clearance of methotrexate;
- Salicylates, phenylbutazone, phenytoin, sulfonamides, derivatives of sulfonylurea, aminobenzoic acid, trimethoprim or pyrimethamine, a number of antibiotics (tetracycline, penicillin, chloramphenicol); sometimes even fatal;
- Antibiotics poorly absorbed in the gastrointestinal tract (tetracyclines, chloramphenicol): reduced absorption of methotrexate and impaired metabolism due to the suppression of the normal intestinal microflora;
- Sulfasalazine, azathioprine, retinoids, ethanol and other hepatotoxic drugs: an increased risk of developing hepatotoxicity;
- L-asparaginase: a decrease in the severity of the antitumor action of methotrexate;
- Dinitrogen oxide: the development of unpredictable severe myelosuppression and stomatitis;
- Hematotoxic drugs: increased risk of hematotoxicity of methotrexate;
- Folate-containing drugs (including multivitamins): reduction in the effectiveness of methotrexate therapy;
- Amiodarone (in the treatment of psoriasis): development of skin manifestation;
- Drugs that block tubular secretion (for example, probenecid): increased toxicity of methotrexate.
Methotrexate can lower the immune response to vaccination with inactivated and live viral vaccines.
The use of cytarabine 48 hours before or within 10 minutes after the start of therapy with methotrexate can lead to the development of a synergistic cytotoxic effect (correction of the dosage regimen should be based on hematological parameters).
When combined with methotrexate radiation therapy may increase the risk of bone marrow depression.
Terms and conditions of storage
Store in a dark, out of reach of children at a temperature up to 25 ° C.
Shelf life - 3 years.