Index of drugs

Severe, active rheumatoid arthritis in adults when DMARD therapy is indicated.

1 ml solution for injection in a pre-filled syringe contains 10 mg of Methotrexate in the form of disodium methotrexate.

An antimetabolite cytostatic, a folic acid antagonist, a dihydrofolate reductase inhibitor - an enzyme that catalyzes the transition of dihydrofolate to a biologically active tetrahydrofolic acid. The result of enzyme inhibition is a disruption of nucleic acid synthesis leading to the death of cells, especially rapidly growing cells (cancer cells, bone marrow, fetus, oral mucosa, small intestine, bladder). The mechanism of action in rheumatoid arthritis is not known, probably the preparation has a slight immunosuppressive and anti-inflammatory effect. About 50% of the drug is bound to plasma proteins. The total half-life is on average 6-7 h and shows significant variability (3-17 h). About 10% of the administered methotrexate is metabolized intrahepatic. The major metabolite is 7-hydroxymetrexate. The drug is excreted (mainly unchanged) primarily as a result of glomerular filtration and active secretion in the proximal tubule. About 5-20% of methotrexate and 1-5% of 7-hydroxymetotrex are excreted in the bile. There is a significant enterohepatic re-uptake.

Hypersensitivity to methotrexate or any of the excipients. Pregnancy and breastfeeding. Severe renal impairment (creatinine clearance <20 ml / min) and liver, including fibrosis, cirrhosis and hepatitis. Disorders of bone marrow function (leukopenia, thrombocytopenia, anemia). Severe acute or chronic infections, such as tuberculosis and HIV infection. Alcohol abuse. Mouth ulcer and diagnosed active gastric or duodenal ulcer. Simultaneous vaccination with bacterial vaccines. Immunodeficiency syndrome.

The drug can be administered only under the supervision of a specialist doctor experienced in the treatment of cytostatics from the antimetabolite group. Doses greater than 20 mg / week they may be associated with significant toxicity, particularly bone marrow suppression. Before starting treatment with methotrexate or re-applying methotrexate after a break, the following should be determined: complete blood count with smear, hepatic enzymes, bilirubin, serum albumin, renal function tests and chest X-ray examinations. If clinically indicated, tuberculosis and hepatitis should be excluded. During the treatment (at least once a month for the first 6 months, and then every 3 months) the following should be performed: examination of the oral cavity and throat to search for mucosal lesions, full blood count with smear, functional tests of the liver and kidneys. In patients with pulmonary exudate or ascites, if necessary, drainage should be used before treatment or treatment should be discontinued. Symptoms of gastrointestinal toxicity, manifesting initially as an inflammation of the mouth, are indications for treatment discontinuation. If continuation of treatment, hemorrhagic enteritis may occur and death due to their perforation. Methotrexate can lower fertility, reduce the number of sperm in semen, menstrual disorders, and amenorrhea. This action disappears after discontinuation of therapy. In addition, methotrexate is toxic to the embryo and causes fetal defects and may result in miscarriage. During treatment with Methotrexate, although one of the sexual partners, one should always use certain methods of contraception and at least for 6 months after the end of therapy. Any significant reduction in the number of leukocytes or platelets is an indication for immediate discontinuation of the drug and the implementation of appropriate supportive care. In order to prevent the precipitation of methotrexate or its metabolites in the kidney tubules, it is recommended to prevent the administration of significant amounts of fluids and to alkalinize the urine to pH 6.5 - 7.0, which can be achieved by administering to the patient orally or intravenously sodium bicarbonate (5 tablets of 625 mg every 3 h) or acetazolamide (orally 500 mg four times a day). Particular attention should be paid to the symptoms of liver toxicity, which do not always correlate with the results of liver function tests.Each finding of liver dysfunction or abnormal liver biopsy is an indication to stop treatment or a contraindication to its beginning. The re-administration of the drug may occur after two weeks from the normalization of the results of liver function tests. Acute or chronic interstitial pneumonitis, often combined with eosinophilia, may occur during treatment. Typical symptoms include: shortness of breath, cough (especially a dry cough with no discharge) and fever. Patients should be informed about the risk of pneumonia and instructed to contact a doctor immediately after a continuous dry cough or shortness of breath. In patients with pulmonary symptoms, methotrexate should be withdrawn and thorough tests should be performed, including chest X-rays, to exclude infection. Patients receiving low doses of methotrexate may develop malignant lymphoma - in this case treatment should be discontinued. Vitamins or other products containing folic acid, folinic acid or their derivatives may reduce the effectiveness of methotrexate.

Do not use. Before beginning treatment with the preparation, pregnancy should be ruled out. Patients of childbearing age (women and men) must use effective contraception during methotrexate therapy and for at least 6 months after completion of treatment.

Very common: stomatitis, indigestion, nausea, decreased appetite, local skin reactions (burning sensation, redness) in the area after intramuscular or subcutaneous administration, elevation of transaminases. Common: mouth sores, diarrhea, rash, erythema, pruritus, headache, fatigue, drowsiness, pneumonia, interstitial pneumonitis, pneumonia, often combined with eosinophilia, interstitial pneumonia, leukopenia, anemia, thrombocytopenia. Uncommon: pharyngitis, intestinal inflammation, vomiting, photosensitivity, hair loss, enlargement of rheumatic nodules, shingles, vasculitis, herpes, urticaria, diabetes, dizziness, confusion, depression, perception disorders, cirrhosis, liver atrophy , renal fibrosis and fatty liver degeneration, pancytopenia, inflammation and ulceration of the bladder or vagina, renal dysfunction, micturition disorders, arthralgia, myalgia, osteoporosis. Rare: gastric and duodenal ulcers, malabsorption, increased pigmentation, acne, ecchymosis, allergic reactions, anaphylactic shock, allergic vasculitis, fever, conjunctivitis, infection, sepsis, wound healing disorder, hypogammaglobulinaemia, visual disturbances, pericarditis, pericardium discharge, cardiac tamponade, reduced blood pressure, cases of thromboembolic complications, pulmonary fibrosis, pneumonia caused byPneumocystis carinii, dyspnea, bronchial asthma, fluid in the pleural cavity, renal failure, oliguria, anuria, electrolyte disturbances. Very rare: vomiting blood, bloody diarrhea, toxic dilation of the colon, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), increased nail pigmentation, acute nausea, palpability, telangiectasia, local lesions (formation of sterile abscesses, lipodystrophy) at the injection site after intramuscular or subcutaneous injection, visual impairment, pain, asthenia or paraesthesia of the limbs, changes in taste (metallic taste), seizures, meningeal symptoms, paralysis, retinopathy, agranulocytosis, severe bone marrow depression, decreased libido, impotence, oligospermia, defective oogenesis, defective spermatogenesis, infertility, menstrual disorders, vaginal discharge, and development of lymphomas.

In patients with rheumatoid arthritis, the recommended starting dose is 7.5 mg methotrexate once a week, given subcutaneously, intramuscularly or intravenously. Depending on the individual's disease severity and tolerability, the dose may be increased by 2.5 mg per week. Do not take a weekly dose of more than 25 mg. The healing effects can be expected after about 4-8 weeks. Once the desired effectiveness has been achieved, the dose should be gradually reduced to the lowest possible effective maintenance dose.In patients with renal impairment, the dose should be adjusted depending on the creatinine clearance value: at> 50 ml / min, 100% dose should be given, at 20-50 ml / min 50% dose, and at <20 ml / min should be given the drug. The drug should not be given if the bilirubin concentration is> 5 mg / dl. In elderly patients, a dose reduction should be considered because of liver and kidney abnormalities and a lower level of folic acid in the elderly. If the drug is changed from an oral to an intravenous route, it may be necessary to reduce the dose due to the variable oral bioavailability of methotrexate. Folic or folate supplementation may be considered in accordance with current treatment guidelines.