Methotrexate Ebeve injection solution 10mg ml 1 ml bottle 1 N1
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Methotrexate
Release form
Solution
Composition
1 ml methotrexate 10 mg. Excipients: sodium hydroxide - 1.
Pharmacological effect
An antitumor drug from the group of antimetabolites - folic acid analogues. Along with antitumor has an immunosuppressive effect. Inhibits dihydrofolate reductase 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. Inhibits synthesis, DNA repair and cell mitosis (during the synthesis phase). Particularly sensitive to the action of methotrexate tissue with high cell proliferation: tumor tissue, bone marrow, mucous membrane epithelium cells, embryonic cells. When cell proliferation of malignant tissue is greater than in most normal tissues, methotrexate can lead to an abnormal growth of malignant tumors without irreversible damage to normal tissue. The mechanism of action for rheumatoid arthritis is unknown, perhaps this action is due to the immunosuppressive properties of methotrexate. In patients with rheumatoid arthritis, the use of methotrexate reduces the symptoms of inflammation (pain, swelling, stiffness), but there is a limited number of studies with long-term use of methotrexate (regarding the ability to maintain remission in rheumatoid arthritis). In 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.
Pharmacokinetics
Absorption and distribution: With intramuscular injection of Cmax of methotrexate in the blood plasma is achieved within 30-60 minutes. For leukemic patients, a wide interindividual variability between 1 and 3 hours is characteristic. After intravenous administration, the primary distribution is 0.18 l / kg (18% of body weight). The saturation dose distribution is about 0.4-0.8 l / kg (40% -80% of body weight). Plasma protein binding is about 50%, predominantly with albumin. Competitive extrusion is possible with simultaneous use with sulfonamides, salicylates, tetracyclines, chloramphenicols, phenytaine. When taken in therapeutic doses, methotrexate does not penetrate the BBB. High concentrations of methotrexate in the CNS can be achieved with intrathecal administration.Metabolism: Methotrexate undergoes hepatic and intracellular metabolism to form a pharmacologically active polyglutamine form, which also inhibits dihydrofolate reductase and thymidine synthesis. A small amount of methotrexate polyglutamate can remain in the tissues for a long period of time. Preservation and prolongation of the active metabolites of the drug vary depending on the type of cells, tissues and tumors. Excretion: The average T1 / 2 values when using methotrexate in a dose of less than 30 mg / m2 are 6-7 hours. In patients receiving high doses of methotrexate, T1 / 2 is from 8 to 17 hours. From 80 to 90% of the dose taken is output to unchanged by glomerular filtration and tubular secretion within 24 hours. With bile, no more than 10% or less of the administered dose is excreted, followed by intestinal reabsorption. Pharmacokinetics in special clinical situations: In chronic renal failure, both phases of drug elimination can be significantly extended. Impaired renal function, pronounced ascites or transudate, as well as the simultaneous use of drugs such as weak organic acids, which are also subject to tubular secretion, can significantly increase the concentration of methotrexate in serum. In accordance with the distribution of methotrexate, it accumulates in the liver, kidneys and spleen in the form of polyglutamates and may linger in these organs for several weeks or months.
Indications
Acute lymphocytic leukemia, trophoblastic disease, skin cancer, cervical and vulvar cancer, esophagus cancer, head and neck squamous cell carcinoma, renal pelvis and ureter cancer, osteogenic and soft cell sarcoma, Ewing's sarcoma, lung cancer, breast cancer, germ cell tumors of the testicle and ovarian , liver cancer, kidney cancer, retinoblastoma, medulloblastoma, penile cancer, lymphogranulomatosis. Severe forms of psoriasis (in case of failure of standard therapy). Severe rheumatoid arthritis (in case of failure of standard therapy).
Contraindications
Severe disorders of the liver and / or kidneys, leukopenia, thrombocytopenia, pregnancy. Methotrexate should not be used in immunodeficiency states.
Use during pregnancy and lactation
Methotrexate is contraindicated for use in pregnancy. If necessary, use during lactation should stop breastfeeding. Women of childbearing age should use reliable methods of contraception during the use of methotrexate. In experimental studies established embryotoxic and teratogenic effects of methotrexate.
Dosage and administration
Accept inside, enter into / in, in / m, intralyumbalno. They establish individually, depending on the evidence and the stage of the disease, the state of the hematopoietic system, the scheme of antitumor therapy.
Side effects
On the part of the digestive system: possible ulcerative stomatitis, anorexia, gingivitis, pharyngitis, nausea; rarely - diarrhea, melena, enteritis, pancreatitis; in some cases (with prolonged daily use) - liver necrosis, cirrhosis, fatty atrophy, periportal fibrosis of the liver. On the part of the hematopoietic system: leukopenia, anemia, thrombocytopenia. From the side of the central nervous system: feeling tired, dizzy; rarely - headache, aphasia, drowsiness, cramps. Reproductive system: disorders of oogenesis and spermatogenesis, oligospermia, menstrual disorders, decreased libido, impotence. On the part of the urinary system: hematuria, cystitis, pronounced renal dysfunction. Allergic reactions: chills, reduced resistance to infection; rarely - urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome. Dermatological reactions: skin rash, photosensitivity, pigmentation disorders, telangiectasia, acne, furunculosis.
Interaction with other drugs
The likelihood of the hepatotoxic effect of methotrexate increases in the case of regular alcohol consumption and concomitant use of other hepatotoxic drugs. With the combination therapy with methotrexate and leflunomide, the incidence of pancytopenia and hepatotoxic effects increases. Antibiotics for oral use (tetracyclines, chloramphenicol and non-absorbable broad-spectrum antibiotics) can reduce the absorption of methotrexate in the gastrointestinal tract and interfere with the enterohepatic circulation due to inhibition of intestinal microflora or inhibition of bacterial metabolism.Penicillins, ciprofloxacin, cefalotin, glycopeptides can reduce the renal clearance of methotrexate, as a result of which its concentration in the blood serum may increase and the toxic effect on the hematopoietic system and gastrointestinal tract may increase. Probenecid, weak organic acids (for example, "loop" diuretics) and pyrazoles (phenylbutazone) can slow down the elimination of methotrexate, as a result of which its concentration in blood serum may increase and hematologic toxicity may increase. The risk of toxic effects of methotrexate is increased in the case of combined use with NSAIDs or salicylates. With concomitant therapy with drugs that may have an adverse effect on the bone marrow (for example, sulfonamides, trimethoprim / sulfamethoxazole, chloramphenicol, pyrimethamine), the possibility of developing more pronounced hematological disorders should be taken into account. With concomitant therapy with drugs that cause folate deficiency (for example, trimethoprim / sulfamethoxazole), the toxic effect of methotrexate may be enhanced. The simultaneous use of indirect anticoagulants and lipid-lowering drugs (cholestyramine) enhances the toxicity of methotrexate. With the combined use of antirheumatic drugs (for example, salts of gold, penicillamine, hydroxychloroquine, azathioprine, cyclosporine) and methotrexate, the toxic effect of the latter does not increase. In the case of simultaneous use of sulfasalazine and methotrexate, the effect of the latter can be potentiated due to inhibition of folic acid synthesis. When combined use of methotrexate and proton pump inhibitors (for example, omeprazole or pantoprazole), renal elimination of methotrexate can be delayed, and pantoprazole can inhibit renal elimination of the 7-hydroxymetotrexate metabolite, which in one case was accompanied by the development of myalgia and tremor. During the period of treatment with methotrexate, excessive consumption of drinks containing caffeine and theophylline (coffee, sweet drinks containing caffeine, black tea) should be avoided. Methotrexate reduces theophylline clearance. It is necessary to take into account the pharmacokinetic interaction between methotrexate and flucloxacillin and anticonvulsants (the concentration of methotrexate in the blood decreases), 5-fluorouracil (the half-life of 5-fluorouracil increases). In the case of joint use with other cytostatics, the clearance of methotrexate may decrease.Vitamin or oral iron supplements containing folic acid may alter the response to methotrexate therapy. When mixing solutions of methotrexate with chlorpromazine hydrochloride, droperidol, idarubicin, metoclopramide hydrochloride, heparin, sodium prednisolone phosphate and promethazine hydrochloride, precipitation or turbidity of the solution may occur. Due to competitive binding with serum albumin with simultaneous use of methotrexate with phenylbutazone, phenytoin, the toxicity of methotrexate can be increased. Several patients with psoriasis or fungal mycosis treated with methotrexate in combination with PUVA therapy (methoxen and ultraviolet radiation) were diagnosed with skin cancer. Caution should be exercised with the simultaneous introduction of erythrocyte mass and methotrexate. Combination with radiotherapy may increase the risk of soft tissue necrosis. Methotrexate can reduce the immunological response to vaccination. When administered simultaneously with a live vaccine, severe antigen reactions can develop. L-asparaginase is antagonist of methotrexate. Anesthesia with dinitrogen oxide can lead to the development of unpredictable severe myelosuppression and stomatitis. Amiodarone may promote ulceration of the skin. Parenteral administration of acyclovir with intrathecal administration of methotrexate increases the risk of neurological disorders.
special instructions
Methotrexate should not be used for ascites, pleural effusion, gastric ulcer and duodenal ulcer, ulcerative colitis, gout or nephropathy (including in history). It is not recommended for use in patients with chickenpox (including recently suffered or after contact with the sick), herpes zoster and other acute infectious diseases. Before starting therapy and on the background of the treatment, a picture of peripheral blood, liver and kidney function, and chest X-ray should be monitored. When treating rheumatoid arthritis or psoriasis, a complete complete blood count should be done at least once a month, and laboratory tests of liver or kidney function at least once every 1-2 months.When applied for psoriasis, local treatment of the disease should not be interrupted. In case of overdose, the use of calcium folinate is recommended (but no later than after 4 hours). When conducting a combination of anticancer therapy, special care should be taken with the simultaneous use of methotrexate in high doses with drugs that have a nephrotoxic effect (for example, cisplatin). Do not recommend vaccinating patients and their families. Caution should be used to combine methotrexate (even in low doses) with acetylsalicylic acid. In experimental studies, the carcinogenic and mutagenic effects of methotrexate have been established.