Intravenously, intramuscularly, intraarterially, intrathecally. Vero-methotrexate is a part of many chemotherapy regimens, therefore, when selecting the route of administration, regimen and dosage in each individual case, one should be guided by the data of specialized literature.
The solution of methotrexate, if necessary, can be further diluted in an isotonic solution of sodium chloride or in a 5% solution of dextrose.
Doses above 100 mg / m2 Enter only intravenously drip. When prescribing high doses of the drug (above 100 mg / m2) necessarily the subsequent introduction of calcium folinata.
For intrathecal administration methotrexate diluted to a concentration of 1 mg / ml in a 0.9% isotonic sodium chloride solution.
The following dosing regimens are used for adults and children:
Trophoblastic tumors: 15-30 mg intramuscularly, daily for 5 days with an interval of one or more weeks (depending on signs of toxicity). Treatment rates are usually repeated 3 to 5 times to a total dose of 300-400 mg.
Leukemia and lymphoma: 200 - 500 mg / m2 by intravenous infusion once every 2-4 weeks.
Neuroleukemia: 12 mg / m2 for 15-30 seconds intrathecally 1 or 2 times a week.
In the treatment of children, the dose is selected depending on the age of the child: children under the age of 1 year are prescribed 6 mg, children aged 1 year 8 mg, children 2 years 10 mg, children 3 years and over 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.
With caution, enter intrathecally.Exceeding the recommended dose with intrathecal administration significantly increases the risk of significant manifestations of toxicity. Caution: do not enter calcium folinate intrathecally!
Solid tumors: in combination with other antitumor drugs 30-40 mg / m2 intravenously sprayed once a week.
Mushroom mycosis: intramuscularly 50 mg once a week or 25 mg twice a week for several weeks or months. Dose reduction or withdrawal of drug administration is determined by the patient's response and hematological parameters.
Psoriasis (including psoriatic arthritis): intramuscularly or intravenously, in doses ranging from 10-25 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. Rheumatoid arthritis: The initial dose is usually 7.5 mg once a week, which is administered simultaneously or intravenously or intramuscularly. To achieve the optimal effect, a weekly dose can be increased, while 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 established.
Juvenile chronic arthritis: children in a dose of 10-30 mg / m2 in Week. The usual effective dose is 10 mg / m2 in Week. Initially, the drug is used in a half dose. Subject to good tolerability, a full dose is used every other week.
Dermatomyositis: adults of 7.5-15 mg per week; children 2.5 to 7.5 mg per week. In the future, the dose is reduced to the lowest effective dose and applied for a long time, months, in conjunction with a maintenance dose of glucocorticosteroids.
Systemic lupus erythematosus: adults 15 mg per week; children 7.5-10 mg / m2. The course of treatment is 6-8 weeks, then a maintenance dose is applied for many months.
When using cytotoxic drugs (including methotrexate) for children as immunosuppressive therapy (for psoriasis, rheumatoid arthritis, juvenile chronic arthritis, dermatomyositis and systemic lupus erythematosus), the relationship between benefit and risk of their use should be carefully considered.
Precautions for use.
Methotrexate is a cytotoxic drug, so care must be taken when handling it.
When high doses of methotrexate are administered, careful monitoring of the patient's condition is necessary to detect early signs of toxic reactions early.
With care, enter intertecally. Exceeding the recommended dose with intrathecal administration significantly increases the risk of significant manifestations of toxicity.
High-dose therapy (at a dose of 2 g / m2 and above) should be performed only by an experienced chemotherapist under the control of methotrexate concentration in plasma under steady conditions under the cover of calcium folinate. Normal decrease in the content of methotrexate in blood plasma is considered 2 times as compared to the initial value in 22 hours after the administration. Increase in plasma concentrations of creatinine (by 50% or more from the original) and / or bilirubin requires intensive detoxification therapy.
During therapy with methotrexate in elevated and high doses, it is necessary to monitor the pH of the urine: on the day of administration and in the next 2-3 days, the urine reaction should be alkaline. This is achieved by intravenous drip of a mixture consisting of 40 ml of 4.2% sodium bicarbonate solution and 400-800 ml of 0.9% sodium chloride solution on the eve, on the day of treatment and in the next 2-3 days. Treatment with methotrexate in high and high doses should be combined with enhanced hydration (up to 2 liters of fluid per day).
For the treatment of psoriasis methotrexate appoint only patients with severe disease that can not be treated by other types of therapy.
When using methotrexate as an immunosuppressive therapy (for rheumatoid arthritis, juvenile chronic arthritis, etc.), simultaneous administration of acetylsalicylic acid and diclofenac should be avoided; If combined therapy with non-steroidal anti-inflammatory drugs (NSAIDs) is required, NSAIDs should be used in a short-acting manner. To reduce the toxic effect of methotrexate, folic acid is prescribed at a dose of 5-10 mg / week after the use of methotrexate or 1 mg per day, on days free of methotrexate. During the treatment should be excluded from drinking alcohol, caffeine and drugs with antifolate activity.
To timely detect symptoms of intoxication during treatment with methotrexate, it is necessary to monitor the parameters of peripheral blood (1 time per week), the functional state of the liver and kidneys.
With the development of diarrhea and ulcerative stomatitis, methotrexate therapy must be discontinued, otherwise it can lead to the development of hemorrhagic enteritis and to 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, therefore, in such patients therapy should be carried out with extreme caution, with the use of reduced doses.
Impaired renal function is dose dependent. Risk of impairment is elevated in patients with reduced renal function or with dehydration, as well as in patients taking other nephrotoxic drugs.
Men and women of childbearing age should be treated with methotrexate and at least 3 months after the use of reliable methods of contraception.