Methortrite, 10 mg/ml, solution for injection, 1 ml, 1 pc.
If a significant amount of fluid in the pleural cavities or ascites is detected in a patient, the fluid should be evacuated by drainage before starting methotrexate therapy, or the use of methotrexate should be discontinued.
The appearance of symptoms of toxic damage to the digestive system, the earliest of which are stomatitis and diarrhea, requires temporary cessation of methotrexate therapy due to the high risk of developing hemorrhagic enteritis and intestinal perforation with a fatal outcome if therapy is continued.
During treatment with methotrexate, patients should be closely monitored in order to promptly identify signs of possible toxicity and adverse effects. Given the risk of severe or even fatal toxic reactions, patients should be thoroughly informed about possible complications and recommended precautions.
Before starting treatment with methotrexate or when resuming therapy after a break, it is necessary to conduct a clinical blood test with counting the leukocyte formula and platelet count, assess the activity of liver enzymes, the concentration of bilirubin, serum albumin, as well as a chest x-ray and renal function tests. If there are clinical indications, studies are prescribed to exclude tuberculosis and hepatitis.
During treatment with methotrexate (monthly in the first 6 months and at least every 3 months thereafter, and as doses increase, it is advisable to increase the frequency of examinations), the following studies are carried out:
1. Examination of the mouth and throat
to detect changes in mucous membranes.
2. Blood test with determination of leukocyte formula and platelet count
.
Even when used in normal therapeutic doses, methotrexate can suddenly cause depression of the hematopoietic system. If there is a significant decrease in the number of leukocytes or platelets, treatment with methotrexate is stopped immediately and symptomatic supportive therapy is prescribed. Patients should be instructed to immediately report any signs and symptoms indicating an infection to their physician. During concomitant therapy with hematotoxic drugs (for example, leflunomide), it is necessary to carefully monitor the number of leukocytes and platelets in the blood.
During long-term treatment with methotrexate, if necessary, a bone marrow biopsy is advisable.
3. Functional liver tests
.
Particular attention should be paid to identifying signs of liver damage. Treatment with methotrexate should not be started or should be suspended if any abnormal results of liver function tests or liver biopsy are detected. Typically, the indicators return to normal within two weeks, after which treatment can be resumed according to the doctor’s decision.
In 13–20% of patients, a short-term increase of 2–3 times in the activity of “liver” enzymes was observed. A persistent increase in liver enzyme activity and/or a decrease in serum albumin concentrations may be indicators of severe hepatotoxicity. Enzyme diagnostics do not in all cases provide adequate prediction of the development of hepatotoxicity detected morphologically; even in the case of normal values of the activity of “liver” enzymes, liver fibrosis, or, much less commonly, liver cirrhosis, can be detected histopathologically.
When using methotrexate for rheumatological indications, there is no reason to perform a liver biopsy to monitor the hepatotoxic effect of the drug.
When treating patients with psoriasis, it is necessary to evaluate the advisability of performing a liver biopsy before or during treatment with methotrexate, based on current scientific recommendations. If biochemical liver function tests or type III collagen propeptide concentrations do not reveal signs of hepatotoxicity, additional studies may be necessary. This assessment should differentiate between patients without risk factors and patients at risk (for example, patients with a history of alcohol abuse, persistently elevated liver enzymes, a history of liver disease, a family history of hereditary liver disease, patients with diabetes mellitus, obese patients, and previously taken hepatotoxic drugs or exposed to hepatotoxic chemicals and received long-term treatment with methotrexate in total doses of 1.5 g or more). In the case of a persistent increase in the activity of liver enzymes, it is necessary to reduce the dose or stop treatment with methotrexate.
Since methotrexate has a toxic effect on the liver, other hepatotoxic drugs should not be prescribed during treatment with the drug unless clearly necessary. You should also avoid or greatly reduce your alcohol consumption. The activity of liver enzymes should be especially carefully monitored in patients receiving concomitant therapy with other hepatotoxic and hematotoxic drugs (in particular, leflunomide).
Particular caution should be observed when treating patients with insulin-dependent diabetes mellitus, since cases of the development of liver cirrhosis have been described with a previous periodic increase in the activity of “liver” enzymes.
4. Renal function tests and urine examination
.
If the serum creatinine concentration increases, the dose of methotrexate should be reduced. At creatinine concentrations exceeding 2 mg/dL, the use of methotrexate is contraindicated.
Since methotrexate is excreted primarily by the kidneys, patients with impaired renal function may experience increased concentrations of methotrexate in the blood, which may result in severe adverse reactions. It is necessary to carefully monitor the condition of patients who may have impaired renal function (for example, elderly patients). This is especially important in the case of concomitant therapy with drugs that reduce the excretion of methotrexate, have an adverse effect on the kidneys (in particular, NSAIDs) or on the hematopoietic system. In the presence of risk factors, such as renal failure, simultaneous use of non-steroidal anti-inflammatory drugs is not recommended. Dehydration may also potentiate the toxic effects of methotrexate.
5. Research of respiratory system function
.
It is necessary to closely monitor symptoms of possible development of pulmonary function disorders and, if necessary, order a pulmonary function test. Pulmonary diseases require rapid diagnosis and discontinuation of methotrexate. The appearance of corresponding symptoms (especially a dry, nonproductive cough) or the development of nonspecific pneumonitis during treatment with methotrexate may indicate a potential danger of lung damage. In such cases, methotrexate is discontinued and the patient is carefully examined. Although the clinical presentation may vary, the typical patient with methotrexate-induced pulmonary disease will have fever, cough with dyspnea, hypoxemia, and pulmonary infiltrates on x-ray. In the differential diagnosis, infectious diseases should be excluded. Lung damage can occur during treatment with methotrexate at any dose.
During treatment with methotrexate, opportunistic infections may develop, including pneumonia caused by Pneumocystis carinii
, which can be fatal.
If the patient exhibits symptoms of pulmonary involvement, pneumonia caused by Pneumocystis carinii
.
Caution is recommended when treating patients with pulmonary insufficiency.
6. Because methotrexate affects the immune system, it may alter the response to vaccinations and affect the results of immunological tests. Particular caution is required when treating patients with inactive, chronic infections (such as herpes zoster, tuberculosis, hepatitis B or C) due to their possible activation. During treatment with methotrexate, vaccination with live vaccines should not be performed.
It is recommended that methotrexate treatment be interrupted one week before surgery and restarted one or two weeks after surgery.
When body temperature rises (more than 38 °C), the elimination of methotrexate slows down significantly.
Methotrexate may increase the risk of developing neoplasms (mainly lymphomas). Malignant lymphomas can also develop in patients receiving low-dose methotrexate. In such cases, the drug is discontinued. If spontaneous regression of lymphoma is not observed, therapy with cytotoxic drugs is prescribed.
Before starting treatment with Methortritis, pregnancy must be excluded. Methotrexate has an embryotoxic effect, promotes abortion and the formation of fetal development abnormalities. Methotrexate therapy is accompanied by inhibition of spermatogenesis and oogenesis, which can lead to decreased fertility. After discontinuation of methotrexate therapy, these effects spontaneously regress. During methotrexate therapy and for 6 months after its completion, patients are advised to use contraception. Patients of reproductive age, as well as their partners, should be informed about the possible effect of methotrexate on reproduction and fetal development.
During high-dose therapy, precipitation of methotrexate or its metabolites in the renal tubules may occur. In such cases, to prevent this complication, it is recommended to carry out infusion therapy and alkalization of urine until a pH of 6.5–7.0 is achieved through oral or intravenous administration of sodium bicarbonate (5 tablets of 625 mg every 3 hours) or acetazolamide (500 mg orally 4 times/day).
Methotrexate should not be mixed with other medications in the same infusion bag or vial.
When handling methotrexate solution, you must follow the rules for handling cytotoxic substances. Pregnant healthcare workers should not work with the drug.
Measures should be taken to prevent methotrexate solution from coming into contact with the skin and mucous membranes. If the drug does get on the skin or mucous membranes, the affected area is immediately washed with plenty of water.
Impact on the ability to drive vehicles and perform work requiring increased speed of psychomotor reactions
During treatment with Methortritis, you should refrain from driving vehicles or operating other machinery, as side effects from the nervous system (fatigue and dizziness) may occur.
Methorthritis
If a significant amount of fluid in the pleural cavities or ascites is detected in a patient, the fluid should be evacuated by drainage before starting methotrexate therapy, or the use of methotrexate should be discontinued.
The appearance of symptoms of toxic damage to the digestive system, the earliest of which are stomatitis and diarrhea, requires temporary cessation of methotrexate therapy due to the high risk of developing hemorrhagic enteritis and intestinal perforation with a fatal outcome if therapy is continued.
During treatment with methotrexate, patients should be closely monitored in order to promptly identify signs of possible toxicity and adverse effects. Given the risk of severe or even fatal toxic reactions, patients should be informed in detail about the possible consequences and recommended precautions.
Before starting treatment with methotrexate or when resuming therapy after a break, it is necessary to conduct a clinical blood test with counting the leukocyte formula and platelet count, assess the activity of liver enzymes, the concentration of bilirubin, serum albumin, as well as a chest x-ray and renal function tests. If there are clinical indications, studies are prescribed to exclude tuberculosis and hepatitis.
During treatment with methotrexate (monthly in the first 6 months and at least every 3 months thereafter, with increasing doses it is advisable to increase the frequency of examinations) the following studies are carried out:
1. Examination of the mouth and throat to identify changes in the mucous membranes.
2. Blood test to determine the leukocyte formula and platelet count.
Even when used in normal therapeutic doses, methotrexate can suddenly cause depression of the hematopoietic system. If there is a significant decrease in the number of leukocytes or platelets, treatment with methotrexate is stopped immediately and symptomatic supportive therapy is prescribed. Patients should be instructed to immediately report any signs and symptoms indicating an infection to their physician. During concomitant therapy with hematotoxic drugs (for example, leflunomide), it is necessary to carefully monitor the number of leukocytes and platelets in the blood. During long-term treatment with methotrexate, bone biopsies should be performed.
3. Functional liver tests. Particular attention should be paid to identifying signs of liver damage. Treatment with methotrexate should not be started or should be suspended if there is any abnormality in the results of liver function tests or liver biopsy. Typically, the indicators return to normal within 2 weeks, after which treatment can be resumed according to the doctor’s decision.
In 13 - 20% of patients, short-term increases of 2 - 3 times in the activity of liver transaminases were observed. Persistent liver enzyme abnormalities and/or decreased serum albumin concentrations may be indicators of severe hepatotoxicity. Enzyme diagnostics do not provide adequate prediction of the development of hepatotoxicity detected morphologically, since in the case of normal values of liver transaminases, only liver fibrosis detected histopathologically and, much less often, cirrhosis of the liver may be present.
When using methotrexate for rheumatological indications, there is no reason to perform a liver biopsy to monitor the hepatotoxic effect of the drug. When treating patients with psoriasis, it is necessary to evaluate the advisability of performing a liver biopsy before or during treatment with methotrexate, based on current scientific recommendations. Additional studies are needed to determine if a battery of liver biochemical tests or type III collagen propeptide testing can sufficiently detect hepatotoxicity. This assessment should differentiate between patients without risk factors and patients at risk (for example, patients with a history of alcohol abuse, persistently elevated liver enzymes, a history of liver disease, a family history of hereditary liver disease, patients with diabetes mellitus, obese patients, and previously taking hepatotoxic drugs or exposure to hepatotoxic chemicals and receiving long-term treatment with methotrexate in total doses of 1.5 g or more). In case of persistent increase in liver enzyme activity, it is necessary to reduce the dose or discontinue treatment with methotrexate. Since methotrexate has a toxic effect on the liver, other hepatotoxic drugs should not be prescribed during treatment with the drug unless clearly necessary. You should also avoid or greatly reduce your alcohol consumption. Liver enzyme activity should be especially closely monitored in patients receiving concomitant therapy with other hepatotoxic and hematotoxic drugs (in particular, leflunomide).
Caution is recommended in patients with insulin-dependent diabetes mellitus, since liver cirrhosis associated with periodic increases in the activity of hepatic transaminases has been observed in isolated cases during treatment with methotrexate.
4. Renal function tests and urine inheritance.
If serum creatinine concentration increases, the dose should be reduced. If creatininemia increases to more than 2 mg/dL, treatment with methotrexate is contraindicated.
Since methotrexate is excreted primarily by the kidneys, patients with impaired renal function may experience increased concentrations of methotrexate in the blood, which may result in severe adverse reactions. It is necessary to carefully monitor the condition of patients who may have impaired renal function (for example, elderly patients). This is especially important in the case of concomitant therapy with drugs that reduce the excretion of methotrexate, have an adverse effect on the kidneys (in particular, NSAIDs) or on the hematopoietic system. In the presence of risk factors such as renal failure, concomitant use of non-steroidal anti-inflammatory drugs is not recommended. Dehydration may also potentiate the toxic effects of methotrexate.
5. Study of the respiratory system. It is necessary to closely monitor symptoms of possible development of pulmonary function disorders and, if necessary, order a pulmonary function test. Pulmonary diseases require rapid diagnosis and discontinuation of methotrexate. The appearance of corresponding symptoms (especially a dry, nonproductive cough) or the development of nonspecific pneumonitis during treatment with methotrexate may indicate a potential danger of lung damage. In such cases, methotrexate is discontinued and the patient is carefully examined. Although the clinical presentation may vary, the typical patient with methotrexate-induced pulmonary disease exhibits fever, cough with dyspnea, hypoxemia, and pulmonary infiltrates on x-ray. In the differential diagnosis, infectious diseases should be excluded. Lung damage can occur during treatment with methotrexate at any dose.
Opportunistic infections may occur during treatment with methotrexate, including Pneumocystis carinii pneumonia, which can be fatal. If the patient exhibits symptoms of pulmonary involvement, the diagnosis of Pneumocystis carinii pneumonia should be considered.
Caution is advised in patients with pulmonary insufficiency.
6. Because methotrexate affects the immune system, it may alter the response to vaccinations and affect the results of immunological tests. Particular caution is required when treating patients with inactive, chronic infections (such as herpes zoster, tuberculosis, hepatitis B or C) due to their possible activation. During treatment with methotrexate, vaccination with live vaccines should not be performed.
It is recommended that methotrexate treatment be interrupted one week before surgery and restarted one or two weeks after surgery. When body temperature rises above 38 degrees, the elimination of methotrexate slows down significantly.
Methotrexate may increase the risk of developing neoplasms (mainly lymphomas). Malignant lymphomas can also develop in patients receiving low-dose methotrexate. In such cases, the drug is discontinued. If spontaneous regression of lymphoma is not observed, therapy with cytotoxic drugs is prescribed.
Before starting treatment with the drug, pregnancy must be excluded. Methotrexate has an embryotoxic effect, promotes abortion and the formation of fetal development abnormalities. Methotrexate therapy is accompanied by inhibition of spermatogenesis and oogenesis, which can lead to decreased fertility. After discontinuation of methotrexate therapy, these effects spontaneously regress. During methotrexate therapy and for 6 months after its completion, patients are advised to use contraception. Patients of reproductive age, as well as their partners, should be informed about the possible effect of methotrexate on reproduction and fetal development.
During high-dose therapy, precipitation of methotrexate or its metabolites in the renal tubules may occur. In such cases, to prevent this complication, it is recommended to carry out infusion therapy and alkalization of urine until a pH of 6.5-7.0 is achieved through oral or intravenous administration of sodium bicarbonate (5 tablets of 625 mg every 3 hours) or acetazolamide (500 mg orally 4 times a day ). Methotrexate should not be mixed with other medications in the same infusion bag or vial.
When manipulating methotrexate solutions, it is necessary to follow the rules for handling cytotoxic substances. Pregnant healthcare workers should not work with the drug.
Measures should be taken to prevent methotrexate solutions from coming into contact with the skin and mucous membranes. If the drug does get on the skin or mucous membranes, the affected area is immediately washed with plenty of water.
During treatment with the drug, you should refrain from driving vehicles or operating other mechanisms, as side effects from the nervous system (fatigue and dizziness) may occur.