METOJECT, METOJECT - instructions for use of the medicine, reviews, description, price

Metoject

Patients should be clearly informed that the drug should be used once a week and not daily.

Methotrexate is cytotoxic and must be handled with caution.

Patients undergoing Metoject therapy should be closely monitored to ensure that signs of potential toxicity and adverse reactions are detected and assessed with minimal delay.

Due to the possible development of severe or even fatal adverse reactions, patients should be fully informed by their physician about the possible risks and recommended safety measures.

Recommended Research and Safety Measures

Before starting or resuming treatment with methotrexate, a complete blood count and platelet count should be performed; biochemical blood test with determination of liver enzyme activity, bilirubin concentration, serum albumin; chest x-ray, kidney function test. If necessary, carry out tests for tuberculosis and hepatitis.

During treatment (at least once a month in the first 6 months of treatment, then at least once every 2 months), the following studies must be carried out:

1. Examination of the oral mucosa and pharynx.

2. Complete general blood test with platelet count determination. Suppression of hematopoiesis caused by methotrexate can occur suddenly, incl. when using the drug in small doses. In any case of a significant decrease in the number of leukocytes or platelets, it is necessary to immediately interrupt treatment with methotrexate and carry out adequate supportive therapy. Patients should be advised to report any signs and symptoms of possible infections. Patients who are concomitantly receiving drugs that suppress hematopoiesis (for example, leflunomide) require careful monitoring of blood counts and platelet counts.

3. Liver function test. Particular attention should be paid to identifying possible toxic effects on the liver. Treatment should not be started or interrupted if, during appropriate examinations, liver function abnormalities that were present before the start of treatment or that developed during treatment are detected. Typically, disorders that develop during treatment return to normal within 2 weeks after interruption of methotrexate therapy, after which, at the discretion of the attending physician, treatment can be resumed.

When methotrexate is used for rheumatoid arthritis, there is no obvious need for liver biopsy to monitor liver toxicity.

Particular attention should be paid to patients with risk factors such as excessive alcohol consumption, persistent elevation of liver enzymes, history of liver disease, diabetes mellitus, obesity, history of use of hepatotoxic drugs or drugs that affect hematopoiesis.

Monitoring of serum liver enzymes: transient 2-3 times higher than normal transaminase values were reported in 13-20% of patients. In the event of a persistent increase in liver enzyme activity, dose reduction or discontinuation of treatment should be considered.

Due to the toxic effects of the drug on the liver during treatment, patients should avoid concomitant use of other hepatotoxic drugs unless clearly necessary; You should also avoid drinking alcohol.

In patients using other hepatotoxic drugs or drugs that inhibit hematopoiesis (for example, leflunomide), liver enzyme activity and complete blood count parameters with platelet count should be carefully monitored.

4. Monitoring kidney function and urine analysis. Because Methotrexate is excreted mainly by the kidneys; in case of insufficiency of renal function, an increase in the concentration of methotrexate in plasma should be expected, which can lead to serious undesirable side effects. In cases of possible decline in renal function (for example, in elderly patients), control examinations should be performed more frequently. This also applies to cases of simultaneous administration of drugs that affect the elimination of methotrexate, drugs that can lead to kidney damage (for example, NSAIDs), as well as drugs that can affect the hematopoietic system. Dehydration may also increase the toxicity of methotrexate.

5. Examination of the respiratory system. Particular attention should be paid to symptoms of deteriorating pulmonary function, and appropriate tests should be carried out if necessary. Symptoms of respiratory damage (especially dry nonproductive cough), nonspecific pneumonitis that occur during methotrexate therapy may indicate a potentially dangerous disease and require interruption of treatment and a thorough examination in order to make a diagnosis. Clinical symptoms of methotrexate-induced lung injury are varied, but typical signs are fever, cough, difficulty breathing, and hypoxemia. An X-ray examination of the chest is mandatory to exclude the presence of infiltrates or infection. The possibility of respiratory disease caused by the use of methotrexate does not depend on the doses of the drug used.

If the dose of methotrexate is increased, the frequency of examinations should be increased.

Methotrexate affects the immune system, can worsen the response to vaccination and affect the results of immunological tests. Particular caution is required when using the drug in patients with chronic infectious diseases outside periods of exacerbation (Herpes zoster, tuberculosis, hepatitis B or C) due to the possibility of exacerbation of the disease. Refusal from immunization is required. The interval between the use of methotrexate and the administration of live and inactivated viral vaccines should be at least 3 months, possibly up to 12 months (depending on the immune status of the patient).

If diarrhea and ulcerative stomatitis develop, methotrexate therapy should be interrupted.

Do not expose unprotected skin to too much sunlight or ultraviolet irradiation for too long (possible photosensitivity reaction).

Patients receiving low doses of methotrexate may develop malignant lymphoma; in these cases, treatment should be discontinued. In the absence of signs of spontaneous regression of lymphoma, cytotoxic therapy is necessary.

When using methotrexate, osteonecrosis and osteoporosis may develop (with a frequency of ≥ 1/1000, < 1/100), which increases the risk of fractures.

Shows mutagenic activity in vivo and in vitro. A carcinogenicity study in rodents did not show an increase in the incidence of tumors with methotrexate.

Impact on the ability to drive vehicles and operate machinery

Since methotrexate can have an effect on the central nervous system (fatigue, dizziness), the patient should refrain from driving and operating machinery during treatment.

Metoject, 50 mg/ml, solution for subcutaneous administration, 0.5 ml, 1 pc.

Patients should be clearly informed that the drug should be used once a week and not daily.

Methotrexate is cytotoxic and must be handled with caution.

Methotrexate affects fertility and is an embryo-, fetotoxic and teratogenic drug. Shows mutagenic activity in vivo

and
in vitro.
A carcinogenicity study in rodents did not show an increase in the incidence of tumors with methotrexate.

Patients undergoing treatment with Metoject should be closely monitored to ensure that signs of potential toxicity and adverse reactions are detected and assessed with minimal delay.

Methoject should only be prescribed by a physician with sufficient knowledge and experience in anti-metabolic therapy.

Due to the possible development of severe or even fatal adverse reactions, patients should be fully informed by their physician about the possible risks and recommended safety measures.

Recommended examinations and safety measures

Before starting or resuming treatment with methotrexate:

a complete general blood count should be performed to determine platelet levels; biochemical blood test with determination of the values of liver enzymes, bilirubin, serum albumin; chest x-ray, kidney function test. If necessary, tests for tuberculosis and hepatitis.

During treatment (at least once a month in the first 6 months of treatment, then at least once every 3 months) it is necessary to:

1. Examination of the oral mucosa and pharynx.

2. Complete general blood test with platelet level determination. Suppression of hematopoiesis caused by methotrexate can occur suddenly, incl. when using the drug in small doses. In case of a significant decrease in the number of leukocytes or platelets, it is necessary to immediately interrupt treatment with methotrexate and carry out adequate supportive therapy. Patients should be advised to report any signs and symptoms of possible infections. Patients concomitantly using hematotoxic drugs (eg leflunomide) should be carefully monitored with monitoring of blood counts and platelet counts.

3. Liver function tests: Particular attention should be paid to identifying possible toxic effects on the liver. Treatment should not be started or should be interrupted if liver function abnormalities that were present before treatment or that developed during treatment are detected during appropriate tests or biopsy. Usually, disorders that develop during treatment return to normal within 2 weeks after interruption of methotrexate therapy, after which, at the discretion of the attending physician, treatment can be resumed.

When methotrexate is used for rheumatological indications, there is no obvious need for liver biopsy to monitor liver toxicity.

Particular attention should be paid to patients with risk factors such as excessive alcohol consumption, persistently elevated liver enzymes, history of liver disease, diabetes mellitus, obesity, history of use of hepatotoxic drugs or drugs that affect hematopoiesis.

Monitoring serum liver enzymes: Transient transaminase levels 2 to 3 times higher than normal have been reported in 13–20% of patients. If there is a persistent increase in liver enzyme levels, dose reduction or discontinuation of treatment should be considered.

Due to the toxic effects of the drug on the liver during treatment, patients should avoid concomitant use of other hepatotoxic drugs unless clearly necessary; Alcohol consumption should also be avoided or significantly reduced.

Liver enzyme levels should be carefully monitored in patients taking other hepatotoxic or hematotoxic drugs (eg leflunomide).

4. Monitoring kidney function and urine analysis.

Since methotrexate is eliminated primarily by the kidneys, increased plasma levels of methotrexate should be expected in cases of renal impairment, which may result in serious adverse side effects.

In cases of possible decline in renal function (for example in elderly patients), control examinations should be carried out more often. This also applies to cases of simultaneous administration of drugs that affect the elimination of methotrexate, drugs that can lead to kidney damage (for example, NSAIDs), as well as drugs that can affect the hematopoietic system.

Dehydration may also increase the toxicity of methotrexate.

5. Examination of the respiratory system.

Particular attention should be paid to symptoms of deteriorating pulmonary function, and appropriate tests should be carried out if necessary. Symptoms of respiratory damage (especially dry nonproductive cough), nonspecific pneumonitis that occur during methotrexate therapy may indicate a potentially dangerous disease and require interruption of treatment and a thorough examination in order to make a diagnosis. Clinical symptoms of methotrexate-induced lung injury are varied, but typical signs are fever, cough, difficulty breathing, and hypoxemia. An X-ray examination of the chest is mandatory to exclude the presence of infiltrates or infection.

The possibility of respiratory disease caused by the use of methotrexate does not depend on the doses of the drug used.

If the dose of methotrexate is increased, the frequency of examinations should be increased!

Methotrexate affects the immune system and may impair the response to vaccinations and affect the results of immunological tests. Particular caution is required when using the drug in patients with chronic infectious diseases outside of periods of exacerbation ( herpes zoster,

tuberculosis, hepatitis B or C) due to the possibility of exacerbation of the disease.

Refusal from immunization is required.

The interval between the use of methotrexate and the administration of live and inactivated viral vaccines should be at least 3 months, possibly up to 12 months (depending on the immune status of the patient).

If diarrhea and ulcerative stomatitis develop, methotrexate therapy should be interrupted.

Do not expose unprotected skin to too much sunlight or overuse UV lamps (photosensitization reaction is possible).

Combination with radiation therapy may increase the risk of bone marrow suppression.

Malignant lymphomas may occur in patients using low doses of methotrexate; in these cases, treatment should be discontinued. In the absence of signs of spontaneous regression of lymphoma, cytotoxic therapy is necessary.

When using methotrexate, osteonecrosis and osteoporosis may develop (≥1/1000, <1/100, “Side effects”), which increases the risk of fractures.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.

Since methotrexate can have an effect on the central nervous system (fatigue, dizziness), patients using the drug should refrain from driving or using machinery.

Arthritis

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis (synovitis) and systemic inflammatory damage to internal organs.

Prevention.

The etiology of RA is unknown, so primary prevention is not carried out.

Screening.

Screening is not carried out. Immunological disorders (increased titers of RF, ACCP and CRP) are detected several months or years before the development of clinical symptoms of RA.

general characteristics

Characterized by a variety of options for the onset of the disease. In most cases, the disease begins with polyarthritis; less often, manifestations of arthritis can be moderately expressed, and arthralgia, morning stiffness in the joints, deterioration in general condition, weakness, weight loss, low-grade body temperature, and lymphadenopathy predominate, which may precede clinically significant joint damage.

The development of arthritis may be preceded by a prodromal period of several weeks or months, manifested by fatigue, weight loss, periodic pain in the joints (often against the background of changes in atmospheric pressure), decreased appetite, increased sweating, low-grade body temperature, moderate anemia, and an increase in ESR.

In many patients, the disease begins with nonspecific joint damage, and it is defined as undifferentiated arthritis (UA). Among patients with AN, 30-50% develop significant RA during the first year of observation. In 40-55% there is spontaneous remission; in the rest, AN remains or another disease is detected.

What happens in joints with arthritis?

Overstimulation and dysregulation of the immune system leads to overproduction of T cells

T cells enter the joint synovium through the blood vessels and release pro-inflammatory cytokines >triggers a cascade of reactions in the joints> leads to the development of inflammation

The synovial membrane begins to proliferate and this leads to excess production of new fluid. This leads to swelling and swelling of the joint.

The cartilage becomes thinner and this leads to decreased joint protection

Pannus (granulation tissue) is formed from the synovial membrane

Bone breakdown (erosion) in areas where the synovial membrane touches the bone (this can be detected by radiographic examination)

In the later stages of the disease, joint cavities can be completely filled with granulation tissue

Scheme of changes in joints

Treatment

Goals of therapy.

The main goal of therapy is to achieve stable remission of the disease. The remaining tasks are:

Suppresses inflammation-related arthritis symptoms and extra-articular manifestations.
Prevention of destruction, dysfunction and deformation of joints.
Improving quality of life.
Reducing the risks of comorbid diseases.

Patients with RA should be treated by a rheumatologist for the following reasons:

The functional state of those under the supervision of rheumatologists is better than that of those supervised by a general practitioner.
The use of modern methods of pharmacotherapy for RA requires special values
It is necessary to inform patients about the nature of the disease and the side effects of the drugs used.
They use an interdisciplinary approach based on the use of non-pharmacological and pharmacological methods, involving, if necessary, specialists from other medical specialties (orthopedist, physiotherapist, cardiologist, neurologist, psychologist and others)

Drug treatment.

The following groups of drugs are used to treat RA:

Non-narcotic analgesic drugs-NSAIDs
"simple" analgesics
GK
DMARDs and GIBPs

General provisions

NSAIDs are prescribed to reduce joint pain
NSAIDs have a good sympomatic (analgesic) effect
NSAIDs do not affect the progression of joint destruction and disease prognosis
Treatment of RA is based on the use of DMARDs and GEBDs

DMARD therapy should be started as early as possible (within 3-6 months from the onset of symptoms), even if patients do not formally meet diagnostic criteria for RA (undifferentiated arthritis)

Early initiation of treatment with DMARDs and biologically active drugs helps improve function and slow the progression of joint destruction. Late administration of DMARDs (3-6 months after the onset of the disease) is associated with a decrease in the effectiveness of DMARD monotherapy.

Nonsteroidal anti-inflammatory drugs

Depending on their selectivity for COX-2, NSAIDs are divided into two categories - non-selective (N-NSAIDs) and selective (C-NSAIDs). NSAIDs are more effective at suppressing pain and inflammation than paracetamol. For RA, NSAIDs are used in combination with DMARDs.

Glucorticoids:

GCs should be used not as monotherapy, but in combination with DMARDs.

GCs in low/moderate doses effectively control clinical manifestations and progression of joint destruction. GCs are more effective than NSAIDs, and the effectiveness/cost ratio of GCs is better than that of NSAIDs.

Basic anti-inflammatory drugs

DMARD therapy should be administered to all patients without exception. DMARD and GEBD therapy reduces pain and inflammation, improves function and slows the progression of joint destruction.

When choosing therapy with DMARDs and GEBD, it is necessary to take into account the duration of the disease (< 6 months - early stage; 6-24 months - intermediate stage; >24 months - advanced stage), the activity of inflammation, the presence of unfavorable prognosis factors, comorbidity. Risk factors for an unfavorable prognosis include high RF titers, an increase in the concentration of ACCP, an increase in ESR and CRP concentration, and the rapid development of destruction in the joints.

Dynamic monitoring of the effectiveness and side effects of DMARD treatment is carried out by a rheumatologist and (as an exception) a general practitioner, but with the advisory support of a rheumatologist. *

Methotrexate is the most effective DMARD, the main component of combination therapy with other DMARDs and biologically active drugs. Compared to other DMARDs, it has the best efficacy/toxicity ratio.

Monotherapy is indicated regardless of the duration of the disease, activity and the presence of unfavorable prognosis factors. In patients starting treatment with methotrexate for the first time. Monotherapy with MTX has a better efficacy/toxicity ratio than combination therapy with MTX and other DMARDs. If MTX monotherapy is ineffective, it is advisable to carry out combination therapy with MTX and DMARDs or MTX and a GEBD.

Genetically engineered biological products (GEBP)

This is a group of drugs characterized by a selective effect on certain mechanisms of the development of chronic inflammation and are monoclonal antibodies to immunocompetent cells or proinflammatory cytokines, hybrid protein molecules that inhibit the activity of cytokines and the interaction of immunocompetent cells. Currently, 4 classes of GIBP are registered.

— TNF-α inhibitors: infliximab, adalimumab, etanercept, certolizumab pegol, golimumab

— Anti-B-cell drugs: rituximab

— IL-6 receptor inhibitors: tocilizumab

— T-lymphocyte costimulation blockers: abatacept

*Clinical guidelines. Rheumatology, 2nd edition, revised and expanded. Ed. acad. RAMS E.L. Nasonova

Methodject solution d/in. 10 mg/ml 2.5 ml No. 1 (syringe)

Methotrexate* (Methotrexatum)

Antitumor agent - antimetabolite [Immunosuppressants]

Solution:
transparent yellow liquid.
Pharmacological action - immunosuppressive, antitumor
Folic acid antagonist, belongs to the group of immunosuppressants. Competitively inhibits the enzyme dihydrofolate reductase, which is 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 DNA synthesis, repair and cellular mitosis. Rapidly proliferating cells are especially sensitive to the action of methotrexate: cells of malignant tumors, bone marrow, embryonic cells, epithelial cells of the mucous membranes.

Along with antitumor, it has an immunosuppressive effect.

It remains unclear whether the effectiveness of methotrexate in the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis (including juvenile chronic arthritis) is due to its anti-inflammatory or immunosuppressive effect. It has also not been established to what extent the effectiveness of therapy is explained by the methotrexate-induced increase in extracellular adenosine concentrations at sites of inflammation. In psoriasis, the use of methotrexate can slow down the significantly accelerated formation of epithelial skin cells.

About 50% of methotrexate is bound to plasma proteins.

Once distributed into tissues, high concentrations of methotrexate in the form of polyglutamates are found in the liver, kidneys and especially the spleen, where methotrexate can be retained for several weeks or even months.

When used in small doses, it penetrates into the cerebrospinal fluid only in minimal quantities.

T1/2 - on average 6–7 hours and is characterized by high variability (3–17 hours). T1/2 can increase to values 4 times higher than the average values in patients with additional Vd (presence of pleural effusion, ascites).

About 10% of the administered dose is metabolized in the liver, the main metabolite is 7-hydroxymethotrexate, which also has pharmacological activity.

It is excreted predominantly unchanged by the kidneys by glomerular filtration and tubular secretion.

About 5–20% of methotrexate and 1–5% of 7-hydroxymethotrexate are excreted in the bile (followed by intestinal reabsorption).

The elimination of the drug in patients with impaired renal function is significantly slower.

There is no evidence of a slower elimination of methotrexate in patients with insufficient liver function.

The most common side effects when using the drug Metoject are reactions from the hematopoietic system and gastrointestinal tract.

To indicate the frequency of effects, the following gradations are further used: very often (≥1/10); often (≥1/100, <1/10); sometimes (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000).

From the gastrointestinal tract:

very often - stomatitis, dyspepsia, nausea, loss of appetite; often - mouth ulcers, diarrhea; sometimes - pharyngitis, enteritis, vomiting; rarely - erosive and ulcerative lesions of the gastrointestinal tract; very rarely - vomiting mixed with blood, bleeding from the gastrointestinal tract (including melena, hematemesis).

From the side of liver function:

very often - increased transaminase levels; sometimes - cirrhosis, fibrosis and fatty degeneration of the liver, hepatotoxicity (acute hepatitis, liver failure).

For the skin and skin appendages:

often - exanthema, erythema, itching;
sometimes - photosensitivity, baldness, enlarged rheumatic nodes, vasculitis, herpes zoster
, herpetiform skin rashes, urticaria; rarely - increased pigmentation; very rarely - changes in nail pigmentation, acute paronychia, Stevens-Johnson syndrome, epidermal necrolysis (Lyell's syndrome).

When treating psoriasis:

burning sensation of the skin; rarely - painful erosive plaques on the skin.

General reactions:

allergic reactions up to anaphylactic shock;
allergic vasculitis, fever, sepsis, life-threatening opportunistic infections (including Pneumocystis pneumonia), CMV infections (including CMV pneumonia), sepsis (including fatal), nocardiosis, histoplasmosis, cryptococcosis ; infections caused by Herpes zoster
and
Herpes simplex
(including disseminated), impaired wound healing, pleural effusion, pancreatitis, diabetes mellitus, soft tissue necrosis, nosebleeds, increased sweating, hypogammaglobulinemia.

From the SSS side:

pericarditis, pericardial effusion, pericardial tamponade, decreased blood pressure, thromboembolism (including arterial thrombosis, cerebral vascular thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, pulmonary embolism).

From the nervous system:

often - headache, feeling tired, drowsiness; sometimes - dizziness, confusion, depression; very rarely - pain, muscle weakness or paresthesia of the limbs, impaired taste (metallic taste), convulsions, meningism, paralysis.

From the side of the organ of vision:

conjunctivitis; very rarely - visual impairment (including transient blindness).

From the respiratory system:

often - interstitial alveolitis/pneumonia; symptoms of potentially serious interstitial pneumonia include a dry, nonproductive cough, shortness of breath, and fever; rarely - pulmonary fibrosis, pulmonary pneumocystis, pulmonary insufficiency and bronchial asthma.

From the hematopoietic system:

often - leukopenia, anemia (including aplastic), neutropenia, thrombocytopenia; sometimes - pancytopenia; very rarely - agranulocytosis, severe suppression of bone marrow function.

From the genitourinary and urinary systems:

sometimes - inflammation and ulceration of the bladder or vagina, painful urination, hematuria, hyperuricemia, renal failure; rarely - severe renal failure, oliguria, anuria, azotemia, electrolyte imbalance; very rarely - vaginal discharge, loss of sexual desire, impotence, oligospermia, menstrual irregularities, infertility.

From the musculoskeletal system:

sometimes - arthralgia, myalgia, osteoporosis, increased risk of fractures.

Neoplasms:

very rarely - isolated cases of lymphoma have been reported. A recent study did not find that methotrexate therapy increased the incidence of lymphoma.

The frequency and severity of side effects of methotrexate treatment depend on the dose and frequency of use. However, severe side effects can also occur when using methotrexate in low doses, so it is necessary that patients using methotrexate undergo regular medical examination at short intervals.

When using methotrexate intramuscularly, local reactions may occur: a burning sensation at the injection site, the formation of a sterile abscess, destruction of fatty tissue.

Alcohol, hepatotoxic and hematotoxic drugs.

Regular consumption of alcohol and the use of hepatotoxic drugs simultaneously with methotrexate increase the risk of methotrexate hepatotoxicity. Patients using other hepatotoxic drugs (eg leflunomide) should be closely monitored. This also applies to cases of simultaneous administration of drugs that inhibit hematopoiesis, which increases the risk of developing hematotoxicity of methotrexate. When leflunomide and methotrexate are administered concomitantly, the risk of pancytopenia and hepatotoxicity increases.

Antibacterial drugs.

Antibiotics such as penicillins, glycopeptides, ciprofloxacin, cephalothin and sulfonamides may in some cases reduce the renal excretion of methotrexate, which leads to an increase in its plasma concentration and thus to the risk of hematological and gastrointestinal toxicity.

Probenecid, weak organic acids, pyrazolone drugs and other NSAIDs.

Probenecid, weak organic acids (such as loop diuretics) and pyrazolone drugs (phenylbutazone) reduce the elimination of methotrexate and may lead to an increase in its plasma concentration and thus to increased hematological toxicity. The risk of increased toxicity occurs when methotrexate is combined with NSAIDs or salicylates.

Concomitant use of salicylates, phenylbutazone, phenytoin, sulfonamides, sulfonylurea derivatives, aminobenzoic acid, pyrimethamine or trimethoprim, a number of antibiotics (penicillin, tetracycline, chloramphenicol), indirect anticoagulants and lipid-lowering drugs (cholestyramine) increases toxicity due to the displacement of methotrexate from its connection with albumin. minami and/ or a decrease in tubular secretion, which in some cases can lead to the development of severe toxic effects, sometimes even fatal.

Drugs affecting the bone marrow.

In the case of using drugs that can affect the bone marrow, incl. as a side effect (for example, sulfonamides, trimethoprim-sulfamethoxazole, chloramphenicol, pyrimethamine), the possibility of inhibition of hematopoiesis must be taken into account.

Sulfasalazine.

The combination of methotrexate with sulfasalazine may increase the effectiveness of methotrexate and, as a result, increase the side effects associated with inhibition of folic acid synthesis by sulfasalazine. However, such side effects were observed in a number of studies only in isolated rare cases.

Proton pump inhibitors.

With the simultaneous administration of proton pump inhibitors (omeprazole, pantoprazole), the elimination of methotrexate may change. The simultaneous use of methotrexate and omeprazole increases the elimination time of methotrexate. One case of decreased excretion of the methotrexate metabolite, 7-hydroxymethotrexate, was reported, accompanied by myalgia and tremors.

Caffeine- and theophylline-containing drinks.

During treatment with methotrexate, you should avoid drinking large quantities of caffeine- and theophylline-containing drinks (including coffee, tea).

Drugs that can cause folate deficiency.

The simultaneous administration of such drugs (for example, sulfonamides, trimethoprim-sulfamethoxazole) may lead to increased toxicity of methotrexate. Therefore, it is recommended to be especially careful when prescribing such drugs to avoid the development of folic acid deficiency.

Folate-containing drugs (including multivitamins)

reduce the toxic effect of methotrexate on the bone marrow.

Methotrexate increases the anticoagulant activity of coumarin or indanedione derivatives and/or increases the risk of bleeding by reducing the synthesis of procoagulant factors in the liver and impairing platelet formation.

It increases the concentration of uric acid in the blood, therefore, when treating patients with concomitant hyperuricemia and gout, dose adjustment of anti-gout drugs (allopurinol, colchicine, sulfinpyrazone) may be required.

Anesthesia using dinitrogen oxide can lead to the development of unpredictable severe myelosuppression and stomatitis.

Reduces the clearance of theophylline.

Several patients with psoriasis treated with methotrexate in combination with PUVA therapy (methoxsalen and UVB) have been diagnosed with skin cancer.

Methotrexate can reduce the immune response to vaccination, therefore the interval between the use of methotrexate and the administration of live and inactivated viral vaccines should be at least 3 months, possibly up to 12 months (depending on the patient’s immune status).

Pharmaceutical incompatibility

Compatibility with other drugs used parenterally has not been studied. It is recommended not to mix Metoject with other drugs and solvents.

Patients should be clearly informed that the drug should be used once a week and not daily.

Methotrexate is cytotoxic and must be handled with caution.

Methotrexate affects fertility and is an embryo-, fetotoxic and teratogenic drug. Shows mutagenic activity in vivo

and
in vitro.
A carcinogenicity study in rodents did not show an increase in the incidence of tumors with methotrexate.

Patients undergoing treatment with Metoject should be closely monitored to ensure that signs of potential toxicity and adverse reactions are detected and assessed with minimal delay.

Methoject should only be prescribed by a physician with sufficient knowledge and experience in anti-metabolic therapy.

Due to the possible development of severe or even fatal adverse reactions, patients should be fully informed by their physician about the possible risks and recommended safety measures.

Recommended examinations and safety measures

Before starting or resuming treatment with methotrexate:

During treatment (at least once a month in the first 6 months of treatment, then at least once every 3 months) it is necessary to:

1. Examination of the oral mucosa and pharynx.

When methotrexate is used for rheumatological indications, there is no obvious need for liver biopsy to monitor liver toxicity.

Liver enzyme levels should be carefully monitored in patients taking other hepatotoxic or hematotoxic drugs (eg leflunomide).

4. Monitoring kidney function and urine analysis.

Since methotrexate is eliminated primarily by the kidneys, increased plasma levels of methotrexate should be expected in cases of renal impairment, which may result in serious adverse side effects.

Dehydration may also increase the toxicity of methotrexate.

5. Examination of the respiratory system.

The possibility of respiratory disease caused by the use of methotrexate does not depend on the doses of the drug used.

If the dose of methotrexate is increased, the frequency of examinations should be increased!

tuberculosis, hepatitis B or C) due to the possibility of exacerbation of the disease.

Refusal from immunization is required.

If diarrhea and ulcerative stomatitis develop, methotrexate therapy should be interrupted.

Do not expose unprotected skin to too much sunlight or overuse UV lamps (photosensitization reaction is possible).

Combination with radiation therapy may increase the risk of bone marrow suppression.

When using methotrexate, osteonecrosis and osteoporosis may develop (≥1/1000, <1/100, “Side effects”), which increases the risk of fractures.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.

Since methotrexate can have an effect on the central nervous system (fatigue, dizziness), patients using the drug should refrain from driving or using machinery.

About the development of pathology

Rheumatoid arthritis is an autoimmune disease that causes inflammation, swelling, pain, and deformation in the joints (mainly the small joints of the hands and feet), leading to impaired mobility. The exact cause of the development of the pathology is still unknown, but scientists are inclined to a multifactorial theory, in which heredity plays a leading role. RA also contributes to:

frequent infections (including herpes virus);
toxic effects of medications or environmental factors;
nervous tension;
exposure to low temperatures;
changes in hormonal levels (menopause, pregnancy).

It is assumed that under the influence of toxic substances or under stress, the immune system malfunctions, and its cells begin to attack the tissues of their own body, destroying them.

Currently, rheumatoid arthritis is, along with gout, the most common inflammatory disease of the joints.

Clinical picture

The disease has several variants of its course. Both an acute onset and a slow gradual onset of symptoms are possible. In the second case, the disease begins with nonspecific manifestations: general weakness, increased body temperature, muscle pain. Subsequently, stiffness and pain in the joints appear. With this course, only one or several joints may be affected, with the gradual involvement of new parts of the musculoskeletal system in the process.

In the classic progression of RA, the disease begins with swelling, pain, and stiffness in the small joints of the hands. The process is symmetrical. A characteristic symptom is increased pain at rest and a decrease in pain with movement. Stiffness is greatest in the morning; its duration reaches several hours.

The danger of untimely treatment of rheumatoid arthritis lies in possible complications both from the musculoskeletal system (deformations and permanent loss of function) and from other internal organs (heart, blood vessels, lungs, kidneys, eyes).

Diagnosis and therapy of rheumatoid arthritis

At the Yauza Clinical Hospital, rheumatoid arthritis is treated by experienced rheumatologists, and if necessary, related specialists are involved (ophthalmologist, cardiologist, neurologist).

Diagnosis of the disease includes: examination by a doctor, general blood test, detailed biochemical and immunological blood test (determining the level of rheumatoid factor, C-reactive protein, antibodies to citrullinated proteins, etc.), radiation methods (radiography, CT or MRI of joints); In some cases, patients are prescribed a microscopic examination of synovial fluid and a biopsy of joint tissue. The set of diagnostic procedures is determined individually, based on the patient’s condition and his wishes.

Treatment of rheumatoid arthritis involves the prescription of anti-inflammatory drugs of various pharmacological groups, the so-called “basic” disease-modifying drugs, physiotherapeutic methods of treatment; in the presence of irreversible joint deformities, surgical treatment is indicated.

Also, extracorporeal hemocorrection (EG, gravitational blood surgery, GCH) has a significant therapeutic effect, especially in the initial stages of the disease and during exacerbation.

Extracorporeal hemocorrection in the treatment of RA

EG methods, as a component of conservative therapy, are indicated for:

High activity of the process, which is confirmed by laboratory tests;
Damage to other organs and systems (pleura, kidneys);
Insufficient effectiveness of standard therapy;
Severe complications of conservative therapy (peptic ulcer, bleeding disorders, fat and carbohydrate metabolism, etc.);
The presence of contraindications to the prescription of hormonal therapy.

At the Yauza Clinical Hospital, the following EG methods are used to treat rheumatoid arthritis:

Combination of cryoapheresis and cell mass incubation. With the help of low temperatures, harmful components (autoantibodies, circulating immune complexes - CIC, pro-inflammatory cytokines) are precipitated and removed from the patient's blood plasma, thereby inhibiting the development of the disease. Isolating cellular elements from the blood and saturating them with a medicinal substance allows us to deliver the medicine in containers exactly to the area of autoimmune inflammation, ensuring its high concentration where it is needed, and significantly reducing the overall effect on the body (leveling side effects).
Granulocytopheresis. Granulocytes are a type of leukocytes (neutrophils), which, in rheumatoid arthritis, support the activity of inflammatory processes in the tissues of the body, in particular in the joints. Their elimination from the blood contributes to the rapid relief of pain and the onset of remission.
Cascade plasma filtration. The patient's plasma is passed through a special filter, in which components that trigger and maintain inflammation in tissues (autoantibodies, CEC, complement components, cytokines) are removed from it. This technique allows you to process from 3 to 6 liters of plasma in one session, depriving it of auto-aggressive immune products.
Lymphocytapheresis. This technique allows you to remove from the blood auto-aggressive blood cells (lymphocytes) that damage body cells (T-lymphocytes), as well as those that produce autoantibodies (B-lymphocytes) that attack your own tissues, which helps to attenuate inflammation processes, reduce doses of immune-suppressing drugs or completely cancellation, increasing the period of remission, slowing down or stopping the patient’s disability and long-term preservation of working capacity.
Photopheresis. Lymphocytes are isolated from the blood, treated with photosensitizers (drugs that increase the sensitivity of blood cells to the effects of ultraviolet radiation) and subjected to ultraviolet irradiation. Treated lymphocytes stop attacking their own cells and tissues, and inflammatory activity quickly subsides.

Each of the techniques can be used either alone or in combination with other EG techniques. Thus, in case of autoimmune diseases, in particular rheumatoid arthritis, it is possible to diversify the pathogenesis of the disease: reduce the auto-aggressive behavior of cells of the immune system, as well as remove from the blood products already produced by lymphocytes that damage one’s own tissues and organs. Our experienced doctors choose EG methods, taking into account the individual characteristics of each patient and clinical case.