The drug methotrexate. Methotrexate injections analogues, synonyms and drugs of the group. From the genitourinary system

In case of lung cancer, the doctor will definitely offer the patient anticancer drugs. One of the effective and well-proven drugs is Methotrexate Vero. The drug is highly toxic, so you need to use it correctly. Doctors resort to it in the most extreme cases, when the tumor is malignant. It is prescribed in combination with other medicines in the chemotherapy regimen or separately. Consider what side effects the medication has and how to properly use methotrexate injections in one article.

Features of prescribing the drug

Methotrexate solution has a Latin name (Methotrexate). Belongs to the antimetabolite group. Has an antitumor effect. It is produced in the form of a concentrated substance for intramuscular and intravenous injection, film-coated pills. The drug enhances the process of reduction of diuglyfolic acid, is involved in the transfer of carbon fragments during protein synthesis. Synthesis slows down and the process of tumor growth slows down. The drug has the greatest effect on cells: malignant formations, mucous gastrointestinal tract, oral cavity and bladder. It fights tumors, but at the same time it has an immunosuppressive effect.

Analogues of methotrexate include drugs: Vero methotrexate, Zeksat, Metozhekt, Methotrexate: Lahema, sodium, LENS, Teva, Ferein, Ebeve, Trexan, Trixil. The price of drugs differs slightly, and starts from 2000 rubles. Their manufacturers and additional components distinguish them. Of the most gentle and effective, Vero Methotrexate stands out.

Prescribing the drug

Assign a solution of methotrexate vero in the following cases:

• cancer: head, mammary glands, lungs, uterus, ovaries, urinary bladder, gastrointestinal tract, testicle, meninges;
• Leukemia lymphoblastic;
• Burkitt's lymphoma;
• acute form of arthritis;
• psoriasis in advanced form;
• rheumatoid arthritis.

The solution is prescribed only in the most extreme cases. Since the active substance kills the patient's immunity. While taking the drug, it is recommended to limit contact with viruses and bacteria.

The patient's health worsens, constant weakness and nausea accompany the intake.

Medication contraindications

The drug is toxic, therefore it has multiple contraindications:

• Individual sensitivity to Methotrexate vero;
• pregnancy and breastfeeding;
• renal and liver failure;
• a viral or bacterial disease;
• contact within 10 days before the first vaccine with patients with: chickenpox, herpes, measles, mumps, rubella;
• inflammation of the gastrointestinal tract and nasopharyngeal mucosa;
• reduced bone marrow circulation.

Before starting treatment, it is necessary to undergo examinations for hidden bacterial and viral infections. Methotrexate vero will reduce immunity and banal herpes will turn into an acute form.

A few days before taking the solution, limit contact with people, since incubation period some viruses and bacteria in the body can reach 1 month, such as hepatitis.

Possible side effects of the medication

Since methotrexate vero belongs to the hypertoxic group, it has many side effects:

• On the part of the blood circulation: a week after the start of administration, leukopenia worsens and platelet production worsens. The syndrome disappears a week after the solution is canceled.
• The gastrointestinal tract responds to chemotherapy: decreased appetite, vomiting, stomatitis in the form of ulcers, nausea, stomach ulcers, bleeding in the gastrointestinal tract, sometimes ending in death.
• On the part of the vessels and the nervous region of the body: drowsiness increases, migraines, vision deteriorates, convulsions with seizures, impaired consciousness, coordination is lost, spatial perception is sometimes disturbed. In case of overdose in patients over 55 years of age or when infected with a viral disease, pain in the spinal region, fainting, high fever.
• From the urinary and genital side of the body: cystitis, kidney failure, early miscarriage, infertility. Dangerous pregnancy during the course of methotrexate vero, abnormal development of the fetus and intrauterine death.
• Skin reactions of the body: skin rashes, itching, redness, sores, acne. The cover changes color to pale blue.
• In people prone to an allergic reaction: fever, febrile manifestations, rashes and itching, shortness of breath in short attacks.
• The reaction of the organs of vision: acute conjunctivitis, vision deteriorates, with an overdose - blindness.
• The organs of the respiratory system react to the drug as follows: pneumonia, fibrosis.
• The rhythm of the heart is disturbed, tamponade and pericardial lunges are possible.
• Other side effects stand out: a decrease in the immune system, exacerbation of diabetes mellitus, bacterial and viral infections immediately after entering the body cause severe damage, since the immune system is unable to fight them. Any disease, flu or acute respiratory infections immediately turns into an acute form, pneumonia.

Side effects can be mitigated only by choosing the right dosage of the medication. The scheme for each patient is selected individually by the attending physician.

Standard dosage regimen

The solution is administered, depending on the form and dosage, intravenously, intramuscularly and in tablets.

The pills must be taken before meals, the dosage is calculated by your doctor. It depends on the complexity of the disease, the weight and volume of the patient's body.

A dosage exceeding 100 mg per m² of the patient's body is administered only intravenously in a hospital. For instillation, Vero is diluted in a solution with calcium phtholinate or 5% deoxtrose, in a ratio of 10 mg per 1 liter. The dosage of intramuscular and intravenous injections depends on the type and complexity of the disease, the age category of the patient, body weight. Let's take a closer look at the dosage of the drug in the form of a table:

The duration of any chemotherapy is unknown, depending on the behavior of the tumor. When the disease goes into remission, the dosage of methotrexate vero is reduced.

How does methotrexate, shown in the video:

Admission rules

Since chemotherapy is extremely dangerous, it is better to inject the solution into medical institution. The patient should know a number of rules that will help to protect himself as much as possible from a disastrous outcome:

1. We recommend contraception during chemotherapy with methotrexate. It is worth protecting yourself from pregnancy: for men during the procedure and after it for 3-4 months, for women: 2 months before the procedure, during it and a year after.
2. To normalize the body after the procedure, it is necessary to control platelets and lymphocytes. To do this, once every 2 days you need to donate blood.
3. To reduce the toxicity of the drug after taking the course, the use of calcium foliant is recommended.
4. Before each use, it is necessary to examine the mucous membrane of the mouth and nose for the presence of sores in it.
5. If stomatitis or intestinal upset occurs in the form of bloody diarrhea, the course is immediately stopped, since most cases with similar phenomena end in death.
6. The course should be postponed in case of exacerbation of diabetes mellitus, obesity of 2-3 degrees.
7. During treatment, liver function is checked, for this, a biopsy is taken every 2-3 months.
8. You can not take sun baths or sunbathe in a solarium during the course.
9. You can not use drugs that stimulate the body's immune system, 1 month before the course and 2 months after.
10. Avoid contact with people who have been vaccinated with polio.
11. Throughout the course and a month after, a protective mask is put on the mouth and nose. Small children are placed in a special sealed sterile ward.

Chemotherapy always brings a lot of unpleasant side effects. But without it it is impossible to cope with cancer. Patience and the right dosage will smooth everything out discomfort at the patient.

Special conditions

Compound

• For 1 ml:
• active ingredient: methotrexate - 10,000 mg;
• excipients: sodium hydroxide - 1.783 mg, sodium chloride - 6.900 mg, water for injection - 988.317 mg.

Methotrexate indications for use

• - trophoblastic tumors;
• - acute leukemias (especially lymphoblastic and myeloblastic variants);
• - neuroleukemia;
• - non-Hodgkin's lymphomas, including lymphosarcoma;
• - breast cancer, squamous cell head and neck cancer, lung cancer, skin cancer, cervical cancer, vulvar cancer, esophageal cancer, kidney cancer, bladder cancer, testicular cancer, ovarian cancer, penile cancer, retinoblastoma, medulloblastoma;
• - osteogenic sarcoma and soft tissue sarcoma;
• - mycosis fungoides (advanced stages);
• - severe forms of psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile chronic arthritis, dermatomyositis, systemic lupus erythematosus, ankylosing spondylitis (if standard therapy is ineffective).

Methotrexate contraindications

• - hypersensitivity to methotrexate and / or any other component of the drug;
• - severe renal failure (creatinine clearance less than 30 ml / min);
• - severe liver failure;
• - alcohol abuse;
• - disorders of the hematopoietic system in history (in particular, bone marrow hypoplasia, leukopenia, thrombocytopenia or clinically significant anemia);
• - severe acute and chronic infectious diseases such as tuberculosis and HIV infection;
• - concomitant vaccination with live vaccines;
• - ulcers of the oral cavity, peptic ulcer of the gastrointestinal tract in the active phase;
• - pregnancy;
• - the period of breastfeeding;
• - simultaneous use of methotrexate at a dose of 15 mg / week or more with acetylsalicylic acid.
• Carefully:
• Use with caution in patients with impaired liver and kidney function, diabetes mellitus, obesity and previous therapy with hepatotoxic drugs, dehydration, ascites, oppression of bone marrow hematopoiesis, pleural

Methotrexate dosage

• 10 mg/ml

methotrexate side effects

• According to the World Health Organization (WHO), adverse events are classified according to the frequency of their development as follows: very often (less than 1/10), often (from less than 1/100 to
• Infectious and parasitic diseases
• often: herpes zoster; infrequently: opportunistic infections, including pneumonia (including fatal); rarely: sepsis (including, very rarely, fatal); very rarely: nocardiosis, histoplasmosis, cryptococcosis, hepatitis and disseminated infections caused by the herpes simplex virus, infections caused by cytomegalovirus (including pneumonia); frequency unknown: reactivation of hepatitis B virus, hepatitis C.
• Benign, malignant and unspecified neoplasms (including cysts and polyps)
• infrequently: lymphoma; very rarely: tumor lysis syndrome.
• Disorders of the blood system and lymphatic system very often: leukopenia, thrombocytopenia; often: anemia, pancytopenia, agranulocytosis; rarely: megaloblastic anemia; very rarely: aplastic anemia, lymphadenopathy and lymphoproliferative diseases, eosinophilia, neutropenia, severe progressive depression of bone marrow function.
• Immune System Disorders
• infrequently: allergic reactions, anaphylactic shock, allergic vasculitis, fever, immunosuppression; very rare: hypogammaglobulin pyemia.
• Metabolic and nutritional disorders
• infrequently: diabetes mellitus.
• Mental disorders
• infrequently: depression; rarely: transient cognitive impairment, emotional lability.
• Nervous System Disorders
• often: headache, fatigue, drowsiness, paresthesia; infrequently: convulsions, development of hemiparesis, vertigo (dizziness), confusion, encephalopathy / leukoencephalonatia (including fatal cases);
• rarely: paresis, speech disorders, including dysarthria and aphasia, myelopathy (with intrathecal administration); very rarely: discomfort in the head, myasthenia gravis, pain in the extremities, taste perversion ( metallic taste in the mouth), acute aseptic meningitis with symptoms of meningism (paralysis, vomiting), insomnia; frequency unknown: increased pressure in the spinal canal (after intrathecal injection), the development of a herniated spinal cord (after intrathecal injection for periventricular lymphoma).
• Violations of the organ of vision
• rarely: visual disturbances (blurred vision, including severe visual impairment of unclear etiology);
• very rarely: periorbital edema, blepharitis, lacrimation, photophobia, conjunctivitis, transient blindness, loss of vision.
• Heart disorders
• rarely: arterial hypotension (decreased blood pressure); very rarely: pericarditis, pericardial effusion (including cardiac tamponade).
• Vascular disorders
• infrequently: vasculitis; rarely: thromboembolic complications (including arterial thrombosis, cerebral thrombosis, thrombophlebitis, deep vein thrombosis, retinal vein thrombosis, pulmonary embolism).
• Respiratory, thoracic and mediastinal disorders
• often: interstitial pneumonitis/alveolitis (including
• fatal, regardless of the dose and duration of methotrexate therapy). Symptoms suggestive of potentially serious lung damage from interstitial pneumonitis include dry, non-productive cough, shortness of breath progressing to shortness of breath at rest, chest pain, fever. If these symptoms occur, treatment with methotrexate should be stopped immediately, and infections of the lower respiratory tract should also be excluded. infrequently: pulmonary fibrosis, effusion in the pleural cavity; rarely: pharyngitis, sleep apnea, epistaxis; very rarely: chronic obstructive pulmonary disease (COPD), asthma-like reactions (accompanied by cough, shortness of breath, abnormal lung function tests), pneumonia caused by Pneumocystis carinii, acute edema lungs; frequency unknown: respiratory paralysis.
• Gastrointestinal disorders
• very often: stomatitis, pain in the abdomen, loss of appetite, nausea and vomiting (especially in the first 24-48 hours after the start of treatment), dyspepsia; often: diarrhea; infrequently: ulceration of the mucous membrane of the gastrointestinal tract (GIT), bleeding from the GIT, pancreatitis; rarely: enteritis, gingivitis, melena, malabsorption syndrome; very rarely: hematemesis (bloody vomiting), toxic megacolon; frequency unknown: non-infectious peritonitis.
• Liver and biliary tract disorders
• very often: an increase in the activity of "liver" transaminases, alkaline phosphatase, an increase in the concentration of bilirubin in the blood plasma; often: the development of steatosis, fibrosis or cirrhosis of the liver, hyioalbuminemia; rarely: acute hepatitis and other manifestations of hepatotoxicity; very rarely: exacerbation of chronic hepatitis, acute liver dystrophy (including against the background of acute herpetic hepatitis), acute liver failure, liver necrosis.
• Skin and subcutaneous tissue disorders
• often: exanthema, erythematous rash, itching of the skin; infrequently: alopecia, erythema multiforme (including malignant exudative erythema [Stevens-Johnson syndrome]), toxic epidermal necrolysis (Lyell's syndrome), skin rashes herpetiformis, photosensitivity, urticaria, increased skin pigmentation, delayed wound healing; rarely: acne, skin ulceration, ecchymosis, the appearance of nodules on the skin, painful erosions, psoriatic plaques, pigmentation of the nails, onycholysis, an increase in the size of rheumatoid nodules; very rarely: furunculosis, telangiectasia, acute paronychia, hidradenitis; frequency unknown: skin necrosis (at the injection site).
• Against the background of methotrexate therapy, complications from psoriatic nodules may develop due to exposure to ultraviolet radiation.
• From the musculoskeletal system and connective tissue
• infrequently: arthralgia, myalgia, osteoporosis; rarely: marching (fatigue) fracture.
• From the side of the kidneys and urinary tract
• very often: decreased creatinine clearance; infrequently: severe nephropathy, renal failure, cystitis with ulceration of the mucous membrane of the bladder, dysuria (urinary disorders), oliguria, anuria; rarely: hypsruricemia, increased plasma urea concentration, increased plasma creatinine concentration; very rarely: azotemia, hematuria, proteinuria.
• Influence on the course of pregnancy, postpartum and perinatal conditions
• infrequently: anomalies in the development of the fetus; rarely: premature termination of pregnancy; very rare: fetal death.
• Genital and breast disorders
• infrequently: vaginitis and ulceration of the vaginal mucosa; rare: disorders menstrual cycle; very rare: disorders of spermatogenesis or egg maturation, impotence, infertility, loss of libido, transient oligospermia, abnormal vaginal discharge, menstrual disorders, gynecomastia.
• Adverse reactions that occur with intrathecal administration of methotrexate: acute chemical arachnoiditis (clinical manifestations include headache, dorsalgia, numbness in the neck and fever), subacute myslopathy (paresis or paraplegia in the area of ​​innervation of one or more affected roots of the spinal cord), chronic leukoencephalopathy, whose manifestations include confusion, irritability, drowsiness, ataxia, dementia, convulsions and the development of a coma. In the case of progression, these manifestations of toxicity can lead to the death of the patient.
• The combined use of intrathecal methotrexate and brain irradiation increases the risk of developing leukoencephalopathy. After intrathecal administration of the drug, the patient's condition should be carefully monitored for development possible signs neurotoxicity (meningismus, paralysis, encephalopathy).

drug interaction

Overdose

Storage conditions

• store at room temperature 15-25 degrees
• keep away from children
• store in a place protected from light

Active substance

Methotrexate (methotrexate)

Release form, composition and packaging

50 pcs. - polymer cans (1) - packs of cardboard.

pharmachologic effect

An antitumor, cytostatic agent of the antimetabolite group, inhibits dihydrofolate reductase, which is involved in the reduction of dihydrofolic acid to tetrahydrofolic acid (the carrier of carbon fragments necessary for the synthesis of purine nucleotides and their derivatives).

Inhibits synthesis, DNA repair and cell mitosis. Rapidly proliferating tissues are especially sensitive to the action: cells of malignant tumors, bone marrow, embryonic cells, epithelial cells of the intestinal mucosa, bladder, and oral cavity. Along with antitumor, it has an immunosuppressive effect.

Pharmacokinetics

Oral absorption depends on the dose: when taken at 30 mg / m 2, it is well absorbed, the average bioavailability is 60%. Absorption is reduced when taken in doses exceeding 80 mg / m 2.

In children with leukemia, absorption ranges from 23% to 95%. The time to reach C max is from 40 minutes to 4 hours. Food slows down absorption and reduces C max. Communication with proteins - about 50%, mainly with albumin.

After distribution in tissues, high concentrations of methotrexate in the form of polyglutamates are found in the liver, kidneys and especially in the spleen, in which methotrexate can be retained for several weeks or even months.

When taken in therapeutic doses, it practically does not penetrate the blood-brain barrier. Penetrates into breast milk.

After oral administration, it is partially metabolized by the intestinal flora, the main part - in the liver (regardless of the route of administration) with the formation of a pharmacologically active polyglutamine form, which also inhibits dihydrofolate reductase and thymidine synthesis. T 1/2 in patients receiving less than 30 mg / m 2 of the drug, in the initial phase is 2-4 hours, and in the final phase (which is long) - 3-10 hours when using small and 8-15 hours - when using large doses of the drug. In chronic renal failure, both phases of drug elimination can be significantly prolonged.

It is excreted mainly by the kidneys in unchanged form by glomerular filtration and tubular secretion, up to 10% is excreted in the bile (with subsequent reabsorption in the intestine). Elimination of the drug in patients with impaired renal function, severe ascites or transudate is significantly slowed down. With repeated administration, it accumulates in tissues in the form of polyglutamates.

Indications

- acute lymphoblastic leukemia and non-Hodgkin's lymphomas;

- trophoblastic tumors;

- fungal mycosis in advanced stages;

- severe forms of psoriasis;

- rheumatoid arthritis (with the ineffectiveness of other methods of therapy).

Contraindications

The use of methotrexate is contraindicated during pregnancy and lactation, with pronounced changes in kidney and liver function, with hematological disorders (such as bone marrow hypoplasia, leukopenia, thrombocytopenia, anemia), with acute stage infectious diseases, immunodeficiency syndrome, with hypersensitivity to methotrexate or other components of the tablet, children under 3 years old.

Carefully. With ascites, effusion into the pleural cavity, peptic ulcer stomach and duodenum, ulcerative colitis, dehydration, gout or nephrolithiasis in history, previous radiation therapy or chemotherapy, infectious diseases of a viral, fungal or bacterial nature.

Dosage

Methotrexate tablets are taken orally. Doses and terms of treatment are set individually depending on the chemotherapy regimen.

Trophoblast tumors:

- 15-30 mg orally daily for 5 days at intervals of one or more weeks (depending on signs of toxicity). Treatment courses are usually repeated 3 to 5 times.

- 50 mg 1 time in 5 days with an interval of at least 1 month. The course of treatment requires 300-400 mg.

Acute lymphoblastic leukemia (as part of complex therapy):

- 3.3 mg / m 2 in combination with until remission is achieved, then 15 mg / m 2 times a week or 2.5 mg / kg every 14 days.

Non-Hodgkin's lymphomas (as part of complex therapy):

- 15-20 mg / m 2 for 1 dose 2 times a week;

- 7.5 mg / m 2 daily for 5 days.

Rheumatoid arthritis:

The initial dose is usually 7.5 mg once a week, which is taken simultaneously or divided into three doses with an interval of 12 hours. For optimal effect, the weekly dose may be increased, while it should not exceed 20 mg. When the optimal clinical effect is achieved, dose reduction should be initiated until the lowest effective dose is reached. The optimal duration of therapy is not known. In juvenile chronic arthritis for children, doses of 10-30 mg / m 2 / week (0.3-1 mg / kg) are effective.

Psoriasis:

Therapy with methotrexate is carried out in doses of 10 to 25 mg per week. The dose is usually increased gradually, when the optimal clinical effect begin dose reduction until the lowest effective dose is reached.

Fungal mycosis:

- 25 mg 2 times a week. Reducing the dose or canceling the administration of the drug is determined by the patient's response and hematological parameters.

Side effects

From the hematopoietic system: anemia (including aplastic), thrombocytopenia, leukopenia, neutropenia, agranulocytosis, eosinophilia, pancytopenia, lymphoproliferative diseases, hypogammaglobulinemia, lymphadenopathy.

From the side digestive system: anorexia, nausea, vomiting, stomatitis, gingivitis, pharyngitis, enteritis, erosive and ulcerative lesions and bleeding from the gastrointestinal tract (including melena, hematemesis), hepatotoxicity (acute hepatitis, fibrosis and cirrhosis of the liver, liver failure, hypoalbuminemia, increased activity of "liver transaminase), pancreatitis.

From the nervous system: headache, dizziness, drowsiness, dysarthria, aphasia, hemiparesis, paresis, convulsions; when used in high doses - transient impairment of cognitive functions, emotional lability; unusual cranial sensitivity, encephalopathy (including leukoencephalopathy).

From the side of the organ of vision: conjunctivitis, visual impairment (including transient blindness).

From the side of cardio-vascular system: pericarditis, pericardial effusion, decreased blood pressure, thromboembolism (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, pulmonary embolism).

From the respiratory system: rarely - pulmonary fibrosis, respiratory failure, alveolitis, interstitial pneumonitis (including fatal), chronic obstructive pulmonary disease (COPD), symptoms of a potentially serious interstitial pneumonia- dry non-productive cough, shortness of breath, fever.

From the genitourinary system: severe nephropathy or renal failure, azotemia, cystitis, hematuria, proteinuria, impaired spermatogenesis and ovogenesis, transient oligospermia, decreased libido, impotence, dysmenorrhea, vaginal discharge, gynecomastia, infertility, miscarriage, fetal death, fetal developmental defects.

From the side of the skin: erythematous rash, skin itching, urticaria, photosensitivity, skin pigmentation disorders, alopecia, ecchymosis, telangiectasia, acne, furunculosis, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis, ulceration and necrosis of the skin, exfoliative dermatitis. In the treatment of psoriasis - a burning sensation of the skin, painful erosive plaques on the skin.

From the musculoskeletal system: arthralgia, myalgia, osteoporosis, osteonecrosis, fractures.

Neoplasms: lymphoma (including reversible).

General reactions: allergic reactions up to anaphylactic shock, allergic vasculitis, tumor lysis syndrome, soft tissue necrosis, sudden death life-threatening opportunistic infections (including pneumocystis pneumonia), cytomegalovirus (CMV) infections (including CMV pneumonia), sepsis (including fatal), nocardiosis, histoplasmosis, cryptococcosis, infections caused by Herpes zoster and Herpes simplex (in including disseminated herpes), diabetes mellitus, excessive sweating.

Overdose

There are no specific symptoms of an overdose of methotrexate, it is diagnosed by the concentration of methotrexate in plasma.

Treatment: The introduction of a specific antidote - calcium folinate, if possible immediately, preferably within the first hour, at a dose equal to or greater than the dose of methotrexate; subsequent doses are administered as needed, depending on the concentration of methotrexate in the blood serum. To prevent precipitation of methotrexate and / or its metabolites in the renal tubules, hydration of the body and alkalinization of urine are carried out, which accelerates the excretion of methotrexate. To minimize the risk of nephropathy as a result of the formation of a precipitate of the drug or its metabolites in the urine, it is necessary to additionally determine the pH of the urine before each administration and every 6 hours throughout the entire period of use of calcium folinate as an antidote, until the plasma methotrexate concentration falls below 0.05 µmol /l, to ensure a pH above 7.

drug interaction

It increases the anticoagulant activity of coumarin or indandione derivatives and / or increases the risk of bleeding by reducing the synthesis of procoagulant factor in the liver and impaired platelet formation.

Increases the concentration of uric acid in the blood, therefore, in the treatment of patients with concomitant hyperuricemia and gout, dose adjustment of drugs (allopurinol, colchicine, sulfinpyrazone) may be required; the use of uricosuric anti-gout drugs may increase the risk of developing nephropathy associated with increased formation of uric acid during treatment with methotrexate (preferably used). Simultaneous intake of salicylates, phenylbutazone, phenytoidine, sulfanilamides, sulfonylumine derivatives, aminobenzoic acid, pyricimetamine or trimetoprime, a number of antibiotics (penicillin, tetracycline, chloramphenicol), indirect anticoagulants and hypolipidemic drugs (collaxation) enhances the fiber due to the displacement of methotrexate from the connection with and/ or a decrease in tubular secretion, which in some cases can lead to the development of severe toxic effects, sometimes even fatal.

Non-steroidal anti-inflammatory drugs (NSAIDs) against the background of high doses of methotrexate increase the concentration and slow down the elimination of the latter, which can lead to death from severe hematological and gastrointestinal intoxication. It is recommended to stop taking phenylbutazone 7-12 days, piroxicam 10 days, diflunisal and indomethacin 24-48 hours, ketoprofen and NSAIDs with a short half-life 12-24 hours before infusion of methotrexate in moderate and high doses and for at least 12 hours (depending on the concentration of methotrexate in the blood) after its completion. Caution should be exercised when combining NSAIDs with low doses of methotrexate (possibly reduced excretion of methotrexate by the renal tubules). Drugs that block tubular secretion (such as probenecid) increase the toxicity of methotrexate by reducing its excretion by the kidneys.

Antibiotics that are poorly absorbed in the gastrointestinal tract (tetracyclines, chloramphenicol) reduce the absorption of methotrexate and disrupt its metabolism due to suppression normal microflora intestines.

Retinoids, azathioprine, sulfasalazine, ethanol and other hepatotoxic drugs increase the risk of hepatotoxicity.

L-asparaginase reduces the antitumor effect of methotrexate by inhibiting cell replication.

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

The use of cytarabine 48 hours before or within 10 minutes after the start of methotrexate therapy may cause the development of a synergistic cytotoxic effect (dosage adjustment is recommended based on the control of hematological parameters).

Hematotoxic drugs increase the risk of methotrexate hematotoxicity.

Methotrexate reduces the clearance of theophylline.

Neomycin for oral administration may reduce the absorption of methotrexate. Several patients with psoriasis or mycosis fungoides treated with methotrexate in combination with PUVA therapy (methoxsalen and ultraviolet irradiation (UVR)) have been diagnosed with skin cancer.

Combination with radiation therapy may increase the risk of bone marrow suppression. Methotrexate may reduce the immune response to vaccination with live and inactivated viral vaccines.

Administration of amiodarone to patients receiving methotrexate therapy for psoriasis may cause skin ulceration.

special instructions

Methotrexate is a cytotoxic drug, so care must be taken when handling it. The drug should be prescribed by a doctor who has experience in the use of methotrexate and is familiar with its properties and features of action. In view of the possible development of severe and even fatal adverse reactions, patients should be fully informed by the doctor about the possible risks and recommended safety measures. Patients undergoing methotrexate therapy should be properly monitored so that signs of possible toxic effects and adverse reactions are identified and evaluated in a timely manner.

Before starting or resuming methotrexate therapy, a complete complete blood count with the determination of platelet levels, a biochemical blood test with the determination of the values ​​of liver enzymes, bilirubin, serum albumin, a chest x-ray examination, a study of kidney function, if necessary, tests for tuberculosis and hepatitis should be performed.

For the timely detection of symptoms of intoxication, it is necessary to monitor the state of peripheral blood (the number of leukocytes and platelets: first every other day, then every 3-5 days during the first month, then 1 time in 7-10 days, during remission - 1 time in 1-2 weeks), the activity of "liver" transaminases, kidney function (urea nitrogen, creatinine clearance and / or serum creatine), the concentration of uric acid in the blood serum, periodically conduct x-ray of the chest, examination of the oral mucosa and pharynx for the presence of ulceration before every application. It is recommended to monitor the state of bone marrow hematopoiesis before treatment, 1 time during treatment and at the end of the course.

Methotrexate can potentially lead to the development of symptoms of acute or chronic hepatotoxicity (including fibrosis and cirrhosis of the liver). Chronic hepatotoxicity usually develops after long-term use of methotrexate (usually for 2 years or more) or reaching a total cumulative dose of at least 1.5 g and can lead to a poor outcome. The hepatotoxic effect may also be due to a burdened concomitant history (alcoholism, obesity, diabetes mellitus) and old age. In view of the toxic effects of the drug on the liver during treatment, patients should be refrained from prescribing other hepatotoxic drugs, unless clearly necessary. Patients taking other hepatotoxic drugs (eg leflunomide) should be closely monitored.

To objectify liver function, along with biochemical parameters, it is recommended to perform a liver biopsy before or 2-4 months after the start of treatment; with a total cumulative dose of 1.5 g and after each additional 1-1.5 g. With moderate liver fibrosis or any degree of cirrhosis, methotrexate therapy is canceled; at pulmonary fibrosis forms generally recommend a repeat biopsy after 6 months. During initial therapy, minor histological changes in the liver (minor portal inflammation and fatty changes) are possible, which is not a reason for refusing or stopping treatment, but indicates the need for caution when using the drug

With the development of diarrhea and ulcerative stomatitis methotrexate therapy must be interrupted due to the high risk of developing hemorrhagic enteritis and perforation of the intestinal wall, which can lead to the death of the patient.

Do not expose unprotected skin to too much sun exposure or abuse the UV lamp (possible photosensitivity reaction). In view of the effect on the immune system, methotrexate may impair the response to vaccination and affect the results of immunological tests. It is necessary to refuse immunization (if it is not approved by a doctor) in the interval from 3 to 12 months after taking the drug; other members of the patient's family living with him should refuse immunization with oral polio vaccine (avoid contact with people who received polio vaccine, or wear a protective mask covering the nose and mouth). Patients of childbearing age of both sexes and their partners should use reliable contraceptive measures during treatment with methotrexate and after treatment for at least 3 months in men and at least one ovulation cycle in women.

After a course of treatment with high doses of methotrexate, the use of calcium folinate is recommended to reduce its toxicity.

Since methotrexate can affect the central nervous system (feeling tired, dizzy), patients taking the drug should refrain from driving vehicles or potentially dangerous mechanisms.

Pregnancy and lactation

It has a teratogenic effect: it can cause fetal death, congenital deformities. In the event that a woman becomes pregnant during methotrexate therapy, consideration should be given to terminating the pregnancy due to the risk side effects to the fruit. Methotrexate is excreted in breast milk, for the period of the entire course of treatment, breastfeeding should be discontinued.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

Store the drug in a place protected from light at a temperature not exceeding 25°C. Keep out of the reach of children.

Shelf life - 3 years. Do not use after the expiry date stated on the packaging.

Methotrexate belongs to the group of anticancer drugs, the action of which is aimed at provoking apoptosis of cancer cells, which is how they differ from drugs of the cytotoxic group, which contribute to the onset of the necrotic process in relation to malignant cells. It is a prominent representative of antimetabolites, folic acid antagonists.

The drug is characterized by a high inhibitory effect on the immune system, even if critically low doses are taken, while it does not have any effect during chemotherapy. negative impact on brain cells. That is why Methotrexate injections and tablets are in great demand among patients and doctors, relatively similar drugs this drug group.

The drug is available in two main forms. Methotrexate tablets contain 2.5 grams of the active substance of the same name, they have a surface shell and are produced in a dosage of 0.0025 grams, in each pack of 50 pieces.

The drug in the form of injections is a solution packed in a dark glass ampoule and placed in a branded cardboard box. In pharmacies, it is available in dosages of 0.005, 0.05 and 0.1 grams.

Pharmacology

Methotrexate is characterized by high immunosuppressive and antitumor activity. The main active ingredient has a detrimental effect on pathological cancer cells that are in the stage of division, bone marrow, embryo, mucous membrane of the oral cavity, bladder and intestines.

Distribution after intravenous administration is rapid and corresponds to the volume of the entire body fluid. Initially, the volume distribution corresponds to 0.18 liters per kilogram of weight, that is, 18% of body weight, the subsequent volume distribution is balanced and ranges from 0.4-0.8 liters per kilogram, that is, from 40 to 80 percent. It binds exactly half to blood plasma proteins.

If a person receives medicinal product in therapeutic doses, regardless of the form of release of the drug, the level of penetration through the blood-brain barrier is critically low. After performing injections into the spinal cord, a high level of drug concentration is noted in the cerebrospinal fluid. The drug has the ability to penetrate into mother's milk, as well as into the placenta, which leads to impaired embryonic development.

Metabolism of Methotrex occurs, to a greater extent, in the liver, together with the production of highly effective non-protein chemical compounds. Due to the production of DHF inhibitors and thymidylate syntheses, in combination with hydrolases, these compounds are converted to Methotrexate. A certain part of the produced polyglutamates can remain in the liver cells for quite a long period of time.

Depending on the type of cells, type of tissue and tumor, their retention time will be different. A small part is metabolized to 7-hydroxymethotrexate, which has a low water solubility (about five times compared to methotrexate), but this only applies to conventional doses. The presented metabolite can accumulate if the patient receives sufficiently high doses of the drug, for example, in the treatment of osteosarcoma.

If the patient is administered a dosage not exceeding 30 milligrams per m2, then the half-life corresponds to 2-4 hours, but only in the initial phase. The final Tsh directly depends on the dose of the drug received by the patient, therefore it can vary from 3 to 10 hours if the dose is minimal. With a higher concentration of the drug, within 80 milligrams per m2, the time interval is 8-15 hours.

Excretion occurs due to glomerular filtration of the kidneys, as well as the secretion of tubules, throughout the day. The concentration of excretion with bile is not more than 10%. Methotrexate is characterized by fluctuations in clearance and its decrease with decreasing dosage.

If patients have pleural effusion or severe ascites, the elimination process will be slow. If a repeated dose is administered, then there is an accumulation in the tissues in the form of metabolites. Prolonged excretion of the drug is noted in patients with chronic renal failure.

Indications

Physicians may prescribe methotrexate to patients for rheumatoid arthritis, including conditions characterized by Felty's syndrome. Among the indications for taking the medicine there are many diseases of an oncological nature:

• Lymphoblastic leukemia;
• myeloblastic leukemia;
• myeloma;
• Trophoblastic formations (chorioepithelioma of the uterus, hydatidiform mole, including the destructive type);
• Cancer (esophagus, head, neck, bladder, lung, liver, kidney, breast and prostate, ureteral glands, cervix, ovaries and testicles, penis);
• Hodgkin's lymphoma and non-Hodgkin's types, including Burkitt;
• Osteogenic sarcoma is not metastatic.

In addition, Methotrexate can be used in the treatment of steroid-dependent bronchial asthma(if patients have contraindications to taking glucocorticosteroids), Crohn's disease, ulcerative colitis (chronic nonspecific), lichen planus, psoriasis and psoriatic arthritis, Reiter's and Cesari's syndrome, multiple sclerosis.

Instruction

Methotrexate injections can be administered intravenously, intramuscularly, intra-arterially and directly into the CSF system (spinal cord). The instruction indicates the fact that the intravenous administration of a drug containing benzyl alcohol is unacceptable, and it is also not recommended to use it for therapy in which the patient needs to take high doses of the drug.

For intravenous administration

Methotrexate in the form of tablets should be taken immediately before the main meal. The tablet should not be chewed, it must be swallowed whole with plenty of warm water.

Depending on the diagnosis, the proposed medical therapeutic regimen, the physiological parameters of the patient's condition, his weight and age, drug tolerance, the duration of therapy and dosage will be calculated individually for each clinical case.

When prescribing a dose, the volume of which is equal to or greater than 100 milligrams, it is recommended to give the drug drip by intravenous administration. Before the procedure, the drug solution is diluted with 5% concentration of dextrose: from half a liter to a liter of dextrose is taken for 10 milligrams of the main drug. The introduction is carried out under the cover of calcium folinate.

Trophoblastic tumors

Therapy may use the form of the drug in the form of tablets or injections. During the day, taken orally or administered by intramuscular injection from 15 to 30 milligrams of funds. The duration of treatment is 5 days. If the treatment involves a course repetition of 3-5 visits, then a break is made between them for 7-14 days.

Approximately after the third course, patients show stabilization normal indicators HCG in the urine, or they are guided by an indicator corresponding to 50 IU per day. This suggests that in the next month, a maximum of one and a half indicators of pathology will disappear. After the level of hCG has stabilized, it is recommended to undergo another 1 or 2 courses of therapy.

Lymphoblastic leukemia

When conducting complex therapy for the acute stage of lymphoblastic leukemia, patients are advised to use 3.3 milligrams of Methotrexate per square meter. To increase the effectiveness, the drug is combined with Prednisolone, the dosage of which is 60 milligrams per square meter.

Another minor medication may also be used to help achieve sustained remission. Upon reaching it, the patient must undergo maintenance therapy. In this case, Methotrexate is administered intramuscularly or taken orally at a dosage not exceeding 30 milligrams per square meter. The dose is divided into two procedures. When administered intravenously, a dosage of 2.5 milligrams per kilogram of body weight is indicated for two weeks.

Burkitt's lymphoma

Therapy of the presented disease with the drug Methotrexate is justified with a diagnosed first, second or third degree of pathology. It is recommended to take orally from 10 to 25 milligrams of the drug during the day (if the disease is stage 1 or 2), for the third stage a combination with additional drugs is necessary.

The preliminary course of therapy is from 4 to 8 days. Most often, therapy is carried out in courses, the interval between which is from one week to 10 days.

With diagnosed lymphosarcoma of the third degree, patients are prescribed to take tablets daily at a dosage of 0.625-2.5 milligrams.

Fungal mycosis

For the treatment of this disease, the instruction for the use of Methotrexate recommends administering to patients intramuscularly 50 milligrams of the drug as a base (the procedure is done 1 time in 7 days). If the dosage is 25 milligrams, then as a basis, the procedure is carried out 2 times in 7 days.

You can take the drug orally at a dosage of 2.5 to 10 milligrams daily. The course of treatment is from several weeks to several months. To decide whether to reduce the dosage or completely cancel the drug, the doctor will have to study the patient's response and evaluate hematological parameters.

osteosarcoma

Slow intravenous administration of Methotrexate is shown (for four hours the patient should receive 12 grams of medication per square meter). After that, as an antidote, the patient is prescribed calcium folinate. This agent is taken orally, and the starting dose is 15 milligrams, which should be taken after a day from the moment of injection, then at intervals of six hours, a total of 10 injections are indicated.

If the patient has signs of intoxication of the gastrointestinal tract, the method of drug administration is changed to intramuscular injections or calcium folinate is administered intravenously in an identical dosage.

The introduction of Methotrexate is indicated at 4-7, 11-12, 15-16, 29-30, 44 and 45 weeks from the date of surgical treatment. It is part of a chemotherapeutic complex, which is complemented by: Doxorubicin, Cisplatin, Bleomycin, Cyclophosphamide, Dactinomycin.

If there is evidence, then the dosage of Methotrexate is increased to 15 milligrams per square meter as a base - this is necessary in order to achieve a maximum drug concentration in the blood serum of 0.001 mol / liter.

Leukemic infiltration

If the patient has leukemic infiltration of the membranes of the brain, then he is shown the introduction of the drug directly into the spinal cord. The dosage is 12 milligrams per square meter, and the interval between treatments ranges from two to five days.

Rheumatoid arthritis

Methotrexate for rheumatoid arthritis in the initial dosage is prescribed in the amount of 7.5 milligrams. The procedure is done once for seven days at once, or two injections can be performed, where the dose of the drug is 2.5 milligrams, and the interval between injections is 12 hours. In this case, three injections are indicated within seven days.

To achieve a better therapeutic effect, the weekly dose can be increased, but the line of 20 milligrams must not be crossed. After that, it is imperative to begin the process of reducing the dosage. It is necessary to achieve the minimum effective amount of the drug per week. There are no unequivocal recommendations regarding the duration of treatment. Everything is individual.

Psoriasis

Increasing the dose most often occurs gradually, and after the therapeutic effect has been achieved, it is carefully reduced until the minimum therapeutic dose is established.

Children

Methotrexate is indicated for children as one of the medicines aimed at combating tumor process. Orally or intramuscularly, it is necessary to take from 20 to 40 milligrams of the drug per square meter, once a week.

Clear doses for the treatment of patients in the pediatric age group, as well as in the treatment rheumatoid arthritis, not defined. The drug is administered intrathecally if leukemic infiltration of the meninges has occurred. For patients under the age of one year, a dose of 6 milligrams per square meter is recommended, older than a year - 8 milligrams per square meter, older than two years - 10 milligrams per square meter, older than three years - 12 milligrams per square meter.

It is necessary to carry out the procedure every 2-5 days until the CSF indicators stabilize and return to normal. As soon as the goal is achieved, another control dose is administered in the appropriate volume, after which they switch to the volumes recommended for prophylactic therapy. In this case, their size will be identical therapeutic doses, but the interval is always individual.

Contraindications

Methotrexate is a potent drug, therefore it has a certain number of contraindications, in the presence of which its appointment is not made:

• individual sensitivity to the constituent components of the drug;
• state of immunodeficiency;
• anemia, hypoanemia, aplastic anemia;
• leukopenia, thrombocytopenia;
• leukemia in combination with hemorrhagic syndrome;
• insufficiency of the hepatic or renal segment;
• effusion in the pleural cavity;
• ascites;
• bone marrow function in a depressed state;
• chickenpox, especially if it has been recently transferred;
• stomatitis;
• ulcerative colitis.

It is unacceptable to prescribe a drug in any trimester of pregnancy, due to the fact that it has the ability to penetrate the placenta, and this can lead to the death of the fetus, or its underdevelopment. When breastfeeding, it is recommended to transfer the child to artificial mixtures because the drug penetrates into the mother's milk.

special instructions

When undergoing treatment with the cytotoxic drug Methotrexate, it is necessary to observe many safety measures that relate to all areas of human activity and life. Let's consider them in more detail.

First of all, you need to take care of compliance the highest level contraception, because the drug has a detrimental effect on the fetus. Men should carefully protect themselves for three months after a course of treatment, women should avoid pregnancy for at least one ovulation cycle.

If a course of treatment was carried out with the introduction of high doses of the drug, in order to reduce its toxicity, it is imperative to take calcium folinate. Immediately before each dose of the drug should be carefully examined oral cavity to detect expressions.

If the patient develops diarrhea or stomatitis with the formation of open sores, Methotrexate is discontinued. This is due to the high probability of occurrence under such conditions of hemorrhagic enteritis and perforation of the intestinal wall. Such conditions can be fatal for the patient.

Instructions for use indicate that conditionally the drug is able to provoke the development of symptoms of hepatotoxicity in acute or chronic form, cirrhosis or liver fibrosis may develop. Most often, such conditions occur during the passage of a long course of methotrexate therapy (from two or more years).

Also, such conditions can occur when a total dose of 1.5 grams is reached, which will lead to an unfavorable outcome. In addition, the hepatotoxic effect develops against the background of the following concomitant conditions in the patient: diabetes mellitus, alcoholism, obesity, old age.

To stabilize and control the functioning of the liver, it is recommended to assess the biochemical parameters of the organ and take a biopsy before the start of the therapeutic course, or no later than four months after the first dose of the drug. The same procedure is recommended when a total body dose of 1.5 grams is reached.

If cirrhosis or fibrosis of the liver was detected during the diagnostic process, the treatment process using this remedy is stopped. If it was detected mild degree liver fibrosis, then a second biopsy is recommended after six months.

When a patient is just starting methotrexate therapy, there may be minor changes in liver histology (portal inflammatory process and fat deposition). Such conditions cannot be the reason for discontinuation of the drug or the selection of analogues, but at the same time, doctors must be especially careful in the process of treating such a patient.

Within 3-12 months after therapy, all types of vaccinations should be abandoned, but only if they are not recommended by a leading specialist. All family members who live with the patient should also refuse oral polio vaccine, should not come into contact with people who have recently received this vaccine. Or you will have to wear a protective medical bandage that hides the oral and nasal cavities.

Overdose

A feature of the state of overdose with Methotrexate is the complete absence of characteristic symptoms. It can only be determined by studying the level of drug concentration in the blood plasma.

It is possible to stop the state of overdose only by introducing calcium folinate. It is necessary to carry out the procedure as soon as possible, preferably immediately. IN last resort, it is necessary to give the patient the drug no later than one hour from the moment the overdose is detected. The amount of Calcium folinate should be equal to or greater than the dose of Methotrexate.

Further restoration of the patient's condition in this way is carried out as necessary, based on the concentration of the drug in the blood plasma. In order to prevent the precipitation of the drug and its metabolites in the renal tubules, it is imperative to hydrate the entire body, and alkalinize the urine, which speeds up the process of excretion of Methotrexate.

Analogues

There are not many substitutes for Methotrexate. The most effective and suitable can be called such means: Alimta, Vero-methotrexate, Zeksat, Metobion, Metojekt, Pemnat. Each of them is more or less effective against diseases and conditions for which doctors prescribe Methotrexate.

It is strictly forbidden to independently select analogues. This procedure is the responsibility and competence of the leading specialist. With the wrong selection of drugs, there is a risk of worsening the patient's condition.

The price of Methotrexate in pharmacies for 50 tablets is from 205 rubles, and for 1 ampoule from 775 rubles.

About the drug (video)

Latin name: Methotrexate
ATX code: L01BA01
Active substance: methotrexate
Manufacturer: Ebewe Pharma, Australia
Vacation from the pharmacy: On prescription
Storage conditions: darkness, cold
Best before date: 2-3 years.

Methotrexate has antitumor and immunosuppressive properties. Therefore, the drug is used to treat cancer and malignant tumors.

The drug is available in the form of tablets and medicinal solution. The drug can be purchased at the pharmacy only with a prescription.

Composition and form of release

Methotrexate is produced in the form of tablets or medicinal solution with different content active ingredient. Thus, tablets containing 2.5 mg of methotrexate have a flat rounded shape. The pills are yellow, the tablets have red or orange blotches.

Methotrexate Ebeve tablets 2.5 mg are placed in polypropylene bottles (50 pieces) and cardboard packs. Also, pills can be packed in blisters of 10 pieces, which are in a pack of cardboard. The cost of the medicine is from 203 rubles.

Methotrexate 5 mg tablets have a round, convex shape. Yellow pills with white or orange patches are separated on one side by a beveled strip. The pills are placed in polypropylene bottles (50 pieces) and cardboard packs. The price of the drug is from 350 rubles.

Methotrexate Ebewe 10mg is a pill yellow color, which have a biconvex oblong shape. There is a separating strip on the tablet, on one side the edges of the pill are bevelled. The cost of the medicine is from 500 rubles.

Regardless of the amount of methotrexate, all tablets have the same auxiliary composition:

• Corn starch
• E 572
• Polysorb
• Milk sugar.

Methotrexate solution is a colorless liquid with a yellowish tint. In ampoules Methotriksat can be contained in the form of a yellow-brown lyophilisate, from which a therapeutic liquid for injection is prepared.

Methotriksat 10 ml is placed in transparent glass bottles, closed with a rubber stopper, on top of which there is a metal run-in. Methotriksat 10 mg is also poured into tinted glass ampoules.

Solution for injection Methotrexate 15 mg is placed in transparent ampoules packed in cardboard packs. Methotrexate 20 mg, 50 g and 1 g is in vials as a concentrate.

Also, the drug solution is placed in transparent glass syringes intended for single use. The kit comes with 1-2 needles. The syringe containing methotrexate, on the basis of which injections are made, is packed in a blister, which is in a pack of cardboard.

Regardless of the amount of medicinal liquid and dosage form, Methotrexate solution has the same additional composition:

• injection water
• E 524.

Methotrexate injection solution costs from 200 rubles. The price of a medicinal liquid placed in a syringe is about 1000 rubles.

Pharmacological properties

Methotrexate is a folic acid substitute belonging to the antimetabolites. The drug has immunosuppressive and antitumor effects, so the use of Methotrexate is justified in sarcoma, thromboblastic formations, lymphoma and cancer.

Methotrexate inhibits dihydrofolate reductase, which reduces the folate derivative to tetrahydrofolate. The latter transports carbon fragments involved in the production of purine bases of their metabolites.

The folic acid antagonist inhibits the production, cell division and DNA repair. Tissues with increased cell proliferation through mitosis are sensitive to the antimetabolite. These are ESCs, cancerous, epithelial cells of the inner membranes and soft tissues bones. Methotrexate is also an immunosuppressant.

Pharmacokinetics of tablets:

• Resorption from the gastrointestinal tract - high at a dose of 30 mgm2, low at a dose of 80 mg/m2
• F is 50%
• Tmax - 60-120 minutes
• The relationship with plasma proteins - 50%
• Metabolism - occurs in the liver, partly in the intestines
• T1 / 2 - initial phase - up to 4 hours, final - up to 10-15 hours
• Excretion - excreted unchanged in urine and bile.

Methotrexate in tablets almost does not cross the placenta, but is absorbed into breast milk.

With leukemia in childhood, resorption is 23-95%. With chronic renal failure, abdominal dropsy, the release of the drug slows down.

With the / m administration of Methotrexate, its optimal amount in the blood is reached within 30-60 minutes, with leukemia - 1-3 hours.

The drug binds 50% to albumin. Metabolism is carried out in cells and liver.

The half-life at a dosage of less than 30 mg / m2 takes up to 7 hours, if the amount of the drug is higher - up to 17 hours. With chronic renal failure, the excretion of methotrexate is reduced. Up to 90% of the solution is excreted by the kidneys throughout the day.

Indications and contraindications for use

Methotrexate is used for osteosarcoma, gestational trophoblastic neoplasm, advanced form of fungal infections, leukoma of the spinal cord or brain. Also, the drug is used for lymphoblastic or myeloid leukemia, soft tissue tumors, non-Hodgkin's lymphomas.

Other indications are cancer affecting the genitals, head, mammary gland, kidneys, neck, eyes, integument, organs of the gastrointestinal tract and urinary system. Also, the solution and tablets are prescribed for severe Bechterov's or Libman's disease, scaly lichen, sporadic or rheumatoid arthritis, lilac disease.

Contraindications:

• withdrawal syndrome
• Kidney or liver dysfunction
• Lactation
• Ulcer of the gastrointestinal tract and oral cavity
• Acute severe chronic infections
• Vaccination with live bacteria
• Pregnancy
• intolerance to methotrexate.

Instructions for use

Methotrexate tablets are taken orally. For leukemia, the adult dose is 30 mg twice a week. The allowable amount per day of the drug for children is 0.02 g / 1 m2.

The duration of therapy is 14 days. Intensive course for adults - 20-25 mg, which are taken for 5 days. After a break, lasting 14-20 days, the treatment is repeated.

For tumors of the uterus, methotrexate is taken for five days at 50 mg per day. After 30 days, the treatment is repeated. Other therapeutic regimen- up to 30 mg per day for 5 days with interruption of admission for 7-14 days.

Methotrexate Ebeve instructions for use in psoriasis:

• 5 mg 1 time per day or 2.5 mg - up to 4 times a day.
• Time of therapy - 5-7 days of admission and 3 days off.

It is noteworthy that during treatment with Methotrexate, it is necessary to examine the blood for the content of platelets and leukocytes three times a week.

Methotrexate solution is administered intravenously, intramuscularly, or an injection is made into the spinal canal. Before use, the concentrate is mixed with a NaCl solution.

The standard therapy regimen is 30 mg twice a week. Intensive treatment - up to 25 mg every day for 5 days. After 14-20 days, repeated therapy is carried out.

The highest dose per day in childhood is 20 mg / m2. With a tumor of the uterus, 50 mg is administered once a day for 5 days. After a 30-day break, the treatment is repeated.

In the case of neuroleukemia, Methotrexate is injected into the cavity in the spinal column. The dosage of the solution (0.2%) is up to 10 mg / m2 every 3-4 days.

The treatment regimen for psoriasis is 10-25 mg once every 7 days.

When Methotrexate is administered to high dose it is important to adjust the pH of the urine.

Side effects, overdose, interactions

After the use of Methotrexate, function may be impaired circulatory system, which is manifested by anemia, low levels of platelets, neutrophils, leukocytes, T-lymphocytes. When using the solution, there are often local reactions in the form of rashes, itching, acne, peeling, dermatitis or baldness.

Other side effects of Methotrexate:

• CNS - vertigo, organic lesion brain, myalgia, malaise, convulsions, coma, nervousness, headache
• Gastrointestinal - pancreatitis, nausea, stool disorder, bleeding, liver dysfunction, ulcer digestive organs, vomit
• Reproductive system - impotence, disorder of spermatogenesis, teratogenic effect
• Respiratory organs - lung infections, fibrosing alveolitis, pulmonary fibrosis
• Genitourinary system - kidney dysfunction, inflammation of the bladder
• Immune system - photophobia, fever, bellarous dermatitis, urticaria, erythema, anaphylactic shock, chills.

Methotrexate can also cause visual disturbances and contribute to the occurrence of immunosuppression, atralgia, osteoporosis, and inflammation of the vascular walls.

In case of overdose, an antidote is used - the calcium salt of folinic acid. The drug must be administered in the first 60 minutes at a dosage similar to the amount previously used Methotrexate. It is equally important to raise the pH of urine and restore water balance.

• Antibiotics
• Probenacid
• Azathioprine
• Phenytoin
• L-asparaginase
• Colestyramine
• Aminobenzoic acid
• Sulfonylureas
• Folic acid
• dinitrogen oxide
• Indirect anticoagulants
• Phenylbutazone and others.

Analogues

The drug Methotrexate has the following analogues - Metortit and Metoject.

Manufacturer - K.O. Rompharm, Romania

Price– 530 rubles

Description - injection solution is used for severe rheumatoid arthritis, psoriasis, cancer of the kidneys, liver, breast, ovaries, blood, sarcoma

pros– efficiency, extensive list of indications

Minuses- many undesirable effects, allergic reactions at the injection site.

Producer - Medak GmbH, Germany

Price– about 700 rubles

Description - drug solution is indicated for arthritis and psoriasis

pros- reduces inflammation and pain syndrome, well tolerated

Minuses- cost, a lot of side effects.