Metarthritis solution for injection 10mg/ml syringe 2.5ml with hypodermic needle

Composition

Per 1 ml of the drug:

active ingredient:  disodium methotrexate 10.97 mg in terms of methotrexate 10.00 mg;

auxiliary components:

sodium chloride-7.00 mg;

2 M sodium hydroxide solution-1.76 mg (22 µl);

1 M sodium hydroxide solution-up to pH = 8.5 ± 0.1;

water for injection – up to 1.00 ml

Pharmacological action

Pharmacotherapy group: Antitumor agent, antimetabolit ATX:

L. 01. B. A Folic acid analogs

L. 01. B. A. 01 Methotrexate

Pharmacodynamics :

Antitumor drug from the group of antimetabolites analogs of folic acid. Along with antitumor, it has an immunosuppressive effect.

Inhibits 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 the synthesis, repair of DNA and cellular mitosis (in the S-phase). Particularly sensitive to the action of methotrexate are tissues with high cell proliferation: tumor tissue, bone marrow, mucosal epithelial cells, and embryonic cells.

The mechanism of action in rheumatoid arthritis is associated with the immunomodulatory and anti-inflammatory effects of the drug and is due to the induction of apoptosis of rapidly proliferating cells (activated T-lymphocytes, fibroblasts, synoviocytes), inhibition of the synthesis of anti-inflammatory cytokines IL-1 (Interleukin 1), TNF-α (Tumor necrosis Factor alpha)), increased synthesis of anti-inflammatory cytokines IL-4 (Interleukin 4), IL-10 (Interleukin 10) and suppression of metalloproteinase activity.

In patients with rheumatoid arthritis, the use of methotrexate reduces the symptoms of inflammation (pain, swelling, stiffness), but there are limited studies on the long-term use of methotrexate (regarding the ability to maintain remission in rheumatoid arthritis).

In psoriasis, the growth rate of keratinocytes in psoriatic plaques increases compared to normal skin cell proliferation. This difference in cell proliferation is the basis for the use of methotrexate for the treatment of psoriasis.

Pharmacokinetics:

Suction and distribution

With intravenous use, the Cmax of methotrexate in blood plasma is reached within 30-60 minutes. Patients with leukemia are characterized by a wide interindividual variability ranging from 1 to 3 hours.

Relative bioavailability in patients with rheumatoid arthritis is comparable with intramuscular and subcutaneous use of the same dose of the drug. Systemic absorption of methotrexate after use under the skin of the abdomen and thigh is the same.

After intravenous use, the primary distribution is 0.18 l/kg (18% of body weight). The saturation dose distribution is about 0.4-0.8 l / kg (40% – 80% of body weight).

Binding to plasma proteins is about 50%, mainly with albumins. Competitive displacement is possible when used simultaneously with sulfonamides, salicylates, tetracyclines, chloramphenicol, and phenytoin.

When taken at therapeutic doses, methotrexate does not cross the blood-brain barrier.

Metabolism

Methotrexate undergoes hepatic and intracellular metabolism to form a pharmacologically active polyglutamine form that also inhibits dihydrofolate reductase and thymidine synthesis.

A small amount of methotrexate polyglutamate can remain in the tissues for an extended period of time. Maintenance and prolongation of the active metabolites of the drug vary depending on the type of cells, tissues and tumors.

Approximately 10% of the administered methotrexate is metabolized in the liver. The main metabolite is 7-hydroxymethotrexate.

Deduction

The average T 1/2 values when using methotrexate at a dose of less than 30 mg / m2 are 6-7 hours. In patients receiving high doses of methotrexate, T 1/2 ranges from 8 to 17 hours.

From 80 to 90% of the received dose is excreted unchanged by glomerular filtration and tubular secretion within 24 hours. Approximately 5-20% of methotrexate and 1-5% of 7-hydrometotrexate is excreted in the bile, followed by intestinal reabsorption.

Pharmacokinetics in special clinical cases

In chronic renal failure, both phases of drug elimination can be significantly prolonged.

Impaired renal function, severe ascites or pleural effusion, as well as concomitant use of drugs such as weak organic acids, which also undergo tubular secretion, can significantly increase the concentration of methotrexate in the blood serum.

According to the distribution, methotrexate accumulates in the liver, kidneys, and spleen as polyglutamates and can linger in these organs for several weeks or months.

Indications

• Rheumatoid arthritis in adults;

• polyarthritic form of juvenile idiopathic arthritis in case of insufficient therapeutic response to therapy with nonsteroidal anti-inflammatory drugs (NSAIDs);

• severe psoriasis in adult patients, especially in the form of plaques, in case of ineffectiveness of standard therapy, including phototherapy, PUVA therapy and retinoid use;

• severe psoriatic arthritis in adult patients.

Use during pregnancy and lactation

Pregnancy

Methotrexate is contraindicated during pregnancy.

Taking methotrexate during pregnancy can cause serious malformations of the fetus (an increase in the frequency of malformations of the skull, cardiovascular system and limbs by 14 times).

If pregnancy occurs during treatment with methotrexate, it is necessary to consult with specialists regarding the risk of adverse effects of methotrexate on the fetus.

Fertility

Patients of reproductive age (women and men) should use effective contraceptives during and for at least 6 months after the end of treatment with Metortrit.

Breast-feeding

Methotrexate passes into breast milk in concentrations that are dangerous for the baby. Therefore, breast-feeding should be discontinued during treatment with methotrexate.

Contraindications

• Hypersensitivity to methotrexate and/or to any other component of the drug;

• severe renal insufficiency (creatinine clearance <20 ml/min);

• severe hepatic impairment;

• alcohol abuse;

• violations of the hematopoietic system in history (in particular, bone marrow hypoplasia, leukopenia, thrombocytopenia or clinically significant anemia);

• immunodeficiency;

• severe acute and chronic infectious diseases such as tuberculosis and HIV;

• concomitant vaccination with live vaccines;

• mouth ulcers, ulcers of the gastrointestinal tract in the active phase;

• concomitant use of methotrexate at a dose of ≥ 15 mg/week. with acetylsalicylic acid;

• pregnancy;

• breastfeeding.

With caution: Use the drug with caution if the patient has impaired liver and kidney function, diabetes mellitus, obesity and previous exposure to hepatotoxic drugs, dehydration, suppression of bone marrow hematopoiesis, pleural or peritoneal effusion, parasitic and infectious diseases of viral, fungal or bacterial etiology (currently or recently transferred, including recent contact with the patient), including such as herpes simplex, herpes zoster (viremic form), chickenpox, measles, amoebiasis, strongyloidosis (established or suspected) due to the risk of developing a severe generalized disease; gout (including in the anamnesis) or systemic nephrourolithiasis (including in the anamnesis), infection and inflammation of the oral mucosa, vomiting, diarrhea, stomach and duodenal ulcer, ulcerative colitis, obstructive gastrointestinal diseases that precede chemotherapy or radiation therapy asthenia, aciduria (urine pH less than 7), as well as in children and elderly patients.

Side effects

According to the WHO classification, undesirable effects are classified according to their frequency as follows: very common (≥ 1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (

Disorders of the cardiovascular system.

Infrequently: vasculitis (as acute toxic symptoms).

Rare: pericarditis, pericardial effusion, cardiac tamponade, decreased blood pressure, thromboembolic complications (including cerebral vascular thrombosis and arterial thrombosis, thrombophlebitis, deep vein thrombosis, retinal vein thrombosis, pulmonary embolism).

Disorders of the blood and lymphatic system:

Common: leukopenia, thrombocytopenia, anemia.

Infrequently: pancytopenia, agranulocytosis, hematopoietic disorders.

Rare: megaloblastic anemia.

Very rare: severe bone marrow suppression, aplastic anemia, enlarged lymph nodes, lymphoproliferative diseases (partially reversible), eosinophilia, neutropenia.

The first signs of these life-threatening complications are fever, sore throat, mouth ulcers, flu-like symptoms, nosebleeds, and skin hemorrhages.The use of methotrexate should be stopped immediately if the number of blood cells is significantly reduced.

Immune system disorders:

Infrequently: allergic reactions, anaphylactic shock, immunosuppression.

Infectious and parasitic diseases:

Very rare: sepsis, opportunistic infections (in some cases may be fatal), infections caused by Cytomegalovirus.

Frequency unknown: cases of nocardiosis, histoplasmosis and cryptococcal fungal infections, disseminated form of herpes simplex have been reported.

Nervous system disorders:

Often: headache, fatigue, drowsiness.

Infrequently: depression, confusion, dizziness, seizures.

Rare: mood swings.

Very rare: pain, muscle weakness or paresthesia in the extremities, impaired taste (metallic taste), acute aseptic meningitis with meningism (paralysis, vomiting), insomnia.

Frequency unknown: tinnitus.

Visual disturbances:

Rare: severe visual impairment.

Very rare: conjunctivitis, retinopathy.

Benign, malignant and unspecified neoplasms:

Infrequently: isolated cases of lymphomas that

regress upon discontinuation of methotrexate treatment. In a recent clinical study, methotrexate therapy was not found to increase the incidence of lymphomas.

Respiratory, thoracic and mediastinal disorders:

Often: pulmonary complications due to interstitial pneumonitis / alveolitis, including fatal ones (regardless of the dose and duration of treatment with methotrexate). Typical symptoms: malaise, dry, unproductive cough, shortness of breath. progressive to shortness of breath at rest, chest pain, fever.

If such complications are suspected, the use of methotrexate is stopped immediately and infections (including pneumonia) are excluded.

Infrequently: pulmonary fibrosis.

Rare: pharyngitis, apnea, bronchial asthma, shortness of breath and abnormal results of instrumental studies of lung function.

Very rare: pneumonia caused by Pneumocystis carinii and other lung infections, difficulty breathing, chronic obstructive pulmonary disease, pleural effusion.

Disorders of the gastrointestinal tract:

Very often: decreased appetite, nausea and vomiting (especially during the first 24-48 hours after use of methotrexate), abdominal pain, inflammation and ulcers in the mucous membrane of the mouth and throat, stomatitis, dyspepsia.

Common: diarrhea (especially in the first 24-48 hours after using methotrexate).

Infrequently: ulcers and bleeding of the gastrointestinal tract.

Rare: enteritis, melena, gingivitis, malabsorption syndrome.

Very rare: vomiting with blood, toxic megacolon.

Liver and biliary tract disorders:

Very often: increased activity of “liver” enzymes (ALT, ACT), increased activity of alkaline phosphatase, increased bilirubin concentration.

Infrequently: hepatic steatosis, liver fibrosis, cirrhosis of the liver (may occur even if regularly detected during monitoring of normal values of “hepatic” transaminases).

Rare: acute hepatitis and hepatotoxicity.

Very rare: reactivation of chronic hepatitis, acute liver dystrophy, liver failure. The most common hepatitis is caused by the herpes simplex virus and accompanied by liver failure.

Skin and subcutaneous tissue disorders:

Often: exanthema, erythema, pruritus of the skin.

Infrequently: urticaria, photosensitization, increased skin pigmentation, hair loss, abnormal wound healing, enlarged rheumatic nodules, shingles, painful manifestations of psoriatic plaques (there may be an exacerbation of plaque psoriasis with UV radiation therapy and simultaneous use of methotrexate), severe toxic reactions, vasculitis, allergic vasculitis, herpetiform skin rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Rare: changes in nail pigmentation, onycholysis, petechiae, ecchymosis, erythema multiforme, erythematous skin rash.

Very rare: acute paronychia, furunculosis, telangiectasia, hydradenitis.

Musculoskeletal and connective tissue disorders:

Infrequently: arthralgia, myalgia, osteoporosis.

Rare: stress fractures, osteonecrosis.

Kidney and urinary tract disorders:

Infrequently: inflammation and ulceration of the bladder, (possibly with

hematuria), dysuria (urination disorder).

Rare: renal failure, oliguria, anuria, azotemia.

Very rare: proteinuria.

Genital and breast disorders:

Infrequently: vaginitis (inflammation of the vagina)

Rare: oligospermia, menstrual disorders.

Very rare: decreased libido, impotence, vaginal discharge, infertility, gynecomastia.

Frequency unknown: violation of oogenesis and spermatogenesis, teratogenic effect.

Endocrine system disorders:

Frequency unknown: diabetes mellitus, metabolic disorders.

General disorders and disorders at the injection site:

Infrequently: with intramuscular use of methotrexate-burning or tissue damage (formation of sterile abscesses, destruction of fat deposits) at the injection site.

Very rare: fever. Usually, methotrexate is well tolerated when administered subcutaneously, but only mild local reactions have been reported to date, which decreased during treatment.

Laboratory and instrumental data:

Infrequently: Decreased serum albumin, hypogammaglobulinemia. The frequency and severity of adverse reactions depend on the dose and frequency of use.

Since severe adverse reactions can also occur at low doses, it is extremely important that patients undergo medical examinations regularly and at short intervals.

Interaction

The probability of hepatotoxic effects of methotrexate increases in the case of regular alcohol consumption and concomitant use of other hepatotoxic drugs.

Combined therapy with methotrexate and leflunomide increases the incidence of pancytopenia and hepatotoxic effects.

Oral antibiotics (tetracyclines, chloramphenicol and nonabsorbable broad-spectrum antibiotics) they can reduce the absorption of methotrexate in the gastrointestinal tract and interfere with enterohepatic circulation due to inhibition of intestinal microflora or inhibition of bacterial metabolism.

Penicillins, ciprofloxacia. cephalotin, glycopeptides can reduce the renal clearance of methotrexate, as a result of which its concentration in the blood serum may increase and the toxic effect on the hematopoietic system and gastrointestinal tract may increase.

Probenecid, weak organic acids (such as loop diuretics) and pyrazoles (phenylbutazone) They can slow down the elimination of methotrexate, as a result of which its concentration in the blood serum may increase and hematological toxicity may increase.

The risk of toxic effects of methotrexate increases in the case of combined use with NSAIDs or salicylates (methotrexate excretion through the renal tubules may decrease, caution should be exercised when combining nonsteroidal anti-inflammatory drugs with methotrexate).

With concomitant therapy with drugs that may have an adverse effect on the bone marrow (for example, sulfonamides. trimethoprim / sulfamethoxazole, chlorampheicol, pyrimethamiom), the possibility of developing more pronounced hematological disorders should be taken into account.

With concomitant therapy with drugs that cause folate deficiency (for example, trimethoprim/sulfamethoxazole), the toxic effect of methotrexate may increase.

Concomitant use of indirect anticoagulants and lipid-lowering drugs (cholestyramia) increases the toxicity of methotrexate.

When combined with antirheumatic drugs (for example, gold salts, penicillamines, hydroxychloroquines, azathioprines, cyclospores) and methotrexate, the toxic effect of the latter does not increase. In the case of simultaneous use of sulfasalazine and methotrexate, the effect of the latter may be potentiated due to inhibition of folic acid synthesis.

When combined with methotrexate and proton pump inhibitors (for example, omeprazole or pantoprazole) renal elimination of methotrexate may be delayed, and pantoprazole may inhibit renal elimination of the 7-hydroxymethotrexate metabolite, which in one case was accompanied by the development of myalgia and tremor.

During treatment with methotrexate, excessive consumption of beverages containing caffeine and theophylline (coffee, sugary drinks containing caffeine, black tea) should be avoided. Methotrexate reduces theophylline clearance.

It is necessary to take into account the pharmacokinetic interaction between methotrexate and flucloxacillin and anticonvulsants (the concentration of methotrexate in the blood decreases),5-fluorouracil (the half-life of 5-fluorouracil increases).

In the case of co-use with other cytostatics, the clearance of methotrexate may decrease.

Concomitant use of vitamin supplements or oral iron supplements containing folic acid may weaken the response to therapy and reduce the toxic effect of methotrexate on the bone marrow.

When mixing methotrexate solutions with chlorpromazine hydrochloride, droperidol, idarubicin, metoclopramide hydrochloride, heparin, prednisone sodium phosphate and promethazine hydrochloride, precipitation or turbidity of the solution may occur.

The use of drugs with an additional hematotoxic effect (for example, metamizole) increases the likelihood of serious hematotoxic effects of methotrexate.

Due to the competitive binding to serum albumin, the toxicity of methotrexate may be increased when methotrexate is co-administered with salicylates, amiylbutazone, phenytoin, barbiturates, tranquilizers, oral contraceptives, tetracycline and amidopyrin derivatives, sulfonamides and p-aminobenzoic acid.

Several patients with psoriasis or fungal mycosis treated with methotrexate in combination with PUVA therapy (metoxalene and ultraviolet radiation) were diagnosed with skin cancer.

Caution should be exercised when red blood cell mass and methotrexate are administered simultaneously.

Combination with radiotherapy may increase the risk of soft tissue necrosis. Methotrexate may reduce the immunological response to vaccination. When administered concomitantly with a live vaccine, severe antigenic reactions may develop.

L-asparaginase is a methotrexate antagonist.

Performing anesthesia using dinitrogen oxide can lead to the development of unpredictable severe myelosuppression and stomatitis. Amiodarone may contribute to skin ulceration.

Pharmaceutical incompatibilities

Do not mix Metorthritol with other medicines and solvents.

How to take, course of use and dosage

Metorgrig is administered subcutaneously, intramuscularly or intravenously. The injection needle included in the package is intended only for subcutaneous use of Metorthritis. To administer the drug intramuscularly or intravenously, it is necessary to use needles suitable for these routes of use.

Doses

Metorthritis can only be prescribed by doctors who are familiar with the various properties of the drug and its mode of action. Metorthritis is given as an injection once a week. It is necessary to clearly explain to the patient that for the treatment of rheumatic diseases, the drug Metorthritis should be used only once a week.

Improper use of methotrexate can lead to the development of adverse events, including death.

Adult patients with rheumatoid arthritis:

Parenteral use of a trial dose of methotrexate is recommended one week before the start of therapy, to detect idiosyncratic adverse reactions.

The initial recommended dose is 7.5 mg of methotrexate once a week, administered either subcutaneously, intramuscularly or intravenously. Depending on the individual manifestation of the disease and the patient’s tolerance to therapy, the initial dose can be gradually increased by 2.5 mg per week. Do not exceed the dose of 25 mg per week.

Doses exceeding 20 mg per week may be associated with a significant increase in toxicity, especially bone marrow suppression. The response to treatment usually occurs in 4-8 weeks.

After achieving the desired therapeutic result, the dose should be gradually reduced to the lowest effective maintenance dose.

Children and adolescents with polyarthritic juvenile idiopathic arthritis (JMA):

The recommended dose is 10-15 mg / m2 of body surface area (BWT)/week. If treatment is not effective enough, the weekly dose may be increased to 20 mg / m2 of body surface area/week.

If the dose is increased, an increase in the frequency of treatment monitoring is recommended.

Due to limited data on intravenous use in children and adolescents, parenteral use is limited to subcutaneous and intramuscular use.

Patients with JIA should always contact specialized departments that have experience in treating children/adolescents.

Use in older children

Adult patients with severe psoriasis or psoriatic arthritis:

Parenteral use of a trial dose of 5-10 mg is recommended one week before the start of therapy, to detect idiosyncratic adverse reactions.

The initial recommended dose is 7.5 mg of methotrexate once a week, administered either subcutaneously, intramuscularly or intravenously. The dose should be gradually increased as needed, but should not exceed the maximum weekly dose of 30 mg of methotrexate.

The response to treatment usually occurs after 2-6 weeks. After achieving the desired therapeutic result, the dose should be gradually reduced to the lowest effective maintenance dose.

Patients with renal insufficiency:

Metorthritis should be used with caution in patients with renal insufficiency.

Doses should be adjusted as follows:

Patients with hepatic insufficiency:

If absolutely necessary, methotrexate should be used with caution in patients with active liver disease or a history of liver disease, especially those associated with alcohol abuse. Methotrexate is contraindicated if the bilirubin concentration exceeds 5 mg / dl (85.5 mmol / L).

Elderly patients

Dose reductions in elderly patients should be considered due to age-related decline in liver and kidney function and reduced folate reserves.

Patients who have an additional volume of distribution (pleural effusion, ascites)

Since the elimination half-life of Metorthritis can be extended 4-fold from the normal value, patients who have an additional volume of distribution may need to reduce the dose or, in some cases, stop using methotrexate.

Method of application and duration:

Metorthritol, a solution for injection, can be administered subcutaneously, intramuscularly, or intravenously.

In adults, intravenous use should be carried out bolus.

Rheumatoid polyarthritis, juvenile idiopathic arthritis, severe psoriasis, and psoriatic arthritis are usually treated with Metorthritis over a long period of time.

The total duration of treatment is determined by the doctor.

The pre-filled syringe with Metortrit is intended for single use only.

Unused medication should be disposed of.

It is necessary to visually check the solution for injection before

use. Use only a clear solution, practically free of particles.

According to the doctor’s decision, the drug can be used by patients independently. In this case, the patient should be trained by medical personnel in the technique of performing subcutaneous injections before using the drug. The first independent use of the drug in patients must necessarily be carried out in the presence of a doctor.

Overdose

Symptoms: the most common symptoms are those associated with suppression of the hematopoietic system.

Treatment: the specific antidote of methotrexate is calcium folinate. It neutralizes the adverse toxic effects.

In case of accidental overdose, no later than one hour after the use of methotrexate, calcium folinate (IV or iv) is administered at a dose equal to or exceeding the dose of methotrexate. use of calcium folinate is continued until the concentration of methotrexate in the blood serum decreases below the level of 10-7 mmol/l.

In case of a significant overdose, rehydration of the body and alkalinization of urine (pH greater than 7) may be required to prevent precipitation of methotrexate and / or its metabolites in the renal tubules. Hemodialysis and peritoneal dialysis do not improve methotrexate elimination.

Intensive intermittent hemodialysis using highly permeable (“high-flux”) dialysers allows for effective clearance of methotrexate.

Special instructions

If the patient has a significant amount of fluid in the pleural cavities or ascites, the fluid should be evacuated by drainage before starting methotrexate therapy, or the use of methotrexate should be discontinued.

The appearance of symptoms of toxic damage to the digestive system, the earliest of which are stomatitis and diarrhea, requires temporary discontinuation of methotrexate therapy due to the high risk of hemorrhagic enteritis and intestinal perforation with a fatal outcome if continued therapy. During treatment with methotrexate

, patients should be carefully monitored for signs of possible toxic effects and adverse effects in a timely manner.Given the risk of severe or even fatal toxic reactions, patients should be informed in detail about possible complications and recommended precautions.

Before starting treatment with methotrexate or when resuming therapy after a break, it is necessary to conduct a clinical blood test with the calculation of the leukocyte formula and the number of platelets, evaluate the activity of “liver” enzymes, the concentration of bilirubin, serum albumin, as well as chest X-ray examination and renal function tests.

If there are clinical indications, studies are prescribed to exclude tuberculosis and hepatitis.

During treatment with methotrexate (monthly in the first 6 months and at least every 3 months in the future, and with increasing doses, it is advisable to increase the frequency of examinations), the following studies are carried out::

1. Examination of the oral cavity and throat to detect changes in the mucous membranes.

2. Blood test with determination of the leukocyte formula and platelet count.

Even when used in normal therapeutic doses, methotrexate can suddenly cause suppression of the hematopoietic system. In case of a significant decrease in the number of white blood cells or platelets, treatment with methotrexate is immediately discontinued and symptomatic maintenance therapy is prescribed.

Patients should be instructed to immediately report any signs and symptoms that indicate the development of an infection to the doctor. When concomitant therapy with hematotoxic drugs (for example, leflunomide), it is necessary to carefully monitor the number of white blood cells and platelets in the blood.

During long-term treatment with methotrexate, if necessary, it is advisable to conduct a bone marrow biopsy.

3. Functional “liver” tests.

Special attention should be paid to identifying signs of liver damage. Treatment with methotrexate should not be initiated or suspended if any abnormalities in liver function tests or liver biopsies are detected.

Usually, the indicators return to normal within two weeks, after which treatment can be resumed by a doctor’s decision.

In 13-20% of patients, a short – term 2-to 3-fold increase in the activity of “liver” enzymes was observed. A persistent increase in the activity of “liver” enzymes and / or a decrease in the concentration of serum albumin can be indicators of severe hepatotoxicity.

Enzyme diagnostics does not always provide an adequate prediction of the development of hepatotoxicity detected morphologically, even in the case of normal values of the activity of “liver” enzymes, liver fibrosis or, much less often, cirrhosis of the liver can be detected histopathologically.

When using methotrexate for rheumatological indications, there is no reason to perform a liver biopsy to monitor the hepatotoxic effect of the drug.

When treating patients with psoriasis, it is necessary to evaluate the feasibility of performing a liver biopsy before or during treatment with methotrexate, based on current scientific recommendations. In the event that no signs of hepatotoxicity are detected using biochemical parameters of liver function or determining the concentration of type III collagen propeptide, additional studies may be required.

Such an assessment should differentiate between patients without risk factors and patients at risk (for example, those who have previously abused alcohol, with persistent increased activity of “liver” enzymes, a history of liver disease, a family history of hereditary liver diseases, patients with diabetes mellitus, obese patients, as well as those who have previously taken hepatotoxic drugs or come into contact with hepatotoxic chemicals and who have received long-term treatment with methotrexate in total doses of 1.5 g or more).

In case of a persistent increase in the activity of “liver” enzymes, it is necessary to reduce the dose or discontinue treatment with methotrexate.

Since methotrexate has a toxic effect on the liver, other hepatotoxic drugs should not be prescribed during treatment with the drug without obvious necessity.

You should also avoid or greatly reduce your alcohol intake. Especially carefully monitor the activity of “liver” enzymes should be in patients receiving concomitant therapy with other hepatotoxic and hematotoxic drugs (in particular, leflunomide).

Special care should be taken when treating patients with insulin-dependent diabetes mellitus, as cases of cirrhosis of the liver have been described with a previous periodic increase in the activity of” liver ” enzymes.

4. Functional renal tests and urinalysis.

If the concentration of serum creatinine increases, the dose of methotrexate should be reduced. When the concentration of creatinine. Methotrexate is contraindicated if the dose exceeds 2 mg/dl.

Since methotrexate is mainly excreted by the kidneys, patients with impaired renal function may experience an increase in the concentration of methotrexate in the blood, which can lead to severe adverse reactions. Patients who may have impaired renal function should be carefully monitored (for example, elderly patients).

This is especially important in the case of concomitant therapy with drugs that reduce the excretion of methotrexate, have an adverse effect on the kidneys (in particular, NSAIDs) or on the hematopoietic system. If there are risk factors, such as kidney failure. concomitant use of nonsteroidal anti-inflammatory drugs is not recommended.

Dehydration can also potentiate the toxic effects of methotrexate.

5. Study of the respiratory

system function. It is necessary to carefully monitor the symptoms of possible development of lung function disorders and, if necessary, prescribe a study of lung function.

Lung diseases require rapid diagnosis and withdrawal of methotrexate. The appearance of appropriate symptoms during treatment with methotrexate (especially dry, unproductive cough) or the development of non-specific pneumonitis may indicate a potential risk of lung damage. In such cases, methotrexate is discontinued and the patient is carefully examined.

Although the clinical picture may vary, a typical patient with lung disease caused by methotrexate use has fever, cough with shortness of breath, hypoxemia, and pulmonary infiltrates on X-rays. In the differential diagnosis, infectious diseases should be excluded. Lung damage can occur when treated with methotrexate in any dose.

During treatment with methotrexate, opportunistic infections may develop, including pneumonia caused by Pneumocystis carinii, which can be fatal. If the patient shows symptoms of lung damage, pneumonia caused by Pneumocystis carinii should be excluded.

Caution is recommended when treating patients with pulmonary insufficiency.

6. Because methotrexate affects the immune system, it can alter the response to vaccination and affect the results of immunological tests.

Special care should be taken when treating patients with inactive, chronic infections (such as shingles, tuberculosis, hepatitis B or C) due to their possible activation. Live vaccines should not be given during treatment with methotrexate.

It is recommended to interrupt treatment with methotrexate one week before surgery and resume one or two weeks after surgery.

With an increase in body temperature (more than 38°C), the elimination of methotrexate slows down significantly.

Methotrexate may increase the risk of developing neoplasms (mainly lymphomas). Malignant lymphomas can also develop in patients receiving low-dose methotrexate. In such cases, the drug is canceled. If spontaneous regression of lymphoma is not observed, therapy with cytotoxic drugs is prescribed.

Before starting treatment with Metortritis, pregnancy should be excluded. Methotrexate has an embryotoxic effect, contributes to the termination of pregnancy and the formation of fetal abnormalities.

Methotrexate therapy is associated with inhibition of spermatogenesis and ovogenesis, which can lead to a decrease in fertility. After discontinuation of methotrexate therapy, these effects spontaneously regress. During the period of methotrexate therapy and for 6 months after its completion, patients are recommended to use contraceptive measures.

Patients of reproductive age, as well as their partners, should be informed about the possible effects of methotrexate on fetal reproduction and development.

With high-dose therapy, precipitation of methotrexate or its metabolites in the renal tubules may occur. In such cases, as a prevention of this complication, it is recommended to conduct infusion therapy and alkalization of urine until pH 6.5-7.0 is reached by oral or intravenous administration of sodium bicarbonate (5 tablets of 625 mg every 3 hours) or acetazolamide (500 mg orally 4 times / day).

Methotrexate should not be mixed with other medications in the same infusion bag or vial.

When manipulating methotrexate solution, it is necessary to observe the rules for handling cytotoxic substances. Pregnant healthcare professionals should not work with the drug.

Measures should be taken to prevent

the methotrexate solution from getting on the skin and mucous membranes. If the drug still gets on the skin or mucous membranes, the affected area is immediately washed with plenty of water.

Influence on the ability to drive vehicles and fur.:During treatment with Metortritis, you should refrain from driving vehicles or working with other mechanisms, as there may be side effects from the nervous system (fatigue and dizziness).

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children!

Do not freeze!

Shelf

life is 2 years.

Active ingredient

Methotrexate

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults as directed by your doctor

Indications

Psoriasis, Rheumatoid Arthritis