Methotrexate, pills 2.5mg 50pcs

Composition

1 tablet contains:

Active ingredients:

methotrexate 2.5 mg.

Auxiliary substances:

sugar (sucrose) – 43.97 mg,

potato starch-21.82 mg,

talc-680 mcg,

calcium stearate-340 mcg,

crospovidone-340 mcg,

povidone-350 mcg.

Shell composition:

sugar (sucrose) – 32,5865 mg, magnesium hydroxycarbonate hydrate – 20,457 mg, flour – 16,144 mg, povidone – 166 µg, gelatin – 138 µg dye azorubin (E122) (karmuazin, the dye acid red 2C) – 16,6 µg, titanium dioxide – 450 µg, wax and 27.9 µg, talc – 14 mcg.

Indications

• Acute lymphoblastic leukemia and non-Hodgkin’s lymphoma;
• trophoblastic tumors;
• fungal mycosis in advanced stages;
• severe forms of psoriasis;
• rheumatoid arthritis (if other methods of therapy are ineffective).

Contraindications

The use of methotrexate is contraindicated:

• during pregnancy and lactation;
• with severe changes in kidney and liver function;
• with hematological disorders (such as bone marrow hypoplasia, leukopenia, thrombocytopenia, anemia);
• with acute infectious diseases;
• with immunodeficiency syndrome;
• with hypersensitivity to methotrexate or other components of the tablet;
• children under 3 years of age.

With caution: for ascites, pleural effusion, gastric and duodenal ulcers, ulcerative colitis, dehydration, gout or nephrolithiasis in the anamnesis, previous radiation therapy or chemotherapy, infectious diseases of a viral, fungal or bacterial nature.

Side effects

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

From the 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” transaminases), pancreatitis.

Nervous system disorders:  headache, dizziness, drowsiness, dysarthria, aphasia, hemiparesis, paresis, convulsions; when used in high doses – transient cognitive impairment, emotional lability; unusual cranial sensitivity, encephalopathy (including leukoencephalopathy).

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

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

Respiratory system disorders:  rarely-pulmonary fibrosis, respiratory failure, alveolitis, interstitial pneumonitis (including fatal), chronic obstructive pulmonary disease (COPD), symptoms of potentially serious interstitial pneumonia – dry, unproductive cough, shortness of breath, fever.

From the genitourinary system:  severe nephropathy or renal failure, azotemia, cystitis, hematuria, proteinuria, impaired sperm 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, pruritus of the skin, urticaria, photosensitivity, skin pigmentation disorders, alopecia, ecchymosis, telangiectasia, acne, furunculosis, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis, skin ulceration and necrosis, 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 (including disseminated herpes), diabetes mellitus, increased sweating.

Interaction

Increases the aiticoagulant activity of coumarin or indanedione derivatives and / or increases the risk of bleeding due to reduced synthesis of procoagulant factor in the liver and impaired platelet formation.

Increases the concentration of uric acid in the blood, so in the treatment of patients with concomitant hyperuricemia and gout, dose adjustment of anti-gouty drugs (allopurinol, colchicine, sulfinpyrazone) may be required; the use of uricosuric anti-gouty drugs may increase the risk of developing nephropathy associated with increased uric acid formation during treatment with methotrexate (preferably use allopurinol). Concomitant use of salicylates, phenylbutazone, phenytoin, sulfonamides, derivatives of sulfonylureas, aminobenzoic acid, pyrimethamine or trimethoprim, a number of antibiotics (penicillin, tetracycline, chloramphenicol), indirect anticoagulants and lipid-lowering drugs (colestyramine) increases toxicity by displacing methotrexate from the connection with albumins and/or reducing tubular activity. secretions, which in some cases can lead to the development of severe toxic effects, sometimes even with a fatal outcome.

Nonsteroidal anti-inflammatory drugs (NSAIDs) with high doses of methotrexate increase the concentration and slow the elimination of the latter, which can lead to death from severe hematological and gastrointestinal intoxication. It is recommended to stop taking phenylbutazone for 7-12 days, piroxicam for 10 days, diflunizal and Indometacin for 24-48 hours, ketoprofen and NSAIDs with a short T1 / 2 for 12-24 hours before the infusion of methotrexate in moderate and high doses and for at least 12 hours (depending on the concentration of methotrexate in the blood) after it ends. Caution should be exercised when combining NSAIDs with low doses of methotrexate (it is possible to reduce the excretion of methotrexate by the renal tubules). Drugs that block tubular secretion (for example, 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 the suppression of normal intestinal microflora.

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.

Performing 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 lead to the development of a synergistic cytotoxic effect (it is recommended to adjust the dosage regimen based on monitoring of hematological parameters).

Hematotoxic drugs increase the risk of methotrexate hematotoxicity.

Methotrexate reduces theophylline clearance.

Oral neomycin may reduce the absorption of methotrexate. Several patients with psoriasis or fungal mycosis treated with methotrexate in combination with PUVA therapy (metoxalene and ultraviolet radiation (UVA)) were diagnosed with skin cancer.

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

Folate-containing medications (including multivitamins) may reduce the effectiveness of methotrexate therapy.

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

How to take it, course of use and dosage

Methotrexate tablets are used orally. The dose and duration of treatment are set individually, depending on the chemotherapy regimen.

Trophoblastic tumors:

• 15-30 mg orally daily for 5 days with an interval of one or more weeks (depending on the signs of toxicity). Courses of treatment are usually repeated from 3 to 5 times.
• 50 mg once every 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 prednisone 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. To achieve an optimal effect, the weekly dose can be increased, but 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, doses of 10-30 mg/m2/week (0.3-1 mg/kg) are effective for children.

Psoriasis:

Methotrexate therapy is given in doses from 10 to 25 mg per week. The dose is usually increased gradually, and when the optimal clinical effect is achieved, the dose is reduced until the lowest effective dose is reached.

Fungal mycosis:

• 25 mg 2 times a week. Dose reduction or discontinuation of the drug is determined by the patient’s reaction and hematological parameters.

Overdose

Specific symptoms of methotrexate overdose are absent, it is diagnosed by the concentration of methotrexate in plasma.

Treatment: use of a specific antidote, calcium folinate, as soon as possible, 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, the body is hydrated and urine is alkalinized, which accelerates the elimination of methotrexate. To minimize the risk of nephropathy due to the formation of sediment of the drug or its metabolites in the urine, it is necessary to additionally determine the pH of the urine before each use and every 6 hours during the entire period of use of calcium folinate as an antidote, until the concentration of methotrexate in plasma is below 0.05 mmol/l, to ensure a pH above 7.

Special instructions

Methotrexate is a cytotoxic drug, so caution should be exercised when handling it. The drug should be prescribed by a doctor who has experience with the use of methotrexate and is familiar with its properties and features of action. Due to the potential for severe and even fatal adverse reactions, patients should be fully informed by their 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 general blood test should be performed to determine the level of platelets, a biochemical blood test to determine the values of liver enzymes, bilirubin, serum albumin, chest X-ray examination, kidney function examination, and, if necessary, tests for tuberculosis and hepatitis.

For timely detection of symptoms of intoxication, it is necessary to monitor the state of peripheral blood (the number of white blood cells and platelets: first every other day, then every 3-5 days during the first month, then once every 7-10 days, during remission – once every 1-2 weeks), the activity of “liver” transaminases, kidney function (urea nitrogen, creatinine clearance and/or serum creatinine), uric acid concentration in the blood serum, periodically perform chest X-rays, examination of the oral mucosa check the mouth and pharynx for ulceration before each application. Monitoring of bone marrow hematopoiesis is recommended before treatment, once 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 prolonged use of methotrexate (usually for 2 years or more) or reaching a total cumulative dose of at least 1.5 g and may lead to an unfavorable outcome. The hepatotoxic effect may also be due to a burdened concomitant history (alcoholism, obesity, diabetes mellitus) and senile age. Due to the toxic effect of the drug on the liver, patients should refrain from prescribing other hepatotoxic drugs during treatment, except in cases of obvious necessity. Patients taking other hepatotoxic drugs (such as 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 every additional 1-1.5 g. For moderate liver fibrosis or any degree of cirrhosis, methotrexate therapy is canceled; for mild fibrosis, a second biopsy is usually recommended after 6 months. During the initial therapy, minor histological changes in the liver (minor portal inflammation and fat changes) are possible, which is not a reason for refusal or discontinuation of treatment, but indicates the need for caution when using the drug

With the development of diarrhea and ulcerative stomatitis, methotrexate therapy should be interrupted due to the high risk of 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 (photosensitization reaction is possible). Due to its effect on the immune system, methotrexate may worsen the response to vaccination and affect the results of immunological tests. It is necessary to refuse immunization (if it is not approved by the doctor) in the interval from 3 to 12 months after taking the drug; other family members of the patient living with them should refuse to be immunized with the oral polio vaccine (avoid contact with people who have received the polio vaccine, or wear a protective mask covering their 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 – men and at least one ovulation cycle-women.

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

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

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

Storage conditions

Store in a dark place at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Methotrexate

Conditions of release from pharmacies

By prescription

Dosage form

Tablets