Metodect solution for subcutaneous injection 50mg/ml 0.35ml ( 17.5mg ) syringe, 1pc

Composition

>1 ml is disodium methotrexate 54.84 mg, which corresponds to the content of methotrexate 50 mg. Excipients: sodium chloride 4 mg, sodium hydroxide up to pH 8.5-8.9 q. s., d/i water up to 1 ml

Pharmacological action

Antitumor agent from the group of antimetabolites – antagonists of folic acid. It acts in the S-phase of mitosis. The mechanism of action is associated with inhibition of the synthesis of purine nucleotides and thymidylate as a result of irreversible binding to dihydrofolate reductase, which prevents the reduction of dihydrofolate to active tetrahydrofolate. It is more active against rapidly growing cells. It has some immunosuppressive effect.

Indications

Acute lymphocytic leukemia, trophoblastic disease, skin cancer, cervical and vulvar cancer, esophageal cancer, squamous cell head and neck cancer, renal pelvis and ureteral cancer, osteogenic and soft cell sarcoma, Ewing’s sarcoma, lung cancer, breast cancer, testicular and ovarian germinogenic tumors, liver cancer, kidney cancer, retinoblastoma, medulloblastoma, penile cancer, lymphogranulomatosis.

Severe forms of psoriasis (if standard therapy is ineffective).

Severe form of rheumatoid arthritis (if standard therapy is ineffective).

Contraindications

Severe liver and/or kidney dysfunction, leukopenia, thrombocytopenia, pregnancy. Methotrexate should not be used in immunodeficiency conditions.

Side effects

From the digestive system:  ulcerative stomatitis, anorexia, gingivitis, pharyngitis, nausea are possible; rarely-diarrhea, melena, enteritis, pancreatitis; in some cases (with prolonged daily use) – liver necrosis, cirrhosis, fatty atrophy, periportal fibrosis of the liver.

From the hematopoietic system:  leukopenia, anemia, and thrombocytopenia.

From the central nervous system:  fatigue, dizziness; rarely-headache, aphasia, drowsiness, convulsions.

From the side of the reproductive system:  disorders of oogenesis and spermatogenesis, oligospermia, menstrual disorders, decreased libido, impotence.

From the urinary system:  hematuria, cystitis, severe renal dysfunction.

Allergic reactions:  chills, decreased resistance to infection; rarely-urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Dermatological reactions:  skin rash, photosensitization, pigmentation disorders, telangiectasia, acne, furunculosis.

Interaction

When used concomitantly with vitamin preparations containing folic acid or its derivatives, the effectiveness of methotrexate may decrease.

Concomitant use of NSAIDs in high doses can lead to an increase in the concentration of methotrexate in plasma and to an elongation of its T_1/2, as well as to an increase in the concentration of methotrexate that is not associated with plasma albumins, which in turn increases the toxic effects of methotrexate (primarily on the gastrointestinal tract and hematopoietic system).

When methotrexate is used simultaneously with penicillins (even in low doses), its toxic effects may increase.

When used concomitantly with sulfonamides, especially co-trimoxazole, there is a risk of increasing the myelodepressive effect.

When nitrous oxide is used in patients receiving methotrexate, severe unpredictable myelodepression and stomatitis may develop.

When valproic acid is used simultaneously with methotrexate, its concentration in blood plasma may decrease.

Colestyramine binds methotrexate, reduces its enterohepatic recirculation, which leads to a decrease in its concentration in blood plasma.

When used concomitantly with mercaptopurine, its bioavailability may increase due to metabolic disorders during the “first pass” through the liver.

Neomycin and paromomycin reduce the absorption of methotrexate from the gastrointestinal tract.

In patients receiving omeprazole, an increase in the concentration of methotrexate in blood plasma may occur.

When used concomitantly with probenecid, a 3-4-fold increase in the concentration of methotrexate in blood plasma is possible due to a decrease in its renal excretion.

Concomitant use of methotrexate with retinoids may increase the risk of hepatotoxic effects.

Salicylates potentiate the effect of methotrexate due to a decrease in its renal excretion.

After a course of treatment with tetracycline, methotrexate, used even in low doses, can have a toxic effect.

When methotrexate and fluorouracil are administered sequentially, a synergistic effect is possible; fluorouracil administered before methotrexate may reduce its toxicity.

Cisplatin has a nephrotoxic effect and therefore can reduce the renal excretion of methotrexate, which leads to an increase in its toxicity.

Increased toxicity may occur with cyclosporine in patients treated with methotrexate.

How to take, course of use and dosage

Except in special cases (see below “Treatment of ST-segment elevation myocardial infarction, medication or percutaneous coronary intervention” and “Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis”) enoxaparin sodium is administered by deep subcutaneous injection. Injections should preferably be performed in the patient’s “lying down” position. Injections should be performed alternately in the left or right anterolateral or posterolateral surface of the abdomen.

The needle should be inserted vertically (not laterally) into the skin fold for the entire length, collected and held until the injection is completed between the thumb and index finger. The skin fold is released only after the injection is completed. Do not massage the injection site after use of the drug.

The pre-filled disposable syringe is ready for use.

The drug should not be administered intramuscularly!

Prevention of venous thrombosis and embolism in surgical procedures especially in orthopedic and general surgical operations

In patients with a moderate risk of developing thrombosis and embolism (general surgical operations), the recommended dose of the drug is 20 mg once a day subcutaneously. The first injection is made 2 hours before surgery.

In patients with a high risk of developing thrombosis and embolism (general surgical and orthopedic operations), the drug is recommended at a dose of 40 mg once a day subcutaneously; the first dose is administered 12 hours before surgery, or 30 mg 2 times a day with the start of use 12-24 hours after surgery.

The average duration of treatment with the drug is 7-10 days. If necessary, therapy can be continued as long as the risk of thrombosis and embolism persists (for example, in orthopedics, enoxaparin sodium is used 40 mg once a day for 5 weeks).

The specific features of prescribing the drug for spinal / epidural anesthesia, as well as for percutaneous coronary angioplasty, are described in the section “Special instructions”.

Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases

The recommended dose of enoxaparin sodium is 40 mg once daily subcutaneously for 6-14 days.

Treatment of deep vein thrombosis with or without pulmonary embolism

Enixum® is administered subcutaneously at the rate of 1.5 mg / kg once a day or at a dose of 1 mg / kg twice a day. In patients with complicated thromboembolic disorders, the drug is recommended to be used at a dose of 1 mg/kg twice a day.

The average duration of treatment is 10 days. It is advisable to immediately start therapy with oral anticoagulants, while enoxaparin sodium therapy should be continued until a sufficient anticoagulant effect is achieved, i. e. the INR should be 2.0-3.0. If necessary, control of the anticoagulant effect should be evaluated by anti-Xa activity.

Treatment of unstable angina and non-Q wave myocardial infarction in combination with acetylsalicylic acid

Enixum® is administered at the rate of 1 mg/kg of body weight every 12 hours subcutaneously, with simultaneous use of acetylsalicylic acid inside at a dose of 100-325 mg once a day.

The average duration of treatment is 2-8 days (until the patient’s clinical condition stabilizes).

Treatment of ST-segment elevation myocardial infarction, by medication or by percutaneous coronary intervention

Treatment begins with intravenous bolus use of enoxaparin sodium at a dose of 30 mg and immediately after it (within 15 minutes) is administered subcutaneously at a dose of 1 mg/kg (and during the first two subcutaneous injections, a maximum of 100 mg of enoxaparin sodium can be administered). Then all subsequent subcutaneous doses are administered every 12 hours at the rate of 1 mg / kg (i. e., with a body weight of more than 100 kg, the dose may exceed 100 mg).

In persons 75 years of age and older, the initial intravenous bolus is not used. Enoxaparin sodium is administered subcutaneously at a dose of 0.75 mg / kg every 12 hours (moreover, during the first two subcutaneous injections, a maximum of 75 mg of enoxaparin sodium can be administered). Then, all subsequent subcutaneous doses are administered every 12 hours at the rate of 0.75 mg / kg (i. e., if the body weight is more than 100 kg, the dose may exceed 75 mg). In combination with thrombolytics (fibrin-specific and fibrin – iespecific) enoxaparin sodium should be administered between 15 minutes before the start of thrombolytic therapy and 30 minutes after it. After detection of acute ST-segment elevation myocardial infarction, acetylsalicylic acid should be started simultaneously as soon as possible, which, in the absence of contraindications, should continue for at least 30 days in doses from 75 to 325 mg daily.The recommended duration of treatment with the drug is 8 days or until the patient is discharged from the hospital, if the period of hospitalization is less than 8 days. Bolus use of enoxaparin sodium should be performed through a venous catheter and enoxaparin sodium should not be mixed or administered together with other medications. In order to avoid the presence of traces of other drugs in the system and their interaction with enoxaparin sodium, the venous catheter should be flushed with a sufficient amount of 0.9% sodium chloride solution or dextrose before and after intravenous bolus use of enoxaparin sodium. Enoxaparin sodium is compatible with 0.9% sodium chloride solution and 5% dextrose solution.

For bolus use of 30 mg of enoxaparin sodium in the treatment of acute ST-segment elevation myocardial infarction, an excessive amount of the drug is removed from glass syringes of 60 mg,80 mg and 100 mg so that only 30 mg (0.3 ml) remains in them. A dose of 30 mg can be directly administered intravenously.

For intravenous bolus use of enoxaparin sodium through a venous catheter, pre-filled syringes for subcutaneous use of the drug 60 mg,80 mg and 100 mg can be used. It is recommended to use syringes of 60 mg, as this reduces the amount of drug removed from the syringe. 20 mg syringes are not used, as they do not contain enough preparation for bolus use of 30 mg of enoxaparin sodium. Syringes of 40 mg are not used, as they do not have divisions and therefore it is impossible to accurately measure the amount of 30 mg.

In patients undergoing percutaneous coronary intervention, if the last subcutaneous injection of enoxaparin sodium was performed less than 8 hours before inflating the balloon catheter inserted into the site of narrowing of the coronary artery, additional use of enoxaparin sodium is not required. If the last subcutaneous injection of enoxaparin sodium was administered more than 8 hours before inflating the balloon catheter, an additional intravenous bolus of enoxaparin sodium should be administered at a dose of 0.3 mg/kg.

To increase the accuracy of additional bolus injection of small volumes into the venous catheter during percutaneous coronary interventions, it is recommended to dilute the drug to a concentration of 3 mg / ml. Dilution of the solution is recommended immediately before use.

To obtain a solution of enoxaparin sodium with a concentration of 3 mg / ml using a pre-filled syringe, it is recommended to use a container with an infusion solution, from which part of the solution is extracted to the required volume using a conventional syringe. Enoxaparin sodium (the contents of the hypodermic syringe) is injected into the remaining infusion solution in the container.

The contents of the container with a diluted solution of enoxaparin sodium are carefully mixed. For use with a syringe, the required volume of diluted enoxaparin sodium solution is extracted, which is calculated by the formula:

Volume of diluted solution = Patient’s body weight (kg) x 0.1 or using the table below.

Volumes to be administered intravenously after dilution

Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis (usually, if the session duration is not more than 4 hours)

The average dose of enoxaparin sodium is 1 mg / kg. For patients with a high risk of bleeding, the dose should be reduced to 0.5 mg / kg for double vascular access or to 0.75 mg for single vascular access.

During hemodialysis, Enixum® should be inserted into the arterial section of the shunt at the beginning of the hemodialysis session. One dose is usually sufficient for a four-hour session, but if fibrin rings are detected during longer hemodialysis, the drug can be additionally administered at the rate of 0.5-1 mg/kg.

Elderly patients

With the exception of treatment of ST – segment elevation myocardial infarction (see above), no dose reduction of enoxaparin sodium is required for all other indications in elderly patients who do not have impaired renal function.

Patients with renal insufficiency

Severe renal impairment (endogenous creatinine clearance less than 30 ml / min). The dose of enoxaparin sodium is reduced in accordance with the tables below, as these patients accumulate the drug.

When using the drug for therapeutic purposes, the following dosage adjustment is recommended::

When using the drug for preventive purposes, the following dosage adjustment is recommended:

The recommended dosage adjustment is not applicable during hemodialysis.

In mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-50 ml/min) renal insufficiency, no dose adjustment is required, but laboratory monitoring of therapy should be carried out more carefully.

Patients with hepatic insufficiency

Due to the lack of clinical studies, caution should be exercised when using enoxaparin sodium in patients with impaired liver function.

Overdose

Symptoms: hemorrhagic complications in case of accidental overdose with subcutaneous use of enoxaparin sodium. With accidental ingestion of even large doses, absorption of the drug is unlikely.

Treatment: neutralize the effect of enoxaparin sodium by slow intravenous (iv) use of protamine sulfate. 1 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of enoxaparin sodium, if the drug was administered no more than 8 hours before the use of protamine sulfate.

0.5 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of enoxaparin sodium, if it was administered more than 8 hours ago or if a second dose of protamine sulfate is necessary.

If 12 or more hours have elapsed since the introduction of enoxaparin sodium, the introduction of protamine sulfate is not required. However, even with high doses of protamine sulfate, the anti-Xa activity of enoxaparin sodium is not completely neutralized (by a maximum of 60%).

Special instructions

Methotrexate should not be used for ascites, pleural effusion, gastric and duodenal ulcers, ulcerative colitis, gout, or nephropathy (including in the anamnesis).

It is not recommended to use in patients with chickenpox (including recently transferred or after contact with sick people), herpes zoster and other acute infectious diseases.

Before starting therapy and against the background of ongoing treatment, the picture of peripheral blood, liver and kidney function, and chest radiography should be monitored.

In the treatment of rheumatoid arthritis or psoriasis, a detailed general blood test should be performed at least once a month, and laboratory tests of liver or kidney function should be performed at least once every 1-2 months.

When used for psoriasis, local treatment of the disease should not be interrupted. In case of overdose, the use of calcium folinate is recommended (but not later than 4 hours).

When conducting combined antitumor therapy, special care should be taken when concomitant use of methotrexate in high doses with drugs that have a nephrotoxic effect (for example, with cisplatin).

It is not recommended to vaccinate patients and their families.

Caution should be exercised when combining methotrexate (even in low doses) with acetylsalicylic acid.

Experimental studies have established the carcinogenic and mutagenic effects of methotrexate.

Storage conditions

At a temperature not exceeding 25 °C. Do not freeze it.

Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Methotrexate

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Cancer, Psoriasis, Rheumatoid Arthritis