Methotrexat-ebeve

Package Leaflet: Information for the User

Methotrexat-Ebewe, 100 mg/ml, Concentrate for Solution for Infusion

Methotrexatum

Read All of This Leaflet Carefully Before You Start Using This Medicine.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet:

• 1. What is Methotrexat-Ebewe and What is it Used For
• 2. Before You Use Methotrexat-Ebewe
• 3. How to Use Methotrexat-Ebewe
• 4. Possible Side Effects
• 5. How to Store Methotrexat-Ebewe
• 6. Contents of the Package and Other Information

1. What is Methotrexat-Ebewe and What is it Used For

Methotrexat-Ebewe is an anticancer medicine belonging to the group of antimetabolites. It is particularly effective against rapidly growing tissues, such as cancer cells, bone marrow cells, fetal cells, mucous membranes of the mouth and gut, and urinary bladder cells. The mechanism of action of the medicine is based on the inhibition of tumor growth. If cell proliferation in tumor tissue is stronger than in normal tissues, methotrexate may inhibit tumor growth without harming normal tissues.

The growth of skin epithelial cells is significantly higher in patients with psoriasis than in healthy individuals; this symptom is the basis for the use of methotrexate in severe forms of psoriasis.

Indications for use:

• malignant tumors, such as acute lymphoblastic leukemia (ALL), including meningeal leukemia, non-Hodgkin's lymphoma (NHL), breast cancer, testicular cancer, ovarian cancer, head and neck cancer, small cell lung cancer, chorionic carcinoma, bone sarcomas;
• psoriasis that is resistant to other treatments.

2. Before You Use Methotrexat-Ebewe

When Not to Use Methotrexat-Ebewe

• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6);
• if you have liver function disorders;
• if you have severe kidney function disorders (in cases of low-dose methotrexate administration (<100 mg m² body surface area) or moderate kidney function disorders (in cases of medium high-dose methotrexate administration (>100 mg/m² body surface area));
• if you have blood system disorders (e.g., after previous radiation therapy or chemotherapy);
• if you have severe and/or active acute infections;
• if you abuse alcohol;
• if you have immune system disorders;
• if you have oral mucositis or active peptic ulcer disease;
• during breastfeeding and additionally during pregnancy, if the patient is using the medicine for non-oncological indications (for the treatment of non-cancerous diseases) (see section "Pregnancy, Breastfeeding, and Fertility");

Warnings and Precautions

Before starting treatment with Methotrexat-Ebewe, you should discuss it with your doctor if:

• you have diabetes and are being treated with insulin;
• you have an inactive, chronic infection (e.g., tuberculosis, hepatitis B or C, shingles);
• you have or have had kidney or liver disease in the past;
• you have lung function disorders;
• you are significantly overweight;
• you have fluid accumulation in the abdominal cavity or in the space between the lungs and the chest wall (ascites, pleural effusion);
• you are dehydrated or have conditions leading to dehydration (vomiting, diarrhea, oral mucositis).

During treatment with methotrexate, a recurrence of radiation-induced skin inflammation (radiation recall) or sunburn (sun recall) may occur.

Exposure to UV radiation during treatment with Methotrexat-Ebewe may exacerbate skin changes associated with psoriasis.

Methotrexate may increase skin sensitivity to sunlight. You should avoid intense sun exposure and not use a sunbed or sunlamp without consulting your doctor.

To protect your skin from intense sunlight, you should wear appropriate clothing or use a sunscreen with a high protection factor.

During treatment with methotrexate, cases of acute pulmonary hemorrhage have been reported in patients with underlying rheumatic disease. If you experience hemoptysis (coughing up blood), you should immediately consult your doctor.

If you, your partner, or caregiver notice new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, you should immediately contact your doctor, as these may be symptoms of a very rare, severe brain infection called progressive multifocal leukoencephalopathy (PML).

Recommended tests and precautions

Even with low doses of Methotrexat-Ebewe, severe side effects may occur. To detect these effects early, your doctor must perform regular tests and laboratory tests.

Before starting treatment

Before starting treatment, your doctor will order blood tests to check your blood cell count and liver and kidney function, as well as to detect hepatitis. Tests for serum albumin levels (protein in the blood), liver inflammation, and kidney function will be performed. Your doctor may also recommend other liver tests, such as imaging tests or liver tissue sampling, to examine the liver more closely. They may also recommend a chest X-ray or lung function test to check for tuberculosis.

During treatment:

• your doctor may order the following tests:
• examination of the mouth and throat to exclude changes in the mucous membranes, such as inflammation or ulcers;
• blood tests and/or complete blood count with assessment of the number of different types of blood cells and measurement of methotrexate levels in the serum;
• blood tests to monitor liver function;
• imaging tests to monitor liver condition;
• liver tissue sampling to examine the liver more closely;
• blood tests to monitor kidney function;
• monitoring of respiratory system function and, if necessary, lung function tests.

You should attend all scheduled blood tests and other tests recommended by your doctor.

If the results of any of these tests are abnormal, treatment will not be resumed until all tested parameters return to normal.

Children and Adolescents

Treatment with methotrexate in children and adolescents should be initiated and monitored by a specialist with experience in diagnosing and treating diseases for which methotrexate is indicated.

During treatment with Methotrexat-Ebewe, your doctor will closely monitor the child's condition to detect any potential side effects as early as possible.

Elderly

During treatment with Methotrexat-Ebewe, your doctor should closely monitor the condition of elderly patients to detect any potential side effects as early as possible.

Doses used in elderly patients should be relatively small, taking into account age-related liver and kidney function disorders and low folate reserves in the body.

Special Precautions for Use of Methotrexat-Ebewe

Methotrexate can temporarily disrupt sperm and egg production. Methotrexate may cause miscarriage and severe birth defects. Female patients should avoid becoming pregnant while taking methotrexate and for at least 6 months after treatment. Male patients should avoid fathering a child while taking methotrexate and for at least 3 months after treatment. See also section "Pregnancy, Breastfeeding, and Fertility".

Methotrexat-Ebewe and Other Medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription, herbal medicines, or natural products.

It is especially important to inform your doctor about the following medicines:

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Information exclusively for professional medical personnel

Shelf life
After opening
The product should be drawn up immediately before use. For microbiological reasons, the product should be used immediately. Otherwise, the user is responsible for the storage conditions and time of the remaining product. After the first draw, the remaining product should not be stored for more than 24 hours at room temperature, unless the draw is done under controlled and checked conditions with asepsis. The product stored in the refrigerator or at room temperature without light access then maintains its physico-chemical stability for up to 28 days.
The medicinal product Methotrexat-Ebewe 100 mg/ml maintains its physico-chemical stability for up to 28 days at room temperature with light access.
After dilution
From a microbiological point of view, the product should be used immediately. Otherwise, the user is responsible for the storage conditions and time of the prepared solution.
Prepared solutions should not be stored for more than 24 hours at a temperature of 2 ° C to 8 ° C, unless the dilution is done under controlled and checked conditions with asepsis.
Physical and chemical stability has been demonstrated for up to 28 days of the Methotrexat-Ebewe 100 mg/ml solution at a concentration of 5 mg/ml and 20 mg/ml diluted in 0.9% NaCl solution or 5% glucose solution stored in the refrigerator or at room temperature without light access, and up to 7 days at room temperature with light access.
For a solution with a concentration of 5 mg/ml diluted in 0.9% NaCl solution, physical and chemical stability has also been demonstrated for up to 28 days at room temperature with light access.
Instructions for preparation, administration of the drug, and disposal of its residues:
Methotrexate can be administered by intravenous injection (bolus or infusion), intra-arterial, intramuscular, or intrathecal. The solution should be diluted with 0.9% sodium chloride or 5% glucose solution.
Due to the different proposed dosing regimens, it is recommended to use the drug only under the guidance of a doctor who has experience in cytotoxic therapy.
The dose of the drug depends on the diagnosis of the underlying disease, the patient's body surface area or body weight, and the method of administration (monotherapy or administration in combination with other cytostatics), as well as the function of the bone marrow and parenchymal organs (liver, kidneys). An exception is intrathecal administration, where the maximum recommended dose is 15 mg, and the recommended maximum concentration is 5 mg/ml.
The dosing regimens of calcium folinate vary depending on the dose of methotrexate administered. Usually, up to 150 mg is administered in divided doses over 12-24 hours by intramuscular injection, intravenous injection in the form of a rapid infusion (bolus), or intravenous infusion, or orally, and then 12-25 mg intramuscularly, intravenously, or 15 mg orally (one capsule) every six hours for the next 48 hours. The protective treatment starts with a delay of 8 to 24 hours from the beginning of the methotrexate infusion. If smaller doses of methotrexate are used (less than 100 mg), it is sufficient to administer one capsule (15 mg) of calcium folinate every six hours for 48 to 72 hours.
In patients with liver, kidney, or bone marrow function disorders, the dose should be reduced.
Large doses of Methotrexat-Ebewe (greater than 100 mg) are usually administered by intravenous infusion for no longer than 24 hours. Part of the dose can be administered as an initial rapid injection.
Administration of large doses of methotrexate may cause precipitation of methotrexate or its

• January 22, 2004 / June, 2005 metabolites in the renal tubules. As a preventive measure, it is recommended to administer large amounts of fluids and alkalize the urine to pH 6.5-7.0 by oral or intravenous administration of sodium bicarbonate (5 tablets x 625 mg every three hours) or acetazolamide (500 mg orally four times a day). In the case of doses greater than 150 mg/m, it is necessary to administer calcium folinate simultaneously to reverse the toxic effect on normal cells. The method of administering calcium folinate depends on the dose of Methotrexat-Ebewe. Usually, up to 150 mg is administered in divided doses over 12-24 hours by intramuscular injection, intravenous injection in the form of a rapid infusion (bolus), or intravenous infusion, or orally, and then 12-25 mg intramuscularly, intravenously, or 15 mg orally (one capsule) every six hours for the next 48 hours. The protective treatment starts with a delay of 8 to 24 hours from the beginning of the methotrexate infusion. If smaller doses of methotrexate are used (less than 100 mg), it is sufficient to administer one capsule (15 mg) of calcium folinate every six hours for 48 to 72 hours.

Due to the toxic properties of the substance, the following safety rules should be observed:
the preparation, administration, and disposal of the product residues can only be carried out by trained personnel, and as with all cytostatic drugs, women who are pregnant should not be exposed to the drug;
persons preparing methotrexate should wear protective clothing: goggles, gowns, single-use gloves, and single-use masks;
methotrexate does not exhibit corrosive properties and should not cause skin damage in contact with the skin; however, the preparation should be rinsed with water immediately; and in case of transient burning, a mild cream can be applied. If there is a risk of systemic absorption of significant amounts of methotrexate by any route, calcium folinate should be administered;
unused or spilled residues should be disposed of by incineration; there are no specific recommendations for the incineration temperature;
follow the guidelines for cytotoxic substances.

Incompatibilities

Strong oxidizers and acids. Combination with chlorpromazine hydrochloride, droperidol, idarubicin, metoclopramide hydrochloride, heparin solution, sodium prednisolone phosphate, and promethazine hydrochloride causes precipitation or clouding of the solution.