5-fluorouracil-ebeve

Leaflet attached to the packaging: patient information

5-Fluorouracil-Ebewe, 50 mg/ml, solution for injection and infusion

Fluorouracil

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• 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 specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is 5-Fluorouracil-Ebewe and what is it used for
• 2. Important information before using 5-Fluorouracil-Ebewe
• 3. How to use 5-Fluorouracil-Ebewe
• 4. Possible side effects
• 5. How to store 5-Fluorouracil-Ebewe
• 6. Contents of the packaging and other information

1. What is 5-Fluorouracil-Ebewe and what is it used for

5-Fluorouracil-Ebewe is an anticancer medicine, belonging to the group of cytostatics and antimetabolites. Its action is based on inhibiting cell division by inhibiting DNA synthesis, resulting in the inhibition of tumor growth. 5-Fluorouracil-Ebewe can be used alone (in monotherapy) or in combination therapy for the treatment of malignant tumors, especially breast, colon, and rectal cancer, stomach, and pancreatic cancer.

2. Important information before using 5-Fluorouracil-Ebewe

When not to use 5-Fluorouracil-Ebewe

• if you are allergic to 5-fluorouracil or any of the excipients listed in section 6;
• if you have:
• bone marrow suppression, especially after radiotherapy or treatment with other anticancer medicines;
• significant changes in blood count (decreased number of blood cells);
• bleeding;
• mouth ulcers and gastrointestinal ulcers;
• severe diarrhea;
• severe liver or kidney dysfunction;
• severe infectious diseases;
• severe weakness;
• bilirubin level in serum greater than 85 micromoles/l (5 mg/dl);
• if you are breastfeeding;
• if you have not detected the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete DPD deficiency);
• if you are currently receiving or have received brivudine (an antiviral medicine used to treat chickenpox or shingles) in the last 4 weeks.

INTERACTIONbetween brivudine and 5-Fluorouracil-Ebewe CAN CAUSE
DEATH.
Live vaccines should be avoided.
Avoid any contact with polio virus vaccines (including people who have recently received such vaccines).
Before starting treatment, your doctor will check if you meet the following criteria:

• liver function indicated by normal bilirubin levels and aminotransferase activity;
• kidney function indicated by normal creatinine levels or creatinine clearance;
• bone marrow function determined by blood test results:
• white blood cell count >4000/microliter, i.e., >4.0 x 10^9/l;
• platelet count >100,000/microliter, i.e., >100 x 10^9/l;
• normal ECG.

Warnings and precautions

Before using 5-Fluorouracil-Ebewe, discuss with your doctor if:
you have been diagnosed with partial deficiency of dihydropyrimidine dehydrogenase (DPD) activity,
if a family member has partial or complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity,
if you have heart problems. Inform your doctor if you experience chest pain during treatment.
Dihydropyrimidine dehydrogenase (DPD) deficiency: DPD deficiency is a genetic disorder that usually does not cause any health problems until you take certain medicines. If you have a DPD deficiency and take 5-Fluorouracil-Ebewe, the risk of severe side effects (listed in section 4 - "Possible side effects") increases. It is recommended to perform a test before starting treatment to check if you have a DPD deficiency. If you have no activity of this enzyme, you should not be treated with 5-Fluorouracil-Ebewe. If the activity of this enzyme is reduced (partial enzyme deficiency), your doctor may prescribe a reduced dose of the medicine. Even if the DPD deficiency test result is negative, severe and life-threatening side effects can still occur.
Immediately contact your doctor if you experience the following symptoms: newly occurring confusion, disorientation, or other mental disorders, balance or coordination disorders, vision disorders. These may be symptoms of encephalopathy, which can lead to coma and death if left untreated.
Special caution is required for patients who have undergone pelvic irradiation with high doses, chemotherapy with alkylating agents, and patients who have had their adrenal glands or pituitary gland removed.
Before, during, and after treatment, your doctor will monitor your heart function, liver, kidney, and bone marrow function.
During treatment, it is possible to experience mouth ulcers and (or) mucositis, diarrhea, and bleeding (especially from the gastrointestinal tract). If you experience the first symptoms of these disorders, you should immediately consult your doctor.
5-Fluorouracil-Ebewe may reduce the effectiveness of the flu vaccine.
If you are going to have blood or urine tests, you should inform the laboratory staff that you are being treated with 5-fluorouracil.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Fluorouracil should only be used during pregnancy if the potential benefits outweigh the potential risk to the fetus. Women of childbearing age should not become pregnant during treatment. Women of childbearing age should use effective contraception during treatment with this medicine and for 6 months after its completion.
If you become pregnant during treatment, you should inform your doctor and consult a genetic counseling center.
It is not known whether fluorouracil passes into breast milk, so breastfeeding should be discontinued before starting treatment with 5-Fluorouracil-Ebewe.
Men taking 5-Fluorouracil-Ebewe should avoid fathering a child during treatment and for 3 months after its completion. Before starting treatment, you should consult about sperm storage due to the possibility of irreversible infertility caused by treatment with 5-Fluorouracil-Ebewe.

Driving and using machines

5-Fluorouracil-Ebewe can cause side effects such as nausea and vomiting, which can affect your ability to drive and use machines.

5-Fluorouracil-Ebewe and other medicines

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

Do not use brivudine (an antiviral medicine used to treat shingles or chickenpox) in patients who have recently received, are receiving, or plan to receive (within 4 weeks) 5-Fluorouracil-Ebewe. The harmful effect of 5-Fluorouracil-Ebewe may increase and may cause death.

5-Fluorouracil-Ebewe may increase the risk of death.

If you have taken brivudine, you should wait at least 4 weeks after stopping brivudine before starting treatment with 5-Fluorouracil-Ebewe. See "When not to use 5-Fluorouracil-Ebewe".

In case of accidental use of brivudine and 5-Fluorouracil-Ebewe:

• stop taking both medicines
• immediately consult your doctor
• go to the hospital for immediate treatment(you should be protected against systemic infections and dehydration).

Symptoms reported by the patient and observed in laboratory tests, toxicity of 5-fluorouracil (and other fluoropyrimidines) resulting from the above interaction include:

• malaise; diarrhea; mouth ulcers and (or) mucositis; weakness, increased susceptibility to infections, fatigue (decreased white blood cell count and decreased bone marrow function); flat red rash all over the body and painful skin to the touch, followed by large blisters leading to extensive skin peeling (toxic epidermal necrolysis) (see also section 4).

It is especially important to inform your doctor about radiation therapy and the use of the following medicines:

• cancer medicines (e.g., cyclophosphamide, vincristine, methotrexate, cisplatin, oxaliplatin, bevacizumab, irinotecan, doxorubicin);
• interferon-alpha;
• calcium folinate;
• anthracyclines;
• aminophenazone;
• phenylbutazone;
• sulfonamides;
• allopurinol;
• chlordiazepoxide;
• disulfiram;
• griseofulvin;
• isoniazid;
• mitomycin;
• cimetidine;
• metronidazole;
• levamisole;
• thiazide diuretics;
• vinorelbine;
• gemcitabine;
• anticoagulant medicines;
• vaccines.

If you are unsure what these medicines are, consult your doctor, pharmacist, or nurse.

5-Fluorouracil-Ebewe contains sodium

1 ml of solution contains 8.4 mg of sodium.
The medicine contains sodium (the main component of common salt) in the following amounts:

• 42 mg per vial or ampoule of 5 ml (which corresponds to 2.1% of the maximum recommended daily intake of sodium in the diet for adults);
• 84 mg per vial or ampoule of 10 ml (which corresponds to 4.2% of the maximum recommended daily intake of sodium in the diet for adults);
• 168 mg per vial of 20 ml (which corresponds to 8.4% of the maximum recommended daily intake of sodium in the diet for adults).

The medicine contains 840 mg of sodium per 100 ml vial. In the maximum daily dose (1 g of 5-FU), there is 168 mg of sodium.
The medicine can be diluted with 0.9% sodium chloride solution (physiological saline). The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used to dilute the medicine, you should consult the product characteristics of the diluent used.

3. How to use 5-Fluorouracil-Ebewe

5-Fluorouracil-Ebewe will be administered under the supervision of an oncologist with experience in the use of anticancer chemotherapy.
The dose of the medicine is determined by the doctor based on the patient's condition, body weight, and administration schedule (monotherapy or in combination with other cytotoxic medicines), as well as bone marrow and organ function.
The doctor will reduce the dose in patients who are: weakened, after major surgery (within the last 30 days), with liver dysfunction, kidney dysfunction, or decreased bone marrow function.
Treatment starts in the hospital.
The total daily dose should not exceed 1 gram.
The doctor will recommend daily platelet and white blood cell counts.
The medicine is administered after dissolution in physiological saline or 5% glucose solution, by intravenous injection or infusion, or by intra-arterial infusion. Infusion is preferable due to lower toxicity.
Example dosing schedule for 5-Fluorouracil-Ebewe in the treatment of colon and rectal cancer:
intravenous infusion: the average daily dose is 15 mg/kg body weight (600 mg/m^2);
intravenous injection: the average initial daily dose is 12 mg/kg body weight (480 mg/m^2), and in maintenance treatment from 5 to 10 mg/kg body weight (200 - 400 mg/m^2).
Example dosing schedule for 5-Fluorouracil-Ebewe in the treatment of breast cancer:
In breast cancer treatment, 5-fluorouracil may be used in combination with, for example, methotrexate and cyclophosphamide or with doxorubicin and cyclophosphamide.
In this schedule, a dose of 10 - 15 mg/kg body weight (400 - 600 mg/m^2) is administered intravenously on the 1st and 8th days of a 28-day treatment cycle.
The medicine can also be administered as a 24-hour continuous intravenous infusion, where the usual dose is 8.25 mg/kg body weight (350 mg/m^2).

Other administration methods

Intra-arterial infusion: a daily dose of 5 to 7.5 mg/kg body weight (200 - 300 mg/m^2) can be administered in a continuous 24-hour intra-arterial infusion. Intra-arterial infusion can also be administered locally, both in the treatment of primary tumors and metastases.

Use of a higher than recommended dose of 5-Fluorouracil-Ebewe

After overdose, the following symptoms may occur: psychotic reactions, drowsiness, increased sedative effect, increased alcohol toxicity.
If you experience any of these symptoms or have taken a higher dose of the medicine than recommended, you should immediately consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following symptoms, you should immediately inform your doctor:

• chest pain
• shortness of breath

If during the first cycle of treatment, severe mouth ulcers (ulcers in the mouth and/or throat), mucositis, diarrhea, neutropenia (increased risk of infections), or neurotoxicity occur, it may be related to DPD deficiency (see section 2: "Warnings and precautions").
Very common side effects(may occur in more than 1 in 10 people):
bone marrow suppression, neutropenia (decreased number of granulocytes), leukopenia (decreased number of white blood cells), thrombocytopenia (decreased number of platelets), anemia (decreased hemoglobin level), nosebleeds, increased uric acid level in the blood, changes in the electrocardiogram (ECG) indicating myocardial ischemia, bronchospasm, mucositis (e.g., mouth, esophagus, throat, or rectum), anorexia, watery diarrhea, nausea and vomiting, hair loss, delayed wound healing, hand-foot syndrome (with sensory disturbances, redness, swelling, pain, and peeling of the skin on the palms and soles), fatigue, general weakness, tiredness, and lack of energy, fever, infections.
Common side effects(may occur in less than 1 in 10 people):
immunosuppression with increased frequency of infections, low white blood cell count with fever (febrile neutropenia), transient and reversible cerebellar syndrome including ataxia, transient confusion, and extrapyramidal and cortical disorders (usually resolving after discontinuation of 5-fluorouracil), chest pain.
Uncommon side effects(may occur in less than 1 in 100 people):
allergic reactions, nystagmus, headache, dizziness, parkinsonian symptoms, extrapyramidal and cortical symptoms, and euphoria, somnolence, excessive tear production, blurred vision, eye movement disorders, optic neuritis, diplopia, decreased visual acuity, photophobia, conjunctivitis, blepharitis, eyelid eversion due to scarring, canalicular stenosis, heart rhythm disorders, myocardial infarction, myocardial ischemia, myocarditis, heart failure, cardiomyopathy (dilated cardiomyopathy), and cardiogenic shock (life-threatening heart failure).
Rare side effects(may occur in less than 1 in 1,000 people):
sepsis, generalized allergic reactions up to anaphylactic shock, peripheral neuropathy (in patients undergoing radiation therapy), thrombophlebitis.
Very rare side effects(may occur in less than 1 in 10,000 people):
agranulocytosis (complete or almost complete lack of granulocytes), pancytopenia (decreased number of red blood cells, white blood cells, and platelets), taste disorders, encephalopathy with symptoms such as ataxia, acute cerebellar syndrome, speech disorders, confusion, disorientation, Wernicke's encephalopathy (brain damage caused by vitamin B1 deficiency), seizures or coma, ischemic stroke (in cases of 5-fluorouracil use with other medicines), sudden cardiac arrest and sudden cardiac death, liver necrosis (sometimes fatal).
Side effects with unknown frequency(frequency cannot be estimated from available data):
cerebral ischemia, intestinal ischemia, and peripheral ischemia, Raynaud's phenomenon, thromboembolism, increased thyroid hormone levels, hyperammonemic encephalopathy (brain disorders caused by increased ammonia levels), cutaneous lupus erythematosus (a skin condition that can cause red, peeling patches, possibly with joint pain and fever), stress cardiomyopathy (a heart condition characterized by chest pain, shortness of breath, dizziness, fainting, and arrhythmias), air accumulation in the intestinal wall, a serious condition characterized by difficulty breathing, vomiting, and abdominal pain with muscle spasms (lactic acidosis), a condition characterized by headache, disorientation, seizures, and vision changes (posterior reversible encephalopathy syndrome, PRES), a serious complication leading to rapid breakdown of cancer cells, causing a significant increase in blood uric acid, potassium, and phosphate levels (tumor lysis syndrome), high blood triglyceride levels (a type of fat), pain, redness, or swelling at the injection site, occurring during or shortly after injection or infusion, possibly due to improper injection technique, vitamin B1 deficiency, and Wernicke's encephalopathy (brain damage caused by vitamin B1 deficiency), small intestine and colon inflammation causing pain and diarrhea, which can lead to tissue death (colitis, enteritis).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 5-Fluorouracil-Ebewe

Store at a temperature of 15°C - 25°C.
Do not store in the refrigerator or freeze.
Store in the original packaging to protect from light.

6. Contents of the packaging and other information

What 5-Fluorouracil-Ebewe contains

The active substance of the medicine is 5-fluorouracil. Each ml of solution contains 50 mg of 5-fluorouracil.
A 5 ml ampoule/vial contains 250 mg of 5-fluorouracil.
A 10 ml ampoule/vial contains 500 mg of 5-fluorouracil.
A 20 ml vial contains 1000 mg of 5-fluorouracil.
A 100 ml vial contains 5000 mg of 5-fluorouracil.
Other ingredients of the medicine are: sodium hydroxide, water for injections.

What 5-Fluorouracil-Ebewe looks like and contents of the pack

5-Fluorouracil-Ebewe is a clear, colorless solution in an ampoule or vial made of colorless glass (type I), in a cardboard box.
Vials may be placed in protective packaging made of plastic (ONKO-Safe or Sleeving).
Pack sizes:
5 ampoules of 5 ml, 5 ampoules of 10 ml, 1 vial of 5 ml, 1 vial of 10 ml, 1 vial of 20 ml, 1 vial of 100 ml.

Marketing authorization holder and manufacturer

EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestrasse 11
4866 Unterach, Austria

Manufacturer

Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria
To obtain more detailed information, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00
{Logo of the company}

Date of last revision of the leaflet:

Information intended for healthcare professionals only:

Shelf life

Before opening: 2 years
After opening
The solution should be withdrawn from the ampoule/vial immediately before use. From a microbiological point of view, the product should be used immediately. If not, the responsibility for the storage conditions and storage time of the remaining product in the ampoule/vial lies with the user. The solution remaining in the ampoule/vial after the first withdrawal should not be stored for more than 24 hours at room temperature, unless the withdrawal was done under controlled, tested aseptic conditions. In this case, the solution stored at room temperature with and without light access retains its physico-chemical stability for 28 days.
After dilution
From a microbiological point of view, the product should be used immediately. If not, the responsibility for the storage conditions and storage time of the prepared solution lies with the user. The prepared solutions should not be stored for more than 24 hours at a temperature of 2°C to 8°C, unless the dilution was done under controlled, tested aseptic conditions. Physical and chemical stability has been demonstrated for 28 days for a solution with a concentration of 0.35 mg/ml and 15 mg/ml diluted in 0.9% sodium chloride solution or 5% glucose solution, stored in a refrigerator or at room temperature with and without light access.

Instructions for preparation of the medicine for administration

As with other cytotoxic medicines, special precautions are required when preparing 5-fluorouracil for administration. Gloves and protective eyewear and clothing should be worn, and the medicine should be prepared in a designated area.
Avoid contact with the skin and mucous membranes. If contact occurs, the area should be thoroughly washed with soap and water. If the medicine gets into the eye, it should be rinsed with a large amount of water and medical attention should be sought immediately. Pregnant women should not work with 5-fluorouracil.
Follow the guidelines for cytostatics.
Handle with care, avoid skin contact.

Incompatibilities

5-Fluorouracil-Ebewe should be diluted with 0.9% sodium chloride solution or 5% glucose solution.
No incompatibilities have been found with the tested diluents.
Calcium folinate
5-Fluorouracil-Ebewe should not be mixed in the same infusion solution with calcium folinate due to the possibility of precipitate formation. Incompatibility of a 50 mg/ml fluorouracil solution with a 20 mg/ml calcium folinate solution, with or without 5% dextrose, has been demonstrated after mixing in different quantities and storage in polyvinyl chloride containers at 4°C, 23°C, or 32°C.
Warning!
A precipitate may form in the medicine stored in the refrigerator. If a precipitate forms due to exposure to too low temperatures, it should be redissolved by heating to 60°C with vigorous shaking. Before administration, cool to body temperature.
The solution should be withdrawn from the ampoule or vial immediately before use.