Epirubicin-ebeve

Leaflet accompanying the packaging: patient information

Epirubicin-Ebewe, 2 mg/ml concentrate for solution for infusion

Epirubicin hydrochloride

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.

Table of contents of the leaflet:

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

1. What is Epirubicin-Ebewe and what is it used for

Epirubicin hydrochloride, the active substance of Epirubicin-Ebewe, belongs to the group of
anticancer antibiotics of the anthracycline type. These drugs have a cytotoxic effect
and are used in the treatment of many cancers. Epirubicin-Ebewe can be used as monotherapy,
but more often in combination with other anticancer drugs.
Epirubicin-Ebewe is used in the treatment of many types of cancer, including:

• breast cancer,
• ovarian cancer,
• stomach cancer,
• lung cancer,
• head and neck cancer,
• colon and rectal cancer,
• multiple myeloma,
• non-Hodgkin's lymphoma,
• acute leukemias.

After administration of Epirubicin-Ebewe into the bladder, its beneficial effect has been observed
in the treatment of the following diseases:

• bladder cancer with transitional cell carcinoma,
• cancer in situ of the bladder,
• postoperative preventive treatment after transurethral resection of bladder cancer.

2. Important information before using Epirubicin-Ebewe

When not to use Epirubicin-Ebewe

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If Epirubicin-Ebewe is administered into the bladder, it must not be used in the following situations:

• urinary tract infection;
• blood in the urine;
• tumor infiltrating the bladder wall;
• difficulty in inserting a catheter into the bladder;
• cystitis;
• urine retention in the bladder;
• reduced bladder capacity (shrinkage of the diseased bladder).

Warnings and precautions

Before starting treatment with Epirubicin-Ebewe, discuss it with your doctor.
The medicine is used with special caution if:

• you have liver or kidney function disorders;
• during administration of the medicine, you experience discomfort or burning at the injection site or in its vicinity (possibility of extravasation into surrounding tissues);
• your blood test shows a decreased number of white and red blood cells and platelets;
• you have oral mucositis (pain in the lips, mouth or aphthae in the mouth);
• you have undergone previous radiation therapy to the chest or have taken drugs that may have an adverse effect on the heart. If in doubt whether this warning applies to you, consult your doctor or pharmacist;
• you have been vaccinated recently or plan to be vaccinated.

Your doctor will monitor your heart, kidney, and liver function, as well as your blood count.
Control tests of heart function are performed even for several weeks after the end of Epirubicin-Ebewe treatment.
You should immediately inform your doctor or nurse if you experience:

• pain when urinating or burning in the urethra
• excessive urination (also at night)
• blood in the urine

Note
The patient's urine may be red for one or two days after administration of Epirubicin-Ebewe.
This is a normal phenomenon related to the color of the medicine and should not cause concern.

Children

There is no data on the safety and efficacy of epirubicin hydrochloride in children.

Epirubicin-Ebewe and other medicines

Tell your doctor about all medicines you are taking or have recently taken, as well as those you plan to take.
Particularly, inform about taking such medicines as:

• other medicines that may affect the bone marrow and blood system
• other medicines that may affect heart function, such as calcium channel blockers (e.g., verapamil, nifedipine, and diltiazem), other anticancer drugs (e.g., 5-fluorouracil, cyclophosphamide, cisplatin, taxanes, doxorubicin, mitomycin-C, dacarbazine, dactinomycin, and cyclophosphamide), and concurrent or previous radiation therapy to the chest.
• other medicines that affect liver function, such as barbiturates (used to treat epilepsy or sleep disorders) and rifampicin (used to treat tuberculosis)
• trastuzumab (epirubicin should not be administered within 27 weeks after trastuzumab administration)
• cimetidine (a medicine that reduces stomach acid secretion)
• paclitaxel and docetaxel (medicines used to treat certain cancers)
• interferon alfa-2b (a medicine used to treat certain cancers and lymphomas, as well as some forms of hepatitis)
• quinine (a medicine used to treat malaria and leg cramps)
• dexrazoxane (a medicine sometimes used with doxorubicin to reduce the risk of heart function disorders)
• devaverapamil (a medicine used to treat certain heart diseases).

If you need to be vaccinated, tell your doctor about treatment with epirubicin hydrochloride, as certain vaccines (live attenuated) may cause severe side effects.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant or plan to have a child, consult your doctor before using this medicine.
Epirubicin hydrochloride, the active substance of Epirubicin-Ebewe, may harm the fetus.
Epirubicin-Ebewe should not be used during pregnancy unless your doctor considers it necessary.
Due to the risk of birth defects, women of childbearing age should use appropriate contraception during epirubicin treatment and for at least 6.5 months after the last dose.
Men should use effective contraception during treatment and for at least 3.5 months after the last dose.
In case of pregnancy of the patient or partner of the patient treated with Epirubicin-Ebewe, genetic counseling is recommended.
Men planning to have children should consult about the possibility of sperm freezing before starting treatment with Epirubicin-Ebewe.
Breastfeeding should be discontinued before and during treatment with Epirubicin-Ebewe.

Driving and using machines

No studies have been conducted on the effect of Epirubicin-Ebewe on driving and using machines.
However, this medicine may cause nausea and vomiting, which can temporarily impair the ability to perform these activities.

Epirubicin-Ebewe contains sodium

The medicine contains 3.54 mg of sodium (the main component of common salt) per 1 ml of concentrate.
The medicine contains 17.7 mg of sodium (the main component of common salt) per 5 ml vial.
This corresponds to 0.88% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 88.5 mg of sodium (the main component of common salt) per 25 ml vial.
This corresponds to 4.42% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 177 mg of sodium (the main component of common salt) per 50 ml vial.
This corresponds to 8.85% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 354 mg of sodium (the main component of common salt) per 100 ml vial.
This corresponds to 17.7% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine can be diluted in 0.9% sodium chloride solution.
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, refer to the patient leaflet of the diluent used.

3. How to use Epirubicin-Ebewe

Epirubicin-Ebewe is administered exclusively intravenously or into the bladder.
The medicine is administered to patients under the supervision of a specialist doctor in the treatment of cancer.
Before and during treatment, the doctor will order blood tests to monitor bone marrow, kidney, and liver function, as well as monitor heart function.
Control tests of heart function are performed even for several weeks after the end of Epirubicin-Ebewe treatment.
The dose of Epirubicin-Ebewe is adjusted by the doctor according to the patient's body surface area (calculated based on height and weight).
Its size depends on the type of cancer, the body's response to treatment, and other medicines used at the same time.
Usually, the dose of Epirubicin-Ebewe is 60 mg - 90 mg per square meter of body surface area.
The medicine is administered as a slow intravenous injection lasting three to five minutes.
The medicine is usually administered every three weeks.
In the treatment of small cell lung cancer, a higher dose of the medicine (120 mg per square meter of body surface area) is administered as an intravenous injection over three to five minutes or as an infusion (drip) lasting up to 30 minutes, also every three weeks.
In the treatment of breast cancer, the doctor determines the dose and method of treatment for each patient individually.
Lower doses are used in patients with a low number of white blood cells and platelets, liver or kidney function disorders, and in patients receiving other cytotoxic drugs.
To prevent unwanted dilution of Epirubicin-Ebewe by urine, the patient should not drink fluids for 12 hours before the procedure.
The patient remains under close observation before, during, and after treatment with Epirubicin-Ebewe.

Using a higher dose of Epirubicin-Ebewe than recommended

Administering a higher dose of Epirubicin-Ebewe than recommended may cause significant bone marrow suppression, resulting in a decreased number of white blood cells or platelets, inflammation of the mucous membranes of the digestive tract, and severe heart function disorders.
More severe side effects than usual may occur.

4. Possible side effects

Like all medicines, Epirubicin-Ebewe can cause side effects, although not everybody gets them.
If you experience any of the following side effects during infusion, tell your doctor immediately, as you may need urgent treatment:

• redness, pain, or swelling at the injection site;
• heart rhythm disorders, such as chest pain, shortness of breath, swelling of the ankles (such symptoms may occur up to several weeks after the end of Epirubicin-Ebewe treatment;
• severe allergic reaction with symptoms such as fainting, rash, itching, fever, chills, swelling of the face, and difficulty breathing. Anaphylaxis is possible.

The following side effects have been observed during treatment with Epirubicin-Ebewe:
Very common (may occur in more than 1 in 10 patients):

• bone marrow suppression
• decreased number of white blood cells (leukopenia)
• decreased number of red blood cells (anemia)
• decreased number of a certain type of white blood cells (granulocytopenia and neutropenia)
• fever associated with a low granulocyte count (febrile neutropenia)
• hair loss, usually temporary
• red urine color for one or two days after administration of Epirubicin-Ebewe; this is a normal phenomenon related to the color of the medicine and should not cause concern.

Common (may occur in less than 1 in 10 patients):

• infection
• loss of appetite (anorexia)
• feeling of dryness and thirst (dehydration)
• hot flashes
• mucositis (including esophagus, mouth)
• nausea, vomiting, diarrhea
• redness at the injection site
• cystitis with pain during urination, sometimes with blood in the urine (chemical and sometimes hemorrhagic cystitis), burning sensation, and frequent urination (after administration into the bladder).

Uncommon (may occur in less than 1 in 100 patients):

• decreased platelet count (thrombocytopenia),
• phlebitis, which may be accompanied by the formation of blood clots (thrombophlebitis), manifested by pain and (or) swelling of the hands or feet

Rare (may occur in less than 1 in 1000 patients):

• acute lymphatic leukemia, acute myeloid leukemia (may occur up to 3 years after the end of treatment)
• severe allergic reaction (anaphylaxis)
• increased uric acid levels in the blood due to rapid breakdown of cancer cells
• dizziness
• congestive heart failure (with shortness of breath, swelling, liver enlargement, fluid in the lungs and abdomen, ankle swelling, and changes in heart rhythm), changes in the ECG, abnormal heart rhythm, heart muscle disease, slowed heart rate, conduction disorders in the heart
• hives
• amenorrhea
• oligospermia
• malaise and weakness
• fever, chills
• changes in liver enzyme activity (transaminases).

Frequency not known (cannot be estimated from the available data):

• septic shock, sepsis (systemic infection), pneumonia
• bleeding and tissue hypoxia due to decreased blood cell production in the bone marrow (bone marrow suppression)
• eye discharge with itching, redness, and swelling (conjunctivitis), eye pain, blurred vision, abnormal light tolerance (keratitis)

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• thromboembolic event (blockage of a blood vessel by a detached blood clot, including pulmonary embolism, in individual cases fatal
• changes in the mouth (ulcers, erosion, pain, burning sensation, bleeding, discoloration)
• local toxic effects, rash, itching, skin changes, redness, flushing, excessive pigmentation of the skin and nails, photosensitivity, skin sensitivity to previously irradiated skin (radiation recall)
• venous sclerosis, local pain, severe connective tissue inflammation, tissue necrosis after accidental extravasation
• asymptomatic decrease in the amount of blood pumped by the left ventricle of the heart (asymptomatic decrease in left ventricular ejection fraction).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181 C, 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.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Epirubicin-Ebewe

Store the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP.
The expiry date refers to the last day of the month stated.
Store in a refrigerator (2°C – 8°C).
Refrigerated storage may cause the medicine to change to a gel-like consistency.
Left at controlled room temperature (15 to 25°C) for 2 to a maximum of 4 hours, it will return to a slightly viscous to fluid solution consistency.

6. Contents of the packaging and other information

What Epirubicin-Ebewe contains

The active substance of the medicine is epirubicin hydrochloride.
1 ml of concentrate for solution for infusion contains 2 mg of epirubicin hydrochloride.
Each 5 ml vial contains 10 mg of epirubicin hydrochloride.
Each 25 ml vial contains 50 mg of epirubicin hydrochloride.
Each 50 ml vial contains 100 mg of epirubicin hydrochloride.
Each 100 ml vial contains 200 mg of epirubicin hydrochloride.
The other ingredients are sodium chloride, hydrochloric acid, and water for injections.

What Epirubicin-Ebewe looks like and contents of the pack

Epirubicin-Ebewe is a clear, red solution.
The medicine is available in vials containing 5 ml, 25 ml, 50 ml, or 100 ml of concentrate.
The vials may be placed in transparent protective packaging made of plastic (ONKO-Safe or Sleeving).

Marketing authorization holder and manufacturer

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

Manufacturer

Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria
Date of last revision of the leaflet:10/2023
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Information intended for healthcare professionals only

Do not mix the concentrate or diluted solution of epirubicin hydrochloride with other medicines.

• The infusion solution should be prepared by trained personnel under aseptic conditions.
• The infusion solution should be prepared in a place designated as aseptic.
• Wear: disposable protective gloves, gown, protective glasses, and a face mask.
• Avoid accidental contact of the medicinal product with the eyes by using appropriate safety measures.
  In case of contact with the eye, rinse immediately with plenty of water and (or) 0.9% sodium chloride solution and seek medical attention immediately.
• In case of skin contact, wash the affected area thoroughly with soap and water or sodium bicarbonate solution.
  Do not scrub the skin with a hard brush.
  Wash your hands after removing gloves.
• Spilled medicinal product should first be flooded with a diluted sodium hypochlorite solution (containing 1% chlorine), preferably by soaking, and then rinsed with water.
  All materials used for cleaning should be disposed of properly.
• Pregnant women should not come into contact with cytotoxic preparations.
• When disposing of objects (syringes, cannulas, etc.) used to reconstitute and (or) dilute cytotoxic medicinal products, exercise caution and take appropriate safety measures.
  Any unused product or waste should be disposed of in accordance with local regulations.
• Medicines should not be poured down the drain or thrown away with household waste.
  This is to ensure environmental protection.

Method of administration

Epirubicin hydrochloride is intended for intravenous or intravesical administration only.
Caution should be exercised to avoid extravasation.
If extravasation occurs, administration of the medicine should be stopped immediately.
Epirubicin hydrochloride can be diluted under aseptic conditions in 5% glucose solution or 0.9% sodium chloride solution and administered as an intravenous infusion.
Physical and chemical stability of the infusion solution has been demonstrated when stored in PVC bags, polypropylene containers, polyethylene containers, or glass containers for 96 hours, at a temperature of 2°C to 8°C and at room temperature (20°C to 25°C), regardless of exposure to light.
For microbiological reasons, the product should be used immediately after dilution.
If not used immediately, the storage conditions and storage time are the responsibility of the user.
The storage time should not exceed 24 hours at a temperature of 2 to 8°C, unless dilution has taken place in controlled, validated aseptic conditions.

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