Etoposid Ebeve

Leaflet accompanying the packaging: patient information

Etoposid-Ebewe, 20 mg/ml, concentrate for solution for infusion

Etoposide

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.
In case of any doubts, consult a doctor, nurse, or pharmacist.
This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, nurse, or pharmacist.
See section 4.

Table of contents of the leaflet

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

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

This medicine is available under the name Etoposid-Ebewe. 1 ml of the concentrate contains 20 mg of etoposide as the active ingredient.
Etoposide belongs to a group of medicines called cytostatics, which are used to treat cancer.
Etoposid-Ebewe is used to treat certain types of cancer in adults:

• testicular cancer,
• small cell lung cancer,
• blood cancer (acute myeloid leukemia),
• tumors in the lymphatic system (Hodgkin's lymphoma, non-Hodgkin's lymphoma),
• cancer of the reproductive system (gestational trophoblastic disease and ovarian cancer).

Etoposid-Ebewe is used to treat certain types of cancer in children:

• blood cancer (acute myeloid leukemia),
• tumors in the lymphatic system (Hodgkin's lymphoma, non-Hodgkin's lymphoma).

The exact reason why Etoposid-Ebewe has been prescribed should be discussed with a doctor.

2. Important information before using Etoposid-Ebewe

Do not use Etoposid-Ebewe in the following cases:

• allergy to etoposide or any of the other ingredients of this medicine (listed in section 6);
• recent vaccination with a live vaccine, including yellow fever vaccination;
• breastfeeding or planning to breastfeed.

If any of the above points apply to the patient or if there are any doubts, consult a doctor.

Warnings and precautions

Before starting to receive Etoposid-Ebewe, discuss the following with a doctor or pharmacist:

• presence of any infections,
• recent radiation therapy or chemotherapy,
• low levels of proteins called albuminsin the blood,
• liver or kidney disease.

Effective anticancer treatment can quickly destroy a large number of cancer cells.
In very rare cases, this can lead to the release of harmful amounts of substances from these cancer cells into the blood.
As a result, liver, kidney, heart, or blood function disorders may occur, which can be fatal if left untreated.
To prevent this, the doctor will need to perform regular blood tests to monitor the levels of these substances during treatment with this medicine.
This medicine may cause a decrease in the number of certain blood cells, which can lead to infections or poor blood clotting.
To ensure this does not happen, blood tests will be performed at the start of treatment and before each dose of the medicine.
If liver or kidney function is impaired, the doctor may also order regular blood tests to monitor them.
Patients with liver or kidney disease should consult their doctor before using the medicine, as a large amount of benzyl alcohol may accumulate in their body and cause side effects (metabolic acidosis).

Etoposid-Ebewe and other medicines

Tell a doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take.
This is especially important in the following cases:

• taking a medicine called cyclosporine (a medicine used to weaken the immune system),
• treatment with cisplatin (a medicine used to treat cancer),
• taking phenytoin or any other medicine for epilepsy,
• taking warfarin (a medicine that prevents blood clots),
• recent vaccination with a live vaccine,
• taking phenylbutazone, sodium salicylate, or acetylsalicylic acid,
• taking any anthracyclines (a group of medicines used to treat cancer),
• taking any medicines with a similar mechanism of action to Etoposid-Ebewe.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult a doctor before using this medicine.
Etoposid-Ebewe should not be used during pregnancy, unless a doctor recommends it.
The medicine should not be used during breastfeeding.
Both women and men who are able to have children should use effective contraceptive methods (e.g., barrier methods or condoms) during and for at least 6 months after treatment with Etoposid-Ebewe.
Men treated with Etoposid-Ebewe should not father a child during treatment and for up to 6 months after treatment.
Before starting treatment, men should consult their doctor about sperm preservation.
Women and men considering having children after treatment with Etoposid-Ebewe should discuss this with their doctor or nurse.
Pregnant women should consult their doctor before using the medicine, as a large amount of benzyl alcohol may accumulate in their body and cause side effects (metabolic acidosis).

Driving and using machines

Due to the alcohol content, do not drive or operate machinery soon after receiving Etoposid-Ebewe.
If drowsiness, fatigue, nausea, dizziness, or other symptoms occur, do not drive or operate machinery until discussing this with a doctor.

Etoposid-Ebewe contains benzyl alcohol and ethanol

The medicine contains 20 mg of benzyl alcohol per 1 ml of concentrate.
Benzyl alcohol may cause allergic reactions.
Administering benzyl alcohol to small children is associated with a risk of serious side effects, including breathing difficulties (so-called "gasping syndrome").
Do not administer the medicine to newborns (up to 4 weeks of age) without a doctor's recommendation.
Do not administer the medicine to small children (under 3 years of age) for more than a week without a doctor's recommendation.
Pregnant women and patients with liver or kidney disease should consult their doctor before using the medicine, as a large amount of benzyl alcohol may accumulate in their body and cause side effects (metabolic acidosis).
The medicine contains 252 mg of ethanol per 1 ml of concentrate. The amount of alcohol in 1 ml of the medicine is equivalent to 7 ml of beer or 3 ml of wine.
The amount of alcohol in the medicine is unlikely to have an effect on adults and adolescents, and its effect on children is likely to be negligible. However, it may cause some effect in younger children, such as drowsiness.
The alcohol in the medicine may interact with other medicines. If the patient is taking other medicines, they should consult their doctor or pharmacist.
If the patient is pregnant, they should consult their doctor or pharmacist before using the medicine.
If the patient is addicted to alcohol, they should consult their doctor or pharmacist before using the medicine.

3. How to use Etoposid-Ebewe

Etoposid-Ebewe will be administered by a doctor or nurse. It will be administered by slow infusion into a vein. This may take 30 to 60 minutes.
The dose will be calculated by the doctor for each individual case. The typical dose, expressed in terms of etoposide, is 50 to 100 mg/m² per day for 5 consecutive days, or 100 to 120 mg/m² on days 1, 3, and 5. This treatment cycle may be repeated depending on the results of blood tests, but not earlier than 21 days after the end of the first cycle.
In children treated for blood cancer or lymphatic system tumors, the dose used is 75 to 150 mg/m² per day for 2 to 5 days.
Sometimes, the doctor may prescribe a different dose, especially if the patient is currently receiving or has recently received another type of cancer treatment or has kidney problems.

Overdose of Etoposid-Ebewe

Since Etoposid-Ebewe is administered by a doctor or nurse, overdose is unlikely. However, if it does occur, the doctor will treat any resulting symptoms.
In case of any further doubts about using this medicine, consult a doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the following symptoms occur, tell a doctor or nurse immediately: swelling of the tongue or throat, difficulty breathing, rapid heartbeat, skin rash or hives. These may be symptoms of a severe allergic reaction.

Severe liver, kidney, or heart damagedue to a complication called tumor lysis syndrome, caused by the release of harmful amounts of substances from cancer cells into the blood, has been reported in some cases when Etoposid-Ebewe was used in combination with other cancer medicines.
Other side effectsthat may occur when using Etoposid-Ebewe include:
Very common side effects(occurring in more than 1 in 10 people)

• blood disorders (which is why blood tests will be performed between treatment cycles)
• temporary hair loss
• nausea and vomiting
• abdominal pain
• loss of appetite
• skin color changes (discoloration)
• constipation
• weakness (asthenia)
• general feeling of being unwell
• liver damage (hepatotoxicity)
• increased liver enzyme activity
• increased bilirubin levels

Common side effects(occurring in up to 1 in 10 people)

• acute leukemia
• irregular heartbeat (arrhythmia) or heart attack (myocardial infarction)
• dizziness
• diarrhea
• reactions at the injection site
• severe allergic reaction
• high blood pressure
• low blood pressure
• herpes simplex, oral herpes, throat ulcers
• skin symptoms, such as itching or rash
• phlebitis
• infections (including those observed in patients with weakened immune systems,

such as Pneumocystis jiroveciipneumonia)
Uncommon side effects(occurring in up to 1 in 100 people)

• tingling or numbness in the hands and feet
• bleeding

Rare side effects(occurring in up to 1 in 1,000 people)

• gastroesophageal reflux
• temporary vision loss
• rash
• difficulty swallowing
• change in taste
• severe allergic reaction
• seizures (epileptic fits)
• severe skin and mucous membrane reactions, including painful blisters and fever, as well as peeling of large skin areas (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• fever
• drowsiness or fatigue
• breathing difficulties
• rash similar to sunburn, sometimes severe, which may occur on skin previously exposed to radiation (radiation recall dermatitis)

Frequency not known(cannot be estimated from available data)

• tumor lysis syndrome (a complication due to the release of substances from treated cancer cells into the blood)
• infertility
• breathing difficulties
• facial and tongue swelling

Reporting side effects

If any side effects occur, including any not listed in the leaflet, tell a 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.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Etoposid-Ebewe

• Keep the medicine out of sight and reach of children.
• Do not use after the expiration date stated on the packaging after EXP. The expiration date refers to the last day of the given month.
• Do not store above 25°C. Store in the original packaging to protect from light.
• Medicines should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of unused medicines. This will help protect the environment.

6. Contents of the packaging and other information

What Etoposid-Ebewe contains

The active substance of the medicine is etoposide. Each 1 ml of the concentrate contains 20 mg of etoposide.
A 2.5 ml vial contains 50 mg of etoposide.
A 5 ml vial contains 100 mg of etoposide.
A 10 ml vial contains 200 mg of etoposide.
A 20 ml vial contains 400 mg of etoposide.
The other ingredients of the medicine are benzyl alcohol, ethanol (96%), anhydrous citric acid, macrogol 300, and polysorbate 80.

What Etoposid-Ebewe looks like and what the packaging contains

Etoposid-Ebewe is a clear, pale yellow solution.
Packaging contains:
1 vial of 2.5 ml, 1 vial of 5 ml, 1 vial of 10 ml, 1 vial of 20 ml.

Marketing authorization holder and manufacturer

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

Manufacturer

Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria
For more information, contact:
Sandoz Polska Sp. z o.o.
ul Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Date of last revision of the leaflet:

Logo Ebewe
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Information intended for healthcare professionals only:

Handle the medicine according to the procedures for handling anticancer medicines and dispose of them properly.
Etoposid-Ebewe solutions should be prepared under sterile conditions.
The concentrate for solution for infusion should be diluted before use with 5% glucose solution or 0.9% sodium chloride solution to achieve a concentration of 0.2 to 0.4 mg/ml. The final concentration is usually no more than 0.25 mg/ml.
The concentration of etoposide in the prepared infusion solution should not exceed 0.4 mg/ml due to the risk of precipitation.
Etoposid-Ebewe should not be physically mixed with any other medicine.
Only use clear solutions. Cloudy or discolored solutions should be discarded.
Etoposid-Ebewe is a single-use product.
Any unused medicine or waste should be disposed of according to local regulations.

Method of administration and dosage

Etoposid-Ebewe is administered by slow intravenous infusion (usually over 30 to 60 minutes).
Etoposid-Ebewe SHOULD NOT BE ADMINISTERED AS A RAPID INTRAVENOUS INJECTION.
Rapid intravenous administration may cause hypotension. Depending on tolerance, some patients may require a longer infusion time. Flushing of the patient's face indicates too rapid infusion.
The recommended doses of Etoposid-Ebewe are 50 to 100 mg/m² per day for 5 days or 100 to 120 mg/m² on days 1, 3, and 5, repeated every 3 to 4 weeks in combination with other anticancer medicines. The dosage should be modified based on the myelosuppressive effects of other medicines used in combination or the effects of prior radiation therapy or chemotherapy, which may have reduced bone marrow reserves.
Precautions for administration: as with other potentially toxic compounds, handle Etoposid-Ebewe with care during preparation and administration. Accidental exposure to Etoposid-Ebewe may cause skin reactions.
Follow these safety rules:

• Preparation, administration, and disposal of the medicine should only be performed by trained personnel, and, as with all cytostatic medicines, precautions should be taken to avoid exposure to pregnant women;
• Personnel preparing etoposide should wear protective clothing: goggles, gowns, single-use gloves, and single-use masks;
• All equipment and materials used to prepare the medicine or clean up spills should be placed in hazardous waste bags and incinerated at high temperatures.

In case of contact between the Etoposid-Ebewe solution and skin or mucous membranes, wash the skin with soap and water and rinse the mucous membrane with water.
Be careful not to spill.

Elderly patients

In elderly patients (>65 years), dose adjustment is not necessary due to age, but only due to renal function.

Use in children

Etoposid-Ebewe has been used in pediatric patients at doses of 75 to 150 mg/m² per day for 2 to 5 days in combination with other anticancer medicines.
To determine the appropriate treatment schedule, consult current specialist protocols and guidelines.
Kidney function disorders
In patients with kidney function disorders, consider the following dose adjustments based on creatinine clearance measurements.

Creatinine clearance measurement Etoposide dose

>50 ml/min
100% of the dose
15-50 ml/min
75% of the dose
Subsequent doses should be determined based on the patient's tolerance and clinical effects. In patients with creatinine clearance below 15 ml/min and those undergoing dialysis, consider further dose reduction.

Storage of the medicine after first opening and after dilution

After opening
The concentrate should be drawn from the vial immediately before use. From a microbiological point of view, the medicine should be used immediately. If it is not used immediately, the user is responsible for the storage conditions and storage time of the remaining medicine in the vial. The medicine remaining in the vial after the first draw should not be stored for more than 24 hours at a temperature between 2°C and 8°C, unless the draw was performed under controlled, verified aseptic conditions. In this case, the concentrate stored in the refrigerator or at room temperature, with light access, retains physical and chemical stability for up to 28 days.
After dilution
From a microbiological point of view, the medicine should be used immediately. If it is not used immediately, the user is responsible for the storage conditions and storage time of the prepared solution. The prepared solutions should not be stored for more than 24 hours at a temperature between 2°C and 8°C, unless the dilution was performed under controlled, verified aseptic conditions. The physical and chemical stability of the solution at a concentration of 0.2 mg/ml diluted with 0.9% NaCl or 5% glucose solution, stored in the refrigerator or at room temperature, with light access, has been demonstrated for up to 28 days, and for up to 24 hours for a solution at a concentration of 0.4 mg/ml diluted with 0.9% NaCl or 5% glucose solution, stored at room temperature with light access.

Procedure in case of extravasation

• Immediately stop administering the medicine.
• Replace the infusion set or syringe with a single-use syringe with a capacity of 5 ml and slowly aspirate the extravasated medicine. NOTE: Do not press the area of extravasation.
• Withdraw the needle while continuously aspirating the fluid from the area of extravasation.
• Inform the doctor.

Incompatibilities

Etoposide should not be mixed with other substances except 5% glucose solution or 0.9% sodium chloride solution. Cases of cracking of plastic devices made of acrylic or ABS polymers used with undiluted Etoposid-Ebewe concentrate for solution for infusion 20 mg/ml have been reported. This effect has not been reported after dilution of the etoposide concentrate for solution for infusion according to the instructions.