Etoposide ebewe

Patient Information Leaflet

Etoposid Ebewe, 20 mg/ml, concentrate for solution for infusion
Etoposidum
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for you.
Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor, nurse or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to other people. It may harm them,
even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor, nurse or
pharmacist. See section 4.

Contents of this leaflet

1. What Etoposid-Ebewe is and what it is used for
2. What you need to know before you are given Etoposid-Ebewe
3. How Etoposid-Ebewe is given
4. Possible side effects
5. How to store Etoposid-Ebewe
6. Contents of the pack and other information

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

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

• testicular cancer,
• small cell lung cancer,
• blood cancer (acute myeloid leukaemia),
• lymphatic system tumours (Hodgkin's lymphoma, non-Hodgkin's lymphoma),
• reproductive system cancer (gestational trophoblastic disease and ovarian cancer).

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

• blood cancer (acute myeloid leukaemia),
• lymphatic system tumours (Hodgkin's lymphoma, non-Hodgkin's lymphoma).

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

2. Important information before using Etoposid Ebewe

Do not take Etoposid Ebewe if you have:

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

If any of the above apply to you or if you are unsure,
you should consult your doctor.
Warnings and precautions
Before you start receiving Etoposid Ebewe, discuss this with your doctor or pharmacist if:

• you have any infections,
• you have recently undergone radiotherapy or chemotherapy,
• you have low levels of proteins called albumin in your blood,
• you have liver or kidney disease.

Effective anticancer treatment may rapidly destroy a large number of cancer cells.
In very rare cases, this may lead to the release of harmful amounts of substances from these cancer cells into the blood. As a consequence, liver, kidney, heart or blood function disorders may occur, which could be fatal if not treated.
To prevent this, your doctor will need to perform regular blood tests to monitor the levels of these substances during treatment with this medicine.
This medicine may reduce the number of certain blood cells, which may increase the risk of infection or cause your blood not to clot as well as it should if you are cut. To ensure this does not happen, blood tests will be performed at the beginning of treatment and before each dose of the medicine.
If liver or kidney function is impaired, your doctor may also order regular blood tests to monitor them.
Patients with liver or kidney disease should consult their doctor before using this medicine, as a large amount of benzyl alcohol may accumulate in their body and cause adverse effects (so-called metabolic acidosis).
Etoposid Ebewe and other medicines
Tell your doctor or pharmacist if you are currently taking, have recently taken or might take any other medicines.
This is particularly important in the following cases:

• if you are taking a medicine called cyclosporine (a medicine used to suppress the immune system);
• if you are being treated with cisplatin (a medicine used in cancer treatment);
• if you are taking phenytoin or any other medicine for epilepsy;
• if you are taking warfarin (a medicine used to prevent blood clots);
• if you have recently been vaccinated with a live vaccine;
• if you are taking phenylbutazone, sodium salicylate or acetylsalicylic acid;
• if you are taking any anthracyclines (a group of medicines used in cancer treatment);
• if you are taking any medicines with a similar mechanism of action to Etoposid Ebewe.

Pregnancy, breastfeeding and effects on fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor before using this medicine.
Etoposid Ebewe must not be used during pregnancy unless specifically prescribed by your doctor.
Breastfeeding is not allowed during treatment with Etoposid Ebewe.
Both women and men capable of having children should use effective contraception (e.g. barrier methods or condoms) during treatment and for at least 6 months after completion of treatment with Etoposid Ebewe.
Men being treated with Etoposid Ebewe should not father children during treatment and for up to 6 months after its completion. In addition, men should consult their doctor about sperm preservation before starting treatment.
Women and men considering the possibility of having children after completing treatment with Etoposid Ebewe should discuss this with their doctor or nurse.
Pregnant women should contact their doctor before using this medicine, as a large amount of benzyl alcohol may accumulate in their body and cause adverse effects (so-called metabolic acidosis).
Driving and operating machinery
Due to its alcohol content, do not drive or operate machinery shortly after receiving Etoposid Ebewe.
If you experience drowsiness, fatigue, nausea or dizziness, do not drive or operate machinery until you have discussed this with your doctor.
Etoposid Ebewe contains benzyl alcohol and ethanol
This medicine contains 20 mg of benzyl alcohol in 1 ml of concentrate.
Benzyl alcohol may cause allergic reactions.
Administration of benzyl alcohol to young children is associated with a risk of severe adverse reactions, including breathing disorders (so-called "gasping syndrome").
Do not administer this medicine to newborns (up to 4 weeks of age) without medical advice.
Do not administer this medicine to young children (under 3 years of age) for longer than one week without medical advice.
Pregnant women and patients with liver or kidney disease should consult their doctor before using this medicine, as a large amount of benzyl alcohol may accumulate in their body and cause adverse effects (so-called metabolic acidosis).
This medicine contains 252 mg of ethanol in 1 ml of concentrate. The amount of alcohol in 1 ml of this medicine is equivalent to 7 ml of beer or 3 ml of wine.
The amount of alcohol in this medicine is unlikely to affect adults and adolescents, and its effect in children is unlikely to be noticeable. It may cause some effects in younger children, such as drowsiness.
The alcohol in this medicine may alter the effects of other medicines. If you are taking other medicines, you should consult your doctor or pharmacist.
If you are pregnant, you should consult your doctor or pharmacist before using this medicine.
If you are alcohol-dependent, you should consult your doctor or pharmacist before using this medicine.

3. How to use Etoposid Ebewe

Etoposid Ebewe will be administered by a doctor or nurse. It will be given by slow intravenous infusion, which may take from 30 to 60 minutes.
The dose will be calculated by the doctor for each individual case. The typical dose, expressed as etoposide amount, is 50 to 100 mg/m^2 of body surface area, given daily for 5 consecutive days, or 100 to 120 mg/m^2 on days 1, 3, and 5. This treatment cycle may be repeated depending on blood test results, but not sooner than 21 days after completion of the first cycle.
In children treated for leukaemia or lymphatic system cancer, the dose used is 75 to 150 mg/m^2 of body surface area, given daily for 2 to 5 days.
Sometimes the doctor may prescribe a different dose, especially if you are currently receiving or have previously received another type of cancer treatment, or if you have 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.
If you have any further questions about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
If any of the following symptoms occur, inform your doctor or nurse immediately: swelling of the
tongue or throat, difficulty breathing, rapid heartbeat, skin flushing or rash. These may be
symptoms of a severe allergic reaction.
Severe liver, kidney or heart damage due to a complication called tumor lysis syndrome, caused by the release into the bloodstream of harmful amounts of substances from cancer cells, has been observed occasionally when Etoposid Ebewe was administered together with other anticancer medicines.

Other adverse reactions occurring during treatment with Etoposid Ebewe include:

Very common adverse reactions (occurring in more than 1 in 10 people)

• blood disorders (for this reason, blood tests will be performed between treatment cycles)
• temporary hair loss
• nausea and vomiting
• abdominal pain
• loss of appetite
• changes in skin color (pigmentation)
• constipation
• weakness (asthenia)
• general malaise
• liver damage (hepatotoxicity)
• increased liver enzyme activity
• elevated bilirubin levels

Common adverse reactions (occurring in not more than 1 in 10 people)

• acute leukaemia
• irregular heartbeat (arrhythmia) or heart attack (myocardial infarction)
• dizziness
• diarrhoea
• reactions at the injection site
• severe allergic reaction
• high blood pressure
• low blood pressure
• cold sores, herpes stomatitis, throat ulceration
• skin reactions such as itching or rash
• phlebitis
• infections (including infections observed in patients with weakened immune systems,
  e.g. pneumonia caused by Pneumocystis jirovecii)

Uncommon adverse reactions (occurring in not more than 1 in 100 people)

• tingling or numbness in hands and feet
• bleeding

Rare adverse reactions (occurring in not more than 1 in 1,000 people)

• gastric acid reflux
• transient loss of vision
• flushing
• difficulty swallowing
• altered taste sensation
• severe allergic reaction
• seizures (epileptic fits)
• severe skin and/or mucous membrane reactions, including painful blisters and fever, as well as detachment of large areas of the epidermis (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• fever
• drowsiness or fatigue
• breathing difficulties
• sunburn-like rash, sometimes severe, which may occur on skin previously exposed to radiotherapy (radiation recall dermatitis)

Frequency not known (cannot be estimated from available data)

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

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 4921301, Fax: +48 22 4921309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Etoposid Ebewe

• Keep the medicine out of sight and reach of children.
• Do not use after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the specified 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 your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Etoposid-Ebewe contains
The active substance is etoposide. Each ml of 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 are: benzyl alcohol, ethanol (96%), anhydrous citric acid,
macrogol 300, polysorbate 80.

What Etoposid-Ebewe looks like and contents of the pack
Etoposid-Ebewe is a clear, light yellow solution.
Pack sizes contain:
1 vial of 2.5 ml, 1 vial of 5 ml, 1 vial of 10 ml, 1 vial of 20 ml.

Marketing Authorisation 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 further information, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw, Poland
Tel. 22 209 70 00

Logo Ebewe

Information intended exclusively for healthcare professionals:

Appropriate procedures for handling and disposal of cytotoxic medicinal products must be observed.
Etoposid-Ebewe solutions must be prepared under sterile conditions.
The concentrate for infusion solution must be diluted before use with 5% glucose solution or 0.9% sodium chloride solution to achieve a concentration between 0.2 and 0.4 mg/ml. The final concentration usually does not exceed 0.25 mg/ml.
The etoposide concentration in the prepared infusion solution must not exceed 0.4 mg/ml due to the risk of precipitation.
Etoposid-Ebewe must not be physically mixed with any other medicinal product.
Only clear solutions should be used. Cloudy or discolored solutions must be discarded.
Etoposid-Ebewe is a single-use product.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

Route and dosage of administration
Etoposid-Ebewe is administered by slow intravenous infusion (typically over 30 to 60 minutes).
Etoposid-Ebewe MUST NOT BE ADMINISTERED AS A RAPID INTRAVENOUS INJECTION.
Rapid intravenous administration may cause hypotension. In some patients, depending on tolerance, prolongation of the infusion time may be necessary. Facial flushing indicates too rapid infusion.

Recommended doses of Etoposid-Ebewe are 50 to 100 mg/m² daily on days 1 to 5, or 100 to 120 mg/m² daily on days 1, 3 and 5, repeated every 3 to 4 weeks, in combination with other medicinal products indicated for the disease being treated. Dose adjustments should be made considering the myelosuppressive effects of other concomitantly administered drugs or the effects of prior radiotherapy or chemotherapy, which may have reduced bone marrow reserves.

Precautions for administration: As with all potentially toxic compounds, care must be taken when handling and preparing the Etoposid-Ebewe solution. Accidental exposure to Etoposid-Ebewe may lead to skin reactions.

The following safety measures must be observed:

• Preparation, administration and disposal of residual medicinal product must be performed only by trained personnel. As with all cytostatic agents, care must be taken to avoid exposing pregnant women to the medicinal product.
• Personnel preparing etoposide should wear protective clothing: goggles, gowns, disposable gloves and disposable masks.
• All equipment and materials used in the preparation of the medicinal product or cleaning of the preparation area, including gloves, must be placed in hazardous waste bags and incinerated at high temperature.

In case of contact of the Etoposid-Ebewe solution with skin or mucous membranes, the skin should be washed immediately with soap and water and the mucous membrane rinsed thoroughly with water. Care must be taken to avoid extravasation.

Elderly patients
In elderly patients (>65 years of age), dose adjustment based on age is not necessary; dosage should be adjusted only according to renal function.

Use in children
Etoposid-Ebewe has been used in pediatric patients at doses of 75 to 150 mg/m² daily for 2 to 5 days in combination with other antineoplastic agents. To determine the appropriate treatment regimen, current specialized protocols and guidelines should be consulted.

Renal impairment
In patients with impaired renal function, the following dose adjustments to the initial dose should be considered based on creatinine clearance values:

Creatinine clearance value Etoposide dose

50 ml/min 100% of dose
15–50 ml/min 75% of dose

Subsequent doses should be adjusted according to the patient's tolerance and clinical response. In patients with a creatinine clearance below 15 ml/min and in patients undergoing dialysis, further dose reduction should be considered.

Storage after first opening and after dilution
After opening
The concentrate should be withdrawn from the vial immediately before use. From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, the user is responsible for storage conditions and duration. The remaining medicinal product in the vial after first withdrawal must not be stored for longer than 24 hours at a temperature of 2°C to 8°C, unless the withdrawal was performed under controlled, validated aseptic conditions. In such cases, the concentrate stored in the refrigerator or at room temperature with exposure to light maintains physical and chemical stability for up to 28 days.

After dilution
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, the user is responsible for storage conditions and duration. Prepared solutions must not be stored for longer than 24 hours at a temperature of 2°C to 8°C, unless dilution was performed under controlled, validated aseptic conditions. Physical and chemical stability has been demonstrated for up to 28 days for a 0.2 mg/ml solution diluted with 0.9% NaCl or 5% glucose solution, stored in the refrigerator or at room temperature with exposure to light, and for up to 24 hours for a 0.4 mg/ml solution diluted with 0.9% NaCl or 5% glucose solution, stored at room temperature with exposure to light.

Management of extravasation

• Immediately stop administration of the medicinal product.
• Replace the infusion line or syringe with a 5 ml single-use syringe and slowly aspirate the extravasated medicinal product. WARNING! Do not apply pressure to the extravasation site.
• Withdraw the needle while continuously aspirating fluid from the extravasation site.
• Inform the physician.

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