Etoposide Sandoz

Package leaflet: Information for the patient

Etoposide Sandoz 20 mg/ml concentrate for solution for infusion

etoposide
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse, or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, nurse, or pharmacist. See section 4.

Contents of this leaflet:

1. What Etoposide Sandoz is and what it is used for
2. What you need to know before using Etoposide Sandoz
3. How to use Etoposide Sandoz
4. Possible side effects
5. How to store Etoposide Sandoz
6. Contents of the pack and other information

1. What Etoposide Sandoz is and what it is used for

The name of this medicine is Etoposide Sandoz. Each vial contains etoposide.
Etoposide belongs to a group of medicines called cytostatics, which are used in the treatment of
tumours.
Etoposide Sandoz is used in the treatment of certain types of tumours in adult patients:

• testicular tumour
• small cell lung carcinoma
• blood cancer (acute myeloid leukaemia)
• tumours of the lymphatic system (Hodgkin's lymphoma, non-Hodgkin's lymphoma)
• reproductive system tumours (gestational trophoblastic neoplasia and ovarian tumour)

Etoposide Sandoz is used in the treatment of certain types of tumours in paediatric patients:

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

The reason why Etoposide Sandoz has been prescribed for you should be discussed with your doctor.

2. What you need to know before using Etoposide Sandoz

Do not take Etoposide Sandoz:

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

If any of the above apply to you, or if you are unsure, consult your doctor for advice.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before receiving Etoposide Sandoz:

• if you have any current infections;
• if you have recently undergone radiotherapy or chemotherapy;
• if you have low blood levels of a protein called albumin;
• if you have liver or kidney problems. Effective cancer treatment can rapidly destroy large numbers of tumour cells. Very rarely, this may cause harmful amounts of substances from these tumour cells to be released into the blood. In such cases, problems affecting the liver, kidneys, heart, or blood 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 could lead to infections or cause your blood not to clot properly if you are cut. To ensure this does not happen, you will have blood tests at the beginning of treatment and before each dose.
If you have reduced liver or kidney function, your doctor may also decide to carry out regular blood tests to monitor these functions.
Other medicines and Etoposide Sandoz
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
This is particularly important

• if you are taking a medicine called cyclosporine (a medicine used to reduce the activity of the immune system);
• if you are undergoing treatment with cisplatin (a medicine used to treat tumours);
• if you are taking phenytoin or other medicines used to treat epilepsy;
• if you are taking warfarin (a medicine used to prevent blood clots);
• if you have recently received live vaccines;
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid;
• if you are taking anthracyclines (a class of anticancer medicines);
• if you are taking medicines with a mechanism of action similar to that of Etoposide Sandoz.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Etoposide Sandoz must not be used during pregnancy unless clearly indicated by your doctor.
Breastfeeding is not allowed during treatment with Etoposide Sandoz.
Men and women of reproductive age must use an effective contraceptive method (e.g., barrier method or condom) during treatment and for at least 6 months after the end of treatment with Etoposide Sandoz.
Male patients receiving Etoposide Sandoz are advised not to father children during treatment and for 6 months after treatment ends. In addition, male patients are advised to seek counselling about sperm preservation before starting treatment.
Male and female patients who intend to have children after treatment with Etoposide Sandoz should discuss this with their doctor or nursing staff.
Driving and using machines
No studies on the effects of etoposide on the ability to drive or use machines have been performed. However, if you feel tired, nauseous, dizzy, or experience a sensation of lightheadedness, you must not drive or use machines until you have discussed this with your doctor.
This medicine contains 33 vol% ethanol (alcohol), i.e. up to 2345 mg per 180 mg (average dose), equivalent to 37 ml of beer or 15 ml of wine per average dose.
Harmful for people suffering from alcoholism.
To be considered in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.
The amount of alcohol in this medicine may alter the effects of other medicines.
The amount of alcohol in this medicine may affect the ability to drive or use machines.
This medicine contains 20 mg of benzyl alcohol per ml, equivalent to 180 mg per 9 ml (average dose).
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with a risk of serious adverse effects, including respiratory problems (gasping syndrome), in young children.
Must not be administered to neonates up to 4 weeks of age unless otherwise recommended by the doctor.
Must not be used for more than one week in young children (under 3 years of age) unless otherwise recommended by the doctor or pharmacist.
Ask your doctor or pharmacist for advice if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).
Ask your doctor or pharmacist for advice if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).

3. How to use Etoposide Sandoz

Etoposide Sandoz will be administered to you by a doctor or nurse as a slow intravenous infusion.
This may take from 30 to 60 minutes.
The dose is individualized and will be calculated by your doctor. The usual dose, based on etoposide, is from 50 mg/m² of body surface area per day to 100 mg/m² of body surface area per day administered for 5 consecutive days, or the dose may range between 100 mg/m² and 120 mg/m² of body surface area given on days 1, 3 and 5. The treatment cycle may be repeated depending on the results of blood tests, but at least 21 days should elapse from the first treatment cycle.
In children being treated for a blood or lymphatic system tumour, the dose used ranges from 75 mg/m² of body surface area per day to 150 mg/m² of body surface area per day for a duration of 2 to 5 days.
Your doctor may sometimes prescribe a different dose, particularly if you are receiving or have received other cancer treatments, or if you have kidney problems.
If you are given more Etoposide Sandoz than you should have
Since Etoposide Sandoz is administered by a doctor or nurse, overdose is unlikely. However, in such a case, the doctor will treat any symptoms that occur.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediately if you develop any of the following symptoms: swelling of the tongue or throat, difficulty breathing, rapid heartbeat, skin redness or skin irritation. These could be signs of a severe allergic reaction.
Sometimes, serious liver, kidney or heart damage has occurred due to a condition called tumour lysis syndrome, caused by harmful amounts of substances released into the bloodstream from tumour cells, when patients have taken Etoposide Sandoz together with other medicines used to treat cancer.
Possible side effects reported with Etoposide Sandoz are:
Very common side effects (may affect more than 1 in 10 people)

• blood disorders (for this reason, blood tests will be carried out between treatment cycles)
• nausea and vomiting
• loss of appetite
• constipation
• temporary hair loss
• liver damage
• increased liver enzymes
• jaundice (increased bilirubin)
• changes in skin colour (pigmentation)
• feeling of weakness (asthenia)
• general malaise
• abdominal pain

Common side effects (may affect up to 1 in 10 people)

• acute leukaemia
• diarrhoea
• infusion site reactions
• irregular heartbeat (arrhythmia), or heart attack (myocardial infarction)
• severe allergic reactions
• dizziness
• low blood pressure
• high blood pressure
• pain in lips, mouth or throat ulcers
• skin problems such as itching or skin irritations
• inflammation of the veins
• infection

Uncommon side effects (may affect up to 1 in 100 people)

• tingling or numbness in hands and feet
• bleeding

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

• acid reflux
• redness
• severe allergic reactions
• seizures (epileptic fits)
• fever
• drowsiness or tiredness
• temporary blindness
• severe skin and/or mucous membrane reactions which may include painful blisters and fever, as well as extensive peeling of the skin (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• sunburn-like irritation which may occur on skin previously exposed to radiotherapy and may be severe (radiation recall dermatitis)
• difficulty swallowing
• altered sense of taste
• breathing problems

Not known (frequency cannot be estimated from the available data)

• tumour lysis syndrome (complications due to substances released into the blood from tumour cells)
• swelling of the face and tongue
• infertility
• breathing difficulties

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Etoposide Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack and vial after EXP. The expiry date refers to the last day of that month.
Etoposide Sandoz will be stored in the pharmacy and prepared in a special area before being administered to you by a doctor or nurse.
Do not store above 25°C. Store in the original packaging.
Validity of diluted solutions: 24 hours at 2°C – 8°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Etoposide Sandoz contains

• The active substance is etoposide.
• The other ingredients are benzyl alcohol, 96% ethanol, anhydrous citric acid, macrogol 300, polysorbate 80.

Description of the appearance of Etoposide Sandoz and package contents
Etoposide Sandoz is a clear, light yellow solution.
Packaging:
Single packs containing 1 vial with 50 mg/2.5 ml, 100 mg/5 ml, 200 mg/10 ml, 400 mg/20 ml or 1000 mg/50 ml.
Multipack containers containing 5 or 10 vials with 50 mg/2.5 ml, 100 mg/5 ml, 200 mg/10 ml, 400 mg/20 ml or 1000 mg/50 ml.

Marketing Authorization Holder
Sandoz S.p.A
Largo U Boccioni 1
21040 Origgio (VA)
Italy

Manufacturer responsible for batch release
Sandoz Spa
Largo U Boccioni 1
21040 Origgio (VA)
Italy
Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium Etoposid Sandoz 20mg/ml concentrate for solution for infusion
Denmark Etoposid "Ebewe"
Germany Neoposid® 20 mg/ml concentrate for preparation of infusion solution
Italy ETOPOSIDE SANDOZ
Luxembourg Etoposid Sandoz 20mg/ml solution to be diluted for perfusion
Netherlands Etoposide Sandoz 20 mg/ml, concentrate for solution for infusion
Norway Etoposid Ebewe 20 mg/ml concentrate for infusion
Portugal Etoposido Sandoz
Sweden Etoposid Ebewe 20 mg/ml - concentrate for infusion solution, solution

This leaflet was last updated on
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The following information is intended for healthcare professionals only.

Instructions for use, handling and disposal:

Handle according to guidelines for cytotoxic substances.
The concentrate for infusion solution must not be used undiluted.
It must be diluted only with isotonic sodium chloride or glucose infusion solutions. The concentration of Etoposide Sandoz in the reconstituted infusion solution must not exceed 0.4 mg/mL due to the risk of precipitation.

Administration and dosage
Etoposide Sandoz is administered by slow intravenous infusion (usually over 30–60 minutes), since hypotension has been reported as a possible adverse effect following rapid intravenous injection.
ETOPESIDE SANDOZ MUST NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.

The recommended dose of Etoposide Sandoz is 50 mg/m²/day to 100 mg/m²/day administered on days 1 to 5, or between 100 mg/m² and 120 mg/m² on days 1, 3 and 5, every 3–4 weeks, in combination with other medicinal products indicated for the disease being treated. The dose should be adjusted to account for the myelosuppressive effects of other medicinal products in the combination, or the effects of prior radiotherapy or chemotherapy, which may have compromised bone marrow reserve.

Precautions for administration: As with other potentially toxic compounds, care must be taken when handling and preparing Etoposide Sandoz solution. Skin reactions associated with accidental exposure to Etoposide Sandoz may occur. The use of gloves is recommended. If Etoposide Sandoz solution comes into contact with skin or mucous membranes, wash the skin immediately with soap and water and rinse the mucous membranes with water.
Take care to avoid extravasation.

Elderly patients
In elderly patients (age > 65 years), no dose adjustment is required unless based on renal function.

Paediatric use
Etoposide Sandoz has been used in paediatric patients at doses ranging from 75 mg/m²/day to 150 mg/m²/day (equivalent to etoposide) for 2–5 days in combination with other antineoplastic agents. Current specialized guidelines and protocols should be consulted to determine the appropriate therapeutic regimen.

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

| Measured creatinine clearance | Etoposide dose |
|-----------------------------------|---------------------|
| >50 mL/min | 100% of dose |
| 15–50 mL/min | 75% of dose |

Subsequent dosing should be based on patient tolerance and clinical response. In patients with creatinine clearance below 15 mL/min and those undergoing dialysis, further dose reduction should be considered.

Incompatibilities
Etoposide Sandoz must not be physically mixed with any other medicinal product. It should be diluted only with isotonic sodium chloride or glucose infusion solutions.
It has been reported that plastic devices made of acrylic or ABS polymers may break when used with undiluted Etoposide Sandoz concentrate for infusion solution (20 mg/mL). This effect has not been described for Etoposide Sandoz after dilution of the concentrate for infusion solution according to instructions.

Special storage precautions
No special storage precautions are required for the concentrate.
The chemical and physical stability of the ready-to-use preparation has been demonstrated for 24 hours at room temperature. From a microbiological standpoint, the diluted product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.