ETOPOSIDE TEVAGEN 20mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Etoposide Tevagen 20 mg/ml Concentrate for Solution for Infusion

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Etoposide belongs to a group of medicines called cytostatics used in the treatment of cancer.

Etoposide is used to treat certain types of cancer in adults:

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

Etoposide is used to treat certain types of cancer in children:

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

It is advisable that you discuss with your doctor the exact reason why you have been prescribed Etoposide Tevagen.

2. What you need to know before you are given Etoposide Tevagen

Do not use Etoposide

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

If any of the above applies to you, or if you are not sure, consult your doctor, who may advise you.

This product contains benzyl alcohol. It must not be given to premature babies or neonates.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Etoposide Tevagen

• if you have any infection.
• if you have recently received radiotherapy or chemotherapy
• if you have low levels of a protein called albumin in your blood.
• if you have liver or kidney problems.

Effective cancer treatment can quickly destroy large amounts of cancer cells. In very rare cases, this can cause harmful amounts of substances from these cancer cells to be released into the blood. If this happens, it can cause problems in the liver, kidneys, heart, or blood, which can lead to death 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 can cause a reduction in the level of some blood cells, which could cause infections or mean that your blood does not clot as it should if you suffer any cuts. To check that this does not happen, you will have blood tests at the start of treatment and before each dose you take.

If you have reduced kidney or liver function, your doctor may also want to perform regular blood tests to monitor these levels.

Other medicines and Etoposide Tevagen

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

This is especially important

• if you are taking a medicine called ciclosporin (a medicine to reduce the activity of the immune system).
• if you are being treated with cisplatin (a medicine used to treat cancer).
• if you are taking phenytoin or any other medicine used to treat epilepsy.
• if you are taking warfarin (a medicine to prevent blood clots).
• if you have recently been given live vaccines.
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.
• if you are taking anthracyclines (a group of medicines used to treat cancer).
• if you are taking any medicine with a mechanism of action similar to etoposide.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Etoposide must not be used during pregnancy unless your doctor clearly indicates it.

You must not breastfeed while receiving etoposide.

Patients, both men and women of childbearing age, must use effective contraceptive methods (such as barrier methods or condoms) during treatment and for at least 6 months after finishing treatment with etoposide.

Male patients treated with etoposide are advised not to father a child during treatment and for up to 6 months after treatment. Additionally, male patients are advised to seek advice on sperm preservation before starting treatment.

Patients, both men and women, who are considering having a child after receiving treatment with etoposide should discuss this with their doctor or nurse.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed. However, if you feel tired, sick to your stomach, dizzy, or excited, do not drive or use machines until you have discussed it with your doctor.

Etoposide Tevagen contains ethanol (alcohol) and benzyl alcohol

Etanol

A vial of Etoposide Tevagen contains 30% vol of alcohol.

This medicine contains 1.2 g of alcohol (ethanol) in each 5 ml vial and 6 g of alcohol (ethanol) in each 25 ml vial, which is equivalent to 243 mg/ml of concentrate. The amount in one ml of this medicine is equivalent to 6 ml of beer or 2 ml of wine.

It is unlikely that the amount of alcohol in this medicine will have an effect on adults and adolescents, and its effects in children are likely to be minimal. It may have some effects in younger children, for example, a feeling of sleepiness.

The amount of alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.

If you are pregnant, talk to your doctor or pharmacist before taking this medicine.

If you are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine.

Since this medicine is usually administered slowly over 30-60 minutes, the effects of the alcohol may be reduced.

Alcohol bencílico

This medicine contains 150 mg of benzyl alcohol in each 5 ml vial and 750 mg of benzyl alcohol in each 25 ml vial, which is equivalent to 30 mg/ml of concentrate.

Benzyl alcohol may cause allergic reactions.

Consult your doctor or pharmacist if you are pregnant or have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (metabolic acidosis).

This product must not be used for more than one week in children under 3 years of age unless advised by your doctor or pharmacist.

Benzyl alcohol has been associated with the risk of serious adverse effects, including respiratory problems ("gasping syndrome") in children.

3. How Etoposide Tevagen will be given

Etoposide will be administered by a doctor or nurse. It will be given as a slow infusion into a vein. This may take between 30 and 60 minutes.

The dose you receive will be specific to you, and your doctor will calculate it. The usual dose, based on etoposide, is 50 to 100 mg/m2 of body surface area per day for 5 consecutive days or 100 to 120 mg/m2 of body surface area on days 1, 3, and 5. This treatment cycle may be repeated, depending on the results of blood tests, but not sooner than 21 days after the first cycle of treatment.

For children receiving treatment for blood or lymphatic system cancer, the dose used is 75 to 150 mg/m2 of body surface area per day for 2 to 5 days.

Your doctor may prescribe a different dose, especially if you are receiving or have received other cancer treatments or if you have kidney problems.

If you are given too much Etoposide Tevagen

An overdose is unlikely because the medicine is administered by a doctor or nurse. However, if this happens, your doctor will treat any symptoms that appear.

In case of overdose or accidental ingestion, consult the Toxicology Information Service on 91 562 04 20, stating the medicine and the amount administered.

If you have any further questions on the use of this medicine, ask 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 experience any of the following symptoms: swelling of the tongue or throat, difficulty breathing, rapid heartbeat, redness of the skin or rash. These may be signs of a severe allergic reaction.

On occasion, severe damage to the liver, kidneys, or heart has been observed due to a disorder called tumour lysis syndrome caused by the release of harmful amounts of substances from cancer cells into the bloodstream when Etoposide Tevagen is administered with other medicines used to treat cancer.

Side effectsexperienced with etoposide are:

Very common side effects(affect more than 1 in 10 people)

• blood disorders (that's why blood tests will be performed between treatment cycles)
• temporary hair loss
• nausea and vomiting
• abdominal pain
• loss of appetite
• changes in skin colour (pigmentation)
• constipation
• feeling of weakness (asthenia)
• general malaise
• liver damage (hepatotoxicity)
• increased liver enzymes
• jaundice (increased bilirubin)

Common side effects(affect between 1 in 10 and 1 in 100 people)

• acute leukaemia
• irregular heartbeat (arrhythmia) or heart attack (myocardial infarction)
• dizziness
• diarrhoea
• reactions at the infusion site
• severe allergic reactions
• high blood pressure
• low blood pressure
• sore lips, mouth ulcers, or throat ulcers
• skin problems such as itching or rash
  • inflammation of a vein, infection (including infections observed in patients with a weakened immune system, e.g., a lung infection called Pneumocystis jirovecii pneumonia)

Uncommon side effects(affect between 1 in 100 and 1 in 1,000 people)

• tingling or numbness in hands and feet
• bleeding

Rare side effects(affect between 1 in 1,000 and 1 in 10,000 people)

• acid reflux
• flushing
• difficulty swallowing
• change in taste
• severe allergic reactions
• seizures
• fever
• drowsiness or fatigue
• respiratory problems
• temporary blindness
• severe skin and/or mucous membrane reactions that can include painful blisters and fever, including widespread skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• a skin rash similar to sunburn that can appear on previously irradiated skin and can be severe (radiation recall dermatitis)

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

• tumour lysis syndrome (complications of substances released from treated cancer cells entering the blood)
• swelling of the face and tongue
• infertility
  • difficulty breathing

• acute kidney failure

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Etoposide Tevagen

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date is the last day of the month stated.

Store below 25°C, protected from light (keep the vials in the outer packaging). Do not freeze.

After dilution, the solution should be used immediately. If this is not possible, the diluted solution can be stored at room temperature (15-25°C) for a maximum of 12 hours. Do not store the diluted product in a refrigerator (2-8°C) as it may precipitate. Any unused solutions should be discarded.

6. Container Contents and Additional Information

Composition of Etopósido Tevagen

-The active ingredient is 20 mg of etoposide per ml of concentrate for solution for infusion.

-The other components are macrogol 300, polysorbate 80, benzyl alcohol, ethanol, citric acid.

Appearance of the Product and Container Contents

Etopósido Tevagen is a viscous yellowish liquid in a transparent glass vial with a rubber stopper with an aluminum closure and a plastic snap-cap.

Each vial with 5 ml of concentrate for solution for infusion contains 100 mg of etoposide.

Each vial with 25 ml of concentrate for solution for infusion contains 500 mg of etoposide.

A container contains 1 vial or 10 vials of Etopósido Tevagen.

Only some package sizes may be marketed.

Marketing Authorization Holder:

Teva Pharma, S.L.U.

C/ Anabel Segura, 11. Edificio Albatros B, 1ª planta

28108 Alcobendas, Madrid

Spain

Manufacturer:

Pharmachemie B.V.

P.O. Box 552, 2003 RN

Haarlem

Netherlands

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Netherlands Eposin, concentrate for solution for infusion 20 mg/ml

Spain Etopósido Tevagen 20 mg/ml, concentrate for solution for infusion

This leaflet was last revised in June 2021

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS)

http://www.aemps.gob.es

This information is intended only for healthcare professionals:

Preparation of the Infusion Solution

The procedures for the proper handling and disposal of cancer medicines should be followed. All preparation stages should be performed under Laminar Air Flow conditions. Solutions should be prepared under aseptic conditions.

The required dose of Etopósido Tevagen 20 mg/ml concentrate for solution for infusion should be diluted with 5% dextrose solution for injection or 0.9% saline solution for injection to achieve a final concentration of 0.2 to 0.4 mg/ml. At higher concentrations, etoposide precipitation may occur.

Etopósido Tevagen should not be physically mixed with any other medicinal product.

Only clear solutions should be used. Turbid or discolored solutions should be discarded.

It has been reported that plastic devices made of acrylic or ABS polymers break when used with undiluted Etopósido Tevagen 20 mg/ml concentrate for solution for infusion. This effect has not been reported with etoposide after dilution of the concentrate for solution for infusion according to the instructions.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Administration and Dosage

Etoposide is administered by slow intravenous infusion (generally over a period of 30 to 60 minutes) since hypotension has been described as a possible adverse effect of rapid intravenous infusion. Etopósido Tevagen SHOULD NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.

The recommended dose of etoposide is 50 to 100 mg/m2/day on days 1 to 5 or 100 to 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 modified taking into account the myelosuppressive effects of other medicinal products in the combination or the effects of previous radiotherapy or chemotherapy that may have compromised bone marrow reserve.

Administration precautions: As with other potentially toxic compounds, caution should be exercised in the handling and preparation of the etoposide solution. Adverse reactions associated with accidental exposure to etoposide may occur. The use of gloves is recommended. If the etoposide solution comes into contact with the skin or mucosa, wash the skin immediately with water and soap and the mucosa with water.

Caution should be exercised to avoid extravasation.

Elderly Patients

No dose adjustment is necessary in elderly patients (> 65 years of age), except based on renal function.

Pediatric Use

In pediatric patients, etoposide has been used in the range of 75 to 150 mg/m2/day for 2 to 5 days in combination with other antineoplastic agents. The treatment regimen should be chosen according to local standards of care.

Renal Impairment

In patients with renal impairment, the following modification of the initial dose based on creatinine clearance should be considered.

Subsequent dosing should be based on patient tolerance and clinical effect. In patients with creatinine clearance less than 15 ml/min and on dialysis, a further dose reduction should be considered.