Etoposide Tevagen 20 mg/ml concentrate for solution for infusion

Patient Information Leaflet

Introduction

Patient Information Leaflet

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 as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Leaflet Contents

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

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

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

Etoposide is used in the treatment of certain types of cancer in adults:

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

Etoposide is used in the treatment of certain types of cancer in children:

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

You should discuss with your doctor the exact reason why Etoposide Tevagen has been prescribed for you.

2. What you need to know before using Etoposide Tevagen

Do not use Etoposide

• 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 intend to breastfeed.

If any of the above applies to you, or if you are unsure whether it does, consult your doctor, who may advise you.

This product contains benzyl alcohol. It must not be administered to premature infants or neonates.

Warnings and precautions

Talk to 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 blood levels of a protein called albumin.
• if you have liver or kidney problems.

Effective cancer treatment can rapidly destroy large numbers of cancer cells. Very rarely, this may lead to harmful levels of substances released from these cancer cells into the bloodstream. If this occurs, it may cause problems in the liver, kidneys, heart, or blood, 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 may mean that your blood does not clot properly if you get a cut. To check for this, you will have blood tests at the start of treatment and before each dose.

If you have impaired kidney or liver function, your doctor may also want to carry out periodic blood tests to monitor these functions.

Other medicines and Etoposide Tevagen

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

This is especially important

• if you are taking a medicine called cyclosporine (a medicine used 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 used to prevent blood clots).
• if you have recently received vaccines containing live microorganisms.
• 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 plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Etoposide must not be used during pregnancy unless clearly indicated by your doctor.

You must not breastfeed while receiving etoposide.

Patients, both men and women of reproductive age, should use an effective contraceptive method (such as barrier methods or condoms) during treatment and for at least 6 months after completion of etoposide treatment.

Male patients treated with etoposide are advised not to father a child during treatment and for up to 6 months afterwards. In addition, men are advised to seek counseling regarding sperm preservation before starting treatment.

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

Driving and using machines

No studies have been conducted on the effects on the ability to drive and use machines. However, if you feel tired, nauseous, dizzy, or agitated, do not drive or operate machinery until you have discussed this with your doctor.

Etoposide Tevagen contains ethanol (alcohol) and benzyl alcohol

Ethanol

One container of Etoposide Tevagen contains 30% vol 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, equivalent to a concentration of 243 mg/ml. The amount in 1 ml of this medicine is equivalent to 6 ml of beer or 2 ml of wine.

The amount of alcohol in this medicine is unlikely to have an effect in adults and adolescents, and its effects in children are unlikely to be noticeable. It may have some effects in younger children, for example, drowsiness.

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

If you are pregnant, speak with your doctor or pharmacist before taking this medicine.

If you are alcohol-dependent, speak with your doctor or pharmacist before taking this medicine.

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

Benzyl alcohol

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

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 may 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 directed 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 you will receive Etoposide Tevagen

Etoposide will be administered to you by a doctor or nurse. It will be given as a slow intravenous infusion. This may last 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 treatment cycle.

For children receiving treatment for cancers of the blood or lymphatic system, 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 previously received other cancer treatments, or if you have kidney problems.

If you are given more Etoposide Tevagen than you should

An overdose is unlikely, as the medicine is administered by a doctor or nurse. However, if it does occur, your doctor will treat any symptoms that arise.

In case of overdose or accidental ingestion, contact the Toxicology Information Service at 91 562 04 20, indicating the medication and the amount administered.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Immediately tell your doctor or nurse 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 serious allergic reaction.

Occasionally, serious damage to the liver, kidneys, or heart has been observed due to a condition called tumor lysis syndrome, which is caused by harmful amounts of substances from cancer cells entering the bloodstream when Etoposide Tevagen is administered together with other drugs used to treat cancer.

Possible adverse effects experienced with etoposide are:

Very common adverse effects (affect 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
• feeling of weakness (asthenia)
• general malaise
• liver damage (hepatotoxicity)
• increased liver enzymes
• jaundice (increased bilirubin)

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

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

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

• tingling or numbness in hands and feet
• bleeding

Rare adverse 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
• breathing problems
• temporary blindness
• severe skin and/or mucous membrane reactions which may include painful blisters and fever, including extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• a sunburn-like skin rash that may appear on skin previously exposed to radiotherapy and may be severe (radiation recall dermatitis)

Not known (frequency cannot be estimated from available data)

• tumor lysis syndrome (complications from substances released by treated cancer cells entering the blood)

• swelling of the face and tongue

• infertility

  • difficulty breathing

• acute kidney failure

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines Website: www.notificaram.es. By reporting adverse 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 stated on the carton and vial after EXP. The expiry date refers to the last day of the month indicated.

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

After dilution, the solution should be used immediately. If this is not possible, the diluted solution may 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 precipitation may occur. Any unused portions of the solution must be discarded.

6. Package contents and other information

Composition of Etoposide Tevagen

• The active substance 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.

Presentation of the product and contents of the container

Etoposide Tevagen is a yellowish, viscous liquid in a clear glass vial sealed with a rubber stopper, aluminum cap, and plastic snap-cap.

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

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

A pack contains 1 vial or 10 vials of Etoposide Tevagen.

Only certain pack sizes may be marketed.

Marketing Authorization Holder:

Teva Pharma, S.L.U.

C/ Anabel Segura, 11. Edificio Albatros B, 1st floor

28108 Alcobendas, Madrid

Spain

Manufacturer:

Pharmachemie B.V.

P.O. Box 552, 2003 RN

Haarlem

The Netherlands

This medicinal product is authorized in the European Economic Area member states under the following names:

Netherlands: Eposin, concentrate for solution for infusion 20 mg/ml
Spain: Etoposide Tevagen 20 mg/ml, concentrate for solution for infusion

This leaflet was last revised in June 2021

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS):
http://www.aemps.gob.es

This information is intended for healthcare professionals only:

Preparation of the infusion solution

Procedures for the proper handling and disposal of anticancer drugs must be followed. All preparation steps must be carried out under laminar air flow conditions. Solutions must be prepared under aseptic conditions.

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

Etoposide Tevagen must not be physically mixed with any other medicinal product.

Use only clear solutions. Cloudy solutions or those showing color changes must be discarded.

It has been reported that plastic devices made of acrylic or ABS polymers may break when used with undiluted Etoposide 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 instructions.

Disposal of unused medicinal product and of all materials that have been in contact with it must be carried out in accordance with local regulations.

Administration and dosage

Etoposide is administered by slow intravenous infusion (usually over a period of 30 to 60 minutes), as hypotension has been described as a possible adverse effect of rapid intravenous infusion. Etoposide Tevagen MUST 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 adjusted according to the myelosuppressive effects of other drugs in the combination, or the effects of prior radiotherapy or chemotherapy that may have compromised bone marrow reserve.

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

Care must be taken to avoid extravasation.

Elderly patients

Dosage adjustment is not required in elderly patients (> 65 years of age), except based on renal function.

Paediatric use

In paediatric 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 selected according to local standards of care.

Renal impairment

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

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