Etoposide Accord 20 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Etoposide Accord 20 mg/ml concentrate for solution for infusion EFG

Read the entire leaflet carefully before you start taking 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.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if these effects are not listed in this leaflet. See section 4.

Leaflet contents:

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

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

Each vial contains etoposide as the active substance.

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

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

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

Etoposide Accord 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 Accord has been prescribed for you.

2. What you need to know before starting Etoposide Accord

Do not take Etoposide Accord

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

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Etoposide Accord:

• 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 anticancer treatment may rapidly destroy large numbers of cancer cells. Very rarely, this may lead to the release of harmful amounts of these cancer cells into the bloodstream. 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 must carry out 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 make you more susceptible to infections or impair your blood's ability to clot properly in case of injury. To ensure this does not happen, you will have blood tests at the beginning of treatment and before each dose.

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

Other medicines and Etoposide Accord

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

This is especially important:

• if you are taking a medicine called cyclosporine (used to reduce the activity of the immune system).
• if you are receiving treatment with cisplatin (a medicine used to treat cancer).
• if you are taking phenytoin or any other medicine used for epilepsy.
• if you are taking warfarin (a medicine used to prevent blood clots).
• if you have recently received any vaccines containing live microorganisms.
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.
• if you are taking any anthracycline (a group of medicines used to treat cancer).
• if you are taking any medicine with a mechanism of action similar to that of Etoposide Accord.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

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

You must not breastfeed while being treated with Etoposide Accord.

Patients of both sexes (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 completion of treatment with Etoposide Accord.

Male patients treated with Etoposide Accord are advised not to father a child during treatment and for at least 6 months after treatment ends. In addition, men are advised to seek counseling regarding sperm preservation before starting treatment.

Patients of both sexes who are considering having a child after treatment with Etoposide Accord should discuss this with their doctor or nurse.

Driving and use of 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 drowsy, you should not drive or operate machinery until you have discussed this with your doctor.

Etoposide Accord contains alcohol

This medicine contains 30.5% alcohol (ethanol), equivalent to 240.64 mg of ethanol per ml of concentrate. This corresponds to up to 1.2 g of ethanol per 5 ml vial (equivalent to 30 ml of beer or 12.55 ml of wine) and up to 3 g of ethanol per 12.5 ml vial (equivalent to 75 ml of beer or 31.4 ml of wine).

This is harmful for patients with alcoholism, brain damage, pregnant women, breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy. The effect of other medicines may be increased or reduced.

Etoposide Accord contains benzyl alcohol

Etoposide Accord contains 30 mg/ml of benzyl alcohol.

Administration of benzyl alcohol has been associated with the risk of serious adverse reactions, including breathing problems in young children (known as "gasping syndrome").

It must not be administered to premature infants or newborns (up to 4 weeks of age).

It should not be used for more than one week in young children (under 3 years of age).

Consult your doctor or pharmacist if you are pregnant or breastfeeding, or if you have liver or kidney disease. This is because high amounts of benzyl alcohol may interact in the body and cause adverse effects (known as "lactic acidosis").

Benzyl alcohol may cause allergic reactions.

Etoposide Accord contains Polysorbate 80

Etoposide Accord contains 80 mg/ml of polysorbate 80.

In newborn children, a vitamin E injectable product containing polysorbate 80 has been reported to be associated with a life-threatening syndrome involving liver and kidney failure, reduced respiratory function, decreased platelet count, and abdominal inflammation.

Etoposide Accord contains Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose and is therefore considered essentially "sodium-free."

3. How Etoposide Accord will be administered

Etoposide Accord will be administered by a doctor or nurse. It will be given as an intravenous infusion. The infusion may take between 30 and 60 minutes.

The dose you will receive is specific to you and will be calculated by your doctor. The usual dose, based on etoposide, is between 50 and 100 mg/m2 of body surface area, given daily for 5 consecutive days, or between 100 and 120 mg/m2 of body surface area on days 1, 3, and 5. This treatment cycle may be repeated later depending on blood test results, but not earlier than 21 days after the first treatment cycle.

In children being treated for cancer of the blood or lymphatic system, the dose used is between 75 and 150 mg/m2 of body surface area, given daily for 2 to 5 days.

On some occasions, 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 receive more Etoposide Accord than you should

Since Etoposide Accord is administered by a doctor or nurse, overdose is unlikely. However, if it occurs, the 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 inform your doctor or nurse if you experience any of the following symptoms: swelling of the tongue or throat, difficulty breathing, rapid heartbeat, skin flushing, or rash. These could be signs of a severe allergic reaction.

Serious liver, kidney, or heart damage has occasionally been observed due to a disorder called tumor lysis syndrome, caused by harmful amounts of substances from cancer cells entering the bloodstream when Etoposide Accord is administered together with other drugs used to treat cancer.

Possible adverse effects experienced with Etoposide Accord are:

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

• blood disorders (for this reason, you will have blood tests between treatment cycles)
• changes in skin color (pigmentation)
• constipation
• temporary hair loss
• feeling of weakness (asthenia)
• nausea and vomiting
• general feeling of being unwell (malaise)
• abdominal pain
• liver damage (hepatotoxicity)
• loss of appetite
• elevated liver enzymes
• jaundice (increased bilirubin)

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

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

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

• tingling or numbness in the hands and feet
• bleeding

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

• seizures (epileptic fits)
• drowsiness or fatigue
• altered taste
• difficulty swallowing
• severe skin and/or mucous membrane reactions, which may include painful blisters and fever, extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• sunburn-like rash that may appear on skin previously exposed to radiotherapy and may be severe (radiation dermatitis)
• fever
• temporary blindness
• acid reflux
• breathing difficulties
• flushing

Frequency not known (cannot be estimated from available data)

• tumor lysis syndrome (complications arising from substances released by treated cancer cells entering the bloodstream)
• swelling of the face and tongue
• infertility
• difficulty breathing
• acute kidney failure

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, 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: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Etoposide Accord

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

Do not use this medicine after the expiry date stated on the container after "EXP". The expiry date refers to the last day of the month indicated.

Store in the original packaging to protect from light.

Do not refrigerate or freeze.

Chemical and physical stability of the diluted solution in sodium chloride (0.9% w/v) and dextrose (5% w/v) has been demonstrated at concentrations of 0.2 mg/ml or 0.4 mg/ml for up to 96 hours and 48 hours at temperatures of 20°C and 25°C, respectively. From a microbiological standpoint, the product should be used immediately. Otherwise, the in-use storage times and conditions prior to use are the responsibility of the user. Do not store the diluted product under refrigeration (2–8°C), as this may result in precipitation.

Do not use Etoposide Accord if you observe signs of precipitation or if visible particles are present.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer require. This will help protect the environment.

6. Contents of the container and additional information

Composition of Etoposide Accord

The active substance is etoposide.

1 ml contains 20 mg of etoposide.

Each 5 ml vial contains 100 mg of etoposide.

Each 10 ml vial contains 200 mg of etoposide.

Each 12.5 ml vial contains 250 mg of etoposide.

Each 20 ml vial contains 400 mg of etoposide.

Each 25 ml vial contains 500 mg of etoposide.

Each 50 ml vial contains 1000 mg of etoposide.

The other components (excipients) are anhydrous citric acid, benzyl alcohol, polysorbate 80, Macrogol 300 and anhydrous ethanol.

Appearance of the product and contents of the container

Etoposide Accord is a clear, colourless to pale yellow solution.

Container sizes:

1 vial of 5 ml

1 vial of 10 ml

1 vial of 12.5 ml

1 vial of 20 ml

1 vial of 25 ml

1 vial of 50 ml

Not all container sizes may be marketed.

Marketing Authorisation Holder:

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Manufacturer:

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens, Lamia, 32009, Greece

Date of the most recent review of this leaflet: February 2024

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

The following information is intended for healthcare professionals only

Dosage and method of administration

For intravenous infusion.

Adults

The recommended dose of etoposide is 60–120 mg/m² i.v. daily for 5 consecutive days. As etoposide causes myelosuppression, treatment repetition intervals should not be less than 10 to 20 days. For non-haematological indications, treatment intervals should not be more frequent than every 21 days. Repeated treatment courses should not be administered until haematological status has been monitored for signs of myelosuppression and found to be satisfactory.

Typically, dosing regimens of 100 mg/m² for 5 days or 120 mg/m² on alternate days (days 1, 3 and 5) are frequently used.

The required dose of etoposide concentrate must be diluted with either 5% glucose solution for injection or 0.9% sodium chloride solution to give a final concentration of 0.2–0.4 mg/ml of etoposide (e.g., 1 ml or 2 ml of concentrate in 100 ml of diluent to achieve concentrations of 0.2 mg/ml and 0.4 mg/ml, respectively). It should be administered by intravenous infusion over a period of not less than 30 minutes and not more than 2 hours.

Duration of use:

The duration of treatment is determined by the physician, taking into account the underlying disease, the combined dosing regimen administered (if applicable), and the individual therapeutic situation. Etoposide should be discontinued if the tumour does not respond to treatment and/or if progression occurs or if intolerable adverse effects develop.

Paravenous injection should be avoided.

Elderly patients:

Dose adjustment is not required.

Patients with renal impairment:

Dose adjustment is required according to creatinine clearance measurements.

Etoposide must not be mixed with other medicinal products when administered. It should not be mixed with any products other than those mentioned above.

Instructions for use/handling

Etoposide Accord must be handled in accordance with guidelines for cytotoxic agents.

If the solution shows signs of precipitation or contains visible particles, it should be discarded.

Etoposide Accord must be diluted before use with sodium chloride (0.9% w/v) or dextrose (5% w/v) to a concentration of 0.2 mg/ml (i.e., 1 ml of concentrate in 100 ml of diluent) to 0.4 mg/ml (i.e., 2 ml of concentrate in 100 ml of diluent). The concentration of the diluted solution must not exceed 0.4 mg/ml due to the risk of precipitation.

Discard any unused content. Infusion fluids containing etoposide should be used immediately.

For disposal and safety information, follow the guidelines for safe handling of antineoplastic drugs.

Avoid all contact with the liquid. During preparation and reconstitution, strictly aseptic techniques must be used; protective measures should include wearing gloves, mask, safety goggles and protective clothing. Use of a vertical laminar airflow cabinet (LAF) is recommended.

Gloves should be worn during administration. Waste disposal procedures must take into account the cytotoxic nature of this substance.

Pregnant personnel are advised not to handle chemotherapeutic agents.

If etoposide comes into contact with skin, mucous membranes or eyes, immediately rinse thoroughly with water. Soap may be used to clean the skin.

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

Stability after dilution

Chemical and physical stability of the diluted solution in sodium chloride (0.9% w/v) and glucose (5% w/v) has been demonstrated for concentrations of 0.2 mg/ml or 0.4 mg/ml up to 96 hours and 48 hours at temperatures of 20°C and 25°C, respectively. From a microbiological standpoint, the product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user. Do not store the diluted product refrigerated (2–8°C), as this may cause precipitation.

Storage

Keep the vial in the original packaging to protect it from light.

Do not refrigerate or freeze.