ETOPOSIDE ACCORD 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

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

Read all of this leaflet carefully before you start taking 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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 Etoposide Accord is and what it is used for.
2. What you need to know before you receive Etoposide Accord.
3. How you will receive Etoposide Accord.
4. Possible side effects.
5. Storage of Etoposide Accord.
6. Contents of the pack and further 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 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 leukaemia)
• lymphatic system tumour (Hodgkin's lymphoma, non-Hodgkin's lymphoma)
• cancers of the reproductive system (gestational trophoblastic neoplasia and ovarian cancer)

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

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

You should discuss with your doctor the exact reason why you have been prescribed Etoposide Accord.

2. What you need to know before you receive Etoposide Accord

Do not take Etoposide Accord

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if you have recently received a live vaccine, including the yellow fever vaccine.
• if you are breast-feeding or plan to breast-feed.

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

Warnings and precautions

Consult 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 anti-cancer treatment can destroy cancer cells quickly in large quantities. In very rare cases, this can lead to the release of harmful amounts of these cancer cells into the blood. This can cause problems in the liver, kidney, heart or blood, which could be life-threatening if not treated.

To prevent this, your doctor will need to perform regular blood tests to check the levels of these substances during treatment with this medicine.

This medicine may cause a reduction in the level of some blood cells, which could make you more likely to get infections or make it more difficult for your blood to clot if you cut yourself. To check that this is not happening, you will have regular blood tests at the start of treatment and before each dose that you receive.

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

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 ciclosporin (which is 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 a live vaccine.
• 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 similar mechanism of action to Etoposide Accord.

Pregnancy, breast-feeding and fertility

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

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

You should not breast-feed while being treated with Etoposide Accord.

Male and female patients of childbearing potential must use effective contraception (e.g. barrier method or condom) during treatment and for at least 6 months after the end of treatment with Etoposide Accord.

Male patients treated with Etoposide Accord are advised not to father a child during treatment and for up to 6 months after treatment. In addition, male patients should seek advice on sperm conservation before starting treatment.

Male and female patients who are planning to have a child after treatment with Etoposide Accord 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, have an upset stomach or feel dizzy or disoriented, you should not do so until you have discussed it with your doctor.

Etoposide Accord contains alcohol

This medicine contains 30.5% alcohol (ethanol), which corresponds to 240.64 mg of ethanol per ml of concentrate, i.e. 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, breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy. The effect of other medicines may be increased or decreased.

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 effects, including breathing problems in small children (so-called "gasping syndrome").

It must not be administered to premature or newborn infants (up to 4 weeks).

It must not be used for more than one week in small children (less than 3 years of age).

Consult your doctor or pharmacist if you are pregnant or breast-feeding, or if you have liver or kidney disease. This is because high levels of benzyl alcohol could interact in the body and cause adverse effects (so-called "lactic acidosis").

Benzyl alcohol may cause allergic reactions.

Etoposide Accord contains Polysorbate 80

Etoposide Accord contains 80 mg/ml of polysorbate 80.

In newborns, it has been reported that an injectable vitamin E product containing polysorbate 80 may be associated with a life-threatening syndrome with liver and kidney failure, respiratory failure, 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 to be "sodium-free"

3. How you will receive Etoposide Accord

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

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

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

On some occasions, 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 receive more Etoposide Accord than you should

Since Etoposide Accord is administered by a doctor or nurse, overdose is unlikely. However, if it does occur, your doctor will treat any symptoms that appear.

In case of overdose or accidental ingestion, contact the Toxicology Information Service on 91-562 04 20, stating the name of the medicine and the amount taken.

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, flushing of the skin or rash. These could be signs of a severe allergic reaction.

On rare occasions, serious liver, kidney or heart damagehas been observed due to a disorder called tumour lysis syndrome, which is caused by the release of harmful amounts of substances from cancer cells into the bloodstream when Etoposide Accord is administered together with other medicines used to treat cancer.

Side effectsthat have been reported with Etoposide Accord are:

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

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

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

• acute leukaemia (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 a weakened immune system, e.g. a lung infection called Pneumocystis jirovecii pneumonia)
• diarrhoea
• skin problems such as itching or rash
• vein inflammation
• severe allergic reactions
• reactions at the infusion site

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)

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

Frequency not known(cannot be estimated from the available data)

• tumour lysis syndrome (complications that occur when substances released from treated cancer cells enter the bloodstream)
• facial and tongue swelling
• infertility
• breathing difficulties
• acute kidney failure

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side 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 which is stated on the carton after "EXP". The expiry date refers to the last day of that month.

Store in the original package 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 for up to 96 hours and 48 hours at temperatures of 20°C and 25°C, respectively. From a microbiological point of view, the product should be used immediately. Otherwise, in-use storage times and conditions are the responsibility of the user. Do not store the diluted product in the refrigerator (2-8°C) as this may cause precipitation.

Do not use Etoposide Accord if you notice signs of precipitation or if it contains visible particles.

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 further information

Composition of Etoposide Accord

The active ingredient 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 packaging content

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

Package 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 package sizes may be marketed

Marketing authorization 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 last revision of this prospectus:February 2024

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

The following information is intended only for healthcare professionals

Posology and method of administration

For intravenous perfusion

Adults

The recommended dose of etoposide is 60-120 mg/m2 i.v. per day for 5 consecutive days. Since etoposide causes myelosuppression, treatment repetition time intervals should not be less than 10 to 20 days. For non-hematological indications, intervals should not be more frequent than every 21 days. Repeated treatment courses should not be administered before the blood condition has been controlled for signs of myelosuppression and has been found satisfactory.

Usually, the dosage of 100 mg/m2 for 5 days or 120 mg/m2 on alternate days on days 1, 3, and 5 is frequently used.

The required dose of etoposide concentrate should be diluted with either 5% glucose solution for injection or 0.9% saline solution to give a final concentration of 0.2 – 0.4 mg/ml of etoposide (for example, 1 ml or 2 ml of concentrate in 100 ml of diluent to give a concentration 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 doctor, taking into account the underlying disease, the combined posology regimen administered (if necessary), and the individual therapeutic situation. Etoposide should be discontinued if the tumor does not respond to treatment and/or if it progresses or if intolerable undesirable effects occur.

Paravenous injection should be avoided.

Elderly patients:

No dose adjustment is necessary.

Patients with renal insufficiency:

Dose adjustment is required according to creatinine clearance measurements.

Etoposide should not be mixed with other medications when administered. It should not be mixed with other products except those mentioned above.

Instructions for use/handling

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

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

Etoposide Accord should be diluted before use with sodium chloride (0.9% p/v) or dextrose (5% p/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 should not exceed 0.4 mg/ml due to the risk of precipitation.

Any unused content should be eliminated. Infusion fluids containing etoposide should be used immediately.

For disposal and safety information, the guidelines on the safe handling of antineoplastic drugs should be followed.

Any contact with the liquid should be avoided. During preparation and reconstitution, a strictly aseptic working technique should be used; protective measures should include the use of gloves, mask, safety glasses, and protective clothing. The use of a vertical laminar airflow cabinet (LAF) is recommended.

During administration, gloves should be worn. The procedure for eliminating residues should take into account the cytotoxic nature of this substance.

Pregnant staff members are recommended not to handle chemotherapeutic agents.

If etoposide comes into contact with the skin, mucous membranes, or eyes, it should be washed immediately and thoroughly with water. For skin cleaning, soap can be used.

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Validity period after dilution

The chemical and physical stability of the diluted solution in sodium chloride (0.9% p/v) and glucose (5% p/v) has been demonstrated up to a concentration of 0.2 mg/ml or 0.4 mg/ml for 96 hours and 48 hours at temperatures of 20°C and 25°C, respectively. From a microbiological point of view, the product should be used immediately. Otherwise, the in-use storage times and conditions prior to use are the responsibility of the user. The diluted product should not be stored refrigerated (2-8°C) as this may cause precipitation.

Storage

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

Do not refrigerate or freeze.