Label: Information for the Patient

Etoposide Accord 20 mg/ml Concentrate for Solution for Infusion EFG

Read this label carefully before starting to take this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label.See section 4.

Each vial contains etopósido as the active ingredient.

Etopósido belongs to a group of medications called cytostatics that are used in the treatment of cancer.

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

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

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

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

It is advisable to speak with your doctor about the exact reason why you have been prescribed Etopósido Accord.

Do not take EtopósidoAccord

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).
• If you have recently received a live virus vaccine, including the yellow fever vaccine.
• If you are breastfeeding or plan to do so.

If any of the above applies to you, or if you are unsure, consult your doctor, who will be able to advise you.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to receive Etopósido Accord:

-If you have any infection.

-If you have recently received radiation or chemotherapy.

-If you have low levels of a protein called albumin in your blood.

-If you have liver or kidney problems.

The effective anticancer treatment can destroy cancer cells quickly in large quantities. In very rare cases, this can cause the release of harmful amounts of these cancer cells into the blood. In this case, it can cause problems in the liver, kidneys, heart, or blood, which could be fatal if not treated.

To prevent this, your doctor must perform regular blood tests to control the level of these substances during treatment with this medication.

This medication can cause a reduction in the level of some blood cells that could make you suffer from infections or prevent blood from clotting as well as it should if you suffer any cuts. To check that this does not occur, you will have blood tests at the beginning of treatment and before each dose you take.

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

Other medications and Etopósido Accord

Inform your doctor if you are using, have used recently, or may use any other medication.

This is especially important

-If you are taking a medication called ciclosporin (which is used to reduce the activity of the immune system).

-If you are receiving treatment with cisplatino (a medication used to treat cancer).

-If you are taking phenytoin or any other medication used to treat epilepsy.

-If you are taking warfarin (a medication used to prevent blood clots).

-If you have recently received any live virus vaccine.

-If you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.

-If you are taking any anthracycline (a group of medications used to treat cancer).

-If you are taking any medication with a similar mechanism of action to Etopósido Accord.

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 medication.

This medication should not be used during pregnancy unless your doctor clearly indicates it.

You should not breastfeed while receiving treatment with Etopósido Accord.

Both male and female patients of childbearing age should use an effective contraceptive method (e.g., barrier method or condom) during treatment and at least 6 months after completing treatment with Etopósido Accord.

Male patients treated with Etopósido Accord are advised not to conceive any children during treatment and for at least 6 months after the same. Additionally, men are advised to seek advice on sperm conservation before starting treatment.

Both male and female patients who plan to have a child after treatment with Etopósido Accord should discuss it with their doctor or nurse.

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive and operate machinery. However, if you are tired, have an upset stomach, feel dizzy or disoriented, you should not do it until you have discussed it with your doctor.

Etopósido Accord contains alcohol

This medication contains 30.5% alcohol (ethanol), which corresponds to 240.64 mg of ethanol per ml of concentrate, which is 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 to 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 medications may be increased or reduced.

Etopósido Accord contains benzyl alcohol

Etopósido Accord contains 30 mg/ml of benzyl alcohol.

The administration of benzyl alcohol has been associated with the risk of severe adverse effects, including respiratory problems in young children (known as "breathing syndrome").

It should not be administered to premature or newborn children (up to 4 weeks old).

It should not be used for more than a week in young children (less than 3 years old).

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 could interact in the body and cause adverse effects (known as "lactic acidosis").

Benzyl alcohol could cause allergic reactions.

Etopósido Accord contains Polisorbato 80

Etopósido Accord contains 80 mg/ml of Polisorbato 80.

In newborn children, a product injectable of vitamin E that contains Polisorbato 80 has been reported to be associated with a vital risk syndrome with liver and kidney insufficiency, respiratory function decrease, decrease in the number of packets, and abdominal inflammation.

Etopósido Accord contains Sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose, so it is considered essentially "sodium-free".

Etopósido Accord will be administered by a doctor or nurse. It will be given to you 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 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 as needed based on blood test results, but not within at least 21 days after the first treatment cycle.

In children treated for blood or lymphatic system cancer, the dose used is between 75 and 150 mg/m² of body surface area given daily for 2-5 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 Receive More Etopósido Accord Than You Should

Since Etopósido Accord is administered by a doctor or nurse, overdose is unlikely. However, if it occurs, your doctor will treat any symptoms that develop.

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

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

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

Inform your doctor or nurse immediately if you experience any of the following symptoms: swelling of the tongue or throat, difficulty breathing, rapid heartbeat, skin redness, or rash. They could be signs of a severe allergic reaction.

In some cases, severe damage to the liver, kidneys, or heart has been observed due to a condition called tumor lysis syndrome caused by the entry of harmful amounts of substances from cancer cells into the bloodstream when Etopósido Accord is administered with other medications used to treat cancer.due to a condition called tumor lysis syndrome caused by the entry of harmful amounts of substances from cancer cells into the bloodstream when Etopósido Accord is administered with other medications used to treat cancer.

Possible side effectsexperienced with Etopósido Accord are:

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

• Blood disorders (so they will do blood tests between treatment cycles)
• Skin color changes (pigmentation)
• Constipation
• Temporary hair loss
• Weakness (asthenia)
• Nausea and vomiting
• General feeling of being unwell (general malaise)
• Abdominal pain
• Liver damage (hepatotoxicity)
• Loss of appetite
• Elevated liver enzymes
• Jaundice (elevated bilirubin)

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

• Acute leukemia (severe blood cancer)
• Irregular heartbeat (arrhythmia) or heart attack (myocardial infarction)
• Dizziness
• High blood pressure
• Low blood pressure
• Sores on the lips, mouth, or ulcers in the throat
• Skin redness
• Infection(including infections observed in patients with a weakened immune system, e.g., Pneumocystis jirovecii pneumonia)
• Diarrhea
• Skin problems such as itching or hives
• Phlebitis (inflammation of a vein)
• Severe allergic reactions
• Reactions at the infusion site

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

• Tickling or tingling in the hands and feet
• Bleeding

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

• Seizures (epileptic crisis)
• Drowsiness or fatigue
• Alteration of 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)
• Radiation dermatitis, a sunburn-like rash that may appear on previously irradiated skin and can be severe
• Fever
• Temporary blindness
• Acid reflux
• Respiratory problems
• Flush

Unknown frequency(cannot be estimated from available data)

• Tumor lysis syndrome (complications that occur when substances released by treated cancer cells enter the bloodstream)
• Swelling of the face and tongue
• Infertility
• Difficulty breathing
• Acute renal failure

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist,even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

Do not refrigerate or freeze.

Chemical and physical stability has been demonstrated during the use of the diluted solution in sodium chloride (0.9% w/v) and dextrose (5% w/v) 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 standpoint, the product should be used immediately. In any other case, the storage times in use and the previous conditions of its use are the responsibility of the user. Do not store the diluted product refrigerated (2-8°C) as this may lead to precipitation.

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

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Etoposide Accord Composition

The active ingredient is etoposide

1 ml contains 20 mg of etoposide.

Each vial of 5 ml contains 100 mg of etoposide.

Each vial of 10 ml contains 200 mg of etoposide.

Each vial of 12.5 ml contains 250 mg of etoposide.

Each vial of 20 ml contains 400 mg of etoposide.

Each vial of 25 ml contains 500 mg of etoposide.

Each vial of 50 ml contains 1000 mg of etoposide.

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

Product Appearance and Packaging Contents

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

Packaging 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 packaging 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

Responsible for Manufacturing:

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

Last Review Date of this Leaflet:February 2024

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es

The following information is intended only for healthcare professionals

Dosage and Administration

For intravenous infusion

Adults

The recommended dose of etoposide is 60-120 mg/m2 i.v. per day for 5 consecutive days. As etoposide causes myelosuppression, treatment 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 count has been controlled for signs of myelosuppression and has been satisfactory.

Generally, the dosing 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 must be diluted with either a 5% glucose injection solution or a 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 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 dosing regimen administered (if necessary), and the individual therapeutic situation. Etoposide should be discontinued if the tumor does not respond to treatment and/or progresses or if unacceptable adverse effects occur.

Injection into a peripheral vein should be avoided.

Geriatric Patients:

No dose adjustment is required.

Patients with Renal Insufficiency:

Dose adjustment is required based on creatinine clearance measurements.

Etoposide cannot 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 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) or 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.

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

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

Avoid all contact with the liquid. During preparation and reconstitution, use a strictly aseptic working technique; 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, wear gloves. The procedure for disposing of waste should take into account the cytotoxic nature of this substance.

It is recommended that pregnant staff members not handle chemotherapeutic agents.

If etoposide comes into contact with the skin, mucous membranes, or eyes, wash immediately with plenty of 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.

Valid Period After Dilution

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

Storage

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

Do not refrigerate or freeze.