Patient Information Leaflet: Product Information

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

Read this 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. Do not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the Leaflet:

1. What Etoposide Hikma is and what it is used for
2. What you need to know before you start using Etoposide Hikma.
3. How you will receive Etoposide Hikma.
4. Possible side effects.
5. Storage of Etoposide Hikma.
6. Contents of the pack and additional information.

This medicine contains etoposide as the active ingredient. Etoposide belongs to a group of medicines called cytostatics that are used in the treatment of cancer.

Etopósido Hikma 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)

Etoposide 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 that you speak with your doctor about the exact reason why you have been prescribed Etopósido.

No use Etopósido

• if you are allergic to the active ingredient or to 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:

• if you have low levels of a protein calledalbuminin the blood.
• if you have recently receivedchemotherapyor radiation therapy.
• if you have anyinfection.
• if you have liver or kidney problems.

Effective cancer treatment can destroy cancer cells quickly in large quantities. In very rare cases, this can cause the release of harmful amounts of substances from 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 may cause a reduction in the level of some blood cells that could make you suffer from infections or prevent your 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 start of treatment and before each dose you take.

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

Other Medications andEtopósidoHikma

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

This is especially important

• if you are taking any medication with a similar mechanism of action to Etopósido.
• if you have recently received any live virus vaccine.
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.
• if you are taking warfarin (a medication used to prevent blood clotting).
• if you are taking phenytoin or any other medication used for epilepsy.
• if you are taking any anthracycline (a group of medications used to treat cancer).
• if you are receiving treatment with cisplatin (a medication used to treat cancer).
• if you are taking a medication called cyclosporine (used to reduce the activity of the immune system).

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.

You should not use Etopósido Hikma during pregnancy unless your doctor clearly indicates it. You should not breastfeed while receiving treatment with this medication.

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. Male patients treated with this medication should not conceive any children during treatment and for at least 6 months after treatment. Additionally, male patients should seek advice on sperm conservation before starting treatment.

Both male and female patients who plan to have a child after treatment with Etopósido 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, do not do it until you have discussed it with your doctor.

EtopósidoHikma containsalcohol

This medication contains 260.6 mg of alcohol (ethanol) per ml.

The amount in a 5 ml vial of this medication is equivalent to 32 ml of beer or 13 ml of wine.

The amount in a 10 ml vial of this medication is equivalent to 64 ml of beer or 27 ml of wine.

The amount in a 20 ml vial of this medication is equivalent to 128 ml of beer or 53 ml of wine.

It is likely that the alcohol in this preparation will affect children. These effects may include drowsiness and changes in behavior. It may also affect your ability to concentrate and participate in physical activities.

The amount of alcohol in this medication may affect your ability to drive or operate machinery. This is because it may affect your judgment and the speed at which you react.

If you have epilepsy or liver problems, consult your doctor or pharmacist before taking this medication.

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

If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medication.

If you are addicted to alcohol, consult your doctor or pharmacist before taking this medication.

Etopósidohikma contains benzyl alcohol

Etopósido Hikma contains 20 mg of benzyl alcohol per ml.

Benzyl alcohol may cause allergic reactions.

Benzyl alcohol has been linked to the risk of severe side effects, including respiratory problems (called "breathing difficulty") in young children.

Do not administer this medication to your newborn (up to 4 weeks old), unless your doctor recommends it.

Do not use it for more than a week in young children (under 3 years old), unless your doctor or pharmacist recommends it.

Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (known as "metabolic acidosis").

Ask your doctor or pharmacist for advice if you have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (known as "metabolic acidosis").

EtopósidoHikma contains Polysorbate 80

This medication contains 80 mg of Polysorbate 80 per ml.

In rare cases, polysorbates can cause severe allergic reactions. If you have difficulty breathing, swelling, or feel dizzy, seek medical help immediately.

Polysorbates may affect circulation and the heart (e.g., low blood pressure, changes in heartbeats).

Ask your doctor or pharmacist for advice if you have liver disease. This is because polysorbates may affect the liver.

E topósido will be administered by a doctor or nurse. It will be given to you in the form of a slow 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 etopósido, is between 50 and 100 mg/m 2 of body surface area, given daily for 5 consecutive days, or between 100 and 120 mg/m 2 of body surface area on days 1, 3, and 5. This treatment cycle may be repeated later, depending on the results of blood tests, but this will not be done for 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/m 2 of body surface area given daily for 2 to 5 days.

In some cases, 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 E topósido H ikma Than You Should

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

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.

Severe damage to theliver, kidneys, or hearthas been observed due to a condition called tumor lysis syndrome caused by the entry of harmful amounts of substances from cancer cells into the circulatory system. This has been seen when Etoposide is administered with other medications used to treat cancer.

Possible side effectsexperienced with Etoposide:

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

• Blood disorders (so they will make blood tests between treatment cycles)
• Nausea and vomiting
• Loss of appetite
• DAbdominal pain
• Constipation
• Temporary hair loss
• Liver damage (hepatotoxicity)
• Elevation of liver enzymes
• Pigmentation changes in the skin
• Icterus (elevated bilirubin)
• Weakness (asthenia)
• General feeling of being unwell (general malaise)

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., a lung infection called Pneumocystis jirovecii pneumonia)
• Diarrhea
• Skin problems such as itching or skin rash
• Phlebitis (inflammation of a vein)
• Severe allergic reactions
• Reactions at the infusion site

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

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

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 of 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 Pharmacovigilance of Medicines 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.

Do not store above 25° C.

Do not refrigerate or freeze.

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

After opening:

Chemical and physical stability has been demonstrated in use of the concentrate after the first puncture for 28 days at room temperature, exposed or protected from light, and for 28 days at 2-8 °C, when protected from light.

From a microbiological standpoint, unless the opening method excludes the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times and conditions during use are the responsibility of the user.

After dilution:

Chemical and physical stability has been demonstrated in use of the diluted solution at a concentration of 0.2 mg/ml insodium chloride (0.9% w/v) and glucose (5% w/v) for up to 24 hours at room temperature.

Chemical and physical stability has been demonstrated in use of the diluted solution at a concentration of 0.4 mg/ml in sodium chloride (0.9% w/v) and glucose (5% w/v) for up to 12 hours at room temperature.

From a microbiological standpoint, the product must be used immediately. If not used immediately, the storage times in use and the conditions prior to its use are the responsibility of the user and should not exceed 24 hours for the concentration of 0.2 mg/ml and 12 hours for the concentration of 0.4 mg/ml.

Do not use Etoposide Hikma if you observe signs of precipitation or it contains visible particles.

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

Composition of Etoposide Hikma

Etoposide Hikma contains the active ingredient 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 20 ml contains 400 mg of etoposide.

Each vial of 25 ml contains 500 mg of etoposide.

Each vial of 50 ml contains 1,000 mg of etoposide.

The other components are anhydrous citric acid, benzyl alcohol, polisorbate 80, polyethylene glycol, and ethanol at 96%.

Appearance of the product and contents of the package

Etoposide Hikma is a transparent, colorless to pale yellow solution for infusion.

Etoposide is presented in a box containing 1 vial of 5 ml, 10 ml, 20 ml, 25 ml, 50 ml.

It is possible that not all sizes of packaging will be marketed.

Holder of the marketing authorization and responsible for manufacturing:

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, nº8, 8A/8B

Fervença

2705-906 Terrugem SNT

Portugal

Responsible for manufacturing: Thymoorgan Pharmazie GmbH

Schiffgraben 23

38690 Goslar

Germany

This medicine is authorized in the Member States of the EEA with the following names:

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

Last review date of this leaflet: 01/2024

More detailed and up-to-date information about 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

Etoposide Hikma is administered by slow intravenous infusion (usually over a period of 30 to 60 minutes) as hypotension has been reported as a possible adverse effect of rapid intravenous injection. Etoposide Hikma MUST NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.

The recommended dose of etoposide in adult patients is between 50 and 100 mg/m2/day for days 1-5 or between 100 and 120 mg/m2on days 1, 3, and 5, every 3-4 weeks in combination with other indicated drugs for the disease being treated. The dosage should be adjusted to take into account the myelosuppressive effects of other drugs in the combination or the effects of previous radiation or chemotherapy that may have compromised the bone marrow reserve.

The required dose of etoposide must be diluted immediately before use with a 5% glucose solution or a 0.9% sodium chloride solution to achieve a final concentration of 0.2 to 0.4 mg/ml of etoposide (i.e., 1 or 2 ml of concentrate in 100 ml of diluent to achieve a concentration of 0.2 mg/ml and 0.4 mg/ml, respectively).

Etoposide should not be mixed with other medications when administered. It should not be mixed with other products that are not mentioned above.

Geriatric population

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

Pediatric use

Etoposide in pediatric patients has been used in the range of 75 to 150 mg/m2/day for 2-5 days in combination with other antineoplastic drugs. Consult current specialized protocols and guidelines to determine the appropriate treatment regimen.

Renal impairment

In patients with renal impairment, the following dose adjustment should be considered based on the measured creatinine clearance:

In patients with creatinine clearance less than 15 ml/min and on dialysis, it is likely that further dose reduction will be necessary, as etoposide clearance is reduced even further in these patients. Administration in moderate to severe renal impairment should be based on the patient's tolerance and clinical effect.

Since etoposide and its metabolites are not dialyzable, it can be administered before and after hemodialysis.

Instructions for use/manipulation

Follow the procedures for proper handling and disposal of anticancer drugs.

Take necessary precautions to avoid exposure when handling cytostatic products. Always take measures to avoid exposure. As with other potentially toxic compounds, caution should be exercised when handling and preparing etoposide solutions. Skin reactions associated with accidental exposure to etoposide may occur. Dilution should be performed in aseptic conditions by trained personnel in a designated area. Take precautions to avoid skin and mucous membrane contact. Gloves are recommended. If etoposide comes into contact with the skin or mucous membranes, wash the skin immediately with water and soap and rinse the mucous membranes with water.

Be careful to avoid extravasation.

If precipitation or visible particles are observed, the reconstituted solution should be discarded.

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

Storage

Do not store above 25° C.

Do not refrigerate or freeze.

Store vials in the original packaging to protect them from light.

For storage conditions of vials after the first puncture and solution after reconstitution of the medication, see below.

Shelf life after opening:

Chemical and physical stability has been demonstrated in use of the concentrate after the first puncture for 28 days at room temperature, exposed or protected from light, and for 28 days at 2-8 °C, when protected from light. From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the times and conditions of storage during use are the responsibility of the user.

Shelf life after dilution

Chemical and physical stability in use of the diluted solution at a concentration of 0.2 mg/ml in sodium chloride (0.9% p/v) and glucose (5% p/v) has been demonstrated for 24 hours at room temperature.

Chemical and physical stability in use of the diluted solution at a concentration of 0.4 mg/ml in sodium chloride (0.9% p/v) and glucose (5% p/v) has been demonstrated for 12 hours at room temperature.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times in use and the conditions prior to use are the responsibility of the user and should not exceed 24 hours for a concentration of 0.2 mg/ml and 12 hours for a concentration of 0.4 mg/ml.