ETOPOSIDE HIKMA 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Prospectus: Patient Information

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

Read the entire prospectus carefully before starting to take this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you only, 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 side effects, consult your doctor or pharmacist, even if they are side effects that do not appear in this prospectus. See section 4.

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1. What is Etoposide Hikma and what is it used for
2. What you need to know before starting to use Etoposide Hikma.
3. How you will receive Etoposide Hikma.
4. Possible side effects.
5. Storage of Etoposide Hikma.
6. Package contents and additional information.

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

This medication contains etoposide as the active ingredient. Etoposide belongs to the group of medications called cytostatics used in cancer treatment.

Etoposide 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)
• cancers of the reproductive system (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 to discuss with your doctor the exact reason why you have been prescribed Etoposide Hikma.

2. What you need to know before starting to use Etoposide Hikma.

Do not use Etoposide

• 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 not sure if it does, consult your doctor, who will be able to advise you.

Warnings and precautions

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

• if you have low levels of a protein called albuminin your blood.
• if you have recently received chemotherapyor radiation therapy.
• if you have any infection.
• if you have liver or kidney problems.

Effective anticancer treatment can quickly destroy cancer cells 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, kidney, heart, or blood, which could be fatal if not treated.

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

This medication may cause a reduction in the level of some blood cells, which 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 happen, 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 monitor these levels.

OtoposideH

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

This is especially important

• if you are taking any medication with a mechanism of action similar to Etoposide.
• if you have recently received a live virus vaccine.
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.
• if you are taking warfarin (a medication used to prevent blood clot formation).
• 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 immune system activity).

E

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.

Etoposide Hikma should not be used during pregnancy unless your doctor clearly indicates it. You should not breastfeed while being treated with this medication.

Patients of both sexes, men and women, of childbearing age must use an effective contraceptive method (e.g., barrier method or condom) during treatment and for at least 6 months after completing treatment with Etoposide. It is recommended that male patients treated with this medication do not conceive a child during treatment and for 6 months after treatment. Additionally, it is recommended that men seek advice on sperm preservation before starting treatment.

Patients of both sexes who plan to have a child after treatment with Etoposide 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 are tired, have an upset stomach, or feel dizzy or disoriented, you should not do so until you have discussed it with your doctor.

EtoposideHalcohol

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 their ability to concentrate and participate in physical activities.

The amount of alcohol in this medication may affect your ability to drive or use machines. This is because it can affect your judgment and reaction speed.

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.

E

Etoposide Hikma contains 20 mg of benzyl alcohol per ml.

Benzyl alcohol may cause allergic reactions.

Benzyl alcohol has been associated with the risk of serious side effects, including respiratory problems (called "gasping syndrome") in small children.

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

Do not use this medication for more than one week in small children (under 3 years of age) 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").

Eikma 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 or swelling or feel dizzy, seek medical help immediately.

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

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

3. How you will receive Etoposide Hikma

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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, 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 the results of blood tests, but this will not be 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 of body surface area 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 moreEikma than you should

Since Etoposide is administered by a doctor or nurse, overdose is unlikely. However, if it occurs, your doctor will treat the symptoms that occur.

In case of overdose or accidental ingestion, consult the Toxicology 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.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience 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, skin flushing, or rash. These could be signs of a severe allergic reaction.

On occasion, severe damage to the liver, kidneys, or hearthas been observed due to a disorder called tumor lysis syndrome, which is caused by the entry of harmful amounts of substances from cancer cells into the bloodstream. This has been seen when Etoposide is administered with other medications used to treat cancer.

Possible side effectsexperienced with Etoposide:

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)
• nausea and vomiting
• loss of appetite
• abdominal pain
• constipation
• temporary hair loss
• liver damage (hepatotoxicity)
• elevation of liver enzymes
• skin color changes (pigmentation)
• jaundice (increased bilirubin)
• feeling of weakness (asthenia)
• feeling unwell in general (general malaise)

Common 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 jiroveciipneumonia)
• diarrhea
• 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 crisis)
• drowsiness or fatigue
• altered taste
• difficulty swallowing
• severe skin and/or mucous membrane reactions, which can include painful blisters and fever, widespread skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• skin rash similar to sunburn that can appear on previously irradiated skin and can be severe (radiation dermatitis)
• fever
• temporary blindness
• breathing problems
• acid reflux
• flushing
• severe allergic reactions

Frequency not known(cannot be estimated from available data)

• tumor lysis syndrome (complications that occur due to substances released by treated cancer cells when they enter the bloodstream)
• swelling of the face and tongue
• infertility
• difficulty breathing
• acute kidney failure

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects that do not appear in this prospectus. You can also report them directly through the Spanish Medication Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Etoposide Hikma

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging after "EXP". The expiration date is the last day of the month indicated.

Do not store above 25°C.

Do not refrigerate or freeze.

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

After opening:

Chemical and physical stability in use of the concentrate after the first puncture has been demonstrated 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 must be used immediately. If it is not used immediately, the storage times and conditions during use are the responsibility of the user.

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% w/v) and glucose (5% w/v) has been demonstrated for up to 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% w/v) and glucose (5% w/v) has been demonstrated for up to 12 hours at room temperature.

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

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

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Etoposide Hikma composition

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

Each 25 ml vial contains 500 mg of etoposide.

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

The other ingredients are anhydrous citric acid, benzyl alcohol, polysorbate 80, polyethylene glycol, and 96% ethanol.

Product appearance and packaging contents

Etoposide Hikma is a clear, 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, or 50 ml.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer:

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, nº8, 8A/8B

Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer: Thymoorgan Pharmazie GmbH

Schiffgraben 23

38690 Goslar

Germany

This medicinal product is authorized in the EEA Member States under the following names:

Further information on this medicinal product can be obtained from 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

Date of last revision of this leaflet: 01/2024

Detailed and updated information on this medicinal product 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 for healthcare professionals only

Posology and method of administration

Etoposide Hikma is administered by slow intravenous infusion (usually over a period of 30 to 60 minutes) since 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 50 to 100 mg/m2/day on days 1-5 or 100 to 120 mg/m2 on days 1, 3, and 5, every 3-4 weeks in combination with other drugs indicated for the disease being treated. The posology should be modified to take into account the myelodepressive effects of other drugs in the combination or the effects of previous radiotherapy or chemotherapy that may have compromised bone marrow reserve.

The required dose of etoposide should be diluted immediately before use with a 5% glucose solution or 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 medicines when administered. It should not be mixed with other products except those mentioned above.

Elderly population

No dose adjustment is necessary in elderly patients (age > 65 years), except based on 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. Current specialized protocols and guidelines should be consulted to determine the appropriate treatment regimen.

Renal impairment

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

In patients with creatinine clearance below 15 ml/min and on dialysis, a further dose reduction is likely to be necessary, as etoposide clearance is further reduced in these patients. Subsequent administration in moderate and severe renal impairment should be based on patient tolerance and clinical effect.

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

Instructions for use/handling

Procedures for the correct handling and disposal of anticancer drugs should be followed.

Precautions should always be taken when handling cytostatic products. Necessary measures should be taken 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 under aseptic conditions by trained personnel in an area specifically designated for this purpose. Precautions should be taken to avoid skin and mucous membrane contact. The use of gloves is recommended. If etoposide comes into contact with the skin or mucous membranes, the skin should be washed immediately with water and soap, and the mucous membrane should be rinsed with water.

Care should be taken to avoid extravasation.

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

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Storage

Do not store above 25°C.

Do not refrigerate or freeze.

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

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

Shelf-life after opening:

Chemical and physical stability in use of the concentrate after the first puncture has been demonstrated 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 precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions 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 up to 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 up to 12 hours at room temperature.

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