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

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

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

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

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

Package leaflet contents:

1. What Etopósido Hikma is and what it is used for
2. What you need to know before starting to use Etopósido Hikma
3. How you will receive Etopósido Hikma
4. Possible side effects
5. How to store Etopósido Hikma
6. Contents of the pack and other information

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

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

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

• testicular cancer
• small cell lung cancer
• blood cancer (acute myeloid leukaemia)
• tumours of the lymphatic system (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 leukaemia)
• tumours of the lymphatic system (Hodgkin's lymphoma, non-Hodgkin's lymphoma)

You should discuss with your doctor the specific reason why Etoposide has been prescribed for you.

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

Do not use Etoposide

• 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 they do, consult your doctor, who can advise you.

Warnings and precautions

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

• if you have low levels of a protein called albumin in the blood.
• if you have recently received chemotherapy or radiotherapy.
• if you have any infection.
• if you have liver or kidney problems.

Effective anticancer treatment can rapidly destroy large numbers of cancer cells. Very rarely, this may cause harmful amounts of substances to be released from the cancer cells into the bloodstream. In such cases, this may lead to problems in the liver, kidneys, heart, or blood, 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 levels of certain blood cells, which could make you more susceptible to infections or may impair your blood's ability to clot properly if you get a cut.

To ensure this does not happen, you will have blood tests at the start of treatment and before each dose you receive.

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

Other medicines and Etoposide Hikma

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

This is especially important

• if you are taking any medicine with a mechanism of action similar to etoposide.
• if you have recently received any vaccine containing live microorganisms.
• if you are taking phenylbutazone, sodium salicylate, or acetylsalicylic acid.
• if you are taking warfarin (a medicine used to prevent blood clots).
• if you are taking phenytoin or any other medicine used for epilepsy.
• if you are taking any anthracycline (a group of medicines used to treat cancer).
• if you are receiving treatment with cisplatin (a medicine used to treat cancer).
• if you are taking a medicine called cyclosporine (which is 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 are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Etoposide Hikma must not be used during pregnancy unless clearly indicated by your doctor. You must not breastfeed while being treated with this medicine.

Patients of both sexes, men and women, of childbearing potential must use an effective method of contraception (e.g., barrier method or condom) during treatment and for at least 6 months after completion of treatment with Etoposide. Male patients treated with this medicine are advised not to father a child during treatment and for up to 6 months after treatment. In addition, men are advised to seek counselling on sperm preservation before starting treatment.

Patients of both sexes who are considering having a child after treatment with Etoposide should discuss this 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 feel tired, nauseous, dizzy, or drowsy, you should refrain from doing so until you have discussed it with your doctor.

Etoposide Hikma contains alcohol

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

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

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

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

The alcohol in this preparation may 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 medicine may affect your ability to drive or operate machinery, as it may impair your judgment and reaction speed.

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

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

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

If you are alcohol-dependent, consult your doctor or pharmacist before taking this medicine.

Etoposide Hikma contains benzyl alcohol

Etoposide Hikma contains 20 mg of benzyl alcohol in each ml.

Benzyl alcohol may cause allergic reactions.

Benzyl alcohol has been associated with the risk of serious side effects, including breathing problems (known as "gasping syndrome") in young children.

Do not administer this medicine to your newborn (up to 4 weeks of age), unless recommended by your doctor.

Do not use for more than one week in young children (under 3 years of age), unless recommended by your doctor or pharmacist.

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

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

EtopósidoHikma contains polysorbate 80

This medicine contains 80 mg of polysorbate 80 in each ml.

Rarely, polysorbates may cause severe allergic reactions. If you experience difficulty breathing, swelling, or dizziness, seek medical help immediately.

Polysorbates may affect circulation and the heart (for example, low blood pressure, changes in heart rate).

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

3. How you will receive Etoposide Hikma

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

Your dose will be individually 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 the results of blood tests, but not earlier than 21 days after the first treatment cycle.

In children treated for cancers of the blood or lymphatic system, the dose used is between 75 and 150 mg/m2 of body surface area 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 Hikma than you should

Since etoposide is administered by a doctor or nurse, overdose is unlikely. However, if an overdose 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, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause side effects, although not everyone experiences 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.

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

Possible side effects with Etoposide:

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

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 ulcers in the throat
• 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 skin 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)
• skin rash resembling sunburn that may appear on skin previously exposed to radiotherapy and can be severe (radiation dermatitis)
• fever
• temporary blindness
• breathing difficulties
• acid reflux
• flushing
• severe allergic reactions

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 reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Etoposide Hikma

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.

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

From a microbiological standpoint, unless the method of opening excludes 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.

After dilution:

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

Chemical and physical in-use stability has been demonstrated for 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 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 must 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 precipitation is observed or if visible particles are present.

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

6. Contents of the pack and other information

Composition of Etoposide Hikma

Etoposide Hikma contains the active substance etoposide.

1 ml contains 20 mg of etoposide.

Each 5 ml vial contains 100 mg of etopide.

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

Appearance of the product and contents of the container

Etoposide Hikma is a clear, colourless to pale yellow infusion solution.

Etoposide is supplied in a carton 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:

You can request further information regarding this medicinal product by contacting 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 review of this leaflet: 01/2024

Detailed and up-to-date 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), 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 50 to 100 mg/m²/day on days 1–5 or 100 to 120 mg/m² on days 1, 3, and 5, repeated every 3–4 weeks in combination with other drugs indicated for the disease being treated. Dosage should be adjusted to account for the myelosuppressive effects of other combination drugs or the effects of prior radiotherapy or chemotherapy that may have compromised bone marrow reserve.

The required dose of etoposide must be diluted immediately before use with 5% w/v glucose solution or 0.9% w/v 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 must not be mixed with other medications when administered. It must not be mixed with any products other than those mentioned above.

Elderly population

Dosage adjustment is not required in elderly patients (age > 65 years), except based on renal function.

Paediatric use

Etoposide in paediatric patients has been used at doses ranging from 75 to 150 mg/m²/day for 2–5 days in combination with other antineoplastic agents. Current specialized protocols and guidelines should be consulted to determine the appropriate treatment regimen.

Renal impairment

In patients with renal impairment, the following initial dose modification 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 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 must be followed.

Caution must always be exercised when handling cytotoxic products. Always take necessary measures to avoid exposure. As with other potentially toxic compounds, caution should be exercised when handling and preparing etoposide solutions. Skin reactions may occur following accidental exposure to etoposide. Dilution must be performed under aseptic conditions by trained personnel in a specifically designated area. Precautions should be taken to avoid contact with skin and mucous membranes. The use of gloves is recommended. If etoposide comes into contact with the skin or mucous membranes, wash the skin immediately with soap and water and rinse the mucous membranes with water.

Care must be taken to avoid extravasation.

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

Disposal of unused medication and of all materials that have come into contact with it must 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 from light.

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

Shelf life after opening:

Chemical and physical in-use stability of the concentrate has been demonstrated for 28 days after the first puncture, 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 method of opening excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions during use are the responsibility of the user.

Validity period after dilution

Chemical and physical in-use stability 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 in-use stability 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 standpoint, 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 must not exceed 24 hours for the 0.2 mg/ml concentration and 12 hours for the 0.4 mg/ml concentration.