Etoposide Hikma

Package leaflet: Information for the user

Etoposide Hikma 20 mg/ml concentrate for solution for infusion

Etoposide
Generic medicine
Please read all of this leaflet carefully before you are given this medicine because
it contains important information for you.

• Keep this leaflet. 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Etoposide Hikma is and what it is used for
2. What you need to know before being given Etoposide Hikma
3. How Etoposide Hikma is given
4. Possible side effects
5. How to store Etoposide Hikma
6. Contents of the pack and other information

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

This medicinal product contains the active substance etoposide. It 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 adult patients:

• testicular cancer
• small cell lung carcinoma
• blood cancer (acute myeloid leukaemia)
• lymphatic system tumour (Hodgkin's lymphoma, non-Hodgkin's lymphoma)
• reproductive system tumours (gestational trophoblastic neoplasia and ovarian tumour)

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

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

The exact reason why Etoposide Hikma has been prescribed for you should be discussed with your doctor.

2. What you need to know before using Etoposide Hikma

Do not use Etoposide Hikma

• if you are allergic to etoposide 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 breastfeeding or plan to breastfeed.
  If any of the above apply to you, or if you are unsure, consult your doctor for advice.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Etoposide Hikma:

• if you have low blood levels of a protein called albumin;
• if you have recently undergone chemotherapy or radiotherapy;
• if you have any infections;
• if you have liver or kidney problems.
  Effective cancer treatment can rapidly destroy large numbers of tumour cells. Very rarely, this may cause harmful amounts of substances released from these tumour cells to enter the bloodstream. In such cases, problems affecting the liver, kidneys, heart, or blood may occur, which could be fatal if not treated. To prevent this, your doctor will need to perform regular blood tests to monitor levels of these substances during treatment with this medicine.
  This medicine can reduce levels of certain blood cells, which may make you more prone to infections or cause your blood not to clot properly if you are cut. To ensure this does not happen, you will have blood tests before starting treatment and before each dose. If you have impaired liver or kidney function, your doctor may decide to carry out regular blood tests to monitor these levels.

Other medicines and Etoposide Hikma
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is particularly important:

• if you are taking medicines with a mechanism of action similar to Etoposide Hikma;
• if you have recently received live vaccines;
• if you are taking phenylbutazone, sodium salicylate, or aspirin;
• if you are taking warfarin (a medicine used to prevent blood clots);
• if you are taking phenytoin or any other medicine used to treat epilepsy;
• if you are taking anthracyclines (a group of medicines used in cancer treatment);
• if you are undergoing cisplatin therapy (a medicine used in cancer treatment);
• if you are taking a medicine called cyclosporine (a medicine used to reduce the activity of the immune system).

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Etoposide Hikma must not be used during pregnancy unless clearly indicated by your doctor.
You must not breastfeed while taking Etoposide Hikma.
Both male and female patients of reproductive age should use an effective method of contraception (e.g. barrier methods or condoms) during treatment and for at least 6 months after completion of treatment with Etoposide Hikma. Male patients treated with Etoposide Hikma are advised not to father a child during treatment and for 6 months after treatment. In addition, men are advised to seek advice about sperm preservation before starting treatment.
Male and female patients who are considering having children after treatment with Etoposide Hikma should discuss this with their doctor or nurse.

Driving and using machines
No studies on the effects on the ability to drive or use machines have been conducted. However, if you feel tired, have stomach discomfort, dizziness, or a sensation of lightheadedness, you should not drive or operate machinery until you have discussed this 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 contained in this preparation may affect children. These effects may include drowsiness and mood swings. It may also impair concentration and physical performance. The amount of alcohol in this medicine may affect your ability to drive or use machinery, as alcohol can impair judgment and reaction speed.
If you have epilepsy or liver problems, talk to 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, talk to your doctor or pharmacist before taking this medicine.
If you have alcohol dependence, talk to your doctor or pharmacist before taking this medicine.

Etoposide Hikma contains benzyl alcohol
This medicine contains 20 mg of benzyl alcohol per ml.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with the risk of serious adverse effects, including breathing problems (gasping syndrome) in young children.
Do not administer to neonates (up to 4 weeks of age) unless otherwise recommended by the doctor.
Do not use for more than one week in young children (under 3 years of age) unless otherwise recommended by the doctor or pharmacist.
Ask your doctor or pharmacist for advice if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such 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 may accumulate in the body and cause adverse effects (such as "metabolic acidosis").

Polysorbate 80
This medicine contains 80 mg of polysorbate 80 per ml.
Rarely, polysorbates may cause severe allergic reactions. If you experience difficulty breathing, swelling, or feel faint, seek immediate medical help.
Polysorbates may affect circulation and the heart (e.g. low blood pressure, changes in heart rhythm).
Ask your doctor or pharmacist for advice if you have liver disease. This is because polysorbates may affect the liver.

3. How to use Etoposide Hikma

Etoposide Hikma will always be administered to you by healthcare professionals. It will be given as a slow infusion into a vein. This may last from 30 to 60 minutes.
The dose you will receive is specific to you and will be calculated by your doctor. The usual dose, based on etoposide, is 50 to 100 mg/m² of body surface area daily for 5 consecutive days, or 100 to 120 mg/m² on days 1, 3, and 5.
This treatment cycle may then be repeated, depending on the results of blood tests, but not sooner than 21 days after the first treatment cycle.
For children being treated for blood or lymphatic system cancer, the dose used is 75 to 150 mg/m² of body surface area per day for 2 to 5 days.
Your doctor may sometimes prescribe a different dose, especially if you are receiving or have received other cancer treatments, or if you have kidney problems.
If you are given more Etoposide Hikma than you should
Since Etoposide Hikma is administered by a healthcare professional, overdose is unlikely. However, if it does occur, your doctor will treat any resulting symptoms.
If you have any doubts about how to use this medicine, consult 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, skin redness or rash. These could be signs of a severe allergic reaction.

Sometimes, when Etoposide Hikma has been taken together with other medicines used to treat cancer, serious liver, kidney or heart damage have been observed due to a condition called tumour lysis syndrome, caused by harmful amounts of substances released from tumour cells entering the bloodstream.

Possible side effects reported with Etoposide Hikma include:

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

• blood disorders (for this reason, blood tests will be performed between treatment cycles)
• nausea and vomiting
• loss of appetite
• abdominal pain
• constipation
• temporary hair loss
• liver damage (hepatotoxicity)
• increased liver enzymes
• changes in skin colour (pigmentation)
• jaundice (increased bilirubin)
• feeling of weakness (asthenia)
• general feeling of being unwell (malaise)

Common (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
• irritated lips, mouth or throat ulcers
• skin redness
• infection
• diarrhoea
• skin problems such as itching or irritation
• inflammation of a vein
• severe allergic reactions
• reactions at the infusion site

Uncommon (may affect up to 1 in 100 people)

• tingling or numbness in hands and feet
• bleeding

Rare (may affect up to 1 in 1,000 people)

• seizures (fits)
• drowsiness or fatigue
• altered sense of taste
• difficulty swallowing
• severe skin and/or mucosal reactions which may include painful blisters and fever, including extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• a sunburn-like irritation may occur on skin previously exposed to radiotherapy, and may be severe (radiation recall dermatitis)
• fever
• temporary blindness
• breathing problems
• acid reflux
• redness
• severe allergic reactions

Not known (frequency cannot be estimated from the available data)

• tumour lysis syndrome (complications due to substances released into the blood from tumour cells)
• swelling of the face and tongue
• infertility
• breathing difficulties

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 label or carton following EXP.
The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not refrigerate or freeze.
Store the vial in the original packaging to protect from light.
Chemical and physical stability of the diluted solution at a concentration of 0.2 mg/ml has been demonstrated in sodium chloride injection (0.9% w/v) and in glucose injection (5% w/v) for up to 24 hours at room temperature.
Chemical and physical stability of the diluted solution at a concentration of 0.4 mg/ml has been demonstrated in sodium chloride injection (0.9% w/v) and in glucose injection (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 you notice signs of precipitation or if visible particles are present.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. These measures will help protect the environment.

6. Pack contents and other information

What Etoposide Hikma contains
Etoposide Hikma contains the active substance etoposide.
Each 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 1000 mg of etoposide.
The other ingredients are: anhydrous citric acid, benzyl alcohol, polysorbate 80, polyethylene glycol, ethanol 96%.

Description of the appearance of Etoposide Hikma and pack contents
Etoposide Hikma is a clear solution for infusion, colourless to pale yellow.
Etoposide Hikma 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 Authorisation Holder and Manufacturer
Marketing Authorisation Holder
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 authorised in the European Economic Area Member States under the following names:

| Member State | Name of the medicinal product | |------------------|-----------------------------------| | Austria | Etoposide Hikma 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung | | Germany | Etoposide Hikma 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung | | France | Etoposide Hikma 20 mg/ml Solution à diluer pour perfusion | | Italy | Etoposide Hikma | | Netherlands | Etoposide Hikma 20 mg/ml, concentraat voor oplossing voor infusie | | Portugal | Etoposido Hikma | | Spain | Etopósido Hikma 20 mg/ml concentrado para solución para perfusión | | United Kingdom | Etoposide 20 mg/ml Concentrate for Solution for Infusion |

The following information is intended for healthcare professionals only:

Etoposide Hikma is administered by slow intravenous infusion (usually over 30–60 minutes) because 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 is 50–100 mg/m² daily on days 1 to 5 or 100–120 mg/m² administered on days 1, 3 and 5 every 3–4 weeks, in combination with other medicinal products indicated for the disease being treated.
The dose should be adjusted to account for the myelosuppressive effects of other medicinal products in the combination regimen or the effects of prior radiotherapy or chemotherapy, which may have compromised bone marrow reserve.
The required dose of etoposide should be diluted with either 5% glucose solution or 0.9% sodium chloride solution to achieve a concentration between 0.2 and 0.4 mg/ml of etoposide (i.e., 1 ml or 2 ml of concentrate in 100 ml of diluent to obtain a concentration of 0.2 mg/ml and 0.4 mg/ml, respectively).
Etoposide must not be mixed with other drugs when administered. It should not be mixed with any products other than those listed above.

Elderly
No dose adjustment is required in elderly patients (age > 65 years) unless based on renal function.

Paediatric use
Etoposide has been used in paediatric patients at doses ranging from 75 to 150 mg/m² daily for 2–5 days in combination with other antineoplastic agents. The treatment regimen should be selected according to local standard treatment protocols.

Renal impairment
In patients with impaired renal function, consider the following initial dose modifications based on measured creatinine clearance:

| Measured creatinine clearance | Etoposide dose | |-------------------------------|----------------| | >50 ml/min | 100% of dose | | 15–50 ml/min | 75% of dose |

In patients with creatinine clearance below 15 ml/min or undergoing dialysis, a further dose reduction is likely required, as etoposide clearance is further reduced in these patients.
Subsequent dosing in moderate to severe renal impairment should be based on patient tolerance and clinical response. Since etoposide and its metabolites are not dialysable, it may be administered before or after haemodialysis.

Instructions for use/handling
Proper procedures for handling and disposal of cytotoxic medicinal products must be followed.
Exercise caution when handling cytotoxic agents. Always take necessary precautions to prevent exposure. As with other potentially toxic compounds, care should be taken 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 designated area.
Precautions must be taken to avoid contact with skin and mucous membranes. Use of gloves is recommended. In case of accidental contact of etoposide with skin or mucous membranes, immediately wash the skin with soap and water and rinse mucous membranes with water.
Care should be taken to avoid extravasation.
If the solution shows signs of precipitation or contains visible particles, it must be discarded.
Any unused product or waste material must be disposed of in accordance with local requirements.

In-use shelf life after dilution:
Chemical and physical stability of the diluted solution at a concentration of 0.2 mg/ml has been demonstrated in 0.9% w/v sodium chloride injection and 5% w/v glucose injection for up to 24 hours at room temperature.
Chemical and physical stability of the diluted solution at a concentration of 0.4 mg/ml has been demonstrated in 0.9% w/v sodium chloride injection and 5% w/v glucose injection for up to 12 hours at room temperature.
From a microbiological standpoint, the product should be used immediately. If not used immediately, 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.

Storage
Do not store above 25°C.
Do not refrigerate or freeze.
Store vials in their original packaging to protect from light.
For storage conditions of the diluted solution, see section 6.3 of the Summary of Product Characteristics.