Etoposide Accord

PACKAGE LEAFLET: INFORMATION FOR THE USER

Etoposide Accord 20 mg/ml Concentrate for Solution for Infusion

Equivalent medicine
Please read this leaflet carefully before taking 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

This medicinal product contains the active substance etoposide. This medicine belongs to a group of medicines
called cytostatics, which are used in the treatment of cancer.
Etoposide Accord is used in the treatment of certain types of tumours in adults:

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

Etoposide Accord is used in the treatment of certain types of tumours in children:

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

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

2. What you need to know before taking Etoposide Accord

Do not take Etoposide Accord

• 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 planning to breastfeed.

If you experience any of the above effects, or are unsure, inform your doctor who will be able to give you
advice.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before receiving Etoposide Accord:

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

Effective cancer treatment can rapidly destroy large numbers of tumour cells. In rare cases,
this may cause harmful amounts of substances to be released from these cancer cells into the blood. If this occurs, it may cause
problems with the liver, kidneys, heart or blood, which could be fatal if not treated.
To prevent this, your doctor may need to carry out regular blood tests to monitor the levels
of these substances during treatment with this medicine.
This medicine can cause a reduction in the levels of certain blood cells, which may lead to infections or
cause blood not to clot properly in case of injury. Blood tests will be performed
at the beginning of treatment and after each dose you receive to ensure this is not occurring.
If you have reduced liver or kidney function, your doctor may wish to carry out regular blood tests to monitor
these levels.
Other medicines and Etoposide Accord
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.
This is especially important:

• if you are taking medicines with a similar mechanism of action to Etoposide Accord.
• if you have recently received any live vaccine.
• 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 any anthracyclines (a group of medicines used to treat cancer).
• if you are about to be treated with cisplatin (a medicine used to treat cancer).
• if you are taking a medicine called cyclosporine (a drug used to reduce the activity of the immune system).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult
your doctor or pharmacist before using this medicine.
Etoposide must not be used during pregnancy unless clearly indicated by your doctor. You must not
breastfeed while receiving Etoposide Accord.
Both male and female patients of reproductive age must use an effective contraceptive method (e.g. a barrier method or condom) during treatment and for at least 6 months after completion of treatment with Etoposide Accord. Male patients receiving Etoposide Accord are advised not to father a child during and for up to six months after treatment. In addition, men are advised to preserve sperm before starting treatment.
Male and female patients considering having children after treatment with Etoposide Accord
should discuss this with their doctor or nurse.
Driving and using machines
No studies have been conducted on the effect on the ability to drive or operate machinery. However, if you feel tired,
nauseous, dizzy or lightheaded, you should not drive or operate machinery until you have discussed this with your doctor.
Etoposide Accord contains alcohol
This medicine contains 30.5% alcohol (ethanol), equivalent to 240.64 mg of ethanol per ml of concentrate,
i.e. 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 may be harmful for patients suffering from
alcoholism, brain damage, pregnant women, breastfeeding women, children and high-risk groups such as patients with liver disease or epilepsy. The effect of other medicines may be reduced or increased.
Etoposide Accord contains benzyl alcohol
Etoposide Accord contains 30 mg/ml of benzyl alcohol.
Benzyl alcohol has been associated with the risk of serious adverse reactions including breathing problems (called
“gasping syndrome”) in young children. It must not be administered to neonates (up to 4 weeks of age) or used for more than one week in young children (under 3 years of age), unless recommended by a doctor.
Consult your doctor or pharmacist if you are pregnant or breastfeeding or if you have liver or kidney disease. This
is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (called “metabolic
acidosis”).
Benzyl alcohol may cause allergic reactions.
Etoposide Accord contains Polysorbate 80
Etoposide Accord contains 80 mg/ml of Polysorbate 80.
In neonates, a life-threatening syndrome of liver and kidney failure, reduced respiratory function, decreased platelet count and abdominal swelling has been associated with administration of injectable vitamin E products containing Polysorbate 80.

3. How to use Etoposide Accord

Etoposide Accord will always be administered to you exclusively by a healthcare professional. It will be given as a slow intravenous infusion. This will take between 30 and 60 minutes.
The dose, which your doctor will calculate, is specific to you. The usual dose is between 50 and 100 mg/m2 of body surface area per day 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 then be repeated, depending on the results of blood tests, but not sooner than 21 days after the first treatment cycle.
For children treated for blood cancer or lymphatic system cancer, the dose used is between 75–150 mg/m2 of body surface area per day for 2–5 days.
Your doctor may sometimes prescribe a different dose, particularly if you are receiving, or have received, other cancer treatments, or if you have kidney problems.
If you have been given more Etoposide Accord than you should
Since this medicine is administered by healthcare professionals, overdose is unlikely. However, if this occurs, your doctor will treat any symptoms that may follow.
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 everyone will experience them.
Immediately tell your doctor or nurse if you notice any of the following symptoms: swelling of the tongue or
throat, difficulty breathing, rapid heartbeat, skin redness or rash. These may be signs of a severe allergic
reaction.
Severe liver, kidney or heart damage have occasionally been reported due to a condition called tumour lysis syndrome, caused by dangerous levels of substances released from tumour cells into the bloodstream, when Etoposide Accord is taken together with other cancer-treating medicines.

Possible side effects experienced with Etoposide Accord 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 (hepatic toxicity),
• increased liver enzymes,
• change in skin colour (pigmentation),
• jaundice (increased bilirubin),
• feeling weak (asthenia),
• feeling unwell.

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,
• lip sores, mouth or throat ulcers,
• skin redness,
• infection,
• diarrhoea,
• skin problems such as itching or rash,
• inflammation of the veins,
• 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,
• drowsiness or fatigue,
• change in taste,
• difficulty swallowing,
• severe skin and/or mucosal reactions including painful blisters and fever, with extensive skin detachment (Stevens-Johnson syndrome and toxic epidermal necrolysis),
• rash-like sunburn that may affect skin previously exposed to radiotherapy and which may be severe (radiation recall dermatitis),
• fever,
• temporary blindness,
• breathing problems,
• acid reflux,
• flushing.

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

• tumour lysis syndrome (complications from substances released by treated tumour cells entering the bloodstream),
• swelling of the face and tongue,
• infertility,
• breathing difficulty,
• acute kidney failure.

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

5. How to store Etoposide Accord

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 after EXP. The expiry date refers to the last day of that month.
Keep the vial in its outer packaging to protect it from light.
Do not refrigerate or freeze.
Chemical and physical in-use stability of the diluted solution has been demonstrated for up to 96 hours at concentrations of 0.2 mg/ml and up to 48 hours at concentrations of 0.4 mg/ml when diluted with either a 0.9% p/v sodium chloride injection solution or a 5% p/v glucose injection solution, respectively, stored at 20°–25°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user. Do not store the diluted product in a refrigerator (2–8°C), as this may cause precipitation.
Do not use Etoposide Accord if you notice any signs of precipitation or if the solution contains visible particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Etoposide Accord contains:
Etoposide Accord contains the active substance 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 12.5 ml vial contains 250 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 components are anhydrous citric acid, benzyl alcohol, polysorbate 80, Macrogol 300 and anhydrous ethanol.

Description of the appearance of Etoposide Accord and contents of the pack:
Etoposide Accord is a clear, colourless or pale yellow infusion solution.
Pack 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 pack sizes may be marketed.

Marketing Authorization Holder:
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer:
Accord Healthcare Polska Sp.z.o.o.,
ul. Lutomierska 50,
95-200 Pabianice,
Poland

This leaflet was last approved on:
The following information is intended exclusively for medical and healthcare professionals.

Administration and Dosage
Etoposide Accord 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 following rapid intravenous injection.
Etoposide Accord MUST NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.

The recommended dose of etoposide is 50–100 mg/m²/day on days 1 to 5 or 100–120 mg/m² on days 1, 3 and 5 every 3–4 weeks, in combination with other drugs indicated for the disease being treated. The dose should be adjusted considering the myelosuppressive effects of concomitant drugs or the effects of prior radiotherapy or chemotherapy that may have compromised bone marrow reserve.

The required dose of etoposide must be diluted in 5% w/v glucose solution or 0.9% w/v sodium chloride solution to achieve a final concentration of 0.2–0.4 mg/ml of etoposide (i.e. 1 ml 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). The concentration of the diluted product must not exceed 0.4 mg/ml due to the risk of precipitation. A strict aseptic technique must be used during preparation and dilution.

Etoposide must not be mixed with other medicinal products during administration. This medicinal product must not be mixed with other medicinal products except those mentioned above.

Elderly
No dosage adjustment is required in elderly patients (age > 65 years) other than that based on renal function.

Paediatric use
Etoposide in paediatric patients should be used at a dose of 75 to 150 mg/m²/day for 2–5 days in combination with other antineoplastic agents. The treatment regimen should be selected according to local standard of care.

Renal impairment
In patients with impaired renal function, the following initial dose adjustments should be considered based on creatinine clearance values.

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 and those on dialysis, a further dose reduction is likely necessary, as etoposide clearance is further reduced in these patients. Subsequent dosing in cases of moderate and 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
Follow procedures for the correct handling and disposal of cytotoxic medicinal products.
Care must be taken when handling cytostatic agents. Appropriate protective measures should always be adopted to prevent exposure. As with other potentially toxic substances, care should be taken during handling and preparation of etoposide solution. Skin reactions may occur following accidental exposure. Use of gloves is recommended.

If etoposide comes into contact with skin or mucous membranes, wash the skin immediately with soap and water and rinse mucous membranes with water.

Take care to avoid spillage.

If the solution shows signs of precipitation or contains visible particles, it must be discarded.

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

Stability after dilution:
Chemical and physical in-use stability of the diluted solution at concentrations of 0.2 mg/ml and 0.4 mg/ml has been demonstrated in 0.9% w/v sodium chloride injection and 5% w/v glucose injection, respectively, for up to 96 hours and 48 hours at a temperature of 20–25°C. From a microbiological standpoint, the diluted product should be used immediately. If not used immediately, the user is responsible for the duration and conditions of storage prior to use. Do not store the diluted product in the refrigerator (2–8°C), as precipitation may occur.

Storage
Keep the vial in the outer packaging to protect the medicine from light.
Do not refrigerate or freeze.