Etoposide accord

Package leaflet: Information for the user

Etoposide Accord, 20 mg/ml, concentrate for solution for infusion
Etoposidum
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Table of contents:

1. What Etoposide Accord is and what it is used for
2. Important information before using 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 medicine contains the active substance etoposide. It 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 cancer in adults, including:

• Testicular cancer;
• Small cell lung cancer;
• Blood cancer (acute myeloid leukaemia);
• Lymphatic system tumours (Hodgkin's lymphoma, non-Hodgkin's lymphoma);
• Reproductive system cancer (gestational trophoblastic disease and ovarian cancer).

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

• Blood cancer (acute myeloid leukaemia);
• Lymphatic system tumours (Hodgkin's lymphoma, non-Hodgkin's lymphoma).

The exact reason why Etoposide Accord has been prescribed should be discussed with your doctor.

2. Important information before using Etoposide Accord
When not to use Etoposide Accord

• If you are allergic to etoposide or any of the other ingredients of this medicine (listed in section 6);
• If you have recently been vaccinated, including with 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.

Warnings and precautions
Before starting treatment with Etoposide Accord, discuss this with your doctor, pharmacist or nurse.
Exercise caution:

• If you have low levels of proteins called albumin in your blood;
• If you have recently undergone radiotherapy or chemotherapy;
• If you have an infection, it should be treated before administration of Etoposide Accord;
• If you have kidney or liver disease.

Effective anticancer treatment may rapidly destroy large numbers of cancer cells. In very rare cases, this may lead to the release of harmful amounts of substances from cancer cells into the bloodstream. As a result, liver, kidney, heart or blood function disorders may occur, which may be fatal if not treated.
To prevent this, your doctor will need to perform regular blood tests to monitor the levels of these substances during treatment.
This medicine may reduce the number of certain blood cells, which may increase the risk of infections or cause poor blood clotting in case of injury. To ensure this does not happen, blood tests will be performed at the beginning of treatment and before each dose of the medicine.
If liver or kidney function is impaired, your doctor may also order regular blood tests to monitor these functions.

Etoposide Accord and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
This is particularly important in the following cases:

• Concomitant use of other medicines with a similar mechanism of action to Etoposide Accord;
• Recent vaccination with a live vaccine;
• Concomitant use of phenylbutazone, sodium salicylate or acetylsalicylic acid (aspirin);
• Concomitant use of warfarin (a medicine used to prevent blood clots);
• Concomitant use of phenytoin or any other antiepileptic medicine;
• Concomitant use of anthracyclines (a group of medicines used in cancer treatment);
• Treatment with cisplatin (a medicine used in cancer treatment);
• Concomitant use of a medicine called cyclosporine (a medicine used to suppress the immune system).

Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child, consult your doctor or pharmacist before using this medicine.
Etoposide Accord must not be used during pregnancy unless clearly prescribed by a doctor.
Breastfeeding is not allowed during treatment with Etoposide Accord.
Both women and men capable of having children should use effective contraception (e.g. a barrier method or condoms) during treatment and for at least 6 months after treatment with Etoposide Accord has ended. Men treated with Etoposide Accord should not father children during treatment and for up to 6 months after its completion. In addition, men should consult their doctor about sperm preservation before starting treatment.
Women and men considering having children after completing treatment with Etoposide Accord should discuss this with their doctor or nurse.

Driving and using machines
No studies on the effect of the medicine on the ability to drive and use machines have been conducted.
If you experience fatigue, nausea or dizziness, do 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 mg ethanol in a 5 ml vial (equivalent to 30 ml of beer or 12.55 ml of wine), and up to 3 mg ethanol in a 12.5 ml vial (equivalent to 75 ml of beer or 31.4 ml of wine). This is harmful for patients with alcoholism, brain damage, pregnant women, breastfeeding women, children, and patients at risk, such as those with liver disease or epilepsy.
In addition, the effects of other medicines may be enhanced or reduced.

Etoposide Accord contains benzyl alcohol
This medicine contains benzyl alcohol at a concentration of 30 mg/ml. Administration of benzyl alcohol to small children carries a risk of severe adverse effects, including breathing disorders (so-called "gasping syndrome"). The medicine must not be given to newborns (up to 4 weeks of age) and should not be used for longer than one week in small children (under 3 years of age) without medical advice.
In case of pregnancy, breastfeeding, or liver or kidney disease, consult your doctor or pharmacist before using this medicine, as large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (so-called "metabolic acidosis").
Benzyl alcohol may cause allergic reactions.

Etoposide Accord contains polysorbate 80
This medicine contains polysorbate 80 at a concentration of 80 mg/ml.
In preterm infants who received an injection of vitamin E containing polysorbate 80, a life-threatening syndrome with liver and kidney failure, reduced respiratory function, low platelet count and abdominal distension has been reported.

3. How to use Etoposide Accord

Etoposide Accord must be administered only by qualified medical personnel.
The medicine is given by slow intravenous infusion, which may take from 30 to 60 minutes.
The dose will be calculated by the doctor for each individual case. The typical dose, expressed as the amount of etoposide, is 50 to 100 mg/m^2 of body surface area, daily for 5 consecutive days, or 100 to 120 mg/m^2 on days 1, 3, and 5. This treatment cycle may be repeated depending on blood test results, but not earlier than 21 days after completion of the first cycle.
In children treated for blood cancer or lymphatic system cancer, the dose used is 75 to 150 mg/m^2 of body surface area, daily for 2 to 5 days.
Sometimes the doctor may prescribe a different dose, especially if the patient is currently receiving or has previously received another type of cancer treatment, or if there are kidney problems.
Use of more Etoposide Accord than prescribed
Since the medicine is administered by qualified medical personnel, overdose is unlikely. However, if it occurs, the doctor will treat any resulting symptoms.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in every patient.
You must immediately inform the doctor or nurse if the patient experiences any of the following symptoms:
swelling of the tongue or throat, difficulty breathing, rapid heartbeat, skin rash or hives. These may be signs of a severe allergic reaction.
Severe liver, kidney or heart damage due to a complication known as tumour lysis syndrome, caused by the release into the bloodstream of harmful amounts of substances from cancer cells, has been observed occasionally when Etoposide Accord was administered together with other anticancer medicines.
Other adverse reactions occurring during treatment with Etoposide Accord include:
Very common (may affect more than 1 in 10 patients):

• 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 enzyme activity;
• Changes in skin colour (pigmentation);
• Jaundice (elevated bilirubin levels);
• Weakness (asthenia);
• General malaise.

Common (may affect up to 1 in 10 patients):

• Acute leukaemia (a serious blood cancer);
• Arrhythmia (irregular heartbeat) and myocardial infarction;
• Dizziness;
• High blood pressure;
• Low blood pressure;
• Cold sores, herpes stomatitis, throat ulceration;
• Skin redness;
• Infection (including infections observed in patients with weakened immune systems, e.g. pneumonia caused by Pneumocystis jirovecii);
• Diarrhoea;
• Skin irritation, such as itching or rash;
• Phlebitis;
• Severe allergic reactions;
• Reactions at the site of administration.

Uncommon (may affect up to 1 in 100 patients):

• Peripheral neuropathy (numbness or weakness in hands and feet);
• Bleeding.

Rare (may affect up to 1 in 1,000 patients):

• Seizures (epileptic fits);
• Feeling of fatigue, drowsiness;
• Taste disturbances;
• Difficulty swallowing;
• Severe skin and/or mucous membrane reactions, including painful blisters and fever, as well as detachment of large areas of the epidermis (Stevens-Johnson syndrome or toxic epidermal necrolysis);
• Sunburn-like rash, sometimes severe, which may occur on skin previously exposed to radiotherapy (radiation dermatitis);
• Fever;
• Transient blindness;
• Breathing difficulties;
• Gastro-oesophageal reflux;
• Hot flushes.

Frequency not known (cannot be estimated from available data):

• Tumour lysis syndrome (a complication resulting from the release into the bloodstream of substances from treated cancer cells);
• Swelling of the face and tongue;
• Infertility;
• Breathing difficulties;
• Acute kidney failure.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the 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 carton and vial after EXP.
The expiry date refers to the last day of the stated month.
Store the vials in the original packaging to protect from light.
Do not store in a refrigerator. Do not freeze.
Physico-chemical stability has been demonstrated for diluted solutions at concentrations of 0.2 mg/ml and 0.4 mg/ml
in sodium chloride injection (0.9% w/v) and glucose injection (5% w/v)
for periods of 96 and 48 hours, respectively, at 20–25°C.
From a microbiological point of view, the medicine should be used immediately. If the medicine is not used
immediately, the user is responsible for the storage conditions and duration after preparation.
Do not store the diluted solution in a refrigerator (2–8°C) due to the risk of precipitation.
Do not use this medicine if you notice that a precipitate has formed in the solution or if it contains visible
particles.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Etoposide Accord contains
The active substance is etoposide.
1 ml of solution 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 ingredients are: anhydrous citric acid, benzyl alcohol, polysorbate 80, macrogol 300 and anhydrous ethanol.

What Etoposide Accord looks like and contents of the pack
The medicine is a clear, colourless to pale yellow solution for injection or infusion.
Available 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 Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer:
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland
Accord Healthcare Single Member S.A.
64th Km National Road Athens, Lamia, 32009
Greece

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Information exclusively for medical professionals or healthcare personnel:
Administration and dosage

Etoposide Accord is administered by slow intravenous infusion (usually over 30 to 60 minutes); cases of sudden drop in blood pressure have been reported following rapid injection. ETOPORIDE ACCORD MUST NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.

The recommended dose of Etoposide Accord is 50 to 100 mg/m²/day (in etoposide equivalents) on days 1 to 5, or 100 to 120 mg/m²/day on days 1, 3, and 5, repeated every 3 to 4 weeks, in combination with other drugs indicated for the treatment of the disease being treated. Dose adjustments should be made considering the myelosuppressive effects of other concomitantly administered drugs, or prior radiotherapy or chemotherapy, which may have reduced bone marrow reserves.

To achieve a final etoposide concentration of 0.2–0.4 mg/mL, dilute the dose with 5% glucose solution or 0.9% sodium chloride solution (i.e., dilute 1 mL or 2 mL of concentrate with 100 mL of diluent to obtain concentrations of 0.2 mg/mL and 0.4 mg/mL, respectively). The concentration of the prepared solution must not exceed 0.4 mg/mL due to the risk of precipitation. Aseptic conditions must be maintained during reconstitution and solution preparation. Etoposide Accord must not be mixed with other drugs during administration. The prepared solution must not be mixed with any solutions other than those specified above.

Elderly patients
In elderly patients (>65 years of age), dose adjustment based on age is not required; however, dose adjustments should be considered based on renal function.

Use in children
Etoposide Accord has been used in pediatric patients at doses of 75 to 150 mg/m²/day (in etoposide equivalents) for 2 to 5 days, in combination with other antineoplastic agents. For appropriate treatment regimens, current specialist protocols and guidelines should be consulted.

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

| Creatinine clearance (mL/min) | 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 in patients undergoing dialysis, further dose reduction should be considered. Subsequent doses should be adjusted based on patient tolerance and clinical response. Since etoposide and its metabolites are not removed by dialysis, the drug may be administered either before or after hemodialysis.

Instructions for administration and preparation
Standard procedures for safe handling and disposal of cytotoxic anticancer drugs must be followed.

All procedures related to the preparation of Etoposide Accord solution must comply with requirements for handling cytotoxic drugs. Precautions must be taken to prevent exposure to the drug.

As with other potentially toxic compounds, caution must be exercised when handling and preparing the Etoposide Accord solution. Accidental exposure may cause skin reactions. The use of protective gloves is recommended. In case of contact with skin or mucous membranes, wash the skin immediately with soap and water, and rinse mucous membranes with water.

Care must be taken to avoid extravasation.

If precipitation occurs or visible particles are present, the prepared solution must be discarded.

Any unused portions or waste material must be disposed of in accordance with local regulations.

In-use shelf life after dilution:
Physicochemical stability of diluted solutions at concentrations of 0.2 mg/mL and 0.4 mg/mL in 0.9% w/v sodium chloride injection and 5% w/v glucose injection has been demonstrated for 96 and 48 hours, respectively, at 20–25°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions after preparation. Do not store the diluted solution in the refrigerator (2–8°C) due to the risk of precipitation.

Storage conditions:
Store vials in the original packaging to protect from light.
Do not store in the refrigerator; do not freeze.