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Etoposide 20mg/ml Concentrate for Solution for Infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or nurse.

•    If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet j What Etoposide is and what it is used for

^ What you need to know before you use Etoposide ^ How to use Etoposide 4| Possible side effects ^1 How to store Etoposide 6| Contents of the pack and other information

Etoposide Concentrate for Solution for Infusion is given only by healthcare personnel, who can reply to any questions, which you may have after reading this package leaflet.

j What Etoposide is and what it is used for

The name of this medicine is Etoposide 20mg/ml Concentrate for Solution for Infusion. It contains the active ingredient etoposide. Etoposide belongs to a group of medicines known as podophyllotoxin derivatives and it slows or stops the growth of cancer cells.

Etoposide is used to treat certain types of cancers in combination with other chemotherapeutic agents.

This medicine is used for the treatment of testicular cancer, lung cancer and certain cases of leukemia (blood cancer).

^ What you need to know before you use Etoposide

Do not receive Etoposide:

•    if you are allergic to etoposide, podophyllotoxins or podophyllotoxin-derivatives or any of the other ingredients of this medicine (listed in section 6)

•    if you need to have a vaccine for 'yellow fever' or other live vaccines.

This medicine should only be given to you as an infusion into a vein.

Warnings and precautions

Talk to your doctor or nurse:

•    if you experience any symptoms that might indicate allergic reactions, such as fever, difficulty breathing, chills, rapid heart beat and low blood pressure.

•    if you notice any reactions at the injection site. Inform your doctor or nurse right away, as the infusion might need to be stopped.

•    if you are receiving, or did receive in the past, radiation therapy.

•    if you are suffering from infections.

•    if you have problems with your liver.

•    if you have severe kidney problems.

Tell your doctor about any other treatment you receive for your illness.

Your doctor will need to do regular blood tests during treatment with Etoposide in order to monitor your blood composition.

Children and adolescents

Safety and effectiveness in children and adolescents have not been established. Therefore etoposide is not recommended for use in this age group.

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Other medicines and Etoposide

Tell your doctor if you are taking, have recently taken or might take any other medicines. In particular you should tell your doctor if you are taking any of the following:

•    anti-coagulants such as warfarin which are used to thin the blood

•    the analgesic (pain killing) and fever lowering medicines phenylbutazone, aspirin and aspirin related medicines (sodium salicylate or salicylic acid)

•    the immunosuppressant ciclosporin (often given after an organ transplant)

•    cisplatin (used to treat cancer)

•    phenytoin (a medicine for epilepsy)

•    vaccines for 'yellow fever' or other live vaccines.

Etoposide can also have effects on other medicines used to treat cancer. Your doctor will take these effects into account when deciding on your treatment.

Etoposide with food and drink

Etoposide is not affected by food or drink.

Pregnancy, breast-feeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you begin to use, or are administered Etoposide.

Women of child bearing age must avoid pregnancy and take effective contraceptive measures during treatment and until at the earliest 6 months after therapy with etopside.

Fathering children whilst taking Etoposide

Men should not father a child whilst being treated with Etoposide and until 6 months after treatment has finished.

It is adviced for men to consider sperm collection (for cryo-conservation) before treatment with etoposide, because infertility after treatment can occur.

Driving and using machines

This medication can cause tiredness and sleepiness. Precaution is advised in undertaking actions which require extra alertness, such as the use of machines and driving.

Etoposide contains ethanol

19.5% ethanol (alcohol) i.e. up to 0.79g per vial. This may be dangerous for patients suffering from alcoholism and for patients in high-risk groups such as those with liver problems or epilepsy (fits). The amount of alcohol in this product may alter the effects of other medicines.

How to use Etoposide

Etoposide Concentrate for Solution for Infusion will always be given to you by a healthcare professional.

This medicine will be diluted with 0.9% sodium chloride or 5% glucose and will be given to you as an infusion (a "drip") into a vein.

Dosage and method of administration

•    The dose of Etoposide will be individually determined by your doctor. The dose you are given depends on your size, i.e. it varies with your surface area. Technically, this is measured in square metres, and is worked out from your height and weight.

•    The recommended dose of etoposide is 60-120mg/m² daily for 3-5 days.

•    You will receive a treatment cycle consisting of one dose a day during 3-5 days, followed by a 10-20 days rest.

•    The administration will take at least 30 to 60 minutes.

•    Usually three or four treatment cycles are given, but the duration of the treatment and the number of treatment is determined by the doctor and may vary for each patient.

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Etoposide 20mg/ml Concentrate for Solution for Infusion

The following information is intended for healthcare professionals only:

For single use only.

Refer to local cytotoxic guidelines.

Like with all anti-neoplastic products caution is needed with the processing of etoposide. Dilution should take place under aseptic conditions in a safety box, by trained personnel in an area specifically intended for this, and protective coats and gloves should be used. If no safety box is available, the equipment should be supplemented with a mask and protective glasses. Precautions should be taken to avoid contact with the skin and mucous membranes. Accidental contact with the skin or eyes or mucous membranes should be treated immediately with copious amounts of water.

In the event of spillage, operators should put on gloves and mop up the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and seal it.

Pregnant women must avoid contact with cytostatic drugs.

Bodily waste matter and vomit should be disposed with care.

If the solution is cloudy or a deposit that does not dissolve is noticed, the bottle should be discarded.

A damaged bottle must be regarded and treated with the same precautions as contaminated waste.

Contaminated waste must be stored in waste containers specifically marked for this. See section "Disposal".

Preparation of the intravenous administration

Dilution

Etoposide 20mg/ml Concentrate for Solution for Infusion must be diluted immediately prior to use with either 5% glucose or 0.9% sodium chloride solution to give a final concentration of 0.2 to 0.4mg/ml, usually not more than 0.25mg/ml. At higher concentrations precipitation of etoposide may occur.

Etoposide needs to be diluted with volumes ranging from 250-1,000ml, based on the individual dosage. Care should be taken not to exceed the final concentration of 0.4mg/ml.

Solutions showing any signs of precipitation should not be used.

•    Etoposide is given in combination with other medicines.

•    Your condition will be closely monitored during treatment. This routinely involves blood tests and controls of your liver function.

•    Your dose may be changed depending on your kidney function.

If you have any questions about your treatment schedule ask your doctor or nurse.

If you receive more Etoposide than you should

As a doctor or nurse will be giving you your medicine, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any concerns about the amount of medicine that you receive.

If you forget to take Etoposide

If you have missed a dose of your treatment, consult your doctor or a nurse.

4| Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.You should discuss them with your doctor who will explain the risks and benefits of your treatment. Some of the side effects can be lessened or treated by other medicines or therapy.

Tell your doctor immediately if you notice any of the following:

Common (may affect up to 1 in 10 people)

•    Severe allergic reactions such as fever, reddening of the face and neck, often with a sudden, subjective feeling of heat (flushing), rapid heartbeat, abnormal contraction of your lungs which can cause a cough and wheezing, abnormally low blood pressure and difficulty breathing.

Other side effects:

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

•    bone marrow suppression which results in changes in the number of white and red blood cells (anaemia, leukopenia, neutropenia) and platelets (thrombocytopenia). This will be monitored by your doctor during your treatment with regular blood tests

•    liver damage. Your doctor will monitor your liver function with blood tests during your treatment

•    abdominal pain

•    constipation

•    nausea

•    vomiting

•    loss of appetite

•    reversible loss of hair (alopecia)

•    darkening of skin (increase in pigmentation)

•    a feeling of weakness or general discomfort

•    feeling of tiredness due to anaemia

Common (may affect up to 1 in 10 people)

•    leukaemia (cancer of the blood)

•    heart attack (myocardial infarction)

•    irregular heartbeat

•    dizziness

•    rash, hives, itching

•    abnormally high blood pressure

•    low blood pressure causing dizziness when Etoposide is administered too quickly

•    diarrhoea

•    inflammation of the mucous membrane of the mouth and gullet

•    leakage of the medicine into the surrounding tissues (extravasation) with symptoms such as pain, irritation and swelling

•    inflammation of a vein

Uncommon (may affect up to 1 in 100 people)

•    damage to nerves of the hand and feet

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

•    convulsions (fits)

•    tiredness and drowsiness

•    reversible loss of vision

•    inflammation of the optic nerve with complete or partial loss of vision

•    inflammation of the tissue in the lungs

•    formation of scar tissue in the lungs

•    difficulty in swallowing

•    taste impairment

•    a potentially life-threatening skin disorder accompanied by severe skin blisters and often sores in the membrains of the mouth, nose, eyes and the anal and gential areas (Stevens-Johnson syndrome, toxic epidermal necrolysis)

•    a sunburn-like rash that may occur on skin that has previously been exposed to radiotherapy and can be severe (radiation recall dermatitis)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard

How to store Etoposide

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial and the outer carton after 'Exp' The expiry date refers to the last day of that month.

Do not store above 25°C. Do not refrigerate or freeze.

Keep the vial in the outer carton in order to protect from light.

If the solution is cloudy or a deposit that does not dissolve is noticed, the bottle should be discarded.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

After dilution:

Chemical and physical in-use stability has been demonstrated the diluted solution 0.2mg etoposide/ ml for 96 hours and for the diluted solution 0.4mg etoposide/ml for 24 hours at 25°C, without any special protection from light.

From a microbiological point of view, the product should be used immediately.

q Contents of the pack and other information

What Etoposide contains

•    The active substance is etoposide. 1ml of concentrate for solution for infusion contains 20mg of etoposide. One vial of 5ml concentrate for solution for infusion contains 100mg etoposide.

•    The other ingredients are macrogol 400, polysorbate 80, ethanol anhydrous and citric acid, anhydrous (for pH adjustment).

What Etoposide looks like and contents of the pack

Etoposide is a clear, pale yellow concentrate for solution for infusion, slightly viscous, free from visible particles in glass injection vials. Etoposide is contained in 8ml Type I colourless glass vial with bromobutyl rubber stop and sealed with aluminium metallic cap with flip off. One vial of 5ml of concentrate for solution for infusion contains 100mg etoposide.

Pack sizes: 1 or 10 vials per carton Vial is packed with a protective plastic overwrap.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Actavis Group PTC ehf. Reykjavikurvegi 76-78 220 HafnarfjorSur Iceland

Manufacturer

S.C. Sindan- Pharma S.R.L 11 Ion Mihalache Blvd 011171 Bucharest Romania

This leaflet was last revised in November 2014.

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Administration

The usual dose of etoposide, in combination with other approved chemotherapeutic agents, ranges from 60-120mg/m²/day for 3-5 days. Chemotherapy courses are repeated at 2 to 4 week intervals after adequate recovery from any toxicity.

Overall, a dosage schedule of 100mg/ m²/day on days 1 through 5 or 120mg/ m²/day on days 1,3, and 5 is used most frequently.

Generally 3 to 4 chemotherapy cycles are administered. Dose and amount of cycles should be adjusted to the level of bone marrow suppression and the reaction of the tumour.

In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance.

Subsequent dosing should be based on patient tolerance and clinical effect. Data are not available in patients with creatinine clearance <15ml/min and further dose reductions should be considered in these patients.

Etoposide is intended for slow intravenous infusion only. Etoposide must not be given by rapid intravenous injection.

^actavis

Actavis, Barnstaple, EX32 8NS, UK

To prevent the occurrence of hypotension, the infusion should be given over a 30 to 60 minute period. Longer infusion times may be required based on patient tolerance.

The intravenous solution is suitable for infusion only in glass and PVC containers.

Always look at the injection before use. Only a clear solution, free from particles should be administered.

Disposal

All materials that have been used for the preparation and administration, or which have been in contact with etoposide in any way, must be disposed of according to local cytotoxic guidelines.

Remnants of the medicinal products as well as all materials that have been used for dilution and administration must be destroyed according to hospital standard procedures applicable to cytotoxic agents and in accordance with local requirements related to the disposal of hazardous waste.

^actavis

Actavis, Barnstaple, EX32 8NS, UK