Document: document 1 change

• document 0
• document 1

---

PATIENT INFORMATION LEAFLET

Epirubicin Hydrochloride 2 mg/ml Injection

In this leaflet:

1.    What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

2.    Before you use Epirubicin Hydrochloride Injection

3.    How to use Epirubicin Hydrochloride Injection

4.    Possible side effects

5.    How to store Epirubicin Hydrochloride    Injection

6.    Further information

What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

Epirubicin Hydrochloride Injection is an anti-cancer medicine. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Epirubicin hydrochloride is used to treat a variety of cancers, either alone or in combination with other medicines. The way in which it is used depends upon the type of cancer that is being treated. It is useful in treating the following conditions:

•    Breast cancer

•    Advanced ovarian cancer

•    Stomach cancer

•    Lung cancer.

Epirubicin is also used to help prevent recurrence of bladder cancer after surgery.

2. Before you use Epirubicin Hydrochloride Injection

Epirubicin Hydrochloride Injection should not be used:

•    if you have shown signs of hypersensitivity (severe allergy) to epirubicin hydrochloride or similar medicines on previous occasions

•    if you have fewer blood cells than normal (your doctor will check this)

•    if you have been treated with high doses of some other anti-cancer medicines including doxorubicin and daunorubicin which belong to the same group of medicines as epirubicin (called anthracyclines). They have similar side effects (including those effects on the heart).

•    if you have suffered or currently have problems with your heart

•    if you have severe liver problems

•    if you are pregnant or breast-feeding

•    if you have a severe infection

When administered intravesically (directly into the bladder), Epirubicin should not be used:

• if your tumour penetrates the bladder wall

• if you have a urine infection

• if you have pain or inflammation in your bladder

• if your doctor has problems inserting a catheter (tube) into your bladder

• if there is a large volume of urine left in your bladder after you attempt to empty it.

Special care will be taken:

•    to ensure the number of cells in your blood does not drop too low. Your doctor will regularly check this.

• if you are experiencing severe inflammation or ulcers in your mouth

•    to check the level of uric acid in your blood. Your doctor will check this.

• if you have liver disease

• if you have kidney disease

•    to ensure your heart is working properly. Your doctor will regularly check this.

• if you have received or are receiving radiotherapy to the chest area.

• if you are planning to start a family, whether you are male or female

Taking/ using other medicines:

Special care is needed if you are taking/ using other medicines as some could interact with epirubicin. These medicines include:

•    other medicines that may affect your heart for example; calcium channel blockers (e.g. verapamil, nifedipine and diltiazem), other cancer treatments such as doxorubicin, mitomycin-C, dacarbazine, dactinomycin and possibly cyclophosphamide and radiotherapy

•    other medicines that may affect your liver e.g. barbiturates (medicines used in epilepsy or sleep disorders) and rifampicin (a medicine used to treat TB)

•    trastuzumab; epirubicin should not be taken within 24 weeks of taking trastuzumab

•    cimetidine (a medicine used to reduce the acid in your stomach)

•    paclitaxel and docetaxel (medicines used in some cancers)

•    interferon alfa-2b (a medicine used in some cancers and lymphomas and for some forms of hepatitis)

•    quinine (medicine used for treatment of malaria and for leg cramps)

•    dexrazoxane (a medicine sometimes used with doxorubicin to reduce the risk of heart problems)

•    dexverapamil (a medicine used to treat some heart conditions).

Please tell your doctor if you are taking, or have recently taken, any other medicines, including ones that are not prescribed for you.

If you need to have any vaccinations, you must inform your doctor that you are being treated with epirubicin before receiving the vaccination as certain types of vaccines (live and live-attenuated) may have serious side effects.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, trying to become pregnant or breast-feeding. Your doctor will decide if you should receive this medicine.

Due to the risk of birth defects, women of childbearing potential should use appropriate contraception methods during treatment with epirubicin.

You must not breast feed if you are taking epirubicin.

Male patients may wish to seek advice on sperm preservation before treatment starts and should use effective contraceptive methods during treatment.

Male patients are advised not to father a child during and for 6-months after stopping epirubicin treatment.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

You may feel and/or be sick after being given this medicine, therefore special care should be taken when driving or using machines.

3. How to use Epirubicin Hydrochloride Injection

The dose of medicine given to you will depend on the type of cancer you have, your health, how well your liver and kidneys are working and any other medicines you may be taking.

By injection or infusion into a vein

The medicine may be given as an injection into a vein over 3-5 minutes. It may also be diluted with glucose (sugar solution) or sodium chloride (salt water) before it is infused slowly, usually via a drip into a vein over 30 minutes. You may be given another dose of this medicine in 3 weeks.

By being put into the bladder (intravesical administration)

The medicine may be given directly into the bladder using a catheter. If this route is used, you should not drink any fluids for 12 hours before treatment so that your urine will not dilute the medicine too much. The solution should be kept in your bladder for 1 hour after instillation. You will be rotated occasionally to ensure even exposure of all parts of the bladder to the medicine.

Care should be taken to ensure that the contents of the bladder, when emptied, do not come into contact with the skin. In case of skin contact, thoroughly wash the affected area with soap and water but do not scrub.

While you are receiving epirubicin your doctor will take regular blood tests. This is to measure the effect the medicine is having. Your doctor will also do regular tests on how your heart is working.

If the injection has been added to a bag of fluid for injection, or for administration to the bladder, it should be labelled with the strength of the medicine, volume and the time after which it should not be used.

As this medicine will be given to you whilst you are in hospital it is unlikely that you will be given too little or too much, however, tell your doctor or pharmacist if you have any concerns.

Possible Side Effects

Like all medicines, epirubicin can have side effects although not everybody gets them. . If you experience any of the following side effects when epirubicin is given by infusion into a vein,

tell your doctor immediately as these are all serious. You may need urgent medical attention or hospitalisation.

•    if there is any redness, pain or swelling at the injection site. Redness may occur commonly.

• if you have symptoms of heart problems/ heart failure such as chest pain, shortness of breath, swelling of your ankles (oedema) (these effects may occur up to several weeks after finishing treatment with epirubicin). These side effects are rare.

• if you have a severe allergic reaction, symptoms include faintness, skin rash, itching, swelling of the face and difficulty in breathing or wheeze. In some cases collapse may occur. This side effect is rare.

Other side effects that may occur:

Very common side effects which may affect more than 1 person in 10 are listed below:

•    Reduction in blood cell counts (eg anaemia, low white cells which may make you more likely to get an infection,)

•    Hair loss (alopecia) and loss of beard growth (in males)

•    Red colouration of urine for 1 to 2-days after administration

Common side effects which may affect more than 1 person in 100 are listed below:

•    Infection

•    Loss of appetite (anorexia)

•    Dehydration

•    Hot flushes

•    Inflammation of the mouth,

•    Feeling and being sick (nausea and vomiting)

•    Diarrhoea

•    Injection site reactions (eg redness)

Uncommon side effects which may affect more than 1 person in 1,000 are listed below:

•    Reduction in blood platelets which increases risk of bruising or bleeding

•    Inflammation of the veins (phlebitis) which may be associated with blood clots (thrombophlebitis) - this may present as pain and/or swelling in your arms or legs

Rare side effects which may affect less than 1 person in 1,000 are listed below:

•    Dizziness

•    Malaise and weakness,

•    Abnormal liver function test which are detected on blood tests

•    Abnormal heart rhythm or rate

•    Nettle rash (urticaria)

•    Lack of periods (amenorrhoea)

•    Reduced levels of sperm in males (azoospermia)

•    Feeling unusually hot or cold (fever or chills)

•    Leukaemia (acute lymphocytic or acute myelogenous) may occur up to 3 years after treatment

•    Raised blood uric acid levels - which may be part of a syndrome associated with tumour breakdown. Your doctor will monitor you with blood tests

Epirubicin may also affect your liver function and the number of cells in your blood. Your doctor will monitor such effects with regular blood tests.

Epirubicin may affect the function of your heart with early onset effects of changes in the ECG (heart trace), and late onset effects (may be several weeks after stopping treatment) of congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm). The risk of developing heart failure increases with higher total dose of epirubicin. Your doctor will monitor your heart function.

Side effects after epirubicin injection into the bladder

If epirubicin is injected directly into the bladder (intravesically), only a small amount is absorbed into the body so the side effects listed above are rare. However, inflammation and infection of the bladder may occur and you may experience discomfort, pain or difficulty when passing urine and blood may be seen in your urine. These side effects are mostly reversible. If you notice these side effects you should inform your doctor.

When given in combination with other anti-cancer medicines, some patients have developed a secondary leukaemia after completing treatment. This is rare.

If you notice any side effects not mentioned in this leaflet, please tell your doctor or pharmacist.

5. How to store Epirubicin Hydrochloride Injection

Keep out of the reach and sight of children.

The vials will be stored at 2-8°C (in the refrigerator).

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

Epirubicin hydrochloride, diluted in either glucose 5% or sodium chloride 0.9%, would not normally be stored for longer than 24 hours in a refrigerator.

Do not use after the expiry date printed on the vial label and carton.

6. Further information

•    The active substance is epirubicin hydrochloride

•    The other ingredients are sodium chloride, water for injections and hydrochloric acid used as a pH adjuster.

Epirubicin Hydrochloride is in the form of a solution for injection.

Each millilitre (ml) of solution contains 2 milligrams (mg) of epirubicin hydrochloride. The medicine is presented in glass containers called vials, containing 10mg (5ml), 50mg (25ml), 100mg (50ml) and 200mg (100ml) of epirubicin hydrochloride.

The vials may be overwrapped with a protective plastic to minimise the risk of spillage if the vials break; these vials are referred to as ONCO-TAIN®.

The vials are available in single packs of 5ml, 25ml, 50ml or 100ml.

The marketing authorisation holder and company responsible for batch release in the EU is Hospira UK Limited, Queensway, Royal Leamington Spa, Warwickshire, CV31 3RW, United Kingdom.

The manufacturer is Hospira Australia Pty Ltd, Lexia Place, Mulgrave, Victoria 3170, Australia or Zydus Hospira Oncology Private Limited (ZHOPL), Plot No. 3, Pharmez Special Economic Zone, Sarkhej Bavla Highway, N.H. No. 8A, Village Matoda, Taluka Sanand, District Ahmedabad - 382213, Gujarat, India.

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria - Epirubicinhydrochlorid Hospira 2 mg/ml Injektionslosung

Belgium - Epirubicin Hydrochloride Hospira 2 mg/ml

Cyprus - Hospira Epirubicin Hydrochloride

Denmark - Epirubicin Hospira

Finland - Epirubicin Hospira

Germany - Epirubicinhydrochlorid Hospira 2 mg/ml Injektionslosung Greece - Epirubicin Hydrochloride/Hospira 2 mg/ml Injection Italy - Epirubicina Hospira 2 mg/ml Soluzione iniettabile Latvia - Epirubicin Hospira Lithuania - Epirubicin Hospira

Luxembourg - Epirubicin Hydrochloride Hospira 2 mg/ml Portugal - Epirrubicina Hospira 2 mg/ml solu^ao injectavel Spain - Epirubicina Hospira 2 mg/ml solution inyectable

This leaflet was last approved in 01/2011

The following information is intended for medical or healthcare professionals only:

Incompatibilities

Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug, which includes sodium bicarbonate containing solutions. Only the diluents detailed in ‘Dilution Instructions’ should be used.

Neither the injection nor any diluted solution should be mixed with any other drugs. (A physical incompatibility with heparin has been reported).

Dilution Instructions

The injection may be given via the tubing of a free-running intravenous saline infusion. Where the injection is to be administered after dilution, the following instructions should be followed.

Epirubicin Hydrochloride solution for injection may be diluted under aseptic conditions in glucose 5% or sodium chloride 0.9% and administered as an intravenous infusion. The infusion solution should be prepared immediately before use.

The injection solution contains no preservative and any unused portion of the vial should be discarded immediately.

Safe Handling

This is a cytotoxic product, please follow your local policy guidelines for instructions on the safe handling/disposal of cytotoxics.

Storage

Store at 2-8°C.

Keep container in the outer carton.

In use: Epirubicin Hydrochloride 2 mg/ml injection may be further diluted as detailed above. The infusion solution is chemically stable when stored in PVC infusion bags prepared under full aseptically controlled conditions for 14 days at room temperature or for 28 days at 2-8°C in the absence of light. From a microbiological point of view however, 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 would normally not be longer than 24 hours at 2 to 8°C.

Marketing Authorisation Holder

Hospira UK Limited Warwickshire, CV31 3RW UK

This leaflet was last approved in 05/2008