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PACKAGE LEAFLET: INFORMATION FOR THE USER

EPiRUBICiN 2 mg/ml SOLUTiON FOR INJECTION

(epirubicin hydrochloride)

What is in this leaflet:

1.    What Epirubicin is and what it is used for

2.    What you need to know before you use Epirubicin

3.    How to use Epirubicin

4.    Possible side effects

5.    How to store Epirubicin

6.    Contents of the pack and other information

1.    WHAT EPIRUBICIN IS AND WHAT IT IS USED FOR

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

Epirubicin is used in the treatment of:

•    Breast and gastric cancers

•    Bladder cancers

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

2.    WHAT YOU NEED TO KNOW BEFORE YOU USE EPIRUBICIN Do not use Epirubicin:

•    if you are allergic to epirubicin hydrochloride, to any of the other ingredients of this medicine (listed in section 6) or to similar medicines,

•    if you are breast-feeding,

•    if your blood cell count is too low as epirubicin can lower your blood count further. This is measured by health care personnel.

•    if you have severe liver disease

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

•    if you have a severe infection

•    if you have been previously treated with epirubicin or similar medicines as previous treatment with epirubicin or similar medicines can increase the risk of side effects

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

•    the cancer has penetrated the bladder wall,

•    you have an infection in your urine,

•    you have pain or inflammation in your bladder,

•    your doctor has problem inserting a catheter (tube) into your bladder,

•    you have blood in your urine,

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

•    if your bladder is contracted Warnings and precautions

Talk to your doctor before using Epirubicin

•    to ensure the number of cells in your blood does not drop too low and you are not ill with a severe infection. 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 regularly check this,

•    if you have liver or kidney disease. Epirubicin may not be suitable for you or a reduced dose may have to be used.

•    to ensure your heart is working properly. Your doctor will regularly check this by doing regular heart function tests.

•    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,

•    if you have received or are receiving trastuzumab (a medicine used to treat certain cancers like breast cancer),

•    if you have had or are due to have any vaccination,

•    if you are elderly.

Extravasation (leakage of the solution out of the vein) of epirubicin may cause local pain, lesions and necrosis (death of living tissue) of surrounding tissue. If this occurs, the injection should be immediately stopped.

Other medicines and Epirubicin

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Epirubicin should not be used:

•    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 drugs as epirubicin (called anthracyclines). They have similar side effects (including their effects on the heart)

Special care will be taken if you are taking any of the following medicines:

•    other medicines that may affect your heart and/or liver,

•    cimetidine (a drug used to reduce the acidity in your stomach),

•    paclitaxel and docetaxel (drugs used in some cancers),

•    interferon alpha-2b (a drug used in some cancers and lymphomas and for some forms of hepatitis),

•    quinine (a drug used for treatment of malaria and for leg cramps),

•    dexrazoxane (a drug sometimes used with doxorubicin),

•    dexverapamil (a drug used to treat some heart conditions),

•    if you have received or are receiving trastuzumab (a medicine used to treat certain cancers like breast cancer),

•    other medicines that may affect your bone marrow or reduce the numbers of cells in your blood.

The use of certain types of vaccines (live vaccines or live-attenuated vaccines) should be avoided if you are receiving epirubicin treatment. Killed or inactivated vaccines may be given; however the response may be diminished.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

If you become pregnant whilst receiving this medicine you should inform your doctor immediately.

Both men and women should use effective contraception during treatment with Epirubicin and for 6 months after treatment with epirubicin has finished.

Epirubicin can have an anti-fertility effect. Therefore, male patients treated with epirubicin are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.

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.

Epirubicin contains sodium.

This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially 'sodium- free'.

3.    HOW TO USE EPIRUBICIN

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

Method of administration, like the frequency of administration and duration of treatment, will depend on the route of administration as detailed below:

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 injection into the bladder through a tube ('catheter')

(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 drug too much. The solution should be kept in your bladder for 1-2 hours after instillation.

You will be rotated occasionally to ensure even exposure of all parts of the bladder to the drug.

-jJf.......................................

The following information is intended for healthcare professionals only:

For intravenous injection and intravesical administration

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 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.

Date: 02 AUG 2014

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 drug 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 drug, 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.

4.    POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the following happen when epirubicin is given by infusion into a vein, tell your doctor immediately:

•    if there is any redness, pain or swelling at the injection site,

•    if you have symptoms of heart problems such as chest pain, shortness of breath, swelling of your ankles, abnormal heart rhythm (these effects may occur several weeks, months or years after finishing treatment with epirubicin),

•    if you have a severe allergic reaction; symptoms include faintness, skin rash, itching, swelling of the face, fever, chills and difficulty in breathing or wheezing. In some cases collapse may occur.

These are very serious side effects. You may need urgent medical attention.

Other side effects may also be noticed after infusion of epirubicin into a vein.

Very common: may affect more than 1 in 10 people

•    Lack of white blood cells (this leads to frequent infections; symptoms include fever, severe chills, sore throat and mouth ulcers)

•    Decreased numbers of red blood cells leading to symptoms such as: tiredness, headaches, being short of breath when exercising, looking pale, dizziness

•    Hair loss (alopecia) - may be quite severe. Beard growth may stop in men. Hair normally re-grows when your treatment course ends

•    Red coloration of urine for 1-2 days after administration of treatment

Common: may affect up to 1 in 10 people

•    Infection;

•    Anorexia (loss of appetite), dehydration

•    Hot flushes

•    Sore, red mouth (may appear 5-10 days after starting treatment; also mouth ulcers or cold sores with swollen/inflamed, painful and bleeding areas in the mouth, along the side and under the tongue)

•    Inflammation of the food pipe

•    Feeling sick (nausea), being sick (vomiting)

•    Diarrhoea

•    Stomach pain

•    Redness along the vein in which the product is administered, local inflammation of a vein

Uncommon: may affect up to 1 in 100 people

•    Low blood platelet count making you bleed or bruise more easily than normal

•    Headache

•    Phlebitis (inflammation of a vein), thrombophlebitis (inflammation of the vein related to a blood clot)

Rare: may affect up to 1 in 1,000 people

•    When given in combination with other anti-cancer drugs, some patients have developed cancers of white blood cells (leukaemia) after completing treatment

•    High levels of uric acid in the blood (indicator of cell destruction)

•    Dizziness

•    Heart disorders: abnormal ECG (electrical recording of the heart), changes in the rhythm or rate of the heart (fast, slow or irregular), heart muscle disease

•    Hives (urticaria)

•    Absence of menstrual periods, reduced or absent sperm in the semen

•    Fever, chills, generally feeling unwell, unusual weakness

•    Increased levels of liver enzymes (indicator of liver damage)

Other side effects (frequency cannot be estimated from the available data):

•    Life-threatening illness caused by body overreacting to infection (sepsis), sometimes with a dangerous drop in blood pressure with symptoms like cold skin and increased heart beat (septic shock)

•    Pneumonia (serious lung infection)

•    Decrease in blood cell count may lead to bleeding and shortage of oxygen to body tissues

•    Discharge with itching of the eyes and crusty eyelids (conjunctivitis), disease of the cornea with symptoms of eye irritation and having something in the eye (keratitis)

•    Shock (a dangerous decrease in blood pressure which may be life-threatening; symptoms include rapid shallow breathing, cold clammy skin, dizziness, weakness, fainting and a rapid weak pulse)

•    Blockage of a blood vessel by a blood clot, including blood vessels in the lungs (symptoms include: sudden severe headache, loss of vision, loss of coordination, slurred speech, shortness of breath, chest pain, numbness, heat or swelling in the arms and legs)

•    Swelling, pain, ulcers or dark areas (pigmentation) in your mouth

•    Rash, itch, skin changes, reddening of skin, dark areas (pigmentation) of skin and nails

•    Sensitivity or hypersensitivity to light

•    Flushes (redness of the face and other areas of the skin)

•    Thickening and hardening of veins, local pain and death of cells and living tissue (tissue necrosis) if product accidentally administered outside the vein

•    Infection of the skin

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

If epirubicin is injected directly into the bladder (intravesically) you may experience an allergic reaction, pain or difficulty when passing urine or you may experience a frequent urge to pass urine. Blood may also be seen in your urine. If you notice either of these side effects, you should inform your doctor.

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

If you get any side effects, talk to your doctor, pharmacist or nurse.

This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

By reporting side effects you can help provide more information on the safety of this medicine.

5.    HOW TO STORE EPIRUBICIN

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

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

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

Do not use this medicine after the expiry date which is stated on the vial label and carton.

6.    CONTENTS OF THE PACK AND OTHER INFORMATION

What Epirubicin contains

•    The active substance is epirubicin hydrochloride.

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

What Epirubicin looks like and contents of the pack

Epirubicin is in the form of a solution for injection.

Each mililitre (ml) of solution contains 2 milligrams (mg) of epirubicin hydrochloride. The medicine is presented in glass containers called vials, containing 10 mg (5 ml), 20 mg (10 ml), 50 mg (25 ml), 100 mg (50 ml) and 200 mg (100 ml) of epirubicin hydrochloride.

The vials are available in packs of 1,5 or 10 vials of 5 ml, 10 ml, 25 ml, 50 ml or 100 ml.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom. Manufacturer(s)

Haupt Pharma GmbH, Pfaffenrieder Strasse 5, 82 515 Wolfratshausen, Germany or Laboratoires Thissen S.A - Rue de la Papyree 2-6 -B-1420 Braine-l'Alleud -

Belgium or MYLAN S.A.S., 117 allee des Parcs - 69800 SAINT-PRIEST, FRANCE. This leaflet was last revised in August2014

-jJf.......................................

The injection solution contains no preservative and any unused portion of the vials 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 in a refrigerator (2°C - 8°C).

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

In use: Epirubicin 2 mg/ml injection may be further diluted as detailed above. The infusion solution is chemically stable when stored in infusion bags prepared under full aseptically controlled conditions for 60 minutes at 25°C. 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 unless dilution has taken place in controlled and validated aseptic conditions.

397775

Date: 02 AUG 2014