PACKAGE LEAFLET: INFORMATION FOR THE USER

Epirubicin Hydrochloride 10mg Powder for Solution for Injection or Infusion Epirubicin Hydrochloride 50mg Powder for Solution for Injection or Infusion

Read all of this leaflet carefully before you start using this medicine.

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

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

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

In this leaflet:

1.    What Epirubicin Hydrochloride Powder for Solution for Injection or Infusion is and what it is used for

2.    Before you use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

3.    How to use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

4.    Possible side effects

5.    How to store Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

6.    Further information

1. What Epirubicin Hydrochloride Powder for Solution for Injection or Infusion 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 part of a group of medicines called anthracyclines. These act upon cells that are actively growing, to slow or stop their growth and increase the chance that the cells die.

Epirubicin is used to treat a variety of cancers. The way in which it is used depends upon the type of cancer that is being treated.

When injected into the bloodstream, Epirubicin is used to treat cancers of the breast, stomach and lung as well as advanced ovarian cancer.

When injected into the bladder through a tube, Epirubicin is used to treat cancers of the bladder wall.

It can also be used after other treatments for prevention of such cells from growing again.

2. Before you use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

Do not use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion if you:

•    are allergic (hypersensitive) to epirubicin hydrochloride, any of the other ingredients of Epirubicin Hydrochloride Powder for Solution for Injection or Infusion (see list in chapter 6, ‘Further Information’) or other similar drugs (belonging to a group of drugs called anthracyclines, which among others include doxorubicin or daunorubicin)

•    are allergic (hypersensitive) to drugs belonging to the group anthracenediones (including drugs used to treat cancer)

•    are breast-feeding.

Epirubicin should not be injected into a vein (intravenous use) if you:

•    are aware your blood counts are low, caused by previous treatment with other anti-tumour drugs or by previous radiotherapy

•    have been treated with other chemotherapy at maximum dose such as epirubicin and/or other anthracyclines (such as doxorubicin or daunorubicin), and anthracenediones, which can increase the risk of side effects

•    suffer with or have suffered with problems with your heart

•    suffer from an acute severe infection

•    have severe liver problems

Epirubicin should not be injected into the bladder if:

•    you suffer from urinary tract infection (including your kidneys, bladder and urethra)

•    there are tumours which penetrate the bladder

•    there are problems placing the tube into the bladder

•    you have an inflammation of the bladder

•    - you have blood in the urine (hematuria)

Take special care with Epirubicin Hydrochloride Powder for Solution for Injection or Infusion if you:

•    have some kidney or liver problems. You should inform your doctor before treatment as he/she needs to take special care.

Your doctor will also be making regular checks

•    so that your blood cell counts will not be too low

•    to control the levels of uric acid and other factors in the blood

•    to see that your heart and liver are working normally

• if you have or are to have radiotherapy to the area around the heart.

You should inform your doctor in case you experience swelling and pain in your mouth or mucous membrane.

You should tell your doctor if you are about to have a vaccination, as it may cause side effects if used with epirubicin.

It is possible that the urine will have a red colour for one or two days after administration.

Using other medicines

Tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Especially:

•    Cimetidine (used to reduce the acid in the stomach).

•    Trastuzumab (used to treat cancer).

•    Paclitaxel and docetaxel (used in some cancers).

•    Interferon alfa-2b (used in some cancers and lymphoma and for some yellow fever).

•    Quinine (used for treatment of malaria and for leg cramps).

•    Dexverapamil (used to treat some heart conditions).

•    Medicines that may affect your heart, such as 5-fluorouracil, cyclophosphamide, cisplatin, taxanes (used to treat cancer) or calcium channel blockers (used to treat high blood pressure or some heart conditions).

•    Medicines that may affect your liver.

•    Live vaccines.

•    Other medicines that may affect the bone marrow (such as other medicines to treat cancer, sulphonamide and cloramphenicol (antibacterial medicines), diphenylhydantoin (antiepileptic), amidopyrine derivatives (some medicines to treat e.g. pain and fever) and some antiviral medicines).

Pregnancy and breast-feeding Fertility

There is a risk of sterility due to therapy with Epirubicin. Male patients should consider storage of sperm before treatment.

Epirubicin may cause absence of menstruation or premature menopause in premenopausal women. Pregnancy

Epirubicin may cause birth defects when used during pregnancy, it is important to tell your doctor if you are pregnant or if you become pregnant during treatment. You must not use Epirubicin during pregnancy unless clearly indicated by your doctor.

If you or your partner are being teated with Epirubicin, effective birth control to prevent pregnancy is advised. If pregnancy occurs during treatment or if you desire to have children after completion of therapy, genetic counselling is recommended.

Breast-feeding

Epirubicin may be harmful to nursing infants, therefore women must stop breast-feeding before starting treatment with this product.

Driving and using machines

Epirubicin may cause episodes of nausea and vomiting, which can temporarily lead to an impairment of the ability to drive or use machines.

Important information about some of the ingredients of Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

This medicinal product contains methyl parahydroxybenzoate which may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

3. How to use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

Epirubicin will be given to you by a doctor or nurse, either into a vein or directly into your bladder. Your doctor will decide the correct dose and the number of days treatment you receive. The dose will depend on the type of cancer you have, your health, height, weight, how well your liver is working and any other treatment you may receive.

By injection or infusion into a vein

Epirubicin Hydrochloride Powder for Solution for Injection or Infusion may be given as an injection into a vein over 3-5 minutes. It may also be diluted before it is infused slowly, usually via a drip into a vein over 30 minutes.

By being put into the bladder

If the injection is given into the bladder, 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 installation. You will need to turn occasionally to make sure all parts of the bladder are exposed to the drug.

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.

Your doctor will regularly check your blood for any unwanted effects. To detect any possible heart damage your doctor will also monitor your heart for several weeks after the treatment.

If you receive more Epirubicin than you should:

It may affect your heart, lower your blood cell count and cause gastrointestinal toxic effects (mainly mucositis). You may notice sores in your mouth. However, 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. Please tell your doctor if you have any concerns.

Like all medicines, Epirubicin Hydrochloride Powder for Solution for Injection or Infusion can cause side effects, although not everybody gets them.

If any of the following side effects happen when epirubicin is given by infusion into a vein tell you doctor immediately, as these are very serious side effects. You may need urgent medical attention:

-    redness, pain or swelling at the injection site; tissue damage may occur after accidental injection outside a vein

-    symptoms of heart problems such as chest pain, shortness of breath, swelling of your ankles (these effects may occur up to several weeks after finishing treatment with epirubicin)

-    severe allergic reaction, symptoms include faintness, skin rash, swelling of the face and difficulty in breathing or wheeze . In some cases collapse may occur.

If you experience any of the following tell your doctor as soon as possible:

Very common (occur in more than 1 in 10 people):

Bone marrow suppression (which leads to low blood cell count), hair loss (usually reversible), reduced growth of beard hair, red coloured urine for 1 to 2 days after being given the medicine.

Common (occur in less than 1 in 10 people):

Severe loss of appetite leading to weight loss (anorexia), loss of fluid from the body (dehydration), feeling or being sick (nausea or vomiting), diarrhoea (which can result in dehydration), loss of appetite, abdominal pain, inflammation of the gullet (oesophagitis), high levels of pigments in the mouth, swelling and pain in your mouth, ulcers involving the lips and/or tongue and/or under the tongue, hot flushes, fever or infections, redness, pain or swelling at the injection site; tissue damage may occur after accidental injection outside a vein, allergic reactions or inflammation of the bladder (sometimes with bleeding) after injection of the medicine into the bladder.

Uncommon (occur in less than 1 in 100 people):

Low levels of blood platelets (thrombocytopenia) often causing unusual bruising or bleeding, headache, high levels of pigments in the skin and nails, skin redness, sensitivity of the skin to light (in case of radiotherapy), vein inflammation including blood clotting (thrombophlebitis).

Rare (occur in less than 1 in every 1,000 people):

Leukaemia (cancer of the blood), severe, whole-body allergic reaction (anaphylaxis), hives (urticaria), increased blood levels of uric acid (hyperuricaemia) possibly leading to gout, fever and/or chills, dizziness, absence of menstrual periods (amenorrhea), lack of sperm, changes in liver function (changes in transaminase levels), heart failure (shortness of breath, oedema, enlargement of the liver , pulmonary oedema which can cause respiratory failure and swelling of the abdomen), abnormal heart rhythm, weaker heart with lower pumping rate which can result in, feeling generally unwell and feeling of weakness.

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

Infection of the lungs (pneumonia), infection of the blood (sepsis), septic shock (severe complication of sepsis), bleeding and lack of oxygen in body tissues, redness, dryness and swelling of the eyes, shock, blockage of a blood vessel by a clot (e.g., in the lungs), skin rash, itching, skin changes, flushes (reddening of the skin). Infected area of the skin can become sore, swollen, red and hot, caused by severe cellulitis. Decreased ability of the heart to pump blood (asymptomatic drops in left ventricular ejection fraction). Colour changes, bleeding, pain, sores, ulcers or burning sensation inside the mouth.

If epirubicin hydrochloride is injected directly into the bladder you may experience pain or difficulty when passing urine. Blood may also be seen in your urine.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. How to store Epirubicin Hydrochloride Powder for Solution for Injection or Infusion

Keep out of the reach and sight of children.

Store in the original package.

Do not use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion after the expiry date which is printed on the label and carton after EXP. The expiry date refers to the last day of that month.

Do not use Epirubicin Hydrochloride Powder for Solution for Injection or Infusion if you notice any visible signs of deterioration.

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

6. Further information

What Epirubicin Hydrochloride Powder for Solution for Injection or Infusion contains

The active substance is epirubicin hydrochloride. One vial contains 10mg epirubicin hydrochloride. The other ingredients are: lactose monohydrate, methyl parahydroxybenzoate.

The active substance is epirubicin hydrochloride. One vial contains 50mg epirubicin hydrochloride. The other ingredients are: lactose monohydrate, methyl parahydroxybenzoate.

What Epirubicin Hydrochloride Powder for Solution for Injection or Infusion looks like and contents of the pack

Epirubicin powder is a red-orange powder delivered in a colourless vial.

Each pack contains a single vial.

Manufacturer(s):

Actavis Italy S.p.A.

Nerviano Plant, Viale Pasteur 10, 20014 Nerviano (Milan), Italy

Marketing Authorisation Holder:

Actavis Group PTC ehf, Reykjavikurvegi 76-78, 220 Hafnarfjordur, Iceland.

Leaflet was last revised in December 2013

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

Epirubicin Hydrochloride Powder for Solution for Injection or Infusion Instructions for use

ANTINEOPLASTIC AGENT

Incompatibilities

Prolonged contact with any solution of an alkaline pH (including sodium bicarbonate containing solutions) should be avoided as it will result in hydrolysis of the drug. Only the diluents detailed in “Instructions for use” should be used.

Epirubicin Hydrochloride Powder for Solution for Injection or Infusion should not be mixed with heparin due to chemical incompatibility which may lead to precipitation when the drugs are in certain proportions.

Epirubicin Hydrochloride Powder for Solution for Injection or Infusion can be used in combination with other antitumour agents, but it is not recommended that it be mixed with other drugs.

Instructions for use

Epirubicin Hydrochloride Powder for Solution for Injection or Infusion is for intravenous or intravesical use only.

The freeze dried powder may be reconstituted with 0.9% sodium chloride for injection or water for injection.

Intravenous administration: It is advisable to administer the reconstituted epirubicin hydrochloride solution via the tubing of a freely flowing intravenous infusion (0.9% sodium chloride). To minimize the risk of thrombosis or perivenous extravasation, the usual infusion times range between 3 and 20 minutes depending upon dosage and volume of the infusion solution. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration.

Intravesical administration: The reconstituted solution should be diluted in sterile water for injection or 0.9% sterile saline solution before administration. Epirubicin should be instilled using a catheter and retained intravesically for 1-2 hours. During instillation, the patient should be rotated to ensure that the vesical mucosa of the pelvis receives the most extensive contact with the solution. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. The patient should be instructed to void at the end of the instillation.

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

Guidelines for the safe handling and disposal of antineoplastic agents:

1.    If an infusion solution is to be prepared, this should be performed by trained personnel under aseptic conditions.

2.    Preparation of an infusion solution should be performed in a designated aseptic area.

3.    Adequate protective disposable gloves, goggles, gown and mask should be worn.

4.    Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. In the event of contact with the eyes, irrigate with large amounts of water and/or 0.9% sodium chloride solution. Then seek medical evaluation by a physician.

5.    In case of skin contact, thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Always wash hands after removing gloves.

6.    Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as detailed below.

7.    Pregnant staff should not handle the cytotoxic preparation.

8.    Adequate care and precautions should be taken in the disposal of items (syringes, needles etc) used to reconstitute and/or dilute cytotoxic medicinal products. Any unused product or waste material should be disposed of in accordance with local requirements.

Storage

Product as packaged for sale: Store in the original package.

After reconstitution according to directions: From a microbiological point of view 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 - 8 °C, unless reconstitution has taken place in controlled and validated conditions.

Please refer to the Summary of Product Characteristics (SPC) for further information about Epirubicin Hydrochloride Powder for Solution for Injection or Infusion.

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