PACKAGE LEAFLET: INFORMATION FOR THE PATIENT Epirubicin Copharma 2 mg/ml Solution for Injection/Infusion

Epirubicin hydrochloride

Read all of this leaflet carefully before you are given this medicine.

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

-    If you have further questions, please ask your doctor or your pharmacist.

-    This medicine has been prescribed for you personally and you should 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 or pharmacist

In this leaflet:

1.    What Epirubicin Copharma is and what it is used for

2.    Before you are given Epirubicin Copharma

3.    How Epirubicin Copharma is given

4.    Possible side effects

5.    How to store Epirubicin    Copharma

6.    Further information

1.    WHAT EPIRUBICIN COPHARMA IS AND WHAT IT IS USED FOR

Epirubicin Copharma - the active substance of Epirubicin hydrochloride - belongs to a group of active substances called anthracyclins. These cytotoxic active substances are used to treat cancer.

Epirubicin Copharma is used in the treatment of

-    breast cancer,

-    advanced ovarian cancer,

-    stomach cancer,

-    small cell lung cancer,

-    superficial cancer of the bladder.

2.    BEFORE YOU ARE GIVEN EPIRUBICIN COPHARMA You will not be given Epirubicin Copharma:

-    if you are allergic (hypersensitive) to epirubicin hydrochloride or any of the other ingredients of Epirubicin Copharma.

-    if you have a very low level of white blood cells due to previous treatment with other cytotoxic medicinal products or radiotherapy.

-    if you have been given the maximum dose of doxorubicin or daunorubicin (other anthracyclins).

-    if you have or have previously had heart problems.

-    if you suffer from a systemic infection.

-    if you are breast-feeding.

For use in the bladder, you will not be given Epirubicin Copharma:

-    if you have an infection of the urinary tract

-    if the tumour has penetrated the bladder wall

-    if there are problems inserting the catheter into the bladder

-    if you suffer from an inflamed bladder

-    if you retain a large volume of urine in the bladder after passing water

-    if your bladder is contracted.

Special care is needed (check with your doctor):

-    if your liver or kidneys are not working properly

-    if you notice a sensation of discomfort close to or at the injection site during the infusion (possible leakage into the surrounding tissue)

-    if your numbers of white and red blood cells and platelets are reduced

-    if you suffer from stomatitis or mucositis (sore lips or mouth ulcers)

-    if you have previously received radiotherapy of the breast or medication that might have side effects on your heart

Taking other medicines

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

Pregnancy and breast-feeding

Epirubicin Copharma - the active ingredient in Epirubicin hydrochloride - may cause birth defects, so it is important to tell your doctor if you think you are pregnant. Avoid becoming pregnant while you or your partner is taking Epirubicin Copharma as well as for 6 months after treatment.

Men who wish to father children in the future should seek advice about freezing sperm before treatment with Epirubicin Copharma is started.

You must discontinue breast-feeding before and during therapy with Epirubicin Copharma.

Ask your doctor for advice before taking any medicine.

Driving and using machines

Epirubicin Copharma may cause nausea and vomiting, which can temporarily affect your ability to drive and use machines.

Important information about some of the ingredients of Epirubicin Copharma

This medicinal product contains 0.154 mmol (or 3.54 mg) of sodium per ml of solution for injection/infusion. The different package sizes of Epirubicin Copharma contain the following amounts of sodium:

5 ml vial:    0.77    mmol    (or    17.7    mg)

10 ml vial:    1.54    mmol    (or    35.4    mg)

25 ml vial:    3.85    mmol    (or    88.5    mg)

50 ml vial:    7.70    mmol    (or    177.0 mg)

100 ml vial: 15.40 mmol (or 354.0 mg)

To be taken into consideration by patients on a controlled sodium diet.

3. HOW EPIRUBICIN COPHARMA IS GIVEN

Epirubicin Copharma will only be given to you under supervision of a doctor specialised in this type of treatment. Before and during treatment with Epirubicin Copharma, your doctor will check various laboratory parameters (e.g. blood cell count, blood uric acid level, your liver function) and carefully monitor your heart function. Monitoring of the heart function will be continued for several weeks following the end of treatment with Epirubicin Copharma.

The dosage of Epirubicin Copharma depends on the condition you are treated for, your response to therapy and other medication you are given.

The dose of Epirubicin Copharma is based on your body surface area. This is calculated from your height and weight.

The usual dosage of Epirubicin Copharma is 60-90 mg per square metre of body surface area, given by injection over three to five minutes every three weeks.

In the treatment of small cell lung cancer, a higher dose of 120 mg per square metre of body surface area is given by injection over three to five minutes or as infusion of up to 30 minutes, every three weeks.

For the treatment of breast cancer your doctor will decide on the dosage and regimen.

The dosage will be reduced if you have a low level of white blood cells and platelets in your body, if you have liver or renal problems, or if the medicinal product is used in combination with other cytotoxic medicinal products.

Epirubicin Copharma can also be given directly into the bladder to treat superficial bladder cancer or to stop recurrence after bladder surgery to remove the cancer. The dose will depend upon the type of bladder cancer.

Your general condition will be closely observed before, during and after the treatment with Epirubicin Copharma.

If you are given more Epirubicin Copharma than you should

As this injection will be given to you by a doctor or nurse it is unlikely that you will be given too much or that you will miss a dose. However, if you are concerned about your treatment, please talk to your doctor or nurse.

In case you were given a higher dosage of Epirubicin Copharma than required especially your heart function and count of blood cells will be closely monitored. The occurring side effects may be more severe.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Epirubicin Copharma can cause side effects, although not everybody gets them.

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.

Epirubicin Copharma may cause a red colouration of the urine for one or two days after administration. This is normal and nothing to worry about.

Frequency:

Very common (more than 1 in 10 patients)

Common (more than 1 in 100 patients, but less than 1 in 10 patients)

Uncommon (more than 1 in 1,000 patients, but less than 1 in 100 patients)

Rare (more than 1 in 10,000 patients, but less than 1 in 1,000 patients)

Very rare (less than 1 in 10,000 patients)

Not known (cannot be estimated from the available data)

Common	•    nausea (feeling sick) •    vomiting (being sick) •    diarrhoea - may result in dehydration •    loss of appetite •    abdominal pain (tummy pain) •    oesophagitis (inflammation of the gullet) •    hyperpigmentation (darkened areas) of the oral mucosa •    hot flushes •    chemical cystitis (bladder inflammation) sometimes haemorrhagic (with blood in the urine) following administration into the bladder •    mucositis (inflammation of membranes in digestive tract) including stomatitis (inflammation of linings of the mouth) •    redness along the infusion vein •    local phlebitis (inflammation of a vein, usually in the legs) •    phlebosclerosis (hardening of the walls of the veins) •    local pain and tissue death may occur (following accidental injection into the surrounding tissue) •    allergic reactions after being given into the bladder
Uncommon	•    hyperpigmentation (darkened areas) of skin and nails •    skin reddening •    thrombophlebitis (inflammation and a blood clot in a vein) •    headache •    photosensitivity (sensitivity to light) or hypersensitivity (allergic reaction) to radiotherapy (referred to as the ‘recall phenomenon’)
Rare	•    increased transaminase levels (increased levels of some liver enzymes) •    ECG-changes (electrocardiogram) •    tachycardia and ventricular tachycardia (rapid heart rate) •    bradycardia (slow heart rate) •    arrhythmias (abnormal heart beats) •    AV block and bundle-branch block (specific forms of arrhythmias) •    cardiomyopathy (heart muscle disease) •    congestive heart disease (heart problems) •    dyspnoea (difficulty in breathing) •    oedema and pulmonary oedema (accumulation of fluid) •    enlargement of the liver •    ascites (accumulation of fluid in the abdominal cavity) •    pleural effusion (accumulation of fluid between chest wall and lungs) •    gallop rhythm (third heart sound) •    urticaria (hives) •    hyperuricaemia (high levels of uric acid in the blood)

•    secondary acute myeloid leukaemia (malignant tumour of blood-forming tissues) results when given in combination with other anti-cancer medicinal products •    fever •    chills •    dizziness •    hyperpyrexia (increased body temperature) •    malaise (feeling of discomfort or uneasiness) •    weakness •    anaphylaxis (severe allergic reactions with or without shock including skin rash, pruritis (itching), fever and chills) •    amenorrhoea (absence of menstrual periods) •    azoospermia (lack of levels of male sperm)

Not known

•    myelosuppression (inhibition of blood cell production in the bone marrow) •    leukopenia (decreased number of white blood cells) •    granulocytopenia and neutropenia (decreased numbers of a specific form of white blood cells) •    febrile neutropenia (neutropenia accompanied by fever) •    thrombocytopenia (decreased number of platelets) •    anaemia (decrease in red blood cells) •    haemorrhage (bleeding) •    tissue hypoxia (inadequate oxygen supply) •    fever •    infections •    pneumonia (inflammation of the lungs) •    sepsis (systemic infection) and septic shock •    thromboembolic events (blockage of blood vessel by dislodged blood clot)

5.    HOW TO STORE EPIRUBICIN COPHARMA

Store in a refrigerator (2 °C - 8 °C).

Storage of diluted product: maximum 24 hours at 2-8°C

Keep the vial in outer carton in order to protect from light. Do not freeze.

Keep out of the reach and sight of children.

Do not use Epirubicin Copharma after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

6.    FURTHER INFORMATION

What Epirubicin Copharma contains

The active substance is epirubicin hydrochloride.

The other ingredients are sodium chloride, hydrochloric acid (for ph-adjustment) and water for injections.

What Epirubicin Copharma looks like and contents of the pack

Epirubicin Copharma is a clear, red solution.

One millilitre of Epirubicin Copharma contains 2 mg of epirubicin hydrochloride. This medicinal product comes in five different vial sizes:

• Each 5 ml vial of Epirubicin Copharma contains 10 mg of epirubicin hydrochloride

•    Each 10 ml vial of Epirubicin Copharma contains 20 mg of epirubicin hydrochloride

•    Each 25 ml vial of Epirubicin Copharma contains 50 mg of epirubicin hydrochloride

•    Each 50 ml vial of Epirubicin Copharma contains 100 mg of epirubicin hydrochloride

•    Each 100 ml vial of Epirubicin Copharma contains 200 mg of epirubicin hydrochloride

Not all pack sizes may be marketed.

Marketing authorisation holder:

COPHARMA ApS, J^gersborg Alle 164, DK-2820 Gentofte, Denmark Manufacturer:

Oncotec Pharma Produktion GmbH Am Pharmapark D-06861 Dessau-Roplau Germany

Company responsible for batch release in the EU:

medac Gesellschaft fur klinische Spezialpraparate mbH FehlandtstraBe 3 D-20354 Hamburg Germany

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

Denmark	Epirubicin " Copharma ”
Finland	Epirubicin Copharma 2 mg/ml Injektio-/infuusioneste, liuos
Norway	Epirubicin Copharma 2 mg/ml Injeksjonsv^ske-/infusjonsv^ske, oplosning
United Kingdom	Epirubicin Copharma 2 mg/ml Solution for injection/Infusion

This leaflet was last approved in

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PACKAGE LEAFLET: TCHNICAL PRESCRIBING INFORMATION Epirubicin Copharma 2 mg/ml Solution for Injection/Infusion

Epirubicin hydrochloride

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

Epirubicin Copharma may be further diluted in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion. The infusion solution should be prepared immediately before use.

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

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

In use stability

Epirubicin hydrochloride may be further diluted, under aseptic conditions, in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion. The infusion solution is chemically and physically stable, for upto 24 hrs when prepared under full aseptically controlled conditions in polypropylene syringes and in PVC infusion bags at 2 to 8°C.

However from a microbiological point of view, it is recommended that 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.

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.