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PACKAGE LEAFLET: INFORMATION FOR THE USER

Epirubicin hydrochloride 2 mg/ml

solution for injection

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 hydrochloride is and what it is used for

2.    Before you are given Epirubicin hydrochloride

3.    How Epirubicin hydrochloride is given

4.    Possible side effects

5.    How to store Epirubicin hydrochloride

6.    Further information

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

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

Epirubicin hydrochloride is used in the treatment of

•    breast cancer.

•    advanced ovarian cancer.

•    stomach cancer.

•    small cell lung cancer (special form of lung cancer).

•    superficial or very localised cancer of the bladder.

2. BEFORE YOU ARE GIVEN EPIRUBICIN HYDROCHLORIDE

You will not be given Epirubicin hydrochloride

•    if you are allergic (hypersensitive) to epirubicin hydrochloride or any of the other ingredients of Epirubicin hydrochloride or to any other similar medicine belonging to a group of medicines called anthracyclines (e.g. doxorubicin and daunorubicin).

•    if you are allergic (hypersensitive) to any drug belonging to a group of medicines known as anthracenediones (medicines that are also used to treat cancer).

•    if you have a persistent inhibition of blood cell production in the bone marrow due to previous treatment with other cytotoxic medicinal products or radiotherapy.

•    if you have been given the maximum dose of epirubicin or other anthracyclines (e.g. doxorubicin and daunorubicin) and anthracenediones (e.g. mitoxantrone).

•    if you have or have previously had heart problems (e.g. heart rhythm disorders, reduced heart function, heart attack, heart muscle disorder, acute inflammation of the heart, unstable angina pectoris).

•    if you have severe liver problems.

•    if you suffer from a systemic infection.

•    if you are breast-feeding.

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

•    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 have blood in your urine.

•    if your bladder has contracted or shrunk.

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

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 medicines that might have side effects on your heart.

•    if you have recently received or want to receive any vaccination.

The safety and efficacy of Epirubicin hydrochloride in children has not been established.

Taking other medicines

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

Pregnancy and breast-feeding

Epirubicin hydrochloride may cause birth defects, so it is important to tell your doctor if you think you are pregnant. You must not use Epirubicin hydrochloride during pregnancy unless clearly indicated by your doctor. Avoid becoming pregnant while you or your partner is taking Epirubicin hydrochloride. If pregnancy occurs during treatment with Epirubicin hydrochloride, genetic counselling is recommended.

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

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

Ask your doctor for advice before taking any medicine. Driving and using machines

Epirubicin hydrochloride 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 hydrochloride

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

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

3. HOW EPIRUBICIN HYDROCHLORIDE IS GIVEN

Epirubicin hydrochloride will only be given to you under supervision of a doctor specialised in this type of treatment. Before and during treatment with Epirubicin hydrochloride, 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 hydrochloride.

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

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

The usual dosage of Epirubicin hydrochloride is 60 - 90 mg per square metre of body surface area. It is given as an intravenous injection, i.e. into a blood vessel, over three to five minutes. The injection is given 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 into a vein over three to five minutes or as an infusion (drip) 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 hydrochloride 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.

To avoid undue dilution of Epirubicin hydrochloride with urine you are advised not to drink 12 hours before the treatment.

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

If you are given more Epirubicin hydrochloride than you should

In case you were given a higher dosage of Epirubicin hydrochloride 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 hydrochloride can cause side effects, although not everybody gets them.

Please tell your doctor immediately if you notice any side effects and discuss any further actions with him.

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 hydrochloride 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)

Very common:

•    Inhibition of blood cell production in the bone marrow (myelosuppression), decreased number of white blood cells (leukopenia), decreased number of a special form of white blood cells (granulocytopenia and neutropenia), decreased number of red blood cells (anaemia) and low level of certain white blood cells accompanied by fever (febrile neutropenia)

•    Flair loss, normally reversible

•    Red coloration of urine for 1 to 2 days after administration

Common:

•    Infection

•    Loss/lack of appetite, loss of water (dehydration)

•    Hot flashes

•    Inflammation of a mucous membrane (mucositis), inflammation of the oesophagus, inflammation inside the mouth (stomatitis), being sick (vomiting), watery stools or bowel movements (diarrhoea), feeling sick (nausea), which can result in loss of appetite and abdominal pain

•    Redness along the vein (infusion site erythema)

•    Bladder inflammation (chemical cystitis), sometimes with blood in the urine, has been observed following administration into the bladder.

Uncommon:

•    Decreased number of platelets (thrombocytopenia)

•    Vein inflammation (phlebitis), vein inflammation related to a blood clot (thrombophlebitis)

Rare:

•    Certain types of blood cancer (acute lymphocytic leukemia, acute myelogenous leukemia)

•    Severe allergic reaction (anaphylaxis) including allergy-like reaction (anaphylactic/anaphylactoid reactions) with or without shock including skin rash, itching, fever and chills; allergic reactions after administration of the medicine into the bladder

•    Increased levels of uric acid in the blood

•    Dizziness

•    Impaired heart function (congestive heart failure) which may lead to shortness of breath (dyspnoea), accumulation of fluid in the legs (oedema), enlargement of the liver, accumulation of fluid in the abdominal cavity (ascites), accumulation of fluid in the lung (pulmonary oedema), accumulation of fluid between thorax and lung (pleural effusions) or third heart sound (gallop rhythm).

•    Toxic effects on the heart like abnormalities in ECG, different forms of irregular heart beat (arrhythmias) or heart muscle disease (cardiomyopathy), life-threatening irregular heart beat (ventricular tachycardia), slow heart rate, defect of the heart's electrical conduction system (AV block, bundle-branch block).

•    Hives

•    Absence of menstruation, lack of sperm in the semen

•    Feeling of discomfort (malaise), feeling of weakness (asthenia), fever, chills

•    Changes in the level of certain liver enzymes (so called transaminases)

Not known:

•    Septic shock, systemic infection (sepsis), infection of the lungs (pneumonia)

•    Bleeding and inadequate oxygen supply of tissue may occur as a result of inhibition of blood cell production in the bone marrow (myelosuppression)

•    Pinkeye (conjunctivitis), inflammation of the cornea of the eye (keratitis)

•    Shock, occlusion of blood vessel by dislodged blood clot (thromboembolism) including occlusion of blood vessel by dislodged blood clot in the lung (pulmonary emboli)

•    Local toxicity, rash, itching, skin changes, skin reddening (erythema), flushes, increased pigmentation of skin and nails, increased sensitivity to light (photosensitivity), increased sensitivity to irradiated skin (radiation-recall reaction)

• Changes in heart function without any symptoms (asymptomatic drops in left ventricular ejection fraction)

5. HOW TO STORE EPIRUBICIN HYDROCHLORIDE

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

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

Keep out of the reach and sight of children.

Do not use Epirubicin hydrochloride after the expiry date stated on the vial and carton labels after ‘EXP’. This date refers to the shelf life of the unopened product and refers to the last day of that month.

6. FURTHER INFORMATION

What Epirubicin hydrochloride contains

The active substance is epirubicin hydrochloride.

The other ingredients are sodium chloride, hydrochloric acid and water for injections.

1 ml of solution contains 2 mg epirubicin hydrochloride.

One 5 ml (10 ml, 25 ml, 50 ml, 100 ml) vial contains 10 mg (20 mg, 50 mg, 100 mg, 200 mg) epirubicin hydrochloride.

What Epirubicin hydrochloride looks like and contents of the pack

Epirubicin hydrochloride is a clear, red solution.

It is supplied as single vials.

Manufacturer:

medac

Gesellschaft fur klinische Spezialpraparate mbH Fehlandtstr. 3 20354 Hamburg, Germany Tel.: +49 4103 8006-0 Fax: +49 4103 8006-100

Production Site:

Theaterstr. 6 22880 Wedel Tel.: +49 4103 8006-0 Fax: +49 4103 8006-100

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

Austria    Epimedac 2 mg/ml Injektionslosung

Czech Republic Epimedac 2 mg/ml injekcnf roztok Denmark    Epirubicin ’’medac” 2 mg/ml

injektionsvaeske, oplosning

Finland    Epirubicin medac 2 mg/ml injektioneste,

liuos

Epirubicin medac 2 mg/ml injektionsvatska, losning

Germany    Epimedac    2    mg/ml Injektionslosung

Greece    Epimedac    2    mg/ml eveaipo SiaAupa

Hungary    Epimedac    2    mg/ml oldatos injekcio

Norway    Epirubicin    medac 2 mg/ml

injeksjonsvaeske, opplosning

Epimedac 2 mg/ml roztwor do wstrzykiwan

Epirrubicina medac 2 mg/ml solugao injectavel

Epimedac 2 mg/ml injekcny roztok Epimedac 2 mg/ml raztopina za injiciranje

Epimedac 2 mg/ml solucion inyectable Epirubicin hydrochloride 2 mg/ml solution for injection

This leaflet was last approved in May 2010.

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

Epirubicin hydrochloride may be further diluted in glucose 5 % solution or sodium chloride 0.9 % solution 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 disposed of immediately in accordance with local requirements.

Incompatibilities

Prolonged contact of the medicinal product with any solution of an alkaline pH (including sodium bicarbonate solutions) should be avoided; this will result in hydrolysis (degradation) of the active substance. Only the diluents detailed in the section below should be used.

A physical incompatibility of the medicinal product with heparin has been reported.

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

In use stability

Epirubicin hydrochloride may be further diluted, under aseptic conditions, in glucose 5 % solution or sodium chloride 0.9 % solution and administered as an intravenous infusion. The chemical and physical in-use stability has been demonstrated for 48 hours at 25 °C in the absence of light.

However, 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 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

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.

90500-VPGB

AC