Epirubicin Hydrochloride 2 mg/ml Solution for Injection and Infusion

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• 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 you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effect not listed in this leaflet. See section 4.

• 1. What Epirubicin Hydrochloride is and what it is used for

• 2. What you need to know before you take Epirubicin

Hydrochloride

• 3. How to take Epirubicin Hydrochloride

• 4. Possible side effects

• 5. How to store Epirubicin Hydrochloride

• 6. Contents of the pack and other information

1. what epirubicin hydrochloride is and what it is used for

Epirubicin hydrochloride belongs to the therapeutic group of antineoplastic agents (medicine against cancer).

Epirubicin hydrochloride is used to treat different types of cancer, i.e.:

• Breast cancer
• Stomach cancer

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

It is used either alone or in combination with other anti-cancer medicines.

2. what you need to know before you take epirubicin hydrochloride

Do not use Epirubicin hydrochloride:

• if you are allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6), 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 drugs as epirubicin hydrochloride (called anthracyclines). These medicines 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 have a severe infection
• if you are experiencing severe inflammation or ulcers in your mouth and gastro-intestinal tract.
• if your tumour penetrates the bladder wall
• if you have a urine infection
• if you have inflammation of your bladder
• if your doctor has problems inserting a catheter (tube) in your bladder
• if there is a large volume of urine left in your bladder after you attempt to empty it.
• if you have a contracted bladder.
• if you have blood in the urine

Warnings and precautions

Special care will be taken:

• to ensure the numbers of white and red blood cells and platelets do not drop too low. Your doctor will regularly check this.
• 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
• if you have an unstable angina pectoris
• 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

Other medicines and Epirubicin Hydrochloride

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).

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

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

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.

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

Epirubicin Hydrochloride Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed with epirubicin. However, epirubicin may cause nausea and vomiting, which can temporarily affect your ability to drive and use machines.

Epirubicin Hydrochloride contains sodium.

This medicinal product contains 0.154 mmol/ml (3.54 mg/ml) sodium.

• 1 vial of 5 ml solution contains 0.77 mmol (17.70 mg) sodium i.e. essentially ‘sodium-free’.

• 1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

3. how to take epirubicin hydrochloride

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.

When given by injection or infusion into a vein

Each dose of Epirubicin hydrochloride is based on your body surface area. This is calculated from your height and weight. The dose of Epirubicin hydrochloride given to you will also depend on the type of cancer you have, your health, how well your liver or kidney is working and any other medicines you may be taking.

When given as a single agent, the usual dose of epirubicin hydrochloride is 60–90 mg/m2 body surface area. Higher dosages (100–120 mg/m2 body surface area) may be given to you if you suffer from breast cancer.

Dosage will be reduced or the following dose could be delayed if you have a low level of white blood cells in your body, if you are elderly, if you have liver problems, or if the drug is used in combination with other anticancer drugs.

Epirubicin hydrochloride 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. Usually it will be given to you every 3 (or 4) weeks.

The needle must remain in the vein while Epirubicin hydrochloride is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) – tell the doctor or nurse immediately.

When given directly 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 drug too much.

The dose will depend upon the type of bladder cancer.

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.

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.

If you received more Epirubicin hydrochloride than you should

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

If you missed a dose of Epirubicin hydrochloride

Epirubicin hydrochloride needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of Epirubicin hydrochloride.

If you stop treatment with Epirubicin hydrochloride

Stopping your treatment with Epirubicin hydrochloride may stop the effect on tumour growth. Do not stop treatment with Epirubicin hydrochloride unless you have discussed this with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

SZ00000LT000

4. possible side effects

Like all medicines, Epirubicin hydrochloride can cause 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
• you have 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 hydrochloride)
• If you have a severe allergic reaction, symptoms include faintness, skin rash, itching, fever, chills, swelling of the face and difficulty in breathing of wheeze. In some cases collapse may occur.

Other side effects that may occur:

Very common, may affect more than 1 in 10 people:

• inhibition of blood cell production in the bone marrow (myelosuppression)
• decreased number of white blood cells (leucocytopenia)
• decreased number of a special form of white blood cells (granulocytopenia and neutropenia)
• neutropenia accompanied by fever (febrile neutropenia)
• decrease in red blood cells (anaemia)
• hair loss (alopecia) normally reversible
• your urine may have a red colour for up to two days after treatment. This is normal and nothing to worry about

Common, may affect up to 1 in 10 people:

• Feeling and being sick (nausea and vomiting)
• Diarrhoea
• feeling very dry and thirsty (dehydration)
• Infection
• Loss of appetite
• inflammation of the oesophagus (oesophagitis)
• Inflammation of the mouth
• Hot flushes
• inflammation of a mucous membrane (mucositis)
• inflammation of the mucosa of the mouth with areas of painful erosions, ulceration and
• bleeding (stomatitis)
• Injection site reactions (eg. redness)
• bladder inflammation with pain when passing urine (chemical cystitis), sometimes with blood in the urine (haemorrhagic) following administration into the bladder

Uncommon, may affect up to 1 in 100 people:

• 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
• decreased number of platelets (thrombocytopenia)

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

• Dizziness
• Severe hypersensitivity (anaphylaxis)
• Malaise and weakness,
• Abnormal heart rhythm or rate; changes in the ECG (heart trace), congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm).
• Enlargement of the liver
• 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

Not known, frequency cannot be estimated from the available data:

• fever, infections, inflammation of the lungs (pneumonia), systemic infection (sepsis) or a state of shock resulting from blood poisoning (septic shock) may occur.
• Bleeding (haemorrhage) and inadequate oxygen supply to tissues (tissue hypoxia) were reported as a result of reduced blood cell production in the bone marrow
• discharge from the eye with itching, redness and swelling (conjunctivitis); eye pain, blurred vision, abnormal intolerance to light (keratitis)
• occlusion of blood vessel due to a blood clot (thromboembolic events) including occlusion of a blood vessel in the lungs (pulmonary embolism [in isolated cases with fatal outcome])
• Inflammation, burning sensation and pain in the mouth, sores and pain on swallowing, pigmentations and bleedings in the mouth.
• Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)
• hardening and loss of elasticity of the veins (phlebosklerosis), severe cellulitis, tissue necrosis after accidental paravenous injection

The quantity of blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction may be reduced (asymtomatic drops in left ventricular ejection fraction).

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.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet.

5. how to store epirubicin hydrochloride

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

Store refrigerated (2°C to 8°C).

Do not use this medicine after the expiry date which is stated on the carton and the vial. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Epirubicin hydrochloride contains

• The active substance is epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid, water for injections.

Each milliliter (ml) of solution contains 2 mg of epirubicin hydrochloride.

• 5 ml vial: each vial contains 10 mg epirubicin hydrochloride.

• 25 ml vial: each vial contains 50 mg epirubicin hydrochloride.

• 50 ml vial: each vial contains 100 mg epirubicin hydrochloride.

100 ml vial: each vial contains 200 mg epirubicin hydrochloride.

What Epirubicin hydrochloride looks like and contents of the pack

The solution for injection and infusion is a clear, red solution.

This medicinal product is a solution for injection.

Packaging with 1 vial, 5 or 10 vials of 5 ml solution.

Packaging with 1 vial, 5 or 10 vials of 25 ml solution.

Packaging with 1 vial, 5 or 10 vials of 50 ml solution.

Packaging with 1 vial, 5 or 10 vials of 100 ml solution.

The vials may be overwrapped with a protective plastic (ONKO-SAFE). The ONKO-SAFE has no contact with the drug product and increases safety during transport for medical and pharmaceutical personnel.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

EBEWE Pharma Ges.m.b.H. Nfg.KG, Mondseestrasse 11

A-4866 Unterach, Austria

Manufacturer

EBEWE Pharma Ges.m.b.H. Nfg.KG, Mondseestrasse 11

A-4866 Unterach, Austria

This leaflet was last revised in 01/2015.

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

Instructions for use and handling for disposal

Epirubicin Hydrochloride 2 mg/ml Solution for Injection and Infusion

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• 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 you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effect not listed in this leaflet. See section 4.

• 1. What Epirubicin Hydrochloride is and what it is used for

• 2. What you need to know before you take Epirubicin

Hydrochloride

• 3. How to take Epirubicin Hydrochloride

• 4. Possible side effects

• 5. How to store Epirubicin Hydrochloride

• 6. Contents of the pack and other information

1. what epirubicin hydrochloride is and what it is used for

Epirubicin hydrochloride belongs to the therapeutic group of antineoplastic agents (medicine against cancer).

Epirubicin hydrochloride is used to treat different types of cancer, i.e.:

• Breast cancer
• Stomach cancer

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

It is used either alone or in combination with other anti-cancer medicines.

2. what you need to know before you take epirubicin hydrochloride

Do not use Epirubicin hydrochloride:

• if you are allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6), 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 drugs as epirubicin hydrochloride (called anthracyclines). These medicines 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 have a severe infection
• if you are experiencing severe inflammation or ulcers in your mouth and gastro-intestinal tract.
• if your tumour penetrates the bladder wall
• if you have a urine infection
• if you have inflammation of your bladder
• if your doctor has problems inserting a catheter (tube) in your bladder
• if there is a large volume of urine left in your bladder after you attempt to empty it.
• if you have a contracted bladder.
• if you have blood in the urine

Warnings and precautions

Special care will be taken:

• to ensure the numbers of white and red blood cells and platelets do not drop too low. Your doctor will regularly check this.
• 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
• if you have an unstable angina pectoris
• 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

Other medicines and Epirubicin Hydrochloride

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).

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

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

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.

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

Epirubicin Hydrochloride Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed with epirubicin. However, epirubicin may cause nausea and vomiting, which can temporarily affect your ability to drive and use machines.

Epirubicin Hydrochloride contains sodium.

This medicinal product contains 0.154 mmol/ml (3.54 mg/ml) sodium.

• 1 vial of 5 ml solution contains 0.77 mmol (17.70 mg) sodium i.e. essentially ‘sodium-free’.

• 1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

3. how to take epirubicin hydrochloride

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.

When given by injection or infusion into a vein

Each dose of Epirubicin hydrochloride is based on your body surface area. This is calculated from your height and weight. The dose of Epirubicin hydrochloride given to you will also depend on the type of cancer you have, your health, how well your liver or kidney is working and any other medicines you may be taking.

When given as a single agent, the usual dose of epirubicin hydrochloride is 60–90 mg/m2 body surface area. Higher dosages (100–120 mg/m2 body surface area) may be given to you if you suffer from breast cancer.

Dosage will be reduced or the following dose could be delayed if you have a low level of white blood cells in your body, if you are elderly, if you have liver problems, or if the drug is used in combination with other anticancer drugs.

Epirubicin hydrochloride 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. Usually it will be given to you every 3 (or 4) weeks.

The needle must remain in the vein while Epirubicin hydrochloride is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) – tell the doctor or nurse immediately.

When given directly 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 drug too much.

The dose will depend upon the type of bladder cancer.

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.

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.

If you received more Epirubicin hydrochloride than you should

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

If you missed a dose of Epirubicin hydrochloride

Epirubicin hydrochloride needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of Epirubicin hydrochloride.

If you stop treatment with Epirubicin hydrochloride

Stopping your treatment with Epirubicin hydrochloride may stop the effect on tumour growth. Do not stop treatment with Epirubicin hydrochloride unless you have discussed this with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, Epirubicin hydrochloride can cause 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
• you have 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 hydrochloride)
• If you have a severe allergic reaction, symptoms include faintness, skin rash, itching, fever, chills, swelling of the face and difficulty in breathing of wheeze. In some cases collapse may occur.

Other side effects that may occur:

Very common, may affect more than 1 in 10 people:

• inhibition of blood cell production in the bone marrow (myelosuppression)
• decreased number of white blood cells (leucocytopenia)
• decreased number of a special form of white blood cells (granulocytopenia and neutropenia)
• neutropenia accompanied by fever (febrile neutropenia)
• decrease in red blood cells (anaemia)
• hair loss (alopecia) normally reversible
• your urine may have a red colour for up to two days after treatment. This is normal and nothing to worry about

Common, may affect up to 1 in 10 people:

• Feeling and being sick (nausea and vomiting)
• Diarrhoea
• feeling very dry and thirsty (dehydration)
• Infection
• Loss of appetite
• inflammation of the oesophagus (oesophagitis)
• Inflammation of the mouth
• Hot flushes
• inflammation of a mucous membrane (mucositis)
• inflammation of the mucosa of the mouth with areas of painful erosions, ulceration and
• bleeding (stomatitis)
• Injection site reactions (eg. redness)
• bladder inflammation with pain when passing urine (chemical cystitis), sometimes with blood in the urine (haemorrhagic) following administration into the bladder

Uncommon, may affect up to 1 in 100 people:

• 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
• decreased number of platelets (thrombocytopenia)

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

• Dizziness
• Severe hypersensitivity (anaphylaxis)
• Malaise and weakness,
• Abnormal heart rhythm or rate; changes in the ECG (heart trace), congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm).
• Enlargement of the liver
• 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

Not known, frequency cannot be estimated from the available data:

• fever, infections, inflammation of the lungs (pneumonia), systemic infection (sepsis) or a state of shock resulting from blood poisoning (septic shock) may occur.
• Bleeding (haemorrhage) and inadequate oxygen supply to tissues (tissue hypoxia) were reported as a result of reduced blood cell production in the bone marrow
• discharge from the eye with itching, redness and swelling (conjunctivitis); eye pain, blurred vision, abnormal intolerance to light (keratitis)
• occlusion of blood vessel due to a blood clot (thromboembolic events) including occlusion of a blood vessel in the lungs (pulmonary embolism [in isolated cases with fatal outcome])
• Inflammation, burning sensation and pain in the mouth, sores and pain on swallowing, pigmentations and bleedings in the mouth.
• Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)
• hardening and loss of elasticity of the veins (phlebosklerosis), severe cellulitis, tissue necrosis after accidental paravenous injection

The quantity of blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction may be reduced (asymtomatic drops in left ventricular ejection fraction).

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.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet.

5. how to store epirubicin hydrochloride

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

Store refrigerated (2°C to 8°C).

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

The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Epirubicin hydrochloride contains

• The active substance is epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid, water for injections.

What Epirubicin hydrochloride looks like and contents of the pack

The solution for injection and infusion is a clear, red solution.

This medicinal product is a solution for injection.

Packaging with 1 vial, 5 or 10 vials of 5 ml solution.

Packaging with 1 vial, 5 or 10 vials of 25 ml solution.

Packaging with 1 vial, 5 or 10 vials of 50 ml solution.

Packaging with 1 vial, 5 or 10 vials of 100 ml solution.

The vials may be overwrapped with a protective plastic (ONKO-SAFE). The ONKO-SAFE has no contact with the drug product and increases safety during transport for medical and pharmaceutical personnel.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

EBEWE Pharma Ges.m.b.H. Nfg.KG, Mondseestrasse 11

A-4866 Unterach, Austria

Manufacturer

EBEWE Pharma Ges.m.b.H. Nfg.KG, Mondseestrasse 11

A-4866 Unterach, Austria

This leaflet was last revised in 01/2015.

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

Instructions for use and handling for disposal

Dilution

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

Handling and disposal

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

Cytotoxics should not be handled by pregnant personnel.

Single use only.

Incompatibilities

Prolonged contact of the medicinal product with any solution of an alkaline pH should be avoided: this will result in hydrolysis (degradation) of the active substance. A physical incompatibility of the product with heparin has been reported. This medicinal product must not be mixed with other medicinal products except 0.9% sodium chloride or 5% glucose solution.

Administration

Epirubicin Hydrochloride is for intravenous or intravesical use only.

Storage and shelf-life

Medicinal product as packaged for sale:

Store refrigerated (2°C to 8°C).

Shelf life: 2 years

Storage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15° to 25°C).

Shelf life after dilution:

Chemical and physical in-use stability has been demonstrated for 7 days at 2 to 8°C in Glucose 5 % or Sodium Chloride 0.9 %.

In use: 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.

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Epirubicin Hydrochloride 2 mg/ml Solution for Injection and Infusion

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• 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 you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effect not listed in this leaflet. See section 4.

• 1. What Epirubicin Hydrochloride is and what it is used for

• 2. What you need to know before you take Epirubicin

Hydrochloride

• 3. How to take Epirubicin Hydrochloride

• 4. Possible side effects

• 5. How to store Epirubicin Hydrochloride

• 6. Contents of the pack and other information

1. what epirubicin hydrochloride is and what it is used for

Epirubicin hydrochloride belongs to the therapeutic group of antineoplastic agents (medicine against cancer).

Epirubicin hydrochloride is used to treat different types of cancer, i.e.:

• Breast cancer
• Stomach cancer

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

It is used either alone or in combination with other anti-cancer medicines.

2. what you need to know before you take epirubicin hydrochloride

Do not use Epirubicin hydrochloride:

• if you are allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6), 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 drugs as epirubicin hydrochloride (called anthracyclines). These medicines 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 have a severe infection
• if you are experiencing severe inflammation or ulcers in your mouth and gastro-intestinal tract.
• if your tumour penetrates the bladder wall
• if you have a urine infection
• if you have inflammation of your bladder
• if your doctor has problems inserting a catheter (tube) in your bladder
• if there is a large volume of urine left in your bladder after you attempt to empty it.
• if you have a contracted bladder.
• if you have blood in the urine

Warnings and precautions

Special care will be taken:

• to ensure the numbers of white and red blood cells and platelets do not drop too low. Your doctor will regularly check this.
• 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
• if you have an unstable angina pectoris
• 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

Other medicines and Epirubicin Hydrochloride

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).

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

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

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.

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

Epirubicin Hydrochloride Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed with epirubicin. However, epirubicin may cause nausea and vomiting, which can temporarily affect your ability to drive and use machines.

Epirubicin Hydrochloride contains sodium.

This medicinal product contains 0.154 mmol/ml (3.54 mg/ml) sodium.

• 1 vial of 5 ml solution contains 0.77 mmol (17.70 mg) sodium i.e. essentially ‘sodium-free’.

• 1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

• 1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

3. how to take epirubicin hydrochloride

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.

When given by injection or infusion into a vein

Each dose of Epirubicin hydrochloride is based on your body surface area. This is calculated from your height and weight. The dose of Epirubicin hydrochloride given to you will also depend on the type of cancer you have, your health, how well your liver or kidney is working and any other medicines you may be taking.

When given as a single agent, the usual dose of epirubicin hydrochloride is 60–90 mg/m2 body surface area. Higher dosages (100–120 mg/m2 body surface area) may be given to you if you suffer from breast cancer.

Dosage will be reduced or the following dose could be delayed if you have a low level of white blood cells in your body, if you are elderly, if you have liver problems, or if the drug is used in combination with other anticancer drugs.

Epirubicin hydrochloride 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. Usually it will be given to you every 3 (or 4) weeks.

The needle must remain in the vein while Epirubicin hydrochloride is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) – tell the doctor or nurse immediately.

When given directly 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 drug too much.

The dose will depend upon the type of bladder cancer.

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.

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.

If you received more Epirubicin hydrochloride than you should

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

If you missed a dose of Epirubicin hydrochloride

Epirubicin hydrochloride needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of Epirubicin hydrochloride.

If you stop treatment with Epirubicin hydrochloride

Stopping your treatment with Epirubicin hydrochloride may stop the effect on tumour growth. Do not stop treatment with Epirubicin hydrochloride unless you have discussed this with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, Epirubicin hydrochloride can cause 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
• you have 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 hydrochloride)
• If you have a severe allergic reaction, symptoms include faintness, skin rash, itching, fever, chills, swelling of the face and difficulty in breathing of wheeze. In some cases collapse may occur.

Other side effects that may occur:

Very common, may affect more than 1 in 10 people:

• inhibition of blood cell production in the bone marrow (myelosuppression)
• decreased number of white blood cells (leucocytopenia)
• decreased number of a special form of white blood cells (granulocytopenia and neutropenia)
• neutropenia accompanied by fever (febrile neutropenia)
• decrease in red blood cells (anaemia)
• hair loss (alopecia) normally reversible
• your urine may have a red colour for up to two days after treatment. This is normal and nothing to worry about

Common, may affect up to 1 in 10 people:

• Feeling and being sick (nausea and vomiting)
• Diarrhoea
• feeling very dry and thirsty (dehydration)
• Infection
• Loss of appetite
• inflammation of the oesophagus (oesophagitis)
• Inflammation of the mouth
• Hot flushes
• inflammation of a mucous membrane (mucositis)
• inflammation of the mucosa of the mouth with areas of painful erosions, ulceration and
• bleeding (stomatitis)
• Injection site reactions (eg. redness)
• bladder inflammation with pain when passing urine (chemical cystitis), sometimes with blood in the urine (haemorrhagic) following administration into the bladder

Uncommon, may affect up to 1 in 100 people:

• 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
• decreased number of platelets (thrombocytopenia)

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

• Dizziness
• Severe hypersensitivity (anaphylaxis)
• Malaise and weakness,
• Abnormal heart rhythm or rate; changes in the ECG (heart trace), congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm).
• Enlargement of the liver
• 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

Not known, frequency cannot be estimated from the available data:

• fever, infections, inflammation of the lungs (pneumonia), systemic infection (sepsis) or a state of shock resulting from blood poisoning (septic shock) may occur.
• Bleeding (haemorrhage) and inadequate oxygen supply to tissues (tissue hypoxia) were reported as a result of reduced blood cell production in the bone marrow
• discharge from the eye with itching, redness and swelling (conjunctivitis); eye pain, blurred vision, abnormal intolerance to light (keratitis)
• occlusion of blood vessel due to a blood clot (thromboembolic events) including occlusion of a blood vessel in the lungs (pulmonary embolism [in isolated cases with fatal outcome])
• Inflammation, burning sensation and pain in the mouth, sores and pain on swallowing, pigmentations and bleedings in the mouth.
• Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)
• hardening and loss of elasticity of the veins (phlebosklerosis), severe cellulitis, tissue necrosis after accidental paravenous injection

The quantity of blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction may be reduced (asymtomatic drops in left ventricular ejection fraction).

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.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet.

5. how to store epirubicin hydrochloride

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

Store refrigerated (2°C to 8°C).

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

The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Epirubicin hydrochloride contains

• The active substance is epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid, water for injections.