EPIRUBICIN HYDROCHLORIDE 2MG/ML SOLUTION FOR INJECTION

PACKAGE LEAFLET: INFORMATION FOR THE USER

Epirubicin Hydrochloride 2 mg/ml Solution for Injection
solution for injection and infusion Epirubicin hydrochloride Read all of this leaflet carefully before you start taking this medicine. - Keep this leaflet. You may need to read it again. - If you have 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 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 use EPIRUBICIN HYDROCHLORIDE 3. How to use EPIRUBICIN HYDROCHLORIDE 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 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. BEFORE YOU USE EPIRUBICIN HYDROCHLORIDE EPIRUBICIN HYDROCHLORIDE should not be used: if you have shown signs of hypersensitive (severe allergy) to epirubicin hydrochloride, similar medicines (anthracyclines) or any of the other ingredients on previous occasions if you have fewer blood cells than normal (your doctor will check this) if you have been treated with the maximum dose of some other anti-cancer medicines including doxorubicin and daunorubicin which belong to the same group of drugs as epirubicin (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 a severe infection if you are breastfeeding




When administered intravesically (directly into the bladder ), EPIRUBICIN HYDROCHLORIDE should not be used:
if the cancer has penetrated the bladder wall if you have an infection in your urine if you have pain or inflammation in 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.

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. if you are experiencing severe inflammation or ulcers in your mouth. to check the level of uric acid in your blood. Your doctor will check this. if your liver and kidneys are not working properly. 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 or are receiving medications that might have side effects on your heart. if you notice a sensation of discomfort close to or at the injection site during the infusion (possible leakage in the surrounding tissue).

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, e.g.: cimetidine (a drug used to reduce the acid in your stomach) paclitaxel and docetaxel (drugs used in some cancers) interferon alpha-2b (a drug used in some cancers and lymphomas and for some forms of hepatitis) quinine (drug used for treatment of malaria and for leg cramps) dexrazoxane (a drug sometimes used with doxorubicin) dexverapamil (a drug used to treat some heart conditions) other medicines that may affect your bone marrow other medicines that may affect your heart and/or liver.
Pregnancy EPIRUBICIN HYDROCHLORIDE may cause births 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 as well as for 6 month after treatment. If pregnancy occurs during treatment with EPIRUBICIN HYDROCHLORIDE, genetic counsellation is recommended. Men who wish to father children in the future should seek advice about freezing sperm before treatment with EPIRUBICIN HYDROCHLORIDE is started. Breast-feeding You must discontinue breast-feeding before and during therapy with 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. Important information about some of the ingredients of EPIRUBICIN HYDROCHLORIDE 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. 1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium. 1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium. 1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium. Doses below 10 ml: This medicinal product contains less than 1mmol sodium (22 mg) per dose, i. e. it is essentially sodiumfree. Doses of 10 ml and above: This medicinal product contains 0.077 mmol/ml. This should be taken into consideration by patients on a controlled sodium diet. 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 is 60-90 mg/m body surface area. Higher dosages (100-120 mg/m 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.





3. HOW TO USE EPIRUBICIN HYDROCHLORIDE





















4. POSSIBLE SIDE EFFECTS Like all medicines, EPIRUBICIN HYDROCHLORIDE can cause side effects, although not everybody gets them. If any of the following happen when EPIRUBICIN HYDROCHLORIDE is given into a vein, tell your doctor immediately: 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. These are very serious side effects. You may need urgent medical attention.

The following side effects may also occur:
Side effects may appear very common (in more than 1 in 10 patients); common (in more than 1 in 100, but less than 1 in 10 patients); uncommon (in more than 1 in 1,000, but less than 1 in 100 patients); rare (in more than 1 in 10,000, but less than 1 in 1,000 patients); very rare (in 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 (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) bleeding (haemorrhage) and tissue hypoxia (inadequate oxygen supply) as a result of myelosupression hair loss (alopecia) normally reversible lack of beard growth in males your urine may have a red colour for up to two days after treatment. This is normal and nothing to worry about Common: allergic reactions feeling sick (nausea) being sick (vomiting) diarrhoea feeling very dry and thirsty (dehydration) loss of appetite
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abdominal pain inflammation of the oesophagus (oesophagitis) increased pigmentation (hyperpigmentation) of the oral mucosa hot flushes inflammation of a mucous membrane (mucositis) inflammation of the mucosa of the mouth with areas of painful erosions, ulceration and bleeding (stomatitis) redness along the infusion vein, local vein inflammation (phlebitis) thickening of the vein walls (phlebosclerosis) local pain and death of tissue (tissue necrosis) following accidental injection into the surrounding tissue (paravenous injection) bladder inflammation with pain when passing urine (chemical cystitis), sometimes with blood in the urine (haemorrhagic) following administration into the bladder




Uncommon: decreased number of platelets (thrombocytopenia) sensitivity to light or hypersensitivity in the case of radiotherapy vein inflammation related to a blood clot (thrombophlebitis) increased pigmentation (hyperpigmentation) of skin and nails skin reddening headache Rare: severe hypersensitivity (anaphylaxis) with or without shock including skin rash, pruritus (itching), fever and chills ECG-changes rapid heart rate (tachycardia) slow heart rate (bradycardia) special forms of arrhythmia (AV block and bundle-branch block) third heart sound (gallop rhythm) heart muscle disease (cardiomyopathy) difficulty in breathing (dyspnoea) accumulation of fluid (oedema) enlargement of the liver accumulation of fluid in the abdominal cavity (ascites) lung oedema accumulation of fluid between thorax and lung (pleural effusions) urticaria (hives) chills dizziness very high body temperature (hyperpyrexia) feeling of discomfort (malaise) weakness absence of menstruation (amenorrhea) lack of sperm in the semen (azoospermia) increased levels of liver enzymes (transaminases) increased levels of uric acid in the blood (hyperuricaemia) malignant tumour of blood-forming tissue (secondary acute myeloid leukaemia), when given in combination with other anti-cancer drugs.



Frequency unknown: fever, infections, inflammation of the lungs (pneumonia), systemic infection (sepsis) or a state of shock resulting from blood poisoning (septic shock) may occur. 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]) 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 Keep out of the reach and sight of children. Store in the refrigerator (2C-8C). Do not use EPIRUBICIN HYDROCHLORIDE after the expiry date which is stated on the carton and the vial. The expiry date refers to the last day of that month. 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

6. FURTHER INFORMATION



This medicinal product is authorised in the Member States of the EEA under the following names:
Belgium Denmark Germany Greece Spain Italy Luxembourg Netherlands Norway United Kingdom Epirubicine Sandoz 2mg/ml oplossning voor injective en infusie Epirubicin Ebewe 2mg/ml Concentrate for solution for infusion Epirubicin Ebewe 2 mg/ml Konzentrat zur Herstellung einer Infusionslsung oder Injektionslsung EPIBICIN SENDRAS 2 mg/ml solucin inyectable o para perfusion EFG Epirubicina Sandoz 2 mg/ml soluzione iniettabile e per infusione Epirubicin Sandoz Epirubicine HCl Ebewe 2mg/ml oplossing voor injectie en infusie Epirubicin Ebewe 2 mg/ml injeksjonsvske/infusjonsvske, opplsning Epirubicin Hydrochloride 2mg/ml Solution for Injection



This leaflet was last approved in December 2010. ---------------------------------------------------------------------------------------------------

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 at 2C to 8C. Shelf life:2 years Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 7 days at 2 to 8C 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 8C.






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