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PACKAGE LEAFLET: INFORMATION FOR THE USER

Epirubicin Hydrochloride 10 mg & 50 mg Powder for Solution for Injection

Epirubicin Hydrochloride

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

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

-    If you have any further questions, ask your doctor or phannacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may hann 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 phannacist.

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 to you

4.    Possible side effects

5.    How to store Epirubicin Hydrochloride

6.    Further infonnation

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

The name of your medicine is Epirubicin Hydrochloride 10 mg or 50 mg powder for Solution for injection.

Epirubicin Hydrochloride belongs to a group of medicines called anthracyclines used to treat cancer. Epirubicin Hydrochloride is a medicine that acts upon cells that are actively growing, such as cancer cells in such a way as to slow or stop their grow th, and increases the likelihood that the cells die. This medicine helps to selectively kill the cancer tissue rather than nonnal, healthy tissue.

Epirubicin Hydrochloride is used to treat a variety of cancers, either alone or in combination with other drags.

The way in which it is used depends upon the type of cancer that is being treated.

When injected into the bloodstream, Epirubicin Hydrochloride has been found to be useful in the treatment of cancers of the breast, ovaries, stomach, bowel and lung. In addition, Epirubicin hydrochloride can be given the same way to treat cancers of the blood fonning tissues such as malignant lymphomas, leukaemias and multiple myeloma.

In addition, Epirubicin Hydrochloride can be injected into the bladder through a tube. This is sometimes used to treat abnonnal cells or cancers of the bladder wall. It can also be used after other treatments to try and prevent such cells from growing again.

2. BEFORE YOU ARE GIVEN EPIRUBICIN HYDROCHLORIDE

Do not use Epirubicin Hydrochloride

-    if you are allergic(hypersensitive) to epirubicin hydrochloride or any of the other ingredients of Epirubicin Hydrochloride Powder for Solution for Injection.

-    if you are aware that your blood counts are too low, as Epirubicin hydrochloride can lower them further.

-    if you have previously been treated with Epirubicin Hydrochloride or similar chemotherapy drags like doxorubicin or daunorabicin, as previous treatment with these similar medicines can increase the risk of side effects with this medicine.

-    if you have suffered from severe heart trouble in the past, or are presently receiving treatment for this.

-    if you suffer from a systemic infection

-    if you are breast-feeding

Epirubicin should not be injected into the bladder if:

-    you suffer from urinary tract infection

-    the tumour has penetrated the bladder wall

-    there are problems inserting the catheter into the bladder

-    you have an inflammation of the bladder

-    you have a large volmne of urine left in your bladder after you attempt to empty

-    your bladder is contracted.

Take special care with Epirubicin Hydrochloride:

-    if your liver or kidneys are not working properly. This will help your doctor decide if this is suitable for you

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

-    if the 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

Using other medicines

Please tell your doctor or phannacist 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. Avoid becoming pregnant while you or your partner is being treated with Epirubicin hydrochloride as well as for 6 months after treatment.

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

You should stop breast feeding before starting treatment with this medicine as some of the drag may get into your milk and possibly hann your child.

Ask your doctor or phannacist for advice before taking any medicine.

Driving and using machines

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

Important information about some of the ingredients of Epirubicin Hydrochloride

Epirubicin Hydrochloride 10 mg & 50 mg powder for solution for injection contains methylhydroxybenzoate, which may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

3. HOW EPIRUBICIN HYDROCHLORIDE IS GIVEN TO YOU

If you are prescribed Epirubicin Hydrochloride, it will be given to you by doctors or nurses experienced in giving chemotherapy.

Epirubicin Hydrochloride will nonnally be given to you by a doctor or a nurse through a drip (infusion) into a vein.

Your doctor will decide what dose to give and the number of days of treatment you will receive depending upon your condition.

The dose is decided by taking into account the condition you have, your height and weight. From your height and weight the doctor will work out your body surface area; and it is this that your dose is calculated from.

Epirubicin Hydrochloride made into a solution can also be put directly into the bladder to treat bladder cancer, or to help prevent it returning. The dose depends on the type of bladder cancer you have.

When this medicine is injected directly into the bladder, you will be instructed not to drink any fluid for 12 hours before treatment to avoid dilution of the medicine with urine in your bladder.

While one course of treatment may sometimes be enough, more often your doctor will advise further courses in three or four weeks time. It may take several courses before your illness is under control and you feel better.

Regular checks by your doctor during Epirubicin Hydrochloride treatment

Before and during treatment your doctor will be making regular checks of your blood cell counts, blood uric acid levels, liver function and carefully monitoring your heart function. Monitoring of the heart function will be continued for several weeks following the end of treatment.

If you receive more Epirubicin Hydrochloride than you should

As this medicine will be given to you by a doctor or nurse it is unlikely that you will be given too little or too much. Please tell your doctor if you have any concerns.

In case you are given a higher dose than required your heart function and blood cells will be closely monitored.

High doses can worsen side effects.

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The following information is intended only for doctors or healthcare professionals: Incompatibilities

Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drag. Epirubicin Hydrochloride should not be mixed with heparin due to chemical incompatibility, which may lead to precipitation when the drugs are in certain proportions.

Epirubicin Hydrochloride can be used in combination with other antitumour agents, but it is not recommended that it be mixed with other drags.

Interaction with other medicinal products and other forms of interaction

It is not recommended that Epirubicin Hydrochloride be mixed with other drugs. But Epirubicin Hydrochloride can be used in combination with other anticancer drags. Cimetidine increases the formation of the active metabolite of epirubicin and the exposure of the unchanged epirubicin by pharmacokinetic interaction.

Instructions for use, handling and disposal Preparation of the freeze-dried powder for intravenous use.

The product should be dissolved in 5 ml or 25 ml 0.9% sodium chloride or water for injections to get the final concentration of 2 mg/ml. The vial contents will be under a

negative pressure. To minimize aerosol formation during reconstitution, particular care should be taken when the needle is inserted. Inhalation of any aerosol produced during reconstitution must be avoided. After gentle agitation the reconstituted solution will be transparent and red in appearance.

Intravenous use

Epirubicin Hydrochloride should be administered into the tubing of a freely flowing infusion (0.9% sodium chloride). To minimize the risk of thrombosis or perivenous extravasation, the usual infusion times range between 3 and 20 minutes depending upon dosage and volume of the infusion solution. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration Discard any unused solution.

Intravesical use

The product should be dissolved in 5 ml or 25 ml 0.9% sodium chloride injection or water for injections to get the final concentration of 2 mg/ ml. Epirubicin Hydrochloride should be instilled using a catheter and retained intravesically for 1 hour. During instillation, the patient should be rotated to ensure that the vesical mucosa of the pelvis receives the most extensive contact with the solution. To avoid undue dilution with

4. POSSIBLE SIDE EFFECTS

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

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

Please contact your doctor or nurse immediately if you notice any of the following side effects:

Very coimnon (occur in more than 1 in 10 patients):

Hair loss (normally reversible), reduced growth of beard.

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

-    feeling or being sick

-    diarrhoea (which can result in dehydration)

-    loss of appetite

-    abdominal pain

-    inflammation of the gullet (oesophagitis)

-    high levels of pigments in the mouth

-    hot flushes

-    bladder inflammation (chemical cystitis) sometimes with blood following administration into the bladder

-    inflammation of membranes in the digestive tract (mucositis) including inflammation of the linings of the mouth (stomatitis)

-    redness along the infusion vein

-    inflammation of a vein, usually in the legs (local phlebitis)

-    hardening of the walls of the vein (phlebosclerosis)

-    local pain and tissue death may occur (following accidental injection into the surrounding tissue)

-    allergic reactions after being given into the bladder

Uncoimnon (occur in more than 1 in 1000 patients, but less than 1 in 1001:

-    darkened areas (hyperpigmentation) of the skin and nails

-    skin reddening

-    inflammation and a blood clot in a vein (thrombophlebitis)

-    sensitivity to light (photosensitivity) or allergic reaction (hypersensitivity) to radiotherapy - referred to as “recall phenomenon”

Rare (occur in more than 1 in 10,000 patients, but less than 1 in 1000):

-    increased transaminase levels (increased levels of some liver enzymes)

-    ECG (electrocardiogram) changes

-    rapid heart rate (tachycardia and ventricular tachycardia)

-    slow heart rate (bradycardia)

-    abnonnal heart beats (arrhythmias)

-    specific fonns of arrhythmias (AV block and bundle-branch block)

-    heart muscle disease (cardiomyopathy)

-    heart problems (congestive heart disease)

-    difficulty in breathing (dyspnoea)

-    accumulation of fluid (oedema and pulmonary oedema)

-    enlargement of the liver

-    accumulation of fluid in the abdominal cavity (ascites)

-    accumulation of fluid between the chest wall and lungs (pleural effusion)

-    third heart sound (gallop rhythm)

-    hives (urticaria)

-    malignant tumour of blood-forming tissues (secondary acute myeloid leukaemia) - results when given in combination with other anti-cancer medicinal products

-    fever

-    chills

-    dizziness

-    increased body temperature (hyperpyrexia)

-    feeling of discomfort or uneasiness (malaise)

-    weakness

-    severe allergic reactions (anaphylaxis) - with or without shock including skin rash, itching (pruritis), fever and chills

-    absence of menstrual periods (amenorrhoea)

-    lack of levels of male spenn (azoospermia)

Not known (cannot be estimated from the available data)

-    inhibition of blood cell production in the bone marrow (myelosuppression)

-    decreased number of white blood cells (leucopenia)

-    decreased number of specific fonn of white blood cells (granulocytopenia)

-    neutropenia accompanied by fever (febrile neutropenia)

-    decreased number of platelets (thrombocytopenia)

-    decrease in red blood cells (anaemia)

-    bleeding (haemorrhage)

-    inadequate oxygen supply (tissue hypoxia)

-    fever

-    infections

-    inflammation of the lungs (pneumonia)

-    systemic infection (sepsis) and septic shock

-    blockage of blood vessels by dislodged blood clot (thromboembolic events)

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

5. HOW TO STORE EPIRUBICIN HYDROCHLORIDE

Keep out of the reach and sight of children.

Do not use Epirubicin Hydrochloride after the expiry date which is stated on the vial label & carton after “EXP”. The expiry date refers to the last day of that month. The pharmacist will check this when your medicine is prepared for you. If the solution is cloudy after preparation, the doctor or nurse who is preparing the medicine for you will dispose off it safely.

The unopened vials should be stored below 30°C in the original container until ready for use.

Reconstituted solution should be used immediately.

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

6. FURTHER INFORMATION

What Epirubicin Hydrochloride contains

-    The active substance is epirubicin hydrochloride

-    The other ingredients are lactose monohydrate, methylhydroxybenzoate, hydrochloric acid (for pH adjustment) and water for injections.

What Epirubicin Hydrochloride looks like and contents of the pack

Epirubicin Hydrochloride is a freeze dried red to orange coloured cake.

Epirubicin Hydrochloride 10 mg is produced inlO ml Type I moulded flint glass vial with 20 mm rubber stoppers and 20 lmn aluminium flip-off tear-off seal.

Epirubicin Hydrochloride 50 mg is produced in 50 ml Type I moulded flint glass vial with 20 lmn rubber stoppers and 20 mm aluminium flip-off tear-off seal.

Each pack contains a single vial Marketing Authorisation Holder

Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey,

KT10 9NW.

Manufacturer:

APC Pharmaceuticals & Chemicals (Europe) Limited,

9th floor, C.P. House, 97 - 107 Uxbridge Road, Ealing, London, W5 5TL.

Distributed By:

APC Pharmaceuticals & Chemicals (Europe) Limited,

9th floor, C.P. House,

97 - 107 Uxbridge Road,

Ealing, London W5 5TL

This leaflet was last revised in November 2012

For any information about this medicine , please contact the local representative of the Marketing Authorisation Holder:

APC Pharmaceuticals & Chemicals (Europe) Ltd.,

9th floor, C.P. House,

97 - 107 Uxbridge Road,

Ealing, London W5 5TL

Telephone number: 0208 326 3220

urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. The patient should be instructed to void at the end of the instillation.

The following protective recommendations are given due to the toxic nature of this substance:

Personnel should be trained in good technique for reconstitution and handling.

•    Pregnant staff should be excluded from working with this drug.

•    Personnel handling Epirubicin Hydrochloride Powder for Solution for Injection should wear protective clothing: goggles, gowns and disposable gloves and masks.

•    A designated area should be defined for reconstitution (preferably under laminar flow system). Hie work surface should be protected by disposable, plastic-backed, absorbent paper.

•    All items used for reconstitution, administration or cleaning including gloves, should be placed in high-risk, waste disposal bags for high temperature incineration.

•    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 indicated previously.

•    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 brash. In case of contact with the eye(s), hold back the eyelid of the affected eye(s), and flush with copious amounts of water for at least 15 minutes. Then seek medical evaluation by a physician.

•    Always wash hands after removing gloves.

Storage

Store unopened vials below 30°C in the original container until ready for use. Keep the vial in the outer carton.

In use:

In-use stability has been demonstrated for 24 hours at 15°C - 25°C and for 48 hours at 2 - 8°C in water for injections and 0.9% w/v sodium chloride solution.

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 tlie user and would normally not be longer than 24 hours at 2 - 8 °C, unless reconstitution has taken place in controlled and validated conditions.