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Epirubicin Hydrochloride 2 Mg/Ml Injection

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This leaflet contains important information about your medicine; read it carefully.

Keep this leaflet; you may want to read it again.

If you have any questions or are not sure about anything, ask your doctor or pharmacist.


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PATIENT INFORMATION LEAFLET

Epirubicin Hydrochloride 2 mg/ml Injection

In this leaflet:

1.    What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

2.    Before you use Epirubicin Hydrochloride

3.    How this medicine is used

4.    Possible side effects

5.    Howto store this medicine

6.    Contents of the pack and other information

1. What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

Epirubicin Hydrochloride Injection is an anti-cancer medicine in the form of a solution for injection. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Epirubicin hydrochloride is used to treat a variety of cancers, either alone or in combination with other medicines. The way in which it is used depends upon the type of cancer that is being treated. It is useful in treating the following conditions:

•    Cancer of the breast, ovary, stomach, lung, bowel or rectum

•    Malignant lymphoma e.g. Hodgkin’s disease and non-Hodgkin’s lymphoma

•    Leukaemia - cancer of the blood

•    Multiple myeloma

•    Non-invasive bladder cancer

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

Taking/using other medicines:

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).

Please tell your doctor if you are taking, or have recently taken, any other medicines, including those you have bought.

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 and breast-feeding:

Tell your doctor if you are pregnant, trying to become pregnant or breast-feeding. 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.

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.

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

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

3. How this medicine is used


2. Before you use Epirubicin Hydrochloride

You should not use this medicine:

•    if you have had an allergic reaction to it or similar medicines in the past

•    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 medicines as epirubicin (called anthracyclines). They 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 pregnant or breast-feeding

For instillation into the bladder, Epirubicin Hydrochloride Injection should not be used:

•    if you have a urine infection

•    if you have inflammation of your bladder

•    if your tumour penetrates the bladder wall

•    if your doctor has problems inserting a catheter (tube) into your bladder

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

Special care will be taken:

•    to make sure the number of cells in your blood does not drop too low. Your doctor will check this regularly

•    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

•    to make sure your heart is working properly. Your doctor will check this regularly

•    if you have received or are receiving radiotherapy to the chest area

The dose of medicine given to you will depend on the type of cancer you have, your health, how well your liver and kidneys are working and any other medicines you may be taking.

By injection or infusion into a vein

The medicine will be given to you as an injection into a vein over 3-5 minutes. Or it may be diluted with glucose (sugar solution) or sodium chloride (salt water) before it is given slowly, usually via a drip into a vein over 30 minutes. You may be given another dose of this medicine in 3 weeks.

By being put into the bladder (intravesical administration)

The medicine may be given directly into the bladder using a catheter. If this method is used, you should not drink any fluids for 12 hours before treatment so that your urine will not dilute the medicine too much. The medicine should be kept in your bladder for 1 hour after being given. You will need to alter your position occasionally to ensure that the medicine reaches all parts of your bladder.

When emptying your bladder after the medicine has been given, take care that your urine does not come into contact with your skin. In case contact does happen, thoroughly wash the affected area with soap and water but do not scrub.

While you are receiving epirubicin your doctor will take regular blood tests. This is to measure the effect the medicine is having. Your doctor will also do regular tests on how your heart is working.

If the medicine has been added to a bag of fluid for injection, or to be given into the bladder, it should be labelled with the strength of the medicine, volume and the time after which it should not be used.

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

Cancer Indication

Epirubicin Dose (mg/m2)ab

Monotherapy

Combination therapy

Ovarian cancer

60-90

50-100

Gastric cancer

60-90

50

SCLC

120

120

NSCLC

135 or 145

Colorectal cancer

60-90

20-50

Leukaemia

60-90

45

Multiple myeloma

60-90

20, or 60-90

Hodgkin’s disease

60-90

25-50

Non-Hodgkin’s lymphoma

60-90

60-90 or lower as needed

Bladder cancer

50 mg/50 ml or 80 mg/50 ml (carcinoma in situ)

Prophylaxis:

50 mg/50 ml weekly for 4 weeks then monthly for 11 months

a Doses generally given Day 1 or Day 1, 2 and 3 at 21-day intervals


Epirubicin Hydrochloride 2 mg/ml Injection

This is an extract from the Summary of Product Characteristics to assist in the administration of Epirubicin Hydrochloride 2 mg/ml Injection. You should be experienced in the handling and use of cytotoxic agents and be familiar with the SmPC. Reference should also be made to the local policy guidelines on the safe handling of cytotoxic agents.

For Intravenous Injection and Intravesical Administration Incompatibilities

Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug, which includes sodium bicarbonate containing solutions. Only the diluents detailed in the ‘Dilution Instructions’ should be used.

Neither the injection nor any diluted solution should be mixed with any other drugs. (A physical incompatibility with heparin has been reported).

Dilution Instructions

The injection may be given via the tubing of a free-running intravenous saline infusion (see below). Where the injection is to be administered after dilution, the following instructions should be followed.

Epirubicin Hydrochloride solution for injection may be diluted under aseptic conditions 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.

Safe Handling

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

The following general advice appears in section 6.6 of the SPC.

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.

Dosage and Administration Intravenous administration

It is advisable to administer epirubicin via the tubing of a free-running intravenous saline infusion. Care should be taken to avoid extravasation.

Conventional dose

When epirubicin is used as a single agent, the recommended dose in adults is 60-90 mg/m2 body area. Epirubicin should be injected intravenously over 3-5 minutes. The dose should be repeated at 21-day intervals, depending upon the patient’s haematomedullary status.

If signs of toxicity, including severe neutropenia/neutropenic fever and thrombocytopenia occur, dose modification or postponement of the subsequent dose may be required.

Epirubicin as a single agent for high dose treatment of lung cancer should be administered according to the following regimens:

•    Small cell lung cancer (previously untreated): 120 mg/m2 on day 1, every 3 weeks

•    Non-small cell lung cancer (squamous, large cell, and adenocarcinoma previously untreated): 135 mg/m2 on day 1 or 45 mg/m2 on days 1, 2 and 3 every 3 weeks.

For high dose treatment, epirubicin may be given as an intravenous bolus over 3-5 minutes or as an infusion of up to 30 minutes duration.

Breast cancer

In the adjuvant treatment of early breast cancer patients with positive lymph nodes, intravenous doses of epirubicin ranging from 100 mg/m2 (as a single dose on day 1) to 120 mg/m2 (in two divided doses on days 1 and 8) every 3-4 weeks, in combination with intravenous cyclophosphamide and 5-fluorouracil and oral tamoxifen, are recommended.

Lower doses (60-75 mg/m2 for high dose treatment) are recommended for patients whose bone marrow function has been impaired by previous chemotherapy or radiotherapy, by age, or neoplastic bone marrow infiltration. The total dose per cycle may be divided over 2-3 successive days.

The following doses of epirubicin are commonly used in monotherapy and combination chemotherapy for various tumours, as shown:

b Recommended doses as presented in Section 4.2 ‘Posology and method of administration’ of Hospira proposed SPC

Combination therapy

If epirubicin is used in combination with other cytotoxic products, the dose should be reduced accordingly. Commonly used doses are shown in the table above.

Impaired liver function

The major route of elimination of epirubicin is the hepatobiliary system. In patients with impaired liver function the dose should be reduced based on serum bilirubin levels as follows:

Serum Bilirubin    Dose Reduction

24-51 pmol/l    50%

51 pmol/l    75%

Impaired renal function

Moderate renal impairment does not appear to require dose reduction in view of the limited amount of epirubicin excreted by this route.

Intravesical administration

Epirubicin may be given by intravesical administration for the treatment of superficial bladder cancer and carcinoma-in-situ. It should not be given intravesically for the treatment of invasive tumours that have penetrated the bladder wall, systemic therapy or surgery is more appropriate in these situations. Epirubicin has also been successfully used intravesically as a prophylactic agent after transurethral resection of superficial tumours to prevent recurrence.

Component Specification

Item number:

Q76917

Request number:

AS3944

Country:

United Kingdom

Ol template:

ZHI003

Amalia version:

6

Mulgrave version:

n/a

Dimensions:

308 x 570 mm

Container(s):

Non Standard vial leaflet

Supplier:

ZHOPL

Stock:

tbc

Folded dimensions:

77 x 142.5 mm

Printed both sides:

Yes

Perforated:

No

Pharma code:

Decimal (Binary)

Max pharma code:

18 mm

Pharma code length:

## mm

Supplier Code:

n/a

Colours

Black:

b

hospira


Requester


I have checked this artwork against the registered text including spelling, layout, size, colours, registration numbers and scientific equations, the name and address and trademarks. Also for any possible changes to related items.

This artwork is in conformance with the Marketing Authorisation and can now proceed to the printing stage.

Previous Item Number: Q76277 Latest QP Release Date:


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Date:

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07/Feb/14

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10/Feb/14

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Version 10

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fl7b3i7


For the treatment of superficial bladder cancer the following regimen is recommended, using the dilution table below:

8 weekly instillations of 50 mg/50 ml (diluted with saline or distilled sterile water).

If local toxicity is observed: A dose reduction to 30 mg/50 ml is advised.

Carcinoma-in-situ: Up to 80 mg/50 ml (depending on individual tolerability of the patient).

For prophylaxis: 4 weekly administrations of 50 mg/50 ml followed by 11 monthly instillations at the same dose.

Dilution table for bladder installation solutions

Dose epirubicin required

Volume of 2 mg/ml epirubicin injection

Volume of diluent sterile water for injection or 0.9% sterile saline

Total volume for bladder instillation

30 mg

15 ml

35 ml

50 ml

50 mg

25 ml

25 ml

50 ml

80 mg

40 ml

10 ml

50 ml

The solution should be retained intravesically for 1 hour. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation.

During the instillation, the patient should be rotated occasionally and should be instructed to void urine at the end of the instillation time.

Storage

Store at 2-8°C.

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

In use: Epirubicin Hydrochloride 2 mg/ml Injection may be further diluted in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion. After dilution, physical and chemical in-use stability has been demonstrated for:

Diluent

Target Concentration

Storage Conditions

Time period

0.9% sodium chloride solution for infusion

0.2 mg/ml and 1.0 mg/ml

2-8°C in the absence of light in PVC infusion bags

84 days

5% glucose solution for infusion

0.2 mg/ml and 1.0 mg/ml

2-8°C in the absence of light in PVC infusion bags

84 days

0.9% sodium chloride solution for infusion

0.2 mg/ml and 1.0 mg/ml

25°C under normal lighting conditions in PVC infusion bags

14 days

5% glucose solution for infusion

0.2 mg/ml and 1.0 mg/ml

25°C under normal lighting conditions in PVC infusion bags

14 days

From a microbiological point of view however, 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.

Marketing Authorisation Holder

Hospira UK Limited Warwickshire, CV31 3RW United Kingdom

Date of Revision

February 2014

Like all medicines, epirubicin can have 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 where the injection has been given

•    you have chest pains, shortness of breath or swelling of your ankles (oedema) (these effects may occur up to several weeks after finishing treatment with epirubicin). These side effects are rare.

•    if you have a severe allergic reaction, noticed by feeling faint, skin rash, swelling of the face and difficulty in breathing or wheeze. In some cases collapse may occur. This side effect is rare.

Other side effects that may occur:

Very common side effects which may affect more than 1 person in 10 are listed below:

•    Reduction in blood cell counts (eg anaemia, low white cells which may make you more likely to get an infection,)

•    Hair loss (alopecia) and loss of beard growth (in males)

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

Common side effects which may affect more than 1 person in 100 are listed below:

•    Infection

•    Loss of appetite (anorexia)

•    Dehydration

•    Hot flushes

•    Inflammation of the mouth

•    Feeling and being sick (nausea and vomiting)

•    Diarrhoea

•    Injection site reactions (eg redness)

Uncommon side effects which may affect more than 1 person in 1,000 are listed below:

•    Reduction in blood platelets which increases risk of bruising or bleeding

•    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

Rare side effects which may affect less than 1 person in 1,000 are listed below:

•    Dizziness

•    Malaise and weakness

•    Abnormal liver function which is detected by blood tests

•    Abnormal heart rhythm or rate

•    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

Epirubicin may also affect your liver function and the number of cells in your blood. Your doctor will monitor such effects with regular blood tests.

Epirubicin may affect the function of your heart with early onset effects of changes in the ECG (heart trace), and late onset effects (may be several weeks after stopping treatment) of congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm). The risk of developing heart failure increases with higher total dose of epirubicin. Your doctor will monitor your heart function.

Side effects after epirubicin injection into the bladder

If this medicine is injected directly into the bladder, 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 find it difficult or painful to pass urine. You may also see blood in your urine. Blood in the urine may cause it to appear pink, red or brown in colour. These side effects are mostly reversible. If you notice these side effects tell your doctor.

If you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.


Keep out of the reach and sight of children.

This medicine should be stored at 2 - 8°C (in the fridge).

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

Epirubicin hydrochloride, when diluted in either glucose 5% or sodium chloride 0.9%, should not normally be stored for longer than 24 hours in a fridge.

Do not use after the expiry date printed on the vial label and carton.


6. Contents of the pack and other information


•    The active substance is epirubicin hydrochloride

•    The other ingredients are sodium chloride, water for injections and hydrochloric acid used as a pH adjuster

Epirubicin Hydrochloride is in the form of a solution for injection.

Each millilitre (ml) of solution contains 2 milligrams (mg) of epirubicin hydrochloride. The medicine comes in glass containers called vials, containing 10 mg (5 ml), 50 mg (25 ml), 100 mg (50 ml) and 200 mg (100 ml) of epirubicin hydrochloride.

The vials may be wrapped in a protective plastic to reduce the risk of spillage if the vials break: these are referred to as ONCO-TAIN™.

The vials are available in single packs of 5 ml, 25 ml, 50 ml or 100 ml.

The marketing authorisation holder and company responsible for batch release in the EU is Hospira UK Limited, Queensway, Royal Leamington Spa, Warwickshire, CV31 3RW, United Kingdom.

Date of Revision

September 2013


Component Specification

Item number:

Q76917

Request number:

AS3944

Country:

United Kingdom

Ol template:

ZHI003

Amalia version:

6

Mulgrave version:

n/a

Dimensions:

308 x 570 mm

Container(s):

Non Standard vial leaflet

Supplier:

ZHOPL

Stock:

tbc

Folded dimensions:

77 x 142.5 mm

Printed both sides:

Yes

Perforated:

No

Pharma code:

Decimal (Binary)

Max pharma code:

18 mm

Pharma code length:

## mm

Supplier Code:

n/a

Colours

Black:

b

Hospira


Requester


I have checked this artwork against the registered text including spelling, layout, size, colours, registration numbers and scientific equations, the name and address and trademarks. Also for any possible changes to related items.

This artwork is in conformance with the Marketing Authorisation and can now proceed to the printing stage.

Previous Item Number: Q76277 Latest QP Release Date:


Signed:

Date:

Version 1

Technician:

Date:

DM

07/Feb/14

Version 2

Technician:

Date:

KN

10/Feb/14

Version 3

Technician:

Date:

XX

dd/mmm/yy

Version 4

Technician:

Date:

XX

dd/mmm/yy

Version 5

Technician:

Date:

XX

dd/mmm/yy

Version 6

Technician:

Date:

XX

dd/mmm/yy

Version 7

Technician:

Date:

XX

dd/mmm/yy

Version 8

Technician:

Date:

XX

dd/mmm/yy

Version 9

Technician:

Date:

XX

dd/mmm/yy

Version 10

Technician:

Date:

XX

dd/mmm/yy


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