EPIRUBICIN HYDROCHLORIDE 2 MG/ML INJECTION

Active substance: EPIRUBICIN HYDROCHLORIDE

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TECHNICAL LEAFLET

Taking/using other medicines:

PATIENT INFORMATION LEAFLET
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.

Epirubicin Hydrochloride 2 mg/ml Injection

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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. How to 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.

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

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
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.

Epirubicin Hdrochloride 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.

High dose
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.

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

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.

Dilution Instructions

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

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 Dose (mg/m2)ab

Cancer Indication

Monotherapy

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.

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

Safe Handling

Leukaemia

60-90

45

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

Multiple myeloma

60-90

20, or 60-90

Hodgkin’s disease

60-90

25-50

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

Non-Hodgkin’s lymphoma

60-90

60-90 or lower as needed

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.

Bladder cancer

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

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

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.

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

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
24-51 μmol/l
51 μmol/l

Dose Reduction
50%
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.

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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

Overdose
Very high single doses of epirubicin may be expected to cause acute myocardial degeneration
within 24 hours and severe myelosuppression within 10-14 days. Treatment should aim to
support the patient during this period and should utilise such measures as blood transfusion
and reverse barrier nursing. Delayed cardiac failure has been seen with the anthracyclines up
to 6 months after the overdose. Patients should be observed carefully and should, if signs of
cardiac failure arise, be treated along conventional lines.

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. The infusion solution is
chemically stable when stored in PVC infusion bags prepared under full aseptically controlled
conditions for 14 days at room temperature or for 28 days at 2-8°C in the absence of light.
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.

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.

Marketing Authorisation Holder

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

Hospira UK Limited
Warwickshire, CV31 3RW
United Kingdom

Warnings
Epirubicin should only be administered under the supervision of a qualified physician who
is experienced in the use of chemotherapeutic agents. Diagnostic and treatment facilities
should be readily available for management of therapy and possible complications due to
myelosuppression, especially following treatment with higher doses of epirubicin.
Extravasation of epirubicin from the vein during injection may cause severe tissue lesions
and necrosis. Venous sclerosis may result from injection into small vessels or repeated
injections into the same vein.
Careful baseline monitoring of various laboratory parameters and cardiac function should
precede initial treatment with epirubicin.
During treatment with epirubicin, red blood cell, white blood cell, neutrophil and platelet
counts should be carefully monitored both before and during each cycle of therapy.
Leucopenia and neutropenia are usually transient with conventional and high-dose
schedules, reaching a nadir between the 10th and 14th day, values should return to
normal by the 21st day; they are more severe with high dose schedules. Thrombocytopenia
(< 100,000 platelets/mm3) is experienced in very few patients, even following high doses of
epirubicin.
In establishing the maximal cumulative dose of epirubicin, consideration should be given
to any concomitant therapy with potentially cardiotoxic drugs. A cumulative dose of
900-1000 mg/m2 should only be exceeded with extreme caution with both conventional
and high doses of epirubicin. Above this level the risk of irreversible congestive heart
failure increases greatly. An ECG is recommended before and after each treatment cycle.
Alterations in the ECG tracing, such as flattening or inversion of the T-wave, depression
of the S-T segment, or the onset of arrhythmias, generally transient and reversible, need
not necessarily be taken as indications to discontinue treatment. With cumulative doses
< 900 mg/m2, there is evidence that cardiac toxicity rarely occurs. However, cardiac
function must be carefully monitored during treatment to minimise the risk of heart failure
of the type described for other anthracyclines.
Cardiomyopathy induced by anthracyclines is associated with persistent reduction of the
QRS voltage, prolongation beyond normal limits of the systolic interval (PEP/LVET) and
a reduction of the ejection fraction. Cardiac monitoring of patients receiving epirubicin
treatment is highly important and it is advisable to assess cardiac function by non-invasive
techniques such as ECG, echocardiography and, if necessary, measurement of ejection
fraction by radionuclide angiography.
Heart failure may appear several weeks after discontinuing therapy with epirubicin and
may be unresponsive to specific medical treatment. The potential risk of cardiotoxicity
may increase in patients who have received concomitant, or prior, radiotherapy to the
mediastinal pericardial area.
Before commencing therapy with epirubicin, and if possible during treatment, liver function
should be evaluated (SGOT, SGT, alkaline phosphatase, bilirubin).
As with other cytotoxic agents, epirubicin may induce hyperuricaemia as a result of rapid
lysis of neoplastic cells. Blood uric acid levels should therefore be checked so that this
phenomenon may be recognised and properly managed.

Date of Revision
September 2013

4. Possible Side Effects
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)

5. How to store this medicine
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

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.

Epirubicin may impart a red colour to the urine for one or two days after administration.
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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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