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EPIRUBICIN HYDROCHLORIDE 2 MG/ML SOLUTION FOR INJECTION
Active substance(s): EPIRUBICIN HYDROCHLORIDE / EPIRUBICIN HYDROCHLORIDE / EPIRUBICIN HYDROCHLORIDE
231-30-87028-P LEA EPIRUBICIN 2MG/ML SOL 5ML TEVAH FrPCH
10 June 2014
The following information is intended for
medical and healthcare professional only:
PREPARATION GUIDE FOR USE WITH
2 mg/ml, SOLUTION FOR INJECTION
It is important that you read the entire
contents of this procedure prior to the
preparation of either the Epirubicin
hydrochloride 2 mg/ml solution for
injection or infusion.
Epirubicin hydrochloride 2 mg per ml
solution for injection or infusion.
hydrochloric acid, for pH adjustment
water for injections.
Store in the refrigerator (2-8°C).
Store and transport refrigerated.
Do not freeze.
Chemical and physical in-use stability is as
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
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 a mobile solution after two to
a maximum of four hours equilibration
at controlled room temperature
2.1 Epirubicin hydrochloride vial:
Epirubicin hydrochloride 2 mg/ml is
delivered in colourless, Type 1 glass
vials with bromobutyl rubber cap,
aluminium closing and snap-cap,
with resp. 5 ml, 10 ml, 25 ml, 75 ml
and 100 ml solution for injection or
Each carton contains a single vial.
Not all pack sizes may be marketed.
2.2 Solvent for epirubicin hydrochloride
Epirubicin hydrochloride 2 mg/ml can
be diluted in NaCl 0.9% or Glucose
5% and be administered
intravenously. The solution must be
prepared immediately prior to use.
For intravesical administration the
product must be diluted with NaCl
0.9% or sterile water. The
concentration of the dilution has to
be 0.6-1.6 mg/ml.
3. RECOMMENDATIONS FOR THE SAFE
If an infusion solution is to be prepared,
this should be performed by trained
personnel under aseptic conditions.
Preparation of an infusion solution
should be performed in a designated
People working with Epirubicin
hydrochloride 2 mg/ml are required to
wear protective gloves, safety goggles
and a mask.
Epirubicin hydrochloride 2 mg/ml can be
diluted in NaCl 0.9% or Glucose 5% and
be administered intravenously. The
solution must be prepared immediately
prior to use.
For intravesical administration the
product must be diluted with NaCl 0.9%
or sterile water. The concentration of the
dilution has to be 0.6-1.6 mg/ml.
Epirubicin hydrochloride 2 mg/ml contains
no preservatives and is therefore only
suitable for single use. After use the
unused remainder should be destroyed
according to the regulations for cytostatic
agents. See also “Disposal”.
Inactivation of spilled or leaked medicinal
product can be obtained with a 1%
sodium hypochlorite solution or simply
with a phosphate buffering agent
(pH >8) until the solution is decolourised.
All cleaning materials are disposed of as
mentioned under “Disposal”.
Pregnant women must avoid contact
with cytostatic agents.
Excreta and vomit should be cleaned up
A damaged vial must be treated with the
same precautions and must be considered
as contaminated waste. Contaminated
waste must be stored in appropriate
specially marked waste containers. See
4. PREPARATION OF THE SOLUTION
Epirubicin is only intended for intravenous
or intravesical use.
4.1 PREPARATION FOR THE
Epirubicin hydrochloride 2 mg/ml can
be diluted in NaCl 0.9% or Glucose 5%
and be administered intravenously.
The solution must be prepared
immediately prior to use.
The concentration of the dilution has
to be 0.6-1.6 mg/ml.
It is advisable that the red solution,
which should be clear and transparent,
is injected via the catheter of a free
running intravenous infusion of a
physiological salt solution or glucose
5% over a period of up to a duration
of 30 minutes (depending on the
dose and the volume of the infusion).
The needle should be properly placed
in the vein. This method reduces the
risk of thrombosis and extravasation
that could lead to severe cellulitis and
necrosis. In case of extravasation,
administration should be stopped
immediately. Injection in small veins
and repeated injection in the same
vein can lead to venous sclerosis.
For the treatment with a high dose
epirubicin can be administered as an
intravenous bolus over 3-5 minutes or as
an infusion up to 30 minutes duration.
4.2 PREPARATION FOR THE
For intravesical administration
Epirubicin hydrochloride 2 mg/ml
must be diluted with NaCl 0.9% or
sterile water. The concentration of
the dilution has to be 0.6-1.6 mg/ml.
DILUTION TABLE FOR BLADDER
epirubicin 2 mg/ml
Any unused product, all materials used in
the preparation and administration, or
which have come in contact with
epirubicin hydrochloride in any way,
must be destroyed in accordance with
PACKAGE LEAFLET: INFORMATION FOR THE USER
EPIRUBICIN HYDROCHLORIDE 2 mg/ml,
SOLUTION FOR INJECTION
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, please ask your doctor or
• 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
• If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. See
IN THIS LEAFLET:
1. What Epirubicin hydrochloride 2 mg/ml is and what it is used for
2. Before you use Epirubicin hydrochloride 2 mg/ml
3. How to use Epirubicin hydrochloride 2 mg/ml
4. Possible side effects
5. How to store Epirubicin hydrochloride 2 mg/ml
6. Further information
WHAT EPIRUBICIN HYDROCHLORIDE
2 mg/ml IS AND WHAT IT IS USED FOR
Medicinal product group
Epirubicin belongs to the group of cytostatics (products to fight cancer).
Epirubicin makes sure that cancer cells cannot grow any more, which
eventually kills them.
Epirubicin is administered for the treatment of:
• breast cancer
• stomach cancer
• Epirubicin hydrochloride is also used intravesically (directly into the
bladder) to treat early (superficial) urinary bladder cancer and to
help prevent recurrence of bladder cancer after surgery.
Epirubicin is often used concomitantly with other cancer fighting
medicinal products (in so-called polychemotherapy schedules).
BEFORE YOU USE EPIRUBICIN
HYDROCHLORIDE 2 mg/ml
Do not use Epirubicin hydrochloride 2 mg/ml
• if you are allergic (hypersensitive) to epirubicin, similar medicines
(called anthracyclines or anthracenediones, see below) or any of
the other ingredients of Epirubicin hydrochloride 2 mg/ml
• if you have been treated before with high doses of some other
anti-cancer medicines including doxorubicin and daunorubicin
which belong to the same group of drugs as epirubicin
hydrochloride 2 mg/ml (called anthracyclines). They have similar
side effects (including those effects on the heart).
• if you suffered or currently have heart problems
• if you are breast-feeding
• if you have a low blood count
• if you have a severe liver function disorder
• if you suffer from an acute severe infection.
When administered intravesically (directly into the bladder), epirubicin
hydrochloride 2 mg/ml should not be used if:
• the cancer has penetrated the bladder wall
• you have an infection in your urine tract
• you have pain or inflammation in your bladder
• your doctor has problems inserting a catheter (tube) into your
• there is a large volume of urine left in your bladder after you
attempt to empty it
• if your urine contains blood
• if you have a contracted bladder.
Take special care with Epirubicin hydrochloride 2 mg/ml
• if you are elderly or a child, because of the higher risk of severe
cardiac side effects. Your cardiac function will be checked before
and after the treatment with epirubicin.
• if you have had problems with your heart in the past or if you are
currently experiencing such problems. You should inform your
doctor. The dose of epirubicin will have to be adjusted. Your doctor
will regularly check if your heart is working properly.
• if you have previously been treated with products to fight cancer
(such as with doxorubicin or daunorubicin, anthracenedion
derivatives or trastuzumab) or if you have had radiation, because
the risk of severe cardiac side effects is greater. Inform your doctor
because this is included in determining the total dose of epirubicin
you will be administered.
• if you have a liver or kidney disorder. This may cause an increase in
side effects. Both the kidney function and the liver function will be
checked regularly and if needed the dose will be adjusted.
• if you desire to have children. Both men and women should use
effective contraceptive measures both during and for 6 months
after the treatment. Men are advised to request information about
the possibility of storing sperm by means of freezing before the
• if you suffer from infections or bleedings. Epirubicin may affect the
bone marrow. The number of white blood cells in your blood will
be reduced, which makes you more susceptible to infections
(leukopenia). Bleedings can occur more easily (thrombocytopenia).
These side effects are temporary in nature. The reduction of the
number of white blood cells is greatest 10-14 days after the
administration and usually returns to normal 21 days after the
• if you have recently received or want to receive any vaccination
• to check the level of uric acid in your blood. Your doctor will check
• to ensure the number of cells in your blood does not drop too low.
Your doctor will regularly check this.
• if you are experiencing severe inflammation or ulcers in your mouth
• if you have received or are receiving radiotherapy to the chest area
• if you get a burning feeling at the site of the administration. This
could indicate that epirubicin is leaking outside the blood vessel.
Warn your doctor about this.
Please consult your doctor if one of the above mentioned warnings is
applicable to you, or has been applicable to you in the past.
Using other medicines
Attention: the following remarks may also be applicable to the recent
use of medicinal products or their use in the near future.
The medicines mentioned in this section may be known to you under
a different name, often the brand name. In this section only the
active ingredient(s) of the medicinal product is mentioned, not the
brand name! Therefore always carefully read on the package or in
the patient leaflet what the active ingredient is of the medicines you
An interaction means that (medicinal) products that are used together
can influence each other's effect and/or side effect. An interaction can
occur with the concomitant use of this solution and:
• prior or concomitant administration of other products related to
epirubicin (so-called anthracyclines; (for instance the cancer fighting
medicines mitomycin-C, dacarbazine, dactinomycin and
cyclophosphamide);), other medicines that may affect the heart (for
instance the cancer fighting medicines 5-fluorouracil,
cyclophosphamide, cisplatin, taxanes, trastuzumab); the
harmfulness to the heart can increase. Extra monitoring of the heart
is then necessary.
• epirubicin can increase the effect of radiation and even after quite
some time after the radiation it can cause serious side effects in the
• rifampicin (product used for the treatment of tuberculosis) and
barbiturates (products that are used for insomnia or epilepsy, such
as for instance phenobarbital); these products decrease the amount
of epirubicin in the blood, which could lead to a reduced effect of
• paclitaxel and docetaxel (products that are used for some cancers);
when paclitaxel is administered before epirubicin or docetaxel is
administered immediately after epirubicin, the amount of epirubicin
in the blood is increased, which could lead to an increase of the
• dexverapamil (a product that is used to treat some cardiac
disorders); when used together with epirubicin it may have a
negative effect on bone marrow
• interferon α2b (a product used in some cancers and lymphomas
and some forms of hepatitis)
• quinine (a product used for treatment of malaria and for leg
cramps); quinine may speed up the distribution of epirubicin into
the body, which may have a negative effect on the red blood cells
• dexrazoxane (a product sometimes used with doxorubicin to
reduce the risk of heart problems); the time that epirubicin is
present in the body may be decreased, which could lead to
decreased effect of epirubicin
• cimetidine (a product to reduce the acid in your stomach); the
amount of epirubicin in the blood is increased, which could lead to
an increase of the side effects
• previous or concomitant treatment with other products which
influence the bone marrow (for instance other products to treat
cancer, sulfonamide, chloramphenicol, diphenylhydantoin,
amidopyrine-derivate, products against certain virus); the
formation of blood cells can be disturbed
• products that cause heart failure
• products that influence the liver function; the degradation of
epirubicin by the liver may be influenced, which may cause a
reduced effect of epirubicin or an increase of the side effects
• live vaccines; there is risk of fatal disease therefore this
combination is not recommended
• cyclosporine (a product that suppresses the immune system); the
immune system may be suppressed too much.
Please tell your doctor or pharmacist if you are using or have recently
used any other medicines, including medicines obtained without a
Using Epirubicin hydrochloride with food and drink
You should not drink within 12 hours before application when
epirubicin will be administered in the bladder.
Fertility, pregnancy and breast-feeding
Fertility and pregnancy
Medicines to fight cancer are only administered during pregnancy in
extreme cases. The benefits for the mother must be weighed against
the possible danger to the unborn child. In animal studies epirubicin
proved to be harmful to the unborn child and can cause deformities.
Both men and women should use good contraceptive measures (pill,
condom) both during and for 6 months after the use of this medicine
to prevent pregnancy.
You should also prevent pregnancy if your partner is treated with
If pregnancy occurs during treatment with epirubicin, genetic
counselling is recommended.
Men who wish to father children in the future should seek advice
about freezing sperm before treatment with epirubicin is started.
It is not known whether epirubicin is excreted in the breast milk. You
should discontinue breast-feeding during treatment with Epirubicin
hydrochloride 2 mg/ml. Ask your doctor or pharmacist for advice
before taking any medicine.
Driving and using machines
Because many people get very nauseous or have to vomit during the
treatment, driving and using machines is not recommended.
Important information about some of the ingredients of Epirubicin
hydrochloride 2 mg/ml
This medicinal product contains 3.5 mg sodium per ml solution for
injection or infusion. To be taken into consideration by patients on a
controlled sodium diet.
HOW TO USE EPIRUBICIN HYDROCHLORIDE
Epirubicin hydrochloride 2 mg/ml will only be given to you under
supervision of a doctor specialised in this type of treatment. You
should check with your doctor or pharmacist if you are not sure.
The dose you are administered will depend on the type of cancer you
have, your health, your age, how well your liver functions are and
other medicines you are taking.
The usual dose is
Depending on your general health and possible previous treatments
the dose schedule is determined, whereby your length and your
weight are taken into account. The amounts in the dose schedule are
expressed in numbers of milligrams per square metre of body surface
This medicine will be administered as an injection in a vein for 3-5
minutes or as an infusion in a vein for a maximum of 30 minutes.
If only epirubicin is administered, so without other cancer medicines,
the recommended dose is 60-90 mg/m² of body surface area. This
dose is administered as a single dose or distributed over 2-3
consecutive days. This is repeated every 21 days. In combination with
other cancer medicines the dose is reduced.
The administration occurs via a catheter or side line of a free running
infusion of a physiological salt solution or glucose (sugar solution).
Higher doses might be given for the treatment of breast cancer
(100-120 mg/m² of body surface area).
Administration via the bladder (intravesical administration)
The product can be given directly into the bladder (for the treatment
of bladder cancer) by means of a catheter. If this method is used, you
must not drink any liquids within 12 hours before the treatment, so
your urine will not dilute the medicine too much. The dissolved
medicine should be kept in your bladder for 1-2 hours after it has been
administered. You will have to change your position occasionally to
make sure the medicine reaches all parts of your bladder.
When you empty your bladder after the medicine has been given,
make sure that your urine does not get in contact with your skin. In
case contact does take place, thoroughly wash the site of contact with
water and soap but do not scrub.
TEVA UK Ref:
While epirubicin is being administered to you your doctor will perform
blood tests. This is to measure the effect of the medicine. Your doctor will
also perform tests to see how your heart functions. Both blood test and
heart function tests are done before and during treatment with epirubicin.
If you notice that Epirubicin hydrochloride 2 mg/ml is too strong or
too weak, consult your doctor or pharmacist.
If more Epirubicin hydrochloride 2 mg/ml was administered than
should have been
Because this medicine is administered by medical personnel the risk of an
overdose is unlikely. Immediately contact your doctor if you suspect that
too much Epirubicin hydrochloride 2 mg/ml has been administered.
If you forget to use Epirubicin hydrochloride 2 mg/ml
Because this medicine is administered by medical personnel it is
unlikely that a dose is missed.
You should check with your doctor if you are not sure.
If you stop using Epirubicin hydrochloride 2 mg/ml
Consult your doctor.
If you have any further questions on the use of this product, ask your
doctor or pharmacist.
POSSIBLE SIDE EFFECTS
Like all medicines Epirubicin hydrochloride 2 mg/ml can cause side
effects, although not everybody gets them.
More than 10% of treated patients can expect to develop undesirable
effects. The most common undesirable effects are decrease in the
production of blood cells (myelosuppression), gastrointestinal side
effects, loss of appetite (anorexia), hair loss (alopecia) and infection.
Skin rash with formation of little
bumps (urticaria) or with severe itching
(pruritis), redness along the
vein that was used for the injection.
Local reactions, rash, itch, skin changes,
redness, flushes, changes in skin and
nail (hyperpigmentation), sensitivity to
light (photosensitivity) or allergic
reaction in the case of radiation
Red coloration of urine for 1 to 2
days after administration
Bladder infection, sometimes bleeding,
local reactions like burning sensations
and frequent urge to urinate have
been observed after administration
into the bladder
Increased blood level of uric acid
Increased amount of proteins in
urine (proteinuria) in patients who
were treated with a high dose
Sexual organs Rare
Absence of menstruation, lack of
sperm cells in sperm
Redness at infusion site
Concomitant administration of certain
medicines for fighting cancer (so-called
substances) can in rare cases lead to
certain forms of cancer of the blood
(secondary acute myeloid leukaemia
(AML) with or without preleukemic
phase). These certain forms of cancer
of the blood can only be observed
after 1-3 years, Malaise, weakness,
(extremely high) fever, chills, changes
in levels of certain enzymes
Local pain, severe cellulitis
(inflammation of cellular tissue), tissue
necrosis (death of tissue), thickening
or hardening of the walls of the veins
(phlebosclerosis) after accidental
injection outside of the vein
The following side effects can, amongst others, occur:
System Organ Frequency
Blood poisoning (sepsis) and shock
as a result of a decrease in the
production of blood cells
Bone marrow depression is an
abnormality in the blood, which means
that fewer new blood cells are
produced (resulting in a shortage of
white blood cells, red blood cells,
platelets; reduced number of a type of
white blood cell (neutrophilic
granulocytes) with fever), and which
involves an increased sensitivity to
infections (due to a shortage of white
blood cells [leukopenia] and anaemia).
Your blood must be checked regularly.
Uncommon Bruising and a tendency to bleed
(due to shortage of platelets
Bleeding, shortage of oxygen in tissue
Severe, immediate allergic reaction
with or without shock including skin
rash and itching; fever and chills.
Certain disorder of the nerves
(peripheral neuropathy), headache
Inflammation of the eye (conjunctivitis
Risk of a reduced effect of the heart
with as a result congestion of the blood
(congestive heart failure), heart
failure,(dyspnoea; accumulation of fluid
in the whole body (oedema),
enlargement of the liver, accumulation
of fluid in the abdominal cavity
(ascites), accumulation of fluid in the
lungs (pulmonary oedema, pleural
effusions), abnormal rhythm of the
heart (gallop rhythm)) cardiotoxicity
(e.g. ECG abnormalities, arrhythmias,
heart muscle disease (cardiomyopathy)),
increased frequency of heart beat
arising from lower chambers of the
heart (ventricular tachycardia), slow
heart rhythm (bradycardia), cessation
of impulse transmission in the heart (AV
block, bundle-branch block).
Decrease of fraction of blood pumped
out of a ventricle with each heart beat
(asymptomatic drops in left ventricular
Uncommon Redness along the veins (phlebitis),
vascular inflammation with the
forming of a blood clot, often felt as a
painful somewhat hard core with
above it red skin (thrombophlebitis)
231-30-87028-P LEA EPIRUBICIN 2MG/ML SOL 5ML TEVAH FrPCH
Shock, forming of blood clots
(thromboembolism), including blood
clot formation in the lungs (pulmonary
emboli, in very rare cases this resulted
Mucous membrane inflammation
(mucositis (can occur 5 to 10 days after
the start of the treatment)), inflammation
of the mucous membrane of the
oesophagus (esophagitis), inflammation
of the mucous membrane of the mouth
(stomatitis), vomiting, diarrhoea which
can result in dehydration, nausea (nausea
and vomiting often occur within the first
24 hours (in nearly all patients)), loss of
Oral mucous membrane erosion,
ulceration of the mouth, oral pain,
burning sensation of the mucous
membrane, bleeding in the mouth
(mouth haemorrhage), coloration of
the mouth cavity (buccal
Hair loss (alopecia, in 60-90% of
treated cases. It involves poor
beard growth in men. Hair loss is
dose-dependent and in most cases
Severe side effects which affect the whole body and allergic reactions are
rare when Epirubicin hydrochloride 2 mg/ml is given into the bladder.
Interpretation of frequency
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Not known: frequency cannot be estimated from the available data
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard. By reporting side effects you can help
provide more information on the safety of this medicine.
HOW TO STORE EPIRUBICIN
HYDROCHLORIDE 2 mg/ml
Store in the refrigerator (2°C-8°C). Store and transport refrigerated.
Do not freeze.
After first opening the product should be used immediately.
Chemical and physical in-use stability is as follows.
Viaflo (non-PVC) bag
0.9% NaCl for injection
5% glucose for injection
0.9% NaCl for injection
Water for injection
15-25°C, ambient light
15-25°C, ambient light
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.
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 a mobile solution after two to a maximum of
four hours equilibration at controlled room temperature (15–25°C).
Keep out of the reach and sight of children.
Do not use Epirubicin hydrochloride 2 mg/ml after the expiry date
mentioned on the package after "exp." The first 2 numbers indicate
the month, the last numbers indicate the year.
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 environment.
What Epirubicin hydrochloride 2 mg/ml contains
• The active substance is epirubicin hydrochloride; 1 ml contains 2 mg
• The other ingredients (excipients) are sodium chloride, hydrochloric
acid and water for injections.
What Epirubicin hydrochloride 2 mg/ml looks like and contents of
Epirubicin hydrochloride 2 mg/ml is a medicine in the form of a clear
red solution for injection or infusion. It is delivered in glass injection
vials with 5 ml (10 mg), 10 ml (20 mg), 25 ml (50 mg), 75 ml (150 mg)
or 100 ml (200 mg) of solution for injection or infusion.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Pharmachemie B.V., Swensweg 5, PO Box 552, 2003 RN Haarlem,
Marketing Authorisation holder:
TEVA UK Limited, Eastbourne, BN22 9AG.
This leaflet was last revised: June 2014
10 June 2014
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.