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BENDAMUSTINE HYDROCHLORIDE ACCORD 2.5 MG/ ML POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): BENDAMUSTINE HYDROCHLORIDE

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Package leaflet: Information for the user

Bendamustine
hydrochloride 2.5 mg / ml
Powder for concentrate
for solution for infusion
Bendamustine hydrochloride

The name of your medicine is Bendamustine
hydrochloride 2.5 mg/ml powder for concentrate
for solution for infusion’ but in the rest of the
leaflet it will be called “Bendamustine
hydrochloride”.
Read all of this leaflet carefully before you start
using this medicine because it contains important
information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your
doctor or pharmacist.
• This medicine has been prescribed for you only.
Do not pass it on to others. It may harm them,
even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor,
pharmacist or healthcare professional. This
includes any possible side effects not listed in
this leaflet. See section 4.
What is in this leaflet
1. What Bendamustine hydrochloride is and what
it is used for
2. What you need to know before you use
Bendamustine hydrochloride
3. How to use Bendamustine hydrochloride
4. Possible side effects
5. How to store Bendamustine hydrochloride
6. Contents of the pack and other information

1. What Bendamustine
hydrochloride is and what it is
used for
Bendamustine hydrochloride is a medicine which
is used for the treatment of certain types of
cancer (cytotoxic medicine).
Bendamustine hydrochloride is used alone
(monotherapy) or in combination with other
medicines for the treatment of the following forms
of cancer:
- chronic lymphocytic leukaemia in cases where
fludarabine combination chemotherapy is not
appropriate for you,
- non-Hodgkin lymphomas, which had not, or only
shortly, responded to prior rituximab treatment,
- multiple myeloma in cases where high-dose
chemotherapy with autologous stem cell
transplantation, thalidomide or bortezomib
containing therapy is not appropriate for you.

2. What you need to know before
you use Bendamustine
hydrochloride
Do not use Bendamustine hydrochloride:
- if you are hypersensitive (allergic) to the active
substance bendamustine hydrochloride or any of the
other ingredients of this medicine (listed in section 6);
- while breast-feeding;
- if you have severe liver dysfunction (damage to
the functional cells of the liver);
- if you have yellowing of the skin or whites of the
eyes caused by liver or blood problems (jaundice);
- if you have severely disturbed bone marrow
function (bone marrow depression) and serious
changes in your number of white blood cells
and platelets in the blood (white blood cells
and/or thrombocyte values drop to < 3,000/µl or
< 75,000/µl, respectively.);
- if you have had major surgical operations less
than 30 days before starting treatment;
- if you have an infection, especially one
accompanied by a reduction in white blood cells
(leucocytopenia);
- in combination with yellow fever vaccines.
Warnings and Precautions
Talk to your doctor before using Bendamustine
hydrochloride
- in case of reduced capability of the bone marrow
to replace blood cells. You should have your
number of white blood cells and platelets in the
blood checked before starting treatment with
Bendamustine hydrochloride, before each
subsequent course of treatment and in the
intervals between courses of treatment.
- in case of infections. You should contact your
doctor if you have signs of infection, including
fever or lung symptoms.
- in case of reactions on your skin during
treatment with Bendamustine hydrochloride.
The reactions may increase in severity.
- in cases of existing heart disease (e.g. heart attack,
chest pain, severely disturbed heart rhythms).
- in case you notice any pain in your side, blood
in your urine or reduced amount of urine. When
your disease is very severe, your body may not
be able to clear all the waste products from the
dying cancer cells. This is called tumour lysis
syndrome and can cause kidney failure and
heart problems within 48 hours of the first dose
of Bendamustine hydrochloride. Your doctor will
be aware of this and may give you other
medicines to help prevent it.
- in case of severe allergic or hypersensitivity
reactions. You should pay attention to infusion
reactions after your first cycle of therapy.
Men receiving treatment with Bendamustine
hydrochloride are advised not to conceive a child
during treatment and for up to 6 months
afterwards. Before starting treatment, you should
seek advice on storing sperm because of the
possibility of permanent infertility.
Unintentional injection into the tissue outside
blood vessels (extravasal injection) should be
stopped immediately. The needle should be
removed after a short aspiration. Thereafter the
affected area of tissue should be cooled. The arm
should be elevated. Additional treatments like the
use of corticosteroids are not of clear benefit (see
section 4).
Other medicines and Bendamustine
hydrochloride
Tell your doctor or pharmacist if you are taking, have
recently taken or might take any other medicines.
If Bendamustine hydrochloride is used in
combination with medicines which inhibit the

The following information is intended for
medical or healthcare professionals only:
As with all similar cytotoxic substances, stricter
safety precautions apply as far as nursing staff
and doctors are concerned, due to the potentially
genome-damaging and cancer-causing effect of
the preparation. Avoid inhalation (breathing in)
and contact with the skin and mucous
membranes when handling Bendamustine
hydrochloride (wear gloves, protective clothing,
and possibly a face mask!). If any parts of the

formation of blood in the bone marrow, the effect
on the bone marrow may be intensified.
If Bendamustine hydrochloride is used in
combination with medicines which alter you immune
response, this effect may be intensified.
Cytostatic medicines may diminish the effectiveness
of live-virus vaccination. Additionally cytostatic
medicines increase the risk of an infection after
vaccination with live vaccines (e.g. viral vaccination).
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you
may be pregnant or are planning to have a baby,
ask your doctor or pharmacist for advice before
using this medicine.
Pregnancy/fertility
Bendamustine hydrochloride can cause genetic
damage and has caused malformations in animal
studies. You should not use Bendamustine
hydrochloride during pregnancy unless certainly
indicated by your doctor. In case of treatment you
should use medical consultation about the risk of
potential adverse effects of your therapy for the
unborn child and genetic consultation is
recommended.
If you are a woman of childbearing potential you
must use an effective method of contraception
both before and during treatment with
Bendamustine hydrochloride. If pregnancy occurs
during your treatment with Bendamustine
hydrochloride you must immediately inform your
doctor and should use genetic consultation.
If you are a man, you should avoid fathering a child
during treatment with Bendamustine hydrochloride
and for up to 6 months after treatment has
stopped. There is a risk that treatment with
Bendamustine hydrochloride will lead to infertility
and you may wish to seek advice on conservation
of sperm before treatment starts.
Breast-feeding
Bendamustine hydrochloride must not be
administered during breast-feeding. If treatment
with Bendamustine hydrochloride is necessary
during lactation you must discontinue
breast-feeding.
Ask your doctor or pharmacist for advice before
taking any medicine.
Driving and using machines
No studies on the effects on the ability to drive
and to use machines have been performed. Do
not drive or operate machines if you experience
side effects, such as dizziness or lack of coordination.

3. How to use Bendamustine
hydrochloride
Bendamustine hydrochloride is administered into
a vein over 30-60 minutes in various dosages,
either alone (monotherapy) or in combination with
other medicines.
Treatment should not be started if your white
blood cells (leukocytes) have fallen to counts
below 3,000 cells/µl and/or your blood platelets
have fallen to counts below 75,000 cells/µl.
Your doctor will determine these values at regular
intervals.
Chronic lymphocytic leukaemia
Bendamustine hydrochloride
on Days 1+2
100 mg per square metre of your
body surface area (based on your
height and weight)
Repeat the cycle after 4 weeks up to 6 times
Non-Hodgkin lymphomas
Bendamustine hydrochloride
on Days 1 + 2
120 mg per square metre of your
body surface area (based on your
height and weight)
Repeat the cycle after 3 weeks at least 6 times
Multiple myeloma
Bendamustine hydrochloride
on Days 1 + 2
120-150 mg per square metre of
your body surface area (based on
your height and weight)
Prednisone 60 mg per square metre on Days 1 - 4
of your body surface area (based
on your height and weight) i.v. or
per os.
Repeat the cycle after 4 weeks at least 3 times
Treatment should be terminated if white blood
cell (leukocyte) and/or platelet values dropped to
< 3,000/µl or < 75,000/µl, respectively. Treatment
can be continued after white blood cell values
have increased to > 4,000/µl and platelet values
to > 100,000/µl.
Impaired liver or kidney function
Dependent on the degree of impairment of your
liver function it may be necessary to adjust your
dose (by 30% in case of moderate liver
dysfunction). No dose adjustment is necessary in
case of impairment of kidney function. Your
attending doctor will decide whether a dosage
adjustment is necessary.
How it is administered
Treatment with Bendamustine hydrochloride should
be undertaken only by doctors experienced in
tumour therapy. Your doctor will give you the exact
dose of Bendamustine hydrochloride and use the
necessary precautions.
Your attending doctor will administer the solution
for infusion after preparation as prescribed. The
solution is administered into a vein as a
short-term infusion over 30 - 60 minutes.
Duration of use
There is no time limit laid down as a general rule
for treatment with Bendamustine hydrochloride.
Duration of treatment depends on disease and
response to treatment.
If you are at all worried or have any questions
regarding treatment with Bendamustine
hydrochloride, please speak to your doctor or
pharmacist.
If you forget to use Bendamustine
hydrochloride
If a dose of Bendamustine hydrochloride has
been forgotten, your doctor will usually retain the
normal dosage schedule.
If you stop using of Bendamustine
hydrochloride
The doctor treating you will decide whether to
interrupt the treatment or to change over to a
different preparation.

body become contaminated, clean them carefully
with soap and water, and flush the eyes with
0.9% (isotonic) saline solution. If possible, it is
advisable to work on a special safety work bench
(laminar flow) with a disposable absorbent sheet
that is impermeable to liquids. Contaminated
articles are cytostatic waste. Please comply with
national guidelines on the disposal of cytostatic
material. Pregnant staff must be excluded from
working with cytostatics.

If you have any further questions on the use of
this product, ask your doctor or pharmacist.

4. Possible Side Effects
Like all medicines, Bendamustine hydrochloride
can cause side-effects, although not everybody
gets them.
Tissue changes (necrosis) have been observed
very rarely following unintentional injection into
the tissue outside blood vessels (extravascular).
A burning sensation where the infusion needle is
inserted may be a sign for administration outside
the blood vessels.
The consequence of administration in this way
can be pain and poorly healing skin defects.
The dose-limiting side-effect of Bendamustine
hydrochloride is impaired bone-marrow function,
which usually returns to normal after treatment.
Suppressed bone marrow function increases the
risk of infection.
Very common (may affect more than 1 in 10
people):
• Low counts of white blood cells (leukocytopenia)
• Decrease in the red pigment of the blood (haemoglobin)
• Low counts of platelets (thrombocytopenia)
• Infections
• Feeling sick (nausea)
• Vomiting
• Mucosal inflammation
• Increased blood level of creatinine
• Increased blood level of urea
• Fever
• Fatigue
Common (may affect up to 1 in 10 people):
• Bleeding (haemorrhage)
• Disturbed metabolism caused by dying cancer
cells releasing their contents into the blood stream
• Reduction in red blood cells which can make
the skin pale and cause weakness or
breathlessness (anaemia)
• Low counts of neutrophils (neutropenia)
• Hypersensitivity reactions such as allergic
inflammation of the skin (dermatitis), nettle rash
(urticaria)
• A rise in liver enzymes AST/ALT
• A rise in the enzyme alkaline phosphatase
• A rise in bile pigment
• Low potassium blood levels
• Disturbed function (dysfunction) of the heart
• Disturbed heart rhythms (arrhythmia)
• Low or high blood pressure (hypotension or
hypertension)
• Disturbed lung function
• Diarrhoea
• Constipation
• Sore mouth (Stomatitis)
• Loss of appetite
• Hair loss
• Skin changes
• Missed periods (amenorrhoea)
• Pain
• Insomnia
• Chills
• Dehydration
Uncommon (may affect up to 1 in 100 people):
• Accumulation of fluid in the heart sac (escape of
fluid into the pericardial space)
Rare (may affect up to 1 in 1,000 people):
• Infection of the blood (sepsis)
• Severe allergic hypersensitivity reactions
(anaphylactic reactions)
• Signs similar to anaphylactic reactions
(anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory collapse
• Reddening of the skin (erythema)
• Inflammation of the skin (dermatitis)
• Itching (pruritus)
• Skin rash (macular exanthema)
• Excessive sweating (hyperhidrosis)
Very rare (may affect up to 1 in 10,000 people):
• Primary atypical inflammation of the lungs (pneumonia)
• Break-down of red blood cells
• Rapid decrease in blood pressure sometimes with
skin reactions or rash (anaphylactic shock)
• Disturbed sense of taste
• Altered sensations (paraesthesia)
• Malaise and pain in the limbs (peripheral
neuropathy)
• Disease of the nervous system (anticholinergic
syndrome)
• Neurological disorders
• Lack of coordination (ataxia)
• Inflammation of the brain (encephalitis)
• Increased heart rate (tachycardia)
• Heart attack, chest pain (myocardial infarct)
• Heart failure
• Inflammation of the veins (phlebitis)
• Formation of tissue in the lungs (fibrosis of the lungs)
• Bleeding inflammation of the gullet (haemorrhagic
oesophagitis)
• Bleeding of stomach or gut
• Infertility
• Multiple organ failure
There have been reports of secondary tumours
(myelodysplastic syndrome, acute myeloid leukemia
(AML), bronchial carcinoma) following treatment
with Bendamustine hydrochloride. No clear
relationship with Bendamustine hydrochloride could
be determined.
A small number of cases of severe skin reactions
(Stevens-Johnson Syndrome and Toxic
Epidermal Necrolysis) have been reported.
The relationship with Bendamustine
hydrochloride is unclear.
Reporting of side effects
If you get any side effects, talk to your doctor,
pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. You can also
report side effects directly via the national
reporting system (see contact details below).
By reporting side effects you can help provide
more information on the safety of this medicine
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

5. How to store Bendamustine
hydrochloride
Keep this medicine out of the sight and reach of
children.

The solution ready for use must be prepared by
dissolving the contents of a vial of Bendamustine
hydrochloride exclusively in water for
Injections, as follows:
1. Preparation of the concentrate
• One vial of Bendamustine hydrochloride
containing 25 mg of bendamustine hydrochloride
is first dissolved in 10 ml by shaking
• One vial of Bendamustine hydrochloride
containing 100 mg of bendamustine
hydrochloride is first dissolved in 40 ml by shaking

Do not use Bendamustine hydrochloride after the
expiry date which is stated on the label and the
carton. The expiry date refers to the last day of
that month.
This medicinal product does not require any
special temperature storage conditions. Keep the
container in the outer carton to protect the
content from light.
Note on shelf-life after opening or preparing
the solution
Solutions for infusions prepared according to the
directions listed at the end of this leaflet are stable
in polyethylene bags at 25ºC for 3.5 hours, and at
2ºC to 8ºC they are stable for 2 days.
Bendamustine hydrochloride contains no
preservatives. From a microbiological point of
view, the solution should be used immediately. If
not used immediately, in-use storage times and
conditions prior to use are the responsibility of the user.
It is the responsibility of the user to maintain
aseptic conditions.
Do not throw away any medicines via wastewater
or household waste. Ask your pharmacist how to
throw away medicines you no longer use. These
measures will help to protect the environment.

6. Contents of the pack and
other information
What Bendamustine hydrochloride contains
The active substance is bendamustine hydrochloride.
One vial contains 25 mg of bendamustine
hydrochloride (as bendamustine hydrochloride
monohydrate).
One vial contains 100 mg of bendamustine
hydrochloride (as bendamustine hydrochloride
monohydrate).
After reconstitution 1 ml of the concentrate
contains 2.5 mg bendamustine hydrochloride (as
bendamustine hydrochloride monohydrate).
The other ingredient is mannitol.
What Bendamustine hydrochloride looks like
and contents of the pack
Amber glass vials with bromobutyl rubber stopper
and an aluminium flip-off cap.
Bendamustine hydrochloride is available in packs
containing 5, 10 and 20 vials with 25 mg of
bendamustine hydrochloride and 1 and 5 vials
with 100 mg of bendamustine hydrochloride.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare Limited
Sage House, 319 Pinner Road, North Harrow,
Middlesex HA1 4HF, United Kingdom.
Manufacturer
Accord Healthcare Limited
Sage House, 319 Pinner Road, North Harrow,
Middlesex HA1 4HF, United Kingdom.
Wessling Hungary Kft
Fòti ùt 56 , Budapest 1047 Hungary
This medicinal product is authorised in the
Member States of the EEA under the following
names:
Name of the
Name of the medicinal
Member State product
Bendamustine Accord 2.5 mg/ml
Austria
Pulver für ein Konzentrat zur
Herstellung einer Infusionslösung
Denmark
Bendamustinhydrochlorid Accord
Finland
Bendamustine Accord 2.5 mg/ml
kuiva-aine välikonsentraatiksi
infuusionestettä varten, liuos
Ireland
Bendamustine 25 mg/100mg
Powder for concentrate for
Solution for Infusion
Bendamustine Accord 2,5 mg/ml
Iceland
stofn fyrir innrennslisþykkni, lausn
Norway
Bendamustine Accord
Poland
Bendamustine Accord
Bendamustina Accord 2.5 mg/ml
Spain
polvo para concentrado para
solución para perfusión
Slovak Republic Bendamustine Accord 2,5 mg/ml
prášok na infúzny koncentrát
Belgium
Bendamustine Accord 2,5 mg/ml
Pulver für ein Konzentrat zur
Herstellung einer Infusionslösung
Bulgaria
Bendamustine Accord 2,5 mg/ml
Прах за концентрат за
инфузионен разтвор
Cyprus
Bendamustine Accord 2.5 mg/ml
Czech Republic Bendamustine Accord 2,5 mg/ml
prášek pro koncentrát pro infuzní
roztok
Bendamustine Accord 2,5 mg/ml
Germany
Pulver zur Herstellung eines
Infusionslösungskonzentrats
Estonia
Bendamustine Accord
Bendamustine Accord 2.5 mg/ml
Greece
powder for concentrated solution
for infusion
Hungary
Bendamustine Accord 2,5mg/ml
por oldatos infúzióhoz való
koncentrátumhoz
Italy
Bendamustina Accord
Bendamustine Accord 2.5 mg/ml
Latvia
pulveris infūziju šķīduma
koncentrāta pagatavošanai
Lithuania
Bendamustine Accord 2.5 mg/ml
milteliai koncentratui infuziniam
tirpalui
Malta
Bendamustine hydrochloride
2.5 mg/ml powder for
concentrate for solution for infusion
The Netherlands Bendamustine Accord 2,5 mg/ml
poeder voor concentraat voor
oplossing voor infusie
Portugal
Bendamustine Accord 2,5 mg/ml
pó para concentrado para
solução para perfusão
Romania
Bendamustina Accord 2,5 mg/ ml
pulbere pentru concentrat pentru
soluţie perfuzabilǎ
Slovenia
Bendamustine Accord 2,5 mg/ ml
prašek za koncentrat za raztopino
za infundiranje
Sweden
Bendamustine Accord 2,5 mg/ ml
pulver till koncentrat till infusions
vätska, lösning
United Kingdom Bendamustine hydrochloride
2.5 mg/ ml Powder for
concentrate for solution for infusion
France
BENDAMUSTINE ACCORD
2,5 mg/ml, poudre pour
solution à diluer pour perfusion
This leaflet was last revised in 11/2015

2. Preparation of the solution for infusion
As soon as a clear solution is obtained (generally
after 5 - 10 minutes), the total recommended
dose of Bendamustine hydrochloride is
immediately diluted with 0.9% (isotonic) saline
solution to obtain a final volume of approximately
500 ml. Bendamustine hydrochloride must not
be diluted with other solutions for infusion or
injection. Bendamustine hydrochloride must not
be mixed in an infusion with other substances.

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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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