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BENDAMUSTINE HYDROCHLORIDE 180 MG/4 ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): BENDAMUSTINE HYDROCHLORIDE

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150 mm
37.5 mm

37.5 mm

37.5 mm

37.5 mm

Package leaflet: Information for the user

150065276

Bendamustine hydrochloride 180 mg/4 ml Concentrate For Solution For Infusion
Bendamustine hydrochloride

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

Bendamustine hydrochloride is a medicine which is
used for the treatment of certain types of cancer
(cytotoxic medicine).

2. What you need to know before you
use Bendamustine hydrochloride
Do not take Bendamustine hydrochloride:









Talk to your doctor or nurse 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 cases of existing heart disease (e.g. heart
attack, chest pain, severely disturbed heart
rhythms).

If you are pregnant or breastfeeding, think you may be
pregnant or are planning to have a baby, ask your
doctor or pharmacist for advice before using this
medicine.

Pregnancy

Bendamustine hydrochloride can cause genetic
damage and has caused malformations in animal
studies. You should not use Bendamustine
hydrochloride during pregnancy unless clearly
indicated by your doctor. In case of treatment you
should have 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 have
genetic consultation.

Breastfeeding

Bendamustine hydrochloride must not be
administered during breastfeeding. If treatment with
Bendamustine hydrochloride is necessary during
lactation you must discontinue breastfeeding.

Fertility

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 storing of sperm before treatment
starts.

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 100 mg on Days 1+2
per square metre of your body
surface area (based on your height
and weight)
Repeat the cycle after 4 weeks

Non-Hodgkin’s lymphomas
Bendamustine hydrochloride 120 mg on Days 1+2
per square metre of your body
surface area (based on your height
and weight)
Repeat the cycle after 3 weeks

Multiple myeloma
on Days 1+2

Prednisone 60 mg per square metre
of your body surface area (based on
your height and weight) i.v. or per
os.

on Days 1-4

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Bendamustine hydrochloride
120-150 mg per square metre of
your body surface area (based on
your height and weight)

Repeat the cycle after 4 weeks

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.

Treatment should be terminated if white blood cell
(leukocyte) and/or platelet values drop 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.

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).

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).
Bendamustine hydrochloride should not be used if you
suffer from severe 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.

There is no experience in children and adolescents
with Bendamustine hydrochloride.

Impaired liver or kidney function

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Children and adolescents

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Talk to your doctor or nurse during uses of
Bendamustine hydrochloride:
• in cases of nausea, vomiting. Your doctor may
give you a drug to reduce nausea (antiemetic)
• 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 may
ensure you are adequately hydrated and give you
other medicines to help prevent it
• in case of reactions on your skin during
treatment with Bendamustine hydrochloride.
The reactions may increase in severity
• in case of painful red or purplish rash that
spreads and blisters and/or other lesions begin to
appear in the mucous membrane (e.g. mouth and
lips), in particular if you had before light
sensitivity, infections of the respiratory system
(e.g. bronchitis) and/or fever
• in case of severe allergic or hypersensitivity
reactions. You should pay attention to infusion
reactions after your first cycle of therapy.

Pregnancy, breastfeeding and fertility

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560 mm

Warnings and precautions

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).

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if you are allergic to the active substance
bendamustine hydrochloride or any of the other
ingredients of this medicine (listed in section 6)
while breastfeeding
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.

If Bendamustine hydrochloride is used in combination
with medicines which alter your immune response,
this effect may be intensified.

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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’s 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.

If Bendamustine hydrochloride is used in combination
with medicines which inhibit the formation of blood in
the bone marrow, the effect on the bone marrow may
be intensified.

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1. What Bendamustine hydrochloride
is and what it is used for

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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.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not
listed in this leaflet. See section 4.

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
Tell your doctor or pharmacist if you are taking or have Bendamustine hydrochloride and use the necessary
precautions.
recently taken or might take any other medicines.
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.

Other medicines and Bendamustine
hydrochloride

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The following information is intended for medical or healthcare professionals only:
It should be noted that the concentration (45 mg/ml) of bendamustine in Bendamustine hydrochloride is higher
than in other bendamustine products for intravenous infusion.
When handling Bendamustine hydrochloride, inhalation, skin contact or contact with mucous membranes
should be avoided (wear gloves and protective clothes!). Contaminated body parts should be carefully rinsed
with water and soap, the eyes should be rinsed with physiological saline solution. If possible it is recommended
to work on special safety workbenches (laminar flow) with liquid-impermeable, absorbent disposable foil.
Pregnant personnel should be excluded from handling cytostatics.
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The concentrate for solution for infusion has to be diluted with sodium chloride 9 mg/ml (0.9%) solution for
injection and then administered by intravenous infusion. Aseptic technique is to be used.

150 mm

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 nurse.

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 Bendamustine
hydrochloride











Not known side effects (cannot be estimated
from the available data):




The doctor treating you will decide whether to interrupt •
the treatment or to change over to a different
preparation.
If you have any further questions on the use of this
medicine, ask your doctor or pharmacist.

4. Possible side effects

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
liver failure
renal failure
irregular and often rapid heart rate (atrial
fibrillation)
painful red or purplish rash that spreads and
blisters and/or other lesions begin to appear in
the mucous membrane (e.g. mouth and lips), in
particular if you had before light sensitivity,
infections of the respiratory system
(e.g. bronchitis) and/or fever

There have been reports of secondary tumours
(myelodysplastic syndrome, acute myeloid leukaemia
Like all medicines, this medicine can cause side
(AML), bronchial carcinoma) following treatment with
effects, although not everybody gets them.
Bendamustine hydrochloride. No clear relationship
Tissue changes (necrosis) have been observed very with Bendamustine hydrochloride could be
rarely following unintentional injection into the tissue determined.
A small number of cases of severe skin reactions
outside blood vessels (extravascular). A burning
sensation where the infusion needle is inserted may (Stevens-Johnson Syndrome and Toxic Epidermal
be a sign for administration outside the blood vessels. Necrolysis) have been reported. The relationship with
The consequence of administration in this way can be Bendamustine hydrochloride is unclear.
pain and poorly healing skin defects.
Reporting of side effects
If you get any side effects, talk to your doctor or
The dose-limiting side-effect of Bendamustine
pharmacist. This includes any possible side effects not
hydrochloride is impaired bone-marrow function,
listed in this leaflet. You can also report side effects
which usually returns to normal after treatment.
Suppressed bone marrow function increases the risk directly via the Yellow Card Scheme, website
www.mhra.gov.uk/yellowcard. By reporting side
of infection.
effects, you can help provide more information on the
Very common side effects (may affect more
safety of this medicine.

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
headache

5. How to store Bendamustine
hydrochloride

bleeding (haemorrhage)
disturbed metabolism caused by dying cancer
cells releasing their contents into the blood
stream (tumor lysis syndrome)
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
(palpitations, angina pectoris)
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
dizziness

Store and transport refrigerated (2-8°C). Do not freeze.
Keep the vial in the outer carton in order to protect
from light.

Keep this medicine out of the sight and reach of
children.
Do not use this medicine after the expiry date which is
stated on the label and the carton. The expiry date
refers to the last day of that month.
Store and transport refrigerated (2-8°C). Do not freeze.
Keep the container in the outer carton to protect the
content from light.

Common side effects (may affect up to 1 in 10 Note on shelf-life after opening or preparing
the solution
people):











560 mm

















Bendamustine hydrochloride 180 mg/4 ml vial is a
multi-use vial. Use within 28 days.
From a microbiological point of view, the diluted
solution should be used immediately after preparation.
If not used immediately, in-use storage times and
conditions prior to use are the responsibility of the
user.
Solutions for infusions prepared according to the
directions listed at the end of this leaflet are stable in
polyethylene bags for 3.5 hours at 25°C/60% RH and
2 days at 2-8°C. Bendamustine hydrochloride
contains no preservatives. The solutions should not
therefore be used after these lengths of time. It is the
responsibility of the user to maintain aseptic
conditions.
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.

6. Contents of the pack and other
information
What Bendamustine hydrochloride contains

Uncommon side effects (may affect up to 1 in
100 people):

The active substance is bendamustine hydrochloride.
1 vial contains 180 mg of bendamustine hydrochloride
(as monohydrate).
1 ml of the concentrate contains 45 mg bendamustine
hydrochloride (as monohydrate).
The other ingredients are butylhydroxytoluene and
Macrogol 300.



What Bendamustine hydrochloride looks like
and contents of the pack





accumulation of fluid in the heart sac (escape of
fluid into the pericardial space)
ineffective production of all blood cells
(myelodysplastic syndrome)
acute leukemia

5 ml amber glass vial with rubber stopper and flip-off
seal.

Rare side effects (may affect up to 1 in 1,000
people):

The clear viscous solution appears pale yellow to
yellow.



Not all pack sizes may be marketed.














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)
reduction in your bone marrow function, which
may make you feel unwell or show up in your
blood tests

Bendamustine hydrochloride is available in pack sizes
of 1 and 4 vials.
Marketing Authorisation Holder and Manufacturer
Dr. Reddy’s Laboratories (UK) Ltd., 6 Riverview Road,
Beverley, East Yorkshire, HU17 0LD, United Kingdom
This leaflet was last revised in 03/2017

Very rare side effects (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)

1. Dilution

Aseptically withdraw the volume needed for the required dose from the Bendamustine hydrochloride
180 mg/4 ml vial. Dilute the total recommended dose of Bendamustine hydrochloride 180 mg/4 ml with 0.9%
sodium chloride solution to produce a final volume of about 500 ml.
While diluting the product it should be noted that the concentration (45 mg/ml) of bendamustine in
Bendamustine hydrochloride is higher than in usual bendamustine concentrates resulting from reconstitution of
bendamustine powder containing medicinal products.
Bendamustine hydrochloride 180 mg/4 ml must be diluted with 0.9% NaCl solution and not with any other
injectable solutions.

2. Administration

The solution is administered by intravenous infusion over 30-60 min.
The vials are for multiple dose use.
Any unused product or waste material should be disposed of in accordance with local requirements.

+ Expand Transcript

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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