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485x120mm (LSN-CON-23) (P) V2

Package leaflet: Information for the user

Levact 2.5 mg/ml powder for concentrate for solution for infusion
Bendamustine hydrochloride
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, ask your doctor or pharmacist.
• 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 yours.
• If any of the side effects gets serious, or if you notice any side effects not listed in this
leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Levact is and what it is used for
2. Before you use Levact
3. How to use Levact
4. Possible side effects
5. How to store Levact
6. Further information

Levact is a medicine which is used for the
treatment of certain types of cancer (cytotoxic
Levact 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

Do not use Levact

–– if you are hypersensitive (allergic) to
the active substance bendamustine
hydrochloride or any of the other
ingredients of Levact;
–– 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 dropped to
< 3,000/µl or < 75,000/µl, respectively.);
–– if you have had major surgical operations
less than 30 days before starting
–– if you have an infection, especially one
accompanied by a reduction in white blood
cells (leucocytopenia);
–– in combination with yellow fever vaccines.

Take special care with Levact

–– 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 Levact, 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 Levact. 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 Levact. 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
Men receiving treatment with Levact 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

chemotherapy is not appropriate for you,
–– non-Hodgkin lymphomas, which had not,
or only shortly, responded to prior rituximab
–– multiple myeloma in cases where
thalidomide or bortezomib containing
therapy is not appropriate for you.

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).

Using other medicines

Please tell your doctor or pharmacist if you
are taking or have recently taken other
medicines, including medicines obtained
without a prescription.
If Levact 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.
If Levact 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 and breast-feeding

Levact can cause genetic damage and has
caused malformations in animal studies.
You should not use Levact 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
If you are a woman of childbearing potential
you must use an effective method of
contraception both before and during
treatment with Levact. If pregnancy occurs
during your treatment with Levact 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 Levact and for
up to 6 months after treatment has stopped.
There is a risk that treatment with Levact
will lead to infertility and you may wish to
seek advice on conservation of sperm before
treatment starts.
Levact must not be administered during
breast feeding. If treatment with Levact
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.

Levact 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
Levact 100 mg per square metre of
your body surface area (based on
your height and weight)

on Days

Repeat the cycle after 4 weeks up to 6 times

Non-Hodgkin lymphomas
Levact 120 mg per square metre of
your body surface area (based on
your height and weight)

on Days

Repeat the cycle after 3 weeks at least 6 times

Multiple myeloma
Levact 120 - 150 mg per square
metre of your body surface area
(based on your height and weight)

on Days

Prednisone 60 mg per square metre
of your body surface area (based on
your height and weight) by injection
or orally.

on Days

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.


LEVACT INJ 2.5MG-ML PIL UK P1242-A V2.indd 2

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 Levact should be undertaken
only by doctors experienced in tumour
therapy. Your doctor will give you the exact
dose of Levact and use the necessary
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
Duration of use
There is no time limit laid down as a general
rule for treatment with Levact. Duration of
treatment depends on disease and response
to treatment.
If you are at all worried or have any questions
regarding treatment with Levact, please
speak to your doctor or nurse.

If you forget to use Levact

If a dose of Levact has been forgotten, your
doctor will usually retain the normal dosage

If you stop using Levact

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 product, ask your doctor or pharmacist.

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485x120mm (LSN-CON-23) (P) V2

Like all medicines, Levact can cause sideeffects, although not everybody gets them.
The following definitions of frequency are
used when assessing side-effects:
Very common

affects more than 1 user in 10


affects 1 to 10 users in 100


affects 1 to 10 users in 1,000


affects 1 to 10 users in

Very rare

affects less than 1 user in

• Sore mouth (Stomatitis)
• Loss of appetite
• Hair loss
• Skin changes
• Missed periods (amenorrhoea)
• Pain
• Insomnia
• Chills
• Dehydration


• Accumulation of fluid in the heart sac
(escape of fluid into the pericardial space)


• Infection of the blood (sepsis)
• Severe allergic hypersensitivity reactions
not known
frequency cannot be
(anaphylactic reactions)
estimated from the
• Signs similar to anaphylactic reactions
available data
(anaphylactoid reactions)
• Drowsiness
Tissue changes (necrosis) have been observed • Loss of voice (aphonia)
very rarely following unintentional injection into • Acute circulatory collapse
the tissue outside blood vessels (extravascular). • Reddening of the skin (erythema)
A burning sensation where the infusion needle • Inflammation of the skin (dermatitis)
is inserted may be a sign for administration
• Itching (pruritus)
outside the blood vessels. The consequence
• Skin rash (macular exanthema)
of administration in this way can be pain and
• Excessive sweating (hyperhidrosis)
poorly healing skin defects.
Very rare:
The dose-limiting side-effect of Levact is
• Primary atypical inflammation of the lungs
impaired bone-marrow function, which usually
returns to normal after treatment. Suppressed • Break-down of red blood cell
bone marrow function increases the risk of
• Rapid decrease in blood pressure
sometimes with skin reactions or rash
Very common:
(anaphylactic shock)
• Low counts of white blood cells
• Disturbed sense of taste
• Altered sensations (paraesthesia)
• Decrease in the red pigment of the blood
• Malaise and pain in the limbs (peripheral
• Low counts of platelets (thrombocytopenia)
• Disease of the nervous system
• Infections
(anticholinergic syndrome)
• Feeling sick (nausea)
• Neurological disorders
• Vomiting
• Lack of coordination (ataxia)
• Mucosal inflammation
• Inflammation of the brain (encephalitis)
• Increased blood level of creatinine
• Increased heart rate (tachycardia)
• Increased blood level of urea
• Heart attack, chest pain (myocardial infarct)
• Fever
• Heart failure

• Fatigue
• Inflammation of the veins (phlebitis)
• Formation of tissue in the lungs (fibrosis of
the lungs)
• Bleeding (haemorrhage)
• Bleeding inflammation of the gullet
• Disturbed metabolism caused by dying
(haemorrhagic oesophagitis)
cancer cells releasing their contents into
• Bleeding of stomach or gut
the blood stream
• Infertility
• Reduction in red blood cells which can
make the skin pale and cause weakness or • Multiple organ failure
breathlessness (anaemia)
Not known:
• Low counts of neutrophils (neutropenia)
• Liver failure
• Hypersensitivity reactions such as allergic
There have been reports of secondary
inflammation of the skin (dermatitis), nettle tumours (myelodysplastic syndrome, AML,
rash (urticaria)
bronchial carcinoma) following treatment with
• A rise in liver enzymes AST/ALT
Levact. No clear relationship with Levact
• A rise in the enzyme alkaline phosphatase
could be determined.
• A rise in bile pigment
A small number of cases of severe skin
• Low potassium blood levels
reactions (Stevens-Johnson Syndrome
• Disturbed function (dysfunction) of the heart and Toxic Epidermal Necrolysis) have been
• Disturbed heart rhythms (arrhythmia)
reported. The relationship with Levact is
• Low or high blood pressure (hypotension or unclear.
If any of the side effects gets serious, or if you
• Disturbed lung function
notice any side effects not listed in this leaflet,
• Diarrhoea
please tell your doctor.
• Constipation

Keep out of the reach and sight of children.
Do not use Levact after the expiry date
which is stated on the label and the carton.
The expiry date refers to the last day of that
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

room temperature / 60% relative humidity for
3.5 hours, and in a refrigerator they are stable
for 2 days. Levact 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.

What Levact contains

Marketing Authorisation Holder

The active substance is bendamustine
1 vial contains 25 mg of bendamustine
1 vial contains 100 mg of bendamustine
After reconstitution 1 ml of the concentrate
contains 2.5 mg bendamustine hydrochloride.
The other ingredient is Mannitol.

What Levact looks like and contents of
the pack

Brown glass vials with rubber stopper and an
aluminium flip-off cap.
The powder appears white and crystalline.
Levact is available in packs containing
5, 10 and 20 injection vials with 25 mg
of bendamustine hydrochloride and 5
injection vials with 100 mg of bendamustine
Not all pack sizes may be available.

Astellas Pharma GmbH
Postfach 50 01 66
D-80971 München
Telephone: 089/45 44 01

Local representative:

Napp Pharmaceuticals Ltd
Cambridge Science Park
Milton Road
Cambridge, CB4 0GW
Telephone: +44 (0) 1223 424444
Fax: +44 (0) 1223 424441


Haupt Pharma Wolfratshausen GmbH
Pfaffenrieder Strasse 5
82515 Wolfratshausen

This leaflet was last revised in
December 2014.

This leaflet is also available in large print, Braille or as
an audio CD. To request a copy, please call the
RNIB Medicine Information line (free of charge) on:

0800 198 5000

You will need to give details of the product name
and reference number. These are as follows:
Product name: Levact 2.5 mg/ml
Reference number: 14427/0026
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 Levact (wear gloves,
protective clothing, and possibly a face mask!).
If any parts of the 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.
The solution ready for use must be prepared
by dissolving the contents of an injection vial of

Levact exclusively in water for Injections,
as follows:
1. Preparation of the concentrate
• One injection vial of Levact
25 mg of bendamustine hydrochloride
is first dissolved in 10 ml by shaking
• One injection vial of Levact
100 mg of bendamustine
hydrochloride is first dissolved in
40 ml by shaking
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 Levact is
immediately diluted with 0.9% (isotonic)
saline solution to obtain a final volume of
approximately 500 ml. Levact must not be
diluted with other solutions for infusion or
injection. Levact must not be mixed in an
infusion with other substances.

® LEVACT, NAPP and the ‘NAPP’ device (logo) are Registered Trade Marks.
© 2010 Napp Pharmaceuticals Limited.

LEVACT INJ 2.5MG-ML PIL UK P1242-A V2.indd 3

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27/11/2014 08:50

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.