LEVACT 2.5 MG/ML POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance: BENDAMUSTINE HYDROCHLORIDE

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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

1. WHAT LEVACT IS AND WHAT IT IS USED FOR
Levact is a medicine which is used for
–– non-Hodgkin’s lymphomas, which had
the treatment of certain types of cancer
not, or only shortly, responded to prior
(cytotoxic medicine).
rituximab treatment,
–– Multiple myeloma in cases where highLevact is used alone (monotherapy) or in
dose chemotherapy with autologous
combination with other medicines for the
stem cell transplantation, thalidomide
treatment of the following forms of cancer:
or bortezomib containing therapy is not
–– chronic lymphocytic leukaemia in
appropriate for you.
cases where fludarabine combination
chemotherapy is not appropriate for you,
2. BEFORE YOU USE LEVACT
Do not use Levact

–– if you are hypersensitive (allergic) to
the active substance bendamustine
hydrochloride or any of the other
ingredients of Levact;
–– 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.

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 therapy.
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.

3. HOW TO USE LEVACT
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
1  + 2

Repeat the cycle after 4 weeks up to 6 times

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

on
Days
1 + 2

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
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

Repeat the cycle after 4 weeks at least 3 times

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).

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 your 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 breastfeeding

Pregnancy
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
recommended.
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.
Breastfeeding
Levact must not be administered during
breastfeeding. If treatment with Levact
is necessary during lactation you must
discontinue breastfeeding.
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.
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 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 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
schedule.

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.

4. POSSIBLE SIDE FFECTS
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
Common:
affects 1 to 10 users in 100
Uncommon: affects 1 to 10 users in 1,000
Rare:
affects 1 to 10 users in
10,000
Very rare:
affects less than 1 user in
10,000
Not known: frequency cannot be
estimated from the available
data
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 Levact is
impaired bone-marrow function, which usually
returns to normal after treatment. Suppressed
bone marrow function increases the risk of
infection.

–– Loss of appetite
–– Hair loss
–– Skin changes
–– Missed periods (amenorrhoea)
–– Pain
–– Insomnia
–– Chills
–– Dehydration

Uncommon:

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

Rare:

–– 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:

–– Primary atypical inflammation of the lungs
(pneumonia)
–– Break-down of red blood cells
Very common:
–– Rapid decrease in blood pressure
–– Low counts of white blood cells
sometimes with skin reactions or rash
(leukocytopenia)
(anaphylactic shock)
–– Decrease in the red pigment of the blood
–– Disturbed sense of taste
(haemoglobin)
–– Low counts of platelets (thrombocytopenia) –– Altered sensations (paraesthesia)
–– Malaise and pain in the limbs (peripheral
–– Infections
neuropathy)
–– Feeling sick (nausea)
–– Disease of the nervous system
–– Vomiting
(anticholinergic syndrome)
–– Mucosal inflammation
–– Neurological disorders
–– Increased blood level of creatinine
–– Lack of coordination (ataxia)
–– Increased blood level of urea
–– Inflammation of the brain (encephalitis)
–– Fever
–– Increased heart rate (tachycardia)
–– Fatigue
–– Heart attack, chest pain (myocardial infarct)
Common:
–– Heart failure
–– Bleeding (haemorrhage)
–– Inflammation of the veins (phlebitis)
–– Disturbed metabolism caused by dying
–– Formation of tissue in the lungs (fibrosis of
cancer cells releasing their contents into the
the lungs)
blood stream
–– Bleeding inflammation of the gullet
–– Reduction in red blood cells which can
(haemorrhagic oesophagitis)
make the skin pale and cause weakness or –– Bleeding of stomach or gut
breathlessness (anaemia)
–– Infertility
–– Low counts of neutrophils (neutropenia)
–– Multiple organ failure
–– Hypersensitivity reactions such as allergic
inflammation of the skin (dermatitis), nettle There have been reports of secondary tumours
(myelodysplastic syndrome, AML, bronchial
rash (urticaria)
carcinoma) following treatment with Levact.
–– A rise in liver enzymes AST/ALT
No clear relationship with Levact could be
–– A rise in the enzyme alkaline phosphatase
determined.
–– A rise in bile pigment
A small number of cases of severe skin
–– Low potassium blood levels
–– Disturbed function (dysfunction) of the heart reactions (Stevens-Johnson Syndrome
and Toxic Epidermal Necrolysis) have been
–– Disturbed heart rhythms (arrhythmia)
–– Low or high blood pressure (hypotension or reported. The relationship with Levact is
unclear.
hypertension)
–– Disturbed lung function
If any of the side effects gets serious, or if you
–– Diarrhoea
notice any side effects not listed in this leaflet,
–– Constipation
please tell your doctor.
–– Sore mouth (Stomatitis)

5. HOW TO STORE LEVACT
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 month.
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.

6. FURTHER INFORMATION

What Levact contains

Marketing Authorisation Holder

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

Astellas Pharma GmbH,
Postfach 50 01 66, 80971 Munich, Germany.

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 and
20 injection vials with 25 mg of bendamustine
hydrochloride and 5 injection vials with 100 mg
of bendamustine hydrochloride.

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

Manufacturer
Temmler Werke GmbH
Weihenstephaner Strasse 28
81673 Munich, Germany

This leaflet was last revised in 07/2010.

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 containing
25 mg of bendamustine hydrochloride is
first dissolved in 10 ml by shaking
–– One injection vial of Levact containing
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.

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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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