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LEVACT 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
®

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, 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. 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.

What is in this leaflet:
1.
2.
3.
4.
5.
6.

What Levact is and what it is used for
What you need to know before you use Levact
How to use Levact
Possible side effects
How to store Levact
Contents of the pack and other information

1. WHAT LEVACT IS AND WHAT IT IS USED FOR
Levact is a medicine which is used for the treatment of
certain types of cancer (cytotoxic medicine).
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 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 thalidomide or
bortezomib containing therapy is not appropriate for you.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE LEVACT
If Levact is used in combination with medicines which
Do not use Levact
–– if you are allergic to bendamustine hydrochloride or any
of the other ingredients of this medicine (listed in section
6);
–– while breast-feeding, if treatment with Levact is
necessary during lactation you must discontinue
breast-feeding (see section warnings and precautions on
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;
–– 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, pharmacist or nurse before
using 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 skin 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 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 may ensure you are adequately
hydrated and 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.

Other medicines and Levact

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 livevirus 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
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.
Breast-feeding
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.
Fertility
Men receiving treatment with Levact are advised not to
father 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.
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.

Driving and using machines

Levact has major influence on the ability to drive and
to use machines. Do not drive or operate machines if
you experience side effects, such as dizziness or lack of
coordination.

Tell your doctor or pharmacist if you are taking, have
recently taken or might take any other medicines.

3. HOW TO USE LEVACT
Always use this medicine exactly as your doctor or
pharmacist has told you. Check with your doctor or
pharmacist if you are not sure.
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) and/or your blood platelets have fallen to counts
below determined levels.
Your doctor will determine these values at regular intervals.

Chronic lymphocytic leukaemia

Levact 100 mg per square meter of your on Days
body surface area (based on your height 1+2
and weight)
Repeat the cycle after 4 weeks up to 6 times

Non-Hodgkin lymphomas
Levact 120 mg per square meter 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 meter
on Days
of your body surface area (based on your 1 + 2
height and weight)
Prednisone 60 mg per square meter of
on Days
your body surface area (based on your
1–4
height and weight) by injection or orally.
Repeat the cycle after 4 weeks at least 3 times

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.

Treatment should be terminated if white blood cell
(leukocyte) and/or platelet values dropped to determined
levels. Treatment can be continued after white blood cell and
platelet values have increased.

4. POSSIBLE SIDE EFFECTS
Like all medicines, Levact can cause side-effects, although
not everybody will experience these effects. Some of the
findings listed below may be found after tests are performed
by your doctor.
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 decay (necrosis) has been observed very rarely
following leakage of Levact into the tissue outside the blood
vessels (extravascular). A burning sensation where the
infusion needle is inserted may be a sign of leakage outside
the blood vessels. The consequence can be pain and poorly
healing skin defects.
The dose-limiting side-effect of Levact is impaired bonemarrow function, which usually returns to normal after
treatment. Suppressed bone marrow function may lead to low
counts of blood cells, which in turn may lead to an increased
risk of infection, anemia or a heightened risk of bleeding.



















• Low counts of white blood cells (disease-fighting cells in
your blood)
• Decrease in the red pigment of the blood (haemoglobin: a
protein in red blood cells that carries oxygen throughout
the body)
• Low counts of platelets (colorless blood cells that help
blood clot)
• Infections
• Feeling sick (nausea)
• Vomiting
• Mucosal inflammation
• Headache
• Increased blood level of creatinine (a chemical waste
product that is produced by your muscle)
• Increased blood level of urea (a chemical waste product)
• Fever
• Fatigue

Rare:

Very common:

Common:

• 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 (a common type of white blood
cell important to fighting off infections)
• Hypersensitivity reactions such as allergic inflammation
of the skin (dermatitis), nettle rash (urticaria)
• A rise in liver enzymes AST/ALT (which may indicate
inflammation or damage to cells in the liver)
• A rise in the enzyme alkaline phosphatase (an enzyme
made mostly in the liver and bones)
• A rise in bile pigment (a substance made during the
normal breakdown of red blood cells)
• Low potassium blood levels (a nutrient that is necessary
for the function of nerve and muscle cells, including those
in your heart)

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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
Dizziness
Itchy rash (urticaria)

Uncommon:

• Accumulation of fluid in the heart sac (escape of fluid into
the pericardial space)
• Ineffective production of all blood cells in the bone
marrow (the spongy material inside your bones where
blood cells are made)
• Acute leukemia
• Heart attack, chest pain (myocardial infarct)
• Heart failure
• Infection of the blood (sepsis)
• Severe allergic hypersensitivity reactions (anaphylactic
reactions)
• Reduction in your bone marrow function, which
may make you feel unwell or show up in your blood
tests
• Signs similar to anaphylactic reactions (anaphylactoid
reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory collapse (failure of blood circulation
mainly from a cardiac origin with failure to maintain the
supply of oxygen and other nutrients to the tissues and
removing toxins)
• 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 cell
• 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)
• Serious condition resulting in the blockade of specific
receptor in the nervous systems
• Disorders of the nervous system
• Lack of coordination (ataxia)
• Inflammation of the brain (encephalitis)
• Increased heart rate (tachycardia)
• 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

Not known:





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.
• Drug rash in combination therapy with rituximab
• Pneumonitis
• Bleeding from the lungs
There have been reports of tumours (myelodysplastic
syndrome, AML, bronchial carcinoma) following treatment
with Levact. No clear relationship with Levact could be
determined.

Contact your doctor or seek medical attention immediately
if you notice any of the following side effects (frequency not
known):
Serious skin rashes including Stevens-Johnson syndrome
and toxic epidermal necrolysis. These can appear as reddish
target-like macules or circular patches often with central
blisters on the trunk, skin peeling, ulcers of mouth, throat,
nose, genitals and eyes and can be preceded by fever and
flu-like symptoms.
Widespread rash, high body temperature, enlarged lymph
nodes and other body organs involvement (Drug Reaction
with Eosinophilia and Systemic Symptoms which is also
known as DRESS or drug hypersensitivity syndrome).
If any of the side effects gets serious, or if you notice any
side effects not listed in this leaflet, please tell your doctor.
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
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.

5. HOW TO STORE LEVACT
Keep this medicine out of the sight and reach 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. CONTENTS OF THE PACK AND OTHER INFORMATION
What Levact contains

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.

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 vials with 25 mg of bendamustine hydrochloride
and 5 vials with 100 mg of bendamustine hydrochloride.
Not all pack sizes may be available.

Marketing Authorisation Holder
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

Manufacturer

Haupt Pharma Wolfratshausen GmbH
Pfaffenrieder Strasse 5
82515 Wolfratshausen

This leaflet was last revised in October 2017

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 cancercausing 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
absorbing 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 a vial of Levact exclusively in water for Injections,
as follows:
1. Preparation of the concentrate
• One vial of Levact containing 25 mg of bendamustine
hydrochloride is first dissolved in 10 ml by shaking
• One vial of Levact containing 100 mg of bendamustine
hydrochloride is first dissolved in 40 ml by shaking
® LEVACT, NAPP and the ‘NAPP’ logo are Registered Trade Marks.
© 2010 Napp Pharmaceuticals Limited.

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

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