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KAPPALKYL 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
Kappalkyl, 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 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, pharmacist or nurse.
− If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.

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

1. What Kappalkyl is and what it is used for
Kappalkyl is a medicine which is used for the treatment of certain types of cancer (cytotoxic medicine).
Kappalkyl 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,

-

2.

multiple myeloma in cases where high-dose chemotherapy with autologous stem cell
transplantation, thalidomide or bortezomib containing therapy is not appropriate for you.

What you need to know before you use Kappalkyl

Do not use Kappalkyl
-

if you are allergic to 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);

-

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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
platelet values dropped 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, pharmacist or nurse before using Kappalkyl
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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
Kappalkyl, 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 Kappalkyl. 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 Kappalkyl. 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 Kappalkyl 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).
Children and adolescents
There is no experience in children and adolescents with Kappalkyl.
Other medicines and Kappalkyl
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
If Kappalkyl 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 Kappalkyl 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, breastfeeding and fertility
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

Kappalkyl can cause genetic damage and has caused malformations in animal studies. You should not use
Kappalkyl 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 Kappalkyl. If pregnancy occurs during your treatment with Kappalkyl
you must immediately inform your doctor and should have genetic consultation.
Breastfeeding
Kappalkyl must not be administered during breastfeeding. If treatment with Kappalkyl is necessary
during lactation you must discontinue breastfeeding.
Fertility
If you are a man, you should avoid fathering a child during treatment with Kappalkyl and for up to 6
months after treatment has stopped. There is a risk that treatment with Kappalkyl 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 Kappalkyl
Kappalkyl 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
Kappalkyl 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
Non-Hodgkin lymphomas
Kappalkyl 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
Multiple myeloma
Kappalkyl 120 - 150 mg per square metre of your body surface area
(based on your height and weight)
Prednisone 60 mg per square metre of your body surface area (based
on your height and weight) intravenous or orally

on Days 1 + 2
on Days 1 - 4

Repeat the cycle after 4 weeks
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). Kappalkyl 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.
How it is administered
Treatment with Kappalkyl should be undertaken only by doctors experienced in tumour therapy. Your
doctor will give you the exact dose of Kappalkyl 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 Kappalkyl. Duration of treatment
depends on disease and response to treatment.
If you are at all worried or have any questions regarding treatment with Kappalkyl, please speak to your
doctor or nurse.
If you forget to use Kappalkyl
If a dose of Kappalkyl has been forgotten, your doctor will usually retain the normal dosage schedule.
If you stop using of Kappalkyl
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, pharmacist or nurse.

4. Possible side effects
Like all medicines, this medicine 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 Kappalkyl 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 (tumour
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

of the skin , such as 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 heart function
such as feeling your
heartbeat (palpitations) or
chest pain (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
(anorexia)








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
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)
• 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

Not known:


Liver failure

There have been reports of secondary tumours (myelodysplastic syndrome, acute myeloid leukaemia
(AML), bronchial carcinoma) following treatment with Kappalkyl. No clear relationship with Kappalkyl
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 Kappalkyl is unclear.
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 Yellow Card Scheme
Website: 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 Kappalkyl

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 after ‘EXP’.The
expiry date refers to the last day of that month.
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 25° C / 60% relative humidity for 3.5 hours, and in a refrigerator they are stable for
1 day. Kappalkyl 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.
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 protect the environment.

6.

Contents of the pack and other information

What Kappalkyl 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 Kappalkyl looks like and contents of the pack
Brown glass vials with bromobutyl rubber stopper and plastic aluminium flip-off cap.
The powder appears white and crystalline.
Kappalkyl is available in packs containing
1, 5, 10 and 20 injection vials with 25 mg of bendamustine hydrochloride
and 1 and 5 injection vials with 100 mg of bendamustine hydrochloride.
Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Helm AG
Nordkanalstr. 28
20097 Hamburg
Germany
Manufacturer (responsible for batch release)
Helm AG
Nordkanalstr. 28
20097 Hamburg
Germany
S.C. POLISANO PHARMACEUTICALS S.R.L.
Sos. Alba Iulia nr. 156,
Sibiu, Jud. Sibiu, cod 550052
ROMANIA
This medicinal product is authorised in the Member States of the EEA under the following
names:
Denmark
United Kingdom

Kappalkyl, 2.5 mg/ ml pulver til koncentrat til infusionsvæske, opløsning
Kappalkyl, 2.5 mg/ ml Powder for concentrate for solution for infusion

This leaflet was last revised in 11/2015.

The following information is intended for 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 Kappalkyl (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% w/v 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 vials are for single use only.
The solution ready for use must be prepared by dissolving the contents of an injection vial of Kappalkyl
exclusively in water for Injections, as follows:
1. Preparation of the concentrate
• One injection vial of Kappalkyl containing 25 mg of bendamustine hydrochloride is first
dissolved in 10 ml by shaking
• One injection vial of Kappalkyl 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
Kappalkyl is immediately diluted with 0.9% w/v saline solution to obtain a final volume of approximately
500 ml. Kappalkyl must not be diluted with other solutions for infusion or injection. Kappalkyl 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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