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FLUDARABINE PHOSPHATE 25MG/ML CONCENTRATE FOR SOLUTION FOR INJECTION OR INFUSION

Active substance(s): FLUDARABINE PHOSPHATE

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10 mm

Package leaflet: Information for the user
10 mm

Fludarabine Phosphate 25 mg/ml Concentrate
for Solution for Injection or Infusion
Fludarabine Phosphate

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

you should mention this to the
doctor.
T here is little information on the
effects of Fludarabine Phosphate
in patients aged 75 years and older.
Your doctor will use it with caution if
you are in this age group.
If you have very severe chronic
lymphocytic leukaemia, your
body may not be able to get rid
of all the waste products from the
cells destroyed by Fludarabine
Phosphate. This is called tumour
lysis syndrome and may cause
dehydration, kidney failure and
heart problems. Your doctor will be
aware of this and may give you other
medicines to stop this happening.

What is in this leaflet:
1  What Fludarabine
Phosphate is and what it is
used for
2 What you need to know
before you use Fludarabine
Phosphate
3 How to use Fludarabine
Phosphate
4 Possible side effects
5 How to store Fludarabine
Phosphate
6 Contents of the pack and
other information

219 mm

If you experience any unusual
symptoms from the nervous system
you should mention it to your
doctor. This is because when used in
patients at doses four times greater
than the recommended dose,
severe central nervous system (brain
and spinal cord) effects including
blindness, coma and death have
been reported.
Tell your doctor if you notice any
changes to your skin either while
you are receiving this medicine or
after you have finished the course
of therapy. The doctor should check
the seriousness of the skin changes.
If you have skin cancer, the damaged
areas of your skin may become
worse when you use this medicine.

1 W
 hat Fludarabine

Phosphate is and what it is
used for

Men and women who may still be
fertile, must use a reliable form of
contraception during and for at least
6 months after stopping treatment.

Fludarabine Phosphate is an anticancer drug.
Fludarabine Phosphate is used to
treat chronic B-cell lymphocytic
leukaemia (B-CLL) in patients
with sufficient healthy blood cell
production. This is a type of cancer
of white blood cells (the cells are
called lymphocytes).

Check with your doctor about any
vaccinations you may need, because
live vaccinations should be avoided
during and after treatment with
Fludarabine Phosphate.

Children and adolescents

First treatment for chronic
lymphocytic leukaemia with
Fludarabine Phosphate should only
be started in patients with advanced
14 mm

Fludarabine Phosphate is not
recommended for use in children
and adolescents below age 18. No

20 mm
ITF high 8 mm

-1 mm

+1 mm
20 mm

14 mm

disease having disease related
symptoms or evidence of disease
progression.

data are available concerning the
use of Fludarabine Phosphate in the
paediatric population.

Other medicines and
Fludarabine Phosphate

2 W
 hat you need to know

before you use Fludarabine
Phosphate

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

Do not use Fludarabine
Phosphate:

It is especially important to tell your
doctor about:
• Pentostatin (deoxycoformycin),
which is also used to treat B-CLL.
Taking these two drugs together
can lead to severe lung problems
(which can be life-threatening),
so combination with Fludarabine
Phosphate is not recommended.
• Dipyridamole (or other similar
substances), which is used to
prevent excessive blood clotting.
They may reduce the effectiveness
of Fludarabine Phosphate.
• Cytarabine (Ara-C), which is
used to treat chronic lymphatic
leukaemia. If Fludarabine
Phosphate is combined with
cytarabine, levels of the active
form of cytarabine (Ara-CTP) in
leukaemic cells may rise. However,
the overall levels of cytarabine in
the blood and its elimination from
the blood were not shown to have
changed.

• If you are allergic to fludarabine
phosphate or any of the other
ingredients of this medicine (listed
in section 6).
• If you are breast feeding.
• If your kidney function is severely
impaired.
• If you have a low number of red
blood cells, because of a certain
type of anaemia (decompensated
haemolytic anaemia). Your doctor
will have told you if you have this
condition.

Warnings and precautions

453 mm

Talk to your doctor or nurse before
using Fludarabine Phosphate if:
• Your liver does not work properly,
as your doctor may give you this
medicine with caution.
• You have any form of kidney
disease, as your kidney function
should be checked regularly. If it
is found that your kidneys do not
work properly you may be given
this medicine at a reduced dose.
If your kidneys work at only a very
low level you will not be given this
medicine at all. Patients aged 65
years or older should have their
kidney function checked before
start of treatment.
• You are not feeling very well, as
your doctor may decide not to
give you this medicine, or may give
you this medicine with caution.
This is very important if your bone
marrow is not working properly or
if you are susceptible to infections.
• You notice any unusual bruising,
excessive bleeding after injury or
if you seem to be catching a lot of
infections. The number of normal
blood cells may be reduced and so
you will have regular blood tests
during treatment.

Pregnancy, breast-feeding and
fertility
If you are pregnant or breastfeeding, think you may be pregnant
or are planning to have a baby, ask
your doctor for advice before taking
this medicine.

Fludarabine Phosphate treatment
has the potential to harm the
unborn child. You should not be
given Fludarabine Phosphate if
you are pregnant unless clearly
necessary and when the potential
benefits justify the potential risks to
the unborn child. If you are a woman
who may still be fertile, you must
avoid becoming pregnant during
treatment and for at least 6 months
after stopping treatment. However,
if you do become pregnant inform
your doctor immediately.

The disease itself and the therapy
may cause a reduction of the
number of blood cells and your
immune system may attack different
parts of your body (autoimmune
disorder). It may also be directed

Men who are treated with
Fludarabine Phosphate and can
father a child must use a reliable
form of contraception during, and
for at least 6 months after stopping
treatment.

10 mm

against your red blood cells (called
‘autoimmune haemolysis’). This
condition can be life threatening.
If this condition occurs you may
receive further medication such as
transfusion of blood (irradiated, see
below) and corticosteroids.

It is not known if this medicine
appears in the breast milk of women
treated with Fludarabine Phosphate.
However, in animal studies the
medicinal product was found in
breast milk. Therefore you must not
breast feed during your treatment
with this medicine.

If you need a blood transfusion
and you are being (or have been)
treated with this medicine, you
should mention this to the doctor.
Your doctor will ensure that you
receive blood only, which has
gone through a special treatment
(irradiation). There have been severe
complications and even death
reported when non-irradiated blood
has been given.

Driving and using machines

Some people get tired, feel weak,
have disturbed vision, become
confused or agitated, or have
seizures while they are treated with
Fludarabine Phosphate. Do not try to
drive or operate machines until you
are sure that you are not affected.

Fludarabine Phosphate
contains sodium

If you need to have stem cells
collected and you are being (or have
been) treated with this medicine,

This medicinal contains less than
1mmol sodium (23mg) per ml, i.e.
essentially ‘sodium-free’.

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AAAI3293

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The following information is intended for healthcare professionals only:

Fludarabine Phosphate 25mg/ml Concentrate for
Solution for Injection or Infusion
Instructions for use, handling and
disposal
ANTINEOPLASTIC AGENT
A crossover from initial treatment
with Fludarabine Phosphate to
chlorambucil for non-responders to
Fludarabine Phosphate should be
avoided because most patients who
have been resistant to Fludarabine
Phosphate have shown resistance
to chlorambucil.
Instructions for use
This medicinal product must not
be mixed with other medicinal
products, other than those
mentioned below.

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AAAI3293

Dilution
The required dose (calculated on
the basis of the patient’s body
surface) is drawn up into a syringe.
For intravenous bolus injection this
dose is further diluted in 10ml of
0.9% sodium chloride. Alternatively,
for infusion, the required dose
may be diluted in 100ml of 0.9%
sodium chloride and infused over
approximately 30 minutes.
Inspection prior to use
Only clear, colourless to yellowish
solutions without particles should
be used. Fludarabine Phosphate
should not be used in case of a
defective container.

continued over page
Supplier coding area

5 mm
10 mm

Fludarabine 50mg (25mg/ml ) PIL - UK/EIRE

approved for print/date

item no: AAAI3293

dimensions: 124 x 700

print proof no: 2

pharmacode:

origination date: 18.09.15

min pt size: 9

colours/plates:
1. Black
2.
3.
4.
5.
6.

originated by: S.Anson
revision date: 24.09.15

Technical Approval

revised by: S.Anson

date sent: 18.09.15

supplier: Nerviano

technically app. date: 21.09.15

Non Printing Colours
1.
2.
3.

• Skin rash;
• Swelling due to excessive fluid
retention (oedema);
• Inflammation of the mucous coat
of the digestive system from the
mouth to the anus (mucositis);
• Chills;
• Generally feeling unwell.

3 H
 ow to use Fludarabine

Phosphate

Fludarabine Phosphate should be
administered under the supervision
of a qualified doctor experienced in
cancer therapy.
The dose you are given depends
on the size of your body. It varies
with your body surface area.
Technically this is measured in
square metres (m2), but is actually
worked out from your height and
weight. The recommended dose
is 25 mg/m2 body surface. This will
be given either as an injection or as
an infusion (with a drip) into a vein
once a day for 5 consecutive days
every 28 days. This five day course of
treatment will be repeated every 28
days until your doctor has decided
that the best effect has been
achieved (usually after 6 cycles). The
dosage may be decreased or the
repeat course delayed if side effects
are a problem. If you have kidney
problems or if you are over the age
of 65, you will have regular tests to
check your kidney function. If your
kidneys do not work properly you
may be given this medicine at a
lower dose. If your kidney function
is severely reduced you will not be
given this medicine at all (see also
section 2, ‘Do not use Fludarabine
Phosphate’).
The safety of this drug in children
and adolescents below age 18 has
not been established and treatment
is not recommended.

Uncommon (may affect up to 1 in
100 people):
• Attack of the immune system on
parts of the body or red blood cells
(autoimmune disorder);
• Confusion;
• Lung toxicity; scaring throughout
the lungs (pulmonary fibrosis),
inflammation of the lungs
(pneumonitis), shortness of breath
(dyspnoea);
• Bleeding in the stomach or
intestines;
• Abnormal levels of the liver or
pancreas enzymes.
Rare (may affect up to 1 in 1,000
people):
• Disorders of the lymph system due
to a viral infection (EBV-associated
lymphoproliferative disorder);
• Coma;
• Seizures;
• Agitation;
• Blindness;
• Inflammation or damage of the
nerve of the eyes (optic neuritis;
optic neuropathy);
• Heart failure;
• Irregular heart beat (arrhythmia);
• Skin cancer;
Not known (frequency cannot be
estimated from the available data)
• Inflammation of the bladder, which
can cause pain when passing urine,
and can lead to blood in the urine
(haemorrhagic cystitis);
• Bleeding in the brain (cerebral
haemorrhage)
• Bleeding in the lungs (pulmonary
haemorrhage)

If any of the Fludarabine Phosphate
solution comes into contact with
your skin or the lining of your nose
or mouth, wash the area thoroughly
with soap and water. If the solution
gets into your eyes, rinse them
thoroughly with lots of water. Try
not to breathe in any fumes coming
from the solution.

Reporting of side effects

If you use more Fludarabine
Phosphate than you should

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:
United Kingdom
Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance, Earlsfort
Terrace, IRL - Dublin 2;
Tel: +353 1 6764971;
Fax: +353 1 6762517.
Website: www.hpra.ie;
E-mail: medsafety@hpra.ie.

In the case of an overdose your
doctor will stop the therapy and
treat the symptoms.
Symptoms of an overdose can be
blindness which may not appear
until later, coma and death due to
irreversible toxicity to the central
nervous system. High doses can also
lead to a severely reduced number
of blood cells.

If you forget to use
Fludarabine Phosphate

Your doctor will set the times
at which you are to receive this
medicine. If you think you may have
missed a dose, contact your doctor
as soon as possible.
If you have any further questions
on the use of this product, ask your
doctor or nurse.

By reporting side effects you can
help provide more information on
the safety of this medicine.

5 How to store Fludarabine

Phosphate

Keep this medicine out of the sight
and reach of children.

4 Possible side effects
Like all medicines, this medicine
can cause side effects, although not
everybody gets them.
If you are not sure what the adverse
reactions below are, ask your doctor
to explain them to you.
Some side effects can be lifethreatening. You must contact your
doctor immediately if you notice
any of the following:
• Difficulty breathing, a cough, or
chest pain with or without fever.
These may be signs of an infection
of the lungs (pneumonia).
• Unusual bruising, more bleeding
than usual after injury or if you
seem to be catching a lot of
infections. These may be caused
by a reduced number of blood
cells. This may also lead to an
increased risk of (serious) infections,
caused by organisms, that usually
do not cause disease in healthy
persons (opportunistic infections)
including a late reactivation of
viruses, for example herpes zoster.
• Pain in your side, blood in your
urine, or reduced amount of
urine. These may be signs of
tumour lysis syndrome (see section
2 ‘Warnings and precautions’).
• Skin and / or mucous coat
reaction with redness,
inflammation, blistering and
tissue break down. These may be
signs of a severe allergic reaction
(Lyell’s syndrome, Stevens-Johnson
syndrome).
•Y
 ou have palpitations (if you
suddenly become aware of your
heart beat) or chest pain. These
may be signs of heart problems.

Vial before opening:
Store between 2‑8°C.
After dilution:
The diluted solution of Fludarabine
Phosphate in 0.9% sodium chloride
is stable for up to 28 days in PVC and
PE bags at 2-8°C and at 25°C when
protected from light.
From a microbiological point of view,
the product must be used immediately.
If not used immediately, in-use
storage times and conditions prior
to use are the responsibility of the
user and would normally not be
longer than 24 hours at 2 to 8°C,
unless dilution has taken place in
controlled and validated aseptic
conditions.
Do not use this medicine after the
expiry date which is stated on the
carton and vial after EXP.
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 Fludarabine Phosphate
contains

• The active substance is fludarabine
phosphate. 1 ml of concentrate
contains 25mg fludarabine
phosphate. Each 2 ml vial contains
50mg fludarabine phosphate.
• The other ingredients are disodium
phosphate dihydrate, water for
injections, sodium hydroxide (for
pH adjustment).

Below we list other possible side
effects by how common they are.
The rare side effects (may affect up
to 1 in 1,000 people) were mainly
identified from post-marketing
experience.

What Fludarabine Phosphate
looks like and contents of the
pack
Fludarabine Phosphate is a clear,
colourless or almost colourless
solution.

Very common (may affect more
than 1 in 10 people):
• Infections (some serious);
• L owered white blood cell count
(neutropenia);
• L owered red blood cell count
(anaemia);
• Cough;
• Vomiting, diarrhoea, feeling sick
(nausea);
• Fever;
• F eeling tired (fatigue);
•W
 eakness.

Colourless glass vial (type I) with
bromobutylic rubber stopper and
metallic cap (aluminium) with
polypropylene disk. Vial will be
packed with or without a protective
plastic overwrap.
Pack sizes
2ml vial
5 x 2ml vial
Not all pack sizes may be marketed.

Common (may affect up to 1 in 10
people):
•O
 ther blood related cancers
(myelodysplastic syndrome,
acute myeloid leukaemia). Most
patients with these conditions
were previously, or at the same
time or later treated with other
cancer drugs (alkylating agents,
topoisomerase inhibitors) or
radiation therapy;
•B
 one marrow depression
(myelosuppression);
• S evere loss of appetite leading to
weight loss (anorexia);
•N
 umbness or weakness in limbs
(peripheral neuropathy);
•D
 isturbed vision;
• Inflammation of the inside of the
mouth (stomatitis);

Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður, Iceland
Manufacturer
Actavis Italy S.p.A
Via Pasteur 10, 20014 Nerviano (Milan)
Italy
This leaflet was last revised in September
2015

If you would like a
leaflet with larger
text, please contact
UK: 01271 385257
IE: 1890 333231

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AAAI3293

Storage conditions after dilution:
The diluted solution of Fludarabine
Phosphate in 0.9% sodium chloride
is stable for up to 28 days in PVC
and PE bags at 2-8°C and at 25°C
when protected from light. From a
microbiological point of view, the
product must be used immediately.
If not used immediately, in-use
storage times and conditions prior
to use are the responsibility of the
user and would normally not be
longer than 24 hours at 2 to 8°C,
unless dilution has taken place in
controlled and validated aseptic
conditions.
Handling and disposal
Fludarabine Phosphate should not
be handled by pregnant staff.
Procedures for proper handling
should be followed according to
local requirements for cytotoxic
drugs. Caution should be exercised
in the handling and preparation
of the Fludarabine Phosphate

solution. The use of protective
gloves and safety glasses is
recommended to avoid exposure in
case of breakage of the vial or other
accidental spillage.
If the solution comes into
contact with the skin or mucous
membranes, the area should be
washed thoroughly with soap and
water. In the event of contact with
the eyes, rinse them thoroughly
with copious amounts of water.
Exposure by inhalation should be
avoided.
The medicinal product is for single
use only. Any unused product or
waste material should be disposed
of in accordance with local
requirements for cytotoxic agents.

AAAI3293

Supplier coding area

Fludarabine 50mg (25mg/ml ) PIL - UK/EIRE

approved for print/date

item no: AAAI3293

dimensions: 124 x 700

print proof no: 2

pharmacode:

origination date: 18.09.15

min pt size: 9

colours/plates:
1. Black
2.
3.
4.
5.
6.

originated by: S.Anson
revision date: 24.09.15

Technical Approval

revised by: S.Anson

date sent: 18.09.15

supplier: Nerviano

technically app. date: 21.09.15

Non Printing Colours
1.
2.
3.

Expand view ⇕

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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