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

Active substance: 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.
•  eep this leaflet. You may need
K
to read it again.
• f you have any further
I
questions, ask your doctor.
•  his medicine has been
T
prescribed for you only. Do not
pass it on to others. It may harm
them, even if their signs of
illness are the same as yours.
• f you get any side effects, talk
I
to your doctor. This includes
any possible side effects not
listed in this leaflet.
What is in this leaflet:
1  hat Fludarabine Phosphate
W
is and what it is used for
2  hat you need to know
W
before you use Fludarabine
Phosphate
3  ow to use Fludarabine
H
Phosphate
4 Possible side effects
5  ow to store Fludarabine
H
Phosphate
6  ontents of the pack and
C
other information

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1 What Fludarabine Phosphate

is and what it is used for

Fludarabine Phosphate is an anti-cancer
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).
First treatment for chronic lymphocytic
leukaemia with Fludarabine Phosphate
should only be started in patients
with advanced disease having disease
14 mm

•  here is little information on the
T
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.
• f you have very severe chronic
I
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.
• f you experience any unusual
I
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.
•  ell your doctor if you notice any
T
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.
•  en and women who may still be
M
fertile, must use a reliable form of
contraception during and for at least
6 months after stopping treatment.
•  heck with your doctor about any
C
vaccinations you may need, because
live vaccinations should be avoided
during and after treatment with
Fludarabine Phosphate.

Children and adolescents

Fludarabine Phosphate is not
recommended for use in children and
adolescents below age 18.
No data are available concerning the
use of Fludarabine Phosphate in the
paediatric population.

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ITF high 8 mm

-1 mm

+1 mm
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related symptoms or evidence of
disease progression.

2  hat you need to know
W

before you use Fludarabine
Phosphate

Do not use Fludarabine Phosphate
• f you are allergic to fludarabine
i
phosphate or any of the other
ingredients of this medicine
(listed in section 6)
• f you are breast-feeding
i
• f your kidney function is severely
i
impaired
• f you have a low number of red
i
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

• f you are not feeling very well you
I
should tell your doctor, 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.
• f you notice any unusual bruising,
I
excessive bleeding after injury or
if you seem to be catching a lot
of infections, tell your doctor. The
number of normal blood cells may
be reduced and so you will have
regular blood tests during treatment.
•  he disease itself and the therapy
T
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
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.

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• f you need a blood transfusion
I
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.

Other medicines and Fludarabine
Phosphate

Tell your doctor if you are taking, have
recently taken or might take any other
medicines. This is especially important if
you are taking a drug called pentostatin
or deoxycoformycin (also used to
treat chronic lymphocytic leukaemia)
as a combination with Fludarabine
Phosphate is not recommended. Some
drugs, e.g. dipyridamole (used to
prevent excessive blood clotting) may
reduce the effectiveness of Fludarabine
Phosphate.
It is especially important to tell your
doctor about:
•  entostatin (deoxycoformycin), also
p
used to treat B-CLL. Taking these two
drugs together can lead to severe
lung problems.
•  ipyridamole, used to prevent
d
excessive blood clotting or other
similar substances. They may reduce
the effectiveness of Fludarabine
Phosphate.
•  ytarabine (Ara-C) used to treat
c
chronic lymphatic leukaemia. If
Fludarabine Phosphate is combined
with cytarabine, levels of the active
form of Fludarabine Phosphate in
leukaemic cells may rise. However,
the overall levels in the blood and its
elimination from the blood were not
shown to have changed.

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
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.
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.
It is not known if this medicine appears
in the breast milk of women treated with

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• f you need to have stem cells
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collected and you are being (or have
been) treated with this medicine, you
should mention this to the doctor.

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.

• f your liver does not work properly,
I
your doctor may give you this
medicine with caution.

Driving and using machines

• f you have any form of kidney
I
disease, 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.

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

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AAAF2649

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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.

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.
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AAAF2649

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.
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.
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Supplier coding area

5 mm
10 mm

Fludarabine 50mg (25mg/ml ) PIL - UK/EIRE
item no: AAAF2649

dimensions: 124x700

print proof no: 8

pharmacode:

origination date: 23/04/13

min pt size: 9pt body text

2.
3.
4.
5.
6.

originated by: C.Paull
approved for print/date

colours/plates:
1. Black

revision date: 12.06.13

Technical Approval

revised by: SA

date sent: 23/04/13

supplier: Nerviano

technically app. date: 02/05/13

Non Printing Colours
1.
2.
3.

10 mm

3  ow to use Fludarabine
H

Phosphate

10 mm

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
actually is 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.
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.

If you use more Fludarabine
Phosphate than you should

•  kin rash
s
•  welling due to excessive fluid
s
retention (oedema)
• nflammation of the mucous coat of
i
the digestive system from the mouth
to the anus (mucositis)
•  hills
c
•  enerally feeling unwell.
g
Uncommon means between 1 and 10
in every 1,000 patients are likely to get
these:
•  ttack of the immune system on
a
parts of the body or red blood cells
(autoimmune disorder)
• ncrease in potassium, phosphate
i
and uric acid in the blood that can
cause kidney problems (tumour lysis
syndrome)
•  onfusion
c
• ung toxicity; scaring throughout
l
the lungs (pulmonary fibrosis),
inflammation of the lungs
(pneumonitis), shortness of breath
(dyspnoea)
•  leeding in the stomach or intestines
b
•  bnormal levels of the liver or
a
pancreas enzymes.
Rare means less than 10 in every 10,000
patients are likely to get these:
•  isorders of the lymph system due
d
to a viral infection (EBV-associated
lymphoproliferative disorder)
•  oma
c
•  eizures
s
•  gitation
a
•  lindness
b
• nflammation or damage of the
i
nerve of the eyes (optic neuritis; optic
neuropathy)
•  eart failure
h
• rregular heart beat (arrhythmia)
i
•  kin cancer
s
•  kin and/or mucous coat reaction
s
with redness, inflammation,
blistering and tissue break down
(Lyell’s syndrome, Stevens-Johnson
syndrome).

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.

Frequency not know

If you forget to use Fludarabine
Phosphate

If you get any side effects, talk to your
doctor. This includes any side effects not
listed in this leaflet.

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
pharmacist.

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.
•  f you have difficulty breathing,
I
have a cough or have chest pain
with or without fever. These may be
signs of an infection of the lungs.
•  f you notice any unusual bruising,
I
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.
•  f you notice any pain in your side,
I
blood in your urine or reduced
amount of urine. These may be
signs of tumour lysis syndrome (see 2
‘Warnings and precautions’).
•  f you notice any skin and /
I
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).
•  you have palpitations (if you
If
suddenly become aware of your
heart beat) or chest pain. These
may be signs of heart problems.

• nflammation of the bladder, which
i
can cause pain when passing urine,
and can lead to blood in the urine
(haemorrhagic cystitis)
•  leeding in the brain (cerebral
b
haemorrhage)
•  leeding in the lungs (pulmonary
b
haemorrhage).

5  ow to store Fludarabine
H

Phosphate

Keep this medicine out of the sight and
reach of children.
Store the vial before opening between
2‑8°C.
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  ontents of the pack and
C

other information

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

What Fludarabine Phosphate looks
like and contents of the pack

Tell your doctor immediately, if you
notice any of these effects.

Fludarabine Phosphate is a clear,
colourless or almost colourless solution.

Below we list possible side effects
by how common they are. The rare
side effects (less than 1 in every 1000
patients) were mainly identified from
post-marketing experience.

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.

Very common means 1 or more in
every 10 patients are likely to get these:
• nfections (some serious)
i
• nfections due to depressed immune
i
system (opportunistic infections)
• nfection of the lungs (pneumonia)
i
with possible symptoms like
breathing difficulties and/or cough
with or without fever
•  eduction in the number of blood
r
platelets (thrombocytopenia) with
the possibility of bruising and
bleeding
• owered white blood cell count
l
(neutropenia)
• owered red blood cell count
l
(anaemia)
•  ough
c
•  omiting, diarrhoea, feeling sick
v
(nausea)
•  ever
f
•  eeling tired (fatigue)
f
•  eakness.
w

Pack sizes
1 x 2 ml vial
5 x 2 ml vial
Not all pack sizes may be marketed.
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 April 2013

If you would like a
leaflet with larger
text, please contact
01271 311257.

Common means between 1 and 10
in every 100 patients are likely to get
these:
•  ther blood related cancers
o
(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
•  one marrow depression
b
(myelosuppression)
•  evere loss of appetite leading to
s
weight loss (anorexia)
•  umbness or weakness in limbs
n
(peripheral neuropathy)
•  isturbed vision
d
• nflammation of the inside of the
i
mouth (stomatitis)
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AAAF2649

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.

AAAF2649

Supplier coding area

Fludarabine 50mg (25mg/ml ) PIL - UK/EIRE
item no: AAAF2649

dimensions: 124x700

print proof no: 8

pharmacode:

origination date: 23/04/13

min pt size: 9pt body text

2.
3.
4.
5.
6.

originated by: C.Paull
approved for print/date

colours/plates:
1. Black

revision date: 12.06.13

Technical Approval

revised by: SA

date sent: 23/04/13

supplier: Nerviano

technically app. date: 02/05/13

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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