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FLUDARABINE PHOSPHATE 50MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION

Active substance(s): FLUDARABINE PHOSPHATE

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PACKAGE LEAFLET: INFORMATION FOR THE USER
Fludarabine Phosphate 50 mg Powder 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 pharmacist.
This medicine has been prescribed for you only. Do not pass it on to
others. It may harm them, even if their sign of illness are the same as
yours.
If you get any side effects talk to your doctor or pharmacist.This includes
any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet:
1.
What Fludarabine Phosphate Powder for Solution for Injection or
Infusion is and what it is used for
2.
What you need to know before you are given Fludarabine Phosphate
Powder for Solution for Injection or Infusion
3.
How to use Fludarabine Phosphate Powder for Solution for Injection or
Infusion
4.
Possible side effects
5.
How to store Fludarabine Phosphate Powder for Solution for Injection
or Infusion
6.
Contents of the pack and other information
1.

What Fludarabine Phosphate Powder for Solution for Injection or
Infusion is and what it is used for

Fludarabine phosphate is an anti-cancer medicine. Fludarabine phosphate is
used in the treatment of B-cell chronic lymphocytic leukaemia (B-CLL) in
patients who have a sufficient amount of healthy blood cells in their bone
marrow.
First treatment for chronic lymphocytic leukaemia with fludarabine phosphate
should only be started in patients with advanced disease having disease
related symptoms or evidence of disease progression.
Fludarabine phosphate works by stopping the growth of new cancer cells. All
cells of the body produce new cells like themselves by dividing. For this
purpose, the cells´ genetic material (DNA) must be copied and reproduced.
Fludarabine phosphate is taken up by the cancer cells and works by hindering
the production of new DNA.
In cancers of the white blood cells (as chronic lymphocytic leukaemia), the
body produces many abnormal white blood cells (lymphocytes) and lymph
nodes start to grow in various parts of the body. The abnormal white blood

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cells cannot carry out the normal disease fighting functions. If there are too
many abnormal white blood cells, they push aside healthy blood cells - which
can result in infections, decrease in number of red blood cells (anaemia),
bruising, unusually severe bleeding or even organ failure.
2.

What you need to know before you are given Fludarabine
Phosphate Powder for Solution for Injection or Infusion

Do not use Fludarabine Phosphate Powder for Solution for Injection or
Infusion
if you are allergic to Fludarabine phosphate or any of the other
ingredients of this medicine (listed in section 6)
if your kidney function is severely reduced
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.
if you are breast-feeding (see section Pregnancy and Breast-feeding)
It is important that you tell your doctor if you have problems even if those are
on the above list or not.
Warnings and precautions
Talk to your doctor or pharmacist before using Fludarabine Phosphate for
Solution for Injection or Infusion


because the active substance of Fludarabine Phosphate Powder for
Solution for Injection or Infusion, fludarabine phosphate, is a very strong
active substance.
Therefore, the side effects can be very serious and toxic (poisonous).
For these reasons, your doctor will watch you closely if he/she
prescribed you fludarabine phosphate. Therefore, it is very important that
you report to your doctor all side effects which occur during the use of
fludarabine phosphate.
This concerns mainly the following adverse events:
- You are not feeling well.
This is especially important to report if your bone marrow is not
working properly, if your immune system is not working well or if you
are susceptible to infections.
- After injury you notice unusual bruising or excessive bleeding.
This can point to a reduction in healthy blood cells.
- Changes of your skin, such as rash or blisters.
This is especially important if you have or have had skin cancer.

Your doctor may decide not to give you fludarabine phosphate, or to give you
this medicine with special precautions, if you experience one of the above
mentioned side effects.

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You will have regular blood checks during treatment
-

if you are catching a lot of infections (if you have a poorly functioning or
depressed immune system or a history of serious infections).

Your immune system may attack different parts of your body (called
‘autoimmune phenomenon’), and this may also be directed against your red
blood cells (called ‘autoimmune haemolysis’). This condition can be life
threatening and even lead to death. If you experience this condition you may
receive further medication such as transfusion of blood (irradiated, see below)
and adrenocorticoids.


when you receive a high dose. When fludarabine phosphate is used in
patients with acute leukaemia at very high doses (up to four times
greater than the recommended dose for CLL) a third of patients
experienced severe central nervous system effects (including blindness,
coma and death). In patients receiving the recommended dose for CLL,
coma, seizures or agitation are rare events. Confusion occasionally
occurs. You should mention to your doctor any unusual symptoms you
experience. Some of these symptoms appeared delayed around 60 days
or more after treatment has been stopped.



when you use fludarabine for a lengthy period. The effect of long-term
use of fludarabine phosphate on the central nervous system is unknown.
However, some people have endured the recommended dose for up to
26 courses of therapy.



if you need a blood transfusion and you are being (or have been)
treated with fludarabine phosphate, you should mention this to your
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.



if you need to have stem cells collected and you are being (or have
been) treated with fludarabine phosphate, tell your doctor that you have
received fludarabine phosphate.



when you need a vaccination; consult your doctor, because live virus
vaccines should be avoided during and after treatment with fludarabine
phosphate.



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 may cause dehydration,
reduced kidney function and heart problems from the first week of
treatment and is called tumour lysis syndrome. Your doctor will be aware
of this and may give you other drugs to deal with this problem.

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if you have skin cancer, the damaged areas of your skin may become
worse when you use this medicine. You may develop skin cancer during
or after treatment with fludarabine phosphate. Tell your doctor if you
notice any changes to your skin either while you are receiving this
medicine or even after you have finished taking this medicine.



with children. The safety and effectiveness of fludarabine phosphate
has not been established. Therefore, fludarabine phosphate is not
recommended for use in children.



with men and women who may still be fertile; see Section “Pregnancy
and breast-feeding”.



if your liver does not work properly; your doctor may decide not to give
you this medicine, or may give you this medicine with caution.



if you have any form of kidney disease or if you are over 65 years old,
your kidney function should be checked regularly. If your kidneys are
found not to work properly you may be given fludarabine phosphate at a
reduced dose. If your kidneys work at only a very low level you will not
be given this medicine at all.



if you are over 75 years old, fludarabine phosphate will be given with
caution.

Consult your doctor if one of the above mentioned warnings is applicable to
you, or has been in the past.
Other medicines and Fludarabine Phosphate
Attention: the following remarks can also apply to the use of medicines in the
past or in the near future.
The medicines mentioned in this section may be known to you under a
different name, often the brand name. In this section only the name of the
active ingredient or group of active ingredients of the medicine is mentioned
and not the brand name! Therefore, check on the package or insert what the
active ingredient is of the medicine you are using.
An interaction means that medicines, when used at the same time, can
influence each other’s action and/or side effects. An interaction can occur with
this medicine when used together with:
pentostatin (=deoxycoformycin) (another medicine that inhibits the
growth of cancer); you may not be treated with fludarabine phosphate
some blood thinning medicines, such as dipyridamole; they 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 fludarabine phosphate in the cell may rise. However, the overall

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levels in the blood and its elimination from the blood were not shown to
have changed
Please tell your doctor if you are taking or have recently taken or might take
any other medicines., including medicines obtained without a prescription.
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 doctore or pharmacist for advice before
taking this medicine, because animal studies and limited experience in
humans have shown a possible risk of abnormalities in the developing foetus.
Your doctor will carefully weigh up the benefit of your treatment against a
possible risk for an unborn child and, if you are pregnant, will only prescribe
fludarabine phosphate if clearly necessary.
If you are a woman who may still be fertile, you must avoid becoming
pregnant. However, if you do become pregnant inform your doctor
immediately.
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.
It is not known if fludarabine appears in the breast milk of women treated with
this medicine. However, in animal studies fludarabine has been found in
breast milk. Therefore you should not breast-feed during your treatment with
this medicine.
Ask your doctor for advice before taking any medicine.
Driving and using machines
Some people get tired, feel weak, have disturbed vision, become confused or
agitated or have seizures while they are being treated with fludarabine
phosphate. Do not try to drive or operate machines until you are sure that you
are not affected.
Important information about some of the ingredients of Fludarabine
Phosphate Powder for Solution for Injection or Infusion
Fludarabine Phosphate Powder for Solution for Injection or Infusion contains
less than 1 mmol sodium (23 mg) per 1 ml (when the contents of the vial is
dissolved in 2 ml of water), i.e. essentially ‘sodium-free’.
3. How to use Fludarabine Phosphate Powder for Solution for Injection
or Infusion
Fludarabine phosphate should be used under the supervision of a qualified
doctor experienced in the use of anticancer therapy.

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Always take this medicine exacty as described in this leaflet or as your doctor
or pharmacist has told you. Check with your doctor or pharmacist if you are
not sure.
Your doctor will decide when and how long fludarabine phosphate will be
given to you. Consult your doctor if you have the feeling that fludarabine
phosphate is acting too strongly or not strongly enough.
The administered amount of fludarabine phosphate (the dose) depends on the
size of your body. Technically this is measured in square metres (m2), but
actually is calculated from your height and weight.
General guidance
The recommended dose is 25 mg/m2 body surface per day. This will be given
either as an injection or as an infusion for 5 consecutive days. This five day
course of treatment will be repeated every 28 days until your doctor has
decided that the best possible effect has been achieved. In general this is
after 6 cycles, in other words after approximately 6 months. The dosage may
be decreased or the repeat course delayed if side effects are a problem.
You will have regular blood tests during your treatment. Your individual
dose will be carefully adjusted according to the number of your blood cells
and your response to the therapy.
If you have kidney problems or are over the age of 70, 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 you take more Fludarabine Phosphate Powder for Solution for
Injection or Infusion than you should
As this medicine is given in a hospital, it is unlikely that you will be g iven too
little or too much, however tell your doctor if you have any concerns.
There is no specific antidote for fludarabine phosphate overdosage. If you
received too much fludarabine phosphate the doctor will stop the therapy and
treat the symptoms.
High doses of fludarabine phosphate have been associated with irreversible
central nervous system side effects characterised by delayed blindness,
coma, and death.
High doses are also associated with severe reduction in the number of certain
types of blood cells (severe thrombocytopenia (decreased number of platelets
attended with bruises and bleeding) and neutropenia (decreased number of
white blood cells attended with increased infection risk)) due to decreased
activity of the bone marrow (bone marrow suppression).

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If you forget to take Fludarabine Phosphate Powder for Solution for
Injection or Infusion.
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.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not
everybody gets them.
Some side effects can be life-threatening.
- If you have difficulty breathing, have a cough, or have chest pain with
or without fever. These may be signs of an infection of the lungs.
- If you notice any 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 people (opportunistic infections), including a late
reactivation of viruses, for example herpes zoster.
- If you notice any pain in your side, blood in your urine, or reduced
amount of urine. These may be signs of a condition called tumour lysis
syndrome.
- If you notice any blistering of the skin, mouth, eyes and genitals,
inflammation, blistering and tissue break down. These may be signs of a
severe reaction (Lyell’s syndrome, Stevens-Johnson syndrome).
- If you have palpitations (awareness of your heart beat) or chest pain.
These may be signs of heart problems.
Tell your doctor immediately, if you notice any of these effects.
If you are not sure what the side-effects listed below are, ask your doctor to
explain them to you.
Very common: affects more than 1 user in 10
- infections (some serious);
- infections due to depressed immune system (opportunistic infections);
- infection of the lungs (pneumonia) with possible symptoms like breathing
difficulties and/or cough with or without fever;
- reduction in the number of blood platelets (thrombocytopenia) with the
possibility of bruising and bleeding;
- lowered white blood cell count (neutropenia);
- lowered red blood cell count (anaemia);
- cough;
- vomiting, diarrhoea, feeling sick (nausea);

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- fever;
- feeling tired (fatigue);
- weakness;
Common: affects 1 to 10 users in 100
- other 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);
- bone marrow depression (myelosuppression);
- severe loss of appetite leading to weight loss (anorexia);
- numbness or weakness in limbs (peripheral neuropathy);
- disturbed vision;
- inflammation of the inside of the mouth (stomatitis);
- 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.
Uncommon: affects 1 to 10 users in 1,000
- autoimmune disorder;
- tumour lysis syndrome;
- 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: affects 1 to 10 users in 10,000
- 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;
- skin and/or mucous coat reaction with redness, inflammation, blistering and
tissue break down (Lyell's syndrome, Stevens-Johnson syndrome).
Not Known: frequency cannot be estimated from the available data
- cerebral haemorrhage (bleeding in the brain);
- pulmonary haemorrhage (bleeding in the lungs);
- inflammation of the bladder, which can cause pain when passing urine, and
can lead to blood in the urine (haemorrhagic cystitis).

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Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. 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 Fludarabine Phosphate Powder for Injection or
Infusion

Keep this medicine out of the sight and reach of children.
As packaged for sale: Do not store above25°C.
For storage conditions after reconstitution and dilution: please refer to section
‘Information for medical and healthcare professionals’
Do not use this medicine after the expiry date which is stated on the carton
and vial after EXP. The expiry date refers to the last day of that month.
Any vials which are damaged in anyway should be discarded.
The reconstituted solution is clear and colourless. Do not use this medicine if
you notice that the solution is not clear, colourless and particle free..
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 to protect the environment.
6.

Contents of the pack and other information

What Fludarabine Phosphate Powder for Solution for Injection or
Infusion contains
The active substance is fludarabine phosphate. Each vial contains 50
mg fludarabine phosphate
The other ingredients are mannitol and sodium hydroxide used as a pH
adjuster
1 ml of reconstituted solution contains 25 mg of fludarabine phosphate.
What Fludarabine Phosphate Powder for Solution for Injection or
Infusion looks like and contents of the pack

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Fludarabine Phosphate Powder for Solution for Injection or Infusion is a sterile
white to off-white powder for solution for injection or infusion in a 10 ml clear,
colourless vial sealed with a rubber closure and a flip-off cap. The powder is
reconstituted with Water for Injection and further diluted.
The reconstituted solution is clear and colourless.
Fludarabine Phosphate Powder for Solution for Injection or Infusion is
available in packs containing 5 vials.
Marketing Authorisation Holder and Manufacturer
Hospira UK Limited
Queensway
Royal Leamington Spa
Warwickshire
CV31 3RW
UK
For any information about this medicinal product, please contact the
Marketing Authorisation Holder detailed above.
This medicinal product is authorised in the Member States of the EEA
under the following names:
Denmark:
Finland:
France:
Ireland:
Italy:
Norway:
Portugal:
Spain:
Sweden:
UK:

Fludarabinphosphat Hospira 50 mg pulver til injektions- og
infusionsvæske, opløsning
Fludarabin Hospira 50 mg injektio-/infuusiokuiva-aine, liuosta
varten
FLUDARABINE PHOSPHATE HOSPIRA 50mg, poudre pour
solution injectable ou perfusion
Fludarabine Phosphate 50 mg Powder for Solution for Injection
or Infusion
Fludarabina Fosfato Hospira 50 mg Polvere per Soluzione per
Iniezione o Infusione
Fludarabinphosphat Hospira 50 mg pulver til injeksjons-/
infusjonsvæske, oppløsning
Fludarabina Hospira 50 mg pó para solução injectável MG
Fosfato de fludarabina Hospira 50 mg polvo para solución
inyectable o para perfusión
Fludarabinphosphat Hospira 50mg pulver till injektions/infusionsvätska, lösning
Fludarabine Phosphate 50 mg Powder for Solution for Injection
or Infusion

This leaflet was last approved 06/2015
----------------------------------------------------------------------------------------------------The following information is intended for healthcare professionals only:

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Fludarabine Phosphate Powder for Solution for Injection or Infusion as other
potiential cytotoxic medicines should be prepared by qualified personnel in a
designated area. Consideration should be given to handling and disposal
according to guidelines used for cytotoxic drugs.
For intravenous use only
Incompatibilities
Must not be mixed with other drugs.
Instructions for use and handling
Reconstitution
Fludarabine Phosphate Powder for Solution for Injection or Infusion should be
prepared for use by aseptically adding sterile Water for Injections.
When reconstituted with 2 ml of sterile Water for Injections, the powder should
fully dissolve in 15 seconds or less. Each ml of the resulting solution will
contain 25 mg of fludarabine phosphate. The solution should be inspected
visually. The reconstituted solution should be clear, colorless and without
particles.
Dilution
The reconstituted solution draws up into a syringe. For intravenous bolus
injection this dose is further diluted into 10 ml 0.9 % sodium chloride. For
intravenous infusion the solution is diluted into 100 ml 0.9 % sodium chloride
and infused over 30 minutes. In clinical studies, the product has been diluted
in 100 ml or 125 ml of 5 % dextrose (for injection) or 0.9 % sodium chloride
solution.
Storage
Shelf-life after reconstitution: After reconstitution with sterile Water for
Injections to concentration of 25 mg/ml, should the product be stored in 2°C8ºC protected against light or in 25°C in normal light up to 8 hours.
Reconstituted solution with sodium chloride 0.9 % or glucose 5 % is
chemically stable stored in infusion bag in 2°C-8ºC protected against light or
in 25°C in normal light up to 8 hours.
From a microbiological point of view, the diluted product should be used
immediately. If not used immediately, in-use storage times and conditions
prior to use are the responsibility of the user. In-use storage times and
conditions prior to use and would normally not be longer than 8 hours at 2-8°C
or 8 hours at room temperature.
If any fludarabine phosphate solution is accidentally spilt:
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 plenty of
tap water. Avoid any exposure by inhalation.

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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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