FLUDARABINE PHOSPHATE 50MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION

Active substance: 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.
• 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.

In this leaflet:
1.
2.
3.
4.
5.
6.

What Fludarabine Phosphate Powder for Solution for Injection or Infusion is and what it is used for
Before you use Fludarabine Phosphate Powder for Solution for Injection or Infusion
How to use Fludarabine Phosphate Powder for Solution for Injection or Infusion
Possible side effects
How to store Fludarabine Phosphate Powder for Solution for Injection or Infusion
Further 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 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. BEFORE YOU USE 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 (hypersensitive) to fludarabine phosphate or any of the other ingredients of
Fludarabine Phosphate Powder for Solution for Injection or Infusion
• 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.

Take special care with Fludarabine Phosphate Powder 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.
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.
• 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 70 years old, your kidney function should
be checked regularly. If you are aged 65 years or older your kidney function should be measured
before treatment is started. 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.

Taking or Using other medicines
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 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 any other medicines, including medicines
obtained without a prescription.

Pregnancy and Breast-feeding
You should not be given fludarabine phosphate if you are pregnant, 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
This medicinal product 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.
Carefully follow the advice of your doctor when using fludarabine phosphate. 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 usual 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.

The following information is intended for medical or healthcare professionals only:

Instructions for use and handling

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.

Reconstitution

For intravenous use only
Incompatibilities

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.

Must not be mixed with other drugs.
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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 given 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).

If administration of Fludarabine Phosphate Powder for Solution for Injection or Infusion is
forgotten.
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, fludarabine phosphate 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.
In the following section, we list possible side effects by how common they are. The frequency of possible
side effects is explained in the table below.

• 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:











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:
• 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).
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.

5. HOW TO STORE FLUDARABINE PHOSPHATE POWDER FOR SOLUTION FOR INJECTION
OR INFUSION
Keep out of the reach and sight of children.
As packaged for sale: Store below 25°C.
For storage conditions after reconstitution and dilution: please refer to section ‘Information for medical and
healthcare professionals’
Do not use Fludarabine Phosphate Powder for Solution for Injection or Infusion 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, only clear, colourless and particle free solutions should
be used.
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.

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

What Fludarabine Phosphate Powder for Solution for Injection or Infusion contains

Rare

affects 1 to 10 users in 10,000

• 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

Very rare

affects less than 1 user in 10,000

1 ml of reconstituted solution contains 25 mg of fludarabine phosphate.

Not known

frequency cannot be estimated from the available data

What Fludarabine Phosphate Powder for Solution for Injection or Infusion looks like and
contents of the pack

If you are not sure what the side-effects listed below are, ask your doctor to explain them to you.

Very common:
• 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);
• fever;
• feeling tired (fatigue);
• weakness.

Common:
• 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:

6. FURTHER INFORMATION

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 50 mg, 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 50 mg pulver till injektions-/infusionsvätska, lösning
Fludarabine Phosphate 50 mg Powder for Solution for Injection or Infusion

This leaflet was last approved on 04/2011 (UK)

• autoimmune disorder;
• tumour lysis syndrome;

Dilution

infusion bag in 2°C-8°C protected against light or in 25°C in normal light up to 8 hours.

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.

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.

Storage

If any fludarabine phosphate solution is accidentally spilt:

Shelf-life after reconstitution: After reconstitution with sterile Water for Injections to concentration of
25 mg/ml, should the product be stored in 2°C-8°C 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

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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