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

Active substance: FLUDARABINE PHOSPHATE

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PACKAGE LEAFLET: INFORMATION FOR THE USER
Cisplatin 1 mg/ml concentrate for solution for infusion

Read all of this leaflet carefully before you start taking this medicine.
Keep this leaflet. You may need to read it again.
If you have further questions, please ask your doctor or your 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.
What Cisplatin is and what it is used for
2.
Before you are given Cisplatin
3.
How you are given Cisplatin
4.
Possible side effects
5.
How to store Cisplatin
6.
Further information

1.

WHAT CISPLATIN IS AND WHAT IT IS USED FOR

Cisplatin forms part of a group of medicines called cytostatics, which are used in the treatment of
cancer. Cisplatin can be used alone but more commonly Cisplatin is used in combination with other
cytostatics.
What is it used for?
Cisplatin can destroy cells in your body that may cause certain types of cancer (tumour of testis,
tumour of ovary, tumour of the bladder, head and neck epithelial tumour, lung cancer and for cervical
cancer in combination with radiotherapy ).
Your doctor will be able to provide you with more information.

2.

BEFORE YOU ARE GIVEN CISPLATIN

Do not take Cisplatin if:

you are allergic (hypersensitive) to cisplatin or to any of the other ingredients of Cisplatin

you are allergic (hypersensitive) to any other medicine that contains platina compounds

you have kidney problems (renal dysfunction)

you suffer from dehydration

you suffer from severe suppression of bone marrow functionality, symptoms may be: extreme
tiredness, easy bruising or bleeding, occurrence of infections

your hearing is impaired

you suffer from nervous disorders caused by cisplatin

you are breast feeding

combined with yellow vaccine and phenytoin (see “Use of Cisplatin with other medicines”
below).
Take special care with Cisplatin:









Your doctor will carry out tests in order to determine the levels of calcium, sodium, potassium
and magnesium in your blood, as well as to check your blood picture and your liver and kidney
functionality and neurological function.
Cisplatin should only be administered under the strict supervision of a specialist doctor
experienced in administrating chemotherapy.
Your hearing will be tested prior to each treatment with Cisplatin.
If you suffer from a nervous disorder not caused by Cisplatin.
If you suffer from an infection. Please consult your doctor.
If you intend to have children (see Pregnancy, breast-feeding and fathering children).
With spillage of ciplatin the contaminated skin must immediately be washed with water and
soap. If cisplatin is injected outside the blood vessels the administration must be stopped
immediately. Infiltration of cisplatin in the skin can result in tissue damage (cellulitis, fibrosis
and necrosis).

Please consult your doctor, even if these statements were applicable to you at any time in the past.
Taking other medicines
Please note that these statements may also apply to products used some time ago or at some time in the
future.
Please inform your doctor or pharmacist if you are taking, of have recently taken, any other medicine
– even those not prescribed.

Simultaneous use of medicines that inhibit the bone marrow function or radiation can potentiat
the adverse effects of cisplatin on the bone marrow.

Cisplatin toxicity may increase when administered simultaneously with other cytostatics
(medicine for cancer treatment), such as bleomycin and methotrexate.

Agents to treat high blood pressure (antihypertensives containing furosemide, hydralazine,
diazoxide, and propranolol) may increase the toxic effect of Cisplatin on kidneys.

Cisplatin toxicity may severely affect the kidneys when administered simultaneously with
agents that may cause side effects in the kidneys, such as those for the prevention/treatment of
certain infections (antibiotics: cephalosporins, aminoglycosides, and/or amphotericin B) and
contrast agents.

Cisplatin toxicity may affect hearing faculties when administered simultaneously with agents
that may have a side effect on hearing faculties, such as aminoglycosides.

If you use agents to treat gout during your treatment with cisplatin, then the dosage of such
agents may need to be adjusted (e.g. allopurinol, colchicine, probenecid and/or sulfinpyrazone).

Administration of drugs that elevate your rate of bodily urine excretion (loop diuretics)
combined with cisplatin (cisplatin dose: more than 60mg/m², urine secretion: less than 1000 ml
per 24 hours) may result in toxic effects on kidneys and hearing.

The first signs of hearing damage (dizziness and/or tinnitus) may remain hidden when – during
your treatment with cisplatin – you are also being administered agents to treat hypersensitivity
(antihistamines, such as buclizine, cyclizine, loxapine, meclozine, phenothiazines,
thioxanthenes and/or trimethobenzamides).

Cisplatin given in combination with ifosphamide may result in hearing impairment or toxic
effects on kidneys.

The effects of treatment with cisplatin can be reduced through simultaneous administration of
pyridoxine and hexamethylmelamine.

Cisplatin given in combination with bleomycin and vinblastine may result in paleness or blue
coloration of the fingers and/or toes (Raynaud`s phenomenon).

Administration of cisplatin prior to treatment with paclitaxel or in combination with docetaxel
may result in severe nerve damage.

The combined use of cisplatin with bleomycin and etoposide may decrease lithium levels in the
blood. Therefore, lithium levels should be checked on a regular basis.

Cisplatin reduces the effects of phenytoin on the treatment of epilepsy.







Penicillamine may reduce the effectiveness of Cisplatin.
Cisplatin may have an adverse impact on the effectivity of agents preventing coagulation
(anticoagulants). Therefore, coagulation should be checked more often during combined use.
Cisplatin and ciclosporin may result in suppression of the immune system with the risk of
increased production of white blood cells (lymphocytes).
You should not receive any vaccinations containing live viruses within three months after the
end of treatment with cisplatin.
When undergoing treatment with cisplatin, you should not receive yellow fever vaccinations
(also see “Do not take Cisplatin”).

Pregnancy, breast-feeding and fathering children
Ask your doctor or pharmacist for advice before you begin to use, or are administered, Cisplatin.
Cisplatin must not be used during pregnancy unless clearly indicated by your doctor.
You must use effective contraception during and at least 6 months after treatment with Cisplatin.
You must not breastfeed while you are treated with Cisplatin.
Male patients treated with Cisplatin are advised not to father a child during treatment and for up to 6
months after treatment. Further, men are advised to seek counseling on sperm preservation before
starting treatment.
Driving and using machines
Cisplatin may cause side effects such as feeling sleepy and/or vomiting. If you suffer from either of
these conditions, then you should not operate any machines that require your full attention.
Important information about some of the ingredients of Cisplatin
Cisplatin contains 3.5 mg sodium per ml. This should be considered if you have to keep to a low
sodium diet.

3.

HOW YOU ARE GIVEN CISPLATIN

Dosage and method of administration
Cisplatin should only be given by a specialist in cancer treatment. The concentrate is diluted with a
sodium chloride solution that contains glucose.
Cisplatin is only given by injection into a vein (an intravenous infusion).
Cisplatin should not come into contact with any materials that contain aluminium.
The recommended dosage of Cisplatin depends on your well-being, the anticipated effects of the
treatment, and whether or not cisplatin is given on its own (monotherapy) or in combination with other
agents (combination chemotherapy).
Cisplatin (monotherapy):
The following dosages are recommended:
- A single dosage of 50 to 120 mg/m² body surface, every 3 to 4 weeks
- 15 to 20 mg/m² per day over a 5-day period, every 3 to 4 weeks
Cisplatin in combination
with other chemotherapeutical agents (combination chemotherapy):
20 mg/m² or more, once every 3 to 4 weeks
For treatment of cervical cancer cisplatin is used in combination with radiotherapy.

A typical dose is 40 mg/m2 weekly for 6 weeks.
In order to avoid, or reduce, kidney problems, you are advised to drink copious amounts of water for a
period of 24 hours following treatment with Cisplatin.
If you believe you have received more Cisplatin than you should
Your doctor will ensure that the correct dose for your condition is given. In case of overdose, you may
experience increased side effects. Your doctor may give you symptomatic treatment for these side
effects. If you think you received too much Cisplatin, immediately contact your doctor.
If you have any further questions on the use of this product, ask your doctor.

4.

POSSIBLE SIDE EFFECTS

Like all medicines, Cisplatin can cause side effects.
If you experience any side effect it is important that you inform your doctor before your next
treatment.
Tell your doctor immediately, if you notice any of the following:

persistent or severe diarrhea or vomiting

stomatitis/mucositis (sore lips or mouth ulcer)

swelling of the face, lips mouth or throat

unexplained respiratory symptoms such as non-productive cough, difficulty in breathing or
crackles

difficulty in swallowing

numbness or tingling in your fingers or toes

extreme tiredness

abnormal bruising or bleeding

signs of infection, such as sore throat and high temperature

sensation of discomfort close to or at the injection site during the infusion.
Side effects may appear very common (in more than 1 in 10 patients);
common (in more than 1 in 100, but less than 1 in 10 patients);
uncommon (in more than 1 in 1,000, but less than 1 in 100 patients);
rare (in more than 1 in 10,000, but less than 1 in 1,000 patients);
very rare (in less than 1 in 10,000 patients);
not known (cannot be estimated from the available data).
The following side effects may occur:
Infections
Common: Infections and blood-poisoning (sepsis).
Blood and lymphatic system
Very common: reduction in the number of white blood cells, which makes infections more likely
(leukopenia), reduction in blood platelets, which increases the risk of bruising and bleeding
(thrombocytopenia), as well as reduction in red blood cells, which can make the skin pale and cause
weakness or breathlessness (anaemia). The bone marrow does not make enough blood cells, or none at
all (bone marrow failure).
Common: reduction in the number of white blood cells (leukopenia; approximately 14 days after use),
reduction in blood platelets (thrombocytopenia; approximately 21 days after use) and reduction in red
blood cells (later onset than leukopenia and thrombocytopenia).

Rare: haemolytic anaemia, suppression of the bone marrow characterised by a severe decrease of
white blood cells, combined with high fever, severe sore throat and mouth ulcers (agranulocytosis), as
well as anaemia as a result of decreased blood cell production.
Immune system
Uncommon: hypersensitivity reactions, including rash, eczema with severe itching and lump formation
(urticaria), redness and inflammation of the skin (erythema) or itching (pruritus).
Rare: severe hypersensitivity (anaphylactic reactions) with low blood pressure (hypotension),
accelerated heartbeat (tachycardia), breathing difficulties (dyspnoea), distress as a result of muscle
cramps in the airways (bronchospasms), swelling of the face and fever; suppression of the immune
system (immunosuppression).
Hormones
Rare: Increased blood amylase (enzyme) levels.
Very rare: insufficient production of the vasopressin hormone in the brain (SIADH).
Nutrition and metabolism
Very common: reduced level of the electrolyte sodium.
Uncommon: reduced level of the electrolyte magnesium.
Rare: reduced level of electrolytes (calcium, phosphate, potassium) in the blood with muscle cramping
and/or changes in an electrocardiogram (ECG). Excessive cholesterol levels in the blood.
Very rare: increased iron levels in the blood.
Not known: dehydration, increased uric acid level (hyperuricaemia), syndrome characterized by
muscle cramps (tetany).
Nervous system
Common: peripheral neuropathy of the sensory nerves (bilateral, sensory neuropathy), characterised
by tickling, itching or tingling without cause and sometimes characterised by a loss of taste, touch,
sight, as well as brain dysfunction (confusion, slurred speech, sometimes blindness, memory loss, and
paralysis); sudden shooting pains from the neck through the back into the legs when bending forwards,
spinal disease.
Rare: loss of certain types of brain function, including brain dysfunction characterised by spasms and
reduced levels of consciousness (encephalopathy), as well as closure of the carotid artery.
Very rare: attacks (seizures).
Not known: stroke (haemorrhiagic or ischaemic), cerebrovascular accident, lose of taste (ageusia).
Eyes
Rare: loss of sight (blindness), difficulties in colour perception and eye movement dysfunction.
Very rare: swelling (papilloedema), inflammation of the eye nerve combined with pain and reduced
nerve function (optic neuritis), blindness as a result of brain dysfunction.
Not known: blurred vision, colour blindness, retinal disorder.
Hearing and balance function
Very common: loss of hearing combined with tinnitus.
Common: deafness and dizziness.
Rare: : unable to hold normal conversation, loss of hearing (in particular among children and elderly
patients).
Heart
Common: arrhythmia, including reduced heartbeat (bradycardia), accelerated heartbeat (tachycardia).
Rare: increased blood pressure levels, coronary artery disease and heart attacks.
Very rare: heart arrest.
Not known: heart problems.
Blood vessels

Common: inflammation of a vein (phlebitis).
Very rare: blood flow dysfunction, e.g. in the brain, but also in the fingers and toes (Raynaud´s
syndrome).
Respiratory disorders
Common: shortness of breath (dyspnoea), inflammation of the lungs (pneumonia) and respiratory
failure.
Not known: blood clot in the lungs which causes chestpan and breathlessness (pulmonary embolism)
Gastrointestinal tract
Very common: loss of appetite (anorexia), nausea, vomiting, diarrhoea.
Uncommon: metallic setting on the gums.
Rare: inflammation of mucous membranes of the mouth (stomatitis), diarrhoea.
Liver and bile
Common: liver dysfunction.
Rare: reduced blood protein levels (albumin).
Skin and dermis
Common: redness and inflammation of the skin (erythema, skin ulcer) in the area of the injection.
Uncommon: loss of hair (alopecia).
Very rare: baldness due to hair loss.
Not known: rash.
Muscles and joints
Not known: muscle spasms.
Kidneys and urinary tracts
Very common: renal dysfunction, such as failure to produce urine (anuria) and urine poisoning of the
blood (uraemia), and excessive urine acid levels (hyperuricaemia) in the blood (e.g. gout).
Not known: acute dysfunction of the kidneys.
Reproductive system and breasts
Uncommon: : dysfunctional spermatogenesis and ovulation, and painful breast growth in men
(gynaecomastia).
General symptoms
Very common: fever.
Common: swelling (oedema), pain.at the area of injection.
Uncommon: hiccups, weakness (asthenia), malaise.
Rare: cancer of blood-forming cells in the bone marrow, characterized by the rapid growth of
abnormal white blood cells (acute leukaemia). Cisplatin, like other similar medicines, increases the
risk of leukaemia (secondary leukaemia).
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 CISPLATIN

Keep Cisplatin out of the reach and sight of children.
Keep the vial in the outer carton (to avoid exposure of Cisplatin to light).
Concentrate for solution for infusion 1 mg/ml
Store at 15-25°C. If the product is stored below 15°C a precipitation may occur.

Do not use Cisplatin concentrate for solution for infusion after the expiry date which is stated on the
vial and the outer carton after ‘exp’. The expiry date refers to the last day of that month
Do not use Cisplatin if you notice visible signs of deterioration.
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.

6.

FURTHER INFORMATION

What Cisplatin contains
The active substance is cisplatin.
Cisplatin 1 mg/ml, concentrate for solution for infusion contains 1 mg cisplatin per ml.
Other ingredients are sodium chloride, dilute hydrochloric acid (for pH adjustment), dilute sodium
hydroxide (for pH adjustment) and water for injections
What Cisplatin looks like and contents of the pack
Cisplatin is a clear, light yellow concentrate for solution for infusion free from visible particles in
glass injection vials.

Cisplatin 1 mg/ml:
Packaging with 1 injection vial of 10 ml, each injection vial containing 10 mg cisplatin.
Packaging with 1 injection vial of 50 ml, each injection vial containing 50 mg cisplatin.
Packaging with 1 injection vial of 100 ml, each injection vial containing 100 mg cisplatin.
Not all pack sizes may be marketed.
Marketing authorisation holder and manufacturer:
Manufacturer
Pharmachemie B.V.
Swensweg 5
Postbus 552
2003 RN Haarlem

OR

Teva Operations Poland Sp. z o.o.,
Mogilska 80 Str.
31-546 Kraków
Poland
Marketing authorisation holder
Teva UK Limited, Eastbourne, BN22 9AG.

This leaflet was last revised: February 2013
PL 00289/1146

Cisplatin 1 mg/ml concentrate for solution for infusion
(Please note this is a Prescriber Information Leaflet NOT the SPC. For full details regarding this
product please refer to the SPC.)
The following information is intended for medical or healthcare professionals only:
Preparation and handling of the product
Like with all anti-neoplastic products caution is needed with the processing of cisplatin. Dilution should
take place under aseptic conditions by trained personnel in an area specifically intended for this.
Protective gloves should be worn for this. Precautions should be taken to avoid contact with the skin and
mucous membranes. If skin contact did occur anyway, the skin should be washed with soap and water
immediately. With skin contact tingling, burns and redness have been observed. In case of contact with
the mucous membranes they should be copiously rinsed with water. After inhalation dyspnoea, pain in the
chest, throat irritation and nausea have been reported.
Pregnant women must avoid contact with cytostatic drugs.
Bodily waste matter and vomit should be disposed with care.
If the solution is cloudy or a deposit that does not dissolve is noticed, the bottle should be discarded.
A damaged bottle must be regarded and treated with the same precautions as contaminated waste.
Contaminated waste must be stored in waste containers specifically marked for this. See section “Waste”.
Preparation of the intravenous administration
Take the quantity of the solution that is needed from the bottle and dilute with at least 1 litre of the
following solutions:

sodium chloride 0.9%

mixture of sodium chloride 0.9%/ glucose 5% (1:1), (resulting final concentrations: sodium
chloride 0.45%, glucose 2.5%)

sodium chloride 0.9% and 1,875% mannitol, for injection

sodium chloride 0.45%, glucose 2.5% and 1,875% mannitol for injection
Always look at the injection before use. Only a clear solution, free from particles should be
administered.
DO NOT bring in contact with injection material that contains aluminium
DO NOT administer undiluted
With respect to microbiological, chemical and physical stability with use of the undiluted solutions, see
section 6.3.
Disposal
All materials that have been used for the preparation and administration, or which have been in contact
with cisplatin in any way, must be disposed of according to local cytotoxic guidelines. Remnants of the
medicinal products as well as all materials that have been used for dilution and administration must be
destroyed according to hospital standard procedures applicable to cytotoxic agents and in accordance
with local requirements related to the disposal of hazardous waste.

Incompatibilities
Do not bring in contact with aluminium. Cisplatin may interact with metal aluminium to form a black
precipitate of platinum. All aluminium-containing IV sets, needles, catheters and syringes should be
avoided.
Cisplatin decomposes with solution in media with low chloride content; the chloride concentration should
at least be equivalent to 0.45% of sodium chloride.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
Antioxidants (such as sodium metabisulphite), bicarbonates (sodium bicarbonate), sulfates,
fluorouracil and paclitaxel may inactivate cisplatin in infusion systems.
Special precautions for storage

Medicinal product as packaged for sale:
Concentrate for solution for infusion 1 mg/ml
Undiluted solution: store at 15-25°C. Keep the vials in the outer carton. If the undiluted solution is
stored below 15°C a precipitation may occur. If the solution is not clear or an undissolvable precipitate
is formed the solution must not be used.
Diluted solution :
For the storage condition of the diluted medicinal product: see below "concentrate for solution for
infusion after dilution".
Do not refrigerate or freeze.

Concentrate for solution for infusion after dilution:
After dilution
After dilution in infusion fluids, the product can be stored for at most 14 days at room temperature
(15–25 °C) under protection from light.
Exposure to ambient light must be limited to at most 6 hours. If exceeding 6 hours, the bags must be
thoroughly wrapped in aluminium foil in order to protect the contents from ambient light.
From a microbiological point of view, the product should 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 reconstitution / dilution (etc)
has taken place in controlled and validated aseptic conditions.

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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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