CISPLATIN 1MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance: CISPLATIN

View full screen / Print PDF » Download PDF ⇩

Transcript
PACKAGE LEAFLET: INFORMATION FOR THE USER

Cisplatin 1 mg/ml Concentrate for
Solution for Infusion
Cisplatin

The name of your medicine is ‘Cisplatin 1 mg/ml Concentrate for Solution
for Infusion’ but in the rest of the leaflet it will be called “Cisplatin Injection”.
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 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 Injection is and what it is used for
2. Before you are given Cisplatin Injection
3. How you are given Cisplatin Injection
4. Possible side effects
5. How to store Cisplatin Injection
6. Further information

1. What Cisplatin Injection 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 Injection
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 live vaccines, including yellow fever vaccine.
• combined with phenytoin in prophylactic use (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.

(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

• 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 cisplatin 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 potentiate 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.
• 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.

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 “Disposal”.
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%)

• Concomitant use of cisplatin with ciclosporin can weaken 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 Injection
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
(combination chemotherapy):
• 20 mg/m² or more, once every 3 to 4 weeks.

agents

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.

- 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 below “Special precautions for storage”.
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. 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.

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 diarrhoea 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);
rarely (in more than 1 in 10,000, but less than 1 in 1,000 patients); very
rarely (in less than 1 in 10,000 patients).
The following side effects may occur:
Very common
Blood and lymphatic system: suppression of the bone marrow
characterised by a severe decrease 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).
Nutrition and metabolism: reduced level of electrolytes (sodium)
Gastrointestinal tract: loss of appetite (anorexia), nausea, vomiting,
diarrhoea.
Kidneys and urinary tracts: excessive uric acid levels (hyperuricaemia)
in the blood (e.g. gout).
General symptoms: fever.
Common
Infections: blood-poisoning (sepsis).
Heart: arrhythmia, including reduced heartbeat (bradycardia), accelerated
heartbeat (tachycardia).
Blood vessels: inflammation of a vein (phlebitis) at injection site.
Respiratory disorders: difficulty of breathing (dyspnoea), inflammation of
the lungs (pneumonia) and respiratory failure.
Uncommon
Immune system: hypersensitivity reactions, including rash, eczema with
severe itching and lump formation (urticaria), redness and inflammation of the
skin (erythema) or itching (pruritus), (anaphylactoid reactions) with symptoms
such as swelling of the face and fever, low blood pressure (hypotension),
accelerated heartbeat (tachycardia), breathing difficulties (dyspnoea), distress
as a result of muscle cramps in the airways (bronchospasms)
Hearing: damage to the ear (ototoxicity)
Nutrition and metabolism: reduced level of electrolytes (Magnesium)
Gastrointestinal tract: metallic setting on the gums.
Skin: loss of hair (alopecia).
Reproductive system and breasts: dysfunctional spermatogenesis and
ovulation, and painful breast growth in men (gynaecomastia).
Rare
Immune system: severe hypersensitivity (anaphylactic reactions) with low
blood pressure (hypotension), accelerated heartbeat (tachycardia),
breathing difficulties (dyspnoea), distress as a result of muscle cramps in

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.

the airways (bronchospasms), swelling of the face and fever; suppression
of the immune system (immunosuppression).
Nervous system: loss of certain types of brain function, including brain
dysfunction characterised by spasms and reduced levels of consciousness
(encephalopathy), 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, sudden
shooting pains from the neck through the back into the legs when bending
forwards, attacks (seizures).
Hearing: unable to hold normal conversation, loss of hearing (in particular
among children and elderly patients).
Heart: increased blood pressure levels, coronary artery disease and heart
attacks.
Liver and bile: reduced albumin (protein) levels in blood.
Gastrointestinal tract: inflammation of mucous membranes of the mouth
(stomatitis).
General: Cisplatin, like other similar medicines, increases the risk of
leukaemia (acute leukaemia).
Very rare
Nutrition and metabolism: increased iron levels in the blood.
Heart: heart (cardiac) arrest.
Not known:
Infections: Infection
Blood and lymphatic system:, haemolytic anaemia.
Hormones: insufficient production of the vasopressin hormone in the brain
(SIADH), blood amylase (enzyme) increased.
Nutrition and metabolism: 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.
Nervous system: spinal disease, brain dysfunction (confusion, slurred
speech, sometimes blindness, memory loss, and paralysis);stroke, loss of
taste (ageusia), as well as closure of the carotid artery.
General symptoms: weakness (asthenia), malaise, dehydration, swelling
(oedema),pain, redness and inflammation of the skin (erythema, skin ulcer)
at the area of injection
Kidneys and urinary tracts: kidney dysfunction, such as failure to
produce urine (anuria) and urine poisoning of the blood (uraemia).
Musculo skeletal: muscle spasms
Skin and dermis: hair loss, rash
Liver and bile: liver dysfunction, liver enzymes increased, bilirubin
increased.
Gastrointestinal tract: loss of appetite (anorexia), nausea, vomiting,
diarrhoea, hiccups.
Blood vessels: blood flow dysfunction, e.g. in the brain, but also in the
fingers and toes (Raynaud’s syndrome), Thrombotic microangiopathy
combined with haemolytic uraemic syndrome.
Heart: cardiac disorder
Hearing and balance function: loss of hearing combined with tinnitus
(ringing in ears).
Eyes: blurred vision, difficulties in colour perception and eye movement
dysfunction. swelling (papilloedema), inflammation of the eye nerve
combined with pain and reduced nerve function (optic neuritis), blindness
as a result of brain dysfunction.
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.

Do not use Cisplatin injection 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.
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
If you find the solution cloudy or a deposit that does not dissolve is noticed,
the bottle should be discarded.

6. Further information
What Cisplatin Injection contains:
Cisplatin Injection contains the active ingredient cisplatin.
Each millilitre (ml) of solution contains 1 milligram (mg) of cisplatin. This
medicine is presented in amber glass containers called vials.
Presentations
Amount of cisplatin

10 ml
10 mg

25 ml
25 mg

50 ml
50 mg

100 ml
100 mg

It is available in packs containing a single vial (not all the presentations
mentioned may be marketed).
The other ingredients include water for injections, sodium chloride,
hydrochloric acid (for pH adjustment) and/or sodium hydroxide (for pH
adjustment).
What Cisplatin Injection looks like and content of the pack:
Cisplatin Injection is clear, colourless to pale yellow solution in an amber
glass vial practically free from particles with flip off transparent seal.
Packaging with 1 injection vial of 10 ml, each injection vial containing 10 mg
cisplatin.
Packaging with 1 injection vial of 25 ml, each injection vial containing 25 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:
Accord Healthcare Limited
Sage House, 319, Pinner Road, North Harrow, Middlesex, HA1 4HF,
United Kingdom
The leaflet was last approved in 11/2011.

5. How to store Cisplatin injection
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
Keep container in the outer carton in order to protect from light. Do not
refrigerate or freeze.

Special precautions for storage
Medicinal product as packaged for sale:
Concentrate for solution for infusion 1 mg/ml
Undiluted solution: Keep container in the outer carton in order to protect
from light. Do not refrigerate or freeze. 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
Chemical and physical in-use stability after dilution with infusion fluids
described in section “Preparation and handling of the product”, indicate that

after dilution with recommended intravenous fluids, Cisplatin Injection
remains stable for 24 hours at 20 - 25 °C room temperature.
From a microbiological point of view, the diluted solution should be used
immediately. If not used immediately, in-use storage times and conditions
prior to use are the responsibility of the user and dilution should taken place
in controlled and validated aseptic conditions.

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.

Hide
(web3)