Cisplatin 1mg/Ml Concentrate For Solution For Infusion
Package leaflet: Information for the patient Cisplatin 1mg/ml concentrate for solution for infusion
cisplatin
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
• 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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
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”.
What is in this leaflet
1. What Cisplatin Injection is and what it is used for
2. What you need to know before you are given Cisplatin Injection
3. How you are given Cisplatin Injection
4. Possible side effects
5. How to store Cisplatin Injection
6. Contents of the pack and other information
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.
Cisplatin is used to treat cancers of the testis, ovary, urinary bladder, head and neck, and lung.
Cisplatin is used to treat cervical cancer in combination with radiotherapy.
Your doctor will be able to provide you with more information
DO NOT take Cisplatin Injection:
• If you are allergic (hypersensitive) to cisplatin or other platinum compounds or to any of the other ingredients of this medicine (listed in section 6),
• If you have kidney problems (renal dysfunction)
• If you suffer from dehydration
• you suffer from severe suppression of bone marrow functionality, symptoms may be: extreme tiredness, easy if there is bruising or bleeding, occurrence of infections
• if your hearing is impaired
• if you suffer from nervous disorders caused by cisplatin
• if you are breast-feeding
• combined with live vaccines, including yellow fever vaccine.
• combined with phenytoin in prophylactic use (see “Other medicines and Cisplatin” below).
Warnings and Precautions:
Talk to your doctor or pharmacist or nurse before using Cisplatin Injection
• 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 fertility)
• 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.
Other medicines and Cisplatin Injection
Please note that these statements may also apply to products used some time ago or at some time in the future.
Tell your doctor or pharmacist if you are taking, have recently taken or might use any other medicine, including medicines obtained without a prescription.
• 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 and other so called chelating agents may reduce the effectiveness of cisplatin
• Cisplatin may have an adverse impact on the efficacy of agents preventing coagulation (anticoagulants). Therefore, coagulation should be checked more often during combined use.
• Cisplatin and cyclosporine may result in suppression of 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 Injection”).
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
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.
Breast-feeding
You must not breastfeed while you are treated with cisplatin.
Fertility
Male patients treated with cisplatin are advised not to father a child during treatment and for up to 6 months after treatment. Further, male patients should seek advice regarding cryoconser-vation of sperm prior to treatment with cisplatin.
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. Cisplatin injection contains 3.5 mg sodium per ml.
This medicinal product contains less than 1 mmol sodium per ml, i.e. essentially ‘sodium-free’. This should be considered if you have to keep to a low sodium diet.
Dosage and method of administration
Cisplatin must 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 receive 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 medicine, ask your doctor.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
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.
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The following side effects may occur:
Very common (may affect more than 1 in 10 people):
• 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),
• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness (anaemia),
• reduced level of electrolytes (sodium),
• Renal dysfunction such as failure to produce urine (anuria),
• fever.
Common (may affect up to 1 in 10 people):
• blood-poisoning (sepsis),
• damage to the nervous system (neurotoxicity),
• irregular heartbeat (arrhythmia), including reduced heartbeat (bradycardia), accelerated heartbeat (tachycardia),
• inflammation of a vein (phlebitis) at injection site,
• difficulty in breathing (dyspnoea), inflammation of the lungs (pneumonia) and respiratory failure,
• redness and inflammation of the skin (erythema, skin ulcer) in the area of the injection, swelling (oedema), pain at the area of injection.
Uncommon (may affect up to 1 in 100 people):
• anaphylactoid reactions with symptoms such as swelling of the face and fever,
• loss of hearing (ototoxicity),
• reduced level of electrolytes (magnesium),
• improper production of sperms and ova, and painful breast growth in men (gynaecomastia).
Rare (may affect up to 1 in 1,000 people):
• increase risk of leukaemia (acute leukaemia),
• suppression of the immune system (immunosuppression),
• high levels of cholesterol in the blood (hypercholesterolemia),
• 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, 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, convulsion,
• inflammation of the eye nerve combined with pain and reduced nerve function (optic neuritis), eye movement dysfunction,
• coronary artery disease, myocardial infarction (heart attacks),
• increase blood pressure levels (hypertension),
• reduced albumin (protein) levels in blood,
• inflammation of mucous membranes of the mouth (stomatitis).
Very rare (may affect up to 1 in 10,000 people):
• attacks (seizures),
• sudden stop in effective and normal blood circulation due to failure of the heart to pump blood (cardiac arrest)
Not known: frequency connot be estimated from the available data
• Infection,
• haemolytic anaemia,
• insufficient production of the anti-diuretic hormone in the brain (SIADH), blood amylase (enzyme) increased,
• loss of sight (blindness), difficulties in colour perception, blurred vision, swelling (papilloedema),
• deafness, ringing in the ears,
• dehydration, reduced level of electrolytes (calcium, phosphate, potassium) in the blood with muscle cramping and/or changes in an electrocardiogram (ECG), involuntary contraction of muscles (tetany),
• stroke, bleeding stroke, loss of taste (ageusia), as well as closure of the carotid artery.
• weakness (asthenia), malaise, fever,
• muscle spasms,
• liver enzymes increased, bilirubin increased,
• loss of appetite (anorexia), nausea, vomiting, diarrhoea, hiccups.
• blood flow dysfunction, e.g. in the brain, but also in the fingers and toes (Raynaud’s syndrome),
• cardiac disorder
• loss of hair (alopecia), rash,
• pulmonary embolism (a blockage of the main artery of the lung or one of its branches).
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 at Website: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and the bottle. The expiry date refers to the last day of that month.
Do not store above 25°C. Do not refrigerate or freeze. Keep container in the outer carton in order to protect from light.
After dilution, chemical and physical in-use stability has been demonstrated for 24 hours at 25°C, protected from light.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
Do not store diluted solutions in the refrigerator or freezer.
Do not use this medicine if you notice cloudy solution or deposit that does not dissolved.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
The other ingredients are sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injections.
What Cisplatin Injection looks like and contents of the pack
This medicinal product is a concentrate for solution for infusion. Cisplatin is a clear, colourless to pale yellow solution in an amber glass vial, which is practically free from particles.
For 10 ml
10 ml type I amber glass vial with a 20 mm Rubber stoppers (Teflon coated), sealed with a 20 mm flip off tear off aluminium seal.
For 50 ml
50 ml type I amber glass vial with a 20 mm Rubber stoppers (Teflon coated), sealed with a 20 mm flip off tear off aluminium seal.
For 100 ml
100 ml type I amber glass vial with a 20 mm Rubber stoppers (Teflon coated), sealed with a 20 mm flip off tear off aluminium seal.
Not all pack sizes may be marketed
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Cipla (EU) Limited
Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, United Kingdom.
S&D Pharma CZ, spol. s r.o
Theodor 28, Pchery (Pharmos a.s. facility), 27308,
CeskaRepublika
Cipla (EU) Limited
4th floor, 1 Kingdom Street, London, W2 6 BY,
United Kingdom
This leaflet was last revised in 12/02/2015
(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 “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:
1. Normal Saline
2. 5% Dextrose in Normal saline
3. 5% Dextrose in 1/2 Normal saline containing 37.5 g of Mannitol.
Always look at the injection before use. If the solution is not clear or an undissolvable precipitate is formed the solution must not be used. 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.
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.
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:
“Do not store above 25°C .Keep container in the outer carton in order to protect from light. Do not refrigerate or freeze
Concentrate for solution for infusion after dilution:
Chemical and physical in-use stability has been demonstrated after dilution with infusion fluids described in section “Preparation and handling of the product” for 24 hours at 25°C, protected from light.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
Do not store diluted solutions in the refrigerator or freezer.
6. Contents of the pack and other information
What Cisplatin Injection contains
The active substance is cisplatin. Each millilitre (ml) of solution contains 1 milligram (mg) of cisplatin.