Cisplatin Sandoz

PACKAGE LEAFLET: INFORMATION FOR THE USER

Cisplatino Sandoz 1 mg/ml

Concentrate for solution for infusion
cisplatin
Please read 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 questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the package leaflet:

1. What Cisplatino Sandoz is and what it is used for
2. What you need to know before using Cisplatino Sandoz
3. How to use Cisplatino Sandoz
4. Possible side effects
5. How to store Cisplatino Sandoz
6. Contents of the pack and other information

1. What Cisplatino Sandoz is and what it is used for

Cisplatin belongs to a group of medicines called cytostatic agents used in the treatment of cancer. Cisplatin
may be used alone, but more frequently it is used in combination with other cytostatic medicines.
Cisplatin can destroy cells in the body that may cause certain types of cancer (testicular tumours, ovarian
tumours, head and neck epithelial tumours (tumours affecting the outer surface layer of the skin), lung tumours).
Your doctor will be able to provide you with further information.

2. What you should know before using Cisplatino Sandoz

Do not use Cisplatino Sandoz if:

• You are allergic to cisplatin or to any of the other ingredients of this medicine (listed in section 6)
• You are allergic (hypersensitive) to any other medicine containing platinum
• You have kidney problems (impaired renal function)
• You are dehydrated
• You have a low red blood cell count
• You have hearing problems
• You are breastfeeding
• You have received the yellow fever vaccine and are taking phenytoin (see "Other medicines and Cisplatino Sandoz").

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Cisplatino Sandoz.

• Your doctor will carry out necessary tests to determine the levels of calcium, sodium, potassium, and magnesium in your blood and will also monitor your red blood cell count, liver function, and kidney function.
• Cisplatin must be administered only under the strict supervision of a physician experienced in chemotherapy administration.
• Before each cisplatin treatment, you must undergo a hearing test.
• If you have a pre-existing neurological condition not caused by cisplatin.
• If you have an infection. Contact your doctor.
• If you experience vomiting and diarrhea after cisplatin administration, fluid loss must be promptly replaced.
• If you intend to have children (see Pregnancy, breastfeeding, and fertility).
• In case of accidental spillage of cisplatin, contaminated skin must be washed immediately with soap and water.
• If cisplatin is injected outside the blood vessels, administration must be stopped immediately. Extravasation of cisplatin into the skin may cause tissue damage (cellulitis, fibrosis, and necrosis).

Please consult your doctor if you have previously experienced any of the conditions listed above.
Other medicines and Cisplatino Sandoz
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

• Concurrent use of medicines that suppress bone marrow function or radiotherapy may enhance the undesirable effects of cisplatin on the bone marrow.
• The toxicity of cisplatin may increase if administered simultaneously with other cytostatic drugs (medicines for cancer treatment), such as bleomycin and methotrexate. Medicines used to treat high blood pressure (antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol) may enhance the nephrotoxic (kidney-damaging) effects of cisplatin.
• Cisplatin nephrotoxicity may be significantly increased when administered concurrently with agents that may cause renal adverse effects, such as medicines used to prevent/treat certain infections (antibiotics: cephalosporins, aminoglycosides, and/or amphotericin B) and contrast media.
• Ototoxicity (hearing damage) caused by cisplatin may be enhanced when administered concurrently with medicines that may cause hearing-related adverse effects, such as aminoglycosides. If you are taking medicines for gout during cisplatin therapy, dose adjustments of these medicines (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone) may be necessary.
• Administration of diuretics (loop diuretics) in combination with cisplatin (cisplatin dose: >60 mg/m²; urinary output: <1000 ml in 24 hours) may result in nephrotoxicity and ototoxicity.
• Early signs of hearing damage (dizziness and/or tinnitus) may be masked when antihistamines used to treat hypersensitivity reactions (such as buclizine, cyclizine, loxapine, meclizine, phenothiazines, thioxanthenes, and/or trimethobenzamide) are taken during cisplatin therapy.
• Cisplatin administered in combination with ifosfamide may cause hearing damage or nephrotoxicity.
• The effects of cisplatin treatment may be reduced by co-administration of pyridoxine and hexamethylmelamine.
• Cisplatin administered in combination with bleomycin and vinblastine may cause pallor or bluish discoloration of fingers and/or toes (Raynaud's phenomenon).
• Co-administration of cisplatin with paclitaxel or docetaxel may cause severe neurotoxicity.
• Combined administration of cisplatin with bleomycin and etoposide may reduce lithium blood levels, which should therefore be monitored regularly.
• Cisplatin reduces the effectiveness of phenytoin used for epilepsy treatment (see also "Do not use cisplatin").
• Penicillamine may reduce the efficacy of cisplatin.
• Cisplatin may negatively affect the efficacy of anticoagulant medicines (blood thinners); therefore, coagulation should be monitored more frequently during combination therapy.
• Cisplatin and cyclosporine may cause immunosuppression, increasing the risk of elevated white blood cell (lymphocyte) production.
• You must not receive live virus vaccines until at least three months after completing cisplatin treatment.
• If undergoing treatment with cisplatin, you must avoid vaccination against yellow fever (see also "Do not use cisplatin").

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using this medicine.
Cisplatin should not be used during pregnancy, unless it is clinically necessary for the mother.
You must use an effective method of contraception during treatment and for at least 6 months after treatment with cisplatin.
Cisplatin must not be used during breastfeeding.
Male patients undergoing cisplatin therapy are advised not to father a child during treatment and for 6 months after treatment. In addition, male patients are advised to discuss sperm preservation options with their doctor before starting treatment.
Driving and use of machines
You should not drive or operate tools or machinery requiring full attention, as cisplatin therapy may cause drowsiness and/or induce vomiting.
Cisplatino Sandoz contains sodium
This medicine contains 354 mg of sodium (a key component of table salt) per 100 ml vial. This corresponds to 17.7% of the maximum daily recommended dietary intake for an adult.

3. How to use Cisplatino Sandoz

Posology and method of administration
Cisplatino must be administered only by an oncology specialist. The concentrate is diluted with
a sodium chloride solution or a sodium chloride solution containing glucose or a sodium chloride solution containing mannitol.
Cisplatino is administered exclusively by intravenous infusion (intravenous infusion).
Cisplatino must not come into contact with materials containing aluminium.
The recommended dosage of cisplatino is determined based on the patient's physical condition, the expected effects of treatment, and whether the drug is administered alone (monotherapy) or in combination with other medicinal products (combination chemotherapy).

Cisplatino (monotherapy):
The recommended doses are as follows:

• A single dose of 50 to 120 mg/m² body surface area every 3–4 weeks;
• 15 to 20 mg/m² body surface area per day for 5 days every 3–4 weeks.

Cisplatino in combination with other chemotherapeutic agents (combination chemotherapy):

• The usual dose is equal to or higher than 20 mg/m² body surface area every 3–4 weeks.
• The usual dose in the treatment of lung tumours is 80 mg/m² body surface area.

To prevent or reduce kidney problems, it is recommended to drink large amounts of water during the 24 hours following treatment with cisplatino.

If you think you have been given too much Cisplatino.
Your doctor will ensure that you receive the appropriate dose for the treatment of your disease. In case of overdose, you may experience an increase in adverse events and your doctor may prescribe therapy to relieve the symptoms.

For any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

• Contact your doctor as soon as possible if you have persistent or severe vomiting or diarrhoea
• have stomatitis/mucositis (inflammation of the lips or ulceration of the mouth)
• have swelling of the face, lips, mouth or throat
• have unexplained respiratory symptoms such as dry cough, difficulty breathing or crackling sounds
• have difficulty swallowing
• have a sensation of numbness or tingling in the fingers of the hands or feet
• have extreme fatigue
• have an abnormal appearance of bruises or bleeding
• have signs of infection such as sore throat or fever
• have a feeling of discomfort near or at the injection site during infusion
• if you have severe pain or swelling in one of your legs, chest pain or difficulty breathing (which may indicate harmful blood clots in a vein) (common: may affect up to 1 in 10 people)

Very common (may affect more than 1 in 10 people)

• decrease in the number of white blood cells, resulting in increased likelihood of infection (leucopenia)
• decrease in the number of platelets, resulting in increased risk of bruising and bleeding (thrombocytopenia)
• decrease in the number of red blood cells, which may cause paleness of the skin and lead to weakness or breathlessness (anaemia)
• bone marrow failure (no production of blood cells)
• low levels of sodium in the blood
• fever

Common (may affect up to 1 in 10 people)

• sepsis
• arrhythmia, including slowing of the heartbeat (bradycardia), acceleration of the heartbeat (tachycardia)
• shortness of breath (dyspnoea), inflammation of the lungs (pneumonitis), and respiratory failure

Uncommon (may affect up to 1 in 100 people)

• .
• decreased sperm production (spermatogenesis abnormalities) and ovulation, and painful breast enlargement in men (gynaecomastia)
• acute leukaemia
• low levels of magnesium in the blood (hypomagnesaemia)
• hearing damage (ototoxicity)
• metallic deposit on the gums

Rare (may affect up to 1 in 1,000 people)

• various brain disorders (leukoencephalopathy)
• high levels of cholesterol in the blood (hypercholesterolaemia)
• seizures
• numbness, tingling, burning sensations (peripheral neuropathy)
• abnormal changes in the brain that may cause a range of symptoms including headache, confusion, seizures and loss of vision, detectable on magnetic resonance imaging (posterior reversible encephalopathy syndrome)
• heart attack
• inflammation of the mucous membranes of the mouth (stomatitis)

Very rare (may affect up to 1 in 10,000 people)

• increased levels of iron in the blood
• the heart stops pumping blood (cardiac arrest)

Not known (frequency cannot be estimated from the available data)

• infection
• destruction of red blood cells (Coombs positive haemolytic anaemia)
• increase in certain enzymes (amylase)
• a group of symptoms that develop when there is too much antidiuretic hormone (ADH) in the body, such as fluid retention, electrolyte imbalances and low sodium levels in the blood (called hyponatraemia or water intoxication)
• dehydration
• low levels of electrolytes in the blood (potassium, phosphate, calcium)
• increased levels of uric acid in the blood, a waste product from the digestion of food
• muscle cramps (tetany)
• stroke
• loss of taste
• inflammation of blood vessels in the brain
• sudden, sharp pain radiating from the neck down the back to the legs when bending forward (Lhermitte's sign)
• spinal cord compression (myelopathy)
• damage to nerves controlling involuntary body functions (may affect blood pressure, temperature control, digestion, bladder function)
• blurred vision
• colour blindness
• loss of vision (blindness)
• inflammation of the optic nerve
• swelling around the nerve responsible for vision (papilloedema)
• retinal pigmentation (multilayered sensory tissue lining the back of the eye responsible for vision)
• ringing in the ears such as whistling, buzzing, humming, tinkling
• deafness
• heart problems
• a set of signs including haemolytic anaemia (destruction of red blood cells), kidney failure and decreased platelets (a type of blood cell that helps blood clotting) (haemolytic uraemic syndrome)
• pale and blue fingers and toes (Raynaud's phenomenon)
• feeling unwell (nausea) and vomiting
• loss of appetite
• hiccups
• diarrhoea
• increased liver enzymes in the blood, which may indicate liver damage
• formation of blood clots in the lungs
• skin rash
• hair loss (alopecia)
• muscle spasms
• reduced or complete loss of kidney function
• weakness, loss of energy
• redness, inflammation, swelling and pain at the injection site as a result of injection into surrounding tissue rather than into a vein

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cisplatino Sandoz

Keep this medicine out of the sight and reach of children.
Do not store at temperatures above 25°C.
Do not refrigerate or freeze.
Keep the vial in the outer packaging to protect it from light.
Do not use this medicine after the expiry date stated on the packaging and on the vial after the word "Exp".
The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

Each milliliter (ml) of solution contains 1 milligram (mg) of cisplatin.
The 100 ml vial contains 100 mg of cisplatin.
What Cisplatino Sandoz Contains

• The active substance is cisplatin.
• The other excipients are sodium chloride, diluted hydrochloric acid, and water for injections.

Description of the Appearance of Cisplatino Sandoz and Contents of the Package
Cisplatino is a clear, colourless to pale yellow infusion solution contained in glass vials.
Pack: 1 injection vial of 100 ml containing 100 mg of cisplatin.
Not all pack sizes may be marketed.
Packaged vials may or may not be supplied with a protective plastic overwrap (OncoSafe®).
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Sandoz Spa
Largo U Boccioni 1
21040 Origgio (VA), Italy
Manufacturer:
EBEWE Pharma Ges.m.b.H. Nfg.KG
Mondseestrasse 11
4866 Unterach, Austria
This medicinal product is authorized in the European Economic Area countries under the following names:
Netherlands
Cisplatine Sandoz, 1mg/ml, concentrate for solution for infusion
Belgium
Cisplatine Sandoz, 1mg/ml, concentrate for solution for infusion
Denmark
Cisplatin "Ebewe" 1mg/ml, concentrate for infusion solution, solution 1mg/ml
Finland
Cisplatin Ebewe 1mg/ml infusion concentrate, for solution
Germany
Cisplatin Neocorp 1 mg/ml, concentrate for the preparation of an infusion solution
Greece
Cisplatin/EBEWE, 1mg/ml Cs.Inj.Sol.
Ireland
Cisplatin Ebewe 1.0 mg/ml, Concentrate for solution for infusion
Italy
Cisplatino Sandoz 1mg/ml – Concentrate for solution for infusion
Luxembourg
Cisplatine Christiaens 1mg/ml
Portugal
Cisplatina Generis 1mg/ml
Spain
CISPLATINO Sandoz 1mg/ml concentrate for solution for perfusion
Sweden
Cisplatin Ebewe 1mg/ml, concentrate for infusion fluid, solution
United Kingdom
Cisplatin ‘Ebewe’ 1 mg/ml, Concentrate for solution for infusion

The following information is intended exclusively for physicians or healthcare professionals:
Special Precautions for Disposal and Handling
Cisplatino Sandoz must be diluted before use. When preparing the infusion solution, avoid using any device containing aluminium that may come into contact with cisplatin (intravenous infusion sets, needles, catheters, syringes).
The preparation of the infusion solution must be carried out under aseptic conditions.
For dilution of the concentrate, one of the following solutions must be used:
0.9% sodium chloride solution;
mixture of 0.9% sodium chloride solution and 5% glucose solution (1:1)
(resulting final concentrations: 0.45% sodium chloride, 2.5% glucose).
If adequate hydration cannot be ensured prior to treatment, the concentrate may be diluted with:
mixture of 0.9% sodium chloride solution and 5% mannitol solution (1:1)
(resulting final concentrations: 0.45% sodium chloride, 2.5% mannitol).

Preparation of Cisplatin Infusion Solution:
The required amount (dose) must be diluted in 1–2 litres of one of the solutions listed above.
The diluted solution must be administered only intravenously by infusion.
Use only clear, colourless to pale yellow solutions free from visible particles.
Single-use.
Cytotoxic agents must be prepared for administration only by personnel trained in safe handling procedures.
Follow local guidelines for handling cytotoxic drugs.
As with any other cytotoxic agent, cisplatin must be handled with extreme caution: gloves, masks, and protective clothing are required and essential. Cisplatin should preferably be prepared under a laminar flow hood. Avoid contact with skin and mucous membranes. Pregnant healthcare personnel must not handle cisplatin.
Skin contact: rinse thoroughly with abundant water. Apply an ointment to soothe any temporary burning sensation. (Note: some individuals are sensitive to platinum and may develop a skin reaction.)
In case of spillage, personnel must wear gloves and absorb the spilled liquid with an appropriate sponge. Rinse the area twice with water. Place all solutions and sponges into a plastic bag and seal it. In the event of spillage, all materials coming into contact with cisplatin must be handled and disposed of according to local guidelines for cytotoxic drugs.
Any unused medicinal product and waste material derived from it must be disposed of in accordance with local regulations.

Incompatibilities
Cisplatin reacts with aluminium, resulting in the formation of a black precipitate of platinum. Therefore, avoid using any device containing aluminium that may come into contact with cisplatin during administration (intravenous infusion sets, needles, catheters, syringes).
The drug must not be mixed with other medicinal products except those listed above.
Cisplatin must not be diluted with 5% glucose solution alone or 5% mannitol solution alone, but only with mixtures also containing sodium chloride as specified above.
Antioxidants (such as sodium metabisulfite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel may inactivate cisplatin in infusion systems.

Special Precautions for Storage
Medicinal product packaged for sale:
Do not store above 25°C. Do not refrigerate or freeze. Keep the vial in the outer packaging to protect from light.

Infusion solution after dilution:
Chemical and physical in-use stability has been demonstrated for 48 hours at a temperature of 2–8°C, when protected from light, for solutions with a final cisplatin concentration of 0.1 mg/ml after dilution of the concentrate with one of the following solutions:
0.9% sodium chloride solution;
mixture of 0.9% sodium chloride solution and 5% glucose solution (1:1);
mixture of 0.9% sodium chloride solution and 5% mannitol solution (1:1).

From a microbiological standpoint, the product should be used immediately.
If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2–8°C, unless reconstitution/dilution (and so on) has been performed under controlled and validated aseptic conditions.

INSTRUCTIONS FOR THE USER: PACKAGE LEAFLET

Cisplatino Sandoz 0.5 mg/ml

Concentrate for solution for infusion
cisplatin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Package leaflet contents:

1. What Cisplatino Sandoz is and what it is used for
2. What you need to know before using Cisplatino Sandoz
3. How to use Cisplatino Sandoz
4. Possible side effects
5. How to store Cisplatino Sandoz
6. Contents of the pack and other information

1. What Cisplatino Sandoz is and what it is used for

Cisplatino belongs to a group of medicines called cytostatic agents used in the treatment of cancer. Cisplatino
may be used alone, but more frequently it is used in combination with other cytostatic medicines.
Cisplatino can destroy cells in the body that may cause certain types of cancer (testicular tumours, ovarian
tumours, head and neck epithelial tumours (tumours affecting the outer surface layer of the skin), lung tumours).
Your doctor will be able to provide you with further information.

2. What you should know before using Cisplatino Sandoz

Do not use Cisplatino Sandoz:

• if you are allergic to cisplatin or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic (hypersensitive) to any other medicine containing platinum
• if you have kidney problems (impaired renal function)
• if you are dehydrated
• if you have low red blood cell count (anaemia)
• if you have hearing problems
• if you are breastfeeding
• if you have received the yellow fever vaccine and are taking phenytoin (See “Other medicines and Cisplatino Sandoz”)

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Cisplatino Sandoz

• Your doctor will carry out necessary tests to determine the levels of calcium, sodium, potassium and magnesium in your blood, and will also monitor your red blood cell count, liver and kidney function.
• Cisplatin must be administered only under the strict supervision of an experienced specialist doctor experienced in chemotherapy administration.
• Before each treatment with cisplatin, you must undergo a hearing test.
• If you have a pre-existing neurological condition not caused by cisplatin. If you have an infection. Contact your doctor if you experience vomiting and diarrhoea after administration of Cisplatino Sandoz; fluid loss must be compensated.
• If you intend to have children (see Pregnancy, breastfeeding and fertility)
• In case of spillage of cisplatin, contaminated skin must be washed immediately with soap and water. Consult your doctor also if you have previously experienced any of the problems listed above.

Other medicines and Cisplatino Sandoz

• Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. The simultaneous use of medicines that suppress bone marrow function, or radiotherapy, may enhance the undesirable effects of cisplatin on the bone marrow.
• The toxicity of cisplatin may increase if the drug is administered concurrently with other cytostatic medicines (medicines for the treatment of cancer), such as bleomycin and methotrexate.
• Medicines used to treat high blood pressure (antihypertensives containing furosemide, hydralazine, diazoxide and/or propranolol) may enhance the toxic effect of cisplatin on the kidneys.
• The kidney toxicity of cisplatin may be significantly increased when administered concurrently with agents that may cause adverse effects on the renal tract, such as medicines for the prevention/treatment of certain infections (antibiotics: cephalosporins, aminoglycosides, and/or amphotericin B) and contrast media.
• The ototoxicity (hearing damage) of cisplatin may be increased when administered concurrently with medicines such as aminoglycosides that may cause adverse effects on hearing.
• If you are taking medicines for the treatment of gout during therapy with cisplatin, dose adjustments of these medicines may be necessary (e.g. allopurinol, colchicine, probenecid and/or sulfinpyrazone).
• The administration of diuretics (loop diuretics) in combination with cisplatin (cisplatin dose: greater than 60 mg/m²; urinary output: less than 1000 ml in 24 hours) may result in toxic effects on the kidneys and hearing.
• Early signs of hearing damage (dizziness and/or tinnitus) may be masked when antihistamines used to treat hypersensitivity reactions (such as buclizine, cyclizine, loxapine, meclizine, phenothiazines, thioxanthenes and/or trimethobenzamide) are taken during cisplatin therapy.
• Cisplatin administered in combination with ifosfamide may cause hearing damage or nephrotoxicity (kidney toxicity).
• The effects of cisplatin treatment may be reduced by the concomitant administration of pyridoxine and hexamethylmelamine.
• Cisplatin administered in combination with bleomycin and vinblastine may cause pallor or bluish discoloration of the fingers of the hands and/or feet (Raynaud's phenomenon).
• The concomitant administration of cisplatin with paclitaxel or docetaxel may cause severe neurotoxicity (nerve damage).
• The combined use of cisplatin with bleomycin and etoposide may reduce blood lithium levels, which therefore must be monitored at regular intervals.
• Cisplatin reduces the effectiveness of phenytoin used for the treatment of epilepsy (see also “Do not use Cisplatino Sandoz”).
• Cisplatin may negatively affect the efficacy of anticoagulant medicines (blood thinners), therefore coagulation must be monitored more frequently during combination therapy.
• Cisplatin and cyclosporine may cause immunosuppression, with a risk of increased white blood cell (lymphocyte) production.
• You must not receive vaccinations with live virus vaccines within three months after treatment with cisplatin.
• If you are undergoing treatment with cisplatin, you must avoid vaccination against yellow fever (see also “Do not use Cisplatino Sandoz”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor for advice before using this medicine.
Cisplatin should not be used during pregnancy, unless it is clinically necessary for the mother.
You must use an effective method of contraception during and for at least 6 months after treatment
with cisplatin.
Cisplatin must not be used during breastfeeding.
Male patients undergoing treatment with cisplatin are advised not to father a child during treatment and for 6 months after. In addition, male patients are advised to seek information about sperm preservation before starting treatment.

Driving and using machines
You should not drive or operate tools or machines requiring full attention, because treatment with cisplatin may cause drowsiness and/or induce vomiting.

Cisplatino Sandoz contains sodium.
This medicine contains 71 mg of sodium (main component of table salt) in each 20 ml vial. This corresponds to 3.55% of the maximum daily recommended dietary intake for an adult.
This medicine contains 177 mg of sodium (main component of table salt) in each 50 ml vial. This corresponds to 8.85% of the maximum daily recommended dietary intake for an adult.
This medicine contains 354 mg of sodium (main component of table salt) in each 100 ml vial. This corresponds to 17.7% of the maximum daily recommended dietary intake for an adult.

3. How to use Cisplatino Sandoz

Dosage and method of administration
Cisplatino must be administered only by an oncology specialist. The concentrate is diluted with
a sodium chloride solution, or a sodium chloride solution containing glucose, or a sodium chloride solution containing mannitol.
Cisplatino is administered exclusively by intravenous infusion (intravenous infusion).
Cisplatino must not come into contact with materials containing aluminium.
The recommended dosage of cisplatino is determined based on the patient's physical condition, the expected treatment effects, and whether the drug is administered alone (monotherapy) or in combination with other medicinal products (combination chemotherapy).

Cisplatino 0.5 mg/ml (monotherapy):
The recommended doses are as follows:

• A single dose of 50 to 120 mg/m² body surface area every 3–4 weeks;
• 15 to 20 mg/m² body surface area per day for 5 consecutive days every 3–4 weeks.

Cisplatino 0.5 mg/ml in combination with other chemotherapeutic agents (combination chemotherapy):

• The usual dose is equal to or greater than 20 mg/m² body surface area every 3–4 weeks.
• The usual dose in the treatment of lung tumours is 80 mg/m² body surface area.

To prevent or reduce kidney problems, it is recommended to drink large amounts of water during the 24 hours following cisplatino treatment.

If you think you have been given too much Cisplatino:
Your doctor will ensure that you receive the appropriate dose for the treatment of your disease. In case of overdose, you may experience an increase in adverse events, and your doctor may prescribe therapy to relieve the symptoms.
For any questions about the use of this medicine, please consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.

• Contact your doctor as soon as possible if you:
  • have persistent or severe vomiting or diarrhoea
  • have stomatitis/mucositis (inflammation of the lips or mouth ulcers)
  • have swelling of the face, lips, mouth or throat
  • have unexplained breathing symptoms such as dry cough, difficulty breathing or crackling sounds
  • have difficulty swallowing
  • have a sensation of numbness or tingling in the fingers or toes
  • have extreme fatigue
  • have unusual bruising or bleeding
  • have signs of infection such as sore throat or fever
  • feel discomfort near or at the injection site during infusion
  • have severe pain or swelling in one of your legs, chest pain or difficulty breathing (possibly indicating harmful blood clots in a vein) (common: may affect up to 1 in 10 people).

Very common (may affect more than 1 in 10 people)

• decrease in white blood cells leading to increased risk of infection (leucopenia)
• decrease in platelets leading to increased risk of bruising and bleeding (thrombocytopenia)
• decrease in red blood cells which may cause paleness of the skin and lead to weakness or breathlessness (anaemia)
• bone marrow failure (no production of blood cells)
• low levels of sodium in the blood
• fever

Common (may affect up to 1 in 10 people)

• sepsis, arrhythmia including slow heart rate (bradycardia), fast heart rate (tachycardia)
• shortness of breath (dyspnoea), lung inflammation (pneumonitis), respiratory failure

Uncommon (may affect up to 1 in 100 people)

• reduced sperm production (spermatogenesis abnormalities) and ovulation, painful breast enlargement in men (gynaecomastia)
• acute leukaemia
• low levels of magnesium in the blood (hypomagnesaemia)
• hearing damage (ototoxicity)
• metallic deposit on the gums

Rare (may affect up to 1 in 1,000 people)

• various brain disorders (leukoencephalopathy)
• high levels of cholesterol in the blood (hypercholesterolaemia)
• seizures
• numbness, tingling, burning sensations (peripheral neuropathy)
• abnormal changes in the brain that may cause a range of symptoms including headache, confusion, seizures and loss of vision, detected by magnetic resonance imaging (posterior reversible encephalopathy syndrome)
• heart attack
• inflammation of the mucous membranes of the mouth (stomatitis)

Very rare (may affect up to 1 in 10,000 people)

• increased iron levels in the blood
• heart stops pumping blood (cardiac arrest)

Not known (frequency cannot be estimated from the available data)

• infection
• destruction of red blood cells (Coombs positive haemolytic anaemia)
• increase in certain enzymes (amylase)
• a group of symptoms that occur when there is too much antidiuretic hormone (ADH) in the body, such as fluid retention, electrolyte imbalances and low sodium levels in the blood (called hyponatraemia or water intoxication)
• dehydration
• low levels of electrolytes in the blood (potassium, phosphate, calcium)
• increased levels of uric acid in the blood, a waste product from food digestion
• muscle cramps (tetany)
• stroke
• loss of taste
• inflammation of blood vessels in the brain
• sudden sharp pain radiating from the neck down the spine to the legs when bending forward (Lhermitte's sign)
• spinal cord compression (myelopathy)
• damage to nerves controlling involuntary body functions (may affect blood pressure, temperature regulation, digestion, bladder function)
• blurred vision
• colour blindness
• loss of vision (blindness)
• inflammation of the optic nerve
• swelling around the nerve responsible for vision (papilloedema)
• retinal pigmentation (multilayered sensory tissue lining the back of the eye responsible for vision)
• ringing in the ears such as whistling, buzzing, humming, tinkling
• deafness
• heart problems
• a set of signs including haemolytic anaemia (destruction of red blood cells), kidney failure and low platelet count (a type of blood cell that helps blood to clot) (haemolytic uraemic syndrome)
• pale and blue fingers and toes (Raynaud's phenomenon)
• feeling unwell (nausea) and vomiting
• loss of appetite
• hiccups
• diarrhoea
• increased liver enzymes in the blood, which may indicate liver damage
• formation of blood clots in the lungs
• skin rash
• hair loss (alopecia)
• muscle spasms
• reduced or complete loss of kidney function
• weakness, loss of energy
• redness, inflammation, swelling and pain at the injection site due to injection into surrounding tissue rather than into a vein

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cisplatino Sandoz

Keep this medicine out of the sight and reach of children.
Do not store at temperatures above 25°C.
Do not refrigerate or freeze.
Store the vial inside the outer packaging to protect it from light.
Do not use this medicine after the expiry date stated on the packaging and on the vial following the word
"Exp".
The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer required. This will help protect the environment.

6. Contents of the Pack and Other Information

Each milliliter (ml) of solution contains 0.5 milligrams (mg) of cisplatin.
The 20 ml vial contains 10 mg of cisplatin, the 50 ml vial contains 25 mg of cisplatin, and the
100 ml vial contains 50 mg of cisplatin.

What Cisplatino Sandoz Contains

• The active substance is cisplatin.
• The other excipients are sodium chloride, diluted hydrochloric acid, and water for injections.

Description of the Appearance of Cisplatino Sandoz and Contents of the Pack
Cisplatin is a clear, colourless to slightly yellow infusion solution contained in glass vials.
Pack containing 1 injection vial of 20 ml with 10 mg of cisplatin each.
Pack containing 1 injection vial of 50 ml with 25 mg of cisplatin each.
Pack containing 1 injection vial of 100 ml with 50 mg of cisplatin each.
Not all pack sizes may be marketed.
The packaged vials may or may not be equipped with a protective plastic overwrap (OncoSafe®).

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Sandoz Spa
Largo U Boccioni 1
21040 Origgio (VA), Italy

Manufacturer:
EBEWE Pharma Ges.m.b.H. Nfg.KG
Mondseestrasse 11
4866 Unterach, Austria

This medicinal product is authorised in European Economic Area member states under the following names:

Netherlands
Cisplatin “Ebewe” 0.5mg/ml, concentrate for infusion solution
Denmark
Cisplatin "Ebewe", concentrate for infusion solution, solution 0.5 mg/ml
Finland
Cisplatin “Ebewe” 0.5mg/ml infusion concentrate, solution for dilution
Germany
Cisplatin Ebewe 0.5 mg/ml, concentrate for preparation of an infusion solution
Greece
Cisplatin/EBEWE, 0.5 mg/ml CS.INJ.SOL
Ireland
Cisplatin ‘Ebewe’, 0.5mg/ml - Concentrate for Solution for Infusion
Italy
Cisplatino Sandoz, 0.5 mg/ml – concentrate for infusion solution, 10 mg
Cisplatino Sandoz, 0.5 mg/ml – concentrate for infusion solution, 25 mg
Cisplatino Sandoz, 0.5 mg/ml – concentrate for infusion solution, 50 mg
Luxembourg
Cisplatin-Sandoz Pdre P. Prep. Inj., 10mg
Cisplatin-SandozPdre P. Prep. Inj., 25mg
Cisplatin-SandozPdre P. Prep. Inj., 50mg
Portugal
Cisplatina Generis 0.5mg/ml, 10mg
Cisplatina Generis 0.5mg/ml, 25mg
Cisplatina Generis 0.5mg/ml, 50mg
Spain
CISPLATINO Sandoz 10 mg concentrate for infusion solution
CISPLATINO Sandoz 50 mg concentrate for infusion solution
Sweden
Cisplatin Ebewe 0.5mg/ml, concentrate for infusion solution, solution
United Kingdom
Cisplatin ‘Ebewe’ 0.5 mg/ml, Concentrate for solution for infusion

The following information is intended exclusively for healthcare professionals:

Special Precautions for Disposal and Handling
Cisplatino Sandoz must be diluted before use. When preparing the infusion solution, avoid using any device containing aluminium that may come into contact with cisplatin (intravenous infusion sets, needles, catheters, syringes).
The preparation of the infusion solution must be carried out under aseptic conditions.
For dilution of the concentrate, one of the following solutions must be used:
0.9% sodium chloride solution;
mixture of 0.9% sodium chloride solution and 5% glucose solution (1:1)
(resulting final concentrations: 0.45% sodium chloride, 2.5% glucose).
If adequate hydration cannot be ensured prior to treatment, the concentrate may be diluted with:
mixture of 0.9% sodium chloride solution and 5% mannitol solution (1:1)
(resulting final concentrations: 0.45% sodium chloride, 2.5% mannitol).

Preparation of cisplatin infusion solution:
The required amount (dose) must be diluted in 1–2 litres of one of the solutions listed above.
The diluted solution must be administered intravenously by infusion only.
Use only clear, colourless to pale yellow solutions free from visible particles.
For single use only.
Cytotoxic agents must be prepared for administration only by personnel trained in safe handling procedures.
Follow local guidelines for handling cytotoxic drugs.
Like any other cytotoxic agent, cisplatin must be handled with extreme caution: gloves, masks, and protective clothing are required and of vital importance. Cisplatin should preferably be prepared in a safety cabinet. Avoid contact with skin and/or mucous membranes. Pregnant healthcare personnel must not handle cisplatin.

Skin contact: rinse thoroughly with abundant water. Apply an ointment to soothe any temporary burning sensation. (Note: some individuals are sensitive to platinum and may develop a skin reaction.)

In case of spillage, personnel must wear gloves and absorb the spilled liquid with a dedicated sponge. Rinse the area twice with water. Place all solutions and sponges into a plastic bag and seal it. In case of spillage, all materials that have come into contact with cisplatin must be handled and disposed of according to local guidelines for cytotoxic drugs.

Any unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.

Incompatibilities
Cisplatin reacts with aluminium, resulting in the formation of a black precipitate of platinum. Therefore, avoid using any device containing aluminium that may come into contact with cisplatin (intravenous infusion sets, needles, catheters, syringes).
The drug must not be mixed with other medicinal products except those specified above.
Cisplatin must not be diluted with 5% glucose solution alone or 5% mannitol solution alone, but only with mixtures also containing sodium chloride as specified above.
Antioxidants (such as sodium metabisulfite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel may inactivate cisplatin in infusion systems.

Special Precautions for Storage
Medicinal product packaged for sale:
Do not store above 25°C. Do not refrigerate or freeze. Keep the vial in its outer packaging to protect from light.

Infusion solution after dilution:
Chemical and physical in-use stability has been demonstrated for 48 hours at 2–8°C when protected from light, for solutions with a final cisplatin concentration of 0.1 mg/ml after dilution of the cisplatin concentrate with one of the following solutions:
0.9% sodium chloride solution;
mixture of 0.9% sodium chloride solution and 5% glucose solution (1:1);
mixture of 0.9% sodium chloride solution and 5% mannitol solution (1:1).

From a microbiological standpoint, the product should be used immediately.
Otherwise, in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless reconstitution/dilution (and so on) has taken place under controlled and validated aseptic conditions.