Cisplatin Teva Italia

Package leaflet: Information for the user

Cisplatino Teva Italia 0.5 mg/ml concentrate for solution for infusion, 1 mg/ml concentrate for solution for infusion

cisplatin
Generic medicine
Read this leaflet carefully before you or someone else uses 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, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Cisplatino Teva Italia is and what it is used for

Cisplatin belongs to a group of medicines called cytostatics, used in the treatment of cancer. Cisplatin may be used alone, but is more commonly used in combination with other cytostatic agents.
Cisplatin is able to destroy cells in the body that can cause certain types of cancer (testicular cancer, ovarian cancer, bladder cancer, head and neck epithelial tumour, lung cancer, cervical cancer in combination with radiotherapy).
Your doctor can provide you with further information.

2. What you should know before using Cisplatin Teva Italia

Do not receive Cisplatin Teva Italia:

• if you are allergic to cisplatin or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to any other medicine containing platinum-based compounds
• if you have kidney problems (renal dysfunction)
• if you are dehydrated
• if you have severe suppression of bone marrow function, the symptoms of which may include: extreme tiredness, easy bruising and bleeding, infections
• if your hearing is impaired
• if you suffer from nervous system disorders caused by cisplatin
• if you are breastfeeding
• if used concomitantly with the yellow fever vaccine and phenytoin (see “Other medicines and Cisplatin Teva Italia” below).

Warnings and precautions
Exercise particular caution with cisplatin:

• Your doctor will perform tests to monitor blood levels of calcium, sodium, potassium, and magnesium, as well as to assess your general blood condition, liver and kidney function, and neurological function.
• Cisplatin must be administered only under the strict supervision of a physician experienced and specialized in chemotherapy administration.
• Your hearing will be checked before each treatment with cisplatin.
• If you have a neurological disorder not caused by cisplatin.
• If you currently have an infection. Contact your doctor.
• If you experience vomiting and diarrhea after receiving cisplatin, the lost fluids must be replaced.
• If you intend to have children (see “Pregnancy, breastfeeding and fertility”).
• In case of cisplatin leakage, contaminated skin must be washed immediately with soap and water.
• If cisplatin is accidentally 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
described above.
Other medicines and Cisplatin Teva Italia
These statements may also apply to products you have used in the past or may use in the future.
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 when administered concomitantly with other cytostatic agents (medicines used in cancer treatment), such as bleomycin and methotrexate.
• Agents used to treat high blood pressure (antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol) may enhance the nephrotoxic effect of cisplatin.
• Cisplatin nephrotoxicity may be severe when administered simultaneously with agents that may cause renal adverse effects, such as those used for prevention or treatment of certain infections (antibiotics: cephalosporins, aminoglycosides and/or amphotericin B) and contrast media.
• Ototoxicity of cisplatin may occur when administered concomitantly with agents known to cause hearing-related adverse effects, such as aminoglycosides.
• If you are taking agents for gout treatment during cisplatin therapy, dose adjustments of these medicines may be necessary (e.g., allopurinol, colchicine, probenecid and/or sulfinpyrazone).
• Administration of diuretics that increase urinary excretion (loop diuretics) in combination with cisplatin (cisplatin dose: more than 60 mg/m², urinary output: less than 1000 ml in 24 hours) may cause nephrotoxic and ototoxic effects.
• Early signs of hearing damage (dizziness and/or ringing in the ears) may be masked when antihistamines used to treat hypersensitivity (such as buclizine, cyclizine, loxapine, meclizine, phenothiazines, thioxanthenes and/or trimethobenzamide) are administered during cisplatin therapy.
• Cisplatin used in combination with ifosfamide may cause hearing damage or nephrotoxicity.
• The effects of cisplatin therapy may be reduced by simultaneous administration of pyridoxine and hexamethylmelamine.
• Cisplatin administered in combination with bleomycin and vinblastine may cause pallor or noticeable discoloration of fingers and/or toes (Raynaud's phenomenon).
• Administration of cisplatin before paclitaxel treatment or in combination with docetaxel may cause severe nerve damage.
• Combined use of cisplatin with bleomycin and etoposide may reduce blood lithium levels. Therefore, lithium levels must be monitored regularly.
• Cisplatin reduces the effectiveness of phenytoin, used to treat epilepsy (see also “Do not receive Cisplatin Teva Italia”).
• Penicillamine may reduce the effectiveness of cisplatin.
• Cisplatin may negatively affect the efficacy of agents used to prevent blood clotting (anticoagulants). Therefore, coagulation should be monitored more frequently during combined use of these medicines.
• Cisplatin and cyclosporine may cause immunosuppression, with a risk of increased white blood cell (lymphocyte) production.
• For 3 months after completion of cisplatin therapy, you must avoid using vaccines containing live viruses.
• If undergoing treatment with cisplatin, you must not receive yellow fever vaccinations (see also “Do not receive Cisplatin Teva Italia”).

Pregnancy, breastfeeding and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before starting or before being administered this medicine.
Cisplatin must not be used during pregnancy, unless explicitly advised by your doctor. You must use an effective contraceptive method during treatment with cisplatin and for 7 months after completion of treatment.
Breastfeeding
You must not breastfeed during treatment with cisplatin.
Fertility
Male patients treated with cisplatin are advised to use effective contraception and to avoid fathering children during treatment and for 4 months after completion of treatment. In addition, men are advised to seek information about sperm preservation before starting therapy.
Driving and using machines
Cisplatin may cause adverse effects such as drowsiness and/or vomiting. If you experience either or both of these symptoms, do not operate machinery requiring full attention.
Cisplatin Teva Italia contains sodium
Cisplatin Teva Italia 0.5 mg/ml
This medicine contains 70.8 mg of sodium (a main component of table salt) per 20 ml vial, 177 mg of sodium per 50 ml vial, and 354 mg of sodium per 100 ml vial. This corresponds to 3.54% / 8.85% / 17.7% of the maximum daily sodium intake recommended in an adult diet.
Cisplatin Teva Italia 1.0 mg/ml
This medicine contains 35.4 mg of sodium (a main component of table salt) per 10 ml vial, 177 mg of sodium per 50 ml vial, and 354 mg of sodium per 100 ml vial. This corresponds to 1.77% / 8.85% / 17.7% of the maximum daily sodium intake recommended in an adult diet.

3. How Cisplatino Teva Italia is administered

Dosage and method of administration
Cisplatin must be administered only by a specialist in cancer treatment.
The concentrate must be diluted before administration.
Cisplatin must be administered exclusively by intravenous infusion.
Cisplatin must not come into contact with any material containing aluminium.
The recommended dose of cisplatin depends on your health status, the expected effects of
therapy, and whether cisplatin is administered alone (monotherapy) or in combination with
other agents (combination chemotherapy).

Cisplatino Teva Italia (monotherapy):
The following doses are recommended:

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

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

• 20 mg/m² or more, once every 3–4 weeks

For the treatment of cervical cancer, cisplatin is used in combination with radiotherapy:
The usual dose is 40 mg/m² once weekly for 6 weeks.

To prevent or reduce kidney-related problems, you are advised to drink plenty of water for
24 hours following cisplatin therapy.

If you think you have been given more Cisplatino Teva Italia than you should have
Your doctor will ensure that you receive the correct dose for your condition. In case of
overdose, you may experience an increase in adverse effects. Your doctor may prescribe
symptomatic treatment for these side effects. If you think you have been given too much
cisplatin, contact your doctor immediately.

If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not
everyone will experience them.
If you notice any side effect, it is important to inform your doctor before the
next treatment.

Serious side effects
Contact your doctor as soon as possible if you notice any of the following symptoms:

• persistent or severe diarrhoea or vomiting
• stomatitis/mucositis (sore lips or mouth ulcers)
• swelling of the face, lips, mouth or throat
• unexplained respiratory symptoms, such as dry cough, difficulty breathing, crackling sounds
• difficulty swallowing
• numbness or tingling in fingers or toes
• extreme tiredness
• unusual bruising or bleeding
• signs of infection, such as sore throat and high fever
• discomfort near or at the injection site during infusion
• severe pain or swelling in one leg, chest pain or difficulty breathing (could indicate dangerous blood clots in a vein) (common: may affect up to 1 in 10 people)

Other possible side effects
Very common: may affect more than 1 in 10 people

• decrease in the number of white blood cells in the blood, making infections more likely (leucopenia), decrease in platelets in the blood, increasing the risk of bruising and bleeding (thrombocytopenia), as well as decrease in red blood cells in the blood, causing pale skin, weakness or breathlessness (anaemia). The bone marrow does not produce enough blood cells, or fails to produce them (bone marrow failure).
• reduction in the level of the electrolyte sodium
• hearing loss associated with tinnitus
• loss of appetite (anorexia), nausea, vomiting, diarrhoea
• kidney dysfunction, such as failure to produce urine (anuria), blood poisoning caused by urine (uraemia) and excessive levels of uric acid in the blood (hyperuricaemia) (e.g., gout)
• fever

Common: may affect up to 1 in 10 people

• infections and blood poisoning (sepsis)
• decrease in the number of white blood cells in the blood (leucopenia; about 14 days after administration), decrease in platelets in the blood (thrombocytopenia; about 21 days after administration), and decrease in red blood cells in the blood (onset delayed compared to leucopenia and thrombocytopenia)
• peripheral sensory nerve neuropathy (bilateral sensory neuropathy), characterised by tingling, itching or pins and needles without any obvious cause, and sometimes characterised by loss of taste, touch, vision, brain dysfunction (confusion, slurred speech, sometimes blindness, memory loss and paralysis); sudden shooting pains from the neck, through the back and down the legs when bending forward, vertebral disease.
• deafness and dizziness
• arrhythmia, including slowing (bradycardia) and acceleration (tachycardia) of the heartbeat
• inflammation of a vein (phlebitis)
• shortness of breath (dyspnoea), lung inflammation (pneumonitis) and respiratory failure
• liver dysfunction
• redness and inflammation of the skin (erythema, skin ulcers) at the injection site
• swelling (oedema) and pain at the injection site

Uncommon: may affect up to 1 in 100 people

• hypersensitivity reactions, including skin rash, eczema with severe itching and pustule formation (urticaria), redness and inflammation of the skin (erythema) or itching
• reduction in the level of the electrolyte magnesium
• metallic deposits on the gums
• hair loss (alopecia)
• dysfunction of spermatogenesis and ovulation, painful breast enlargement in men (gynaecomastia)
• hiccups, weakness (asthenia), malaise

Rare: may affect up to 1 in 1,000 people

• cancer of the blood-forming cells in the bone marrow, characterised by rapid growth of abnormal white blood cells (acute leukaemia). Cisplatin, like other similar medicines, increases the risk of leukaemia (secondary leukaemia).

• haemolytic anaemia, bone marrow suppression characterised by a severe reduction in the number of white blood cells, combined with high fever, severe sore throat and mouth ulcers (agranulocytosis), as well as anaemia due to reduced blood cell production

• severe hypersensitivity (anaphylactic reactions) with low blood pressure (hypotension), rapid heartbeat (tachycardia), breathing difficulties (dyspnoea), discomfort caused by muscle cramps in the airways (bronchospasm),
  facial swelling and fever; suppression of the immune system
  (immunosuppression)

• increased levels of amylase (an enzyme) in the blood

• reduced levels of electrolytes (calcium, phosphate, potassium) in the blood with muscle cramps and/or changes in the electrocardiogram (ECG). Excessively high cholesterol levels in the blood.

• loss of certain types of brain functions, including brain dysfunction characterised by spasms and reduced levels of consciousness (encephalopathy), degeneration of the brain's white matter (leukoencephalopathy), as well as blockage of the carotid artery; seizures; symptoms such as headache, altered mental function, seizures and abnormal vision, which may range from blurred vision to loss of sight (posterior reversible encephalopathy syndrome)

• loss of vision (blindness), difficulty perceiving colours and dysfunction of eye movement

• inability to sustain normal conversation, hearing loss (particularly in children and elderly people)

• increased blood pressure, coronary artery disease and heart attacks

• inflammation of the mucous membranes of the mouth (stomatitis)

• reduction in protein levels in the blood (albumin)

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

• insufficient production of the hormone vasopressin in the brain (SIADH)
• increased levels of iron in the blood
• epileptic seizures (convulsions)
• swelling of the optic disc (papilloedema), inflammation of the optic nerve associated with pain and reduced nerve function (optic neuritis), blindness due to brain dysfunction
• cardiac arrest
• dysfunction affecting blood flow, for example in the brain, but also in the fingers of hands and feet (Raynaud's syndrome)

Not known: frequency cannot be determined from the available data

• dehydration, increased level of uric acid (hyperuricaemia), syndrome characterised by muscle cramps (tetany)
• cerebrovascular accident, stroke (haemorrhagic or ischaemic), loss of taste (ageusia)
• blurred vision, colour blindness, retinal disorders
• heart problems
• changes in kidneys and blood (haemolytic uremic syndrome)
• blood clots in the lungs causing chest pain and breathlessness (pulmonary embolism)
• skin rash
• muscle spasms
• acute kidney dysfunction.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet,
please contact your doctor, pharmacist or nurse. You can also report side
effects directly via the national reporting system at the following website:
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 Teva Italia

Keep this medicine out of the sight and reach of children.
Store the vial in the outer packaging to protect the medicine from light.

Concentrate for solution for infusion 0.5 mg/ml
Store below 25°C. Do not refrigerate or freeze.

Concentrate for solution for infusion 1 mg/ml
Store between 15°C and 25°C. If the product is stored below 15°C, a precipitate may form. If the solution is not clear, or a precipitate has formed that does not dissolve, the solution must not be used.

Do not use this medicine after the expiry date stated on the vial and carton after “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 you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Cisplatino Teva Italia Contains
The active substance is cisplatin.
Cisplatino Teva Italia 0.5 mg/ml, concentrate for solution for infusion contains 0.5 mg of
cisplatin per ml.
Cisplatino Teva Italia 1 mg/ml, concentrate for solution for infusion contains 1 mg of
cisplatin per ml.
The other components are sodium chloride (see section 2), diluted hydrochloric acid (for pH adjustment), diluted sodium hydroxide (for pH adjustment), and water for injections.

Description of the Appearance of Cisplatino Teva Italia and Contents of the Package
Cisplatin is a clear, light yellow concentrate for infusion solution, free from visible particles, supplied in glass vials for injectable preparations.

Cisplatino Teva Italia 0.5 mg/ml:
Pack containing 1 vial for injectable preparations of 20 ml, each vial contains 10 mg of cisplatin.
Pack containing 1 vial for injectable preparations of 50 ml, each vial contains 25 mg of cisplatin.
Pack containing 1 vial for injectable preparations of 100 ml, each vial contains 50 mg of cisplatin.

Cisplatino Teva Italia 1 mg/ml:
Pack containing 1 vial for injectable preparations of 10 ml, each vial contains 10 mg of cisplatin.
Pack containing 1 vial for injectable preparations of 50 ml, each vial contains 50 mg of cisplatin.
Pack containing 1 vial for injectable preparations of 100 ml, each vial contains 100 mg of cisplatin.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milan, Italy
Cisplatino Teva Italia 0.5 mg/ml

Manufacturer
Pharmachemie B.V. - Swensweg 5 - Postbus 552 - 2003 RN Haarlem (The Netherlands)
Cisplatino Teva Italia 1 mg/ml

Manufacturer
Pharmachemie B.V. - Swensweg 5 - Postbus 552 - 2003 RN Haarlem (The Netherlands)

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Belgium: Cisplatine Teva 1 mg/ml concentrate for solution for infusion
Germany: Cisplatin Teva 1 mg/ml concentrate for the preparation of an infusion solution
Greece: Platosin
Italy: Cisplatino Teva Italia 1 mg/ml concentrate for solution for infusion
Cisplatino Teva Italia 0.5 mg/ml concentrate for solution for infusion
Latvia: Cisplatin Teva 0.5 mg/ml concentrate for preparation of infusion solution
Luxembourg: Cisplatine Teva 1 mg/ml solution to be diluted for perfusion
Netherlands: Cisplatine 0.5 mg/ml PCH, concentrate for solution for infusion
Cisplatine 1 mg/ml PCH, concentrate for solution for infusion
Portugal: Cisplatina TEVA 1 mg/ml concentrate for solution for perfusion - IV
United Kingdom (Northern Ireland): Cisplatin 1 mg/ml Concentrate for Solution for Infusion

The following information is intended exclusively for physicians or healthcare professionals:

Preparation and Handling of the Product
As with all antineoplastic agents, caution must be exercised when handling cisplatin. Dilution must be performed under aseptic conditions by trained personnel in a specifically designated area. Protective gloves must be worn. Adequate precautions should be taken to avoid contact with skin and mucous membranes. If contact with skin occurs, immediately wash the affected area with soap and water. Tingling, burning, and redness have been observed following skin contact. In case of contact with mucous membranes, rinse thoroughly with water. Dyspnea, chest pain, throat irritation, and nausea have been reported after inhalation.

Pregnant women should avoid contact with cytotoxic agents.

Body waste products and vomit must be handled and disposed of carefully.

If the solution appears cloudy or if an insoluble deposit is observed, the vial must be discarded.

A damaged vial must be considered and handled with the same precautions as contaminated waste. Contaminated waste must be stored in appropriately labeled waste containers.

Incompatibilities
Avoid contact with aluminium. Cisplatin may react with metallic aluminium, forming a black precipitate of platinum. Avoid using any intravenous infusion sets, needles, catheters, or syringes containing aluminium.

Cisplatin decomposes in solutions with low chloride content; the chloride concentration must be at least equivalent to 0.45% sodium chloride.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Antioxidants (such as sodium metabisulfite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel may inactivate cisplatin in infusion systems.

Preparation for Intravenous Administration
Withdraw the required amount of solution from the vial and dilute it in at least 1 litre of one of the following solutions:

• Sodium chloride 0.9%
• Mixture (1:1) of sodium chloride 0.9%/glucose 5% (resulting final concentrations: sodium chloride 0.45%, glucose 2.5%)
• Sodium chloride 0.9% and mannitol 1.875%, for injectable preparations
• Sodium chloride 0.45%, glucose 2.5% and mannitol 1.875%, for injectable preparations

Always inspect the solution before use. Only a clear, particle-free solution should be administered.

DO NOT allow contact with injection materials containing aluminium.
DO NOT administer the concentrate undiluted.

Disposal
All materials used in the preparation and administration of the product, or that have come into contact with cisplatin in any way, must be disposed of in accordance with local guidelines for cytotoxic products. Any unused medicinal product residue and all materials used for dilution and administration must be disposed of in compliance with standard hospital procedures applicable to cytotoxic agents and in accordance with local laws governing the disposal of hazardous waste.

Special Precautions for Storage
Undiluted solution (Medicinal product in the original retail package):

Concentrate for solution for infusion 0.5 mg/ml
Store below 25°C. Do not freeze or refrigerate. Keep vials in their original packaging to protect from light.

Concentrate for solution for infusion 1 mg/ml
Store between 15°C and 25°C. Keep vials in their original packaging to protect from light.

If the undiluted product is stored below 15°C, a precipitate may form. If the solution is not clear or if an insoluble precipitate is present that does not dissolve, the solution must not be used.

After dilution:
Do not refrigerate or freeze the diluted solution.

After dilution in infusion fluids, the product may be stored for up to 14 days at room temperature (15°C–25°C), protected from light.

Exposure to ambient light should be limited to a maximum of 6 hours. If this period is exceeded, infusion bags must be completely wrapped in aluminium foil to protect the contents from light.

From a microbiological standpoint, the product should be used immediately.
If not used immediately, the responsibility for the storage conditions and duration prior to use lies with the user.