CISPLATIN PHARMACIA 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Cisplatino Pharmacia 1 mg/ml Concentrate for Solution for Infusion EFG

Read all of 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 further questions, ask your doctor, pharmacist, or nurse.
• 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.

Contents of the Package Leaflet

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

Cisplatino Pharmacia concentrate for solution for infusion is only prescribed by healthcare professionals who can answer any questions you may have after reading this leaflet.

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

Cisplatino belongs to a group of medicines called cytostatics, which are used in the treatment of cancer. Cisplatino can be used alone, but it is commonly used in combination with other cytostatics.

Cisplatino is able to destroy the cells in your body that can cause certain types of cancer (testicular tumor, ovarian tumor, bladder tumor, epithelial head and neck tumor, lung cancer, and cervical cancer in combination with radiotherapy).

Your doctor will provide you with more information.

2. What you need to know before you start using Cisplatino Pharmacia

Do not use Cisplatino Pharmacia:

• if you are allergic to cisplatino or any of the other components of this medicine (listed in section 6);
• if you are allergic to any other medicine that contains platinum;
• if you have kidney problems (renal insufficiency);
• if you have dehydration;
• if you have severe suppression of bone marrow function, these are some of the symptoms: extreme fatigue, easy bleeding or bruising, appearance of infections;
• if you have hearing problems;
• if you have nervous system disorders caused by cisplatino;
• if you are breastfeeding (see the section "Pregnancy, breastfeeding, and fertility");
• in combination with certain types of vaccines such as the yellow fever vaccine and phenytoin (a medicine used to prevent seizures) (see the section "Taking Cisplatino Pharmacia with other medicines").

Warnings and Precautions:

Consult your doctor or pharmacist or nurse before starting to use Cisplatino Pharmacia.

• If you have a higher amount of uric acid or proteins in the blood, which can be seen in blood tests.
• If you have nerve damage (tingling and numbness of hands and feet) not induced by cisplatino.
• If you have received radiotherapy in the head.
• If you have an infection.
• If you want to have children (see the section "Pregnancy, breastfeeding, and fertility"). You should use an effective contraceptive method during at least 6 months after treatment with cisplatino.

Tell your doctor, even if any of the above circumstances have occurred to you at any time.

Monitoring before and during treatment: Your doctor should perform tests to determine the levels of calcium, sodium, potassium, and magnesium in the blood, as well as to check your blood count and liver and kidney function and neurological function. The tests may be performed once a week throughout the duration of your treatment.

Your hearing will be tested before each treatment with Cisplatino Pharmacia. Cases of late-onset hearing loss have been reported in the pediatric population. Long-term follow-up is recommended in this population.

During treatment:

In case of cisplatino spill, the contaminated skin should be washed immediately with water and soap. If cisplatino is injected outside the blood vessels, administration should be stopped immediately. Cisplatino on the skin can cause tissue damage (cellulitis, fibrosis, and necrosis).

Taking Cisplatino Pharmacia with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

Note that these instructions may also apply to medicines that have been used before or may be used in the future.

• The use of medicines that inhibit bone marrow function or radiation may increase the adverse effects of cisplatino on the bone marrow.
• The toxicity of bleomycin and methotrexate (other cancer medicines) may increase when administered with or after cisplatino, because the renal elimination potentially caused by cisplatino's nephrotoxicity is reduced.
• Medicines for the treatment of high blood pressure (antihypertensives with furosemide, hydralazine, diazoxide, or propranolol) may increase the toxic effect of cisplatino on the kidneys.
• The toxicity of cisplatino may seriously affect the kidneys when administered with medicines that can cause adverse effects on the kidneys, such as those used in the prevention/treatment of certain infections (antibiotics: cephalosporins, aminoglycosides, and/or antifungals: Amphotericin B) and contrast media (used in medical imaging).
• The toxicity of cisplatino may also affect hearing when administered with aminoglycosides.
• If you take medicines to treat gout during your treatment with cisplatino, it may be necessary to adjust the dose of these medicines (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone), because cisplatino can cause an increase in uric acid in the blood.
• The administration of diuretic medicines (loop diuretics) in combination with cisplatino (when the dose of cisplatino is not higher than 60 mg/m2, and urine secretion is not lower than 1,000 ml per 24 hours) may produce toxic effects on the kidneys and ears.
• The first signs of hearing problems (such as dizziness and tinnitus) may be masked if, during treatment with cisplatino, you are given medicines to treat hypersensitivity, feeling sick, or mental problems (antihistamines such as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes, and/or trimethobenzamides).
• Cisplatino in combination with ifosfamide may produce ear damage, increased loss of body proteins, and increased kidney toxicity.
• The administration of pyridoxine and altretamine may reduce the response to treatment with cisplatino.
• Cisplatino in combination with bleomycin and vinblastine may cause paleness or bluish discoloration of the fingers and/or toes (Raynaud's phenomenon).
• The administration of cisplatino for treatment with paclitaxel or in combination with docetaxel may cause severe nerve damage.
• It is recommended to regularly check lithium levels, as a reduction in lithium levels in the blood has been observed after treatment with cisplatino combined with bleomycin and etoposide.
• Cisplatino reduces the amount of certain medicines used to treat epilepsy (such as phenytoin) in the blood, reducing the effect of the treatment of epilepsy. You should not start a new treatment for epilepsy while being treated with cisplatino. (See "Do not take Cisplatino Pharmacia")
• Penicillamine may decrease the efficacy of Cisplatino Pharmacia.
• Cisplatino may have a negative impact on the efficacy of medicines that prevent blood clotting (anticoagulants, such as coumarins/warfarin). Therefore, it is recommended to increase the frequency of coagulation monitoring during the combined use of these medicines.
• Cisplatino in combination with cyclosporin may produce suppression of the immune system with a risk of proliferation of white blood cells (lymphocytes).
• You should not receive live virus vaccines (including the yellow fever vaccine) when undergoing this treatment or in the first three months after completing a treatment with cisplatino.

(See the section "Do not use Cisplatino Pharmacia").

E

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist, or nurse for advice before using this medicine.

Cisplatino should not be used during pregnancy unless your doctor considers it necessary.

If you are of childbearing potential, you should take measures to avoid becoming pregnant during and at least 29 weeks (at least 7 months) after the last dose.

Cisplatino Pharmacia should not be used by women during breastfeeding and for 4 weeks after treatment, as cisplatino is excreted in breast milk.

Men with female partners of childbearing potential should be advised to use effective contraceptive methods during treatment with cisplatino and for at least 17 weeks (at least 4 months) after the last dose.

Both men and women should seek advice on preserving fertility before treatment.

Driving and using machines

Cisplatino may cause drowsiness and/or vomiting. If you experience any of these effects, avoid driving or operating machines that require special attention.

Cisplatino Pharmacia contains sodium

This medicine contains 177 mg of sodium (the main component of cooking/table salt) in each 50 ml vial. This is equivalent to 8.9% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 354 mg of sodium (the main component of cooking/table salt) in each 100 ml vial. This is equivalent to 17.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use Cisplatino Pharmacia

Posology and method of administration

Cisplatino can only be administered by a specialist in cancer treatment. The concentrate is diluted with sodium chloride solution, which may also contain glucose.

Cisplatino should be administered only by intravenous injection. The prepared infusion should be administered over a period of 6 to 8 hours. Support equipment should be available to control allergic reactions.

Cisplatino should not come into contact with materials that contain aluminum.

Cisplatino is recommended for children, adolescents, and adults.

The recommended dose of cisplatino depends on your state of health, the expected effects of the treatment, and whether cisplatino is used alone (monotherapy) or in combination with other medicines (combination chemotherapy).

Cisplatino Pharmacia (monotherapy):

The following doses are recommended:

• Singledose of 50 to 120 mg/m² of body surface area every 3-4 weeks.
• 15 to 20 mg/m² per day for 5 days, every 3-4 weeks.

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

• The recommended dose is 20 mg/m² or more, every 3-4 weeks.

For the treatment of cervical cancer, cisplatino is used in combination with radiotherapy.

A usual dose is 40 mg/m² per week for 6 weeks.

Your doctor may reduce the dose if you have kidney problems or bone marrow problems.

In order to avoid or reduce kidney problems, it is recommended that you drink large amounts of water during a 24-hour period after treatment with cisplatino.

If you receive more Cisplatino Pharmacia than you should

Your doctor will ensure that you are given the correct dose. In case of overdose, you may experience increased side effects, which may include kidney failure, liver failure, deafness, changes in vision, decreased production of blood cells, and conditions such as feeling sick, being sick, and nerve inflammation. Your doctor may give you symptomatic treatment for these side effects. If you think you have received too much cisplatino, contact your doctor immediately.

If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

If you experience any adverse effect, it is essential that you inform your doctor before the next treatment.

Report immediately to your doctor if you experience any of the following effects:

• Sudden signs of allergy such as rash, itching, or hives on the skin, swelling of the face, lips, mouth, or throat, shortness of breath or wheezing, increased heart rate, and decreased blood pressure,
• Decrease in the number of all types of blood cells due to bone marrow depression, including white blood cells (which can cause, for example, increased infections or fever, sore throat, mouth ulcers), red blood cells (can cause pale skin and weakness or shortness of breath), and platelets (which increases the risk of bruising and bleeding (thrombocytopenia)),
• A condition characterized by a reduction in the number of red blood cells, platelets, and kidney failure (hemolytic uremic syndrome),
• Suppression of the immune system may cause more frequent infections, and blood poisoning (sepsis) may occur,
• Overproduction of a hormone that causes fluid and sodium retention, resulting in weakness, fatigue, or confusion,
• Damage to the nervous system, characterized by tingling, itching, or numbness without cause,
• Seizures, loss of certain types of brain function, including brain dysfunction characterized by spasms and reduced levels of consciousness,
• Damage to a part of the brain due to bleeding or decreased blood flow, which can cause weakness in the arms or legs, headache, dizziness, and confusion, difficulty swallowing, and difficulty speaking (stroke),
• A rapid increase in abnormal white blood cells (symptoms may include feeling very tired, bleeding, bruising, and an increased risk of infections), (acute leukemia),
• Problem with the spinal cord, which can lead to numbness, weakness, loss of balance, back pain, neck, and legs,
• Loss of certain brain functions that can lead to excessive fatigue, rapid or slow heart rate, fluctuations in blood pressure, difficulty breathing, and abdominal distension,
• Inflammation of the optic nerve combined with pain and reduced nerve function,
• Loss of vision (blindness), inflammation of the nerves in the back of the eye,
• Hearing loss or deafness,
• Blockage in the blood vessels of the heart that can cause chest pain that can extend to the shoulders, neck, or jaw (heart attack),
• Disease of the blood vessels of the heart that can be due to the thickening of the walls of these blood vessels, which reduces their size and restricts blood flow to the heart,
• Lung infection that can cause fever, chills, difficulty breathing, cough, phlegm, and coughing up blood (pneumonia) or respiratory failure,
• Blockage of the blood vessels of the lungs,
• Kidney problems (you may notice back pain, producing little or no urine, or urine that is cloudy or bloody) or kidney failure,
• Infection or injury at the injection site.

Other possible side effects may appear:

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

Alteration of the bone marrow, decrease in platelets (thrombocytopenia), decrease in white blood cells (leucopenia), decrease in the number of red blood cells (anemia).

Decrease in sodium levels in the blood (hyponatremia).

Fever.

Frequent (may affect up to 1 in 10 people)

Infection (sepsis).

Damage to the nervous system.

Changes in heartbeats (arrhythmias), including decreased heart rate (bradycardia) and increased heart rate (tachycardia).

Inflammation of a vein (phlebitis), formation of blood clots in the veins (venous thromboembolism).

Difficult breathing (dyspnea), pneumonia, and respiratory failure.

Redness and ulceration of the skin, inflammation due to fluid retention (edema), and pain.

Severe pain or inflammation in any of your legs, chest pain, or difficulty breathing (which may indicate harmful blood clots in a vein).

Uncommon (may affect up to 1 in 100 people)

Low magnesium levels in the blood.

Hearing problems (ototoxicity).

Alteration in sperm formation and abnormal ovulation, painful abnormal development of the breasts in men (gynecomastia).

Rare (may affect up to 1 in 1000 people)

A type of blood cancer (leukemia).

Decrease in the immune system.

Increased normal cholesterol levels in the blood (hypercholesterolemia).

Seizure, alteration of the nerves that carry information to the brain and spinal cord (peripheral neuropathy), alteration of the white matter of the brain (leukoencephalopathy and reversible posterior leukoencephalopathy syndrome).

Inflammation of the optic nerve, dysfunction of eye movement.

Myocardial infarction, alteration of the coronary arteries.

Increased blood pressure (hypertension).

Mouth ulcers (stomatitis).

Increased albumin in the blood.

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

Lesion, thickening, and partial obstruction of small blood vessels and alteration of the kidney capillaries (thrombotic microangiopathy combined with hemolytic uremic syndrome).

Allergic reaction.

Increased iron levels in the blood.

Seizures.

Cardiac arrest.

Frequency not known (cannot be estimated from the available data)

Infections that have led to the patient's death.

A type of alteration of red blood cells.

Increased amylase levels in the blood (enzymes), alteration in the secretion of antidiuretic hormone.

Dehydration, decreased potassium and phosphorus levels in the blood, increased uric acid levels in the blood, muscle cramps.

Stroke, loss of taste, sensation of electric discharge that runs through the entire spine (Lhermitte's syndrome), myelopathy, and other nerve disorders.

Blurred vision, difficulty perceiving colors, pigmentation of the inner part of the eyes that can lead to blindness, and other vision disorders.

Ringing in the ears (tinnitus), deafness.

Heart disorders.

Changes in blood flow to the fingers and toes, causing blue discoloration of the skin (Raynaud's syndrome).

Blockage of a pulmonary artery (pulmonary embolism).

Vomiting, nausea, loss of appetite, hiccups, diarrhea.

Skin rash, hair loss (alopecia).

Muscle cramps.

Alteration in kidney function.

Fatigue, discomfort.

Alteration at the injection site that can cause pain, fluid retention, and redness.

Alteration of some laboratory tests.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Cisplatino Pharmacia

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the vial and on the outer packaging after 'CAD'. The expiration date is the last day of the month indicated.

Keep the vial in the outer packaging to protect it from light.

Store below 25°C.

Do not refrigerate or freeze.

After dissolution:

The cisplatin injection remains stable for 24 hours at room temperature of 20-25°C. The diluted solution must be protected from light. Do not store the diluted solutions in the refrigerator or freezer.

From a microbiological point of view, the diluted solution should be used immediately. If it is not used immediately, the storage time of the solution ready for use and the conditions prior to use are the responsibility of the handler; furthermore, the dilution must be carried out in validated and controlled aseptic conditions.

Do not use this medicine if you notice that the solution is cloudy or a deposit is observed that does not dissolve. In this case, the vial must be discarded.

Medicines should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Cisplatino Pharmacia

The active ingredient is cisplatin.

1 ml of concentrate for solution for infusion contains 1 mg of cisplatin.

A 50 ml vial of concentrate for solution for infusion contains 50 mg of cisplatin.

A 100 ml vial of concentrate for solution for infusion contains 100 mg of cisplatin.

The other components are mannitol, sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injectable preparations.

Appearance of Cisplatino Pharmacia and package contents

Cisplatino Pharmacia is a clear, colorless to pale yellow concentrate for solution for infusion in a glass vial with a rubber stopper (latex-free).

Package with 1 vial of 50 ml concentrate containing 50 mg of cisplatin.

Package with 1 vial of 100 ml concentrate containing 100 mg of cisplatin.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Pharmacia Nostrum, S.A.

Avda. de Europa 20B

Parque Empresarial La Moraleja

28108 Alcobendas, Madrid

Spain

Manufacturer:

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

Date of the last revision of this prospectus: July 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) https://www.aemps.gob.es/

This information is intended only for doctors or healthcare professionals:

Preparation and handling of the product

For single use.

Consult local guidelines for cytotoxics.

As with all antineoplastic products, caution is required when handling cisplatin. The dilution should be carried out in aseptic conditions in a protective box and should be performed by trained personnel in an area specifically intended for this purpose. If no protective box is available, the equipment should be supplemented with a mask and protective gloves. Precautions should be taken to avoid contact with the skin and mucous membranes. In case of skin contact, wash with water and soap immediately. In cases of skin contact, tingling, burning, and redness have been observed. In case of contact with mucous membranes, they should be rinsed with plenty of water. After inhalation, dyspnea, chest pain, throat irritation, and nausea have been reported.

In case of cisplatin spillage, operators should wear gloves and clean the spilled material with a sponge in the area intended for this purpose. Rinse the area twice with water. Put all solutions and sponges in a plastic bag and seal it.

Pregnant women should avoid contact with cytostatics.

Organic waste and vomit should be disposed of carefully.

If the solution is cloudy or a deposit is observed that does not dissolve, the vial should be discarded.

Damaged vials should be considered and treated with the same precautions as contaminated waste. Contaminated waste should be deposited in specific containers for this purpose. See the "Elimination" section.

Preparation for intravenous administration

Take the necessary amount of solution from the vial and dilute it with at least 1 liter of the following solutions:

• sodium chloride at 9 mg/ml (0.9%);
• mixture of sodium chloride at 9 mg/ml (0.9%)/glucose 50 mg/ml (5%) (1:1), (resulting final concentrations: sodium chloride at 4.5 mg/ml (0.45%), glucose at 25 mg/ml (2.5%));
• sodium chloride at 9 mg/ml (0.9%) and mannitol at 18.75 mg/ml (1.875%) for injection;
• sodium chloride at 4.5 mg/ml (0.45%), glucose at 25 mg/ml (2.5%), and mannitol at 18.75 mg/ml (1.875%) for injection.

Always check the injection before use. Only clear solutions without visible particles should be administered.

DO NOT bring it into contact with injection material containing aluminum.

DO NOT administer it undiluted.

To consult the chemical and physical stability in the use of undiluted solutions, see the section "Special precautions for storage: undiluted solution".

Elimination

All materials used for preparation and administration, or those that have come into contact with cisplatin in any way, should be disposed of in accordance with local requirements for cytotoxics. Medicinal waste and materials used for preparation and administration should be destroyed according to standard hospital procedures applicable to cytotoxic agents and in compliance with local requirements for the elimination of cytotoxic agents.

Incompatibilities

It should not come into contact with aluminum. Cisplatin can react with aluminum, causing the formation of a black platinum precipitate. Contact with any intravenous administration utensils, needles, catheters, and syringes containing aluminum should be avoided. Cisplatin decomposes if dissolved in media with low chloride content; the chloride concentration should be at least equivalent to 0.45% sodium chloride.

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

This medicine should not be mixed with others except those mentioned in the previous section "Preparation for intravenous administration".

Special precautions for storage

Medicine packaged for sale:

Concentrate for solution for infusion 1 mg/ml

Undiluted solution:store below 25°C. Do not refrigerate or freeze. Keep the vial in the outer packaging to protect it from light. If the solution is not transparent or insoluble precipitates are formed, the solution should not be used.

Diluted solution:

Do not store the diluted solutions in the refrigerator or freezer.

After dilution in the indicated perfusion fluids:

The cisplatin injection remains stable for 24 hours at room temperature of 20-25°C, protected from light.

From a microbiological point of view, the diluted solution should be used immediately.