Package Insert: Information for the Patient

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

Read this entire package insert carefully before starting to use this medication, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• Ifyouexperienceadverse effects,consult your doctor or pharmacist or nurse, evenifthey are not listed in this package insert. See section 4.

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

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

Cisplatino is able to destroy the cells in your body that may cause certain types of cancer (testicular tumor, ovarian tumor, bladder tumor, epidermoid carcinoma of the head and neck, lung cancer, and cervical cancer in combination with radiation therapy).

Your doctor will provide you with more information.

Do not use Cisplatino Pharmacia:

• if you are allergic to cisplatin or any of the other ingredients 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 are dehydrated;
• if you have severe bone marrow suppression, which can cause symptoms such as extreme fatigue, easy bleeding or bruising, and the appearance of petechiae, and infections;
• if you have hearing problems;
• if you have nerve problems caused by cisplatin;
• 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 high levels of uric acid or proteins in your blood, which can be seen in blood tests.
• If you have nerve damage (tingling and numbness in hands and feet) not caused by cisplatin.
• If you have received radiation therapy to 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 for at least 6 months after treatment with cisplatin.

Inform your doctor, even if any of the circumstances mentioned above have occurred at any time..

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

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

During treatment:

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

Taking Cisplatino Pharmacia with other medicines:

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

Be aware 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 can increase the adverse effects of cisplatin on the bone marrow.
• The toxicity of bleomycin and methotrexate (other cancer medicines) may increase when administered with or after cisplatin, as it may potentially reduce renal elimination caused by cisplatin nephrotoxicity.
• Antihypertensive medicines (furosemide, hydralazine, diazoxide, or propranolol) may increase the toxic effect of cisplatin on the kidneys.
• Cisplatin toxicity may severely affect the kidneys when administered with medicines that can cause adverse effects on the kidneys, such as those used to prevent or treat certain infections (cephalosporins, aminoglycosides, and/or antifungals: amphotericin B) and contrast media (used in medical imaging).
• Cisplatin toxicity may also affect hearing when administered with aminoglycosides.
• If you take medicines to treat gout during your treatment with cisplatin, you may need to adjust the dose of these medicines (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone), as cisplatin can cause an increase in uric acid in the blood.
• The administration of diuretics (e.g., furosemide) in combination with cisplatin (when the cisplatin dose is not greater than 60 mg/m2, and the urine output is not less 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 cisplatin, you are given medicines to treat hypersensitivity, nausea, or mental problems (antihistamines such as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes, and/or trimethobenzamides).
• Cisplatin in combination with ifosfamide may cause ear damage, increased protein loss from your body, and increased kidney toxicity.
• The administration of pyridoxine and altretamine may reduce the response to cisplatin treatment.
• Cisplatin in combination with bleomycin and vinblastine may cause pallor or blue discoloration of the fingers of the hands and/or feet (Raynaud's phenomenon).
• The administration of cisplatin for treatment with paclitaxel or in combination with docetaxel may cause severe nerve damage.
• It is recommended to regularly control lithium levels, as a reduction in lithium levels in the blood has been observed after treatment with cisplatin combined with bleomycin and etoposide.
• Cisplatin reduces the amount of certain medicines used to treat epilepsy (such as phenytoin) in the blood, thereby reducing the effect of these medicines in the treatment of epilepsy.
• Penicillamine may reduce the effectiveness of Cisplatino Pharmacia.
• Cisplatin may have a negative impact on the effectiveness of anticoagulant medicines (such as warfarin). Therefore, it is recommended to increase the frequency of coagulation control during combined use of these medicines.
• Cisplatin in combination with cyclosporine may cause immunosuppression with a risk of proliferation of white blood cells (lymphocytes).
• You should not receive live virus vaccines (including the yellow fever vaccine). When you are undergoing this treatment or in the three months after completing a treatment with cisplatin.

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

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor, pharmacist, or nurse before using this medicine.

Cisplatino Pharmacia should not be used during pregnancy unless your doctor tells you to.

If you are fertile, 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 cisplatin is excreted in breast milk.

Men with fertile partners should 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 to preserve fertility before treatment.

Driving and operating machinery

Cisplatino Pharmacia may cause drowsiness and/or nausea. If you experience either of these effects, avoid operating machinery that requires special attention.

Cisplatino Pharmacia contains sodium

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

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

Posology and Administration

Cisplatincan only be administered by a specialist in cancer treatment. Theconcentrate is diluted with sodium chloride solution that may also contain glucose.

Cisplatinshould be administered only by intravenous injection (intravenous perfusion). The prepared perfusion should be administered over a period of 6 to 8 hours. There should be support equipment to have under control any allergic reactions.

Cisplatinshould not come into contact with materials containing aluminum.

Cisplatin is recommended for children, adolescents, and adults.

The recommended dose ofcisplatindepends on your health status, the expected effects of treatment, and whether cisplatin is used alone (monotherapy) or in combination with other medications (combination chemotherapy)

Cisplatin Pharmacia (monotherapy):

The following doses are recommended:

Cisplatin Pharmaciain combination with other chemotherapeutic agents (combination chemotherapy):

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

For cervical cancer treatment, cisplatin is used in combination with radiation therapy.

A typical dose is 40 mg/m2per week, for 6 weeks.

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

To avoid or reduce kidney problems, it is recommended that you drink large amounts of water for 24 hours after treatment withcisplatin.

If you receive more Cisplatin Pharmacia than you should

Your doctor will ensure that you receive the correct dose. In case of overdose, you may experience increased adverse effects, which may include renal insufficiency, hepatic insufficiency, hearing loss, changes in vision, decreased blood cell production, and conditions such as nausea, vomiting, and nerve inflammation. Your doctor may give you symptomatic treatment for these adverse effects.If you believe you have received too much cisplatin, contact your doctor immediately.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medications, this medication may cause side effects, although not everyone will experience them.

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

Inform your doctor immediately if you experience any of the following side effects::

• Sudden signs of allergy such as skin rash, itching, or hives, facial swelling, lip, mouth, or throat swelling, shortness of breath or wheezing, rapid heart rate, and low blood pressure,decreased blood pressure.
• Decreased number of all types of blood cells due to bone marrow depression, including white blood cells (which may cause, for example, increased infections or fever, sore throat, mouth ulcers), red blood cells (which may 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 renal insufficiency (hemolytic-uremic syndrome),
• Suppression of the immune system can cause more frequent infections, and may cause blood poisoning (sepsis),
• 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,
• Convulsions, loss of certain types of brain function, including cerebral dysfunction characterized by spasms and reduced levels of consciousness,
• Damage to a part of the brain due to bleeding or decreased blood flow that may cause weakness of the arms or legs, headache, dizziness, and confusion, difficulty swallowing, and difficulty speaking (stroke),
• A rapid increase in abnormal white blood cells (the symptoms may include feeling very tired, bleeding, bruising, and an increased risk of infections) (acute leukemia),
• Problem with the spinal cord, which may cause numbness, weakness, loss of balance, back pain, neck pain, and leg pain,
• Loss of certain brain functions that may 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,
• Loss of hearing or deafness,
• Blockage in the coronary arteries that may cause chest pain that may extend to shoulders, neck, or jaw (heart attack),
• Disease of the coronary arteries that may be due to thickening of the walls of these blood vessels, which reduces their size and restricts blood flow to the heart,
• Pulmonary infection that may cause fever, chills, difficulty breathing, cough, sputum, and coughing up blood (pneumonia) or respiratory failure,
• Blockage of the pulmonary arteries,
• Renal problems (you may notice back pain, produce little or no urine, or that the urine is cloudy or bloody) or renal insufficiency,
• Infection or injury at the injection site.

Other possible side effects may appear:

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

Bone marrow depression, decreased platelets (thrombocytopenia), decreased white blood cells (leucopenia),decreased red blood cells (anemia).

Decreased sodium levels in the blood (hyponatremia).

Fever.

Common (may affect up to 1 in 10 people)

Infection (sepsis).

Damage to the nervous system.

Changes in heart rhythm (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).

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

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

You experience intense 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.

Auditory problems (ototoxicity).

Alteration in sperm formation and abnormal ovulation, painful and abnormal breast development in men (gynecomastia).

Rare (may affect up to 1 in 1000 people)

A type of blood cancer (leukemia).

Decreased immune system.

Increased normal cholesterol levels in the blood (hypercholesterolemia).

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

Inflammation of the optic nerve, eye movement dysfunction.

Myocardial infarction, alteration of the heart arteries.

Increased blood pressure (hypertension).

Mouth ulcers (stomatitis).

Increased albumin levels in the blood.

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

Damage, thickening, and partial obstruction of small blood vessels and alteration of kidney capillaries (microangiopathic hemolytic anemia combined with hemolytic-uremic syndrome).

Allergic reaction.

Increased iron levels in the blood.

Convulsions.

Cardiac arrest.

Unknown frequency (cannot be estimated from 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 the 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 an electric discharge that runs through the entire spine (Lhermitte syndrome), myelopathy, and other nerve alterations.

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

Tinnitus, deafness.

Heart alterations.

Changes in blood flow to the fingers and feet causing blue discoloration of the skin (Raynaud syndrome).

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 may cause pain, fluid retention, and redness.

Alteration in some laboratory tests.

Reporting of side effects

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

Keep this medication out of the sight and reach of children.

Do not use this medicationafter 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.

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

Store below 25ºC.

Do not refrigerate or freeze.

After dissolution:

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

From a microbiological standpoint, the diluted solution must be used immediately. If not used immediately, the storage time of the ready-to-use solution and the conditions prior to use are the responsibility of the handler; in addition, the dilution must be carried out in validated and controlled aseptic conditions.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Cisplatino Pharmacia Composition

The active ingredient is cisplatino.

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

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

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

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

Appearance of Cisplatino Pharmacia and packaging contents

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

Packaging with 1 vial of 50 ml of concentrate containing 50 mg of cisplatino.

Packaging with 1 vial of 100 ml of concentrate containing 100 mg of cisplatino.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Pharmacia Nostrum, S.A.

Avda. de Europa 20B

Parque Empresarial La Moraleja

28108 Alcobendas, Madrid

Spain

Responsible manufacturer:

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

Last review date of this leaflet: July 2024

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)https://www.aemps.gob.es/

This information is intended solely for medical professionals or healthcare professionals:

Preparation and handling of the product

Single-use only.

Consult local guidelines for cytotoxics.

As with all antineoplastic products, caution is required in the processing of cisplatino. Dilution should be carried out in aseptic conditions in a protective box and should be performed by trained personnel in a designated area. If no protective box is available, the equipment should be supplemented with a mask and protective gloves. Extreme caution should be taken to avoid contact with the skin and mucous membranes. In the event of skin contact, wash with water and soap immediately. In cases of cutaneous contact, tingling, burns, and redness have been observed. In the event of contact with mucous membranes, they should be rinsed with abundant water. After inhalation, dyspnea, chest pain, throat irritation, and nausea have been reported.

In the event of cisplatino spillage, operators should use gloves and clean the spilled material with a sponge in the designated area. Rinse the area twice with water. Introduce all solutions and sponges into 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 turbid or a deposit that does not dissolve is observed, the vial should be discarded.

Damaged vials should be considered and treated with the same precautions as contaminated waste.Contaminated waste should be disposed of in specific containers for this purpose. See section “Disposal”.

Preparation for intravenous administration

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

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

Always inspect the injection before use. Only clear and particle-free solutions should be administered.

Do not place it in contact with aluminum-containing injection materials.

Do not administer without dilution.

To consult the chemical and physical stability in the use of undiluted solutions, see

section “Special precautions for storage: undiluted solution”.

Disposal

All materials used for preparation and administration, or those that have come into contact with cisplatino in any way, should be disposed of in accordance with local cytotoxic requirements. The remains of the medication and the materials used for preparation and administration should be destroyed in accordance with standard hospital procedures applicable to cytotoxic agents and in compliance with local requirements for the disposal of cytotoxic agents.

Incompatibilities

It should not come into contact with aluminum.Cisplatino can react with aluminum, forming a black precipitate of platinum.It should be avoided to come into contact with any utensils for i.v. administration, needles, catheters, and syringes containing aluminum. Cisplatino decomposes if it is 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 cisplatino in perfusion systems.

This medicine should not be mixed with any other except those mentioned in the previous section“Preparation for intravenous administration”.

Special precautions for storage

Medicament packaged for sale:

Concentrate for infusion solution 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 precipitates are formed that do not dissolve, the solution should not be used.

Diluted solution:

Do not store diluted solutions in the refrigerator or freezer.

After dilution in the indicated perfusion fluids:

The cisplatino 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.