Cisplatin Pharmacia 1 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

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

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

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

Cisplatin is capable of destroying cells in your body that can cause certain types of cancer (testicular tumour, ovarian tumour, bladder tumour, head and neck epithelial tumour, lung cancer, and cervical cancer in combination with radiotherapy).

Your doctor will provide you with further information.

2. What you need to know before using Cisplatino Pharmacia

Do not use Cisplatino Pharmacia:

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

Warnings and Precautions:

Talk to your doctor, pharmacist, or nurse before starting treatment with Cisplatino Pharmacia.

• If you have high levels of uric acid or proteins in your blood, which may be detected in blood tests.
• If you have nerve damage (tingling and numbness in hands and feet) not caused by cisplatin.
• If you have previously received radiotherapy to the head.
• If you currently have an infection.
• If you plan to have children (see section "Pregnancy, breastfeeding and fertility"). You should use an effective method of contraception for at least 6 months after treatment with cisplatin.

Inform your doctor, even if any of the above conditions occurred in the past.

Monitoring before and during treatment:

Your doctor should perform tests to check levels of calcium, sodium, potassium, and magnesium in your blood, as well as your blood count, liver and kidney function, and neurological function. These tests may be performed weekly throughout your treatment.

Your hearing should be tested before each dose of Cisplatino Pharmacia. Cases of delayed-onset hearing loss have been reported in pediatric populations. Long-term follow-up is recommended in these patients.

During treatment:

If cisplatin spills, contaminated skin must be washed immediately with soap and water. If cisplatin is accidentally injected outside the blood vessels (extravasation), administration must be stopped immediately. Cisplatin on the skin may cause tissue damage (cellulitis, fibrosis, and necrosis).

Taking Cisplatino Pharmacia with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Please note that these instructions may also apply to medicines you have taken previously or may take in the future.

• Medicines that suppress bone marrow function or radiation therapy may increase the adverse effects of cisplatin on the bone marrow.
• The toxicity of bleomycin and methotrexate (other anticancer medicines) may increase when administered with or after cisplatin, due to potentially reduced renal elimination caused by cisplatin-induced nephrotoxicity.
• Medicines used to treat high blood pressure (antihypertensives such as furosemide, hydralazine, diazoxide, or propranolol) may increase the kidney toxicity of cisplatin.
• Cisplatin kidney toxicity may be worsened when given with other medicines that can harm the kidneys, such as those used to prevent/treat certain infections (antibiotics: cephalosporins, aminoglycosides, and/or antifungals: amphotericin B) and contrast agents (used in medical imaging).
• Cisplatin may also affect hearing when given with aminoglycosides.
• If you take medicines for gout during treatment with cisplatin, the dose of these medicines (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone) may need to be adjusted, as cisplatin may increase blood uric acid levels.
• Administration of medicines that increase urine production (loop diuretics) together with cisplatin (when the cisplatin dose does not exceed 60 mg/m² and urine output is not less than 1,000 ml in 24 hours) may cause kidney and ear toxicity.
• Early signs of hearing problems (such as dizziness and tinnitus) may be masked if you are given medicines for hypersensitivity, nausea, or mental health conditions (antihistamines such as buclizine, cyclizine, loxapine, meclizine, phenothiazines, thioxanthenes, and/or trimethobenzamides) during cisplatin treatment.
• Cisplatin in combination with ifosfamide may cause ear damage, increased protein loss from the body, and increased kidney toxicity.
• Administration of pyridoxine and altretamine may reduce the response to cisplatin treatment.
• Cisplatin in combination with bleomycin and vinblastine may cause pale or bluish discoloration of fingers and/or toes (Raynaud's phenomenon).
• Administration of cisplatin with paclitaxel or in combination with docetaxel may cause severe nerve damage.
• Regular monitoring of lithium levels is recommended, as reduced blood lithium levels have been observed after treatment with cisplatin in combination with bleomycin and etoposide.
• Cisplatin reduces blood levels of certain antiepileptic medicines (such as phenytoin), thereby reducing their effectiveness in treating epilepsy. You should not start a new epilepsy treatment while receiving cisplatin. (See "Do not take Cisplatino Pharmacia").
• Penicillamine may reduce the effectiveness of Cisplatino Pharmacia.
• Cisplatin may negatively affect medicines that prevent blood clotting (anticoagulants, such as coumarins/warfarin). Therefore, more frequent monitoring of blood clotting is recommended when these medicines are used together.
• Cisplatin in combination with cyclosporine may cause immunosuppression with risk of white blood cell (lymphocyte) proliferation.
• You should not receive live virus vaccines (including the yellow fever vaccine) while undergoing this treatment or within the first three months after completing cisplatin treatment.

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

Pregnancy, breastfeeding and fertility

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

Cisplatin must not be used during pregnancy unless specifically prescribed by your doctor.

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

Cisplatin Pharmacia must not be used by women who are breastfeeding and for 4 weeks after treatment, as cisplatin is excreted in breast milk.

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

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

Driving and use of machinery

Cisplatin may cause drowsiness and/or vomiting. If you experience any of these effects, avoid operating machinery requiring special attention.

Cisplatin Pharmacia contains sodium

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

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

3. How to use Cisplatino Pharmacia

Dosage and method of administration

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

Cisplatino must be administered only by intravenous infusion (injection into a vein). The prepared infusion should be given over a period of 6 to 8 hours. Supportive equipment must be available to manage possible allergic reactions.

Cisplatino must not come into contact with materials containing aluminum.

Cisplatino is recommended for use in children, adolescents, and adults.

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

Cisplatino Pharmacia (monotherapy):

The following doses are recommended:

• A single dose 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 typical dose is 40 mg/m² weekly for 6 weeks.

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

To prevent or reduce kidney problems, it is recommended that you drink large amounts of water for a period of 24 hours after treatment with cisplatino.

If you receive more Cisplatino 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 kidney failure, liver failure, hearing loss, changes in vision, decreased production of blood cells, and conditions such as nausea, vomiting, and nerve inflammation. Your doctor may provide symptomatic treatment for these adverse effects. If you think you have been given too much cisplatino, contact your doctor immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

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

• Sudden signs of allergy such as rash, itching, or hives, swelling of the face, lips, mouth or throat, shortness of breath or wheezing, increased heart rate, and drop in blood pressure,
• Decrease in the number of all types of blood cells due to bone marrow suppression, 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, weakness, or shortness of breath), and platelets (which increases the risk of bruising and bleeding (thrombocytopenia)),
• A disease state characterized by a reduction in red blood cells, platelets, and kidney failure (hemolytic uremic syndrome),
• Suppression of the immune system may lead to more frequent infections, and blood poisoning (sepsis) may occur,
• Overproduction of a hormone causing 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 part of the brain due to bleeding or reduced blood supply, which may cause weakness in arms or legs, headache, dizziness and confusion, difficulty swallowing, and difficulty speaking (stroke),
• Rapid increase in abnormal white blood cells (symptoms may include feeling very tired, bleeding, bruising, and increased risk of infections) (acute leukemia),
• Problems with the spinal cord, which may lead to numbness, weakness, loss of balance, and pain in the back, neck, and legs,
• Loss of certain brain functions that may lead to excessive fatigue, fast 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 at the back of the eye,
• Loss of hearing or deafness,
• Blockage in blood vessels of the heart, which may cause chest pain spreading to shoulders, neck, or jaw (heart attack),
• Heart blood vessel disease, possibly due to thickening of the walls of these vessels, reducing their size and restricting blood flow to the heart,
• Lung infection, which may cause fever, chills, difficulty breathing, cough, sputum, and coughing up blood (pneumonia) or respiratory failure,
• Blockage of blood vessels in the lungs,
• Kidney problems (you may notice back pain, produce little or no urine, or have cloudy or bloody urine) or kidney failure,
• Infection or injury at the injection site.

Other possible side effects may occur:

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

Bone marrow disorder, decreased platelets (thrombocytopenia), decreased white blood cells (leukopenia), decreased number of red blood cells (anemia).

Decreased levels of sodium in the blood (hyponatremia).

Fever.

Common (may affect up to 1 in 10 people)

Infection (sepsis).

Nervous system damage.

Changes in heart rhythm (arrhythmias), including slow heart rate (bradycardia) and fast heart rate (tachycardia).

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

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

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

Severe pain or swelling 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 levels of magnesium in the blood.

Hearing problems (ototoxicity).

Sperm formation disorder and abnormal ovulation, painful abnormal breast development in men (gynecomastia).

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

A type of blood cancer (leukemia).

Decreased immune system function.

Increased levels of cholesterol in the blood (hypercholesterolemia).

Seizures, nerve damage affecting signals to the brain and spinal cord (peripheral neuropathy), damage to the white matter of the brain (leukoencephalopathy and reversible posterior leukoencephalopathy syndrome).

Inflammation of the optic nerve, impaired eye movement.

Myocardial infarction, heart artery disorders.

Increased blood pressure (hypertension).

Mouth ulcers (stomatitis).

Increased blood albumin levels.

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

Damage, thickening, and partial blockage of small blood vessels and capillary disorders in the kidneys (thrombotic microangiopathy combined with hemolytic uremic syndrome).

Allergic reaction.

Increased levels of iron in the blood.

Seizures.

Cardiac arrest.

Frequency not known (cannot be estimated from available data)

Infections that have led to patient death.

A type of red blood cell disorder.

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

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

Stroke, loss of taste, electric shock-like sensation running down the spine (Lhermitte's syndrome), myelopathy, and other nerve disorders.

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

Ringing in the ears (tinnitus), deafness.

Heart disorders.

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

Blockage of a pulmonary artery (pulmonary embolism).

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

Skin rash, hair loss (alopecia).

Muscle cramps.

Kidney function disorders.

Tiredness, malaise.

Reaction at the injection site, which may cause pain, fluid retention, and redness.

Abnormalities in certain 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 not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cisplatin Pharmacia

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

Do not use this medicine after the expiry date which is stated on the vial and on the outer packaging after 'EXP'. The expiry date refers to the last day of the month indicated.

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

Store below 25°C.

Do not refrigerate or freeze.

After reconstitution:

Cisplatin injection remains stable for 24 hours at room temperature (20–25°C). 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 should be used immediately. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user; additionally, dilution must be carried out under validated and controlled aseptic conditions.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers that you no longer need. This will help protect the environment.

6. Contents of the package and other information

Composition of Cisplatin Pharmacia

The active substance is cisplatin.

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

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

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

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

Appearance of Cisplatin Pharmacia and contents of the package

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

Pack containing 1 vial of 50 ml concentrate containing 50 mg of cisplatin.

Pack containing 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

Hermeslaan 11

1932 Zaventem

Belgium

Date of the most recent review of this leaflet: July 2024

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

This information is intended for healthcare professionals only:

Preparation and handling of the product

For single use only.

Refer to local guidelines for cytotoxic drugs.

As with all antineoplastic agents, caution is required when handling cisplatin. Dilution must be performed under aseptic conditions in a safety cabinet by trained personnel in a designated area. If a safety cabinet is not available, personnel should use a protective mask and gloves. Extreme care must be taken to avoid contact with skin and mucous membranes. In case of skin contact, wash immediately with soap and water. Cases of skin contact have been associated with tingling, burning, and redness. In case of contact with mucous membranes, they should be thoroughly rinsed with water. Following inhalation, dyspnea, chest pain, throat irritation, and nausea have been reported.

In case of cisplatin spillage, personnel should wear gloves and clean up the spilled material using a sponge in a designated area. Rinse the area twice with water. Place all solutions and sponges into a plastic bag and seal it.

Pregnant women should avoid contact with cytostatic agents.

Biological waste and vomit must be handled carefully.

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

Damaged vials should be considered and handled with the same precautions as contaminated waste. Contaminated waste must be placed in specific waste containers. See section "Disposal".

Preparation for intravenous administration

Withdraw the required amount of solution from the vial and dilute it with at least 1 litre of one of the following solutions:

• Sodium chloride 9 mg/ml (0.9%);
• Mixture 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 solution before use. Only clear solutions without visible particles should be administered.

DO NOT allow contact with injection materials containing aluminium.

DO NOT administer undiluted.

For information on chemical and physical stability of undiluted solutions, see section "Special precautions for storage: undiluted solution".

Disposal

All materials used in the preparation and administration of cisplatin, or that have come into contact with it in any way, must be disposed of in accordance with local requirements for cytotoxic agents. Leftover medication and materials used in preparation and administration must be destroyed according to standard hospital procedures applicable to cytotoxic agents and in compliance with local regulations for disposal of cytotoxic agents.

Incompatibilities

Cisplatin must not come into contact with aluminium. Cisplatin may react with aluminium, leading to the formation of a black precipitate of platinum. Contact with any intravenous administration equipment, needles, catheters, or syringes containing aluminium must be avoided. Cisplatin decomposes when dissolved in media with low chloride content; the chloride concentration must be at least equivalent to 0.45% sodium chloride.

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

This medicinal product must not be mixed with other products except those mentioned in the section above "Preparation for intravenous administration".

Special Storage Precautions

Medicinal product 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 from light. If the solution is not clear or insoluble precipitates form, the solution must not be used.

Diluted solution:

Do not store diluted solutions in the refrigerator or freezer.

After dilution in the infusion fluids indicated above:

Cisplatin injection remains stable for 24 hours at room temperature (20–25°C), protected from light.

From a microbiological standpoint, the diluted solution should be used immediately.