CISPLATIN ACCORD 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Leaflet: information for the user

Cisplatino Accord 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.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

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

Cisplatino Accord contains the active substance cisplatin, which is part of a group of medicines called cytostatics used in the treatment of cancer. Cisplatin can be used alone, but it is most commonly used in combination with other cytostatics.

Cisplatin is able to destroy 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 be able to give you more information.

You should talk to a doctor if you do not feel better or if you feel worse.

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

Do not use cisplatin

• if you are allergic to cisplatin, similar cancer medicines, other platinum-containing compounds, or any of the other components of this medicine (listed in section 6)
• if you have a very low number of cells in your blood (called myelosuppression), (your doctor will check with a blood test)
• if you are breastfeeding.
• if you have severe kidney disease
• if you have hearing difficulties
• if you are dehydrated
• if you need to be vaccinated against "yellow fever"

Tell your doctor if any of the above applies to you before using this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Cisplatino Accord:

• If you have any symptoms of nerve damage (peripheral neuropathy) such as pins and needles, numbness, or poor sense of touch. You will be examined periodically to detect these symptoms and, if necessary, treatment may be interrupted.
• If you have received radiation therapy to the head

Your doctor will perform tests to determine the levels of calcium, sodium, potassium, and magnesium in your blood, as well as to check your blood count and liver and kidney function and your neurological function.

Cisplatin can affect the bone marrow, causing changes in the production of blood cells in the body, inform your doctor if you have unusual bleeding or bruising. Do not take aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other medicines without telling your doctor. Your doctor will perform regular blood tests and check for signs of infection.

Cisplatin can cause hearing problems (ototoxicity) and kidney problems (nephrotoxicity). Kidney function and hearing will be monitored before and during treatment. If you experience changes in your hearing, you should inform your doctor.

Tell your doctor if you plan to be vaccinated during treatment with Cisplatino, some live vaccines should be avoided as they can cause serious infections, and your response to other types of vaccines (inactivated) may be reduced.

Other medicines and Cisplatino Accord

Consult your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines, for example:

• Some antibiotics, such as cephalosporins, aminoglycosides, and amphotericin B, and some substances used for medical imaging can make the adverse effects of cisplatin worse, particularly kidney problems
• Some diuretic tablets called loop diuretics, antibiotics called aminoglycosides, and a cancer medicine called ifosfamide can make the adverse effect of hearing loss worse
• Bleomycin (cancer medicine), methotrexate (cancer or arthritis medicine), and paclitaxel (cancer medicine) may produce more side effects if cisplatin is also used
• Cisplatin may reduce the effectiveness of anticonvulsants (used to treat epilepsy), it may be necessary to monitor phenytoin levels in the blood
• The effectiveness of oral anticoagulants (e.g., warfarin) may be affected. Your doctor will monitor you with blood tests
• Buclizine, cyclizine, and meclozine (antihistamine medicines), loxapine, phenothiazines, and thioxanthenes (medicines used to treat psychiatric disorders) or trimethobenzamide (medicines used to prevent nausea and vomiting) may hide the symptoms of balance changes (such as dizziness or tinnitus)
• Cisplatin may worsen the adverse effects of the cancer medicine ifosfamide
• Pyridoxine (vitamin B6) and altretamine (cancer medicine) used in combination with cisplatin for the treatment of advanced ovarian cancer may reduce the recovery time. Your doctor will discuss this with you
• Bleomycin and etoposide (cancer medicines) used in combination with cisplatin and lithium (used to treat mental illnesses) may reduce lithium levels in the blood. It is recommended to monitor lithium levels
• The yellow fever vaccine should not be used at the same time as treatment with cisplatin due to the risk of death resulting from vaccination. An inactivated vaccine is recommended
• Medicines for gout such as allopurinol, colchicine, probenecid, or sulfinpyrazone reduce uric acid levels in the blood. Your doctor may need to change the dose of Cisplatino Inyectable.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

Due to the possible risk of birth defects, male and female patients must use contraceptive measures during treatment with cisplatin and for at least six months after the end of treatment.

Cisplatin should not be used during pregnancy unless your doctor clearly indicates it.

Ask your doctor or pharmacist for advice before taking any medicine.

Breastfeeding

Do not use this medicine if you are breastfeeding.

Fertility

Male patients treated with Cisplatino are advised not to have children during treatment and for six months after treatment. Treatment with cisplatin can cause permanent infertility in men. It is recommended that men who wish to be fathers in the future seek advice on sperm cryopreservation (freezing) before treatment.

Driving and using machines

Do not drive or use machines if any side effect occurs that may reduce your ability to do so.

Cisplatino Accord contains sodium

This medicine contains 3.5 mg of sodium (main component of table salt) per ml. This is equivalent to 0.18% of the maximum recommended sodium intake for an adult.

This medicine may be prepared with a solution that contains sodium. This should be taken into account if you are on a low-salt diet (sodium).

3. How to use Cisplatino Accord

Dosage and administration

Cisplatino Accord should only be administered by a specialist in cancer treatment.

The concentrate is diluted with a sodium chloride solution.

Cisplatin is usually administered by injection into a vein (intravenous infusion) over a period of 6 to 8 hours.

Support equipment should be available for the control of anaphylactic reactions.

Cisplatin should not come into contact with any material that contains aluminum.

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

Recommended dose

Cisplatin (monotherapy):

The following doses are recommended:

• Single dose of 50 to 120 mg/m² of body surface area (BSA), every 3-4 weeks.
• 15 to 20 mg/m²/day for 5 days, every 3-4 weeks.

Cisplatin in combination with other anticancer medicines (combination chemotherapy):

• 20 mg/m² of BSA or more, once every 3-4 weeks.

For the treatment of cervical cancer, cisplatin is used in combination with radiotherapy or other chemotherapy medicines.

A common dose is 40 mg/m² of BSA weekly for 6 weeks.

To avoid or reduce kidney problems, you should drink plenty of water in the 24 hours following treatment with Cisplatino Accord.

If you think you have received more Cisplatino Accord than you should

Your doctor will make sure you receive the correct dose for your condition. In case of overdose, you may experience more side effects. Your doctor will provide symptomatic treatment for these side effects. If you think you have received too much Cisplatino Accord, contact your doctor immediately.

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

4. Possible side effects

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

Tell your doctor immediately if you notice any of the following symptoms

• Severe allergic reaction; you may experience sudden rash, itching (hives), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), flushing, and you may feel like you are going to faint
• Severe chest pain radiating to the jaw or arm with sweating, shortness of breath, and nausea (heart attack)
• Fainting or seizures
• Hearing problems - you may experience ringing in the ears or hearing loss (ototoxicity)
• Kidney and urinary problems
• Excessive tiredness and general feeling of being unwell, which could be symptoms of a decrease in blood cell levels (myelosuppression). This would be confirmed by a blood test.

These are serious side effects. You may need urgent medical attention.

Very common: may affect more than 1 in 10 people:

• Reduction of bone marrow function (which can affect the production of blood cells)
• Reduction of white blood cells, which makes infections more likely (leukopenia)
• Reduction of platelets, which increases the risk of bruising and bleeding (thrombocytopenia)
• Reduction of red blood cells, which can cause weakness and pale skin (anemia)
• Reduction of sodium levels in the blood
• High temperature

Common: may affect up to 1 in 10 people:

• Severe pain or swelling in any of your legs, chest pain, difficulty breathing (possibly indicating painful blood clots in a vein)
• Fast, irregular, or slow heartbeats
• Sepsis (blood poisoning)

Uncommon: may affect up to 1 in 100 people:

• Severe allergic reaction (see above)
• Hearing problems (ototoxicity)
• Decrease in magnesium levels in the blood
• Abnormal sperm production

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

• Increased risk of acute leukemia
• Seizures
• Fainting, headache, confusion, and loss of vision
• Loss of certain types of brain function, including brain dysfunction characterized by spasms and decreased level of consciousness
• Brain dysfunction (confusion, difficulty speaking, sometimes blindness, memory loss, and paralysis)
• Heart attack
• Inflammation of the mucous membranes of the mouth (stomatitis),
• Peripheral neuropathy of the sensory nerves, characterized by tingling, itching, or numbness without cause and sometimes with loss of taste, touch, vision, sudden stabbing pains from the neck down to the legs when leaning forward

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

• Cardiac arrest

Frequency not known: frequency cannot be estimated from the available data

• Signs of infection such as fever or sore throat
• Hemolytic anemia
• Inadequate release of the vasopressin hormone (ADH) that can lead to low sodium levels in the blood and fluid retention
• Increase in amylase (enzyme) in the blood
• Dehydration
• Decrease in calcium, phosphate, and potassium levels in the blood
• High levels of uric acid in the blood
• Muscle cramps
• Spinal disease that can cause a sensation of electric shocks passing through your limbs
• Brain dysfunction (confusion, unintelligible speech, sometimes blindness, memory loss, and paralysis)
• Stroke
• Loss of taste
• Vision problems (blurred vision, unusual colors, loss of vision, or eye pain)
• Ringing in the ears or deafness
• Heart problems
• Unusually cold or white hands and feet
• Tingling, numbness, or tremors in your hands, feet, arms, or legs
• Persistent headache
• Feeling of nausea
• Loss of appetite, anorexia
• Hiccups
• Diarrhea
• Increase in liver enzymes, increase in bilirubin
• Difficulty breathing
• Difficulty breathing, chest pain, especially when inhaling, and coughing up blood
• Kidney or urinary problems
• Hair loss
• Rash
• Extreme fatigue and weakness
• Inflammation or pain at the injection site
• Cramps or spasms
• Burning or stinging sensation
• Unexpected bleeding or bruising
• Hemolytic-uremic syndrome that can cause changes in the kidneys and blood

Cisplatino Accord may cause problems with your blood, liver, and kidneys. Your doctor will perform blood tests to monitor these problems and check the levels of electrolytes.

Reporting of side effects:

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cisplatino Accord

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

Store the vial in the outer packaging to protect it from light. Do not refrigerate or freeze.

If a precipitate or crystals form as a result of exposure to low temperatures, redisolve by keeping the vials at room temperature until a clear solution is obtained.

The product should be discarded if the solution does not become clear after vigorous shaking.

Do not use this medicine after the expiry date stated on the outer carton after "EXP". The expiry date is the last day of the month indicated.

Do not use this medicine if you notice any visible signs of deterioration.

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.

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

6. Container contents and additional information

Composition of Cisplatino Accord

The active ingredient is cisplatin.

Each milliliter (ml) of solution contains 1 milligram (mg) of cisplatin. This medication is presented in amber glass containers called vials.

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

Appearance of Cisplatino Accord and container contents

Cisplatino Accord is a clear, colorless to pale yellow solution in an amber glass vial with a practically particle-free, transparent stopper.

Container with 1 vial of 10 ml injection containing 10 mg of cisplatin.

Container with 1 vial of 25 ml injection containing 25 mg of cisplatin.

Container with 1 vial of 50 ml injection containing 50 mg of cisplatin.

Container with 1 vial of 100 ml injection containing 100 mg of cisplatin.

Only some pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona, Spain.

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,

95-200 Pabianice,

Poland

Accord Healthcare Single Member S. A

64th Km National Road Athens

Lamia, 32009

Greece

This pharmaceutical product is authorized in the Member States of the EEA under the following names

Date of last revision of this leaflet: April 2023

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

Information intended exclusively for healthcare professionals:

Preparation and handling of the product

As with all antineoplastic products, caution is required when handling cisplatin. Dilution should be carried out under aseptic conditions and should be performed by trained personnel in an area specifically designated for this purpose. Protective gloves should be worn and precautions should be taken to avoid contact with the skin and mucous membranes. In case of skin contact, wash immediately with water and soap. 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.

Pregnant women should avoid contact with cytostatics. Cisplatin should not be used during pregnancy unless clinicians consider that the risk is justified in an individual patient.

Organic waste material 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 placed in specific waste 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:

• 0.9% sodium chloride
• 0.9% sodium chloride / 5% glucose mixture (1:1), (resulting final concentrations: 0.45% sodium chloride, 2.5% glucose)
• 0.9% sodium chloride and 1.875% mannitol for injection
• 0.45% sodium chloride, 2.5% glucose, and 1.875% mannitol for injection

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

If a precipitate or crystals are observed inside the vial, keep the vial at room temperature (20°C - 25°C) until a clear solution is obtained. Protect the unopened container from light. The product should be discarded if the solution does not become clear after vigorous shaking.

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

DO NOT administer it undiluted.

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

Although cisplatin is usually administered intravenously, it has also been administered by intraperitoneal instillation to patients with malignant intraperitoneal neoplasms (e.g., ovarian tumors). This route of administration allows high concentration gradients to be achieved between intraperitoneal and plasma levels of the medication.

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. Medicines should not be thrown away via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

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.

In the absence of compatibility studies, this medication should not be mixed with others.

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

Special precautions for storage

Medicament packaged for sale:

Concentrate for Solution for Infusion 1 mg/ml

Undiluted solution: store the vial in the outer packaging to protect it from light. Do not refrigerate or freeze. If the solution is not transparent or insoluble precipitates form, the solution should not be used.

Diluted solution:

To consult the storage conditions of the diluted medication: see below.

"Concentrate for Solution for Infusion after dilution".

Do not refrigerate or freeze.

Concentrate for Solution for Infusion after dilution.

After dilution

The chemical and physical stability in use after dilution with the recommended infusion liquids indicates that, after dilution with the recommended intravenous liquids, the cisplatin injection remains stable for 24 hours at room temperature (20-25°C).

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