Label:Information for the User

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

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

• Keep this label,as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

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

2.What you need to know before starting to use Cisplatino Accord

3.How to use Cisplatino Accord

4.Possible adverse effects

5.Storage of Cisplatino Accord

6.Contents of the container and additional information

Cisplatino Accord contains the active substancecisplatino which is part of a group of medicines called cytostatics used in the treatment of cancer.Cisplatino may be used alone, but it is most often used in combination with other cytostatics.

Cisplatino is able to destroy 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 may provide you with more information.

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

No use cisplatino

• If you are allergic to cisplatin, similar cancer medications, other platinum-containing compounds, or any of the other components of this medication (listed in section 6)
• If you have a very low number of blood cells (myelosuppression), (your doctor will monitor it 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

Inform your doctor if any of the above affect you before using this medication.

Warnings and precautions

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

• If you have any symptoms of nerve damage (peripheral neuropathy) such as pins and needles, numbness, or poor sensation. 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 your blood calcium, sodium, potassium, and magnesium levels, as well as to check your blood count and liver and kidney function and neurological function.

Cisplatin may affect the bone marrow, causing changes in blood cell production in the body. Inform your doctor if you have unusual bleeding or bruising. Do not take aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or other medications without informing your doctor. Your doctor will perform blood tests frequently and check for signs of infection.

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

Inform your doctor if you plan to be vaccinated during treatment with Cisplatin, as some live vaccines may cause severe infections, and your response to other types of vaccines (inactivated) may be reduced.

Other medications and Cisplatin Accord

Contact your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication, for example:

• Some antibiotics, such as cephalosporins, aminoglycosides, and amphotericin B, and some substances used for medical imaging may worsen the adverse effects of cisplatin, particularly kidney problems
• Some tablets called diuretics, antibiotics called aminoglycosides, and a cancer medication called ifosfamide may worsen the adverse effect of hearing loss
• Bleomycin (cancer medication), methotrexate (cancer medication or arthritis medication), and paclitaxel (cancer medication) may produce more adverse effects if used with cisplatin
• 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 (antihistamines), loxapine, phenothiazines, and thioxanthenes (medications used to treat psychiatric disorders) or trimethobenzamide (medications used to prevent nausea and vomiting)may mask symptoms of balance changes (such as dizziness or tinnitus)
• Cisplatin may worsen the adverse effects of the cancer medication ifosfamide
• Piridoxine (vitamin B6) and altretamine (cancer medication) used in combination with cisplatin for the treatment of advanced ovarian cancer may reduce recovery time. Your doctor will discuss this with you
• Bleomycin and etoposide (cancer medications) 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 cisplatin treatment due to the risk of death from vaccination. It is recommended to use an inactivated vaccine
• Medications such as allopurinol, colchicine, probenecid, or sulfinpyrazone reduce uric acid levels in the blood. It may be necessary for your doctor to change your Cisplatin Injection dose.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

Due to the potential risk of birth defects, male and female patients should take contraceptive measures during treatment with cisplatin and, at least, for six months after completing treatment.

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

Consult your doctor or pharmacist before taking any medication.

Breastfeeding

Do not use this medication if you are breastfeeding.

Fertility

Male patients treated with Cisplatin are advised not to father children during treatment and for at least six months after treatment. Cisplatin treatment may cause permanent sterility in men.in men. It is recommended that men who wish to become fathers in the future seek advice on sperm cryopreservation (freezing) before treatment.

Driving and operating machinery

Do not drive or operate machinery if any adverse effect may impair your ability to do so.

Cisplatin Accord contains sodium

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

This medication may be prepared with a solution that contains sodium. This should be taken into account if you follow a low-sodium diet.

Dosage and Administration

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

The concentrate is diluted with a sodium chloride solution.

Cisplatino is administered primarily through an injection into a vein (intravenous infusion) over a period of 6 to 8 hours.

Equipment for supporting the control of anaphylactic reactions should be available.

Cisplatino should not come into contact with any material containing aluminum.

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

Recommended Dose

Cisplatino (monotherapy):

The following doses are recommended:

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

Cisplatino in combination with other anticancer medications (combination chemotherapy):

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

For the treatment of cervical cancer, cisplatino is used in combination with radiation therapy or other chemotherapy medications.

A typical dose is 40 mg/m² of SC weekly for 6 weeks.

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

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

Your doctor will ensure that you receive the correct dose for your condition.In the event of an overdose, you may experience more side effects.Your doctor will provide symptomatic treatment for these side effects.If you believe you have received too much Cisplatino Accord, contact your doctor immediately.

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

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

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

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

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

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

• Reduction of bone marrow function (which may affect blood cell production)
• Reduction of white blood cells, which makes infections more likely (leucopenia)
• Reduction of platelets, which increases the risk of bruising and bleeding (thrombocytopenia)
• Reduction of red blood cells, which may cause weakness and make your skin appear pale (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 clots in a vein)
• Irregular, rapid, or slow heartbeats
• Sepsis (blood poisoning)

Rare: may affect up to 1 in 100 people:

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

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

• Increased risk of acute leukemia
• Convulsions
• Fainting, headache, confusion, and loss of vision
• Loss of certain types of brain function, including cerebral dysfunction characterized by spasms and decreased level of consciousness
• Cerebral dysfunction (confusion, difficulty speaking, sometimes blindness, memory loss, and paralysis)
• Heart attack
• Mucous membrane inflammation of the mouth (stomatitis)
• Peripheral neuropathy of sensory nerves, characterized by tingling, itching, or numbness without cause and sometimes with loss of taste, touch, vision, sudden pinching sensations from the neck to the back and down to the legs when leaning forward

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

• Cardiac arrest

Unknown frequency: the frequency cannot be estimated from available data

• Signs of infection such as fever or sore throat
• Hemolytic anemia
• Inadequate release of vasopressin hormone (ADH), which may lead to low sodium levels in the blood and fluid retention
• Increased amylase (enzyme) in the blood
• Dehydration
• Decreased levels of calcium, phosphate, and potassium in the blood
• High levels of uric acid in the blood
• Muscle cramps
• Spinal disease that may cause a sensation of electric discharges passing through your limbs
• Cerebral dysfunction (confusion, incoherent speech, sometimes blindness, memory loss, and paralysis)
• Stroke
• Loss of taste
• Visual problems (blurred vision, strange colors, loss of vision, or eye pain)
• Tinnitus or hearing loss
• Heart problems
• Unusually cold or pale hands and feet
• Tingling, numbness, or tremors in your hands, feet, arms, or legs
• Persistent headache
• Nausea sensation
• Loss of appetite, anorexia
• Hiccups
• Diarrhea
• Increased liver enzymes, increased bilirubin
• Difficulty breathing
• Difficulty breathing, chest pain, especially when inhaling, and coughing up blood
• Renal 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
• Syndrome of hemolytic uremia that may cause changes in the kidneys and blood

Cisplatino Accord may cause problems with your blood, liver, and kidneys. Your doctor will make blood tests to monitor these problems and check your electrolyte levels.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of 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 medicine.

Keep this medication 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 precipitation or crystals form as a result of exposure to low temperatures, redisolve by storing 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 medication after the expiration date that appears on the outer carton after “CAD.”The expiration date is the last day of the month indicated.

Do not use this medication if you observe visible signs of deterioration.

All materials used for preparation and administration, or those that have come into contact with cisplatino in any way, must be disposed of in accordance with local cytotoxic requirements.

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

Composition of Cisplatino Accord

The active principle is cisplatino.

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

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

Aspect of Cisplatino Accord and contents of the container

Cisplatino Accord is a transparent, colorless to pale yellow solution in an amber glass vial with a transparent flip-off cap.

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

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

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

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

Only some sizes of containers may be commercially available.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona. Spain.

Responsible for manufacturing

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 medicinal product is authorized in the member states of the EEA under the following names

Last review date of this leaflet: April 2023

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

Information intended exclusively for medical or health professionals:

Preparation and handling of the product

As with all antineoplastic products, caution is required in the processing of cisplatino.The dilution must be carried out in aseptic conditions and must be carried out by trained personnel in a specifically designated area.Protective gloves andextreme precautions must be taken to avoid contact with the skin and mucous membranes.In the event of skin contact, wash with water and soap immediately.After skin contact, tingling, burns, and redness have been observed.In the event of contact with mucous membranes, they must be rinsed with abundant water.After inhalation, dyspnea, chest pain, throat irritation, and nausea have been reported.

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

Organic waste and vomit must be disposed of carefully.

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

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

Preparation for intravenous administration

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

• sodium chloride 0.9%
• mezcla de cloruro de sodio al 0.9%/glucosa al 5% (1:1), (concentraciones finales resultantes: cloruro de sodio al 0.45%, glucosa al 2.5%)
• sodium chloride 0.9% and manitol 1.875%, for injection
• sodium chloride 0.45%, glucose 2.5% and manitol 1.875%, for injection

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

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

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

Do not administer without diluting.

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

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

Disposal

All materials used for preparation and administration, or that have come into contact with cisplatino in any way, must be disposed of in accordance with local requirements for cytotoxics.Medicines must not be thrown away through the drains or in the trash.Ask your pharmacist how to dispose of medicines that you do not need.This will help protect the environment.

Incompatibilities

It must not come into contact with aluminum.Cisplatino reacts with aluminum, forming a black precipitate of platinum.Aluminum-containing utensils for i.v. administration, needles, catheters, and syringes must be avoided.

Cisplatino decomposes when dissolved in media with low chloride content; the chloride concentration must be at least equivalent to 0.45% sodium chloride.

Without compatibility studies, this medication should not be mixed with other medications.

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

Special Precautions for Storage

Medicinal product packaged for sale:

Concentrate for Solution for Infusion 1mg/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 precipitates are formed that do not dissolve, the solution must 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 infusion liquids described in the “Preparation and handling of the product”section indicates that, after dilution with the recommended intravenous liquids, the cisplatino injection remains stable for 24hours at room temperature (20-25°C).

From a microbiological point of view, 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 manipulator; in addition, the dilution must be carried out in validated and controlled aseptic conditions.