Package Insert: Information for the User

Carboplatin Accord 10 mg/ml Concentrate for Solution for Infusion EFG

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

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

Carboplatino Accord is a cancer medication. Treatment with a cancer medication is sometimes referred to as cancer chemotherapy.

Carboplatino Accord is used in adults for the treatment of certain types of lung cancer and ovarian cancer.

Do not use Carboplatino Accord

• If you are allergic to Carboplatino or any of the other components of this medication (listed in section 6).
• If in the past you have had hypersensitivity to similar medications that contain platinum.
• If you have severe kidney problems.
• If you have fewer blood cells than normal (your doctor will check this with a blood test).
• If you have bleeding tumors.
• If you are to receive the yellow fever vaccine or have recently received it.

Consult your doctor if any of the above applies to you before using it.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before receiving the Carboplatino infusion.

• If you are pregnant or if there is a possibility that you are pregnant.
• If you are breastfeeding.
• If you have mild kidney disease. Your doctor will monitor you more regularly.
• If you are over 65 years old.
• If you experience any hearing problems.
• If you have been treated with cisplatino or similar oncological medications in the past, carboplatino may cause abnormalities in your nervous system, such as numbness or hearing and vision problems. Your doctor will advise you regularly.
• If you have headaches, altered mental function, seizures, and abnormal vision, from blurred vision to loss of vision.
• If you experience extreme fatigue and difficulty breathing, with a decrease in the number of red blood cells (hemolytic anemia), alone or combined with a low platelet count, abnormal bleeding (thrombocytopenia), and kidney disease if you urinate little or not at all (symptoms of uremic-hemolytic syndrome).
• If you have a fever (temperature equal to or greater than 38°C), or chills, which may be signs of infection. You may be at risk of contracting a blood infection.

During treatment with carboplatino, you will be given medications to help reduce a potentially fatal complication, known as tumor lysis syndrome, caused by chemical changes in the blood due to the breakdown of cancer cells that die and release their contents into the bloodstream.

Children and adolescents

The safety and efficacy of carboplatino have not yet been established in children and adolescents.

Other medications and Carboplatino Accord

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication, for example:

• Medications that may reduce the number of blood cells, at the same time as carboplatino, may require changes in the dose and frequency of carboplatino treatment.
• Some antibiotics called aminoglycosides, vancomycin, or capreomycin, at the same time as carboplatino, may increase the risk of kidney or hearing problems.
• Some water tablets (diuretics), simultaneously with carboplatino, may increase the risk of kidney or hearing problems.

Live or attenuated vaccines (for the yellow fever vaccine see section 2 “Do not use Carboplatino Accord”)

• Anticoagulants, such as warfarin, simultaneously with carboplatino, may require an increase in the frequency of blood coagulation monitoring.
• Phenobarbital and fosphenytoin (used to treat various types of seizures and attacks) simultaneously with carboplatino may increase the risk of seizures.
• Other medications that reduce the activity of the immune system (for example, cyclosporine, tacrolimus, or sirolimus)

Inform your doctor if you are using, have used recently, or may need to take other medications, even those purchased without a prescription.

Use of Carboplatino Accord with alcohol

No interactions between carboplatino and alcohol are known. However, you should discuss it with your doctor, as carboplatino may affect the liver's ability to process alcohol.

Pregnancy, breastfeeding, and fertility

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

Contraception in men and women

Women of childbearing age should avoid becoming pregnant and use effective contraceptive methods during treatment and for at least 6 months after the last dose. Inform your doctor immediately if you become pregnant during this period.

Men should use effective contraceptive methods and not father children during treatment and for at least 3 months after the last dose.

Pregnancy

This medication should not be used during pregnancy unless your doctor considers it necessary. This medication may cause severe birth defects.

Breastfeeding

You should not breastfeed during treatment and for at least one month after the last dose.

Fertility in men and women

Treatment with this medication may temporarily or permanently reduce fertility in men and women. Discuss fertility preservation with your doctor before starting treatment.

Driving and operating machinery

Do not drive or operate machinery if you experience any adverse effects that may impair your ability to do so, such as nausea, vomiting, worsening vision, or changes in hearing and vision.

This medication will be administered through intravenous infusion (drip), between 15 and 60 minutes.

Dose

Your doctor will calculate the correct dose of carboplatino for you and the frequency at which it will be given.

The dose will depend on your physical condition, weight, and kidney function. Your doctor will tell you the state of your kidneys through blood and urine tests. Blood tests will be performed after your carboplatino dose. You will also undergo checks for nerve damage and hearing loss.

There is a possibility of being approximately 4 weeks between each carboplatino dose.

If you use more Carboplatino Accord than you should

This medication will be administered in a hospital, under the supervision of a doctor. It is unlikely that you will be given too much or too little, nonetheless, consult with your doctor or nurse if you have any doubts.

If you interrupt treatment with Carboplatino Accord

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

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

Inform your doctor immediatelyif you notice any of the following symptoms:

• Unusual bruises, bleeding, or signs of infection such as sore throat and fever (very common, may affect more than 1 in 10 people).
• Severe allergic reactions (anaphylaxis/anaphylactic reactions) – you may experience a sudden rash with itching (urticaria), swelling of the hands, feet, ankles, face, lips, or throat (which may cause difficulty swallowing or breathing) and may feel like you are going to faint (common, may affect up to 1 in 10 people)
• Haemolytic-uraemic syndrome (a disease characterized by acute renal failure), decreased urination or blood in the urine (not known, the frequency cannot be estimated from the available data)
• Muscle cramps, muscle weakness, confusion, visual disturbances or loss, irregular heartbeats, renal insufficiency, or abnormal results in blood tests (symptoms of tumour lysis syndrome that may be caused by the rapid breakdown of cancer cells) (see section 2) (not known, the frequency cannot be estimated from the available data).
• Stroke (numbness or weakness in the face, arm, or leg, especially on one side of the body) (not known, the frequency cannot be estimated from the available data)
• Obstruction of a blood vessel (embolism and veno-occlusive disease), swelling or sensitivity in the leg or arm (not known, the frequency cannot be estimated from the available data)
• Chest pain that may be a sign of a potentially severe allergic reaction called Kounis syndrome (not known, the frequency cannot be estimated from the available data)
• Swelling of the skin, often on the face and lips (angioedema) (rare, may affect up to 1 in 1,000 people)

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

Other side effects that may occur:

Very common (may affectmore than 1 in 10 patients):

• Fatigue, difficulty breathing, and paleness caused by anemia (a condition in which the number of red blood cells decreases)
• Feeling sick (nausea) or being sick (vomiting)
• Abdominal pain and cramps

Tests may also show:

• Abnormalities in red blood cells, white blood cells, and platelets (myelosuppression).
• Increased levels of urea in the blood
• Decreased levels of sodium, potassium, calcium, and magnesium in the blood
• Decreased creatinine clearance
• Abnormal levels of liver enzymes

Common (may affectup to 1 in 10 patients):

• Diarrhea or constipation.
• Rash and/or itching on the skin
• Tinnitus or changes in hearing
• Hair loss
• Flu-like symptoms
• Infections
• Numbness and/or tingling in the hands, feet, arms, or legs
• Feeling of burning or prickling
• Decreased tendon reflexes
• Alteration or loss of taste
• Temporary visual disturbances or changes in vision
• Cardiac problems
• Pressure in the chest or wheezing
• Pulmonary interstitial disease (a group of lung disorders in which the deep lung tissue inflames)
• Pain or discomfort in the lips or mouth (mucous membrane disorders)
• Pain or discomfort in the bones, joints, muscles, or adjacent structures (musculoskeletal disorders)
• Problems with your kidneys or urine
• Extreme fatigue/weakness (asthenia)

Tests may also show:

• Increased levels of bilirubin and creatinine in the blood
• Increased levels of uric acid in the blood, which may cause gout

Rare (may affectless than 1 in 1,000 patients):

• Temporary loss of vision
• Exfoliation of the skin (dermatitis exfoliativa)

Very rare (may affectup to 1 in 10,000 patients):

• Pulmonary fibrosis that causes breathing difficulties and/or coughing.

Notknown (cannot be estimated from the available data)

• Cancer caused by carboplatin treatment (secondary neoplasms)
• Febrile neutropenia (fever due to low white blood cell count)
• Bone marrow insufficiency (the bone marrow does not produce enough blood cells)
• Severe dehydration (excessive loss of body water) causing dry mouth, fatigue, and headache
• Loss of appetite, anorexia
• Severe liver dysfunction, liver cell damage, or death.
• Heart failure
• Changes in blood pressure (hypertension or hypotension)
• Skin disorders such as urticaria, rash, redness of the skin (erythema), and itching
• Swelling or pain at the injection site
• A set of symptoms such as headache, alteration of mental function, convulsions, and abnormal vision. These are symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder
• Pancreatitis
• Pain or inflammation inside the mouth (stomatitis)
• Pulmonary infection
• Cerebral disorders (encephalopathy)
• Anemia due to abnormal breakdown of red blood cells (hemolytic anemia)

Carboplatin may cause blood, liver, and kidney problems. Your doctor will make blood tests to check for these problems.

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 leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products 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.

Do not use Carboplatino Accord after the expiration date that appears on the packaging after CAD or EXP. The expiration date is the last day of the month indicated.

Store below 25°C. Do not refrigerate or freeze. Store the vial in the outer packaging to protect it from light.

In use: physical-chemical stability has been demonstrated for 24 hours at room temperature and for 30 hours at 2-8°C.

From a microbiological point of view, the product must be used immediately. If not used immediately, storage times in use and pre-use conditions will be the responsibility of the user and generally will not be more than 24 hours at 2-8°C, except when the dilution has taken place in controlled and validated aseptic conditions.

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

Composition of Carboplatin Accord

The active ingredient of Carboplatin Accord is carboplatin.

Each ml of concentrate for solution for infusion contains 10 mg of carboplatin.

Each vial of 5 ml contains 50 mg of carboplatin.

Each vial of 15 ml contains 150 mg of carboplatin.

Each vial of 45 ml contains 450 mg of carboplatin.

Each vial of 60 ml contains 600 mg of carboplatin.

The other component is water for injections.

Appearance of the product and contents of the container

Concentrate for solution for infusion

Carboplatin Accord is a clear, colorless to pale yellow solution free of particles.

It is supplied in an amber type I glass vial of 5 ml, 15 ml, 50 ml or 100 ml that contains 5 ml, 15 ml, 45 ml or 60 ml of concentrate for solution, respectively. The vials are closed with a grey butyl rubber stopper or a grey siliconized and pre-sterilized Westar stopper with a removable aluminium seal.

Only some sizes of containers may be marketed.

Marketing Authorization Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Responsible Person

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska

50,95-200 Pabianice

Poland

or

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 European Economic Area with the following names

This leaflet was approved in June 2024

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

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

Instructions for use –Cytotoxic

The recommended dose of carboplatin in adult patients not previously treated and with normal renal function, i.e. with a creatinine clearance > 60 ml/min, is 400 mg/m² as a single intravenous dose given over a period of 15 to 60 minutes. Alternatively, the Calvert formula indicated below may be used to determine the dose:

Dose (mg) = target AUC (mg/ml x min) x [FG ml/min + 25]

Note:The Calvert formula calculates the total dose of carboplatin in mg, not in mg/m². The Calvert formula should not be used in patients who have received previous intensive treatment**

**Patients will be considered to have received previous intensive treatment if they have been treated with any of the following regimens:

• Mitomycin C
• Nitrosurea
• Combination treatment with doxorubicin/cyclophosphamide/cisplatin,
• Combination treatment with 5 or more agents,
• Radiation therapy > 4,500 rad, focused on a field of 20 x 20 cm or in more than one treatment field.

Carboplatin treatment should be discontinued in the case of resistant tumor, progressive disease, and/or intolerable adverse effects.

Carboplatin treatment should not be repeated until at least 4 weeks have elapsed since the last administration of carboplatin and/or until the neutrophil count is at least 2,000 cells/mm³ and the platelet count is at least 100,000 cells/mm³.

It is recommended to reduce the initial dose by 20-25% in patients with risk factors such as previous myelosuppressive treatment and poor functional status (ECOG Zubrod 2-4 or Karnofsky < 80).

It is recommended to determine the minimum hematological level by weekly hemograms during the initial treatment sessions with carboplatin for future dose adjustment.

Renal insufficiency:

Patients with creatinine clearance values below 60 ml/min have a higher risk of developing myelosuppression.

The optimal use of carboplatin in patients with renal insufficiency requires appropriate dose adjustments and frequent monitoring of minimum hematological levels and renal function.

In the case of a glomerular filtration rate <20

Combination treatment:

The optimal use of carboplatin in combination with other myelosuppressive agents requires dose adjustments according to the regimen and treatment schedule adopted.

Pediatric population:

The safety and efficacy of carboplatin in children and adolescents have not yet been established. There are no data available.Since there is no sufficient experience with carboplatin in children and adolescents, no specific dose recommendations can be given.

Geriatric population:

It may be necessary to adjust the dose, either initially or subsequently, depending on the patient's physical condition.

Dilution and reconstitution:

The product must be diluted before use. It can be diluted with dextrose or sodium chloride, to concentrations as low as 0.5 mg/ml (500 micrograms/ml).

Administration form

Carboplatin should only be used intravenously.

Incompatibilities

Needles or intravenous equipment containing aluminum parts that may come into contact with Carboplatin Accord should not be used in the preparation or administration of Carboplatin Accord.

This medicinal product should not be mixed with any other medicinal product, except with dextrose or sodium chloride.

Carboplatin may react with aluminum to form a black precipitate. In the preparation or administration of carboplatin, needles, syringes, catheters, or intravenous equipment containing aluminum parts that may come into contact with carboplatin should not be used.

Shelf life and storage

Carboplatin Accord is for single use.

Before opening

Store below 25°C. Do not refrigerate or freeze. Store the vial in the outer packaging to protect it from light.

After dilution

In use: the physical and chemical stability has been demonstrated for 24 hours at room temperature and for 30 hours at 2-8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times in use and the storage conditions prior to use will be the responsibility of the user and will generally not be more than 24 hours at 2-8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

INSTRUCTIONS FOR USE/MANIPULATION, PREPARATION AND DISPOSAL GUIDE FOR THE USE OF CARBOPLATIN

Manipulation of carboplatin

As with other antineoplastic agents, carboplatin should be prepared and handled with caution.

The following protective measures will be followed when handling carboplatin.

Staff should receive training on the appropriate techniques for reconstitution and handling.

1. Carboplatin should only be prepared for administration by professionals who have been trained in the safe use of chemotherapeutic agents. Staff handling Carboplatin Accord should wear protective clothing: glasses, gown, gloves, and disposable masks.

2. A designated area should be defined for the preparation of syringes (preferably under a laminar flow system), and the working surface should be protected with disposable absorbent paper with a plastic backing.

3. All materials used for reconstitution, administration, or cleaning (including gloves) should be placed in high-risk waste bags for incineration at high temperature.

4. Leaks or spills should be treated with diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, and then with water. All contaminated and cleaning materials should be placed in high-risk waste bags for incineration at high temperature. Accidental contact with the skin or eyes should be treated immediately with abundant water, or with water and soap, or sodium bicarbonate solution. However, avoid scrubbing the skin with a brush. Medical attention should be sought. Always wash hands after removing gloves.

Preparation of the infusion solution

The product must be diluted before use. It can be diluted with dextrose or sodium chloride, to concentrations as low as 0.5 mg/ml (500 micrograms/ml).

Disposal

Medicines should not be thrown away through the drains or in the trash. All materials used for preparation, administration, or that otherwise come into contact with carboplatin should be disposed of in accordance with local regulations for the handling of cytotoxic compounds.