CARBOPLATIN AUROVITAS 10 mg/mL concentrate for solution for infusion

2. What you need to know before you use Carboplatin Aurovitas

Do not use Carboplatin Aurovitas

• If you are allergic to carboplatin or any of the other ingredients of this medicine (listed in section 6).
• If you have severe kidney problems (creatinine clearance of 30 ml/min or less).
• If you have a severe blood cell disorder (severe myelosuppression).
• If you have a bleeding tumor.
• If you are taking the yellow fever vaccine at the same time.

If you are in any of these situations and have not already discussed them with your doctor or nurse, you should tell your doctor or nurse as soon as possible and before receiving the infusion.

Carboplatin is usually given to patients in the hospital. You should not handle this medicine yourself. Your doctor or nurse will give you the medicine and closely monitor your condition frequently during and after treatment. They will usually perform blood tests before each administration.

Warnings and Precautions

Tell your doctor or nurse before starting treatment with carboplatin:

• If you are pregnant or think you may be pregnant.
• If you are breast-feeding.
• If you are likely to drink alcohol during treatment with this medicine.
• If you have a headache, altered mental function, seizures, and abnormal vision from blurred vision to loss of vision, tell your doctor.
• Tell your doctor if you feel extreme fatigue with a decrease in the number of red blood cells and shortness of breath (symptoms of hemolytic anemia) alone or combined with a decrease in the number of platelets, abnormal bruising (thrombocytopenia), and kidney disease that leads to little or no urination (symptoms of hemolytic uremic syndrome).
• If you have a fever (temperature greater than or equal to 38°C) or chills, which could be signs of infection, tell your doctor immediately. You may be at risk of contracting a blood infection.

If your kidneys do not work properly, the effects of carboplatin on the blood (hematopoietic system) increase and are prolonged compared to patients with normal kidney function. Your doctor will perform regular checks if your kidneys do not work properly.

During treatment with carboplatin, you will be given medicines that help reduce the risk of a potentially fatal complication known as tumor lysis syndrome, which is caused by chemical changes in the blood due to the destruction of dead cancer cells that release their contents into the blood.

If you are in any of these situations and have not already discussed them with your doctor or nurse, you should tell your doctor or nurse as soon as possible and before receiving this medicine.

This medicine can be diluted with another solution before administration. You should discuss this with your doctor and make sure it is suitable for you.

Other Medicines and Carboplatin Aurovitas

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines.

You should tell your doctor if you are taking any of the following medicines, as they may interfere with carboplatin:

• Other medicines that are toxic to your kidneys (e.g., aminoglycoside antibiotics).
• Other medicines that damage hearing or balance in the ear (e.g., aminoglycoside antibiotics, furosemide (used to treat heart failure and edema)).
• Other medicines that reduce the activity of the immune system (e.g., cyclosporines, tacrolimus, sirolimus, and other cancer medicines).
• The yellow fever vaccine and other live vaccines.
• Medicines to prevent blood clots, e.g., warfarin.
• Phenytoin and fosphenytoin (used to treat various types of seizures and attacks).
• Chelating agents (substances that bind to carboplatin, reducing its effect).
• Loop diuretics (used to treat high blood pressure and edema).

Using Carboplatin Aurovitas with Food, Drinks, and Alcohol

No interaction is known between carboplatin and alcohol. However, you should discuss this with your doctor, as carboplatin may affect the liver's ability to process alcohol.

Pregnancy, Breast-feeding, and Fertility

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

If you are in any of these situations and have not already discussed them with your doctor or nurse, you should tell your doctor or nurse as soon as possible and before receiving this medicine.

Pregnancy

You should not be treated with carboplatin during pregnancy unless your doctor clearly indicates it.

Animal studies have shown a possible risk of fetal abnormalities. If you are being treated with carboplatin while pregnant, you should discuss the possible risks to the fetus with your doctor. Women of childbearing age should use an effective contraceptive method before and during treatment with carboplatin. Since carboplatin can cause genetic damage, if pregnancy occurs during treatment with carboplatin, genetic counseling is recommended. Genetic counseling is also recommended for patients who wish to have children after treatment with carboplatin.

Breast-feeding

It is not known if carboplatin is excreted in breast milk. Therefore, breast-feeding should be discontinued during treatment with carboplatin.

Fertility

Carboplatin can cause genetic damage. Women are advised to avoid pregnancy during treatment and to use an effective contraceptive method. Women who become pregnant during treatment should receive genetic counseling. Men treated with carboplatin are advised to avoid fathering a child during and up to 6 months after treatment. They should seek advice on sperm preservation before treatment because carboplatin may cause irreversible infertility.

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

Driving and Using Machines

Carboplatin does not affect the ability to drive and use machines. However, you should be careful when you are given carboplatin for the first time, especially if you feel dizzy or unsteady.

3. How to Use Carboplatin Aurovitas

This medicine will always be given by a nurse or doctor. It is usually given by intravenous infusion, and it will usually take between 15 and 60 minutes. If you are unsure, ask your doctor or the nurse who gave you the infusion. Your dose will depend on your height and weight, the state of your blood system (hematopoietic system), and the state of your kidneys. Your doctor will choose the best dose for you. The infusion will usually be diluted before use.

Adults

The usual dose is 400 mg/m2 of body surface area (calculated from your weight and height).

Elderly

The usual dose for adults can be used, although the doctor may choose to use a different dose.

Kidney Problems

The amount given may vary depending on kidney function. If you have kidney problems, your doctor may reduce the dose and may perform frequent blood tests in addition to monitoring your kidney function. The infusion will be given by a doctor experienced in the use of cancer treatments.

Use in Children and Adolescents

There is not enough experience with carboplatin in children to recommend a specific dose.

You may feel dizzy while being treated with carboplatin. Your doctor may give you another medicine to reduce these effects before treating you with this medicine.

There will usually be an interval of 4 weeks between each dose of carboplatin. Your doctor will perform blood tests every week after giving you the medicine to decide what the next suitable dose is for you.

If You Receive More Carboplatin Aurovitas Than You Should

It is unlikely that you will be given too much carboplatin. However, if this happens, you may develop kidney, liver, vision, or hearing problems, and you may have a low white blood cell count. If you are concerned that you have been given too much, or if you have any doubts about the dose given, you should talk to the doctor who gave you the medicine.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, telephone 91 562 04 20, indicating the medicine and the amount administered.

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

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:

• Unusual bruising or bleeding, or signs of infection such as sore throat and fever.
• Severe itching of the skin (with lumps) or swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing or breathing (angioedema), and chest pain, which can be a sign of a possible severe allergic reaction called Kounis syndrome, you may feel like you are going to faint.
• Stomatitis/mucositis (irritated lips or mouth ulcers).

Very Common: may affect more than 1 in 10 people

• Suppression of the bone marrow, which is characterized by a significant decrease in white blood cells, making you more prone to infections (leucopenia, neutropenia).
• Reduction of platelets, which increases the risk of bruising and bleeding (thrombocytopenia)
• Anemia (a disorder in which red blood cells decrease, causing fatigue).
• Decreased kidney function (increase in creatinine and urea levels in your blood). You may need medical monitoring.
• Mild loss of hearing (high-frequency hearing loss).
• Abnormal liver enzyme levels and abnormal liver function tests. You may need medical monitoring.
• Increased uric acid levels in the blood, which can cause gout (hyperuricemia).
• Feeling dizzy or nauseous.
• Abdominal pain and cramps.
• Unusual feelings of tiredness or weakness.
• Decreased levels of salts in your blood (sodium, potassium, calcium, magnesium). You may need medical monitoring.

Common: may affect up to 1 in 10 people

• Unusual bruising or bleeding (hemorrhagic complications).
• Diarrhea, constipation, irritated lips, or mouth ulcers (mucositis).
• Allergic reactions, including skin rash, hives, redness of the skin, itching, fever.
• Ringing in the ears (tinnitus), hearing impairment, and loss of hearing.
• Numbness (peripheral neuropathy), weakness, numbness, or tingling.
• Hair loss.
• Feeling unwell.
• Pseudogrippal syndrome.
• Loss or lack of body strength.
• Lung disorders, scarring, and thickening of the lungs with difficulty breathing, sometimes fatal (interstitial lung disease), difficulty breathing.
• Decreased reflexes of the bones and tendons.
• Infections.
• Sensory disturbances.
• Taste disturbances.
• Visual disturbances, including temporary loss of vision.
• Cardiovascular disorders.
• Skin disorders.
• Hives (urticaria).
• Itching (pruritus).
• Red rash (erythematous rash).
• Musculoskeletal disorders.
• Disorders of the urinary and genital tract (urogenital disorders).
• Increased levels of creatinine, bilirubin, and uric acid in the blood. You may need medical monitoring.

Uncommon: may affect up to 1 in 100 people

• Cancer caused by chemotherapy or radiation (secondary malignant neoplasms).
• Fever and chills without signs of infection.
• Redness, swelling, and pain, or dead skin around the injection site (injection site reaction).

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

• Feeling unwell with fever due to low white blood cell count in the blood (febrile neutropenia).
• Lack of appetite (anorexia).
• Severe liver dysfunction, damage, or death of liver cells. You may need medical monitoring.
• Inflammation of the optic nerve that can cause partial or total loss of vision (optic neuritis).
• Severe allergic reactions (anaphylaxis/anaphylactoid reactions).
• Symptoms of a severe allergic reaction include wheezing or sudden chest tightness, swelling of the eyelids, face, or lips, redness of the face, low blood pressure, rapid heart rate, hives, difficulty breathing, dizziness, and anaphylactic shock.
• Low sodium levels in the blood (hyponatremia).

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

• Heart failure.
• Cerebral hemorrhage, which can cause a stroke or loss of consciousness.
• Sudden blockage of an artery (embolism), high blood pressure, low blood pressure.

Frequency Not Known: cannot be estimated from the available data

• Hemolytic uremic syndrome (a disease characterized by acute kidney failure/little or no urine production, decrease in the number of red blood cells with extreme fatigue, and low platelet count).
• Bruising or abnormal bleeding and signs of infection.
• Dehydration.
• Pain in the lips or ulcers in the mouth (stomatitis).
• Muscle cramps, muscle weakness, confusion, vision loss or disturbances, irregular heartbeats, kidney failure, or abnormal blood test results (symptoms of tumor lysis syndrome, which can be caused by the rapid destruction of cancer cells) (see section 2).
• A group of symptoms such as headache, altered mental function, seizures, and abnormal vision from blurred vision to loss of vision (symptoms of posterior reversible leukoencephalopathy syndrome, a rare neurological disorder).
• Pancreatitis.
• Lung infection.

Reporting of Side Effects

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

5. Storage of Carboplatin Aurovitas

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 carton and vials after EXP. The expiry date is the last day of the month stated.

Store below 30°C.

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

Carboplatin should not come into contact with the eyes or skin. If any accidental spillage occurs, inform your doctor or nurse immediately.

After the infusion is finished, carboplatin should be disposed of with caution by your doctor or nurse.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofCarboplatin Aurovitas

• The active ingredient is carboplatin. 1 ml of concentrate for solution for infusion contains 10 mg of carboplatin. Available in vials with 50 mg, 150 mg, 450 mg, and 600 mg of carboplatin.
• The other components are mannitol and water for injectable preparations.

Appearanceof the productand container content

Concentrate for solution for infusion.

Clear or slightly yellowish transparent solution, essentially free of visible particles. Each vial contains 5 ml, 15 ml, 45 ml, or 60 ml of carboplatin concentrate for solution for infusion, respectively.

Package sizes: 1 vial and 10 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

You can request more information about this medication by contacting the local representative of the Marketing Authorization Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medication is authorized in the Member States of the European Economic Area under the following names:

Germany: Carboplatin PUREN 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Carboplatin Eugia 10 mg/ml concentraat voor oplossing voor infusie / solution à diluer pour perfusion / Konzentrat zur Herstellung einer Infusionslösung

Spain: Carboplatino Aurovitas 10 mg/ml concentrado para solución para perfusión EFG

France: Carboplatine Arrow Lab 10 mg/ml, solution à diluer pour perfusion

Italy: Carboplatino Aurobindo Italia

Poland: Carboplatin Eugia

Portugal: Carboplatina Generis

Date of the last revision of this prospectus: July 2023

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

This information is intended only for healthcare professionals:

The medication is for single use. The unused infusion solution must be discarded.

Instructions for dilution

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

The product must be diluted before infusion, with a 5% glucose injectable solution or a 0.9% sodium chloride injectable solution, to achieve concentrations as low as 0.5 mg/ml (500 micrograms/ml).

Carboplatin can be further diluted with 5% glucose and administered as an intravenous infusion. Chemical and physical stability has been demonstrated during use for 56 days at final concentrations of 0.2 mg/ml and 3.5 mg/ml when stored at 2-8°C in non-PVC (polyolefin) infusion bags protected from light.

Carboplatin can also be further diluted with 0.9% sodium chloride and administered as an intravenous infusion. Chemical and physical stability has been demonstrated during use at final concentrations of 0.2 mg/ml and 3.5 mg/ml for 24 hours at 2-8°C and up to 8 hours at 22°C in non-PVC (polyolefin) infusion bags protected from light.

However, from a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has been performed under validated and controlled aseptic conditions.

The solution should be visually inspected for particles or discoloration before administration. The solution should only be used if it is transparent and free of particles.

Guidelines for the safe handling of antineoplastic agents:

1. Carboplatin should only be prepared for administration by professionals who have been trained in the safe use of chemotherapeutic agents.
2. This will be done in a designated area.
3. Protective gloves, masks, and gowns should be used.
4. Precautions should be taken to avoid accidental contact of the drug with the eyes. In case of eye contact, rinse with water and/or saline solution.
5. Cytotoxic preparations should not be handled by pregnant employees.
6. Care should be taken and adequate precautions should be taken in the disposal of materials (syringes, needles, etc.) used to reconstitute cytotoxic drugs. Residual materials and bodily waste can be disposed of by placing them in double-sealed polyethylene bags and incinerating them at a temperature of 1,000°C.
7. The work surface should be covered with absorbent paper with a disposable plastic lining.
8. Luer-Lock type closure accessories should be used on syringes and equipment. The use of large-caliber needles is recommended to reduce pressure and possible aerosol formation. The latter can also be reduced using a vented needle.

Disposal

Disposal of unused medication and materials used for reconstitution, dilution, and administration will be carried out in accordance with hospital procedures for antineoplastic agents, taking into account local regulations for the disposal of hazardous waste.