Carboplatin accord

Package leaflet: Information for the patient

Carboplatin Accord, 10 mg/mL, concentrate for solution for infusion
Carboplatinum
Please read carefully the entire leaflet before using this medicine, as it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Leaflet contents:

1. What Carboplatin Accord is and what it is used for
2. Important information before using Carboplatin Accord
3. How to use Carboplatin Accord
4. Possible side effects
5. How to store Carboplatin Accord
6. Contents of the pack and other information

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

Carboplatin Accord is an anticancer medicine. Treatment with anticancer medicines is sometimes called chemotherapy.
Carboplatin Accord is used in adults to treat certain types of lung cancer and ovarian cancer.

2. Important information before using Carboplatin Accord

When not to use Carboplatin Accord

• if the patient is allergic to carboplatin or any of the other ingredients of this medicine (listed in section 6),
• if the patient has previously experienced hypersensitivity to similar platinum-containing medicines,
• in patients with severe kidney disease,
• if the patient has a lower than normal number of blood cells (the doctor will check this by ordering a blood test),
• if the patient has a bleeding tumour,
• if the patient plans to receive or has recently received the yellow fever vaccine.

If any of the above apply to the patient, they must inform their doctor before taking this medicine.

Warnings and precautions

Before starting treatment with Carboplatin Accord, discuss with the doctor, pharmacist or nurse:

• if the patient is pregnant or suspects she may be pregnant,
• if the patient is breastfeeding,
• if the patient has mild kidney disease; the doctor will monitor the patient more frequently,
• if the patient is elderly (over 65 years of age),
• if the patient experiences any hearing problems,
• if the patient has previously received treatment with cisplatin or similar anticancer medicines; carboplatin may cause nervous system disorders such as tingling sensations or hearing and vision disturbances. The doctor may perform regular examinations of the patient,
• if the patient experiences headaches, psychiatric disturbances, seizures, or visual disturbances ranging from blurred vision to loss of vision,
• if the patient experiences extreme tiredness, breathlessness due to reduced red blood cells (haemolytic anaemia), either alone or in combination with low platelet count, unusual bruising (thrombocytopenia), and kidney disease with reduced urine output or anuria (symptoms of haemolytic-uraemic syndrome),
• if the patient develops fever (temperature of 38°C or higher) or chills, which may indicate an infection. Blood infection may occur.

During treatment with carboplatin, medications will be administered to help reduce the risk of a potentially life-threatening complication known as tumour lysis syndrome, caused by biochemical disturbances in the blood due to the breakdown of dying tumour cells, which release their contents into the bloodstream.

Children and adolescents

The safety and efficacy of carboplatin treatment in children and adolescents have not been established.

Carboplatin Accord and other medicines

Tell your doctor, pharmacist or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, for example:

• medicines that may reduce the number of blood cells, taken concomitantly with carboplatin: dosage adjustment and changes in the frequency of carboplatin treatment may be necessary,
• certain antibiotics called aminoglycosides, vancomycin or capreomycin, administered concomitantly with carboplatin: may increase the risk of kidney function disorders or hearing disturbances,
• certain diuretics, administered concomitantly with carboplatin: may increase the risk of kidney function disorders or hearing disturbances,
• live or live attenuated vaccines (e.g. yellow fever vaccine; see section 2, When not to use Carboplatin Accord),
• anticoagulant medicines, e.g. warfarin, taken concomitantly with carboplatin: more frequent monitoring of blood coagulation parameters may be required,
• phenytoin and fosphenytoin (used to treat various types of seizures), administered concomitantly with carboplatin: may increase the risk of seizure attacks,
• other medicines that suppress the immune system (e.g. cyclosporine, tacrolimus, sirolimus).

Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription.

Carboplatin Accord and alcohol

The interaction between Carboplatin Accord and alcohol is not known. Consult your doctor about whether it is safe to consume alcohol during treatment with Carboplatin Accord, due to the potential effect of the medicine on the liver's ability to process alcohol.

Contraception in men and women

Women of childbearing age should avoid becoming pregnant and use effective contraception during treatment and for at least 7 months after the last dose. If pregnancy occurs during this period, inform the doctor immediately.

Men should use effective contraception and avoid fathering a child during treatment and for 4 months after the last dose.

Pregnancy

This medicine should not be used during pregnancy unless considered essential by the doctor. The medicine may cause severe congenital malformations.

Breastfeeding

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

Fertility in men and women

Use of this medicine may temporarily or permanently reduce fertility in both men and women. Before starting treatment, consult the doctor about the possibility of preserving fertility.

Driving and operating machinery

Do not drive or operate machinery if any adverse effects occur that may impair such ability, such as nausea, vomiting, worsening or disturbances of vision or hearing.

3. How to use Carboplatin Accord

This medicine is administered by intravenous infusion (drip) lasting from 15 to 60 minutes.
Dosage:
Your doctor will determine the appropriate dose of carboplatin and how often it should be given.
The dose depends on the patient's health status, height and body weight, as well as kidney function. Your doctor will inform you about your kidney function after blood or urine tests.
Regular blood tests will be performed after each dose of carboplatin. The patient may also undergo tests to detect nerve damage and hearing loss. Carboplatin doses are usually given at 4-week intervals.
If more Carboplatin Accord than recommended has been administered
The medicine is administered in a hospital under medical supervision, so it is unlikely that the patient will receive too high or too low a dose. However, if the patient has any doubts, they should inform their doctor or nurse.
Stopping Carboplatin Accord treatment
If there are any doubts regarding the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should contact your doctor immediately if you notice any of the following symptoms:

• Unexpected bruising, bleeding, or signs of infection such as sore throat and high temperature (very common, may occur in more than 1 in 10 patients).
• Severe allergic reactions (anaphylactic reactions/anaphylaxis): sudden itchy rash (urticaria), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), and feeling faint (common, may occur in up to 1 in 10 patients).
• Haemolytic uraemic syndrome (a disease characterized by acute kidney failure), reduced urine output or presence of blood in the urine (frequency unknown, cannot be estimated from available data).
• Muscle cramps, muscle weakness, disorientation, loss of vision or visual disturbances, irregular heartbeat, kidney failure or abnormal blood test results (symptoms of tumour lysis syndrome, which may be caused by rapid breakdown of tumour cells) (see section 2) (frequency unknown, cannot be estimated from available data).
• Stroke (sudden numbness or weakness of the face, arm or leg, especially on one side of the body) (frequency unknown, cannot be estimated from available data).
• Vascular occlusion (thromboembolism and venous thrombotic disease), swelling or tenderness in the leg and/or arm (frequency unknown, cannot be estimated from available data).
• Chest pain, which may be a symptom of a potentially serious allergic reaction called Kounis syndrome (frequency unknown, cannot be estimated from available data).
• Skin swelling, often affecting the face and lips (angioedema) (rare, may occur in up to 1 in 1000 patients).

These are serious adverse reactions and you may require urgent medical attention.
Other adverse reactions that may occur:
Very common adverse reactions (may occur in more than 1 in 10 patients):

• Tiredness, breathlessness and pale skin due to anaemia (a condition in which there is a reduction in the number of red blood cells).
• Nausea and vomiting.
• Abdominal pain and cramps.

Tests may also show:

• Changes in red and white blood cells and platelets (myelosuppression).
• Increased blood urea levels.
• Decreased levels of sodium, potassium, calcium and magnesium in the blood.
• Reduced creatinine renal clearance.
• Abnormal liver enzyme values.

Common adverse reactions (may occur in up to 1 in 10 patients)

• Diarrhoea or constipation.
• Rash and/or itching of the skin.
• Ringing in the ears or hearing disturbances.
• Hair loss.
• Flu-like symptoms.
• Infections.
• Tingling or numbness in hands, feet, arms or legs.
• Burning or pricking sensations.
• Diminished tendon reflexes.
• Taste disturbances or loss of taste.
• Transient worsening of vision or visual disturbances.
• Heart disorders.
• Chest tightness or wheezing.
• Interstitial lung disease (a group of lung disorders involving inflammation of the deep lung tissues).
• Pain or ulceration of the lips or mouth (mucosal disorders).
• Pain or discomfort in bones, joints, muscles or surrounding structures (musculoskeletal disorders).
• Kidney function or urinary disorders.
• Extreme tiredness/weakness (asthenia).

Tests may also show:

• Increased levels of bilirubin and creatinine in the blood.
• Increased blood uric acid levels, which may lead to development of gout.

Rare adverse reactions (may occur in up to 1 in 1000 patients):

• Transient loss of vision.
• Skin peeling (exfoliative dermatitis).

Very rare adverse reactions (may occur in up to 1 in 10,000 patients):

• Lung scarring causing breathlessness and/or cough (pulmonary fibrosis).

Frequency unknown (cannot be estimated from available data)

• Tumours caused by carboplatin treatment (secondary malignancies).
• Feeling unwell with high temperature due to low white blood cell count (febrile neutropenia).
• Bone marrow failure (bone marrow does not produce enough blood cells).
• Dry mouth, fatigue and headache due to excessive fluid loss from the body (dehydration).
• Loss of appetite, anorexia.
• Severe liver function disorders, liver damage or liver cell necrosis.
• 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 group of symptoms such as headache, mental disturbances, seizures and visual disturbances from blurred vision to loss of vision. These are symptoms of reversible posterior leukoencephalopathy syndrome (a rare neurological disorder).
• Pancreatitis.
• Pain or inflammation in the mouth (mucositis).
• Lung infection.
• Brain disorders (encephalopathy).
• Anaemia caused by abnormal breakdown of red blood cells (haemolytic anaemia).

Carboplatin may cause blood, liver and kidney disorders. Your doctor will order blood tests to monitor these conditions.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported directly to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Carboplatin Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton under EXP.
The expiry date refers to the last day of the stated month.
Store below 25°C. Do not refrigerate or freeze.
Store the vial in the outer packaging to protect from light.
In-use stability: Chemical and physical stability of the medicine 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. Otherwise,
the responsibility for the storage duration and conditions of the prepared solution lies with the user.
In such a case, the solution should not be stored for longer than 24 hours at a temperature of 2°C to 8°C,
unless dilution has been carried out under controlled and validated aseptic conditions.
Medicines must 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. Contents of the package and other information

What Carboplatin Accord contains
The active substance is carboplatin.
One mL of concentrate for solution for infusion contains 10 mg of carboplatin.
Each 5 mL vial contains 50 mg of carboplatin.
Each 15 mL vial contains 150 mg of carboplatin.
Each 45 mL vial contains 450 mg of carboplatin.
Each 60 mL vial contains 600 mg of carboplatin.
The other ingredient is: water for injections.

What Carboplatin Accord looks like and contents of the pack
Concentrate for solution for infusion
Carboplatin Accord is a clear, colourless to pale yellow solution free from visible particles.
5 mL, 15 mL, 45 mL or 60 mL of concentrate for solution for infusion in amber glass type I vials with a capacity of 5 mL, 15 mL, 50 mL or 100 mL, respectively.
The vials are closed with a grey chlorobutyl rubber stopper or a chlorobutyl rubber stopper coated with silicone and sealed with an aluminium cap.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: + 48 22 577 28 00

Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Accord Healthcare Single Member S.A.
64th Km National Road Athens
32009 Lamia
Greece

This medicinal product is authorised in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Austria: Carboplatin Accord 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Belgium: Carboplatin Accord Healthcare 10mg/ml concentré pour solution de perfusion / concentraat voor oplossing voor infusie / Konzentrat zur Herstellung einer Infusionslösung
Czech Republic: Carboplatin Accord 10 mg/ml koncentrát pro přípravu infuzního roztoku
Denmark: Carboplatin Accord 10mg/ml koncentrat til infusionsvæske, opløsning
Estonia: Carboplatin Accord 10 mg/ml infusioonilahuse kontsentraat
Finland: Carboplatin Accord 10 mg/ml infuusiokonsentraatti, liuosta varten / koncentrat till infusionsvätska, lösning
Spain: Carboplatin Accord 10 mg/ml Concentrado para solución para perfusión EFG
Netherlands: Carboplatin Accord 10 mg/ml concentraat voor oplossing voor infusie
Ireland: Carboplatin 10 mg/ml Concentrate for Solution for Infusion
Lithuania: Carboplatin Accord 10mg/ml koncentratas infuziniam tirpalui
Latvia: Carboplatin Accord 10 mg/ml koncentrāts infūziju šķīduma pagatavošanai
Germany: Carboplatin Accord 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Norway: Carboplatin Accord 10 mg/ml konsentrat til infusjonsvæske
Poland: Carboplatin Accord
Portugal: Carboplatina Accord 10 mg/ml concentrado para solução para perfusão
Slovakia: Carboplatin Accord 10 mg/ml infúzny koncentrát
Sweden: Carboplatin Accord 10 mg/ml koncentrat till infusionsvätska, lösning
United Kingdom (Northern Ireland): Carboplatin 10 mg/ml concentrate for solution for infusion
Italy: Carboplatino AHCL 10 mg/ml Concentrato per soluzione per infusione
Hungary: Carboplatin Accord 10 mg/ml koncentrátum oldatos infúzióhoz

The following information intended exclusively for professional medical personnel:

Instructions for use - cytotoxic drugs
The recommended dose of carboplatin for previously untreated adult patients with normal renal
function, i.e. creatinine clearance > 60 mL/min, is 400 mg/m² BSA administered as a single dose by short intravenous infusion lasting from 15 to 60 minutes. An alternative method for determining the dose is the Calvert formula (see below):
Dose (mg) = target AUC (mg/mL x min) x [GFR mL/min + 25]

Note: According to the Calvert formula, the total dose of carboplatin is calculated in mg, not in
mg/m² BSA.
Treatment should not be repeated earlier than four weeks after the previous course of
carboplatin therapy and (or) until the neutrophil count is at least
2000 cells/mm³ and the platelet count is at least 100,000 cells/mm³.
A 20–25% reduction of the initial dose is recommended in patients with risk factors such as
prior myelosuppressive therapy and poor performance status (ECOG-Zubrod score 2–4 or Karnofsky
score below 80).
It is recommended to determine the lowest blood counts (nadir) by performing
weekly blood tests during the initial treatment cycles with carboplatin to better
adjust future dosing.
Renal function disorders:
In patients with impaired renal function, the carboplatin dose should be reduced (according to the
Calvert formula), and hematological nadir values and renal function should be monitored.
In patients with creatinine clearance values below 60 mL/min, there is an increased
risk of bone marrow suppression.
The incidence of severe leukopenia, neutropenia, or thrombocytopenia was approximately 25%
according to the following dosing recommendations:
Combination therapy:
Optimal use of carboplatin in combination with other myelosuppressive agents requires
adjustment depending on the chosen treatment regimen and protocol.
Children and adolescents:
The safety and efficacy of carboplatin in children and adolescents have not yet been
established.
No data are available. Due to insufficient data on the use of carboplatin in children and adolescents,
specific dosing recommendations cannot be provided.
Elderly patients:
In patients over 65 years of age, dose adjustment of carboplatin based on overall health status is
essential at the beginning of treatment and during subsequent treatment cycles.
Dilution and preparation of solution:
Before infusion, the product should be diluted with 5% (50 mg/mL) glucose solution or 0.9% (9
mg/mL) sodium chloride solution to achieve final concentrations as low as
0.5 mg/mL.
Method of administration:
Carboplatin Accord must be administered intravenously only.
Pharmaceutical incompatibilities
Carboplatin may react with aluminium, forming a black precipitate. Needles, syringes, catheters, or
intravenous sets containing aluminium components that may come into contact with the drug should
not be used for preparation or administration of carboplatin. The precipitate may lead to reduced
antitumor activity.
Shelf life and storage
The vial is intended for single use only.
Before opening
Do not store above 25°C. Do not store in a refrigerator or freeze.
Keep the vial in its outer packaging to protect from light.
After dilution
In use: Chemical and physical stability of the product 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. Otherwise, the
user is responsible for the storage conditions and duration of the prepared solution.
Generally, the storage time should not exceed 24 hours at a temperature of 2°C to
8°C, unless dilution was performed under controlled and validated aseptic conditions.
INSTRUCTIONS FOR PREPARING CARBOPLATIN ACCORD FOR
ADMINISTRATION AND DISPOSAL OF REMAINDERS
Instructions for preparing Carboplatin Accord
As with other antineoplastic drugs, caution should be exercised when handling and
preparing Carboplatin Accord for administration.
The following procedures for proper handling of carboplatin should be followed:
Personnel should be trained in the preparation and handling of the product.

1. Carboplatin should be prepared for administration only by personnel qualified in the safe use of chemotherapeutic agents. Personnel handling Carboplatin Accord should wear appropriate protective clothing, including protective eyewear, gowns, disposable gloves, and masks.
2. Preparation of the syringe should be carried out in a designated area (preferably using a laminar flow system). The work surface should be covered with absorbent paper with a plastic backing.
3. All materials used during preparation, administration, or cleaning (including gloves) should be placed in high-risk waste bags for incineration at high temperatures.
4. Liquid waste may be treated with a diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, then flushed with water. All contaminated and cleaning materials should be placed in high-risk waste bags for incineration. In case of accidental contact of the drug with skin or eyes, immediately flush thoroughly with water, soapy water, or sodium bicarbonate solution. Do not scrub the skin with a brush. Seek medical advice. Always wash hands after removing gloves.

Preparation of infusion solution
The product must be diluted before use. It may be diluted with glucose or
sodium chloride solution to achieve a concentration of 0.5 mg/mL (500 micrograms/mL).
Disposal of remnants
Medicines should not be disposed of via sewage or household waste. All
materials used during preparation, administration, or any materials that have come into
contact with carboplatin must be disposed of in accordance with local regulations for handling
waste from cytotoxic agents.