Carboplatin Pfizer

Package leaflet: Information for the user

CARBOPLATIN PFIZER 10 mg/ml solution for infusion

Carboplatin
Generic medicine
Please read this leaflet carefully before you are given this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What Carboplatin Pfizer is and what it is used for
2. What you need to know before Carboplatin Pfizer is administered
3. How Carboplatin Pfizer is administered
4. Possible side effects
5. How to store Carboplatin Pfizer
6. Contents of the pack and other information

1. What Carboplatino Pfizer is and what it is used for

Carboplatino Pfizer contains the active substance carboplatin, which belongs to a group of medicines
called antineoplastics that act against tumours. Carboplatin works by interfering with the growth of
tumour cells.
It is used to treat:

• advanced ovarian cancer;
• small cell lung cancer;
• head and neck (epidermoid) cancer.

2. What you need to know before Carboplatino Pfizer is administered

Carboplatino Pfizer must not be administered:

• if you are allergic to carboplatin, to other platinum-containing medicines (such as cisplatin), or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe kidney problems (creatinine clearance < 30 ml/min);
• if you have a low number of blood cells ( myelosuppression);
• if you are experiencing severe bleeding or bleeding caused by a tumour;
• if you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”);
• if you need to be vaccinated against yellow fever (see section “Other medicines and Carboplatino Pfizer”).

Warnings and precautions
Please consult your doctor or nurse before receiving Carboplatino Pfizer.
Inform your doctor or nurse if any of the following conditions appear or worsen during treatment with Carboplatino Pfizer (also see section 4 “Possible side effects”):

• bone marrow problems, which produces blood cells. In particular, a reduction in white blood cells (leukopenia, neutropenia), red blood cells (anaemia), and/or
  platelets (thrombocytopenia) may occur. These effects can be particularly severe if you have kidney problems, if you are taking other medicines toxic to the bone marrow, or if you are undergoing radiotherapy. Therefore, before starting another treatment cycle with Carboplatino Pfizer, your doctor will prescribe blood tests to ensure that your white blood cell and platelet counts are within normal limits;

• kidney problems, which may occur especially if you have previously received other cancer treatments (e.g. cisplatin) or if you are taking antibiotics called aminoglycosides (see section “Other medicines and Carboplatino Pfizer”);

• nervous system problems, such as altered sensation in limbs or other body parts and reduced muscle reflexes. These effects occur mainly in elderly patients (see section “Elderly patients”) and/or in individuals who have previously undergone treatment with cisplatin;

• ear problems, such as hearing loss. During treatment with Carboplatino Pfizer, your doctor will perform regular hearing and balance check-ups. The risk of ear-related disorders may increase if Carboplatino Pfizer is administered concomitantly with other ototoxic medicines, such as aminoglycoside antibiotics. In case of severe ear problems, your doctor may decide to reduce the dose or discontinue treatment with this medicine;

• vision disturbances (including loss of vision), which occur mainly if you have kidney problems and are receiving high doses of this medicine. These effects usually resolve after stopping treatment with this medicine;

• vomiting;

• allergic reactions, even severe (anaphylactic-type) reactions. If you experience symptoms of an allergic reaction, your doctor must stop administration of this medicine immediately;

• headache, altered mental function, seizures, abnormal vision ranging from blurred vision to loss of vision;

• severe fatigue and shortness of breath due to reduced red blood cells (symptoms of haemolytic anaemia), either alone or associated with low platelet count, abnormal bruising (thrombocytopenia), and kidney disorders with reduced or absent urination (symptoms of haemolytic-uremic syndrome);

• fever (temperature equal to or greater than 38°C) or chills, which could be signs of infection. You may be at risk of developing blood infection (sepsis).

During treatment with carboplatin, you will receive medications that help prevent a potentially fatal complication known as tumour lysis syndrome, caused by changes in blood chemistry due to the release of contents from dead tumour cells into the bloodstream following their breakdown.
During treatment with Carboplatino Pfizer, you must not receive vaccinations with “live” or “attenuated” vaccines, as serious or even fatal infections may occur due to your weakened immune defences. However, you may receive “killed” or “inactivated” vaccines, although the effectiveness of such vaccinations may be reduced.
Laboratory tests
Before starting treatment, during therapy, and between treatment cycles with this medicine, your doctor will perform careful and regular medical checks to monitor your health status.
Children
There are insufficient data to determine the recommended dose in children and adolescents.
Children are more susceptible to ototoxic (ear-related) effects of Carboplatino Pfizer (see section “Warnings and precautions”).
Elderly patients
If you are elderly, you have a higher risk of developing nervous system problems and reduced platelet count in the blood, especially if you are receiving combination therapy including Carboplatino Pfizer and other anticancer medicines.
Other medicines and Carboplatino Pfizer
Inform your doctor or nurse if you are currently taking, have recently taken, or might take any other medicines.
Administration of the following medicines is not recommended during treatment with this medicine:

• phenytoin, fosphenytoin (medicines for epilepsy), as worsening of seizures may occur.

Caution is required when Carboplatino Pfizer is administered together with the following medicines, as they may increase its toxicity:

• other antineoplastic medicines (for cancer treatment)
• other myelosuppressive medicines (which reduce bone marrow activity)
• other medicines that induce vomiting
• cyclosporine, tacrolimus, sirolimus (medicines used after organ transplantation)
• aminoglycosides (antibiotics)
• certain types of diuretics (medicines that increase urine elimination)

Additionally, this medicine will be administered with great caution if you are undergoing radiotherapy.
Inform your doctor if you are taking the following medicines:

• oral anticoagulants (to reduce blood clot formation in blood vessels). In this case, your doctor will perform regular and frequent blood tests.

Carboplatino Pfizer must not be administered together with the yellow fever vaccine, as this may lead to a potentially fatal condition (fatal generalized vaccine disease) (see section “Carboplatino Pfizer must not be administered”). If deemed necessary by your doctor, an inactivated vaccine may be administered (see section “Warnings and precautions”).
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or nurse before receiving this medicine.
Pregnancy
This medicine must not be administered during pregnancy, as it may cause harm to the unborn baby.
If you are a woman of childbearing potential, you must use effective methods of birth control (contraception) to prevent pregnancy during treatment with this medicine and for at least seven months after the last dose.
Breastfeeding
If you are starting treatment with this medicine, discontinue breastfeeding for at least one month after the last dose.
Fertility
Carboplatino Pfizer may have negative effects on fertility in both men and women and, in severe cases, may cause irreversible sterility. Your doctor may advise you to consult a specialist before starting treatment with carboplatin. Men who wish to father children in the future are advised to undergo sperm preservation procedures (cryopreservation) before starting therapy. During treatment with Carboplatino Pfizer and for at least four months after the last dose, men must use an effective method of birth control (contraception) to prevent pregnancy.
Please consult your doctor to identify the most suitable contraceptive methods for you and your partner.
Driving and use of machines
It is not advisable to drive or operate machinery during treatment cycles with this medicine, as Carboplatino Pfizer may cause nausea, vomiting, visual disturbances, and ototoxic (ear-related) effects.
The container of this medicine contains latex rubber, which may cause severe allergic reactions.

3. How to administer Carboplatino Pfizer

This medicine must be administered under the supervision of physicians experienced in cancer therapy and only in suitable facilities (hospitals, clinics, and healthcare centers).
Carboplatino Pfizer will be administered directly into your vein by intravenous infusion.
If considered necessary by your doctor, Carboplatino Pfizer may be given in combination with other medicines.

Adults
If this is the first time you are receiving Carboplatino Pfizer, the recommended dose is 400 mg/m², given as a single dose by intravenous injection lasting 15–60 minutes.
Your doctor will determine when to administer the next dose, based on your condition.

Use in children and adolescents
Insufficient data are available to establish the recommended dose in children and adolescents.

Use in the elderly
In elderly patients, kidney function may be reduced compared to younger adults. Therefore, the doctor must perform specific tests and consider reducing the dose.

Use in particular patients
If you have previously received treatment with medicines that reduce bone marrow activity, if your tumor causes a particularly evident state of general malaise, or if you have kidney problems, Carboplatino Pfizer must be administered with great caution.

If more Carboplatino Pfizer is administered than prescribed
If you have been given more Carboplatino Pfizer than prescribed, inform your doctor or nurse immediately if you experience any of the following symptoms (see also section “Possible side effects”):

• severe reduction in bone marrow activity;
• intractable nausea and vomiting;
• neurotoxic effects;
• severe liver or kidney problems;
• hearing problems;
• loss of vision.

In severe cases, these symptoms may even lead to death. Your doctor will take the most appropriate measures to manage these symptoms, depending on your condition.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following side effects because they may be serious:

Common side effects (may affect up to 1 in 10 people):

• infections
• bleeding
• severe allergic reactions (anaphylactoid reactions) such as swelling of the face, difficulty breathing, increased heart rate, hives, shock, drop in blood pressure
• blindness
• loss of hearing
• heart problems such as heart attack, cardiac arrest, sudden severe chest pain, blockage of blood flow to part of the heart

Uncommon side effects (may affect up to 1 in 100 people):

• inability of the bone marrow to produce all blood cells (bone marrow failure)
• severe reduction in neutrophils (a type of white blood cells), associated with fever

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• development of new tumours
• problems with blood vessels in the brain (cerebrovascular accidents)
• blockage of a blood vessel by a blood clot (embolism)
• inability of the heart to pump blood to the body (heart failure)
• chest pain that may indicate a potentially serious allergic reaction called Kounis syndrome
• marked reduction in red blood cells and haemoglobin levels due to excessive destruction of red blood cells (haemolytic anaemia, which can be life-threatening)
• acute fulminant necrosis of liver cells
• leakage of the injected solution from the vein (extravasation), resulting in damage to the surrounding tissues at the injection site such as burning, pain, redness, swelling, hives, and cell death. In case of extravasation, administration of Carboplatino Pfizer must be immediately stopped (see section 2 “Warnings and precautions”)

The following side effects may also occur:

Very common side effects (may affect more than 1 in 10 people)

• reduction in the number of platelets, white blood cells, and red blood cells in the blood
• vomiting
• nausea
• abdominal pain
• fever (pyrexia)
• changes in blood test results: decreased creatinine clearance, increased urea, increased alkaline phosphatase, increased aspartate aminotransferase, decreased sodium, potassium, calcium, and magnesium

Common side effects (may affect up to 1 in 10 people)

• hypersensitivity
• problems with the peripheral nervous system
• altered sensation in the legs, arms, or other parts of the body (paraesthesia)
• reduced muscle reflexes
• altered or reduced ability to taste (dysgeusia)
• vision disorders, such as temporary decrease in vision and ability to perceive colours
• ringing in the ears (tinnitus), decreased hearing
• respiratory disorders (pulmonary interstitial disease, bronchospasm)
• diarrhoea
• constipation
• inflammation and ulceration of the mucous membranes of the oesophagus, stomach, and intestine
• hair loss (alopecia)
• skin problems
• muscle and bone disorders (e.g. muscle pain and joint pain)
• urinary and genital disorders
• weakness
• changes in blood test results (bilirubin, creatinine, uric acid)

Uncommon side effects (may affect up to 1 in 100 people)

• a disease characterised by blood and kidney disorders (haemolytic-uraemic syndrome)
• inflammation of the mucous membrane of the mouth (stomatitis)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• a group of symptoms such as headache, altered mental function, seizures, and visual disturbances ranging from blurred vision to vision loss (symptoms of reversible posterior leucoencephalopathy syndrome, a rare neurological condition)
• pneumonia
• inflammation of the pancreas (pancreatitis)
• reduction in body fluids (dehydration)
• muscle cramps, muscle weakness, confusion, loss or disturbances of vision, cardiac arrhythmias, kidney failure, or abnormalities in blood test results (symptoms of tumour lysis syndrome, which may be caused by the rapid breakdown of tumour cells) (see section 2)
• loss of appetite (anorexia)
• reduction in sodium levels in the blood
• increase in blood pressure (hypertension)
• drop in blood pressure (hypotension)
• hives
• skin rash
• redness of the skin
• itching
• malaise

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Carboplatin Pfizer

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.".
The expiry date refers to the last day of that month.
Store below 25°C.
Do not freeze.
Keep in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Carboplatino Pfizer contains
The active substance is 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.
The other component is: water for injections.

Description of the appearance of Carboplatino Pfizer and contents of the pack
Carboplatino Pfizer 10 mg/ml infusion solution is available in packaging containing:

• 1 vial of 5 ml infusion solution in polypropylene with rubber stopper, aluminium seal and plastic "flip-off" cap.
• 1 vial of 15 ml infusion solution in polypropylene with rubber stopper, aluminium seal and plastic "flip-off" cap.
• 1 vial of 45 ml infusion solution in polypropylene with rubber stopper, aluminium seal and plastic "flip-off" cap.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Italy

Manufacturer
Pfizer Service Company bvba
Hoge Wei 10
1930 Zaventem (Belgium)

The following information is intended exclusively for physicians or healthcare professionals

DOSAGE AND ADMINISTRATION
Carboplatino Pfizer must be used only by intravenous route. The recommended dose for adult patients not previously treated, with normal renal function, is 400 mg/m² as a single dose, administered via intravenous infusion lasting 15–60 minutes. Further cycles should not be repeated before four weeks and/or until the neutrophil count is at least 2,000 cells/mm³ and the platelet count is at least 100,000 cells/mm³.
In patients with risk factors due to prior myelosuppressive treatments, elderly patients, or patients with low performance status (ECOG-Zubrod 2–4 or Karnofsky below 80), an initial dose reduction of 20–25% is advisable.
It is recommended to determine the hematological nadir by weekly blood count monitoring during the first treatment cycle with injectable carboplatin, in order to perform subsequent dose adjustments for following therapy cycles.
Patients with impaired renal function: Since carboplatin is excreted renally and is nephrotoxic, the optimal dosage must be determined based on frequent monitoring of hematological nadir and renal function.
The recommended dosage in patients with impaired renal function is based on creatinine clearance. Patients with creatinine clearance values below 60 ml/min are at higher risk of severe myelosuppression. The incidence of severe leukopenia, neutropenia, or thrombocytopenia remains around 25% with the following recommended dosages:

There are insufficient data on the use of carboplatin in patients with creatinine clearance of 15 ml/min or less to allow treatment recommendations.
All recommended doses listed above apply to the initial treatment cycle.
Subsequent doses should be adjusted according to patient tolerance and an acceptable level of myelosuppression.

Instructions for preparation and use
Carboplatin is a cytotoxic drug; appropriate safety measures must therefore be taken during handling and administration.
As with all other antineoplastic agents, Carboplatin Pfizer should be handled only by trained personnel in a specifically designated area (preferably within a properly functioning laminar flow hood suitable for handling cytotoxic compounds).
Personnel should wear protective gloves, and in case of accidental contact of the solution with skin or mucous membranes, the affected area must be immediately washed thoroughly with copious amounts of water and soap.
It is recommended that cytotoxic drugs such as carboplatin should not be handled by pregnant female personnel.
The use of Luer-Lock syringes is recommended. Preferably, wide-bore needles should be used to minimize pressure and the potential for gas formation.
All materials used in the preparation of Carboplatin Pfizer solutions or for the collection of bodily waste should be disposed of in double-sealed polyethylene bags and incinerated at 1100°C.

Dilution: Carboplatin Pfizer may be diluted with 5% dextrose injection or 0.9% sodium chloride injection solutions to minimum concentrations of 0.5 mg/ml.
It is recommended not to dilute carboplatin with 0.9% sodium chloride solution for prolonged intravenous infusion, as carboplatin undergoes approximately 5% degradation of the initial concentration within 24 hours and may be converted to cisplatin, thereby increasing the risk of toxicity.

Procedures to follow in case of solution spillage
In the event of a spill, access to the affected area must be restricted. Personnel should wear two pairs of gloves (latex rubber), a respiratory mask, a protective gown, and safety goggles. Limit the spread of spilled solution by using absorbent materials such as paper, sawdust, or absorbent gravel (e.g., animal bedding). Alternatively, the following may be used: 3M sulfuric acid, 0.3M potassium permanganate (2:1), or 5% sodium hypochlorite. Used absorbent materials and any other waste should be collected, placed in plastic containers, sealed, and properly labeled. Cytotoxic waste must be considered hazardous or toxic and clearly labeled with the following statement: "CYTOTOXIC WASTE TO BE INCINERATED AT 1100°C". Waste must be incinerated at 1100°C for at least 1 second. Clean the spill area thoroughly with abundant water.

OVERDOSE
No antidotes are known for carboplatin overdose; therefore, every possible precaution must be taken to avoid overdose, including full awareness of the potential harm caused by overdose, careful dose calculation, and availability of adequate equipment for diagnosis and treatment. Hemodialysis is the only measure that is partially effective, but only if performed within 3 hours of administration, due to the rapid and extensive binding of platinum to plasma proteins. Signs and symptoms of overdose should be managed with supportive measures.

INCOMPATIBILITIES
Carboplatin interacts with aluminum, causing the formation of a black precipitate and/or loss of potency. No other incompatibilities have been reported.
Needles, syringes, catheters, or intravenous administration sets containing aluminum must not be used for the administration of carboplatin.

SHELF LIFE
Carboplatin Pfizer does not contain preservatives or bacteriostatic agents. Vials should therefore be used only once, and any unused product should be discarded after use.
From a microbiological standpoint, the product should be used immediately after dilution.
If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

For further information, consult the Summary of Product Characteristics.