Carboplatin Hikma

Patient Information Leaflet

Carboplatino Hikma, 10 mg/ml, Solution for infusion

(50 mg/5ml, 150 mg/15 ml, 450 mg/45ml and 600 mg/60ml)
Carboplatin
Generic Medicine
Please read all of this leaflet carefully before you start using this medicine, as 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Carboplatino Hikma is an antineoplastic medicinal product containing carboplatino as an infusion solution (a solution that can be administered as a slow, drop-by-drop infusion).
Treatment with an antineoplastic medicinal product is called chemotherapy.
Carboplatino is used in the treatment of certain types of lung tumours and advanced ovarian cancer, and as adjuvant treatment for testicular germ cell tumours.

2. What you need to know before using Carboplatino Hikma

Do not use Carboplatino Hikma:

• if you are allergic (hypersensitive) to carboplatin or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe kidney problems;
• if you have lower than normal blood cell counts (your doctor will monitor you);
• if you are breastfeeding;
• if you have a tumour that is bleeding;
• if you have received a yellow fever vaccination.

Warnings and precautions
Talk to your doctor or pharmacist before using Carboplatino Hikma:

• if you experience headache, altered mental function, seizures, or visual disturbances ranging from blurred vision to loss of vision;
• if you develop extreme fatigue and shortness of breath due to a reduced number of red blood cells (symptoms of haemolytic anaemia), alone or in combination with low platelet count, unusual bruising (thrombocytopenia), and kidney disease with little or no urine output (symptoms of haemolytic-uraemic syndrome);
• if you have fever (temperature greater than or equal to 38°C) or chills, which could be signs of infection. You may be at risk of developing a blood infection.

Carboplatin must be administered with particular caution in:

• Patients with myelosuppression (reduced number of blood cells produced by the bone marrow). Combination treatment with other myelosuppressive drugs (which reduce blood cell production) may require dose adjustment;
• Patients with haematological toxicity (reduced production of blood cells);
• Patients with impaired renal function;
• Patients with allergic reactions to platinum-based medicines;
• Patients over 65 years of age and/or patients previously treated with cisplatin (medicines used to treat cancer);
• Patients receiving treatment with a live vaccine;
• Children. In this population, long-term audiometric follow-up is recommended.

Carboplatin may react with aluminium; therefore, needles, syringes, catheters, or intravenous administration systems containing aluminium must not be used in the preparation or administration of carboplatin, to avoid any interaction.
During treatment with carboplatin, medicines will be administered to help reduce a potentially life-threatening complication known as tumour lysis syndrome, caused by chemical disturbances in the blood due to the breakdown of dead cancer cells releasing their contents into the bloodstream.

Other medicines and Carboplatino Hikma
Tell your doctor if you are using, have recently used, or might use any other medicine.
Treatment of patients with oral anticoagulants (medicines to thin the blood) requires more frequent monitoring of the International Normalized Ratio (INR).
The administration of Carboplatino Hikma:

• Is contraindicated with concomitant use of the yellow fever vaccine;
• Is not recommended with concomitant use of live attenuated vaccines (except the yellow fever vaccine), phenytoin, or fosphenytoin (medicines used to treat seizures);
• Must be administered with particular caution when used concomitantly with ciclosporin, tacrolimus, and sirolimus (medicines that suppress the body's natural defences against foreign substances), aminoglycosides, vancomycin, or capreomycin (antibiotics), phenytoin and fosphenytoin (used to treat various types of seizures), and loop diuretics (medicines used to lower blood pressure).

Combination treatment with other myelosuppressive agents (medicines that reduce blood cell counts) may require dose adjustment.

Pregnancy, breastfeeding, and fertility

If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
The safe use of carboplatin during pregnancy is unknown, but it is suspected to cause severe birth defects when administered during pregnancy.
Carboplatin is not indicated during pregnancy or in women of childbearing potential who could become pregnant, unless the potential benefit to the mother outweighs the possible risks to the foetus.
If the medicine is used during pregnancy, or if the patient becomes pregnant while using the medicine, the patient must be informed of the potential risk to the foetus. Women of childbearing potential must be advised of the potential danger to the foetus and must avoid pregnancy and use contraception during and for at least 7 months after the end of therapy.
Men of reproductive age undergoing treatment with carboplatin are advised not to father a child during treatment and to use effective contraception during treatment and for 4 months after completion of therapy.

Fertility
Gonadal suppression, leading to amenorrhoea or azoospermia, may occur in patients undergoing antineoplastic therapy. These effects appear to be dose- and duration-dependent and may be irreversible. Predicting the degree of testicular or ovarian dysfunction is complicated by the frequent use of combinations of different antineoplastic agents, making it difficult to assess the effects of individual drugs. Before starting therapy, both male and female patients should seek advice regarding fertility preservation due to the possibility of irreversible infertility caused by carboplatin therapy.

Breastfeeding
Carboplatin and its metabolites are excreted in breast milk. To avoid potential harmful effects on the newborn, breastfeeding must be discontinued during carboplatin therapy and for one month after the last dose.

Driving and use of machines
No studies on the ability to drive vehicles or operate machinery have been conducted. However, carboplatin may cause nausea, vomiting, visual disturbances, and ototoxicity; therefore, patients should be informed of the potential impact of these events on their ability to drive or operate machinery.

3. How to use Carboplatino Hikma

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
The dose you will be given depends on your age, your general health, the proper functioning of your kidneys, and other medications you may be taking.
The product may be diluted with glucose (sugar solution) or sodium chloride (saline solution) before administration. It will be given slowly, usually by intravenous infusion over 15–60 minutes. Another dose of this medicine may be administered after 4 weeks.
During treatment with carboplatin, your doctor will perform regular blood tests. These are to assess the effect of the medicine and to determine whether additional doses of carboplatin are needed.
Since this medicine will be administered while you are in hospital, it is unlikely that too little or too much will be given; however, inform your doctor or nurse if you have any concerns.
Standard safety precautions must be followed during the preparation and administration of substances classified as hazardous. Preparation must be carried out by trained professionals using protective gloves, face masks, and protective clothing.
If you have further questions about the use of this medicine, please consult your doctor or pharmacist.

Use in children
Use in children and newborns is not recommended due to insufficient data in this area.

If you use more Carboplatino Hikma than you should
This medicine will be administered in a hospital setting under the supervision of a doctor. It is unlikely that you will receive too much or too little; however, inform your doctor or nurse if you have any doubts.
There is no known antidote for carboplatin overdose.
During clinical studies, there were no reported cases of overdose. In the event of overdose, appropriate supportive treatment should be provided for complications related to myelosuppression, renal and hepatic failure, and impaired hearing function.
In reports involving doses up to 1,600 mg/m², patients experienced severe illness, with diarrhea and alopecia.
The use of carboplatin doses higher than recommended has been associated with loss of vision.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The frequency of observed side effects is defined as follows:
Very common (may affect more than 1 in 10 people)
Common (may affect up to 1 in 10 people)
Uncommon (may affect up to 1 in 100 people)
Rare (may affect up to 1 in 1,000 people)
Very rare (may affect up to 1 in 10,000 people)
Not known (frequency cannot be estimated from the available data).

If you experience any of the following side effects, inform your doctor immediately:

• Unusual bruising, bleeding, or signs of infection such as sore throat and high fever;
• Severe allergic reaction (anaphylaxis/anaphylactic reactions): a severe itchy rash (urticaria), swelling of the face, lips, mouth or throat (which may cause difficulty swallowing or breathing), or a feeling of fainting may occur;
• Chest pain, which may indicate a potentially severe allergic reaction called Kounis syndrome;
• Stomatitis/mucositis (e.g., sore lips or mouth ulcers);
• Haemolytic-uraemic syndrome (a disease characterised by acute kidney failure), reduced urination or blood in the urine;
• Muscle cramps, muscle weakness, confusion, loss or disturbances of vision, irregular heartbeat, kidney failure or abnormal blood test results (symptoms of tumour lysis syndrome, which may be caused by the rapid breakdown of tumour cells) (see section 2);
• Stroke (sudden numbness or weakness of the face, arm or leg, especially on one side of the body);
• Blockage of blood vessels (embolism and veno-occlusive disease), swelling or tenderness in the leg/arm.

Other side effects that may occur during treatment are listed below:
Very common side effects (may affect more than 1 in 10 people)

• Thrombocytopenia (reduced number of platelets in the blood), neutropenia and leucopenia (reduced white blood cell count), anaemia (reduced number of red blood cells);
• Decreased creatinine clearance;
• Increased serum levels of: urea, alkaline phosphatase, aspartate aminotransferase;
• Abnormal liver function tests;
• Decreased serum levels of sodium, potassium, calcium, magnesium;
• Vomiting, nausea, abdominal pain.

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

• Infections;
• Bleeding;
• Hypersensitivity (allergies);
• Peripheral neuropathy (nerve disease), decreased osteotendinous reflexes (related to bones and tendons), altered sensitivity;
• Paresthesia (tingling or pins and needles), dysgeusia (altered taste perception);
• Visual disturbances, including rare cases of vision loss;
• Ringing in the ears (tinnitus), hearing impairment and hearing loss;
• Cardiovascular problems;
• Respiratory problems, interstitial lung disease (lung disease with inflammation), bronchospasm (contraction of bronchial muscles causing breathing difficulties);
• Diarrhoea, constipation;
• Hair loss (alopecia), skin problems;
• Musculoskeletal disorders;
• Disorders of the reproductive tract or urinary system;
• Asthenia (weakness);
• Increased bilirubin in the blood, increased creatinine in the blood, increased uric acid in the blood.

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

• Central nervous system symptoms, often associated with medicines used to control nausea or vomiting;
• Muscle and joint pain;
• Flu-like symptoms, chills, headache.

Rare side effects (may affect up to 1 in 1,000 people)

• Temporary vision loss;
• White blood cell cancer originating from the bone marrow (acute myeloid leukaemia);
• Bone marrow disease in which blood cell production is impaired (myelodysplastic syndrome (MDS));
• Fever, sepsis/septic shock;
• Angioedema (swelling);
• Dermatitis with skin peeling.

Very rare side effects (may affect up to 1 in 10,000 people)

• Lung scarring causing shortness of breath and/or cough (pulmonary fibrosis).

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

• Cancer caused by previous treatment with carboplatin and radiotherapy (secondary neoplasms);
• Bone marrow failure (reduced ability to produce blood cells), febrile neutropenia (fever accompanied by low white blood cell count);
• Disease involving loss of red blood cells due to damage to small blood vessels (haemolytic uraemic syndrome);
• Reduced number of red blood cells due to excessive breakdown (haemolytic anaemia);
• Mental disturbances (encephalopathy);
• Blockage of a blood vessel (embolism and veno-occlusive disease), swelling or tenderness in one leg/arm;
• Dehydration, anorexia (loss of appetite), hyponatraemia (sodium levels below normal values);
• Stomatitis (inflammation of the mouth);
• A group of symptoms such as headache, altered mental function, seizures, and visual disturbances ranging from blurring to vision loss (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder);
• Optic neuritis (inflammation of the optic nerve);
• Vision loss due to brain damage;
• Cerebrovascular event;
• Heart failure (abnormal heart rate – fast, slow or irregular – or chest pain);
• Coronary artery disease (e.g. myocardial infarction, cardiac arrest, angina pectoris, myocardial ischaemia), allergic angina (Kounis syndrome);
• Hypertension (blood pressure above normal), hypotension (blood pressure below normal);
• Pancreatitis;
• Pulmonary infection;
• Urticaria, rash, erythema (redness), pruritus (itching);
• Muscle cramps, muscle weakness, confusion, vision loss or disturbances, irregular heartbeat, kidney failure or abnormal blood test results (symptoms of tumour lysis syndrome which may be caused by the rapid breakdown of tumour cells) (see section 2);
• Redness, pain or swelling at the injection site, 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: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Carboplatino Hikma

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

6. Package contents and other information

What Carboplatino Hikma contains

• The active substance is carboplatin. Each millilitre (ml) of solution contains 10 milligrams (mg) of carboplatin.
• Each vial of Carboplatino Hikma contains 50 mg, 150 mg, 450 mg or 600 mg of carboplatin.
• The other ingredients are water for injections, hydrochloric acid (to adjust pH) and sodium hydroxide (to adjust pH).

Description of the appearance of Carboplatino Hikma and contents of the pack
Carboplatino Hikma is a clear, colourless infusion solution contained in an amber glass vial sealed with a rubber stopper and aluminium cap.
The pack containing 1 vial includes 5 ml, 15 ml, 45 ml or 60 ml of infusion solution, respectively.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Hikma Farmacêutica (Portugal) S.A.
Estrada do Rio da Mó, 8, 8A and 8B, Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer:
Thymoorgan Pharmazie GmbH
Schiffgraben 23, 38690 Goslar
Germany

This medicinal product is authorised in European Economic Area (EEA) Member States under the following names:
Belgium Carboplatine Hikma 50 mg/5ml Solution for infusion / Oplossing voor infusie / Infusionslösung
Carboplatine Hikma 150 mg/15ml Solution for infusion / Oplossing voor infusie / Infusionslösung
Carboplatine Hikma 450 mg/45ml Solution for infusion / Oplossing voor infusie / Infusionslösung
Carboplatine Hikma 600 mg/60ml Solution for infusion / Oplossing voor infusie / Infusionslösung
Italy Carboplatino Hikma 10 mg/ml Solution for Infusion
Portugal Carboplatina Hikma
United Kingdom Carboplatin 10 mg/ml Solution for Infusion
Spain Carboplatino Hikma 10 mg/ml Solucion para Perfusion