CABAZITAXEL 60 MG CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

The name of your medicine is Cabazitaxel 60 mg Concentrate and Solvent For Solution For Infusion.

Its common name is cabazitaxel. It belongs to a group of medicines called „taxanes“ used to treat cancers. i

Cabazitaxel is used to treat prostate cancer that has progressed after having had other chemotherapy.

It works by stopping cells from growing and multiplying. i

As part of your treatment, you will also take a corticosteroid medicine (prednisone or prednisolone) by mouth every day.

Ask your doctor to give you information about this other medicine.

Do not use Cabazitaxel if:

• you are allergic (hypersensitive) to cabazitaxel, to other taxanes, or polysorbate 80 or any of the other ingredients of this medicine (listed in section 6)
• the number of your white blood cells is too low (neutrophil counts less than or equal to 1,500 /mm3)
• you have severe abnormal liver function
• you have recently received or are about to receive a vaccine against yellow fever.

You should not be given Cabazitaxel if any of the above apply to you. If you are not sure, talk to your doctor before having Cabazitaxel.

• you have yellowing of the skin and eyes, darkening of the urine, severe nausea (feeling sick) or vomiting as they could be signs or symptoms of liver problems.
• liver problems occur during the treatment
• you experience any significant increase or decrease in daily urinary volume
• you have blood in your urine.

If any of the above applies to you, tell your doctor immediately. Your doctor may reduce the dose of Cabazitaxel or stop the treatment.

Other medicines and Cabazitaxel

Please tell your doctor, pharmacist or nurse if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription. This is because some medicines can affect the way cabazitaxel works or cabazitaxel can affect how other medicines work. These medicines include the following:

• ketoconazole, rifampicin (for infections)
• carbamazepine, phenobarbital or phenytoin (for seizures)
• St John’s Wort (Hypericum perforatum) (herbal remedy for depression and other conditions)
• statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (for reducing the cholesterol in your blood)
• valsartan (for hypertension)
• repaglinide (for diabetes).

Talk to your doctor before getting vaccinations while you are receiving Cabazitaxel.

Pregnancy, breastfeeding and fertility

Cabazitaxel should not be used in pregnant women or women of childbearing age not using contraception.

Cabazitaxel should not be used during breastfeeding.

Use a condom during sex if your partner is or could become pregnant. Cabazitaxel could be present in your semen and may affect the foetus. You are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment because Cabazitaxel may alter male fertility.

Driving and using machines

You may feel tired or dizzy when having this medicine.

If this happens, do not drive or use any tools or machines until you feel better.

Cabazitaxel Concentrate contains alcohol ethanol alcohol.

This medicine contains 573.3 mg of alcohol (ethanol) in each solvent vial. The amount in the dose of this medicine is equivalent to less than 15 ml beer or 6 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects.

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Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will discuss these with you and will explain the potential risks and benefits of your treatment.

See a doctor immediately if you notice any of the following side effects:

• fever (high temperature). This is common (may affect up to 1 in 10 people)
• severe loss of body fluids (dehydration). This is common (may affect up to 1 in 10 people). This can occur if you have severe or long-lasting diarrhoea, or fever, or if you are being sick (vomiting)
• severe stomach pain or stomach pain that doesn't go away. This can occur if you have a hole in the stomach, food pipe, gut or bowel (gastrointestinal perforation). This can lead to death.

If any of the above applies to you, tell your doctor immediately.

Other side effects include:

• skin feeling hot
• redness of the skin
• nail disorder (change in the colour of your nails; nails may detach)
• inflammation of the bladder, which can occur when your bladder has been previously exposed to radiation therapy (cystitis due to radiation recall phenomenon)

Frequency not known (cannot be estimated from the available data):

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing)

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Reporting of side effects

If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme website or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

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Warnings and precautions

Before each treatment with Cabazitaxel you will have blood tests to check that you have enough blood cells and sufficient liver and kidney functions to receive Cabazitaxel.

Tell your doctor immediately if:

• you have fever. During treatment with Cabazitaxel it is more likely that your white blood cell count may be reduced. Your doctor will monitor your blood and general condition for signs of infections. He/she may give you other medicines to maintain the number of your blood cells. People with low blood counts can develop life-threatening infections. The earliest sign of infection may be fever, so if you experience fever, tell your doctor right away
• you have ever had any allergies. Serious allergic reactions can occur during treatment with Cabazitaxel
• you have severe or long-lasting diarrhoea, you feel sick (nausea) or you are being sick (vomiting). Any of these events could cause severe dehydration. Your doctor may need to treat you
• you have feeling of numbness, tingling, burning or decreased sensation in your hands or feet
• you have any bleeding problems from the gut or have changes in the colour of your stool or stomach pain. If the bleeding or pain is severe, your doctor will stop your treatment with Cabazitaxel. This is because Cabazitaxel may increase the risk of bleeding or developing holes in the gut wall
• you have kidney problems

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The following information is intended for healthcare professionals only:

PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS ON PREPARATION, ADMINISTRATION AND HANDLING OF CABAZITAXEL 60 mg CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION

This information supplements sections 3 and 5 for the user.

It is important that you read the entire content of this procedure prior to the preparation of the infusion solution.

Incompatibilities

This medicine must not be mixed with other medicines except those used for the dilutions. PVC infusion containers or polyurethane infusion sets should not be used for the preparation and administration of the infusion solution.

Shelf life and special precautions for storage

For the pack of Cabazitaxel 60 mg Concentrate and Solvent

Do not refrigerate.

After opening

The concentrate and solvent vials must be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user. From a microbiological point of view, the two-step dilution process must take place in controlled and aseptic conditions (see below “Preparation and administration precautions”).

After initial dilution of Cabazitaxel 60 mg Concentrate with the entire contents of the solvent vial chemical and

physical in-use stability has been demonstrated for

1 hour at ambient temperature and for 21 days at

2°C-8°C.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hour at 2°C – 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

After final dilution in the infusion bag/bottle

Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at ambient temperature (15°C – 30°C) including the 1-hour infusion time and for 48 hours at refrigerated conditions (2°C – 8°C) including the 1-hour infusion time in infusion bag and for 8 hours at ambient temperature (15°C – 30°C) including the 1-hour infusion time in glass bottle.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hour at 2°C – 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Preparation and administration precautions

As for any other antineoplastic agent, caution should be exercised when handling and preparing Cabazitaxel solutions, taking into account the use of containment

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

• decrease in the number of red (anaemia), or white blood cells (which are important in fighting infection)
• decrease in the number of platelets (which results in increased risk of bleeding)
• loss of appetite (anorexia)
• stomach upsets including feeling sick (nausea), being sick (vomiting), diarrhoea or constipation
• back pain
• blood in the urine
• feeling tired, weak or lack of energy

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

• alteration of taste
• shortness of breath
• cough
• abdominal pain
• short term hair loss (in most cases normal hair growth should return)
• joint painurinary tract infection
• lack of white blood cells associated with fever and infection
• feeling of numbness, tingling, burning or decreased sensations in hands and feet
• dizziness
• headache
• decrease or increase in blood pressure
• uncomfortable feeling in the stomach, heart burn or belching
• stomach pain
• haemorrhoids
• muscle spasm
• painful or frequent urination
• urinary incontinence
• kidney disease or problems
• sore in the mouth or on lips
• infections or risk of infections
• high blood sugar
• insomnia
• mental confusion
• feeling anxious
• abnormal feeling or loss of sensation or pain in hands and feet
• trouble with balance
• rapid or irregular heartbeat
• blood clot in the leg or in the lung
• skin feeling flushed
• pain in mouth or throat
• rectal bleeding
• muscle discomfort, weakness aches or pain
• swelling of the feet or legs
• chills

Uncommon (may affect up to 1 in 100 people): low blood potassium ringing in the ear

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 outer carton and on the label of the vials after EXP. The expiry date refers to the last day of that month.

Do not refrigerate.

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Information about storage and the time to use Cabazitaxel, once it has been diluted and is ready to use, are described in the section “PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS ON PREPARATION, ADMINISTRATION AND HANDLING OF CABAZITAXEL 60 mg CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION„. i i

Any unused product or waste material should be disposed of in accordance with local requirements. These measures will help to protect the environment.

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What Cabazitaxel Concentrate contains

The active substance is cabazitaxel. One ml of concentrate contains 40 mg cabazitaxel. Each vial of concentrate contains 60 mg cabazitaxel.

The other ingredients are polysorbate 80 and citric acid in the concentrate, and ethanol 96% and water for injections in the solvent (see section 2 “Cabazitaxel concentrate contains alcohol”).

Note: Both the Cabazitaxel 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1­.83 ml) and the solvent vial (fill volume: 5.70 ml) contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the ENTIRE contents of the accompanying solvent, there is solution containing 10 mg/ml cabazitaxel.