JEVTANA 60 mg concentrate and solvent for solution forinfusion

The name of your medicine is JEVTANA. It belongs to a group of medicines called ?taxanes? used to treat cancers.

JEVTANA is used to treat prostate cancer that has progressed after having had other chemotherapy. It works by stopping cells from growing and multiplying.

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 JEVTANA if:

• you are allergic (hypersensitive) to cabazitaxel, to other taxanes, or to any of the other excipients of the formulation including polysorbate 80,
• the number of your white blood cells is too low (neutrophil counts less than or equal to 1,500 /mm 3),
• you have abnormal liver function,
• you have recently received or are about to receive a vaccine against yellow fever.

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

Take special care with JEVTANA

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

Tell your doctor immediately if:

• you have fever. During treatment with JEVTANA, 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 JEVTANA.
• 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 kidney problems.
• liver problems occur during the treatment.
• you experience any significant increase or decrease in daily urinary volume.

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

Taking other medicines

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 JEVTANA works or JEVTANA 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.

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

Fertility, pregnancy and breast-feeding

Use a condom during sex if your partner is or could become pregnant. JEVTANA 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 JEVTANA may alter male fertility.

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

JEVTANA should not be used during breast-feeding.

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.

Important information about some of the ingredients of JEVTANA

This medicine contains 15% v/v ethanol (alcohol), equivalent to 14 ml of beer or 6 ml of wine. This medicine may be harmful for those suffering from alcoholism.

To be taken into account if you are in a high-risk group such as patients with liver disease, or epilepsy.

Instructions for use

Anti-allergic medicines will be given to you before you have JEVTANA to reduce the risk of allergic reactions.

• JEVTANA will be given to you by a doctor or a nurse.
• JEVTANA must be prepared (diluted) before it is given. Practical information for handling and administration of JEVTANA for doctors, nurses and pharmacists is provided with this leaflet.
• JEVTANA will be given by a drip (infusion) into one of your veins (intravenous use) in hospital for about an hour.
• As part of your treatment, you will also take a corticosteroid medicine (prednisone or prednisolone) by mouth every day.

How much and how often to have

• The usual dose depends on your body surface area. Your doctor will calculate your body surface area in square meters (m²) and will decide the dose you should have.
• You will usually have an infusion once every 3 weeks.

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

Like all medicines, JEVTANA 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 very common (affects more than 1 in 10 patients).
• severe loss of body fluids (dehydration). This is common (affects less than 1 in 10 patients). This can occur if you have severe or long-lasting diarrhoea, or fever, or if you are being sick (vomiting). If any of the above applies to you, tell your doctor immediately.

Other side effects include:

Very common (affects more than 1 in 10 patients):

• 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)
• alteration in sense of taste
• shortness of breath
• cough
• stomach upsets including feeling sick (nausea), being sick (vomiting), diarrhoea or constipation
• abdominal pain
• short term hair loss (in most cases normal hair growth should return)
• back pain
• joint pain
• blood in the urine
• feeling tired, weak or lack of energy.

Common (affects less than 1 in 10 patients):

• urinary 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
• low blood potassium
• mental confusion
• feeling anxious
• abnormal feeling or loss of sensation or pain in hands and feet
• ringing in the ear
• trouble with balance
• rapid or irregular heartbeat
• blood clot in the leg
• skin feeling hot or flushed
• pain in mouth or throat
• rectal bleeding
• redness of the skin
• muscle discomfort, aches or pain
• swelling of the feet or legs
• chills.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, pharmacist or nurse.

Keep out of the reach and sight of children.

Do not use JEVTANA 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.

Information about storage and the time to use JEVTANA, once it has been diluted and is ready to use, are described in the section ?practical information for handling and administration?.

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

What JEVTANA 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.

What JEVTANA looks like and contents of the pack

JEVTANA is a concentrate and solvent for solution for infusion (sterile concentrate). The concentrate is a clear yellow to brownish-yellow oily solution.
The solvent is a clear and colourless solution.

One pack of JEVTANA contains:

• One single-use vial of 1.5 ml concentrate in a clear glass vial closed with a grey chlorobutyl rubber closure sealed by an aluminium cap with a light green plastic flip-off cover.
• One single-use vial of 4.5 ml solvent in clear glass vial closed with a grey chlorobutyl rubber closure sealed by a gold colour aluminium cap with a colourless plastic flip-off cover.

Marketing Authorisation Holder

sanofi-aventis
174, avenue de France
F - 75013 Paris
France

Manufacturer

Aventis Pharma, Dagenham
Rainham Road South
Dagenham
Essex RM10 7XS
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien sanofi-aventis Belgium TélTel 32 02 710 54 00 LuxembourgLuxemburg sanofi-aventis Belgium TélTel 32 02 710 54 00 BelgiqueBelgien

sanofi-aventis Bulgaria EOOD . 359 02 970 53 00 Magyarország sanofi-aventis zrt., Magyarország Tel. 36 1 505 0050

eská republika sanofi-aventis, s.r.o. Tel 420 233 086 111 Malta sanofi-aventis Malta Ltd. Tel 356 21493022

Danmark sanofi-aventis Denmark AS Tlf 45 45 16 70 00 Nederland sanofi-aventis Netherlands B.V. Tel 31 0182 557 755

Deutschland Sanofi-Aventis Deutschland GmbH Tel 49 0180 2 222010 Norge sanofi-aventis Norge AS Tlf 47 67 10 71 00

Eesti sanofi-aventis Estonia OÜ Tel 372 627 34 88 Österreich sanofi-aventis GmbH Tel 43 1 80 185 0

sanofi-aventis AEBE 30 210 900 16 00 Polska sanofi-aventis Sp. z o.o. Tel. 48 22 280 00 00

España sanofi-aventis, S.A. Tel 34 93 485 94 00 Portugal sanofi-aventis - Produtos Farmacêuticos, Lda Tel 351 21 35 89 400

România sanofi-aventis România S.R.L. Tel 40 0 21 317 31 36 France sanofi-aventis France Tél 0 800 222 555 Appel depuis létranger 33 1 57 63 23 23 Ireland sanofi-aventis Ireland Ltd. Tel 353 0 1 403 56 00 Slovenija sanofi-aventis d.o.o. Tel 386 1 560 48 00

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika sanofi-aventis Pharma Slovakia s.r.o. Tel 421 2 33 100 100

Italia sanofi-aventis S.p.A. Tel 39 02 393 91 SuomiFinland sanofi-aventis Oy PuhTel 358 0 201 200 300

sanofi-aventis Cyprus Ltd. 357 22 871600 Sverige sanofi-aventis AB Tel 46 08 634 50 00

Latvija sanofi-aventis Latvia SIA Tel 371 67 33 24 51 United Kingdom sanofi-aventis Tel 44 0 1483 505 515

Lietuva

UAB sanofi-aventis Lietuva
Tel: +370 5 2755224

This leaflet was last approved in .

The following information is intended for medical or healthcare professionals only.

PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS ON PREPARATION AND HANDLING OF JEVTANA 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.

Shelf life and special precautions for storage

For the pack of JEVTANA 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 JEVTANA 60 mg concentrate with the solvent:
Chemical and physical in-use stability has been demonstrated for 1 hour at ambient temperature.

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.

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 conditons.

Preparation and administration precautions

As for any other antineoplastic agent, caution should be exercised when handling and preparing JEVTANA solutions, taking into account the use of containment devices, personal protective equipment (e.g. gloves), and preparation procedures.
If JEVTANA, at any step of its handling, should come into contact with the skin, wash immediately and thoroughly with soap and water. If it should come into contact with mucous membranes, wash immediately and thoroughly with water.

JEVTANA should only be prepared and administered by personnel trained in handling cytotoxic agents. Pregnant staff should not handle it.

Always dilute the concentrate for solution for infusion with the supplied solvent before adding to infusion solutions.

Preparation steps

The following two-step dilution process must be carried out in an aseptic manner for preparing the solution for infusion.

Step 1: Initial dilution of the concentrate for solution for infusion with the supplied solvent.

• Set aside the JEVTANA concentrate vial and the supplied solvent. The solution in the concentrate vial should be clear.
• Withdraw the entire content of the supplied solvent using a syringe, by partially inverting the vial, and inject it into the corresponding vial of JEVTANA concentrate. To limit foaming as much as possible when injecting the solvent, direct the needle onto the inside wall of the vial of concentrate solution and inject slowly.
• Remove the syringe and needle and mix manually and gently by repeated inversions until obtaining clear and homogeneous solution. It could take approximately 45 seconds.
• Let this solution stand for approximately 5 minutes and then check that the solution is homogeneous and clear. It is normal for foam to persist after this time period.

This resulting concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (at least 6 ml deliverable volume). It should be immediately diluted as detailed in step 2.

Step 2: Preparation of the infusion solution.

• Based on the required dose for the patient, withdraw the corresponding volume of the concentrate-solvent mixture containing 10 mg/ml of JEVTANA, with a graduated syringe. As an example, a dose of 45 mg JEVTANA would require 4.5 ml of the concentrate-solvent mixture prepared following step 1. More than one vial of the concentrate-solvent mixture may be necessary for preparing the appropriate dose.
• Since foam may persist on the wall of the vial of this solution, following its preparation described in step 1, it is preferable to place the needle of the syringe in the middle when extracting.
• Use PVC-free infusion containers and inject the withdrawn volume into either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. The concentration of the infusion solution should be between 0.10 mg/ml and 0.26 mg/ml.
• Remove the syringe and mix the content of the infusion bag or bottle manually using a rocking motion.

The JEVTANA infusion solution should be used immediately. However, in-use storage time can be longer under specific conditions mentioned in section Shelf life and special precautions for storage above.

As with all parenteral products, the resulting infusion solution should be visually inspected prior to use. As the infusion solution is supersaturated, it may crystallize over time. In this case, the solution must not be used and should be discarded.

Any unused product or waste material should be disposed of in accordance with local requirements.

Method of administration

JEVTANA is administered as a 1 hour infusion.
An in-line filter of 0.22 micrometer nominal pore size is recommended during administration. PVC infusion containers and polyurethane infusion sets should not be used for the preparation and administration of the infusion solution.