JEVTANA 60 mg concentrate and solvent for solution for infusion – patient leaflet, side effects, dosage

1. What JEVTANA is and what it is used for

The name of your medicine is JEVTANA. Its common name is cabazitaxel. 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.

2. What you need to know before you are given JEVTANA

Do not use JEVTANA if

• you are allergic (hypersensitive) to cabazitaxel, to other taxanes, or polysorbate 80 or any of the other excipients 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 JEVTANA if any of the above apply to you. If you are not sure, talk to your doctor before having JEVTANA.

Warnings and precautions

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 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 JEVTANA. This is because JEVTANA may increase the risk of bleeding or developing holes in the gut wall.
• you have kidney problems.
• 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.
• 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 JEVTANA or stop the treatment.

Other medicines and JEVTANA

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);
• 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 JEVTANA.

Pregnancy, breast-feeding and 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.

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.

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.

JEVTANA contains ethanol (alcohol)

This medicine contains 573 mg of alcohol (ethanol) in each solvent vial. The amount in the dose of this medicine is equivalent to less than 11 ml beer or 5 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects. If you are addicted to alcohol, have liver disease or epilepsy, talk to your doctor or pharmacist before taking this medicine.

3. How to use JEVTANA

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.

4. Possible side effects

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:

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 pain
• 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
• 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, aches, weakness 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
• 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).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store JEVTANA

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 store above 30°C. Do not refrigerate.

Information about storage and the time to use JEVTANA, once it has been diluted and is ready to use, is described in the section “Practical information for medical or healthcare professionals on preparation, administration and handling of Jevtana“.

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

6. Contents of the pack and other information

What JEVTANA contains

The active substance is cabazitaxel. One ml of concentrate contains 40 mg cabazitaxel. One 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 “JEVTANA contains alcohol”).

Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) and the solvent vial (fill volume: 5.67 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.

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 useclear glass vial, closed with a grey rubber stopper sealed by an aluminium cap with a light green plastic flip-off cover, containing 1.5 ml (nominal volume) concentrate.
• One single use clear glass vial, closed with a grey rubber stopper sealed by a gold colour aluminium cap with a colourless plastic flip-off cover, containing 4.5 ml (nominal volume) solvent.

Marketing Authorisation Holder

sanofi-aventis groupe

54, rue La Boétie

F - 75008 Paris

France

Manufacturer

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst

65926 Frankfurt am Main

Germany

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

Belgie/Belgique/Belgien

Sanofi Belgium

Tél/Tel: +32 (0)2 710 54 00

Efcarapua

Swixx Biopharma EOOD

Tea.: +359 (0)2 4942 480

Česká republika

sanofi-aventis, s.r.o.

Tel: +420 233 086 111

Danmark

Sanofi A/S

Tlf: +45 45 16 70 00

Deutschland

Sanofi-Aventis Deutschland GmbH

Tel.: 0800 04 36 996

Tel. aus dem Ausland: +49 69 305 70 13

Eesti

Swixx Biopharma OÜ

Tel: +372 640 10 30

EMáSa

sanofi-aventis AEBE

Tql: +30 210 900 16 00

España

sanofi-aventis, S.A.

Tel: +34 93 485 94 00

Lietuva

Swixx Biopharma UAB

Tel: +370 5 236 91 40

Luxembourg/Luxemburg

Sanofi Belgium

Tel/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Magyarorszag

SANOFI-AVENTIS Zrt.,

Tel.: +36 1 505 0050

Malta

Sanofi S.r.l

Tel: +39 02 39394275

Nederland

Genzyme Europe B.V.

Tel: +31 20 245 4000

Norge

sanofi-aventis Norge AS

Tlf: +47 67 10 71 00

Österreich

sanofi-aventis GmbH

Tel: +43 1 80 185 - 0

Polska

sanofi-aventis Sp. z o.o.

Tel.: +48 22 280 00 00

France

sanofi-aventis France

Tél: 0 800 222 555

Appel depuis l’étranger : +33 1 57 63 23 23

Hrvatska

Swixx Biopharma d.o.o.

Tel: +385 1 2078 500

Ireland

sanofi-aventis Ireland Ltd. T/A SANOFI

Tel: +353 (0) 1 403 56 00

Island

Vistor hf.

Simi: +354 535 7000

Italia

Sanofi S.r.l.

Tel: +39.800.536389

Knnpoç

C.A. Papaellinas Ltd.

Tql: +357 22 741741

Latvija

Swixx Biopharma SIA

Tel: +371 6 616 47 50

This leaflet was last revised in MMM/YYYY.

Other sources of information

Portugal

Sanofi - Produtos Farmacêuticos, Lda

Tel: +351 21 35 89 400

Romania

Sanofi Romania SRL

Tel: +40 (0) 21 317 31 36

Slovenija

Swixx Biopharma d.o.o.

Tel: +386 1 235 51 00

Slovenská republika

Swixx Biopharma s.r.o.

Tel: +421 2 208 33 600

Suomi/Finland

Sanofi Oy

Puh/Tel: +358 (0) 201 200 300

Sverige

Sanofi AB

Tel: +46 (0)8 634 50 00

United Kingdom (Northern Ireland) sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +44 (0) 800 035 2525

Detailed information on this medicine is available on the European Medicines Agency web site http://www.ema.europa.eu.

The following information is intended for healthcare professionals only.

PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS

ON PREPARATION, ADMINISTRATION 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 store above 30°C.

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 entire contents of the solvent vial 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 including the 1-hour infusion time.

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 entire supplied solvent before adding to infusion solutions.

Preparation steps

Read this ENTIRE section carefully before mixing and diluting. JEVTANA requires TWO dilutions prior to administration. Follow the preparation instructions provided below.

Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) and the solvent vial (fill volume: 5.67 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.

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.

Step 1.1

Inspect the concentrate vial and the supplied solvent. The concentrate solution and the solvent should be clear.

Solvent vial

Concentrate vial (60 mg - 1.5 ml)

Step 1.2

Using a syringe fitted with a needle, aseptically withdraw the entire contents of the supplied solvent by partially inverting the vial.

Solvent vial

Step 1.3

Inject the entire contents into the corresponding concentrate vial.

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.

Once reconstituted, the resultant solution contains 10 mg/ml of cabazitaxel.

Concentratesolvent mixture 10 mg/ml

Solvent vial

Step 1.4

Remove the syringe and needle and mix manually and gently by repeated inversions until obtaining a clear and homogeneous solution. It could take approximately 45 seconds.

Step 1.5

Let this solution stand for approximately 5 minutes and check then that the solution is homogeneous and clear.

It is normal for foam to persist after this time period.

Concentrate-solvent mixture 10 mg/ml

Concentrate-solvent mixture 10 mg/ml

This resulting concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (at least 6 ml deliverable volume). The second dilution should be done immediately (within 1 hour) as detailed in Step 2.

More than one vial of the concentrate-solvent mixture may be necessary to administer the prescribed dose.

Step 2: Second (final) dilution for infusion

Step 2.1

Aseptically withdraw the required amount of concentrate-solvent mixture (10 mg/ml of cabazitaxel), with a graduated syringe fitted with a needle. As an example, a dose of 45 mg JEVTANA would require 4.5 ml of the concentrate solvent mixture prepared following Step 1.

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.

Concentrate-solvent mixture 10 mg/ml

Step 2.2

Inject in a sterile PVC-free container of 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.

Step 2.3

Remove the syringe and mix the content of the infusion bag or bottle manually using a rocking motion.

Step 2.4

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.

Required amount of concentrate-solvent mixture

5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion

The 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.

Any unused medicinal 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 (also referred to as 0.2 micrometer) is recommended during administration.

PVC infusion containers or polyurethane infusion sets should not be used for the preparation and administration of the infusion solution.

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