Jevtana

Package leaflet: Information for the patient

JEVTANA 60 mg concentrate and solvent for solution for infusion

cabazitaxel
Please read all of this leaflet carefully before you start using 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4. Contents of this leaflet:
  1. What JEVTANA is and what it is used for
  2. What you need to know before you are given JEVTANA
  3. How JEVTANA is given
  4. Possible side effects
  5. How to store JEVTANA
  6. Contents of the pack and other information

1. What JEVTANA is and what it is used for

The name of the medicine is JEVTANA. The common name is cabazitaxel. It belongs to a group of
medicines called "taxanes" used to treat cancer.
JEVTANA is used to treat prostate cancer that has progressed after prior chemotherapy treatments. It works by blocking the growth and spread of cancer cells.
As part of your treatment, you will also take an oral corticosteroid (prednisone or prednisolone) daily. Please consult your doctor for information about this second medicine.

2. What you need to know before using JEVTANA

Do not use JEVTANA if:

• you are allergic to cabazitaxel, to other taxanes, to polysorbate 80, or to any of the other ingredients of this medicine (listed in section 6);
• your white blood cell count is too low (neutrophil count less than or equal to 1,500/mm³);
• you have severe liver function impairment;
• you have recently received or are about to receive the yellow fever vaccine.
  If you think any of these apply to you, you must not receive JEVTANA. If in doubt, consult your doctor before using JEVTANA.

Warnings and precautions

Before each treatment with JEVTANA, you will need to have blood tests to ensure that your blood cell counts are adequate and that your liver and kidney functions are sufficient to allow administration of JEVTANA. Inform your doctor immediately:

• if you have a fever. During treatment with JEVTANA, a decrease in white blood cell count is more likely. Your doctor will monitor your blood and general condition to detect any signs of infection. You may be given additional medications to maintain stable blood cell counts. Patients with low blood cell counts may develop potentially life-threatening infections. Fever may be the first sign of an infection; therefore, inform your doctor immediately if you develop a fever;
• if you have ever had any allergies. Severe allergic reactions may occur during treatment with JEVTANA;
• if you have severe or prolonged diarrhea, nausea, or vomiting. Any of these conditions may lead to severe dehydration. Your doctor may consider it necessary to initiate treatment;
• if you experience numbness, tingling, burning sensations, or reduced sensitivity in your hands or feet;
• if you have intestinal bleeding problems or notice changes in stool color or stomach pain. If bleeding or pain is severe, your doctor will discontinue JEVTANA treatment. This is because JEVTANA may increase the risk of gastrointestinal bleeding or intestinal perforation;
• if you have kidney problems;
• if you develop liver problems during treatment;
• if you notice yellowing of the skin or eyes (jaundice), darkening of the urine, severe nausea (feeling unwell), or vomiting, as these may be signs or symptoms of liver problems;
• if you notice a significant increase or decrease in daily urine volume;
• if you notice blood in your urine.

If any of the above conditions apply to you, inform your doctor immediately. Your doctor may reduce the dose of JEVTANA or discontinue treatment.

Other medicines and JEVTANA

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription. This is because some medicines may affect how JEVTANA works, or JEVTANA may affect the action of other medicines. These include:

• ketoconazole, rifampicin (for infections);
• carbamazepine, phenobarbital, or phenytoin (for epileptic seizures);
• St. John’s wort (Hypericum perforatum) (a herbal product used for depression and other conditions);
• statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (to lower blood cholesterol);
• valsartan (for hypertension);
• repaglinide (for diabetes).

Consult your doctor before receiving any vaccination during treatment with JEVTANA.

Pregnancy, breastfeeding, and fertility

JEVTANA is not indicated for use in women. Use a condom during sexual intercourse if your partner is pregnant or could become pregnant. JEVTANA may be present in semen and could affect the fetus. It is recommended not to father a child during treatment and for 4 months after treatment ends. You should seek advice on sperm preservation before starting treatment, as JEVTANA may impair male fertility.

Driving and use of machines

While taking this medicine, you may feel tired or dizzy. If this occurs, do not drive or operate machinery until you feel better.

JEVTANA contains ethanol (alcohol)
This medicine contains 573 mg of alcohol (ethanol) in each vial of solvent. The amount per dose of this medicine is equivalent to less than 11 mL of beer or 5 mL of wine. The small amount of alcohol in this medicine will not have any noticeable effect. However, if you are alcohol-dependent, or suffer from liver disease or epilepsy, consult your doctor or pharmacist before taking this medicine.

3. How to use JEVTANA

Instructions for use
Before starting treatment with JEVTANA, you must take antiallergic medicines to reduce the
risk of allergic reactions:

• JEVTANA will be administered to you by a doctor or a nurse.
• JEVTANA must be prepared (diluted) before administration. This patient information leaflet contains practical information on the handling and administration of JEVTANA for doctors, nurses, and pharmacists.
• JEVTANA will be administered to you in a hospital setting by intravenous infusion lasting approximately 1 hour.
• As part of your treatment, you will also take a corticosteroid (prednisone or prednisolone) orally every day. What doses and how often will it be administered?
• The usual dose depends on your body surface area. Your doctor will calculate your body surface area in square meters (m²) and determine the appropriate dose for you.
• Normally, you will receive one infusion every 3 weeks.

If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. Discuss this with your doctor, who will also explain the potential risks and benefits of the treatment.
Contact your doctor immediately if you notice any of the following side effects:

• fever (elevated body temperature). This is a common side effect (may occur in up to 1 in 10 people);
• severe loss of body fluids (dehydration). This is a common side effect (may occur in up to 1 in 10 people). It may occur if you have severe or prolonged diarrhoea, fever, or vomiting;
• severe stomach pain or persistent stomach discomfort. This may occur if you have a perforation in the stomach, oesophagus, or intestine (gastrointestinal perforation). This condition can be fatal. If any of these apply to you, inform your doctor immediately.

Other side effects:

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

• decrease in red blood cells (anaemia) or white blood cells (which are important in fighting infections)
• decrease in platelets (leading to an increased risk of bleeding)
• loss of appetite (anorexia)
• stomach problems including nausea, vomiting, diarrhoea or constipation
• back pain
• blood in the urine
• feeling tired, weak or lacking energy.

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

• altered taste
• shortness of breath
• cough
• abdominal pain
• temporary hair loss (in most cases, hair will regrow)
• joint pain
• urinary tract infection
• low white blood cell count associated with fever and infection
• numbness, tingling, burning sensation or reduced sensitivity in hands and feet
• dizziness
• headache
• low or high blood pressure
• stomach discomfort, burning sensation or belching
• stomach pain
• haemorrhoids
• muscle spasms
• pain or increased frequency of urination
• urinary incontinence
• kidney diseases or disorders
• mouth or lip ulcers
• infections or increased risk of infections
• high blood sugar
• insomnia
• mental confusion
• feeling anxious
• abnormal sensation or loss of sensitivity or pain in hands and feet
• balance problems
• rapid or irregular heartbeat
• blood clots in the legs or lungs (thrombosis)
• skin redness
• mouth or throat pain
• rectal bleeding
• discomfort, weakness or muscle pain
• swelling of feet or legs
• chills
• nail disorders (changes in nail colour; nails may detach).

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

• low levels of potassium in the blood
• ringing in the ears
• skin burning sensation
• skin redness
• inflammation of the bladder, which may occur when the bladder has previously been exposed to radiotherapy (radiation recall cystitis).

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

• interstitial lung disease (lung inflammation causing cough and breathing difficulties)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex 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 carton and on the label of the
vials after Exp. The expiry date refers to the last day of the month.
Do not store above 30 °C. Do not store in the refrigerator.
For information on storage and duration of use of JEVTANA after dilution and preparation, refer to the
section on “ Practical information for physicians or healthcare professionals on the preparation,
administration and handling of Jevtana”.
Any unused medicine and waste material resulting from this medicine should be disposed of in
accordance with local regulations. This will help protect the environment.

6. Package contents and other information

What JEVTANA contains
The active substance is cabazitaxel. One mL of concentrate contains 40 mg of cabazitaxel. One vial of concentrate contains 60 mg of cabazitax el.
The other components in the concentrate are polysorbate 80 and citric acid; in the solvent they are 96% ethanol and water for injections (see section 2 “JEVTANA contains alcohol”).
Note: both the vial containing the JEVTANA 60 mg/15 mL concentrate (fill volume 73.2 mg cabazitaxel/1.83 mL) and the vial containing the solvent (fill volume 5.67 mL) include overfill to compensate for liquid loss during preparation. The overfill ensures that after dilution of the concentrate with the ENTIRE contents of the provided solvent vial, a solution containing 10 mg/mL of cabazitaxel is obtained.

Description of the appearance of JEVTANA and contents of the pack
JEVTANA consists of a concentrate and a solvent for infusion solution (sterile concentrate).
The concentrate is an oily, transparent solution ranging from yellow to yellowish-brown.
The solvent is a transparent, colourless solution.
A JEVTANA pack contains:

• one single-use clear glass vial with grey rubber stopper sealed with an aluminium cap covered by a green plastic flip-off cap, containing 1.5 mL (nominal volume) of concentrate.
• one single-use clear glass vial with grey rubber stopper sealed with a golden-coloured aluminium cap and transparent plastic flip-off cap, containing 4.5 mL (nominal volume) of solvent.

Marketing Authorisation Holder
Sanofi Winthrop Industrie
82 avenue Raspail
94250 Gentilly
France

Manufacturer
Sanofi-Aventis Deutschland GmbH
Industriepark Höchst
65926 Frankfurt am Main
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sanofi Belgium Swixx Biopharma UAB
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 236 91 40

България Luxembourg/Luxemburg
Swixx Biopharma EOOD Sanofi Belgium
Тел.: +359 (0)2 4942 480 Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika Magyarország
sanofi-aventis, s.r.o. SANOFI-AVENTIS Zrt.,
Tel: +420 233 086 111 Tel.: +36 1 505 0050

Danmark Malta
Sanofi A/S Sanofi S.r.l
Tlf: +45 45 16 70 00 Tel: +39 02 39394275

Deutschland Nederland
Sanofi-Aventis Deutschland GmbH Sanofi B.V.
Tel.: 0800 04 36 996 Tel: +31 20 245 4000
Tel. aus dem Ausland: +49 69 305 70 13

Eesti Norge
Swixx Biopharma OÜ sanofi-aventis Norge AS
Tel: +372 640 10 30 Tlf: +47 67 10 71 00

Ελλάδα Österreich
Sanofi-Aventis Μονοπρόσωπη AEBE sanofi-aventis GmbH
Τηλ: +30 210 900 16 00 Tel: +43 1 80 185 – 0

España Polska
sanofi-aventis, S.A. sanofi-aventis Sp. z o.o.
Tel: +34 93 485 94 00 Tel.: +48 22 280 00 00

France Portugal
Sanofi Winthrop Industrie Sanofi - Produtos Farmacêuticos, Lda
Tél: 0 800 222 555 Tel: +351 21 35 89 400
Appel depuis l’étranger : +33 1 57 63 23 23

Hrvatska România
Swixx Biopharma d.o.o. Sanofi Romania SRL
Tel: +385 1 2078 500 Tel: +40 (0) 21 317 31 36

Ireland Slovenija
sanofi-aventis Ireland Ltd. T/A SANOFI Swixx Biopharma d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 235 51 00

Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 208 33 600

Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: +39.800.536389 Puh/Tel: +358 (0) 201 200 300

Κύπρος Sverige
C.A. Papaellinas Ltd. Sanofi AB
Τηλ: +357 22 741741 Tel: +46 (0)8 634 50 00

Latvija United Kingdom (Northern Ireland)
Swixx Biopharma SIA sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6 616 47 50 Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals.

PRACTICAL INFORMATION FOR PHYSICIANS OR HEALTHCARE PROFESSIONALS ON THE PREPARATION, ADMINISTRATION AND HANDLING OF JEVTANA 60 mg CONCENTRATE AND SOLVENT FOR INFUSION SOLUTION

This information supplements sections 3 and 5 for the user.
Before preparing the infusion solution, it is important to read the entire content of this procedure.

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those used for dilution.

Shelf life and special precautions for storage
For the JEVTANA 60 mg concentrate and solvent pack
Do not store above 30 °C.
Do not refrigerate.

After opening
The concentrate and solvent vials must be used immediately. If not used immediately, the times and conditions of in-use storage are the responsibility of the user.
From a microbiological point of view, the two-step dilution procedure must be performed under controlled and aseptic conditions (see section “Precautions for preparation and administration” below).

After initial dilution of JEVTANA 60 mg concentrate with the ENTIRE contents of the solvent vial provided, chemical and physical in-use stability has been demonstrated for 1 hour at room temperature.

After final dilution in the infusion bag/vial
Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at room temperature (15 °C – 30 °C), including the 1-hour infusion time, and for 48 hours under refrigeration (2 °C – 8 °C), including the 1-hour infusion time.
From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should normally not exceed 24 hours at 2 °C – 8 °C, unless dilution occurs under validated and controlled aseptic conditions.

Precautions for preparation and administration
As with any other antineoplastic agent, caution should be exercised during handling and preparation of JEVTANA-based solutions, and consideration should be given to using containment devices, personal protective equipment (e.g., gloves), and preparation procedures.
If JEVTANA comes into contact with the skin at any stage of handling, wash the affected area immediately and thoroughly with soap and water. If contact with mucous membranes occurs, rinse immediately and thoroughly with water.
JEVTANA must be administered and prepared only by personnel qualified in handling cytotoxic agents. The medicine should not be handled by pregnant personnel.
Always dilute the concentrate for infusion solution with the ENTIRE solvent provided before adding it to the infusion solution.

Steps for preparation
Read ENTIRELY the paragraph below before mixing and diluting. JEVTANA requires TWO dilutions before administration. Follow the instructions below for preparation.
Note: both the vial containing the JEVTANA 60 mg/1.5 mL concentrate (fill volume 73.2 mg cabazitaxel/1.83 mL) and the vial containing the solvent (fill volume 5.67 mL) include overfill to compensate for liquid loss during preparation. The overfill ensures that after dilution of the concentrate with the ENTIRE contents of the provided solvent vial, a solution containing 10 mg/mL of cabazitaxel is obtained.
For preparation of the infusion solution, the two-step dilution process described below must be performed aseptically.

Step 1: Initial dilution of the concentrate for infusion solution

Step 1.1
Check the vial containing the concentrate and the provided solvent. The concentrate solution and solvent must be transparent.

Concentrate vial Solvent vial

Step 1.2
Using a syringe with a needle, aseptically withdraw the ENTIRE contents of the provided solvent by partially inverting the solvent vial.

Solvent vial
Step 1.3

Inject the ENTIRE contents into the corresponding vial containing the concentrate.
To minimize foam formation while injecting the solvent, orient the needle against the inner wall of the concentrate vial and inject slowly.
Once reconstituted, the resulting solution

Vial

Concentrate vial
10 mg/mL solvent
contains 10 mg/mL of cabazitaxel.

Step 1.4
Remove the syringe and needle and mix manually by gently inverting the vial. Repeat inversion until a clear, homogeneous solution is obtained. Approximately 45 seconds may be required.

Concentrate-solvent mixture 10 mg/mL
Step 1.5

Allow the solution to stand for approximately 5 minutes, then check that it is homogeneous and transparent.
The persistence of foam after the indicated time is normal.
The concentrate-solvent mixture thus obtained contains 10 mg/mL of cabazitaxel (at least 6 mL of administrable volume). The second dilution must be performed immediately (within 1 hour) as specified in Step 2.
More than one vial of the concentrate-solvent mixture may be required to administer the prescribed dose.

Concentrate-solvent mixture 10 mg/mL
Step 2: Final (second) dilution for infusion

Step 2.1
Aseptically withdraw with a graduated syringe with needle the required amount of the concentrate-solvent mixture (10 mg/mL cabazitaxel). For example, a 45 mg dose of JEVTANA requires 4.5 mL of the concentrate-solvent mixture prepared according to Step 1.
Since foam may persist on the walls of the vial prepared according to Step 1, it is preferable to insert the syringe needle into the center of the vial during withdrawal.

Concentrate-solvent mixture 10 mg/mL
Step 2.2

Inject the solution into a sterile, non-PVC container containing 5% glucose solution or 9 mg/mL (0.9%) sodium chloride solution for infusion. The concentration of the infusion solution must be between 0.10 mg/mL and 0.26 mg/mL.

5% glucose solution or
Concentrate-solvent mixture
0.9% sodium chloride
required
for infusion

Step 2.3
Remove the syringe and mix the contents of the infusion vial manually with a gentle rocking motion.
Step 2.4
As with all parenteral products, the resulting infusion solution should be visually inspected. Since the infusion solution is supersaturated, it may crystallize over time. In such a case, the solution must not be used and must be discarded.
The infusion solution should be used immediately. However, the in-use storage period may be longer if the specific conditions mentioned in the section Shelf life and special precautions for storage above are respected.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.

Method of administration
JEVTANA is administered as a 1-hour infusion.
During administration, use of an in-line filter with a nominal pore size of 0.22 micrometers (also referred to as 0.2 micrometers) is recommended.
Do not use PVC infusion containers or polyurethane infusion sets for the preparation and administration of the infusion solution.