JEVTANA 60 mg Concentrate and Solvent for Solution for Infusion

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

Do not use JEVTANA

• if you are allergic (hypersensitive) to cabazitaxel, other taxanes, polysorbate 80, or any of the other ingredients of this medicine (listed in section 6),
• if your white blood cell count is very low (neutrophil count less than or equal to 1,500/mm3),
• if you have severe liver problems,
• if you have recently been or are going to be vaccinated against yellow fever.

Do not receive JEVTANA if any of the above applies to you. If you are not sure, consult your doctor before receiving JEVTANA.

Warnings and precautions

Before starting treatment with JEVTANA, you will have blood tests to check that you have enough blood cells and that your kidneys and liver are working properly to receive JEVTANA.

Tell your doctor immediately if:

• you have a fever. During treatment with JEVTANA, it is more likely that your white blood cell count will decrease. Your doctor will check your blood and general condition to detect signs of infection. You may be given other medicines to keep your blood cell count up. People with low cell counts can develop life-threatening infections. The first sign of infection may be a fever, so if you have a fever, tell your doctor immediately.

• you have ever had any allergy. During treatment with JEVTANA, severe allergic reactions can occur.

• you have severe or persistent diarrhea, feel unwell (nausea) or are being sick (vomiting). Any of these situations can cause severe dehydration. Your doctor should give you treatment.

• you have a feeling of numbness, tingling, burning, or decreased sensation in your hands and feet.

• you have any bleeding problems in the intestine or have changes in the color of your stools 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 development of perforations in the intestinal wall.

• you have kidney problems.

• you have yellowing of the skin and eyes, dark urine, severe nausea (feeling unwell) or vomiting, as these may be signs or symptoms of liver problems.
• you notice that the volume of your urine increases or decreases significantly.

• you have blood in your urine.

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

Using JEVTANA with other medicines

Tell your doctor, pharmacist, or nurse if you are using or have recently used other medicines, including those obtained without a prescription. This is because some medicines can affect the efficacy of JEVTANA or JEVTANA can affect the efficacy of other medicines. These medicines include:

• ketoconazole, rifampicin (for infections);
• carbamazepine, phenobarbital, or phenytoin (for seizures);
• St. John's Wort or hypericum (Hypericum perforatum) (a medicinal plant used to treat depression and other problems);
• statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (to reduce cholesterol in your blood);
• valsartan (for hypertension);
• repaglinide (for diabetes).

While you are being treated with JEVTANA, consult your doctor before getting vaccinated.

Pregnancy, breastfeeding, and fertility

JEVTANA is not indicated for use in women.

Use condoms in your sexual relations if your partner is or may be pregnant. JEVTANA may be present in your semen and can affect the fetus. It is recommended not to father a child during and up to 4 months after treatment and to ask for information about sperm preservation before treatment, as JEVTANA may alter male fertility.

Driving and using machines

During treatment with this medicine, you may feel tired or dizzy. If this happens, do not drive or use tools or machines until you feel better.

JEVTANA contains ethanol (alcohol)

This medicine contains 573 mg of alcohol (ethanol) in each vial of solvent. The amount in the 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 does not produce any noticeable effect. If you have alcohol addiction, have liver disease, or have epilepsy, consult your doctor or pharmacist before taking this medicine.

3. How to use JEVTANA

Instructions for use

Before you receive JEVTANA, you will be given anti-allergic medicines to reduce the risk of allergic reactions.

• JEVTANA will be administered by a doctor or nurse.

• JEVTANA must be prepared (diluted) before administration. This leaflet provides practical information for the handling and administration of JEVTANA for doctors, nurses, and pharmacists.

• JEVTANA will be administered in the hospital through a drip (infusion) in one of your veins (intravenously) for about 1 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 it is administered

• The usual dose depends on your body surface area. Your doctor will calculate your body surface area in square meters (m2) and decide the dose you should receive.

• Usually, you will receive an infusion every 3 weeks.

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

4. Possible side effects

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

Go to your 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 happen if you have severe or persistent diarrhea, or fever, or if you have been vomiting.

• severe stomach pain or stomach pain that does not go away. This can happen if you have a perforation in the stomach, esophagus, or intestine (gastrointestinal perforation). This can be life-threatening.

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

Other side effects include:

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

• reduction in the number of red blood cells (anemia), or white blood cells (which are important for fighting infections)
• reduction in the number of platelets (which results in an increased risk of bleeding)
• loss of appetite (anorexia)
• stomach upset, including nausea, vomiting, diarrhea, or constipation
• back pain
• blood in the urine
• fatigue, weakness, or lack of 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 grows back normally)
• joint pain
• urinary tract infection
• low white blood cell count associated with fever and infections
• numbness, tingling, burning, or decreased sensation in hands and feet
• dizziness
• headache
• increase or decrease in blood pressure
• indigestion, heartburn, or belching
• stomach pain
• hemorrhoids
• muscle spasms
• frequent or painful urination
• urinary incontinence
• kidney problems
• mouth or lip ulcers
• infections or risk of infections
• high blood sugar levels
• insomnia
• confusion
• feeling anxious
• strange sensation or loss of sensation or pain in hands and feet
• balance problems
• rapid or irregular heartbeat
• blood clots in the legs or lungs
• flushing of the skin
• mouth or throat pain
• rectal bleeding
• muscle disorders, weakness, or pain
• swelling of feet or legs
• chills.
• nail disorders (change in nail color; nails may come off).

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

• low potassium levels in the blood
• ringing in the ears
• feeling of heat in the skin
• red skin
• inflammation of the bladder, which can occur when your bladder has been previously exposed to radiation (radiation recall cystitis).

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

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

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of 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 is the last day of the month stated.

Do not store above 30°C. Do not refrigerate.

In the section "PRACTICAL INFORMATION FOR DOCTORS OR HEALTHCARE PROFESSIONALS ON THE PREPARATION, ADMINISTRATION, AND HANDLING OF JEVTANA" information is included on the storage and shelf-life of JEVTANA, once it has been diluted and is ready for use.

Disposal of unused medicine and all materials that have come into contact with it will be done in accordance with local regulations. These measures will help protect the environment.

6. Contents of the pack and additional information

Composition of JEVTANA

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

The other components are polysorbate 80 and citric acid in the concentrate, and ethanol 96% and water for injectable preparations in the solvent (see section 2 "JEVTANA contains ethanol (alcohol)").

Note: both the vial of JEVTANA 60 mg/1.5 ml concentrate (fill volume: 73.2 mg of cabazitaxel/1.83 ml) and the vial of solvent (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the complete contents of the provided solvent, there is a solution containing 10 mg/ml of cabazitaxel.

Appearance of the product and pack contents

JEVTANA is a concentrate and solvent for solution for infusion (sterile concentrate).

The concentrate is a clear, oily solution, yellow to yellowish-brown in color.

The solvent is a clear, colorless solution.

A pack of JEVTANA contains:

• A single-use glass vial, closed with a gray rubber stopper, sealed with an aluminum cap, covered with a greenish-clear plastic flip-off cap, containing 1.5 ml (nominal volume) of concentrate.
• A single-use glass vial, closed with a gray rubber stopper, sealed with a golden aluminum cap, covered with a colorless plastic flip-off cap, containing 4.5 ml (nominal volume) of solvent.

Marketing authorization holder and manufacturer

Marketing authorization holder

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Manufacturer

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst

65926 Frankfurt am Main

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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The following information is intended for healthcare professionals only.

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

This information complements sections 3 and 5 for the user.

It is essential that you read the entire content of this procedure before preparing the infusion solution.

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those used for 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 vial

The vials of concentrate and solvent must be used immediately. If not used immediately, the time and conditions of storage are the responsibility of the user. From a microbiological point of view, the two-stage dilution process must be carried out under controlled and aseptic conditions (see below "Precautions for preparation and administration").

After initial dilutionof JEVTANA 60 mg concentrate with the complete contents of the vial of solvent:

chemical and physical stability in use has been demonstrated for 1 hour at room temperature.

After final dilution in the infusion bag/bottle

Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at room temperature (15°C - 30°C) including 1 hour of infusion time and for 48 hours in the refrigerator, including infusion time.

From a microbiological point of view, the infusion solution must be used immediately. If not used immediately, the times and conditions of storage are the responsibility of the user and normally should not exceed 24 hours at 2°C - 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.

Precautions for preparation and administration

As with other antineoplastic agents, it is recommended to handle the JEVTANA solutions with caution, taking into account the use of safety devices, personal protective equipment (e.g., gloves), and preparation procedures.

If, at any stage of preparation, JEVTANA comes into contact with the skin, wash immediately and thoroughly with water and soap. If it comes into contact with mucous membranes, wash immediately and thoroughly with water.

JEVTANA should only be prepared and administered by personnel trained in the handling of cytotoxic agents. Pregnant healthcare workers should not handle it.

Always dilute the concentrate for solution for infusion with the complete solvent provided before adding it to the infusion solutions.

Preparation stages

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

Note: both the vial of JEVTANA 60 mg/1.5 ml concentrate (fill volume: 73.2 mg of cabazitaxel/1.83 ml) and the vial of solvent (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the complete contents of the provided solvent, there is a solution containing 10 mg/ml of cabazitaxel.

To prepare the infusion solution, the following two-stage dilution process must be carried out aseptically.

Stage1: initial dilution of the concentrate for solution for infusion with the provided solvent.

This resulting concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (at least 6 ml of released volume). The second dilution must be carried out immediately (before 1 hour) as detailed in Stage 2.

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

Stage2: final (second) dilution for infusion

The infusion solution must be used immediately. However, the in-use storage time may be longer under the specific conditions mentioned in the section Shelf life and special precautions for storage.

Disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations.

Method of administration

JEVTANA is administered by infusion over 1 hour.

The use of an in-line filter with a nominal pore size of 0.22 microns (also known as 0.2 microns) is recommended during administration.

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