Introduction

Cabazitaxel Zentiva 60 mg Concentrate and Diluent for Solution for Infusion EFG

Read this entire product information carefully before starting to use this medicine, as it contains important information for you.

Keep this product information, as you may need to read it again.
If you have any questions, consult your doctor, pharmacist, or nurse.
If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What is Cabazitaxel Zentivaand for what it is used

2. What you need to know before receiving Cabazitaxel Zentiva

3. How to use Cabazitaxel Zentiva

4. Possible side effects

5. Storage of Cabazitaxel Zentiva

6. Contents of the package and additional information

1. What is Cabazitaxel Zentiva and what is it used for

Cabazitaxel Zentivacontains the active ingredient cabazitaxel which belongs to a group of medicines called “taxanes”, used to treat cancers.

Cabazitaxel is used to treat prostate cancer that has progressed after receiving another chemotherapy. It works by stopping the growth of cells and their multiplication.

As part of your treatment, you will also take a corticosteroid (prednisone or prednisolone) every day by mouth. Ask your doctor for information about this other medicine.

2. What you need to know before starting to use Cabazitaxel Zentiva

No use Cabazitaxel Zentiva:

if you are allergic (hypersensitive) to cabazitaxel, other taxanes, polysorbate 80, or any of the other components of this medication (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 to be vaccinated against yellow fever.

You should not receive Cabazitaxel Zentivaif any of the above circumstances apply. If you are unsure, consult your doctor before receiving Cabazitaxel Zentiva.

Warnings and precautions

Before starting treatment with Cabazitaxel Zentiva, blood tests will be performed to check that you have sufficient blood cells and that your kidneys and liver are functioning properly to receive Cabazitaxel Zentiva.

Inform your doctor immediately if:

you have a fever. During treatment with Cabazitaxel Zentivait is more likely that your white blood cell count will decrease. Your doctor will monitor your blood and overall condition to detect signs of infection. You may be given other medications to maintain your blood cell count. People with low blood cell counts may develop life-threatening infections. The first sign of infection could be fever, so if you have a fever, inform your doctor immediately.
you have ever had any allergy. During treatment with Cabazitaxel Zentivasevere allergic reactions may occur.
you have severe or prolonged diarrhea, feel unwell (nausea) or are vomiting. Any of these situations may cause severe dehydration. Your doctor should provide treatment.
you have numbness, tingling, burning, or decreased sensation in your hands and feet.
you have intestinal bleeding problems or changes in the color of your stools or stomach pain. If bleeding or pain is severe, your doctor will interrupt your treatment with Cabazitaxel Zentiva. This is because Cabazitaxel Zentivamay increase the risk of bleeding or development of intestinal wall perforations.
you have kidney problems.
you have yellow skin and eyes, dark urine, intense nausea (feeling of discomfort) or vomiting, as these may be signs or symptoms of liver problems.
you notice a significant increase or decrease in the volume of your urine.
you have blood in your urine.

If any of the above circumstances occur, inform your doctor immediately. Your doctor may reduce the dose of Cabazitaxel Zentivaor interrupt treatment.

Use of Cabazitaxel Zentivawith other medications

Inform your doctor, pharmacist, or nurse if you are using or have recently used other medications, even those purchased without a prescription. This is because some medications may affect the efficacy of Cabazitaxel Zentivaor Cabazitaxel Zentivamay affect the efficacy of other medications. These medications include the following:
ketoconazole, rifampicin (for infections);
carbamazepine, phenobarbital, or phenytoin (for seizures);
St. John's Wort or hypericum (Hypericum perforatum) (medicinal plant used to treat depression and other conditions);
statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (to reduce cholesterol in your blood);
valsartan (for hypertension);
repaglinide (for diabetes).

While receiving treatment with Cabazitaxel Zentiva, consult your doctor before being vaccinated.

Pregnancy, breastfeeding, and fertility

Cabazitaxel Zentivais not indicated for use in women.

Use condoms during sexual intercourse if your partner is or may be pregnant. Cabazitaxel may be present in your semen and affect the fetus. It is recommended not to father a child during and up to 4 months after treatment and to request information on sperm preservation before treatment, as Cabazitaxel Zentivamay alter male fertility.

Driving and operating machinery

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

Cabazitaxel Zentivacontains ethanol (alcohol)

This medication contains 709.8 mg of alcohol (ethanol) in each vial of solvent. The amount in the dose of this medication is equivalent to 14 ml of beer or 6 ml of wine. The small amount of alcohol contained in this medication does not produce any perceptible effect. If you have an alcohol addiction, liver disease, or epilepsy, consult your doctor or pharmacist before taking this medication.

3. How to use Cabazitaxel Zentiva

Usage Instructions

Before receiving cabazitaxel, you will be given antiallergic medications to reduce the risk of allergic reactions.

Cabazitaxel will be administered by a doctor or a nurse.
Cabazitaxel must be prepared (diluted) before administration. This leaflet provides practical information for the manipulation and administration of cabazitaxel for doctors, nurses, and pharmacists.
Cabazitaxel will be administered in the hospital through a drip (infusion) in one of your veins (intravenous route) for approximately 1 hour.
As part of your treatment, you will also take a corticosteroid medication (prednisone or prednisolone) orally 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 on the dose you should receive.
You will usually receive an infusion every 3 weeks.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

4. Possible Adverse Effects

Like all medicines, Cabazitaxel Zentivamay cause side effects, although not everyone will experience them. Your doctor will discuss this with you and explain the potential risks and benefits of your treatment.

Seek immediate medical attention if you notice any of the following side effects:

·fever (high temperature). This is common (it may affect up to 1 in 10 people).

·severe loss of body fluids (dehydration). This is common (it may affect up to 1 in 10 people). This can occur if you have severe or prolonged diarrhea, fever, or have been vomiting.

·severe stomach pain or stomach pain that does not resolve. This can happen if you have a perforation in the stomach, esophagus, or intestine (gastrointestinal perforation). This can be fatal.

If any of the above circumstances occur, inform 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 discomfort, 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):

·alteration of taste

·breathing difficulties

·cough

·abdominal pain

·temporary hair loss (in most cases, hair will grow back normally)

·joint pain

·urinary tract infection

·leukopenia associated with fever and infections

·sensation of numbness, tingling, burning, or decreased sensation in hands and feet

·dizziness

·headache

·increase or decrease in blood pressure

·stomach discomfort, heartburn, or belching

·abdominal pain

·hemorrhoids

·muscle spasms

·urinating frequently or with pain

·urinary incontinence

·kidney problems or alteration

·mouth or lip ulcers

·infections or risk of infections

·elevated blood sugar levels

·insomnia

·confusion

·feeling of anxiety

·unusual or loss of sensation or pain in hands and feet

·balance problems

·rapid or irregular heartbeat

·blood clots in the legs or lungs

·sensation of suffocation on the skin

·mouth or throat pain

·rectal bleeding

·muscle discomfort, weakness, or pain

·inflammation of the feet or legs

·chills.

·problems with nails (change in color of nails; nails may fall off).

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

·low potassium levels in the blood

·tinnitus (ringing in the ears)

·sensation of heat on the skin

·inflammation of the bladder, which may occur if the bladder has been previously exposed to radiation (radiation-induced cystitis).

Unknown frequency (cannot be estimated from available data):

·pulmonary interstitial disease (inflammation of the lungs causing cough and difficulty breathing).

Reporting of side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Cabazitaxel Zentiva

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the vial label after CAD. The expiration date is the last day of the month indicated.

Do not refrigerate.

For information on the conservation and use time of Cabazitaxel Zentiva, once it has been diluted and is ready to use, see the section “Practical information for healthcare professionals on the preparation, administration, and handling of Cabazitaxel Zentiva”.

Unused medication will be disposed of in accordance with local regulations. These measures will help protect the environment.

6. Contents of the packaging and additional information

Composition of Cabazitaxel Zentiva

The active ingredient is cabazitaxel. One milliliter of concentrate contains 40 mg of cabazitaxel. One vial of concentrate contains 60 mg of cabazitaxel.

The other components are: polysorbate 80, citric acid, and absolute ethanol in the concentrate, and 96% ethanol and water for injectable preparations in the solvent (see section 2 “Cabazitaxel Zentiva contains ethanol (alcohol)”).

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

Appearance of the product and contents of the package

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

The concentrate is a viscous, transparent, and colorless to pale yellow solution.

The solvent is a transparent and colorless solution.

A package of Cabazitaxel Zentiva contains:

Concentrate: 1.5 ml of concentrate in a 15 ml transparent glass tubular vial (type I), closed with a gray rubber stopper, sealed with an aluminum abatable seal with a yellow plastic disc. Each vial contains 60 mg of cabazitaxel in 1.5 ml (nominal volume).

Solvent: 5.67 ml in a 15 ml transparent glass vial (type I), closed with a gray rubber stopper, sealed with an aluminum abatable seal with a dark blue plastic disc. Each vial contains 5.67 ml (nominal volume).

Marketing authorization holder and responsible person for manufacturing

Marketing authorization holder

Zentiva, k.s.,

U kabelovny 130,

Prague 10 – Dolní Mecholupy,

102 37 Czech Republic

Responsible person for manufacturing

Mias Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co.Dublin

Ireland

Tillomed Malta Limited,

Malta Life Sciences

Park, LS2.01.06

Industrial Estate,

San Gwann, SGN 3000,

Malta

You can request more information about thismedicamentby contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Country	Product name
Germany	Cabazitaxel Tillomed 60 mg Concentrate and Solvent for the Preparation of an Infusion Solution

Spain	Cabazitaxel Zentiva 60 mg concentrate and solvent for solution for perfusion EFG
Italy	Cabazitaxel Tillomed
France	Cabazitaxel Tillomed 60 mg solution to be diluted and solvent for solution for perfusion

Last review date of this leaflet:July 2023

The detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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The following information is intended only for healthcare professionals.

INFORMATION FOR MEDICAL PRACTITIONERS OR HEALTHCARE PROFESSIONALS ABOUT THE PREPARATION, ADMINISTRATION, AND HANDLING OF Cabazitaxel Zentiva 60 mg CONCENTRATE AND SOLVENT FOR SOLUTION FOR PERFUSION

This information complements sections 3 and 5 for the user.

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

Incompatibilities

This medicinal product should not be mixed with other medicinal products except those used for dilutions.

Period of validity and special storage precautions

For the package of Cabazitaxel Zentiva 60 mg concentrate and solvent

Do not refrigerate.

After opening the vial

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

After the initial dilutionof Cabazitaxel Zentiva 60 mg concentrate with the complete content of the solvent vial provided, it has been demonstrated that the chemical and physical stability is maintained for 1 hour at room temperature (15°C - 30°C).

After the final dilution in the infusion bag/bottle

It has been demonstrated that the chemical and physical stability of the infusion solution is maintained for 8 hours at room temperature (15°C – 30°C) including 1 hour of infusion time and for 48 hours in the refrigerator including 1 hour of infusion time.

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

Precautions for preparation and administration

As with other anticancer agents, caution should be exercised during the preparation and administration of cabazitaxel solutions, taking into account the use of safety devices, personal protective equipment (e.g. gloves) and preparation procedures.

If cabazitaxel 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.

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

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

Steps for preparation

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

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

Stage 1: initial dilution of the concentrate for infusion solution with the solvent provided.

Stage 1.1

Inspect the vial of concentrate and the solvent provided. The concentrate and solvent solutions must be transparent

Stage 1.2 Using a syringe provided with a fixed needle, extract the complete content of the solvent provided in an aseptic manner by inverting the vial partially.

Stage 1.3 Inject the complete content into the corresponding vial of concentrate. To limit as much as possible the formation of foam when injecting the solvent, direct the needle towards the inner wall of the vial of concentrate solution and inject slowly. Once reconstituted, the resulting solution contains 10 mg/ml of cabazitaxel.
Stage 1.4 Remove the syringe and needle and mix the solution manually and gently, by repeated inversion, until a transparent and homogeneous solution is obtained. This may take about 45 seconds.

Stage 1.5 Leave the solution to stand for approximately 5 minutes and then check that the solution is homogeneous and transparent. It is normal for foam to persist after this time.

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

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

Stage 2: final dilution (for infusion)

Stage 2.1 Extract the required amount of the concentrate-solvent mixture (10 mg/ml of cabazitaxel) with a graduated syringe provided with a fixed needle. For example, a dose of 45 mg of Cabazitaxel Zentiva would require 4.5 ml of the concentrate-solvent mixture prepared in Stage 1. As foam may still be present in the wall of the vial of this solution after the preparation described in Stage 1, it is preferable to place the needle of the syringe in the middle of the content during extraction.
Stage 2.2 Inject into a sterile infusion bag or bottle without PVC of a 5% glucose solution or a 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.
Stage 2.3 Remove the syringe and mix the content of the infusion bag or bottle manually, by shaking motion. Stage 2.4 As with all parenteral products, the resulting infusion solution must be visually inspected before use. Since the infusion solution is supersaturated, it may crystallize over time. In this case, the solution should not be used and should be discarded.

The infusion solution must be used immediately. However, the infusion time may be longer under the specific conditions mentioned in the sectionPeriod of validity and special storage precautions.

The disposal of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.

Method of administration

Cabazitaxel Zentiva is administered by infusion over 1 hour.

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

Do not use PVC infusion bags or polyurethane infusion sets for the preparation and administration of the infusion solution.