Eleber

Package leaflet: Information for the patient

Eleber, 60 mg, concentrate and solvent for solution for infusion
cabazitaxel
Please read carefully all of this leaflet before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Eleber is and what it is used for
2. What you need to know before using Eleber
3. How to use Eleber
4. Possible side effects
5. How to store Eleber
6. Contents of the pack and other information

1. What Eleber is and what it is used for

The name of the medicine is Eleber. Its international non-proprietary name is cabazitaxel. Eleber belongs to a group of medicines called "taxanes", used in cancer treatment.
Eleber is used in the treatment of prostate gland cancer (prostate cancer) when disease progression has been observed after administration of another chemotherapy. The medicine works by stopping the growth and division of cells.
As part of the treatment, daily oral administration of a corticosteroid (prednisone or prednisolone) is also required. Please consult your doctor for information about this medicine.

2. Important information before using Eleber

When not to use Eleber:

• if the patient is allergic (hypersensitive) to cabazitaxel, other taxanes, polysorbate 80, or any of the other ingredients of the medicine (listed in section 6),
• if white blood cell count is too low (absolute neutrophil count less than or equal to 1500/mm³),
• if the patient has severe liver function impairment,
• if the patient has recently received or is scheduled to receive yellow fever vaccine.

Do not use Eleber if any of the above apply to the patient.
If in doubt, consult a doctor before using Eleber.
Warnings and precautions
Before each administration of Eleber, blood tests will be performed to check whether blood cell counts, and liver and kidney function are adequate for administration of Eleber.

Immediately inform the doctor if:

• fever occurs. During treatment with Eleber, there is a risk of reduced white blood cell count. The doctor will monitor blood counts and the patient’s general condition for signs of infection. The doctor may also prescribe other medications to maintain normal white blood cell levels. Life-threatening infections may occur in patients with low blood counts. Fever may be the earliest sign of infection, so immediate medical attention is required if fever develops.

• the patient has previously experienced any allergies. Severe allergic reactions may occur during treatment with Eleber.

• severe or prolonged diarrhea, nausea, or vomiting occur. These symptoms may lead to severe dehydration and may require medical treatment.

• tingling, numbness, burning sensations, or reduced sensation in hands and feet occur.

• any gastrointestinal bleeding, change in stool color, or abdominal pain occurs. If bleeding or pain is severe, the doctor will discontinue treatment with Eleber, as Eleber may increase the risk of gastrointestinal bleeding or perforation.

• kidney function impairment occurs.

• the patient develops jaundice (yellowing of the skin or eyes), dark-colored urine, severe nausea, or vomiting, as these may be signs of liver problems.

• a significant increase or decrease in daily urine volume occurs.

• blood appears in the urine.

Immediately inform the doctor if any of the above occur.
The doctor may reduce the dose of Eleber or discontinue treatment.
Eleber and other medicines
Inform the doctor, pharmacist, or nurse about all medicines currently used or recently used, including those obtained without a prescription. This is because some medicines may affect the action of Eleber, or Eleber may affect the action of other medicines. This includes the following medicines:

• ketoconazole, rifampicin (medicines used to treat infections);
• carbamazepine, phenobarbital, or phenytoin (medicines used to treat seizures);
• St. John’s wort (Hypericum perforatum) (a herbal remedy for depression and other conditions);
• statins (e.g., simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (medicines that lower blood cholesterol);
• valsartan (a medicine used to treat high blood pressure);
• repaglinide (a medicine used to treat diabetes).

Before receiving any vaccination, inform the doctor that Eleber is being taken.
Pregnancy, breastfeeding, and effects on fertility
Eleber is not indicated for use in women.
The patient should use condoms during sexual intercourse if his partner is pregnant or could become pregnant. Eleber may be present in semen and may harm the unborn child.
Patients taking Eleber should not father children within 4 months after the end of treatment. Before starting treatment, patients should consult their doctor about sperm storage, as Eleber may affect male fertility.
Driving and operating machinery
Fatigue or dizziness may occur during treatment. In such cases, do not drive, operate machinery, or use tools until these symptoms resolve.
Eleber contains ethanol (alcohol)
The medicine contains 542.4 mg of ethanol (alcohol) in each vial of solvent. The amount in a single dose corresponds to less than 10 ml of beer or 4 ml of wine.
The small amount of alcohol in this medicinal product is unlikely to cause any noticeable effects.

3. How to use Eleber

Instructions for use
Before administration of Eleber, patients are given antiallergic medications to reduce the risk of
allergic reactions.

• Eleber is administered by a doctor or nurse.
• Eleber must be properly prepared (diluted) before administration. This leaflet contains practical information for doctors, nurses and pharmacists on handling Eleber and on the method of administration.
• Eleber is administered in a hospital setting as an intravenous infusion (drip) lasting approximately one hour into one of the patient's veins (intravenous administration).
• As part of treatment, patients must also take a corticosteroid (prednisone or prednisolone) orally every day.

Dosage and frequency of administration

• The usual dose is based on the patient's body surface area. The doctor calculates the patient's body surface area in square meters (m²) and determines the dose accordingly.
• Infusions are usually given every 3 weeks.

If you have any further questions regarding the use of this medicine, please consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
The treating physician should discuss possible adverse reactions with the patient and explain
the risks and benefits associated with treatment.
Contact a doctor immediately if any of the following adverse reactions occur:

• Fever (high body 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). Dehydration may occur as a result of severe or prolonged diarrhoea, fever or vomiting.
• Severe abdominal pain or abdominal pain that does not go away. These symptoms may occur if the patient has a perforated stomach, oesophagus or intestine (gastrointestinal perforation). This may lead to death.

Patients should immediately inform their doctor if any of the above apply.
Other adverse reactions:
Very common (may affect more than 1 in 10 people):

• Decreased number of red blood cells (anaemia) or white blood cells (important for fighting infections)
• Decreased number of platelets (increasing the risk of bleeding)
• Loss of appetite (anorexia)
• Stomach irritation, including nausea, vomiting, diarrhoea or constipation
• Back pain
• Presence of blood in urine
• Feeling of fatigue, weakness or lack of energy.

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

• Changes in taste perception
• Shortness of breath
• Cough
• Abdominal pain
• Temporary hair loss (in most cases, normal hair regrowth should return)
• Joint pain
• Urinary tract infection
• Lack of white blood cells associated with fever and infection
• Sensation of numbness, tingling, burning or reduced sensation in hands and feet
• Dizziness
• Headache
• Decreased or increased blood pressure
• Feeling of stomach discomfort, heartburn or burping
• Stomach pain
• Haemorrhoids
• Muscle cramps
• Pain during urination or frequent urination
• Urinary incontinence
• Kidney disease or impaired kidney function
• Mouth or lip ulcers
• Infections or risk of infections
• Increased blood sugar levels
• Insomnia
• Confusion
• Feeling of anxiety
• Abnormal sensation, loss of sensation or pain in hands and feet
• Difficulty maintaining balance
• Fast or irregular heartbeat
• Blood clot in the leg or lung
• Feeling of warmth or flushing of the skin
• Pain in the mouth or throat
• Bleeding from the rectum
• Muscle discomfort, aches or weakness
• Swelling of feet or legs
• Chills
• Nail disorders (change in nail colour; nails may become detached)

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

• Low blood potassium levels
• Ringing in the ears
• Sensation of hot skin
• Skin redness
• Cystitis, which may occur if the patient has previously undergone radiotherapy (cystitis caused by radiation recall phenomenon).

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

• Interstitial non-infectious pneumonia (lung inflammation causing cough and breathing difficulties).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform a doctor, pharmacist or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: +48 22 49-21-301
fax: +48 22 49-21-309
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Eleber

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the vial label after "EXP". The expiry date refers to the last day of the stated month.
Information on the storage conditions and duration of Eleber after reconstitution and preparation for use is provided in the section "PRACTICAL INFORMATION FOR PHYSICIANS AND HEALTHCARE PROFESSIONALS ON THE PREPARATION, ADMINISTRATION AND HANDLING OF THE ELEBER MEDICINAL PRODUCT".
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Eleber contains

• The active substance is cabazitaxel. One ml of concentrate contains 40 mg of cabazitaxel. Each vial of concentrate contains 60 mg of cabazitaxel.
• The other components are: polysorbate 80 and citric acid in the concentrate, and 96% ethanol and water for injections in the solvent (see section 2, "Eleber contains alcohol").

Note: both the vial containing the Eleber 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) contain an overage of liquid to compensate for losses during preparation. This overage ensures that after dilution with the ENTIRE contents of the supplied solvent, the resulting solution contains 10 mg/ml of cabazitaxel.

What Eleber looks like and contents of the pack

Eleber is a concentrate and solvent for solution for infusion (sterile concentrate). The concentrate is a clear, colourless to pale yellow, viscous solution. The solvent is a clear, colourless solution.

One pack of Eleber in a cardboard carton contains:

• One vial made of colourless type I glass, closed with a chlorobutyl rubber stopper coated with fluoropolymer, and with an aluminium seal (flip-off closure), containing 1.5 ml (nominal volume) of concentrate.
• One vial made of colourless type I glass, closed with a chlorobutyl rubber stopper coated with fluoropolymer, and with an aluminium seal (flip-off closure), containing 4.5 ml (nominal volume) of solvent.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Zentiva k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Importer:
Pharmadox Healthcare Ltd.
Kordin Industrial Park KW20A
PLA 3000 Paola
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Bulgaria: Елебер 60 mg концентрат и разтворител за инфузионен разтвор
Croatia: Eleber 60 mg koncentrat i otapalo za otopinu za infuziju
Estonia: Eleber
Iceland: Eleber
Lithuania: Eleber 60 mg koncentratas ir tirpiklis infuziniam tirpalui
Latvia: Eleber 60 mg koncentrāts un šķīdinātājs infūziju šķīduma pagatavošanai
Poland: Eleber
Czech Republic: Eleber
Romania: Eleber 60 mg concentrat şi solvent pentru soluţie perfuzabilă
Slovakia: Eleber 60 mg koncentrát a rozpúšťadlo na infúzny roztok
Slovenia: Eleber 60 mg koncentrat in vehikel za raztopino za infundiranje
Hungary: Eleber 60 MG KONCENTRÁTUM ÉS OLDÓSZER OLDATOS INFÚZIÓHOZ

For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel: + 48 22 375 92 00
[logo of the Marketing Authorisation Holder]

Information intended exclusively for healthcare professionals:

PRACTICAL INFORMATION FOR PHYSICIANS AND HEALTHCARE PROFESSIONALS
REGARDING THE PREPARATION, ADMINISTRATION, AND HANDLING
OF THE MEDICINAL PRODUCT ELEBER, 60 mg, CONCENTRATE AND
SOLVENT FOR PREPARATION OF INFUSION SOLUTION
The following information supplements sections 3 and 5 of the user instructions.
Before preparing the infusion solution, read the entire procedure described below.

Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products except those used for dilution.

Shelf life and special precautions for storage
Applies to the Eleber 60 mg concentrate and solvent packaging
No special storage precautions required.

After opening
Vials of concentrate and solvent must be used immediately after opening. Otherwise, the user assumes responsibility for the duration and conditions of storage.
From a microbiological standpoint, the two-step dilution process must be carried out under controlled and aseptic conditions (see below: "Precautions during preparation and administration").

After initial dilution
After diluting the concentrate vial of the medicinal product Eleber 60 mg using the entire contents of the solvent vial, physical and chemical stability has been demonstrated for 30 minutes at room temperature.

After final dilution in an infusion bag and/or bottle
Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at room temperature (15°C – 30°C), including a 1-hour infusion time, and for 24 hours under refrigerated conditions (2°C – 8°C), including a 1-hour infusion time.
From a microbiological standpoint, the infusion solution should be used immediately after preparation. If not used immediately, the user assumes responsibility for the storage time and conditions, and storage should generally not exceed 24 hours at 2°C – 8°C, unless dilution was performed under controlled and validated aseptic conditions.

Precautions during preparation and administration
As with other antineoplastic agents, caution should be exercised when handling the medicinal product Eleber and preparing its solutions, including the use of equipment limiting exposure to the medicinal product, personal protective equipment (e.g., gloves), and procedures for preparing the medicinal product for use.
In case of contact of the medicinal product Eleber with the skin at any stage of handling, the affected area should be washed immediately and thoroughly with soap and water. In case of contact with mucous membranes, the affected area should be rinsed immediately and thoroughly with water.
The medicinal product Eleber must be prepared and administered only by personnel trained in handling cytotoxic substances. Pregnant healthcare personnel should not handle this product.
The concentrate for infusion solution must always be diluted using the entire volume of the supplied solvent before being added to the infusion solution.

Preparation steps
Before mixing and dilution, carefully read the ENTIRE section below. Preparation of the medicinal product Eleber prior to administration requires TWO dilution steps. Follow the instructions provided below.

Note: Both the vial containing the Eleber 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) contain an overfill to compensate for potential losses during preparation. This overfill ensures that after dilution with the entire contents of the supplied solvent, the resulting solution contains 10 mg/ml cabazitaxel.

The two-step dilution process described below must be performed aseptically to prepare the infusion solution.

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

Step 1.1
Carefully inspect the concentrate vial and the vial containing the supplied solvent.
The concentrate solution and solvent should be clear and transparent.

Vial with concentrate
Vial with solvent
(60 mg – 1.5 ml)

Step 1.2
Using a syringe with an attached needle under aseptic conditions, withdraw the entire contents of the supplied solvent, partially inverting the vial.

Vial with solvent

Step 1.3
Inject the entire volume of solvent into the appropriate concentrate vial.
To minimize foam formation during solvent injection, direct the needle against the inner wall of the concentrate vial and inject slowly.
After the first dilution, the resulting solution contains 10 mg/ml cabazitaxel.

Mixture of concentrate
and solvent
10 mg/ml

Step 1.4
Remove the syringe and needle and gently mix manually by repeated inversion until a clear and homogeneous solution is obtained. This may take approximately 45 seconds.

Mixture of concentrate
and solvent
10 mg/ml

Step 1.5
Allow the solution to stand for approximately 5 minutes, then check whether the solution is homogeneous and clear. The presence of residual foam after this time is normal.

Mixture of concentrate
and solvent
10 mg/ml

The resulting mixture of concentrate and solvent contains cabazitaxel at a concentration of 10 mg/ml (yielding at least 6 ml for administration). The second dilution must be performed immediately (within 1 hour) as described in Step 2.
More than one vial of the concentrate-solvent mixture may be required to administer the prescribed dose.

Step 2: Second (final) dilution of the infusion solution

Step 2.1
Under aseptic conditions, transfer the required volume of the concentrate-solvent mixture (cabazitaxel concentration 10 mg/ml) using a calibrated syringe with an attached needle. For example, a 45 mg dose of Eleber will require administration of 4.5 ml of the concentrate-solvent mixture prepared as described in Step 1.

Mixture of concentrate
and solvent
10 mg/ml

During extraction, it is recommended to insert the syringe needle inside the vial as described in Step 1, as foam may persist on the vial walls.

Step 2.2
Inject into a sterile infusion bag made of non-PVC material containing 5% glucose solution or 9 mg/ml (0.9%) sodium chloride solution for infusion.
The final concentration of the infusion solution should range from 0.10 mg/ml to 0.26 mg/ml.

Required volume of 5% glucose solution
of concentrate-solvent mixture or 9 mg/ml (0.9%)
sodium chloride solution for infusion

Step 2.3
Remove the syringe and mix the contents of the infusion bag or bottle manually by gentle rocking.

Step 2.4
As with any parenteral medicinal product, the resulting infusion solution should be visually inspected before use. Since the infusion solution is supersaturated, crystallization may occur over time. In such cases, the solution must not be used and should be discarded.

The infusion solution should be used immediately after preparation. However, the storage time of the prepared solution may be extended under specific conditions as described above in the section Shelf life and special precautions for storage.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

Administration method
The medicinal product Eleber is administered as a 1-hour infusion.
During administration, it is recommended to use an in-line filter with a nominal pore size of 0.22 micrometers (also referred to as 0.2 micrometers) attached to the infusion set.
Do not use PVC infusion bags or polyurethane infusion sets.