Cabazitaxel TilloMed

PACKAGE LEAFLET

Package leaflet: Information for the patient

Cabazitaxel Tillomed 60 mg concentrate and solvent for solution for infusion

Please read this leaflet carefully before 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

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

Cabazitaxel Tillomed contains the active substance cabazitaxel, which belongs to a group of
medicines called "taxanes" used to treat cancer.
Cabazitaxel Tillomed is used to treat prostate cancer that has progressed after receiving other chemotherapy treatments. It works by blocking the growth and spread of cancer cells.
As part of your treatment, you will also take a corticosteroid (prednisone or prednisolone) by mouth every day. Please consult your doctor for information about this second medicine.

2. What you should know before using Cabazitaxel Tillomed

Do not use Cabazitaxel Tillomed if:

• you are allergic (hypersensitive) 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 1500/mm³)
• you have severe impairment of liver function
• you have recently received or are about to receive the yellow fever vaccine.

If you think any of these applies to you, you must not receive Cabazitaxel Tillomed. If you
have any doubts, consult your doctor before using Cabazitaxel Tillomed.
Warnings and precautions
Before each treatment with Cabazitaxel Tillomed, you will need to have blood tests to
check that your blood cells are sufficient and that your liver and kidney functions are adequate
to allow administration of Cabazitaxel Tillomed.
Inform your doctor immediately if:

• you have a fever. During treatment with Cabazitaxel Tillomed, your white blood cell count is more likely to decrease. Your doctor will monitor your blood and general condition to detect any signs of infection. You may be prescribed other medicines to maintain stable blood cell counts. People with low blood cell counts may develop potentially life-threatening infections. Fever may be the first sign of an infection, so inform your doctor immediately if you develop a fever.
• you have ever had any allergies. Severe allergic reactions may occur during treatment with Cabazitaxel Tillomed.
• you have severe or prolonged diarrhea, nausea, or vomiting. Any of these conditions can lead to severe dehydration. Your doctor may consider it necessary to treat you accordingly.
• you experience numbness, tingling, burning sensations, or reduced sensitivity in your hands or feet.
• you have intestinal bleeding problems or have noticed changes in stool color or stomach pain. If bleeding or pain is severe, your doctor will stop treatment with Cabazitaxel Tillomed. This is because Cabazitaxel Tillomed may increase the risk of bleeding or the development of perforations in the intestinal wall.
• you have kidney problems.
• you develop liver problems during treatment.
• you notice a significant increase or decrease in your daily urine volume.
• you have blood in your urine.

If any of the above situations apply to you, inform your doctor immediately. Your doctor
may reduce the dose of Cabazitaxel Tillomed or discontinue treatment.
Other medicines and Cabazitaxel Tillomed

• Inform your doctor, pharmacist, or nurse if you are taking or have recently taken any other medicines, including those without a prescription. This is necessary because some medicines may affect how Cabazitaxel Tillomed works, or Cabazitaxel Tillomed may affect the action of other medicines. These include the following:
• ketoconazole, rifampicin – for infections
• carbamazepine, phenobarbital, or phenytoin – for epileptic seizures
• St John’s wort (Hypericum perforatum) – herbal product for depression and other conditions
• statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) – for lowering blood cholesterol
• valsartan – for hypertension
• repaglinide – for diabetes

Consult your doctor before receiving any vaccination during treatment with
Cabazitaxel Tillomed.
Pregnancy, breastfeeding, and fertility
Cabazitaxel Tillomed must not be used in pregnant women or in women of childbearing age who are not using contraceptive methods.
Cabazitaxel Tillomed must not be used in women who are breastfeeding.
Use a condom during sexual intercourse if your partner is pregnant or could become pregnant. Cabazitaxel Tillomed may be present in semen and could affect the fetus. It is recommended not to father a child during treatment and for 6 months after treatment ends, and to seek advice on sperm preservation before starting treatment, as Cabazitaxel Tillomed may impair male fertility.
Driving and using machines
While taking this medicine, you may feel tired or dizzy. If this happens, do not drive or operate machinery until you feel better.
Cabazitaxel Tillomed contains ethanol (alcohol)
This medicine contains 13% v/v ethanol (alcohol), equivalent to 14 ml of beer and 6 ml of wine.
This medicine may be harmful to people suffering from alcoholism.
This should be taken into account if you belong to a high-risk group, for example patients
with liver disease or epilepsy.

3. How to use Cabazitaxel Tillomed

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

• Cabazitaxel Tillomed will be administered to you by a doctor or nurse.
• Cabazitaxel Tillomed must be prepared (diluted) before administration. This patient information leaflet contains information on the handling and administration of Cabazitaxel Tillomed for doctors, nurses, and pharmacists.
• Cabazitaxel Tillomed will be administered to you in hospital by intravenous infusion (a drip into a vein) lasting approximately 1 hour.
• As part of your treatment, you will also take a corticosteroid (prednisone or prednisolone) orally every day. The dose and duration will be determined by your doctor.
• The usual dose depends on body surface area. Your doctor will calculate your body surface area in square meters (m²) and decide which dose should be administered to you.
• Normally, you will receive one infusion every 3 weeks.

If you have any doubts about how to use 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.
You should discuss this with your doctor, who will explain the potential risks and benefits of the treatment.
Contact a doctor immediately if you notice any of the following side effects:

• fever (high body temperature). This is a very common side effect (may affect more than 1 in 10 people)
• severe loss of body fluids (dehydration). This is a common side effect (may affect up to 1 in 10 people). This 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 may 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 (which increases the risk of bleeding)
• loss of appetite (anorexia)
• altered sense of taste
• shortness of breath
• cough
• stomach problems including nausea, vomiting, diarrhoea, or constipation
• abdominal pain
• temporary hair loss (in most cases, hair grows back)
• back pain
• joint pain
• blood in the urine
• feeling of tiredness, weakness, or lack of energy.

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

• urinary tract infection
• decrease in white blood cells associated with fever and infection
• sensation of numbness, tingling, burning, or reduced sensitivity in hands and feet
• dizziness
• headache
• decrease or increase in blood pressure
• feeling of stomach discomfort, burning sensation, or belching
• stomach pain
• haemorrhoids
• muscle spasms
• pain or increased frequency when urinating
• urinary incontinence
• kidney diseases or disorders
• mouth or lip ulcers
• infections or increased risk of infections
• high blood sugar levels
• low blood potassium levels
• mental confusion
• feeling of anxiety
• unusual sensation or loss of sensitivity or pain in hands and feet
• ringing in the ears
• balance problems
• rapid and irregular heartbeat
• blood clot in the leg
• sensation of warm, red skin
• mouth or throat pain
• rectal bleeding
• skin redness
• muscle discomfort or pain
• swelling of feet or legs
• chills.

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

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

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 Cabazitaxel Tillomed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and
on the label of the vial after Exp. The expiry date refers to the last day of
that month.
This medicine does not require any special storage conditions.
Unused medicine and waste material derived from this medicine must be disposed of in
accordance with local regulations. This will help protect the environment.

6. Package contents and other information

What Cabazitaxel Tillomed 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 in the concentrate are polysorbate 80, citric acid and absolute ethanol; in the
solvent they are 96% ethanol and water for injections (see section 2, “Cabazitaxel Tillomed contains alcohol”).
Note: Both the vial containing the Cabazitaxel 60 mg/1.5 ml concentrate (fill volume: 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 diluting 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 Cabazitaxel Tillomed and contents of the pack
Cabazitaxel Tillomed is a concentrate and solvent for infusion solution (sterile concentrate).
The concentrate is a clear, oily solution ranging from colourless to pale yellow.
The solvent is a clear, colourless solution.
Each pack of Cabazitaxel Tillomed contains:
One pack contains one vial of concentrate and one vial of solvent.
One single-use transparent tubular glass vial with grey rubber stopper sealed with an aluminium flip-off cap and yellow plastic disc, containing 1.5 ml (nominal volume) of concentrate.
One single-use transparent glass vial with grey rubber stopper sealed with an aluminium flip-off cap and red plastic disc, containing 5.67 ml (nominal volume) of solvent.
Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale G. Richard 1, Torre A
20143 Milano (MI)
Italy
Manufacturer:
MIAS Pharma Limited
Suite 2, Stafford House, Strand Road
Portmarnock, Co. Dublin
Ireland
This medicinal product is authorised in the European Economic Area Member States
under the following names:
Country Name of the medicinal product
Germany Cabazitaxel Tillomed 60 mg Konzentrat und Lösungsmittel zur
Herstellung einer Infusionslösung
United Kingdom Cabazitaxel Tillomed 60 mg concentrate and solvent for solution
for infusion
Spain Cabazitaxel Tillomed 60 mg concentrado y disolvente para
solución para perfusión EFG
Italy Cabazitaxel Tillomed
France Cabazitaxel Tillomed 60 mg solution à diluer et solvant pour
solution pour perfusion
The following information is intended exclusively for healthcare professionals
PRACTICAL INFORMATION FOR PHYSICIANS OR HEALTHCARE PROFESSIONALS ON THE
PREPARATION, ADMINISTRATION AND HANDLING OF
CABAZITAXEL TILLOMED 60 mg CONCENTRATE AND SOLVENT FOR
INFUSION SOLUTION
These instructions supplement 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 different from those used for dilution.
Shelf life and special precautions for storage
For the Cabazitaxel Tillomed 60 mg concentrate and solvent pack
This medicinal product requires no special storage conditions.
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.
After initial dilution of the concentrate with the solvent
Do not refrigerate.
Chemical and physical in-use stability has been demonstrated for 1 hour at room temperature (15°C–30°C). From a microbiological point of view, the mixture of concentrate and solvent should be used immediately. If not used immediately, the times and conditions of in-use storage are the responsibility of the user.
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 (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 point of view, the infusion solution should be used immediately. If not used immediately, the times and conditions of in-use storage are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under validated aseptic and controlled conditions.
Precautions for preparation and administration
As with any other antineoplastic agent, caution should be exercised during handling and preparation of solutions containing Cabazitaxel Tillomed, and consideration should be given to the use of containment devices, personal protective equipment (e.g. gloves), and preparation procedures.
If Cabazitaxel Tillomed comes into contact with the skin at any stage of handling, wash the affected area immediately and thoroughly with soap and water.
If contact occurs with mucous membranes, rinse immediately and thoroughly with water. Cabazitaxel Tillomed must be administered and prepared only by personnel qualified in the handling of cytotoxic agents. The product must 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.
Preparation steps
Read carefully the ENTIRE section before mixing and diluting. Cabazitaxel Tillomed requires TWO dilutions before administration. Follow the instructions below for preparation.
Note: Both the vial containing the Cabazitaxel Tillomed 60 mg/1.5 ml concentrate (fill volume: 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 diluting the concentrate with the entire contents of the provided solvent vial, a solution containing 10 mg/ml of cabazitaxel is obtained.
To prepare the infusion solution, the two-step aseptic dilution process described below must be followed.
Step 1: Initial dilution of the concentrate for infusion solution with the provided solvent

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

Step 1.2
Using a syringe with a needle, aseptically withdraw the entire contents of the provided solvent by partially inverting the vial.
Step 1.3

Inject the entire contents into the corresponding vial containing the concentrate.
To minimize foam formation while injecting the solvent, direct the needle against the inner wall of the concentrate vial and inject slowly.
After reconstitution, the resulting solution contains 10 mg/ml of cabazitaxel.
Step 1.4

Remove the syringe and needle and mix gently by inverting the vial slowly; repeat inversion until a clear, homogeneous solution is obtained. This may take approximately 45 seconds.
Step 1.5
Allow the solution to stand for about 5 minutes, then check that it is homogeneous and transparent.
The presence of foam even after the indicated time is normal.
The resulting concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (providing 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 concentrate-solvent mixture may be required to administer the prescribed dose.
Step 2: Second (final) dilution for infusion
Step 2.1

Aseptically withdraw with a graduated syringe fitted with a needle the required amount of the concentrate-solvent mixture (10 mg/ml of cabazitaxel). For example, a 45 mg dose of Cabazitaxel Tillomed requires 4.5 ml of the concentrate-solvent mixture prepared according to Step 1.
Since foam may persist on the walls of the vial of this solution prepared according to Step 1, it is preferable to insert the syringe needle into the center of the vial during withdrawal.
Step 2.2
Inject the solution into a sterile, non-PVC container containing either 5% glucose solution or 9 mg/ml (0.9%) sodium chloride solution for infusion.
The final concentration of the infusion solution must be between 0.10 mg/ml and 0.26 mg/ml.

Step 2.3
Remove the syringe and mix the contents of the infusion bag or bottle manually with a gentle rocking motion.
Step 2.4
As with all parenteral products, the resulting infusion solution should be inspected visually. Since the infusion solution is supersaturated, crystallization may occur over time. In such cases, the solution must not be used and must be discarded.
The infusion solution should be used immediately. However, the in-use storage time may be longer if the specific conditions mentioned in section 6.3 are respected.
Method of administration
Cabazitaxel Tillomed is administered as a 1-hour infusion.
During administration, use of an in-line filter with a nominal pore size of 0.22 micrometres (also referred to as 0.2 micrometres) is recommended.
Dilute the concentrate for infusion solution with the entire solvent provided. The resulting concentrate-solvent mixture contains 10 mg/ml of cabazitaxel.
Do not use PVC infusion containers or polyurethane infusion sets for the preparation and administration of Cabazitaxel Tillomed.