Cabazitaxel medical valley

Cabazitaxel Medical Valley
60 mg, concentrate and solvent for solution for infusion
cabazitaxel

Please read the following leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

1. What Cabazitaxel Medical Valley is and what it is used for
2. Important information before receiving Cabazitaxel Medical Valley
3. How to use Cabazitaxel Medical Valley
4. Possible side effects
5. How to store Cabazitaxel Medical Valley
6. Contents of the pack and other information

1. What Cabazitaxel Medical Valley is and what it is used for

The common name is cabazitaxel. It belongs to a group of medicines called "taxanes", which are used in cancer treatment.
Cabazitaxel Medical Valley is used in the treatment of prostate cancer when disease progression has been observed after treatment with another type of chemotherapy. The medicine works by stopping the growth and division of cells.
As part of the treatment, a corticosteroid (prednisone or prednisolone) must also be taken orally every day. Please consult your doctor for information about this medicine.

2. Important information before using Cabazitaxel Medical Valley

When not to use Cabazitaxel Medical Valley:

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

Cabazitaxel Medical Valley must not be used if any of the above apply to the patient. If in doubt, consult a doctor before using Cabazitaxel Medical Valley.

Warnings and precautions

Before each administration of Cabazitaxel Medical Valley, blood tests will be performed to check whether blood cell counts, liver function, and kidney function are adequate for treatment with Cabazitaxel Medical Valley.

Immediately inform the doctor if:

• Fever occurs. Treatment with Cabazitaxel Medical Valley may reduce the number of white blood cells. 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 an adequate white blood cell count. Patients with low blood counts may develop life-threatening infections. Fever may be the first sign of infection, so it is essential to contact the doctor immediately if fever develops.
• The patient has previously experienced any allergies (allergic reactions). Severe allergic reactions may occur during treatment with Cabazitaxel Medical Valley.
• Severe or prolonged diarrhea, nausea, or vomiting occur. These symptoms may lead to severe dehydration and may require medical treatment.
• Numbness, tingling, burning sensations, or reduced sensation in the hands or feet occur.
• Any intestinal bleeding, changes in stool color, or abdominal pain occur. If bleeding or pain is severe, the doctor will discontinue treatment with Cabazitaxel Medical Valley. This is because Cabazitaxel Medical Valley may increase the risk of intestinal bleeding or perforation.
• Kidney problems occur.
• Yellowing of the skin or eyes, dark-colored urine, severe nausea, or vomiting occur, which may be symptoms of liver disease.
• A significant increase or decrease in daily urine output occurs.
• Blood appears in the urine.

Immediately inform the doctor if any of the above symptoms occur. The doctor may reduce the dose of Cabazitaxel Medical Valley or discontinue treatment.

Inform the doctor, pharmacist, or nurse about all medicines currently used or recently used by the patient, including those obtained without a prescription. This is because certain medicines may interact with Cabazitaxel Medical Valley or Cabazitaxel Medical Valley 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 (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (cholesterol-lowering medicines);
• valsartan (a medicine used to treat high blood pressure);
• repaglinide (a medicine used to treat diabetes).

Before receiving any vaccinations, inform the doctor that the patient is being treated with Cabazitaxel Medical Valley.

Pregnancy, breastfeeding, and fertility

Cabazitaxel Medical Valley is not indicated for use in women.

Patients should use condoms during sexual intercourse if their partner is pregnant or could become pregnant. Cabazitaxel Medical Valley may be present in semen and could affect the fetus. Patients receiving Cabazitaxel Medical Valley should not father a child within 4 months after the end of treatment. Before starting treatment, patients should consult their doctor about sperm preservation, as Cabazitaxel Medical Valley may impair male fertility.

Driving and operating machinery

Fatigue or dizziness may occur during treatment. In such cases, patients should not drive, operate machinery, or use tools until these symptoms have resolved.

This medicine contains 573 mg of alcohol (ethanol) per vial of solvent. The amount of alcohol in a 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 is unlikely to cause noticeable effects. However, if the patient is alcohol-dependent, has liver disease, or epilepsy, they should consult a doctor or pharmacist before using this medicine.

Polysorbates may affect the circulatory system and heart function (e.g., low blood pressure, heart rhythm disturbances).

3. How to use Cabazitaxel Medical Valley

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

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

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 appropriate dose accordingly.
• Infusions are usually given every 3 weeks.

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

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
The treating physician should discuss with the patient the possible adverse reactions and explain
the potential risks and benefits of treatment.
You should contact your doctor immediately if any of the following adverse reactions occur:

• fever (high body temperature). This occurs commonly (may affect up to 1 in 10 people).
• severe loss of body fluids (dehydration). This occurs commonly (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.

You should inform your doctor immediately if any of the above apply to you.
Other adverse reactions include:
Very common (may affect more than 1 in 10 people):

• decrease in red blood cells (anaemia) or white blood cells (important for fighting infections)
• decrease in platelets (which increases the risk of bleeding)
• loss of appetite (anorexia)
• stomach irritation, including nausea, vomiting, diarrhoea, or constipation
• back pain
• presence of blood in the urine
• feeling of tiredness, weakness, or lack of energy.

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

• taste disturbances
• shortness of breath
• cough
• abdominal pain
• temporary hair loss (in most cases normal hair growth should return)
• joint pain
• urinary tract infection
• lack of white blood cells associated with fever and infection
• tingling, pricking, burning sensation, or reduced sensation in hands and feet
• dizziness
• headache
• decrease or increase in 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 kidney function disorders
• 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
• rapid or irregular heartbeat
• blood clot in the legs or lungs
• hot flushes
• mouth or throat pain
• bleeding from the rectum
• discomfort, weakness, or muscle pain
• swelling of the feet or legs
• chills
• nail disorders (change in nail colour; nails may detach).

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

• low blood potassium levels
• ringing in the ears
• feeling of warmth or hot flushes
• skin redness
• cystitis, which may occur if the patient has previously undergone radiotherapy (cystitis due to radiation recall phenomenon).

Frequency not known (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 reactions occur, including any adverse reactions not listed
in this leaflet, you should inform your 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, PL-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 responsible entity.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Cabazitaxel Medical Valley

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 label on the vial
after “Expiry date (EXP)”. The expiry date refers to the last day of the specified month.
This medicine does not require any special storage conditions.
Information regarding the storage conditions and duration for Cabazitaxel Medical Valley
after dilution and preparation for use is provided in the section “PRACTICAL INFORMATION FOR
PHYSICIANS AND HEALTHCARE PROFESSIONALS ON THE PREPARATION,
ADMINISTRATION AND HANDLING OF CABAZITAXEL MEDICAL VALLEY
MEDICINAL PRODUCT”.
Any unused product or waste materials should be disposed of in accordance with local
regulations. This will help protect the environment.

6. Contents of the pack and other information

What Cabazitaxel Medical Valley contains
The active substance is cabazitaxel. One millilitre of concentrate contains 40 mg of cabazitaxel.
Each vial of concentrate contains 60 mg of cabazitaxel.
The other ingredients are: polysorbate 80 and citric acid in the concentrate, and 96% ethanol and water for injections in the solvent (see section 2, "Cabazitaxel Medical Valley contains alcohol").
Note: both the vial containing the Cabazitaxel Medical Valley medicinal product concentrate 60 mg/1.5 ml (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 Cabazitaxel Medical Valley looks like and contents of the pack
Cabazitaxel Medical Valley is a concentrate and solvent for solution for infusion (sterile concentrate).
The concentrate is a clear, colourless or slightly yellow, oily solution.
The solvent is a clear, colourless solution.
One pack of Cabazitaxel Medical Valley contains:

• One single-use vial made of colourless glass (type I), closed with a chlorobutyl rubber stopper and aluminium cap with a plastic flip-off cap, containing 1.5 ml (nominal volume) of concentrate.
• One single-use vial made of colourless glass (type I), closed with a chlorobutyl rubber stopper and aluminium cap with a plastic flip-off cap, containing 4.5 ml (nominal volume) of solvent.

Marketing Authorisation Holder
Medical Valley Invest AB
Brädgårdsvägen 28
236 32 Höllviken
Sweden
Importer
Pharmadox Healthcare Ltd.
This medicinal product is authorised in the European Economic Area countries under the following names:

Information intended exclusively for healthcare professionals.

PRACTICAL INFORMATION FOR PHYSICIANS AND HEALTHCARE WORKERS
REGARDING THE PREPARATION, ADMINISTRATION, AND HANDLING
OF THE MEDICINAL PRODUCT CABAZITAXEL MEDICAL VALLEY
The following information supplements sections 3 and 5 of the user instructions.
The entire procedure described below must be read before preparing the infusion solution.

Pharmaceutical 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 Cabazitaxel Medical Valley 60 mg medicinal product pack: concentrate and solvent
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 performed under controlled and aseptic conditions (see below: "Precautions during preparation and administration").

After initial dilution, the vial of concentrate of Cabazitaxel Medical Valley 60 mg medicinal product diluted using the entire content of the solvent vial has demonstrated physical and chemical stability for 1 hour 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 48 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 storage time and conditions, and storage should generally not exceed 24 hours at 2°C–8°C, provided dilution was performed under controlled and validated aseptic conditions.

Precautions during preparation and administration
As with other antineoplastic agents, caution must be exercised when handling Cabazitaxel Medical Valley 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 Cabazitaxel Medical Valley with the skin at any stage of handling, the affected area must be washed immediately and thoroughly with soap and water. In case of contact with mucous membranes, the contaminated area must be immediately and thoroughly rinsed with water.

Cabazitaxel Medical Valley must be prepared and administered only by personnel trained in handling cytotoxic substances. Pregnant healthcare workers should not handle this medicinal product.

The concentrate for infusion solution must always be diluted with the entire volume of the provided solvent before being added to the infusion solution.

Preparation steps
Carefully read the entire section before mixing and dilution. Preparation of Cabazitaxel Medical Valley prior to administration requires TWO dilution steps. Follow the instructions below.

Note: Both the vial of Cabazitaxel Medical Valley concentrate (60 mg/1.5 ml; fill volume: 73.2 mg cabazitaxel/1.83 ml) and the solvent vial (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 content of the provided solvent, the resulting solution contains 10 mg/ml of cabazitaxel.

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

Step 1: Initial dilution of the concentrate using the provided solvent

Step 1.1
Carefully inspect the concentrate vial and the solvent vial. The concentrate and solvent solutions should be clear and practically free of particles.
Concentrate vial  Solvent vial
(60 mg – 1.5 ml)

Step 1.2

Using a syringe with an attached needle, under aseptic conditions, withdraw the entire content of the provided solvent, partially inverting the vial.
Solvent vial

Step 1.3

Inject the entire solvent content 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.
Mixture of concentrate  Solvent vial
and solvent

After the first dilution, the resulting solution contains 10 mg/ml of cabazitaxel.

Step 1.4

Remove the syringe and needle and gently mix by hand through repeated inversion until a clear, 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 for homogeneity and clarity.
The presence of foam after this time is normal.
Mixture of concentrate and solvent 10 mg/ml
The resulting mixture of concentrate and solvent contains 10 mg/ml of cabazitaxel (at least 6 ml available 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 for infusion

Step 2.1
Under aseptic conditions, transfer the required volume of the concentrate-solvent mixture (10 mg/ml cabazitaxel) using a graduated syringe with an attached needle. For example, a 45 mg dose of Cabazitaxel Medical Valley 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, non-PVC infusion bag containing 5% glucose solution or 9 mg/ml (0.9%) sodium chloride solution for infusion. The final concentration of the infusion solution should be between 0.10 mg/ml and 0.26 mg/ml.

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

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

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 must be discarded.
The infusion solution should be used immediately after preparation. However, storage time may be extended under specific conditions 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.

Method of administration
Cabazitaxel Medical Valley is administered as a 1-hour infusion.
A filter with a nominal pore size of 0.22 microns (also referred to as 0.2 microns) should be used during administration, incorporated into the infusion set.

Infusion bags made of PVC and polyurethane infusion sets must not be used for the preparation or administration of this medicinal product.