Cabazitaxel Accord

Patient Information Leaflet

Cabazitaxel Accord 20 mg/ml concentrate for solution for infusion

cabazitaxel
Read all of 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.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
  Contents of this leaflet:
  • What Cabazitaxel Accord is and what it is used for
  • What you need to know before using Cabazitaxel Accord
  • How to use Cabazitaxel Accord
  • Possible side effects
  • How to store Cabazitaxel Accord
  • Contents of the pack and other information

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

The name of the medicine is Cabazitaxel Accord. The common name is cabazitaxel. It belongs to a group of medicines called "taxanes" used to treat cancer.
Cabazitaxel Accord 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 need to 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 Accord

Do not use Cabazitaxel Accord if:

• you are allergic 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 1,500/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 situations apply to you, you must not receive Cabazitaxel Accord. If you are unsure, consult your doctor before using Cabazitaxel Accord.

Warnings and precautions
Before each treatment with Cabazitaxel Accord, you will need to have blood tests to ensure that your blood cell counts are adequate and that your liver and kidney functions are sufficient to allow administration of Cabazitaxel Accord.
Immediately inform your doctor:

• if you have fever. During treatment with Cabazitaxel Accord, 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 additional medicines to maintain stable blood cell counts. Patients with low blood cell counts may develop potentially life-threatening infections. Fever may be the first sign of infection, so inform your doctor immediately if you develop fever;
• if you have ever had any allergies. Severe allergic reactions may occur during treatment with Cabazitaxel Accord;
• if you have severe or prolonged diarrhoea, nausea, or vomiting. Any of these may lead to severe dehydration. Your doctor may consider it necessary to treat you accordingly;
• if you experience numbness, tingling, burning sensations, or reduced sensitivity in your hands or feet;
• if you have intestinal bleeding or notice changes in the colour of your stools or stomach pain. If bleeding or pain is severe, your doctor will stop treatment with Cabazitaxel Accord. This is necessary because Cabazitaxel Accord may increase the risk of bleeding or the development of perforations in the intestinal wall;
• if you have kidney problems;
• if you notice yellowing of the skin or eyes, dark urine, severe nausea (feeling unwell), or vomiting, as these may be signs or symptoms of liver problems;
• if you notice a significant increase or decrease in your daily urine volume;
• if you notice 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 Accord or discontinue treatment.

Other medicines and Cabazitaxel Accord
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription. This is important because some medicines may affect how Cabazitaxel Accord works, or Cabazitaxel Accord may affect the action of other medicines. These include:

• ketoconazole, rifampicin (for infections);
• carbamazepine, phenobarbital, or phenytoin (for epileptic seizures);
• St John’s wort (Hypericum perforatum) (a herbal product used for depression and other conditions);
• statins (such as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (to lower blood cholesterol);
• valsartan (for hypertension);
• repaglinide (for diabetes).
  Consult your doctor before receiving any vaccination during treatment with Cabazitaxel Accord.

Pregnancy, breastfeeding, and fertility
Cabazitaxel Accord is not indicated for use in women. Women must not be exposed to Cabazitaxel Accord through breastfeeding with human milk. Use a condom during sexual intercourse if your partner is pregnant or could become pregnant. Cabazitaxel Accord may be present in semen and may affect the fetus. It is recommended not to father a child during treatment and for 4 months after treatment ends. You should seek advice on sperm preservation before starting treatment, as Cabazitaxel Accord may impair male fertility.

Driving and using machines
While taking this medicine, you may feel tired or experience dizziness. If this occurs, do not drive or operate machinery until you feel better.

Cabazitaxel Accord contains ethanol (alcohol)
This medicine contains 1185 mg of alcohol (ethanol) per vial, equivalent to 395 mg/ml. The amount of alcohol in each vial is equivalent to less than 30 ml of beer or 12 ml of wine.
The amount of alcohol in this medicine is unlikely to have an effect in adults and adolescents, and its effects in children are not evident. However, some effects may occur in young children, for example, drowsiness.
The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.
If you are pregnant or breastfeeding, talk to your doctor or pharmacist before taking this medicine.
If you have alcohol dependence, talk to your doctor or pharmacist before taking this medicine.

3. How to use Cabazitaxel Accord

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

• Cabazitaxel Accord will be administered to you by a doctor or nurse.
• Cabazitaxel Accord must be prepared (diluted) before administration. This leaflet contains practical information on the handling and administration of

Cabazitaxel Accord for physicians, nurses, and pharmacists.

• Cabazitaxel Accord will be administered to you in hospital by intravenous infusion lasting approximately 1 hour.
• As part of your treatment, you will also take an oral corticosteroid (prednisone or prednisolone) daily. What doses and how frequently is administration carried out?
• The usual dose depends on body surface area. Your doctor will calculate your body surface area in square meters (m²) and determine the appropriate dose for you.
• Normally, an infusion will be administered every 3 weeks. If you have any doubts about the use of this medicine, please 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 also explain the potential risks and benefits of the treatment.
Contact your doctor immediately if you notice any of the following side effects:

• fever (high body temperature). This is a very common side effect (may occur in up to 1 in 10 people);
• severe loss of body fluids (dehydration). This is a common side effect (may occur in up to 1 in 10 people). It 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 condition can 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)
• stomach disorders including nausea, vomiting, diarrhoea, or constipation
• back pain
• blood in the urine
• feeling tired, weak, or lacking 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 will regrow)
• joint pain
• urinary tract infection
• decrease in white blood cells associated with fever and infection
• numbness, tingling, burning, or reduced sensation in hands and feet
• dizziness
• headache
• decrease or increase in blood pressure
• stomach discomfort, burning sensation, or burping
• stomach pain
• haemorrhoids
• muscle spasms
• pain or increased frequency of urination
• urinary incontinence
• kidney disease or disorders
• mouth or lip ulcers
• infections or increased risk of infections
• high blood sugar
• insomnia
• mental confusion
• feeling of anxiety
• unusual sensation, loss of sensation, or pain in hands and feet
• balance problems
• rapid or irregular heartbeat
• blood clots in legs or lungs (thrombosis)
• skin redness
• mouth or throat pain
• rectal bleeding
• discomfort, weakness, or muscle pain
• swelling of feet or legs
• chills
• nail disorders (change in nail colour; nails may fall off).

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

• low levels of potassium in the blood
• ringing in the ears
• skin burning sensation
• skin redness
• 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 breathing difficulties).

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 Accord

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 vial label after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from light.

After opening
Each vial is for single use only and must be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

After final dilution in the infusion bag/bottle
Chemical and physical in-use 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 when refrigerated (2°C–8°C), including a 1-hour infusion time.
From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the storage times and conditions of the prepared solution are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Disposal
Unused medicine and waste materials 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 Accord contains
The active substance is cabazitaxel. One ml of concentrate contains 20 mg of cabazitaxel. Each
3 ml vial of concentrate contains 60 mg of cabazitaxel.
The other components in the concentrate are polysorbate 80, citric acid and anhydrous ethanol (see
section 2 “Cabazitaxel Accord contains alcohol”).

Description of the appearance of Cabazitaxel Accord and contents of the pack
Cabazitaxel Accord is a concentrate for solution for infusion (sterile concentrate). The concentrate is a clear solution ranging from colourless to pale yellow or yellow-brown.
It is supplied in a single-use 6 ml clear glass vial providing a deliverable volume of 3 ml of concentrate.

Pack size:
Each pack contains one single-use vial.

Marketing Authorisation Holder
Accord Healthcare S.L.U
World Trade Center, Moll de Barcelona s/n,
Edifici Est, 6th floor, Barcelona,
08039 Barcelona, Spain

Manufacturer
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca,
Barcelona, 08040, Spain
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
Accord Healthcare Polska Sp. z o.o.,
ul. Lutomierska 50, Pabianice, 95-200
Poland
Accord Healthcare B.V
Winthontlaan 200, UTRECHT, 3526KV
Netherlands

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PT / PL / RO / SE / SI / SK / ES
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64

EL
Win Medica Α.Ε.
Tel: +30 210 7488 821

Further sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals.

PRACTICAL INFORMATION FOR PHYSICIANS OR HEALTHCARE PROFESSIONALS ON THE PREPARATION, ADMINISTRATION AND HANDLING OF CABAZITAXEL ACCORD 20 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION

This information supplements sections 3 and 5 for the user.
It is important to 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 dilution.

Shelf life and special precautions for storage
For the pack of Cabazitaxel Accord 20 mg/ml concentrate for solution for infusion:
This medicinal product requires no special storage conditions.
Store in the original packaging to protect from light.

After opening
Each vial is for single use only and must be used immediately after opening. If not used immediately, the times and conditions of storage in use are the responsibility of the user.

After final dilution in the infusion bag/bottle
The 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. If not used immediately, the times and conditions of storage in use are the responsibility of the user and should normally not exceed 24 hours at 2°C – 8°C, unless dilution has taken place under controlled, validated aseptic conditions.

Precautions for preparation and administration
As with any other antineoplastic agent, caution should be exercised during handling and preparation of solutions containing Cabazitaxel Accord, and consideration should be given to using containment devices, personal protective equipment (e.g. gloves), and proper preparation procedures.

If Cabazitaxel Accord comes into contact with the skin at any stage during 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 Accord must be administered and prepared only by personnel qualified in handling cytotoxic agents. The medicinal product must not be handled by pregnant personnel.

Preparation steps
DO NOT use concurrently with other medicinal products containing cabazitaxel at different concentrations. Cabazitaxel Accord contains 20 mg/ml of cabazitaxel (at least 3 ml deliverable volume).

Each vial is for single use only and must be used immediately. Unused solution must be discarded. More than one vial of Cabazitaxel Accord may be required to administer the prescribed dose.

The dilution process must be carried out aseptically to prepare the infusion solution.

Preparation of the infusion solution
Step 1
Aseptically withdraw the required amount of Cabazitaxel Accord (20 mg/ml of cabazitaxel) using a graduated syringe fitted with a needle.
For example, a 45 mg dose of cabazitaxel requires 2.25 ml of Cabazitaxel Accord.

Concentrate 20 mg/ml

Step 2
Inject the solution into a sterile, non-PVC container containing 5% glucose solution or 9 mg/ml (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.

5% glucose solution or 9 mg/ml (0.9%) sodium chloride solution for infusion

Required amount of concentrate

Step 3

Remove the syringe and mix the contents of the infusion bag or bottle manually by gentle agitation. The infusion solution appears clear and colourless.

Step 4

As with all parenteral products, the resulting infusion solution should be inspected visually. Since the infusion solution is supersaturated, crystallisation may occur over time.
In such cases, the solution must not be used and must be discarded.

The infusion solution must be used immediately. Information on the shelf life and special precautions for storage is provided above.

Any unused medicinal product and waste materials derived from it must be disposed of in accordance with local regulations.

Method of administration
Cabazitaxel Accord 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.
Do not use PVC infusion containers or polyurethane infusion sets for the preparation and administration of the infusion solution.