Consumer medicine information

Cabazitaxel Juno

Cabazitaxel

BRAND INFORMATION

Brand name

Cabazitaxel Juno

Active ingredient

Cabazitaxel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cabazitaxel Juno.

What is in this leaflet

This leaflet answers some common questions about Cabazitaxel Juno.

It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given this medicine against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor.

Keep this leaflet in a safe place as you may need to read it again.

What Cabazitaxel Juno is used for

The name of your medicine is Cabazitaxel Juno. It belongs to a group of medicines called 'taxanes' used to treat cancers. Cabazitaxel Juno is used to treat prostate cancer that has progressed after having had other chemotherapy. It works by stopping cells from growing and multiplying.

Ask your doctor if you have any questions about why it has been prescribed for you.

This medicine is only available with a doctor's prescription.

There is no evidence that this medicine is addictive.

Before you are given Cabazitaxel Juno

Do not receive Cabazitaxel Juno if:

  • the number of your white blood cells is too low (neutrophil counts of 1,500 per cubic millimetre, or less - your doctor will advise you on this),
  • you have a liver disease
  • you are pregnant or breast-feeding
  • you have recently received or are about to receive a vaccine against yellow fever.

Do not receive Cabazitaxel Juno if you are allergic to it or any of the ingredients listed at the end of this leaflet. Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Do not receive Cabazitaxel Juno if you are pregnant or intend to become pregnant. Cabazitaxel Juno may affect your developing baby if you are given Cabazitaxel Juno during pregnancy. If your partner is pregnant or is planning on becoming pregnant, ensure to use a condom.

The use of effective contraception in male patients with partners who may become pregnant is recommended during treatment and for 6 months after the final treatment is given. Cabazitaxel Juno might be present in your semen. Therefore, the use of a condom is always recommended during sexual intercourse.

Do not receive Cabazitaxel Juno if you are breastfeeding or planning to breastfeed. Cabazitaxel Juno could pass into breast milk and there is a possibility your baby may be affected.

Do not give Cabazitaxel Juno to a child or adolescent.

Do not receive Cabazitaxel Juno after the expiry date (EXP) printed on the vial. If you receive it after the expiry date has passed, it may not work as well.

Do not receive Cabazitaxel Juno if the packaging is damaged or shows signs of tampering.

Before you are given Cabazitaxel Juno

Tell your doctor if:

  • you have allergies to the ingredients listed at the end of this leaflet
  • you are taking other medicines including medicines used to prevent blood clots and oral non-steroidal anti-inflammatories (NSAIDS).

Tell your doctor if you are pregnant or intend to become pregnant. Like most medicines of this kind, Cabazitaxel Juno is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of receiving Cabazitaxel Juno if you are pregnant.

Tell your doctor if you are breastfeeding or planning to breastfeed. It is not known whether Cabazitaxel Juno passes into breast milk. Your doctor will discuss the risks and benefits of receiving Cabazitaxel Juno if you are breastfeeding or planning to breastfeed.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • a fever (during treatment with Cabazitaxel Juno, it is more likely that your white blood cell count may be reduced). Your doctor will monitor your blood and general condition for signs of infections.
  • any allergies
  • lung, liver or kidney problems
  • any stomach problems past or present (including ulcers)
  • severe or long-lasting diarrhoea, nausea or vomiting. Any of these events could cause dehydration. Your doctor may need to treat you.
  • if you have a feeling of numbness, tingling, burning or decreased sensation in your hands or feet
  • if you have any bleeding from the gut that may cause changes in the colour of your stool or stomach pain.

This medicine contains 13% w/w ethanol (alcohol), equivalent to 14 ml of beer or 6 ml of wine. To be taken into account if:

  • if suffer from alcoholism
  • have a liver disease
  • have epilepsy/seizures

Tell your doctor if you plan to have surgery.

If you have not already told your doctor about any of the above, tell them before you are given Cabazitaxel Juno.

Taking other medicines

Tell your doctor if you are taking any other medicines including herbal supplements and vitamins and those that you buy without a prescription from your pharmacy, supermarket or health food store.

This is because some medicines can affect the way Cabazitaxel Juno works or Cabazitaxel Juno can affect how other medicines work. These include:

  • medicines used to treat bacterial, fungal or viral infections (e.g. clarithromycin, ketoconazole, rifampicin)
  • medicines used to treat seizures or epilepsy (e.g. carbamazepine, phenobarbital, phenytoin)
  • herbal remedy for depression and other conditions (St John's Wort (Hypericum perforatum)

Talk to your doctor before getting vaccinations while you are receiving Cabazitaxel Juno.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while being given Cabazitaxel Juno.

How Cabazitaxel Juno is given

How much to be given

The dose will depend on your height and weight. Your doctor will calculate your body surface area in square meters (m2) and will determine the dose you should receive.

The standard dose of Cabazitaxel Juno is 25mg per square metre. Your doctor may decide on an alternative dose depending on your condition.

Additional medications

As part of your treatment for prostate cancer, you will also take an oral corticosteroid medicine (prednisone or prednisolone) daily.

Half an hour before you receive Cabazitaxel Juno, you will be given the following medications to reduce your chance of developing an allergic reaction or nausea:

  • antihistamine (diphenhydramine or equivalent)
  • corticosteroid (dexamethasone or equivalent)
  • H2 antagonist (ranitidine or equivalent)
  • anti-nausea medication (if required)

How Cabazitaxel Juno is given

Cabazitaxel Juno will be given by infusion into one of your veins (intravenous use). The infusion will last approximately 1 hour during which you will be in the hospital.

Duration of treatment

You should usually receive your infusion once every 3 weeks.

Each 3 week period is called one cycle of chemotherapy. Your doctor will decide how many of these cycles you will need.

If you have any further questions about how you will receive this medicine, ask your doctor, pharmacist or nurse.

If you receive too much (overdose)

As Cabazitaxel Juno is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any unexpected or worrying side effects after being given Cabazitaxel Juno immediately telephone your doctor, or the Poisons Information Centre (telephone Australia 13 11 26 or go to Accident and Emergency at your nearest hospital.

If you receive too much Cabazitaxel Juno, you may experience one or more of the following symptoms: fever, nausea, diarrhoea, vomiting, constipation, abdominal pain, including upper abdominal pain, indigestion, and reflux.

While you are being given Cabazitaxel Juno

Things you must do

Use a condom during sex if your partner is or could become pregnant. Cabazitaxel Juno could be present in your semen and may affect the foetus.

You are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment because Cabazitaxel Juno may alter male fertility.

If your partner becomes pregnant while you are being given thismedicine, tell your doctor immediately.

Tell all the doctors, dentists and pharmacists who are treating you that you are being given Cabazitaxel Juno.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are being given Cabazitaxel Juno.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are being given this medicine.

Things you must not do

Do not receive more than the recommended dose unless your doctor tells you to.

Do not stop using Cabazitaxel Juno without checking with your doctor. If you do not complete the full course prescribed by your doctor, Cabazitaxel Juno may not work as well as it's supposed to.

Things to be careful of

Be careful driving or operating machinery until you know how Cabazitaxel Juno affects you. Cabazitaxel Juno may cause side effects such as fatigue or dizziness that may affect your ability to drive and use machinery. Make sure you know how you react to Cabazitaxel Juno before you drive a car, operate machinery, or do anything else that could be dangerous if you feel dizzy or fatigued.

If you experience these symptoms, do not drive or use any tools or machines until they have fully resolved.

Side effects

Cabazitaxel Juno helps most people with prostate cancer, but it may have unwanted side effects in some people.

All medicines have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor or pharmacist has weighed the risks of using this medicine against the benefits they expect it will have for you.

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given Cabazitaxel Juno.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

If any of the following happen while you are being given Cabazitaxel Juno in the hospital/clinic, Cabazitaxel Juno should be stopped immediately. Tell your doctor or nurse immediately. If you are outside of the hospital/clinic go to Accident and Emergency at your nearest hospital:

  • swelling of the face, lips, mouth or throat, which may cause difficultly in swallowing or breathing.
  • hives
  • fainting
  • yellowing of the skin and eyes (jaundice)

These are very serious side effects. If you have them, you may have had a serious allergic reaction to Cabazitaxel Juno. You may need urgent medical attention or hospitalisation.

These side effects are very rare.

See a doctor immediately if you notice any of the following side effects:

  • fever (high temperature). This is very common (affects more than 1 in 10 patients)
  • severe loss of body fluids (dehydration). This is common (affects less than 1 in 10 patients). This can occur if you have severe diarrhoea (increase of more than 4 or more stools more than usual a day) or long-lasting diarrhoea, or fever, or if you are vomiting

Tell your doctor, nurse or pharmacist if you notice any of the following:

Very common side effects (affects more than 1 in 10 patients):

  • feeling tired, weak or lack of energy
  • symptoms of anaemia like tiredness, and inability to perform daily tasks (due to a decrease in the number of red blood cells)
  • increased bleeding (due to a decrease in the number of platelets)
  • loss of appetite (anorexia)
  • alteration in sense of taste
  • shortness of breath
  • cough
  • stomach upsets including nausea, vomiting and diarrhoea, constipation
  • abdominal pain
  • short term hair loss (in most cases normal hair growth should return after treatment has stopped)
  • back pain
  • joint pain
  • blood in the urine

Common side effects (affects less than 1 in 10 patients):

  • urinary tract infection
  • fever and infection (associated with a reduction of white blood cells)
  • feeling of numbness, tingling, burning or decreased sensations in hands and feet
  • dizziness
  • headache
  • decrease or increase in blood pressure
  • uncomfortable feeling in the stomach or belching after eating
  • gastro-oesophageal reflux or heartburn
  • stomach pain
  • haemorrhoids
  • muscle spasm
  • pain when passing urine
  • urinary incontinence
  • sores in the mouth or on the lips
  • high blood sugar
  • low blood potassium
  • rapid or irregular heartbeat
  • kidney disease or problems
  • ringing in the ear
  • trouble with balance
  • blood clot in the leg
  • pain in mouth or throat
  • rectal bleeding
  • redness of skin
  • skin infections
  • skin feeling hot or flushed
  • muscle discomfort, aches or pain
  • swelling of the feet or legs
  • lung infection
  • chills

Inflammation of the bladder may also occur if you have previously received radiation therapy. Tell your doctor, nurse or pharmacist if you have burning sensation when passing urine.

Tell your doctor, nurse or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some patients.

Ask your doctor, nurse or pharmacist to answer any questions you may have if you experience any side effects.

After being given Cabazitaxel Juno

If you have any queries about any aspect of your medicine, or any questions regarding the information in this leaflet, discuss them with your doctor, nurse or pharmacist.

Storage

Cabazitaxel Juno is stored in the pharmacy or on the ward. Do not store at home.

Product description

What Cabazitaxel Juno looks like

One pack of Cabazitaxel Juno consists of:

  • One vial of 60mg/1.5ml concentrate (which is a clear yellow to brownish-yellow oily solution)
  • One vial of 60mg/1.5ml diluent (which is a clear and colourless solution)

Ingredients

Active Ingredient:
The active substance is cabazitaxel. One ml of concentrate contains 40mg cabazitaxel. Each vial of concentrate contains 60mg cabazitaxel.

Inactive Ingredients:
The other ingredients are polysorbate 80 and citric acid monohydrate in the concentrate and ethanol 96% and water for injections in the diluent.

Cabazitaxel Juno does not contain gluten, sucrose, lactose, tartrazine or any other azo dyes.

Name and Address of the Sponsor

Dr Reddy’s Laboratories (Australia) Pty Ltd
Suite 3.03, Level 3, 390 St Kilda Road
Melbourne, VIC, 3004 Australia

Distributed by:

Juno Pharmaceuticals Pty Ltd
Level 2, 6 Bond Street
South Yarra, VIC 3141

Australian Registration Number: AUST R 287929

This leaflet was prepared in September 2020.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Cabazitaxel Juno

Active ingredient

Cabazitaxel

Schedule

S4

 

Notes

Distributed by Juno Pharmaceuticals Pty Ltd

1 Name of Medicine

Cabazitaxel.

2 Qualitative and Quantitative Composition

Cabazitaxel Juno injection concentrate contains 60 mg cabazitaxel in 1.5 mL.
The diluent for Cabazitaxel Juno contains ethanol in water for injections.
Excipients with known effect: diluent contains alcohol as 16.4% v/v ethanol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Cabazitaxel Juno (cabazitaxel) 60 mg/1.5 mL concentrate is a sterile, non-pyrogenic, clear yellow to brownish-yellow viscous solution, free from visible extraneous matter.
The diluent for Cabazitaxel Juno is a clear, colourless, sterile, and non-pyrogenic, solution, free from visible extraneous matter.

4 Clinical Particulars

4.1 Therapeutic Indications

Cabazitaxel Juno in combination with prednisone or prednisolone is indicated for the treatment of patients with metastatic castration resistant prostate cancer previously treated with a docetaxel containing regimen.

4.2 Dose and Method of Administration

The use of cabazitaxel should be confined to units specialised in the administration of cytotoxics and it should only be administered under the supervision of a physician experienced in the use of anticancer chemotherapy.
Do not use PVC infusion containers (bags or bottles) for the preparation of the infusion solution.
Do not use polyurethane infusion sets (tubing, filter, pumps) for the administration of the infusion solution.

Premedication.

Premedicate at least 30 minutes prior to each administration of cabazitaxel with the following intravenous medications to reduce the risk and severity of a hypersensitivity reaction:
antihistamine (equivalent to dexchlorpheniramine 5 mg or diphenhydramine 25 mg);
corticosteroid (dexamethasone 8 mg or equivalent); and with
H2 antagonist (ranitidine or equivalent).
Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed (see Section 4.4 Special Warnings and Precautions for Use).

Preparation process.

As for any other antineoplastic agent, caution should be exercised when handling and preparing cabazitaxel solutions. The use of gloves is recommended.
If cabazitaxel, at any step of its handling, should come into contact with the skin, wash immediately and thoroughly with soap and water. If it should come into contact with mucous membranes, wash immediately and thoroughly with water.
Cabazitaxel should only be prepared and administered by personnel trained in handling cytotoxic agents. Pregnant staff should not handle it. Cabazitaxel is for single use in one patient only. Discard any residue.
Read this entire section carefully before mixing and diluting. Cabazitaxel requires a two step dilution process prior to administration. Follow the preparation instructions provided below.

Note.

Both the cabazitaxel concentrate vial and the diluent vial contain an overfill to compensate for liquid loss during preparation. The overfill ensures that the pre-mix concentration will be 10 mg/mL cabazitaxel provided that the entire contents of the diluent are transferred into the cabazitaxel concentrate vial.
The following 2-step dilution process must be carried out in an aseptic manner for preparing the solution for infusion:

Step 1: Preparation of pre-mix (initial dilution of cabazitaxel 60 mg/1.5 mL concentrate with the supplied diluent).

Inspect the cabazitaxel 60 mg/1.5 mL concentrate vial and the supplied diluent. The concentrate solution should be clear (see Section 6.4 Special Precautions for Storage; Section 6.5 Nature and Contents of Container).
Withdraw the entire content of the supplied diluent using a syringe, by partially inverting the vial, and inject it into the corresponding cabazitaxel 60 mg/1.5 mL concentrate vial. To limit foaming as much as possible when injecting the diluent, direct the needle onto the inside wall of the vial of concentrate and inject slowly.
Remove the syringe and needle and mix manually and gently by repeated inversions until the solution is clear and homogeneous. It could take approximately 45 seconds.
Let the solution stand for approximately 5 minutes and check then that the solution is homogeneous and clear. It is normal for foam to persist after this time period.
This resulting pre-mix (concentrate-diluent mixture) contains 10 mg/mL of cabazitaxel (at least 6 mL deliverable volume). It should be immediately diluted as detailed in step 2.
Unused pre-mix should be discarded.

Step 2: Preparation of the infusion solution.

Withdraw the required amount of initial diluted (pre-mix) cabazitaxel solution (10 mg/mL of cabazitaxel), with a graduated syringe and inject into a sterile PVC-free container (bags or bottles) of either 5% glucose solution or 0.9% sodium chloride solution for infusion. The concentration of the infusion solution should be between 0.10 mg/mL and 0.26 mg/mL.
As an example, a dose of 45 mg cabazitaxel would require 4.5 mL of the concentrate-diluent mixture prepared following step 1. More than one vial of the initial diluted solution may be necessary to administer the prescribed dose.
Since foam may persist on the wall of the vial of this solution, following its preparation described in step 1, it is preferable to place the needle of the syringe in the middle when extracting.
Remove the syringe and mix the content of the infusion bag or bottle manually using a rocking motion.
As with all parenteral products, the resulting infusion solution should be visually inspected prior to use. Solution containing a precipitate should be discarded.

Administration.

Use an in-line filter of 0.22 micrometer (also referred to as 0.2 micrometer) nominal pore size during administration.
Do not use polyurethane infusion sets (tubing, filter, pumps) for the administration of the infusion solution.
The cabazitaxel infusion solution should be used immediately. However, in-use storage time can be longer under specific conditions mentioned, see Section 6.4 Special Precautions for Storage.
Any unused product or waste material should be disposed of in accordance with local requirements.

Recommended dosage.

The recommended dose of cabazitaxel is 25 mg/m2 administered as a 1-hour intravenous infusion every 3 weeks in combination with oral prednisone (or prednisolone) 10 mg administered daily throughout cabazitaxel treatment.

Dosage adjustments.

Dosage modifications should be made if patients experience the following adverse reactions. See Table 1.
Discontinue cabazitaxel treatment if a patient continues to experience any of these reactions at 20 mg/m2.

Special populations.

Patients with hepatic impairment.

Cabazitaxel is extensively metabolised by the liver. No formal studies have been carried out in patients with hepatic impairment. As a precautionary measure, cabazitaxel should not be given to patients with hepatic impairment (bilirubin ≥ 1 x Upper Limit of Normal (ULN), or AST and/or ALT ≥ 1.5 x ULN) (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).

Concomitant medicinal products use.

Concomitant medicines that are strong inducers or inhibitors of CYP3A should be avoided (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). However if patients require co-administration of a potent CYP3A inhibitor, a cabazitaxel dose reduction should be considered.

Patients with renal impairment.

Cabazitaxel is minimally excreted through the kidney. No dose adjustment is necessary in patients with mild renal impairment (creatinine clearance (CLCR): 50 to 80 mL/min). Limited data are available for patients with moderate impairment (CLCR: 30 to 50 mL/min) and no data are available for patients with severe renal impairment (CLCR < 30 mL/min) or end stage renal disease. Therefore, these patients should be treated with caution and monitored carefully during treatment.

Elderly.

No specific dose adjustment for the use of cabazitaxel in elderly patients is recommended (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Children.

The safety and efficacy of cabazitaxel in children have not been established.

4.3 Contraindications

History of severe hypersensitivity reactions to cabazitaxel, any of the excipients of cabazitaxel or other drugs formulated with polysorbate 80.
Neutrophil counts ≤ 1,500/mm3.
Hepatic impairment (bilirubin ≥ 1 x ULN, or AST/SGOT and/or ALT/SGPT ≥ 1.5 x ULN).
Pregnancy and breast-feeding.
Concomitant vaccination with yellow fever vaccine (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Bone marrow suppression.

Bone marrow suppression manifested as neutropenia, anaemia, thrombocytopenia or pancytopenia may occur, (see additional information in the Neutropenia and Anaemia precautions below).

Neutropenia.

Neutropenic deaths have been reported with cabazitaxel. Neutropenia is the most common adverse reaction of cabazitaxel (see Section 4.8 Adverse Effects (Undesirable Effects)). Monitoring of complete blood count is essential on a weekly basis during cycle 1 and before each treatment cycle thereafter so that the dose can be adjusted, if needed (see Section 4.2 Dose and Method of Administration).
Dose reduction is recommended in the case of febrile neutropenia, or prolonged neutropenia despite appropriate treatment (see Section 4.2 Dose and Method of Administration).
Restart treatment only when neutrophils recover to a level > 1.5 cells x 109/L (see Section 4.3 Contraindications).
The use of G-CSF has been shown to limit the incidence and severity of neutropenia.
Patients treated with cabazitaxel may receive prophylactic G-CSF as per American Society of Clinical Oncology (ASCO) and/or current institutional guidelines, to reduce the risk or manage neutropenia complications (febrile neutropenia, prolonged neutropenia or neutropenic infection).

Hypersensitivity reactions.

All patients should be premedicated prior to the initiation of the infusion of cabazitaxel (see Section 4.2 Dose and Method of Administration).
Patients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of cabazitaxel, thus facilities and equipment for the treatment of hypotension and bronchospasm should be available. Severe reactions can occur and may include generalised rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of cabazitaxel and appropriate therapy. Patients who have a history of severe hypersensitivity reactions should not be rechallenged with cabazitaxel (see Section 4.3 Contraindications).

Gastrointestinal symptoms.

Nausea, vomiting and severe diarrhoea may occur. A death related to diarrhoea and electrolyte imbalance occurred with cabazitaxel in the efficacy trial. Intensive measures may be required for severe diarrhoea and electrolyte imbalance. Patients should be treated with rehydration, anti-diarrhoeal or anti-emetic medications as needed. Monitor and correct serum electrolyte levels particularly potassium. Delay in cabazitaxel treatment or reduction in dose may be necessary if patients experience Grade ≥ 3 diarrhoea (see Section 4.2 Dose and Method of Administration). Diarrhoea can also occur more frequently in patients who have received prior abdomino-pelvic irradiation. Dehydration is more common in patients aged 65 or older.
Gastrointestinal (GI) haemorrhage and perforation, ileus, colitis, including fatal outcome, have been reported in patients treated with cabazitaxel. Caution is advised with treatment of patients most at risk of developing gastrointestinal complications: those with neutropenia, the elderly, concomitant use of NSAIDs, antiplatelet therapy or anti-coagulants, and patients with a prior history of pelvic radiotherapy, gastrointestinal disease, such as ulceration and GI bleeding.
Symptoms such as abdominal pain and tenderness, fever, persistent constipation, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly. Cabazitaxel treatment delay or discontinuation may be necessary.

Peripheral neuropathy.

Cases of peripheral neuropathy, both sensory (e.g. paraesthesia, dysaesthesia) and motor, have been observed in patients treated with cabazitaxel. Patients should be advised to consult their doctor prior to continuing treatment if neuropathy symptoms such as pain, burning, tingling, numbness or weakness develop. Physicians should assess patients for the presence or worsening of neuropathy before each treatment. Treatment should be delayed until improvement of symptoms. For persistent Grade ≥ 2 peripheral neuropathy, the dose of cabazitaxel should be reduced (see Section 4.2 Dose and Method of Administration).

Urinary disorders.

Cystitis due to radiation recall phenomenon has been reported with cabazitaxel therapy in patients who have previously received pelvic radiation therapy and docetaxel containing regimen (see Section 4.8 Adverse Effects (Undesirable Effects)). Appropriate measures should be initiated. Interruption or discontinuation of cabazitaxel therapy may be necessary.

Respiratory disorders.

Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome have been reported and may be associated with fatal outcome (see Section 4.8 Adverse Effects (Undesirable Effects)). If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly investigated and appropriately treated. Interruption of cabazitaxel therapy is recommended until diagnosis is available. Early use of supportive care measures may improve the condition. The benefit of resuming cabazitaxel treatment must be carefully evaluated.

Eye disorders.

Subcapsular lens fibre swelling/degeneration was observed in rats during a 10-cycle toxicity study at 10 mg/kg (60 mg/m2 [approximately 2-fold the AUC in cancer patients at the recommended human dose]). The No-Observable Effect Level for microscopic lens findings was 5 mg/kg (30 mg/m2 [approximately the AUC in cancer patients at the recommended human dose]). The clinical relevance of these findings is unknown. Adverse reactions were not observed in clinical studies.

Anaemia.

Anaemia has been observed in patients receiving cabazitaxel (see Section 4.8 Adverse Effects (Undesirable Effects)). Caution is recommended in patients with haemoglobin < 100 g/L and appropriate measures should be taken as clinically indicated.

Risk of cardiac arrhythmias.

Cardiac arrhythmias have been reported, most commonly tachycardia and atrial fibrillation (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in hepatic impairment.

Treatment with cabazitaxel is contraindicated (see Section 4.3 Contraindications). No formal studies in patients with hepatic impairment have been conducted. Cabazitaxel should not be given to patients with hepatic impairment [bilirubin ≥ Upper limit of Normal (ULN), or AST/SGOT and/or ALT/SGPT ≥ 1.5 x ULN] (see Section 4.3 Contraindications).
Cabazitaxel is extensively metabolised by the liver, and hepatic impairment is likely to increase cabazitaxel concentrations (see Section 5.2 Pharmacokinetic Properties).
Hepatic impairment increased the risk of severe and life-threatening complications in patients receiving other drugs belonging to the same class as cabazitaxel.
Bile ductule hyperplasia, arteriolar/periarteriolar necrosis, and/or hepatocellular necrosis were observed in dogs after a single dose (0.25 mg/kg [5 mg/m2]) 5-day (0.2 mg/kg [4 mg/m2]) and weekly (0.325 mg/kg [6.5 mg/m2]) administration. Kupffer cell pigmentation and bile duct degeneration/regeneration were observed in the liver at the highest tested dose of 10 mg/kg (60 mg/m2) in a 10-cycle study in rats.

Use in renal impairment.

Cabazitaxel is minimally excreted via the kidney (2.3% of the dose excreted as the unchanged drug). No formal pharmacokinetic studies were conducted with cabazitaxel in patients with renal impairment. However, the population pharmacokinetic analysis carried out in 170 patients that included 14 patients with moderate renal impairment (creatinine clearance in the range of 30 to 50 mL/min) and 59 patients with mild renal impairment (creatinine clearance in the range of 50 to 80 mL/min) showed that mild to moderate renal impairment did not have meaningful effects on the pharmacokinetics of cabazitaxel (see Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties).

Use in the elderly.

Elderly patients (≥ 65 years of age) may be more likely to experience certain adverse reactions including neutropenia or febrile neutropenia with cabazitaxel (see Section 4.8 Adverse Effects (Undesirable Effects)).
In the randomized clinical trial, 3 of 131 (2%) patients < 65 years of age and 15 of 240 (6%) ≥ 65 years of age died of causes other than disease progression within 30 days of the last cabazitaxel dose.
In the population pharmacokinetic analysis in 70 patients of 65 years and older (57 from 65 to 75 and 13 ≥ 75), there was no age effect on the pharmacokinetics of cabazitaxel. No specific dose adjustment is recommended in the elderly.

Paediatric use.

The safety and the efficacy of cabazitaxel in children have not been established.

Effects on laboratory tests.

No information available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No formal clinical drug-drug interaction studies have been performed.
In vitro studies have shown that cabazitaxel is mainly metabolized through CYP3A (80% to 90%).

CYP3A inhibitors.

Though no formal drug interaction trials have been conducted for cabazitaxel, concomitant administration of potent CYP3A inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) is expected to increase concentrations of cabazitaxel. Therefore, coadministration with potent CYP3A inhibitors should be avoided. If co-administration with a potent CYP3A inhibitor cannot be avoided, close monitoring for toxicity and a cabazitaxel dose reduction should be considered. Caution should be exercised with concomitant use of moderate CYP3A inhibitors.

CYP3A inducers.

Though no formal drug interaction trials have been conducted for cabazitaxel, the concomitant administration of CYP3A inducers (e.g. phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital) is expected to decrease cabazitaxel concentrations. Therefore, coadministration with CYP3A inducers should be avoided (see Section 5.2 Pharmacokinetic Properties). In addition, patients should also refrain from taking St. John's Wort.
In vitro, cabazitaxel has also been shown to inhibit the transport proteins of the Organic Anion Transport Polypeptides OATP1B1. The risk of interaction with OATP1B1 substrates (e.g. statins, valsartan, repaglinide) is possible notably during the infusion duration (1 hour) and up to 20 minutes after the end of the infusion, and may lead to an increase of exposure of OATP1B1 substrates.
Prednisone/prednisolone administered at 10 mg daily did not affect the pharmacokinetics of cabazitaxel.
In vitro, cabazitaxel did not inhibit Multidrug Resistant Proteins (MRP): MRP1 and MRP2. Cabazitaxel inhibited the transport of P-glycoprotein (P-gp) (digoxin, vinblastine) and Breast Cancer Resistant Proteins (BRCP) (methotrexate), at concentrations at least 37 fold what is observed in clinical settings. Therefore the risk of interaction, with MRP, P-gp and BCRP substrates, is unlikely in vivo at the dose of 25 mg/m2.

Vaccinations.

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapy may result in serious or fatal infections. Vaccination with a live attenuated vaccine should be avoided in patients receiving cabazitaxel (see Section 4.3 Contraindications). Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of cabazitaxel on human fertility is unknown. Cabazitaxel did not affect mating performances or fertility of male or female rats at intravenous cabazitaxel doses of up to 0.2 mg/kg/day (resulting in AUCs below those in patients at the recommended dose). However, in multi-cycle toxicity studies following the clinically recommended dosing schedule in rats and dogs, the male reproductive system was identified as a target organ in both species and the female reproductive system was identified as a target organ in rats. Toxic effects, including seminiferous tubular atrophy and degeneration of seminal vesicles in males, and atrophy of the uterus and necrosis of corpora lutea in females, were observed at exposures (AUC) similar to or less than the AUC in patients at the recommended dose.
Animal studies showed that cabazitaxel affected the reproductive system in male rats and dogs without any functional effect on fertility. Nevertheless, considering the pharmacological activity of taxanes, their genotoxic potential and effect of several compounds of this class on fertility in animal studies, effect on male fertility could not be excluded in human.
Due to potential effects on male gametes and to potential exposure via seminal liquid, men treated with cabazitaxel should use effective contraception throughout treatment and are recommended to continue this for up to 6 months after the last dose of cabazitaxel. Due to potential exposure via seminal liquid, men treated with cabazitaxel should prevent contact with the ejaculate by another person throughout treatment. Men being treated with cabazitaxel are advised to seek advice on conservation of sperm prior to treatment.
(Category D)
Cabazitaxel is not recommended during pregnancy.
Due to potential exposure via seminal liquid, men with partners of childbearing potential should use reliable contraception throughout treatment and are recommended to continue this for up to 6 months after the last dose of cabazitaxel.
There are no adequate and well-controlled studies in pregnant women using cabazitaxel. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential should be advised to avoid becoming pregnant during treatment with cabazitaxel.
Studies in rats have shown that cabazitaxel crosses the placenta barrier. When female rats were given cabazitaxel intravenously once daily during the period of organogenesis embryofoetal toxicity was observed at a dose of 0.16 mg/kg/day, (resulting in exposures (AUC) well below those in patients at the recommended dose) consisting of foetal deaths and decreased mean foetal weight associated with a delay in skeletal ossification. Similar findings have been reported with docetaxel or paclitaxel.
Cabazitaxel did not produce foetal abnormalities in rats and rabbits.
 Cabazitaxel should not be used during breast-feeding.
Data in rats have shown excretion of cabazitaxel and/or its metabolites in milk.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, based on the safety profile, cabazitaxel may have moderate influence on the ability to drive and use machines as it may cause fatigue and dizziness. Patients should be advised to not drive or use machines if they experience these adverse reactions during treatment.

4.8 Adverse Effects (Undesirable Effects)

The following Council for International Organizations of Medical Sciences (CIOMS) frequency rating is used, when applicable: Very common ≥ 10%; Common ≥ 1 and < 10%; Uncommon ≥ 0.1 and < 1%; Rare ≥ 0.01 and < 0.1%; Very rare < 0.01%, not known (cannot be estimated from the available data).
The safety of cabazitaxel in combination with prednisone or prednisolone was evaluated in 371 patients with hormone refractory metastatic prostate cancer, in a randomised open label, controlled phase III study (TROPIC). Patients received a median of 6 cycles of cabazitaxel or 4 of mitoxantrone.
The most commonly (≥ 5%) occurring Grade ≥ 3 adverse reactions in the cabazitaxel group were neutropenia (81.7%), febrile neutropenia (7.5%), diarrhoea (6.2%), leukopenia (68.2%) and anaemia (10.5%).
Discontinuation of treatment due to adverse drug reactions occurred in 68 patients (18.3%) in the cabazitaxel group and 31 patients (8.4%) in the mitoxantrone group. The most common adverse reaction leading to treatment discontinuation in the cabazitaxel group was neutropenia. See Table 2.

Neutropenia and associated clinical events.

Incidence of Grade ≥ 3 neutropenia based on laboratory data was 81.7%. The incidence of clinical neutropenia and febrile neutropenia adverse reactions were 21.3% and 7.5%, respectively. Neutropenia was the most common adverse reaction leading to drug discontinuation (2.4%). Neutropenic complications included neutropenic infections (0.5%), neutropenic sepsis (0.8%), and septic shock (1.1%), which in some cases resulted in a fatal outcome.
The use of G-CSF has been shown to limit the incidence and severity of neutropenia (see Section 4.4 Special Warnings and Precautions for Use).

Cardiac disorders and arrhythmias.

All Grade events among cardiac disorders were more common on cabazitaxel of which 6 patients (1.6%) had Grade ≥ 3 cardiac arrhythmias. The incidence of tachycardia on cabazitaxel was 1.6%, none of which were Grade ≥ 3. The incidence of atrial fibrillation was 1.1% in the cabazitaxel group. Cardiac failure events were more common on cabazitaxel, the event term being reported for 2 patients (0.5%). One patient in the cabazitaxel group died from cardiac failure. Fatal ventricular fibrillation was reported in 1 patient (0.3%), and cardiac arrest in 2 patients (0.5%). None were considered related by the investigator, however an indirect relationship cannot be ruled out (e.g. electrolyte imbalance).

Other laboratory abnormalities.

The incidence of Grade ≥ 3 anaemia, increased AST/SGOT, increased ALT/SGPT, and increased bilirubin based on laboratory abnormalities were 10.6%, 0.9%, 1.1%, and 0.6%, respectively.

Post marketing experience.

The following adverse reactions have been identified from clinical trials and/or post-marketing surveillance. Because they are reported from a population of unknown size, precise estimates of frequency cannot be made:

Gastrointestinal disorders.

Colitis, enterocolitis, gastritis, neutropenic enterocolitis have been observed. Gastrointestinal haemorrhage and perforation, ileus and intestinal obstruction have also been reported.

Respiratory disorders.

Cases of interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome, including cases with fatal outcomes have been reported (see Section 4.4 Special Warnings and Precautions for Use).

Elderly population.

Of the 371 patients treated with cabazitaxel in the prostate cancer study, 240 patients were 65 years or over including 70 patients older than 75 years. The following adverse reactions reported at rates ≥ 5% higher in patients 65 years of age or greater compared to younger patients: fatigue (40.4% vs. 29.8%), neutropenia (24.2% vs. 17.6%), asthenia (23.8% vs. 14.5%), pyrexia (14.6% vs. 7.6%), dizziness (10.0% vs. 4.6%), urinary tract infection (9.6% vs 3.1%) and dehydration (6.7% vs 1.5%), respectively.
The incidence of the following Grade ≥ 3 adverse reactions were higher in patients ≥ 65 years of age compared to younger patients: neutropenia based on laboratory abnormalities (86.3% vs. 73.3%), clinical neutropenia (23.8% vs. 16.8%) and febrile neutropenia (8.3% vs. 6.1%) (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).

Renal and urinary disorders.

Cystitis due to radiation recall phenomenon was reported uncommonly (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

The anticipated complications of overdose would be exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders.

Management.

There is no known antidote to cabazitaxel. In case of overdose, the patient should be kept in a specialised unit and closely monitored. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Class.

Antineoplastic agent ATC code: L01CD04.

Mechanism of action.

Cabazitaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells. Cabazitaxel binds to tubulin and promotes the assembly of tubulin into microtubules while simultaneously inhibiting their disassembly. This leads to the stabilisation of microtubules, which results in the inhibition of mitotic and interphase cellular functions.

Pharmacodynamics.

Cabazitaxel demonstrated a broad spectrum of antitumour activity against advanced human tumours xenografted in mice, including intracranial human glioblastomas. Cabazitaxel is active in docetaxel-sensitive tumours. In addition cabazitaxel demonstrated activity in some tumour models insensitive to chemotherapy, including docetaxel.

Clinical trials.

The efficacy and safety of cabazitaxel in combination with prednisone or prednisolone were evaluated in a randomised, open-label, international, multi-centre, phase III study (TROPIC), in patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Overall survival (OS) was the primary efficacy end-point of the study.
Secondary endpoints included Progression Free Survival [PFS (defined as time from randomisation to tumour progression, Prostatic Specific Antigen (PSA) progression, pain progression, or death due to any cause, whichever occurred first], Tumor Response Rate based on Response Evaluation Criteria in Solid Tumors (RECIST), PSA Progression (defined as a ≥ 25% increase or ≥ 50% in PSA non-responders or responders respectively), PSA response (declines in serum PSA levels of at least 50%), pain progression [assessed using the Present Pain Intensity (PPI) scale from the McGill-Melzack questionnaire and an Analgesic Score (AS)] and pain response (defined as 2 point greater reduction from baseline median PPI with no concomitant increase in AS, or reduction of ≥ 50% in analgesic use from baseline mean AS with no concomitant increase in pain).
A total of 755 patients were randomized to receive either cabazitaxel 25 mg/m2 intravenously every 3 weeks for a maximum of 10 cycles with prednisone or prednisolone 10 mg orally daily (n=378), or to receive mitoxantrone 12 mg/m2 intravenously every 3 weeks for a maximum of 10 cycles with prednisone or prednisolone 10 mg orally daily (n=377).
This study included patients over 18 years with hormone-refractory metastatic prostate cancer either measurable by RECIST criteria or non-measurable disease with rising PSA levels or appearance of new lesions, and Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. Patients had to have neutrophils > 1.5 cells x 109/L, platelets > 100 cells x 109/L, haemoglobin > 100 g/L, creatinine < 1.5 x ULN, total bilirubin < 1 x ULN, AST/SGOT < 1.5 ULN, and ALT/SGPT < 1.5 ULN.
Patients with a history of congestive heart failure, or myocardial infarction within the last 6 months, or patients with uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension were not included in the study.
Demographics, including age, race, and ECOG performance status (0 to 2), were balanced between the treatment arms. In the cabazitaxel group, the mean age was 68 years range (46 to 92) and the racial distribution was 83.9% Caucasian, 6.9% Asian, 5.3% Black, and 4% Others.
The median number of cycles was 6 in the cabazitaxel group and 4 in the mitoxantrone group. The number of patients who completed the study treatment (10 cycles) was 29.4% in the cabazitaxel group and 13.5% in the comparator group.
Overall survival was significantly longer with cabazitaxel compared to mitoxantrone (15.1 months versus 12.7 months, respectively), with a 30% reduction in the risk of death compared to mitoxantrone (see Table 3 and Figure 1).
See Table 4.
There were no significant differences in pain progression or pain response between treatments.

5.2 Pharmacokinetic Properties

A population pharmacokinetic analysis was carried out in 170 patients including patients with advanced solid tumours (n=69), metastatic breast cancer (n=34) and metastatic prostate cancer (n=67). These patients received doses of cabazitaxel ranging from 10 to 30 mg/m2 weekly or every 3 weeks.

Absorption.

After a 1-hour IV administration dose of cabazitaxel at 25 mg/m2, in patients with metastatic prostate cancer (n=67), the mean Cmax was 226 nanogram/mL (coefficient of variation, CV 107%) and was reached at the end of the 1-hour infusion (Tmax). The mean AUC was 991 nanogram.h/mL (CV: 34%).
No major deviation to the dose proportionality was observed from 10 to 30 mg/m2 in patients with advanced solid tumours (n=126).

Distribution.

The volume of distribution (Vss) was 4870 L (2640 L/m2 for a patient with a median BSA of 1.84 m2) at steady state.
In vitro, the binding of cabazitaxel to human serum proteins was 89% to 92% and was not saturable up to 50,000 nanogram/mL, which covers the maximum concentration observed in clinical studies. Cabazitaxel is mainly bound to human serum albumin (82.1%) and lipoproteins (87.9% for HDL, 69.8% for LDL, and 55.8% for VLDL). The in vitro blood-to-plasma concentration ratios in human blood ranged from 0.90 to 0.99 indicating that cabazitaxel was equally distributed between blood and plasma.

Metabolism.

Cabazitaxel is extensively metabolised in the liver (≥ 95%), mainly by the CYP3A4 isoenzyme (80% to 90%). Cabazitaxel is the main circulating compound in human plasma. Seven metabolites were detected in plasma (including 3 active metabolites issued from Odemethylation), with the main one accounting for approximately 5% of the parent exposure. Around 20 metabolites of cabazitaxel are excreted into human urine and faeces.
Based on in vitro studies, the potential risk of inhibition by cabazitaxel at clinically relevant concentrations is possible towards drugs that are mainly substrates of CYP3A. However, there is no potential risk of inhibition of drugs that are substrates of other CYP enzymes (1A2, 2B6, 2C9, 2C8, 2C19, 2E1, and 2D6) as well as no potential risk of induction by cabazitaxel on drugs that are substrates of CYP1A, CYP2C9, and CYP3A.
Potent CYP3A inducers or inhibitors could affect cabazitaxel, as cabazitaxel is mainly metabolised by CYP3A.

Excretion.

After a 1-hour IV infusion [14C]-cabazitaxel at 25 mg/m2 in patients, approximately 80% of the administered dose was eliminated within 2 weeks. Cabazitaxel is mainly excreted in the faeces as numerous metabolites (76% of the dose); while renal excretion of cabazitaxel and metabolites account for less than 4% of the dose (2.3% as unchanged drug in urine).
Cabazitaxel has a high plasma clearance of 48.5 L/h (26.4 L/h/m2 for a patient with a median BSA of 1.84 m2) and a long terminal half-life of 95 hours.
Cabazitaxel is minimally excreted via the kidney (2.3% of the dose excreted as the unchanged drug). No formal pharmacokinetic studies were conducted with cabazitaxel in patients with renal impairment. However, the population pharmacokinetic analysis carried out in 170 patients that included 14 patients with moderate renal impairment (creatinine clearance in the range of 30 to 50 mL/min) and 59 patients with mild renal impairment (creatinine clearance in the range of 50 to 80 mL/min) showed that mild to moderate renal impairment did not have meaningful effects on the pharmacokinetics of cabazitaxel (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

5.3 Preclinical Safety Data

Genotoxicity.

Cabazitaxel was negative in the bacterial reverse mutation (Ames) test. Cabazitaxel was not clastogenic in an in vitro test in human lymphocytes (no induction of structural chromosomal aberrations) but it increased number of polyploid cells and it induced an increase of micronuclei in the in vivo micronucleus test in rats. However, these genotoxicity findings are inherent to the pharmacological activity of the compound (inhibition of tubulin depolymerisation) and have been observed with other compounds with the same pharmacological activity.

Carcinogenicity.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of cabazitaxel.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each Cabazitaxel concentrate glass vial with a chlorobutyl rubber stopper and polypropylene flip off seal contains 2.25 mg citric acid and 1.56 g polysorbate 80.
The diluent glass vial with a chlorobutyl rubber stopper and polypropylene flip off seal contains 13% (w/w) ethanol in water for injection, 4.5 mL.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Do not refrigerate undiluted Cabazitaxel Juno concentrate.
Store below 30°C. Do not refrigerate.

Stability of the initial diluted solution in the vial.

After initial dilution (pre-mix) of Cabazitaxel Juno 60 mg/1.5 mL concentrate with the diluent (pre-mix), the resulting concentrate-diluent mixture is stable for 1 hour if stored below 30°C.

Stability of the final dilution solution in the infusion bag.

After final dilution in the infusion bag/bottle, the infusion solution may be stored up to 8 hours below 25°C (including the 1 hour infusion).
To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, the infusion solution may be stored for up to 8 hours below 30°C (including the 1 hour infusion) or for not more than 24 hours at 2°-8°C.
As the infusion solution is supersaturated, it may crystallise over time. In this case, the infusion solution must not be used and should be discarded.

6.5 Nature and Contents of Container

Cabazitaxel Juno Injection concentrate 60 mg/1.5 mL is supplied as a pack consisting of the following:

Concentrate.

Contains 60 mg cabazitaxel in 1.5 mL polysorbate 80.
Each vial contains 60 mg of cabazitaxel per 1.5 mL nominal volume. The actual fill volume is 1.83 mL (containing 73.2 mg cabazitaxel). This fill volume compensates for liquid loss during preparation of the premix. This overfill ensures that after dilution with the entire content of the accompanying diluent for Cabazitaxel Juno, there is a minimal extractable premix volume of 6 mL containing 10 mg/mL cabazitaxel which corresponds to the labeled amount of 60 mg per vial.

Diluent.

Contains 4.5 mL of 13% (w/w) ethanol in Water for Injection.
Each vial has a 4.5 mL nominal volume and an actual fill volume of 5.67 mL. The entire contents of the diluent vial need to be transferred into the Cabazitaxel Juno concentrate vial. This ensures that the premix solution will have a concentration of 10 mg/mL cabazitaxel.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Cabazitaxel is a white to off-white powder. It is lipophilic, practically insoluble in water and soluble in alcohol.
Cabazitaxel belongs to the taxanes class. It is prepared by semi synthesis with a precursor extracted from yew needles.
Chemical name of cabazitaxel is (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S)-3-[(tertbutoxycarbonyl) amino]-2-hydroxy-3-phenylpropanoyl} oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate, with a molecular formula of C45H57NO14 and a molecular weight of 835.93.

Chemical structure.

The chemical structure of cabazitaxel is:

CAS number.

183133-96-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes