Cabazitaxel

Registered South African indications:

• Hormone refractory metastatic prostate cancer

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other taxanes
• Hypersensitivity to polysorbate 80
• Pregnancy
• Severe hepatic impairment
• Neutrophil counts < 1500/mm³
• Concomitant vaccination with yellow fever vaccine

Cautions

• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Febrile neutropenia, or prolonged neutropenia
• Patients at risk of developing gastrointestinal complications
• Haemoglobin <10 g/dl 
• Alcoholism
• Epilepsy
• History of gastrointestinal haemorrhage
• Chronic nausea and vomiting
• Cardiac arrhythmias
• Interstital lung disease
• Peripheral neuropathy

Forms avail. in SA and covered in this monograph: inj

Used for the treatment of

Hormone refractory metastatic prostate cancer (additional agent required)
- In patients previously treated with a docetaxel containing regimen

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Consult specialist for dosages and regimens

Not established for use in children

Pregnancy 

• Contraindicated
• There is no data from the use of cabazitaxel in pregnant women
• Cabazitaxel is not recommended during pregnancy and in women of childbearing potential not using contraception
• Studies in animals have shown reproductive toxicity at meternotoxic doses that cabazitaxel crosses the placenta barrier. As with other cytotoxic medicinal products, cabazitaxel may cause foetal harm in exposed pregnant woment

Breastfeeding

• Caution; not recommended
• Cabazitaxel should not be used during breastfeeding
• Available pharmacokinetics data in animals have shown excretion of cabazitaxel and its metabolites in milk
• A risk to the suckling child cannot be excluded
• Cabazitaxel should not be used during breastfeeding

Fertility 

• 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 humans
• See more information related to Fertility under Additional Prescriber Points

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated

Elderly            

• Caution; no dose adjustment recommended

Central Nervous System Disorders

• Anxiety
• Confusional state
• Dysgeusia
• Neuropathy peripheral
• Peripheral sensory neuropathy
• Dizziness
• Headache
• Paraesthesia
• Lethargy
• Hypoaesthesia
• Sciatica
• Fatigue

Cardiovascular Disorders

• Atrial fibrillation
• Tachycardia
• Hypotension
• Deep vein thrombosis
• Hypertension
• Orthostatic hypotension
• Hot flush
• Flushing
• Chest pain

Respiratory Disorders

• Dyspnoea
• Cough
• Oropharyngeal pain
• Pneumonia
• Upper respiratory tract infection

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Constipation
• Dyspepsia
• Abdominal pain 
• Haemorrhoids
• Gastroesophageal reflux disease
• Rectal haemorrhage
• Dry mouth
• Abdominal distension

Hepatobiliary Disorders

• Increased aspartate aminotransferase 
• Increased transaminases 

Genitourinary Disorders

• Acute renal failure
• Renal failure
• Dysuria
• Renal colic
• Haematuria
• Pollakiuria
• Hydronephrosis
• Urinary retention
• Urinary incontinence
• Ureteric obstruction
• Pelvic pain
• Urinary tract infection
• Cystitis

Endocrine and Metabolic Disorders

• Anorexia
• Dehydration
• Hyperglycaemia
• Hypokalemia
• Decreased weight

Musculoskeletal Disorders

• Back pain
• Arthralgia
• Pain in extremity
• Muscle spasms
• Myalgia
• Musculoskeletal chest pain
• Flank pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Dry skin
• Cellulitis
• Erythema
• Peripheral oedema
• Mucosal inflammation

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Hypersensitivity
• Anaemia 
• Leukopenia
• Thrombocytopenia
• Febrile neutropenia
• Septic shock
• Sepsis
• Influenza
• Herpes zoster
• Candidiasis
• Pyrexia

Sensory Disorders

• Conjunctivitis
• Increased lacrimation
• Tinnitus
• Vertigo

• CYP3A inhibitors 
• CYP3A inducers
• Organic Anion Transport Polypeptides OATP1B1
• Live or live-attenuated vaccines

• Full blood count with differential
• Renal function
• Hepatic function

Fertility Information

• 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 teh ejaculate by another person throughout treatment
• Men being treated with cabazitaxel are advised to seek advice on conservation of sperm prior to treatment

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.

Injection (per 1.5ml) 60mg

• Cabazitaxel Adco (Adcock Ingram Critical Care)
• Jevtana (Sanofi Aventis) originator

Injection (per ml) 20mg

• Cabitas (Accord)