Jevtana

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 
 
 
 
 
 
  
 



 

2 

1. NAME OF THE MEDICINAL PRODUCT  
 
JEVTANA 60 mg concentrate and solvent for solution for infusion.  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One ml of concentrate contains 40 mg cabazitaxel. 
Each vial of 1.5 ml (nominal volume) of concentrate contains 60 mg cabazitaxel.  
After initial dilution with the entire solvent, each ml of solution contains 10 mg cabazitaxel. 
 
Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) 
and the solvent vial (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during 
preparation. This overfill ensures that after dilution with the ENTIRE contents of the accompanying 
solvent, there is solution containing 10 mg/ml cabazitaxel. 
 
Excipient with known effect 
Each vial of solvent contains 573.3 mg of ethanol 96%.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate and solvent for solution for infusion (sterile concentrate).  
The concentrate is a clear yellow to brownish-yellow oily solution. 
The solvent is a clear and colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
JEVTANA in combination with prednisone or prednisolone is indicated for the treatment of adult 
patients with metastatic castration resistant prostate cancer previously treated with a 
docetaxel-containing regimen (see section 5.1).  
 
4.2 Posology and method of administration 
 
The use of JEVTANA 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. Facilities and equipment for the treatment of serious hypersensitivity reactions like 
hypotension and bronchospasm must be available (see section 4.4). 
 
Premedication 
The recommended premedication regimen should be performed at least 30 minutes prior to each 
administration of JEVTANA with the following intravenous medicinal products to mitigate the risk 
and severity of hypersensitivity: 

• antihistamine (dexchlorpheniramine 5 mg or diphenhydramine 25 mg or equivalent), 
• corticosteroid (dexamethasone 8 mg or equivalent), and   
• H2 antagonist (ranitidine or equivalent) (see section 4.4). 
 

Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed. 
 
Throughout the treatment, adequate hydration of the patient needs to be ensured, in order to prevent 
complications like renal failure. 



 

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Posology 
The recommended dose of JEVTANA 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 treatment.  
 
Dose adjustments  
Dose modifications should be made if patients experience the following adverse reactions (Grades 
refer to Common Terminology Criteria for Adverse Events [CTCAE 4.0]): 
 

Table 1 - Recommended dose modifications for adverse reaction in patients treated with cabazitaxel 
 

Adverse reactions Dose modification 

Prolonged grade ≥3 neutropenia (longer than 
1 week) despite appropriate treatment including 
G-CSF 

Delay treatment until neutrophil count is 
>1,500 cells/mm3, then reduce cabazitaxel dose 
from 25 mg/m2 to 20 mg/m2.  

Febrile neutropenia or neutropenic infection Delay treatment until improvement or resolution, 
and until neutrophil count is >1,500 cells/mm3, 
then reduce cabazitaxel dose from 25 mg/m2 to 
20 mg/m2. 

Grade ≥3 diarrhoea or persisting diarrhoea 
despite appropriate treatment, including fluid and 
electrolytes replacement 

Delay treatment until improvement or resolution, 
then reduce cabazitaxel dose from 25 mg/m2 to 
20 mg/m2. 

Grade >2 peripheral neuropathy  Delay treatment until improvement, then reduce 
cabazitaxel dose from 25 mg/m2 to 20 mg/m2. 

 
If patients continue to experience any of these reactions at 20 mg/m2, further dose reduction to 15 
mg/m2 or discontinuation of JEVTANA may be considered. Data in patients below the 20 mg/m2 dose 
are limited. 
 
Special populations  
 
Patients with hepatic impairment 
Cabazitaxel is extensively metabolised by the liver. Patients with mild hepatic impairment (total 
bilirubin >1 to ≤1.5 x Upper Limit of Normal (ULN) or AST >1.5 x ULN), should have cabazitaxel 
dose reduced to 20 mg/m2. Administration of cabazitaxel to patients with mild hepatic impairment 
should be undertaken with caution and close monitoring of safety. 
In patients with moderate hepatic impairment (total bilirubin >1.5 to ≤ 3.0 x ULN), the maximum 
tolerated dose (MTD) was 15 mg/m2. If the treatment is envisaged in patients with moderate hepatic 
impairment the dose of cabazitaxel should not exceed 15 mg/m2. However, limited efficacy data are 
available at this dose. 
Cabazitaxel should not be given to patients with severe hepatic impairment (total bilirubin >3 x ULN) 
(see sections 4.3, 4.4 and 5.2). 
 
Patients with renal impairment  
Cabazitaxel is minimally excreted through the kidney. No dose adjustment is necessary in patients 
with renal impairment, not requiring hemodialysis. Patients presenting end stage renal disease 
(creatinine clearance (CLCR< 15 mL/min/1.73 m2), by their condition and the limited amount of data 
available should be treated with caution and monitored carefully during treatment (see sections 4.4 and 
5.2). 
 
Elderly 
No specific dose adjustment for the use of cabazitaxel in elderly patients is recommended (see also 
sections 4.4, 4.8 and 5.2). 
 



 

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Concomitant medicinal products use 
Concomitant medicinal products that are strong inducers or strong inhibitors of CYP3A should be 
avoided. However, if patients require co-administration of a strong CYP3A inhibitor, a 25% 
cabazitaxel dose reduction should be considered (see sections 4.4 and 4.5). 
 
Paediatric population 
There is no relevant use of JEVTANA in the paediatric population.  
The safety and the efficacy of JEVTANA in children and adolescents below 18 years of age have not 
been established (see section 5.1).  
 
Method of administration 
For instructions on preparation and administration of the product, see section 6.6. 
PVC infusion containers and polyurethane infusion sets should not be used. 
JEVTANA must not be mixed with any other medicinal products than those mentioned in section 6.6. 
 
4.3 Contraindications  
 

 Hypersensitivity to cabazitaxel, to other taxanes, or polysorbate 80 or  any excipients listed in 
section 6.1. 

 Neutrophil counts less than 1,500/mm3. 
 Severe hepatic impairment (total bilirubin >3 x ULN). 
 Concomitant vaccination with yellow fever vaccine (see section 4.5). 

 
4.4 Special warnings and precautions for use 
 
Hypersensitivity reactions  
All patients should be pre-medicated prior to the initiation of the infusion of cabazitaxel (see 
section 4.2).  
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 with a hypersensitivity reaction must 
stop treatment with JEVTANA (see section 4.3). 
 
Bone marrow suppression 
Bone marrow suppression manifested as neutropenia, anaemia, thrombocytopenia, or pancytopenia 
may occur (see “Risk of neutropenia” and “Anaemia” in section 4.4 below).  
 
Risk of neutropenia 
Patients treated with cabazitaxel may receive prophylactic G-CSF, as per American Society of Clinical 
Oncology (ASCO) guidelines and/or current institutional guidelines, to reduce the risk or manage 
neutropenia complications (febrile neutropenia, prolonged neutropenia or neutropenic infection). 
Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features (age 
>65 years, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation 
ports, poor nutritional status, or other serious comorbidities) that predispose them to increased 
complications from prolonged neutropenia. The use of G-CSF has been shown to limit the incidence 
and severity of neutropenia. 
Neutropenia is the most common adverse reaction of cabazitaxel (see section 4.8). Monitoring of 
complete blood counts is essential on a weekly basis during cycle 1 and before each treatment cycle 
thereafter so that the dose can be adjusted, if needed. 
The dose should be reduced in case of febrile neutropenia, or prolonged neutropenia despite 
appropriate treatment (see section 4.2). 
Patients should be re-treated only when neutrophils recover to a level ≥1,500/mm3 (see section 4.3). 
 



 

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Gastrointestinal disorders 
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. 
 
Risk of nausea, vomiting, diarrhoea and dehydration 
If patients experience diarrhoea following administration of cabazitaxel they may be treated with 
commonly used anti-diarrhoeal medicinal products. Appropriate measures should be taken to 
re-hydrate patients. Diarrhoea can occur more frequently in patients that have received prior 
abdomino-pelvic radiation. Dehydration is more common in patients aged 65 or older. Appropriate 
measures should be taken to rehydrate patients and to monitor and correct serum electrolyte levels, 
particularly potassium. Treatment delay or dose reduction may be necessary for grade ≥3 diarrhoea 
(see section 4.2). If patients experience nausea or vomiting, they may be treated with commonly used 
anti-emetics. 
 
Risk of serious gastrointestinal reactions 
Gastrointestinal (GI) hemorrhage and perforation, ileus, colitis, including fatal outcome, have been 
reported in patients treated with cabazitaxel (see section 4.8). Caution is advised with treatment of 
patients most at risk of developing gastrointestinal complications: those with neutropenia, the elderly, 
concomitant use of NSAIDs, anti-platelet therapy or anti-coagulants, and patients with a prior history 
of pelvic radiotherapy or gastrointestinal disease, such as ulceration and GI bleeding. 
 
 
Peripheral neuropathy 
Cases of peripheral neuropathy, peripheral sensory neuropathy (e.g., paraesthesias, dysaesthesias) and 
peripheral motor neuropathy have been observed in patients receiving cabazitaxel. Patients under 
treatment with cabazitaxel should be advised to inform their doctor prior to continuing treatment if 
symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop. Physicians 
should assess for the presence or worsening of neuropathy before each treatment. Treatment should be 
delayed until improvement of symptoms. The dose of cabazitaxel should be reduced from 25 mg/m2 to 
20 mg/m2 for persistent grade >2 peripheral neuropathy (see section 4.2). 
 
Anaemia 
Anaemia has been observed in patients receiving cabazitaxel (see section 4.8). Haemoglobin and 
haematocrit should be checked before treatment with cabazitaxel and if patients exhibit signs or 
symptoms of anaemia or blood loss. Caution is recommended in patients with haemoglobin <10 g/dl 
and appropriate measures should be taken as clinically indicated. 
 
Risk of renal failure  
Renal disorders, have been reported in association with sepsis, severe dehydration due to diarrhoea, 
vomiting and obstructive uropathy. Renal failure including cases with fatal outcome has been 
observed. Appropriate measures should be taken to identify the cause and intensively treat the patients 
if this occurs. 
Adequate hydration should be ensured throughout treatment with cabazitaxel. The patient should be 
advised to report any significant change in daily urinary volume immediately. Serum creatinine should 
be measured at baseline, with each blood count and whenever the patient reports a change in urinary 
output. Cabazitaxel treatment should be discontinued in case of any degradation of renal function to 
renal failure ≥CTCAE 4.0 Grade 3. 
 
Respiratory disorders 
Interstitial pneumonia/pneumonitis and interstitial lung disease have been reported and may be 
associated with fatal outcome (see section 4.8).  
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 
investigated, and appropriately treated. Interruption of cabazitaxel therapy is recommended until 



 

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diagnosis is available. Early use of supportive care measures may help improve the condition. The 
benefit of resuming cabazitaxel treatment must be carefully evaluated. 
 
Risk of cardiac arrhythmias 
Cardiac arrhythmias have been reported, most commonly tachycardia and atrial fibrillation (see 
section 4.8).  
 
Elderly 
Elderly people (≥65 years of age) may be more likely to experience certain adverse reactions including 
neutropenia and febrile neutropenia (see section 4.8). 
 
Patients with liver impairment  
Treatment with JEVTANA is contraindicated in patients with severe hepatic impairment (total 
bilirubin > 3 x ULN) (See sections 4.3 and 5.2). 
Dose should be reduced for patients with mild (total bilirubin >1 to ≤1.5 x ULN or AST >1.5 x ULN), 
hepatic impairment (see sections 4.2 and 5.2). 
 
Interactions  
Co-administration with strong CYP3A inhibitors should be avoided since they may increase the 
plasma concentrations of cabazitaxel (see sections 4.2 and 4.5). If co-administration with a strong 
CYP3A inhibitor cannot be avoided, close monitoring for toxicity and a cabazitaxel dose reduction 
should be considered (see sections 4.2 and 4.5).  
Co-administration with strong CYP3A inducers should be avoided since they may  decrease plasma 
concentrations of cabazitaxel (see sections 4.2 and 4.5).   
 
Excipients  
The solvent contains 573.3 mg ethanol 96% (15% v/v), equivalent to 14 ml of beer or 6 ml of wine. 
Harmful for those suffering from alcoholism. 
To be taken into account in high-risk groups such as patients with liver disease, or epilepsy. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro studies have shown that cabazitaxel is mainly metabolised through CYP3A (80% to 90%) (see 
section 5.2). 
  
CYP3A inhibitors 
Repeated administration of ketoconazole (400 mg once daily), a strong CYP3A inhibitor, resulted in a 
20% decrease in cabazitaxel clearance corresponding to a 25% increase in AUC. Therefore 
concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, 
clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) 
should be avoided as an increase of plasma concentrations of cabazitaxel may occur (see sections 4.2 
and 4.4).  
 
Concomitant administration of aprepitant, a moderate CYP3A inhibitor, had no effect on cabazitaxel 
clearance. 
 



 

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CYP3A inducers 
Repeated administration of rifampin (600 mg once daily), a strong CYP3A inducer, resulted in an 
increase in cabazitaxel clearance of 21% corresponding to a decrease in AUC of 17%.  
Therefore concomitant administration of strong CYP3A inducers (e.g., phenytoin, carbamazepine, 
rifampin, rifabutin, rifapentin, phenobarbital) should be avoided as a decrease of plasma 
concentrations of cabazitaxel may occur (see sections 4.2 and 4.4). In addition, patients should also 
refrain from taking St. John’s Wort. 
 
OATP1B1  
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. A time interval of 12 hours is recommended before the infusion and at 
least 3 hours after the end of infusion before administering the OATP1B1 substrates. 
 
Vaccinations 
Administration of live or live-attenuated vaccines in patients immunocompromised by 
chemotherapeutic agents may result in serious or fatal infections. Vaccination with a live attenuated 
vaccine should be avoided in patients receiving cabazitaxel. Killed or inactivated vaccines may be 
administered; however, the response to such vaccines may be diminished. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no data from the use of cabazitaxel in pregnant women. Studies in animals have shown 
reproductive toxicity at maternotoxic doses (see section 5.3) and that cabazitaxel crosses the placenta 
barrier (see section 5.3). As with other cytotoxic medicinal products, cabazitaxel may cause foetal 
harm in exposed pregnant women. 
Cabazitaxel is not recommended during pregnancy and in women of childbearing potential not using 
contraception. 
 
Breast-feeding 
Available pharmacokinetics data in animals have shown excretion of cabazitaxel and its metabolites in 
milk (see section 5.3). A risk to the suckling child cannot be excluded. 
Cabazitaxel should not be used during breast-feeding. 
 
Fertility 
Animal studies showed that cabazitaxel affected reproductive system in male rats and dogs without 
any functional effect on fertility (see section 5.3). 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. 
 
4.7 Effects on ability to drive and use machines 
 
Cabazitaxel may influence the ability to drive and use machines as it may cause fatigue and dizziness. 
Patients should be advised not to drive or use machines if they experience these adverse reactions 
during treatment. 
 
4.8 Undesirable effects 
 



 

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Summary of safety profile 
The safety of JEVTANA in combination with prednisone or prednisolone was evaluated in 
371 patients with metastatic castration resistant prostate cancer who were treated with 25 mg/m2 
cabazitaxel once every three weeks in a randomised open label, controlled phase III study. Patients 
received a median duration of 6 cycles of cabazitaxel.  
 
The most commonly (≥10%) occurring adverse reactions in all grades were anaemia (97.3%), 
leukopenia (95.7%), neutropenia (93.5%), thrombocytopenia (47.4%), and diarrhoea (46.6%). The 
most commonly (≥5%) occurring grade ≥3 adverse reactions in the cabazitaxel group were 
neutropenia (81.7%), leukopenia (68.2%), anaemia (10.5%), febrile neutropenia (7.5%), diarrhoea 
(6.2%).  
 
Discontinuation of treatment due to adverse reactions occurred in 68 patients (18.3%) receiving 
cabazitaxel. The most common adverse reactions leading to cabazitaxel discontinuation was 
neutropenia. 
 
Tabulated list of adverse reactions 
Adverse reactions are listed in table 2 according to MedDRA system organ class and frequency 
categories. Within each frequency grouping, adverse reactions are presented in order of decreasing 
seriousness. Intensity of the adverse reactions is graded according to CTCAE 4.0 (grade ≥3 = G≥3). 
Frequencies are based on all grades and defined as: very common (≥1/10), common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known 
(cannot be estimated from the available data). 
 
Table 2: Reported adverse reactions and haematological abnormalities with cabazitaxel in combination 

with prednisone or prednisolone in the TROPIC study (n=371) 
 
System Organ Class Adverse reaction 

 
All grades 

n (%) 
Grade>3 
n (%) 

  Very common Common  

Infections and 
infestations 

Septic shock  4 (1.1) 4 (1.1) 
Sepsis  4 (1.1) 4 (1.1) 
Cellulitis  6 (1.6) 2 (0.5) 
Urinary tract 
infection 

 27 (7.3) 4 (1.1) 

Influenza  11 (3) 0 
Cystitis  10 (2.7) 1 (0.3) 
Upper respiratory 
tract infection 

 10 (2.7) 0 

Herpes zoster  5 (1.3) 0 
Candidiasis  4 (1.1) 0 

Blood and lymphatic 
system disorders 

Neutropeniaa* 347 (93.5)  303 (81.7) 
Anaemia a 361 (97.3)  39 (10.5) 
Leukopeniaa 355 (95.7)  253 (68.2) 
Thrombocytopeniaa 176 (47.4)  15 (4) 
Febrile neutropenia  28 (7.5) 28 (7.5) 

Immune system 
disorders 

Hypersensitivity  5 (1.3) 0 

Metabolism and 
nutrition disorders 

Anorexia 59 (15.9)  3 (0.8) 
Dehydration  18 (4.9) 8 (2.2) 
Hyperglycaemia  4 (1.1) 3 (0.8) 
Hypokalemia  4 (1.1) 2 (0.5) 

Psychiatric disorders Anxiety  11 (3) 0 Confusional state  5 (1.3) 0 
Nervous system Dysgeusia 41 (11.1)  0 



 

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System Organ Class Adverse reaction 
 

All grades 
n (%) 

Grade>3 
n (%) 

  Very common Common  
disorders Neuropathy 

peripheral 
 30 (8.1) 2 (0.5) 

Peripheral sensory 
neuropathy 

 20 (5.4) 1 (0.3) 

Dizziness  30 (8.1) 0 
Headache  28 (7.5) 0 
Paraesthesia  17 (4.6) 0 
Lethargy  5 (1.3) 1 (0.3) 
Hypoaesthesia  5 (1.3) 0 
Sciatica 
 

 4 (1.1) 1 (0.3) 

Eye disorders 
Conjunctivitis  5 (1.3) 0 
Lacrimation 
increased 

 5 (1.3) 0 

Ear and labyrinth 
disorders 

Tinnitus  5 (1.3) 0 
Vertigo  5 (1.3) 0 

Cardiac disorders* Atrial fibrillation  4 (1.1) 2 (0.5) Tachycardia  6 (1.6) 0 

Vascular disorders 

Hypotension  20 (5.4) 2 (0.5) 
Deep vein 
thrombosis 

 8 (2.2) 7 (1.9) 

Hypertension  6 (1.6) 1 (0.3) 
Orthostatic 
hypotension 

 5 (1.3) 1 (0.3) 

Hot flush  5 (1.3) 0 
Flushing  4 (1.1) 0 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea 44 (11.9)  5 (1.3) 
Cough 40 (10.8)  0 
Oropharyngeal pain  13 (3.5) 0 
Pneumonia  9 (2.4) 6 (1.6) 

Gastrointestinal 
disorders 

Diarrhoea 173 (46.6)  23 (6.2) 
Nausea 127 (34.2)  7 (1.9) 
Vomiting 84 (22.6)  7 (1.9) 
Constipation 76 (20.5)  4 (1.1) 
Abdominal pain 43 (11.6)  7 (1.9) 
Dyspepsia  25 (6.7) 0 
Abdominal pain 
upper 

 20 (5.4) 0 

Haemorrhoids  14 (3.8) 0 
Gastroesophageal 
reflux disease 

 12 (3.2) 0 

Rectal haemorrhage  8 (2.2) 2 (0.5) 
Dry mouth  8 (2.2) 1 (0.3) 
Abdominal 
distension 

 5 (1.3) 1 (0.3) 

Skin and subcutaneous 
tissue disorders 

Alopecia 37 (10)  0 
Dry skin  9 (2.4) 0 
Erythema  5 (1.3) 0 

Musculoskeletal and 
connective tissue 
disorders 

Back pain 60 (16.2)  14 (3.8) 
Arthralgia 39 (10.5)  4 (1.1) 
Pain in extremity  30 (8.1) 6 (1.6) 



 

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System Organ Class Adverse reaction 
 

All grades 
n (%) 

Grade>3 
n (%) 

  Very common Common  
Muscle spasms  27 (7.3) 0 
Myalgia  14 (3.8) 1 (0.3) 
Musculoskeletal 
chest pain 

 11 (3) 1 (0.3) 

Flank pain  7 (1.9) 3 (0.8) 

Renal and urinary 
disorders  

Acute renal failure  8 (2.2) 6 (1.6) 
Renal failure  7 (1.9) 6 (1.6) 
Dysuria  25 (6.7) 0 
Renal colic   5 (1.3) 1 (0.3) 
Haematuria 62 (16.7)  7 (1.9) 
Pollakiuria  13 (3.5) 1 (0.3) 
Hydronephrosis  9 (2.4) 3 (0.8) 
Urinary retention  9 (2.4) 3 (0.8) 
Urinary 
incontinence 

 9 (2.4) 0 

Ureteric obstruction  7 (1.9) 5 (1.3) 
Reproductive system 
and breast disorders 

Pelvic pain  7 (1.9) 1 (0.3) 

General disorders and 
administration site 
conditions 

Fatigue 136 (36.7)  18 (4.9) 
Asthenia 76 (20.5)  17 (4.6) 
Pyrexia 45 (12.1)  4 (1.1) 
Peripheral oedema  34 (9.2) 2 (0.5) 
Mucosal 
inflammation 

 22 (5.9) 1 (0.3) 

Pain  20 (5.4) 4 (1.1) 
Chest pain  9 (2.4) 2 (0.5) 
Oedema  7 (1.9) 1 (0.3) 
Chills  6 (1.6) 0 
Malaise  5 (1.3) 0 

Investigations 

Weight decreased  32 (8.6) 0 
Aspartate 
aminotransferase 
increased 

 4 (1.1) 0 

Transaminases 
increased 

 4 (1.1) 0 

a based on laboratory values  
* see detailed section below 
 
Description of selected adverse reactions 
 
Neutropenia, and associated clinical events  
Incidence of grade ≥3 neutropenia based on laboratory data was 81.7%. The incidence of grade ≥3 
clinical neutropenia and febrile neutropenia adverse reactions were 21.3% and 7.5% respectively. 
Neutropenia was the most common adverse reaction leading to medicinal product 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 sections 4.2 
and 4.4). 
 
Cardiac disorders and arrhythmias 



 

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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.  
 
Haematuria 
Haematuria all grades frequency was 20.8% at 25 mg/m2 in EFC11785 study (see section 5.1). 
Confounding causes such as disease progression, instrumentation, infection or 
anticoagulation/NSAID/aspirin therapy were identified in nearly two thirds of the cases. 
 
Other laboratory abnormalities 
The incidence of grade ≥3 anaemia, increased AST, ALT, and bilirubin based on laboratory 
abnormalities were 10.5%, 0.7%, 0.9%, and 0.6%, respectively. 
 
Gastrointestinal disorders 
Colitis, enterocolitis, gastritis, neutropenic enterocolitis have been observed. Gastrointestinal 
hemorrhage and perforation, ileus and intestinal obstruction have also been reported (see section 4.4). 
 
Respiratory disorders 
Cases of interstitial pneumonia/pneumonitis and interstitial lung disease, sometimes fatal have been 
reported with an unknown frequency (cannot be estimated from the available data) (see section 4.4). 
 
Renal and urinary disorders  
Cystitis due to radiation recall phenomenon, including haemorrhagic cystitis, were reported 
uncommonly. 
 
Paediatric population 
See section 4.2 
 
Other special populations 
 
Elderly population  
Among 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 were fatigue (40.4% versus 29.8%), clinical neutropenia (24.2% versus 
17.6%), asthenia (23.8% versus 14.5%), pyrexia (14.6% versus 7.6%), dizziness (10.0% versus 4.6%), 
urinary tract infection (9.6% versus 3.1%) and dehydration (6.7% versus 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% versus 73.3%), 
clinical neutropenia (23.8% versus 16.8%) and febrile neutropenia (8.3% versus 6.1%) (see 
sections 4.2 and 4.4).  
 
Of the 595 patients treated with cabazitaxel 25 mg/m2 in the prostate cancer EFC 11785 study, 420 
patients were 65 years or over. The adverse reactions reported at rates of at least 5% higher in patients 
65 years of age or greater compared to younger patients were diarrhoea (42.9% vs. 32.6%), fatigue 
(30.2% vs. 19.4%), asthenia (22.4% vs. 13.1%), constipation (20.2% vs. 12.6%), clinical neutropenia 
(12.9% vs. 6.3%), febrile neutropenia (11.2% vs. 4.6%) and dyspnoea (9.5% vs. 3.4%). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



 

12 

professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known antidote to cabazitaxel. The anticipated complications of overdose would consist of 
exacerbation of adverse reactions as bone marrow suppression and gastrointestinal disorders. 
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.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, taxanes, 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. 
 
Pharmacodynamic effects 
Cabazitaxel demonstrated a broad spectrum of antitumour activity against advanced human tumours 
xenografted in mice. Cabazitaxel is active in docetaxel-sensitive tumours. In addition, cabazitaxel 
demonstrated activity in tumour models insensitive to chemotherapy including docetaxel. 
 
Clinical efficacy and safety 
The efficacy and safety of JEVTANA in combination with prednisone or prednisolone were evaluated 
in a randomised, open-label, international, multi-center, phase III study (EFC6193 study), in patients 
with metastatic castration resistant prostate cancer previsouly treated with a docetaxel containing 
regimen.  
 
Overall survival (OS) was the primary efficacy endpoint of the study.  
Secondary endpoints included Progression Free Survival [PFS (defined as time from randomization to 
tumour progression, Prostatic Specific Antigen (PSA) progression, pain progression, or death due to 
any cause, whichever occurred first], Tumour Response Rate based on Response Evaluation Criteria in 
Solid Tumours (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 randomised to receive either JEVTANA 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 of age with metastatic castration resistant 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 >1,500/mm3, platelets >100,000/mm3, haemoglobin >10 g/dl, creatinine 
<1.5 x ULN, total bilirubin <1 x ULN, AST and ALT <1.5 x ULN.  



 

13 

 
Patients with a history of congestive heart failure, or myocardial infarction within 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 JEVTANA group, the mean age was 68 years, range (46-92) and the racial 
distribution was 83.9% Caucasian, 6.9% Asian/Oriental, 5.3% Black and 4% Others. 
 
The median number of cycles was 6 in the JEVTANA group and 4 in the mitoxantrone group. The 
number of patients who completed the study treatment (10 cycles) was respectively 29.4% and 13.5% 
in the JEVTANA group and in the comparator group.  
 
Overall survival was significant longer with JEVTANA compared to mitoxantrone (15.1 months 
versus 12.7 respectively), with a 30% reduction in the risk of death compared to mitoxantrone (see 
table 3 and figure 1).  
 
A sub-group of 59 patients received prior cumulative dose of docetaxel <225 mg/m² (29 patients in 
JEVTANA arm, 30 patients in mitoxantrone arm). There was no significant difference in overall 
survival in this group of patients (HR (95%CI) 0.96 (0.49-1.86)). 
 

Table 3 - Efficacy of JEVTANA in EFC6193 study in the treatment of patients with metastatic 
castration resistant prostate cancer 

 
 JEVTANA + prednisone 

n=378 
mitoxantrone + prednisone 

n=377 
Overall survival   
Number of patients with deaths (%) 234 (61.9%) 279 (74%) 
Median survival (months) (95% CI) 15.1 (14.1-16.3) 12.7 (11.6-13.7) 
Hazard Ratio (HR)1 (95% CI) 0.70 (0.59-0.83) 
p-value <0.0001 
1HR estimated using Cox model; a hazard ratio of less than 1 favours JEVTANA 
 



 

14 

Figure 1: Kaplan Meier overall survival curves (EFC6193) 
 

 
 
There was an improvement in PFS in the JEVTANA arm compared to mitoxantrone arm, 
2.8 (2.4-3.0) months versus 1.4 (1.4-1.7) respectively, HR (95%CI) 0.74 (0.64-0.86), p<0.0001.  
 
There was a significant higher rate of tumour response of 14.4% (95%CI: 9.6-19.3) in patients in the 
JEVTANA arm compared to 4.4% (95%CI: 1.6-7.2) for patients in the mitoxantrone arm, p=0.0005. 
 
PSA secondary endpoints were positive in the JEVTANA arm. There was a median PSA progression 
of 6.4 months (95%CI: 5.1-7.3) for patients in JEVTANA arm, compared to 3.1 months 
(95%CI: 2.2-4.4) in the mitoxantrone arm, HR 0.75 months (95%CI: 0.63-0.90), p=0.0010. The PSA 
response was 39.2% in patients on JEVTANA arm (95%CI: 33.9-44.5) versus 17.8% of patients on 
mitoxantrone (95%CI: 13.7-22.0), p=0.0002.  
 
There was no statistical difference between both treatment arms in pain progression and pain response. 
 
In a non-inferiority, multicenter, multinational,  randomized, open label phase III study (EFC11785 
study), 1200 patients with metastatic castration resistant prostate cancer, previously treated with a 
docetaxel-containing regimen, were randomized to receive either cabazitaxel 25 mg/m2 (n=602) or 20 
mg/m2 (n=598) dose. Overall survival (OS) was the primary efficacy end-point. 
The study met its primary objective of demonstrating the non-inferiority of cabazitaxel 20 mg/m2 in 
comparison with 25 mg/m2 (see table 4). A statistically significantly higher percentage (p<0.001) of 
patients showed a PSA response in the 25 mg/m2 group (42.9%) compared to the 20 mg/m2 group 
(29.5%). A statistically significantly higher risk of PSA progression in patients with the 20 mg/m2 
dose with respect to the 25 mg/m2 dose was observed (HR 1.195 ; 95%CI: 1.025 to 1.393). There was 
no statistically difference with regards to the other secondary endpoints (PFS, tumour and pain 
response, tumour and pain progression, and four subcategories of FACT-P). 
 



 

15 

Table 4 - Overall survival in EFC11785 study in cabazitaxel 25 mg/m2 arm versus cabazitaxel 20 
mg/m2 arm (Intent-to–treat analysis) – Efficacy primary endpoint 

 
 CBZ20+PRED 

n=598 
CBZ25+PRED 

n=602 
Overall Survival   
Number of deaths, n (%) 497 (83.1 %) 501 (83.2%) 
Median survival (95% CI) (months)  13.4 (12.19 to 14.88) 14.5 (13.47 to 15.28) 
Hazard Ratioa    
 versus CBZ25+PRED 1.024 - 
 1-sided 98.89% UCI 1.184 - 
 1-sided 95% LCI 0.922 - 
CBZ20=Cabazitaxel 20 mg/m2, CBZ25=Cabazitaxel 25 mg/m2, PRED=Prednisone/Prednisolone  
CI=confidence interval, LCI=lower bound of the confidence interval, UCI=upper bound of the 
confidence interval  
a Hazard ratio is estimated using a Cox Proportional Hazards regression model. A hazard ratio < 1 

indicates a lower risk of cabazitaxel 20 mg/m2 with respect to 25 mg/m2.  

The safety profile of cabazitaxel 25 mg/m2 observed in study EFC11785 was qualitatively and 
quantitatively similar to that observed in the study EFC6193. Study EFC11785 demonstrated a better 
safety profile for the cabazitaxel 20 mg/m2 dose. 
 
Table 5 - Summary of safety data for cabazitaxel 25 mg/m2 arm versus cabazitaxel 20 mg/m2 

arm in EFC11785 study 
 

 CBZ20+PRED 
n=580 

CBZ25+PRED 
n=595 

Median number of cycles/ 
median duration of treatment 

6/ 18 weeks 

 

7/ 21 weeks 

Number of patients with 
dose reduction 
n (%) 

 

From 20 to 15 mg/m2: 58 (10.0%)
From 15 to 12 mg/m2: 9 (1.6%) 

From 25 to 20 mg/m2: 128 (21.5%)
From 20 to 15 mg/m2: 19 (3.2%) 
From 15 to 12 mg/m2: 1 (0.2%) 

All grade adverse reactionsa (%)  

Diarrhoea 30.7 39.8 

Nausea 24.5 32.1 

Fatigue 24.7 27.1 

Haematuria 14.1 20.8 

Asthenia 15.3 19.7 

Decreased appetite 13.1 18.5 

Vomiting 14.5 18.2 

Constipation 17.6 18.0 

Back pain 11.0 13.9 

Clinical neutropenia 3.1 10.9 

Urinary tract infection 6.9 10.8 

Peripheral sensory 
neuropathy 

6.6 10.6 

Dysgeusia 7.1 10.6 



 

16 

 

Grade ≥ 3 adverse reactionsb (%)  

Clinical neutropenia 2.4 9.6 

Febrile neutropenia 

 

2.1 9.2 

Haematological abnormalitiesc (%)  

Grade ≥ 3 neutropenia 41.8 73.3 

Grade ≥ 3 anaemia 9.9 13.7 

Grade ≥ 3 thrombocytopenia 2.6 4.2 
CBZ20=Cabazitaxel 20 mg/m2, CBZ25=Cabazitaxel 25 mg/m2, PRED=Prednisone/Prednisolone  
a  All grade adverse reactions with an incidence higher than 10%  
b Grade ≥ 3 adverse reactions with an incidence higher than 5%  
c Based on laboratory values 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
JEVTANA in all subsets of the paediatric population in the indication of prostate cancer (see 
section 4.2 for information on paediatric use). 
 
JEVTANA was evaluated in an open label, multi-center Phase 1/2 study conducted in a total of 39 
paediatric patients (aged between 4 to18 years for the phase 1 part of the study and between 3 to 16 
years for the phase 2 part of the study). The phase 2 part did not demonstrate efficacy of cabazitaxel as 
single agent in paediatric population with recurrent or refractory diffuse intrinsic pontine glioma 
(DIPG) and high grade glioma (HGG) treated at 30 mg/m². 
 
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 cabazitaxel at doses of 10 to 30 mg/m2 weekly or every 3 weeks. 
 
Absorption  
After 1-hour intravenous administration at 25 mg/m2 cabazitaxel in patients with metastatic prostate 
cancer (n=67), the Cmax was 226 ng/ml (Coefficient of Variation (CV): 107%) and was reached at the 
end of the 1-hour infusion (Tmax). The mean AUC was 991 ng.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 89-92% and was not saturable up to 
50,000 ng/ml, which covers the maximum concentration observed in clinical studies. Cabazitaxel is 
mainly bound to human serum albumin (82.0%) 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.  
 
Biotransformation 
Cabazitaxel is extensively metabolised in the liver (>95%), mainly by the CYP3A isoenzyme (80% to 
90%). Cabazitaxel is the main circulating compound in human plasma. Seven metabolites were 
detected in plasma (including 3 active metabolites issued form O-demethylations), with the main one 



 

17 

accounting for 5% of 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 medicinal products that are mainly substrate of CYP3A. 
However a clinical study has shown that cabazitaxel (25 mg/m2 administered as a single 1-hour 
infusion) did not modify the plasma levels of midazolam, a probe substrate of CYP3A. Therefore, at 
therapeutic doses, co-administration of CYP3A substrates with cabazitaxel to patients is not expected 
to have any clinical impact.  
There is no potential risk of inhibition of medicinal products 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 
medicinal products that are substrates of CYP1A, CYP2C9, and CYP3A. Cabazitaxel did not inhibit in 
vitro the major biotransformation pathway of warfarin into 7-hydroxywarfarin, which is mediated by 
CYP2C9. Therefore, no pharmacokinetic interaction of cabazitaxel on warfarin is expected in vivo.  
In vitro cabazitaxel did not inhibit Multidrug-Resistant Proteins (MRP): MRP1 and MRP2 or Organic 
Cation Transporter (OCT1). Cabazitaxel inhibited the transport of P-glycoprotein (PgP) (digoxin, 
vinblastin), Breast-Cancer-Resistant-Proteins (BCRP) (methotrexate) and Organic Anion Transporting 
Polypeptide OATP1B3 (CCK8) at concentrations at least 15 fold what is observed in clinical setting 
while it inhibited the transport of OATP1B1 (estradiol-17β-glucuronide) at concentrations only 5 fold 
what is observed in clinical setting. Therefore the risk of interaction with substrates of MRP, OCT1, 
PgP, BCRP and OATP1B3 is unlikely in vivo at the dose of 25 mg/m2. The risk of interaction with 
OATP1B1 transporter is possible, notably during the infusion duration (1 hour) and up to 20 minutes 
after the end of the infusion (see section 4.5).  
 
Elimination 
After a 1-hour intravenous 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 medicinal product in urine). 
 
Cabazitaxel had 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.  
 
Special populations 
Elderly patients 
In the population pharmacokinetic analysis in 70 patients of 65 years and older (57 from 65 to 75 and 
13 patients above 75), no age effect on the pharmacokinetics of cabazitaxel was observed. 
 
Paediatric patients 
Safety and effectiveness of JEVTANA have not been established in children and adolescents below 
18 years of age. 
 
Hepatic impairment  
Cabazitaxel is eliminated primarily via liver metabolism. 
A dedicated study in 43 cancer patients with hepatic impairment showed no influence of mild (total 
bilirubin >1 to ≤1.5 x ULN or AST >1.5 x ULN) or moderate (total bilirubin >1.5 to ≤3.0 x ULN) 
hepatic impairment on cabazitaxel pharmacokinetics. The maximum tolerated dose (MTD) of 
cabazitaxel was 20 and 15 mg/m2, respectively. 
In 3 patients with severe hepatic impairment (total bilirubin >3 ULN), a 39% decrease in clearance 
was observed when compared to patients with mild hepatic impairment, indicating some effect of 
severe hepatic impairment on cabazitaxel pharmacokinetics. The MTD of cabazitaxel in patients with 
severe hepatic impairment was not established. 
Based on safety and tolerability data, cabazitaxel dose should be reduced in patients with mild hepatic 
impairment (see sections 4.2, 4.4). JEVTANA is contraindicated in patients with severe hepatic 
impairment (see section 4.3). 
 
Renal impairment 



 

18 

Cabazitaxel is minimally excreted via the kidney (2.3% of the dose). A 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. This was confirmed by a 
dedicated comparative pharmacokinetic study in solid cancer patients with normal renal function 
(8 patients), moderate (8 patients) and severe (9 patients) renal impairment, who received several 
cycles of cabazitaxel in single IV infusion up to 25 mg/m2. 
 
5.3 Preclinical safety data  
 
Adverse reactions not observed in clinical studies, but seen in dogs after single dose, 5-day and weekly 
administation at exposure levels lower than clinical exposure levels and with possible relevance to 
clinical use were arteriolar/periarterolar necrosis in the liver, bile ductule hyperplasia and/or 
hepatocellular necrosis (see section 4.2). 
 
Adverse reactions not observed in clinical studies, but seen in rats during repeat-dose toxicity studies 
at exposure levels higher than clinical exposure levels and with possible relevance to clinical use were 
eye disorders characterized by subcapsular lens fiber swelling/degeneration. These effects were 
partially reversible after 8 weeks. 
 
Carcinogenicity studies have not been conducted with cabazitaxel. 
Cabazitaxel did not induce mutations in the bacterial reverse mutation (Ames) test. It was not 
clastogenic in an in vitro test in human lymphocytes (no induction of structural chromosomal 
aberration but it increased number of polyploid cells) and induced an increase of micronuclei in the in 
vivo test in rats. However these genotoxicity findings are inherent to the pharmacological activity of 
the compound (inhibition of tubulin depolymerization) and have been observed with medicinal 
products exhibiting the same pharmacological activity. 
 
Cabazitaxel did not affect mating performances or fertility of treated male rats. However, in 
repeated-dose toxicity studies, degeneration of seminal vesicle and seminiferous tubule atrophy in the 
testis were observed in rats, and testicular degeneration (minimal epithelial single cell necrosis in 
epididymis), was observed in dogs. Exposures in animals were similar or lower than those seen in 
humans receiving clinically relevant doses of cabazitaxel. 
 
Cabazitaxel induced embryofoetal toxicity in female rats treated intravenously once daily from 
gestational days 6 through 17 linked with maternal toxicity and consisted of foetal deaths and 
decreased mean foetal weight associated with delay in skeletal ossification. Exposures in animals were 
lower than those seen in humans receiving clinically relevant doses of cabazitaxel. Cabazitaxel crossed 
the placenta barrier in rats. 
 
In rats, cabazitaxel and its metabolites are excreted in maternal milk at a quantity up to 1.5% of 
administered dose over 24 hours.  
 
Environmental Risk Assessment (ERA) 
Results of environmental risk assessment studies indicated that use of JEVTANA will not cause 
significant risk to the aquatic environment (see section 6.6 for disposal of unused product). 
 
 
6. PHARMACEUTICAL PARTICULARS  
 
6.1 List of excipients 
 
Concentrate 
Polysorbate 80 
Citric acid 



 

19 

 
Solvent  
Ethanol 96%  
Water for injections  
 
6.2 Incompatibilities  
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
PVC infusion containers or polyurethane infusion sets should not be used for the preparation and 
administration of the infusion solution. 
 
6.3 Shelf life  
 
Unopened vials 
3 years. 
 
After opening  
The concentrate and solvent vials must be used immediately. If not used immediately, in-use storage 
times and conditions are the responsibility of the user.  
 
After initial dilution of the concentrate with the solvent 
Chemical and physical in-use stability has been demonstrated for 1 hour at ambient temperature 
(15°C-30°C). From a microbiological point of view, the concentrate-solvent mixture should be used 
immediately. If not used immediately, in-use storage times and conditions are the responsibility of the 
user and would normally not be longer than 24 hour at 2°C – 8°C, unless dilution has taken place in 
controlled and validated aseptic conditions. 
 
After final dilution in the infusion bag/bottle 
Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at ambient 
temperature (including the 1-hour infusion time) and for 48 hours at refrigerated conditions (including 
the 1-hour infusion time). 
From a microbiological point of view, the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user and would normally 
not be longer than 24 hour at 2°C – 8°C, unless dilution has taken place in controlled and validated 
aseptic conditions. 
 
6.4 Special precautions for storage  
 
Do not store above 30°C. 
Do not refrigerate. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 



 

20 

6.5 Nature and contents of container 
 
One pack contains one vial of concentrate and one vial of solvent: 
 
 Concentrate: 1.5 ml of concentrate in a 15 ml clear glass vial (type I) closed with a grey 

chlorobutyl rubber closure sealed by an aluminium cap covered with a light green plastic 
flip-off cap. Each vial contains 60 mg cabazitaxel per 1.5 ml nominal volume (fill volume: 
73.2 mg of cabazitaxel/1.83 ml).  This fill volume has been established during the development 
of JEVTANA to compensate for liquid loss during preparation of the premix.  This overfill 
ensures that after dilution with the entire content of the accompanying solvent for JEVTANA, 
there is a minimal extractable premix volume of 6 ml containing 10 mg/ml JEVTANA which 
corresponds to the labelled amount of 60 mg per vial. 

 Solvent: 4.5 ml of solvent in a 15 ml clear glass vial (type I) closed with a grey chlorobutyl 
rubber closure sealed by a gold colour aluminium cap covered with a colourless plastic flip-off 
cap. Each vial contains 4.5 ml nominal volume (fill volume: 5.67 ml).  This fill volume has been 
established during the development and the overfill ensures, after the addition of the entire 
content of the solvent vial to the content of JEVTANA 60 mg concentrate vial, a concentration 
of the premix solution of 10 mg/ml JEVTANA. 

 
6.6 Special precautions for disposal and other handling 
 
JEVTANA should only be prepared and administered by personnel trained in handling cytotoxic 
agents. Pregnant staff should not handle the product. As for any other antineoplastic agent, caution 
should be exercised when handling and preparing JEVTANA solutions, taking into account the use of 
containment devices, personal protective equipment (e.g. gloves), and preparation procedures. If 
JEVTANA, 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. 
 
Always dilute the concentrate for solution for infusion with the entire supplied solvent before adding 
to infusion solution. 
 
Read this ENTIRE section carefully before mixing and diluting. JEVTANA requires TWO dilutions 
prior to administration. Follow the preparation instructions provided below.  
 
Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) 
and the solvent vial (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during 
preparation. This overfill ensures that after dilution with the ENTIRE contents of the accompanying 
solvent, there is solution containing 10 mg/ml cabazitaxel. 
 
The following two-step dilution process must be carried out in an aseptic manner for preparing the 
solution for infusion. 
 
Step 1: Initial dilution of the concentrate for solution for infusion with the supplied solvent. 
 

Step 1.1 

Inspect the concentrate vial and the supplied 
solvent. The concentrate solution and the 
solvent should be clear.  

 

 

 

 

 

 

 
Solvent vial 

Concentrate vial 
(60 mg - 1.5 ml) 



 

21 

Step 1.2  

Using a syringe fitted with a needle, 
aseptically withdraw the entire contents of 
the supplied solvent by partially inverting the 
vial. 

 

 

 

Step 1.3  

Inject the entire contents into the corresponding 
concentrate vial. 

To limit foaming as much as possible when 
injecting the solvent, direct the needle onto the 
inside wall of the vial of concentrate solution 
and inject slowly. 

Once reconstituted, the resultant solution 
contains 10 mg/ml of cabazitaxel. 

 

 

Step 1.4  

Remove the syringe and needle and mix 
manually and gently by repeated inversions 
until obtaining a clear and homogeneous 
solution. It could take approximately 
45 seconds. 

  

Step 1.5  

Let this 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 concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (at least 6 ml deliverable 
volume). The second dilution should be done immediately (within 1 hour) as detailed in Step 2. 

More than one vial of the concentrate-solvent mixture may be necessary to administer the prescribed 
dose. 

Solvent vial 

Solvent vial Concentrate-
solvent mixture 
10 mg/ml 

Concentrate-solvent 
mixture 10 mg/ml  

Concentrate-solvent 
mixture 10 mg/ml 



 

22 

Step 2: Second (final) dilution for infusion 

Step 2.1 

Aseptically withdraw the required amount of 
concentrate-solvent mixture (10 mg/ml of 
cabazitaxel), with a graduated syringe fitted 
with a needle. As an example, a dose of 45 mg 
JEVTANA would require 4.5 ml of the 
concentrate-solvent mixture prepared following 
Step 1. 

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. 

 

Step 2.2 

Inject in a sterile PVC-free container of either 
5% glucose solution or sodium chloride 
9 mg/ml (0.9%) solution for infusion. The 
concentration of the infusion solution should be 
between 0.10 mg/ml and 0.26 mg/ml.   

 

Step 2.3 

Remove the syringe and mix the content of the 
infusion bag or bottle manually using a rocking 
motion. 

 

 

 

 

Step 2.4 

As with all parenteral products, the resulting 
infusion solution should be visually inspected 
prior to use.  As the infusion solution is 
supersaturated, it may crystallize over time. In 
this case, the solution must not be used and 
should be discarded.  

 

 

 

 
The infusion solution should be used immediately. However, in-use storage time can be longer under 
specific conditions mentioned in section 6.3.  

Required amount of 
concentrate-solvent 
mixture

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

Concentrate-solvent 
mixture 10 mg/ml 



 

23 

An in-line filter of 0.22 micrometer nominal pore size (also referred to as 0.2 micrometer) is 
recommended during administration. 
 
Do not use PVC infusion containers or polyurethane infusion sets for the preparation and 
administration of JEVTANA. 
 
JEVTANA must not be mixed with any other medicinal products than those mentioned. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54, rue La Boétie 
F - 75008 Paris 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/676/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 March 2011 
Date of latest renewal: 19 November 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 



 

24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS RESPONSIBLE FOR BATCH 

RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

  
 



 

25 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 
65926 Frankfurt am Main 
Germany 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.      OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic Safety Update Reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83 EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
 At the request of the European Medicines Agency;  
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 



 

26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



 

27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
JEVTANA 60 mg concentrate and solvent for solution for infusion  
cabazitaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml concentrate contains 40 mg cabazitaxel. 
Each 1.5 ml vial of concentrate contains 60 mg cabazitaxel. 
The concentrate vial (fill: 73.2 mg of cabazitaxel/1.83 ml) and the solvent vial (5.67 ml) contain an 
overfill to compensate for liquid loss during preparation. This overfill ensures that after initial 
dilution with the ENTIRE content of the solvent vial, the concentration of cabazitaxel is 10 mg/ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients 
Concentrate vial: polysorbate 80 and citric acid; 
Solvent vial: ethanol 96% and water for injections.  
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate and solvent for solution for infusion. 
1 vial of 1.5 ml concentrate and 1 vial of 4.5 ml solvent. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Single-use vials. 
 
CAUTION: Two-step dilution required. Read the package leaflet before use.  
 
 
For intravenous use (infusion) AFTER final dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children.  
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
CYTOTOXIC  
 



 

29 

 
8. EXPIRY DATE 
 
EXP 
Read the leaflet for the shelf life of the diluted solution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C.  
Do not refrigerate. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54, rue La Boétie 
F - 75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/676/001  
 
 
13. BATCH NUMBER 
 
Batch: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 

30 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



 

31 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL for CONCENTRATE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
JEVTANA 60 mg sterile concentrate 
cabazitaxel 
 
 
2. METHOD OF ADMINISTRATION 
 
Dilute with the ENTIRE supplied solvent. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.5 ml  
10 mg/ml after first dilution. 
 
 
6. OTHER 
 
Solution for IV infusion after final dilution (see package leaflet). 
Contains an overfill.



 

32 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL for SOLVENT 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SOLVENT for JEVTANA  
 
 
2. METHOD OF ADMINISTRATION 
 
Use the ENTIRE content for dilution (see package leaflet). 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4.5 ml (ethanol 96% and water for injections). 
 
 
6. OTHER 
 
This vial contains an overfill. 



 

33 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



 

34 

Package leaflet: Information for the patient 
 

JEVTANA 60 mg concentrate and solvent for solution for infusion  
cabazitaxel 

 
 

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.  
 Keep this leaflet. You may need to read it again. 
 If you have any further 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. 
 
What is in this leaflet  
 
1. What JEVTANA is and what it is used for 
2. What you need to know before you are given JEVTANA 
3. How to use JEVTANA 
4. Possible side effects 
5. How to store JEVTANA 
6. Contents of the pack and other information 
 
 
1. What JEVTANA is and what it is used for  
 
The name of your medicine is JEVTANA. Its common name is cabazitaxel. It belongs to a group of 
medicines called “taxanes” used to treat cancers.  
 
JEVTANA is used to treat prostate cancer that has progressed after having had other chemotherapy. It 
works by stopping cells from growing and multiplying. 
 
As part of your treatment, you will also take a corticosteroid medicine (prednisone or prednisolone) by 
mouth every day. Ask your doctor to give you information about this other medicine. 
 
 
2. What you need to know before you are given JEVTANA 
 
Do not use JEVTANA if: 
 
 you are allergic (hypersensitive) to cabazitaxel, to other taxanes, or polysorbate 80 or any of the 

other excipients of this medicine (listed in section 6),  
 the number of your white blood cells is too low (neutrophil counts less than or equal to 

1,500 /mm3), 
 you have severe abnormal liver function, 
 you have recently received or are about to receive a vaccine against yellow fever.  
 
You should not be given JEVTANA if any of the above apply to you. If you are not sure, talk to your 
doctor before having JEVTANA. 
 
Warnings and precautions 
 
Before each treatment with JEVTANA, you will have blood tests to check that you have enough blood 
cells and sufficient liver and kidney functions to receive JEVTANA. 
 
Tell your doctor immediately if:  
 you have fever. During treatment with JEVTANA, 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 



 

35 

infections. He/she may give you other medicines to maintain the number of your blood cells. 
People with low blood counts can develop life-threatening infections. The earliest sign of 
infection may be fever, so if you experience fever, tell your doctor right away. 

 
 you have ever had any allergies. Serious allergic reactions can occur during treatment with 

JEVTANA.  
 
 you have severe or long-lasting diarrhoea, you feel sick (nausea) or you are being sick 

(vomiting). Any of these events could cause severe dehydration. Your doctor may need to treat 
you. 

 
 you have feeling of numbness, tingling, burning or decreased sensation in your hands or feet. 
 
 you have any bleeding problems from the gut or have changes in the colour of your stool or 

stomach pain. If the bleeding or pain is severe, your doctor will stop your treatment with 
JEVTANA. This is because JEVTANA may increase the risk of bleeding or developing holes in 
the gut wall.  

 
 you have kidney problems. 
 
 liver problems occur during the treatment. 
 
 you experience any significant increase or decrease in daily urinary volume.  
 
 you have blood in your urine. 

 
If any of the above applies to you, tell your doctor immediately. Your doctor may reduce the dose of 
JEVTANA or stop the treatment. 
 
Other medicines and JEVTANA  
 
Please tell your doctor, pharmacist or nurse if you are taking or have recently taken any other 
medicines. This includes medicines obtained without a prescription. This is because some medicines 
can affect the way JEVTANA works or JEVTANA can affect how other medicines work. These 
medicines include the following: 
- ketoconazole, rifampicin (for infections); 
- carbamazepine, phenobarbital or phenytoin (for seizures); 
- St John’s Wort (Hypericum perforatum) (herbal remedy for depression and other conditions); 
-  statins (such  as simvastatin, lovastatin, atorvastatin, rosuvastatin, or pravastatin) (for reducing the 
cholesterol in your blood); 
-  valsartan (for hypertension); 
-  repaglinide (for diabetes). 
 
Talk to your doctor before getting vaccinations while you are receiving JEVTANA.  
 
Pregnancy, breast-feeding and fertility 
 
JEVTANA should not be used in pregnant women or women of childbearing age not using 
contraception.  
 
JEVTANA should not be used during breast-feeding. 
 
Use a condom during sex if your partner is or could become pregnant. JEVTANA 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 JEVTANA may 
alter male fertility.  
 



 

36 

 
 
Driving and using machines 
 
You may feel tired or dizzy when having this medicine. If this happens, do not drive or use any tools 
or machines until you feel better. 
 
JEVTANA contains ethanol (alcohol) 
 
This medicine contains 15% v/v ethanol (alcohol), equivalent to 14 ml of beer or 6 ml of wine. This 
medicine may be harmful for those suffering from alcoholism.  
 
To be taken into account if you are in a high-risk group such as patients with liver disease, or epilepsy. 
 
 
3. How to use JEVTANA 
 
Instructions for use 
 
Anti-allergic medicines will be given to you before you have JEVTANA to reduce the risk of allergic 
reactions. 
 
 JEVTANA will be given to you by a doctor or a nurse. 
 
 JEVTANA must be prepared (diluted) before it is given. Practical information for handling and 

administration of JEVTANA for doctors, nurses and pharmacists is provided with this leaflet. 
 
 JEVTANA will be given by a drip (infusion) into one of your veins (intravenous use) in hospital 

for about an hour. 
 
 As part of your treatment, you will also take a corticosteroid medicine (prednisone or 

prednisolone) by mouth every day. 
 
How much and how often to have 
 
 The usual dose depends on your body surface area. Your doctor will calculate your body surface 

area in square meters (m²) and will decide the dose you should have. 
 
 You will usually have an infusion once every 3 weeks. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.Your 
doctor will discuss these with you and will explain the potential risks and benefits of your treatment. 
 
See a doctor immediately if you notice any of the following side effects: 
 
 fever (high temperature). This is very common (may affect more than 1 in 10 people). 
 
 severe loss of body fluids (dehydration). This is common (may affect up to 1 in 10 people). 

This can occur if you have severe or long-lasting diarrhoea, or fever, or if you are being sick 
(vomiting). 

 



 

37 

 severe stomach pain or stomach pain that doesn't go away. This can occur if you have a hole in 
the stomach, food pipe, gut or bowel (gastrointestinal perforation). This can lead to death. 

 
If any of the above applies to you, tell your doctor immediately. 
 
Other side effects include: 
 
Very common (may affect more than 1 in 10 people): 
 decrease in the number of red (anaemia), or white blood cells (which are important in fighting 

infection) 
 decrease in the number of platelets (which results in increased risk of bleeding) 
 loss of appetite (anorexia) 
 alteration in sense of taste 
 shortness of breath 
 cough 
 stomach upsets including feeling sick (nausea), being sick (vomiting), diarrhoea or constipation 
 abdominal pain 
 short term hair loss (in most cases normal hair growth should return) 
 back pain 
 joint pain 
 blood in the urine 
 feeling tired, weak or lack of energy. 
 
Common (may affect up to 1 in 10 people): 
 urinary tract infection 
 lack of white blood cells associated with fever and infection 
 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, heart burn or belching  
 stomach pain  
 haemorrhoids 
 muscle spasm 
 painful or frequent urination 
 urinary incontinence 
 kidney disease or problems 
 sore in the mouth or on lips 
 infections or risk of infections  
 high blood sugar 
 low blood potassium  
 mental confusion 
 feeling anxious 
 abnormal feeling or loss of sensation or pain in hands and feet 
 ringing in the ear 
 trouble with balance 
 rapid or irregular heartbeat 
 blood clot in the leg 
 skin feeling hot or flushed  
 pain in mouth or throat 
 rectal bleeding 
 redness of the skin 
 muscle discomfort, aches or  pain 
 swelling of the feet or legs 



 

38 

 chills. 
 
Uncommon (may affect up to 1 in 100 people):  
 inflammation of the bladder, which can occur when your bladder has been previously exposed 

to radiation therapy (cystitis due to radiation recall phenomenon). 
 

Frequency not known (cannot be estimated from the available data): 
 interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store JEVTANA 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 
the vials after EXP. The expiry date refers to the last day of that month. 
 
Do not store above 30°C. Do not refrigerate. 
 
Information about storage and the time to use JEVTANA, once it has been diluted and is ready to use, 
are described in the section “PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE 
PROFESSIONALS ON PREPARATION, ADMINISTRATION AND HANDLING OF JEVTANA“. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What JEVTANA contains 
The active substance is cabazitaxel. One ml of concentrate contains 40 mg cabazitaxel. Each vial of 
concentrate contains 60 mg cabazitaxel.  
The other ingredients are polysorbate 80 and citric acid in the concentrate, and ethanol 96% and water 
for injections in the solvent (see section 2 “JEVTANA contains alcohol”). 
Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) 
and the solvent vial (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during 
preparation. This overfill ensures that after dilution with the ENTIRE contents of the accompanying 
solvent, there is solution containing 10 mg/ml cabazitaxel. 
 
What JEVTANA looks like and contents of the pack 
JEVTANA is a concentrate and solvent for solution for infusion (sterile concentrate). 
The concentrate is a clear yellow to brownish-yellow oily solution. 
The solvent is a clear and colourless solution. 
 
One pack of JEVTANA contains: 

 One  single useclear glass vial, closed with a grey chlorobutyl rubber closure sealed by an 
aluminium cap with a light green plastic flip-off cover, containing 1.5 ml (nominal volume) 
concentrate.  



 

39 

 One single use clear glass vial, closed with a grey chlorobutyl rubber closure sealed by a gold 
colour aluminium cap with a colourless plastic flip-off cover, containing  4.5 ml (nominal 
volume) solvent. 

 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54, rue La Boétie 
F - 75008 Paris 
France 
 
Manufacturer 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 
65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA»  
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
 SANOFI-AVENTIS Zrt.,  
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.p.A 
Tel: +39 02 39394275 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 



 

40 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd.  T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: +39.800.536389  
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 

 
This leaflet was last revised in MMM/YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 



 

41 

The following information is intended for healthcare professionals only. 
 
PRACTICAL INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS 
ON PREPARATION, ADMINISTRATION AND HANDLING OF JEVTANA 60 mg 
CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION 
 
This information supplements sections 3 and 5 for the user. 
It is important that you read the entire content of this procedure prior to the preparation of the infusion 
solution. 
 
Incompatibilities 
 
This medicine must not be mixed with other medicines except those used for the dilutions. 
 
Shelf life and special precautions for storage 
 
For the pack of JEVTANA 60 mg concentrate and solvent  
Do not store above 30°C. 
Do not refrigerate. 
 
After opening 
The concentrate and solvent vials must be used immediately. If not used immediately, in-use storage 
times and conditions are the responsibility of the user. From a microbiological point of view, the 
two-step dilution process must take place in controlled and aseptic conditions (see below “Preparation 
and administration precautions”). 
 
After initial dilution of JEVTANA 60 mg concentrate with the entire contents of the solvent vial  
chemical and physical in-use stability has been demonstrated for 1 hour at ambient temperature. 

After final dilution in the infusion bag/bottle 
Chemical and physical stability of the infusion solution has been demonstrated for 8 hours at ambient 
temperature (15°C - 30°C) including the 1-hour infusion time and for 48 hours at refrigerated 
conditions including the 1-hour infusion time. 
 
From a microbiological point of view, the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user and would normally 
not be longer than 24 hour at 2°C – 8°C, unless dilution has taken place in controlled and validated 
aseptic conditons.  
 
Preparation and administration precautions  
 
As for any other antineoplastic agent, caution should be exercised when handling and preparing 
JEVTANA solutions, taking into account the use of containment devices, personal protective 
equipment (e.g. gloves), and preparation procedures. 
If JEVTANA, 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. 
 
JEVTANA should only be prepared and administered by personnel trained in handling cytotoxic 
agents. Pregnant staff should not handle it. 
 
Always dilute the concentrate for solution for infusion with the entire supplied solvent before adding 
to infusion solutions. 
 
Preparation steps 
 
Read this ENTIRE section carefully before mixing and diluting. JEVTANA requires TWO dilutions 
prior to administration. Follow the preparation instructions provided below.  



 

42 

 
Note: Both the JEVTANA 60 mg/1.5 ml concentrate vial (fill volume: 73.2 mg of cabazitaxel/1.83 ml) 
and the solvent vial (fill volume: 5.67 ml) contain an overfill to compensate for liquid loss during 
preparation. This overfill ensures that after dilution with the ENTIRE contents of the accompanying 
solvent, there is solution containing 10 mg/ml cabazitaxel. 
 
The following two-step dilution process must be carried out in an aseptic manner for preparing the 
solution for infusion. 
 
Step 1: Initial dilution of the concentrate for solution for infusion with the supplied solvent. 
 

Step 1.1 

Inspect the concentrate vial and the supplied 
solvent. The concentrate solution and the 
solvent should be clear.  

 

 

 

 

 

 

 

Step 1.2  

Using a syringe fitted with a needle, 
aseptically withdraw the entire contents of 
the supplied solvent by partially inverting the 
vial. 

 

 

 

Step 1.3  

Inject the entire contents into the corresponding 
concentrate vial. 

To limit foaming as much as possible when 
injecting the solvent, direct the needle onto the 
inside wall of the vial of concentrate solution 
and inject slowly. 

Once reconstituted, the resultant solution 
contains 10 mg/ml of cabazitaxel. 

 

 

Solvent vial Concentrate vial 
(60 mg - 1.5 ml) 

Solvent vial 

Solvent vial Concentrate-
solvent mixture 
10 mg/ml 



 

43 

Step 1.4  

Remove the syringe and needle and mix 
manually and gently by repeated inversions 
until obtaining a clear and homogeneous 
solution. It could take approximately 
45 seconds. 

 

Step 1.5  

Let this 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 concentrate-solvent mixture contains 10 mg/ml of cabazitaxel (at least 6 ml deliverable 
volume). The second dilution should be done immediately (within 1 hour) as detailed in Step 2. 

More than one vial of the concentrate-solvent mixture may be necessary to administer the prescribed 
dose. 

Step 2: Second (final) dilution for infusion 

Step 2.1 

Aseptically withdraw the required amount of 
concentrate-solvent mixture (10 mg/ml of 
cabazitaxel), with a graduated syringe fitted 
with a needle. As an example, a dose of 45 mg 
JEVTANA would require 4.5 ml of the 
concentrate solvent mixture prepared following 
Step 1. 

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. 

 

Concentrate-solvent 
mixture 10 mg/ml 

Concentrate-solvent 
mixture 10 mg/ml 

Concentrate‐solvent 
mixture 10 mg/ml 



 

44 

Step 2.2 

Inject in a sterile PVC-free container of either 
5% glucose solution or sodium chloride 
9 mg/ml (0.9%) solution for infusion. The 
concentration of the infusion solution should be 
between 0.10 mg/ml and 0.26 mg/ml.   

 

Step 2.3 

Remove the syringe and mix the content of the 
infusion bag or bottle manually using a rocking 
motion. 

 

 

Step 2.4 

As with all parenteral products, the resulting 
infusion solution should be visually inspected 
prior to use. As the infusion solution is 
supersaturated, it may crystallize over time. In 
this case, the solution must not be used and 
should be discarded. 

 

 
 
 
The infusion solution should be used immediately. However, in-use storage time can be longer under 
specific conditions mentioned in section Shelf life and special precautions for storage above. 
 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Method of administration 
 
JEVTANA is administered as a 1 hour infusion. 
An in-line filter of 0.22 micrometer nominal pore size (also referred to as 0.2 micrometer) is 
recommended during administration. 
PVC infusion containers or polyurethane infusion sets should not be used for the preparation and 
administration of the infusion solution. 

Required amount of 
concentrate-solvent 
mixture

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