Cabazitaxel Injection Taj Pharma-SMPC

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The solvent is a clear and colourless

Cabazitaxel Injection 60mg/ solution.
1.5ml Taj Pharma
4. CLINICAL PARTICULARS
1. NAME OF THE MEDICINAL
PRODUCT 4.1 Therapeutic indications
CABAZITAXEL in combination with
CABAZITAXEL 60 mg concentrate and prednisone or prednisolone is indicated for
solvent for solution for infusion, Taj Pharma the treatment of adult patients with
metastatic castration resistant prostate
2. QUALITATIVE AND cancer previously treated with a docetaxel-
QUANTITATIVE COMPOSITION containing regimen (see section 5.1).
One ml of concentrate contains 40 mg 4.2 Posology and method of
cabazitaxel. administration
Each vial of 1.5 ml (nominal volume) of The use of CABAZITAXEL should be
concentrate contains 60 mg cabazitaxel. confined to units specialised in the
administration of cytotoxics and it should
After initial dilution with the entire solvent, only be administered under the supervision
each ml of solution contains 10 mg of a physician experienced in the use of
cabazitaxel. anticancer chemotherapy. Facilities and
Note: Both the CABAZITAXEL 60 mg/1.5 equipment for the treatment of serious
ml concentrate vial (fill volume: 73.2 mg of hypersensitivity reactions like hypotension
cabazitaxel/1.83 ml) and the solvent vial (fill and bronchospasm must be available (see
volume: 5.67 ml) contain an overfill to section 4.4).
compensate for liquid loss during Premedication
preparation. This overfill ensures that after
dilution with the ENTIRE contents of the The recommended premedication regimen
accompanying solvent, there is solution should be performed at least 30 minutes
containing 10 mg/ml cabazitaxel. prior to each administration of
CABAZITAXEL with the following
Excipient with known effect intravenous medicinal products to mitigate
Each vial of solvent contains 573.3 mg of the risk and severity of hypersensitivity:
ethanol 96%. • antihistamine (dexchlorpheniramine 5 mg
For the full list of excipients, see section 6.1. or diphenhydramine 25 mg or equivalent),
• corticosteroid (dexamethasone 8 mg or
3. PHARMACEUTICAL FORM
equivalent), and
Concentrate and solvent for solution for
• H2 antagonist (ranitidine or equivalent)
infusion (sterile concentrate).
(see section 4.4).
The concentrate is a clear yellow to
Antiemetic prophylaxis is recommended and
brownish-yellow oily solution.
can be given orally or intravenously as
needed.
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Throughout the treatment, adequate despite appropriate resolution, then

hydration of the patient needs to be ensured, treatment, including reduce cabazitaxel
in order to prevent complications like renal fluid and electrolytes dose from 25
failure. replacement mg/m2 to 20 mg/m2.
Posology Grade >2 peripheral Delay treatment until
neuropathy improvement, then
The recommended dose of CABAZITAXEL reduce cabazitaxel
is 25 mg/m2 administered as a 1 hour dose from 25
intravenous infusion every 3 weeks in mg/m2 to 20 mg/m2.
combination with oral prednisone or
If patients continue to experience any of
prednisolone 10 mg administered daily
these reactions at 20 mg/m2, further dose
throughout treatment.
reduction to 15 mg/m2 or discontinuation of
Dose adjustments CABAZITAXEL may be considered. Data
in patients below the 20 mg/m2 dose are
Dose modifications should be made if limited.
patients experience the following adverse
reactions (Grades refer to Common Special populations
Terminology Criteria for Adverse Events
Patients with hepatic impairment
[CTCAE 4.0]):
Cabazitaxel is extensively metabolised by
Table 1 - Recommended dose modifications
the liver. Patients with mild hepatic
for adverse reaction in patients treated with
impairment (total bilirubin >1 to ≤1.5 x
cabazitaxel
Upper Limit of Normal (ULN) or AST >1.5
Adverse reactions Dose modification x ULN), should have cabazitaxel dose
reduced to 20 mg/m2. Administration of
Prolonged grade ≥3 Delay treatment until cabazitaxel to patients with mild hepatic
neutropenia (longer neutrophil count is impairment should be undertaken with
than 1 week) despite >1,500 cells/mm3, caution and close monitoring of safety.
appropriate treatment then reduce
including G-CSF cabazitaxel dose from In patients with moderate hepatic
25 mg/m2 to 20 impairment (total bilirubin >1.5 to ≤ 3.0 x
mg/m2. ULN), the maximum tolerated dose (MTD)
Febrile neutropenia Delay treatment until was 15 mg/m2. If the treatment is envisaged
or neutropenic improvement or in patients with moderate hepatic
infection resolution, and until impairment the dose of cabazitaxel should
neutrophil count is not exceed 15 mg/m2. However, limited
>1,500 cells/mm3, efficacy data are available at this dose.
then reduce Cabazitaxel should not be given to patients
cabazitaxel dose from with severe hepatic impairment (total
25 mg/m2 to 20 bilirubin >3 x ULN) (see sections 4.3, 4.4
mg/m2. and 5.2).
Grade ≥3 diarrhoea or Delay treatment until
persisting diarrhoea improvement or Patients with renal impairment
Cabazitaxel is minimally excreted through CABAZITAXEL must not be mixed with

the kidney. No dose adjustment is necessary any other medicinal products than those
in patients with renal impairment, not mentioned in section 6.6.
requiring hemodialysis. Patients presenting
end stage renal disease (creatinine clearance 4.3 Contraindications
(CLCR< 15 mL/min/1.73 m2), by their • Hypersensitivity to cabazitaxel, to other
condition and the limited amount of data taxanes, or polysorbate 80 or any excipients
available should be treated with caution and listed in section 6.1.
monitored carefully during treatment (see • Neutrophil counts less than 1,500/mm3.
sections 4.4 and 5.2).
• Severe hepatic impairment (total bilirubin
Elderly >3 x ULN).
No specific dose adjustment for the use of • Concomitant vaccination with yellow fever
cabazitaxel in elderly patients is vaccine (see section 4.5).
recommended (see also sections 4.4, 4.8 and
5.2). 4.4 Special warnings and precautions for
use
Concomitant medicinal products use Hypersensitivity reactions
Concomitant medicinal products that are All patients should be pre-medicated prior to
strong inducers or strong inhibitors of the initiation of the infusion of cabazitaxel
CYP3A should be avoided. However, if (see section 4.2).
patients require co-administration of a
strong CYP3A inhibitor, a 25% cabazitaxel Patients should be observed closely for
dose reduction should be considered (see hypersensitivity reactions especially during
sections 4.4 and 4.5). the first and second infusions.
Hypersensitivity reactions may occur within
Paediatric population a few minutes following the initiation of the
There is no relevant use of CABAZITAXEL infusion of cabazitaxel, thus facilities and
in the paediatric population. equipment for the treatment of hypotension
and bronchospasm should be available.
The safety and the efficacy of Severe reactions can occur and may include
CABAZITAXEL in children and generalised rash/erythema, hypotension and
adolescents below 18 years of age have not bronchospasm. Severe hypersensitivity
been established (see section 5.1). reactions require immediate discontinuation
of cabazitaxel and appropriate therapy.
Method of administration Patients with a hypersensitivity reaction
For instructions on preparation and must stop treatment with CABAZITAXEL
administration of the product, see section (see section 4.3).
6.6. Bone marrow suppression
PVC infusion containers and polyurethane Bone marrow suppression manifested as
infusion sets should not be used. neutropenia, anaemia, thrombocytopenia, or
pancytopenia may occur (see “Risk of
neutropenia” and “Anaemia” in section 4.4 evaluated and treated promptly. Cabazitaxel
below). treatment delay or discontinuation may be
necessary.
Risk of neutropenia
Risk of nausea, vomiting, diarrhoea and
Patients treated with cabazitaxel may dehydration
receive prophylactic G-CSF, as per
American Society of Clinical Oncology If patients experience diarrhoea following
(ASCO) guidelines and/or current administration of cabazitaxel they may be
institutional guidelines, to reduce the risk or treated with commonly used anti-diarrhoeal
manage neutropenia complications (febrile medicinal products. Appropriate measures
neutropenia, prolonged neutropenia or should be taken to re-hydrate patients.
neutropenic infection). Primary prophylaxis Diarrhoea can occur more frequently in
with G-CSF should be considered in patients patients that have received prior abdomino-
with high-risk clinical features (age >65 pelvic radiation. Dehydration is more
years, poor performance status, previous common in patients aged 65 or older.
episodes of febrile neutropenia, extensive Appropriate measures should be taken to
prior radiation ports, poor nutritional status, rehydrate patients and to monitor and correct
or other serious comorbidities) that serum electrolyte levels, particularly
predispose them to increased complications potassium. Treatment delay or dose
from prolonged neutropenia. The use of G- reduction may be necessary for grade ≥3
CSF has been shown to limit the incidence diarrhoea (see section 4.2). If patients
and severity of neutropenia. experience nausea or vomiting, they may be
treated with commonly used anti-emetics.
Neutropenia is the most common adverse
reaction of cabazitaxel (see section 4.8). Risk of serious gastrointestinal reactions
Monitoring of complete blood counts is
essential on a weekly basis during cycle 1 Gastrointestinal (GI) hemorrhage and
and before each treatment cycle thereafter so perforation, ileus, colitis, including fatal
that the dose can be adjusted, if needed. outcome, have been reported in patients
treated with cabazitaxel (see section 4.8).
The dose should be reduced in case of Caution is advised with treatment of patients
febrile neutropenia, or prolonged most at risk of developing gastrointestinal
neutropenia despite appropriate treatment complications: those with neutropenia, the
(see section 4.2). elderly, concomitant use of NSAIDs, anti-
platelet therapy or anti-coagulants, and
Patients should be re-treated only when patients with a prior history of pelvic
neutrophils recover to a level radiotherapy or gastrointestinal disease, such
≥1,500/mm3 (see section 4.3). as ulceration and GI bleeding.
Gastrointestinal disorders Peripheral neuropathy
Symptoms such as abdominal pain and Cases of peripheral neuropathy, peripheral
tenderness, fever, persistent constipation, sensory neuropathy (e.g., paraesthesias,
diarrhoea, with or without neutropenia, may dysaesthesias) and peripheral motor
be early manifestations of serious neuropathy have been observed in patients
gastrointestinal toxicity and should be
receiving cabazitaxel. Patients under of renal function to renal failure ≥CTCAE

treatment with cabazitaxel should be advised 4.0 Grade 3.
to inform their doctor prior to continuing
treatment if symptoms of neuropathy such as Respiratory disorders
pain, burning, tingling, numbness, or Interstitial pneumonia/pneumonitis and
weakness develop. Physicians should assess interstitial lung disease have been reported
for the presence or worsening of neuropathy and may be associated with fatal outcome
before each treatment. Treatment should be (see section 4.8).
delayed until improvement of symptoms.
The dose of cabazitaxel should be reduced If new or worsening pulmonary symptoms
from 25 mg/m2 to 20 mg/m2 for persistent develop, patients should be closely
grade >2 peripheral neuropathy (see section monitored, promptly investigated, and
4.2). appropriately treated. Interruption of
cabazitaxel therapy is recommended until
Anaemia diagnosis is available. Early use of
Anaemia has been observed in patients supportive care measures may help improve
receiving cabazitaxel (see section 4.8). the condition. The benefit of resuming
Haemoglobin and haematocrit should be cabazitaxel treatment must be carefully
checked before treatment with cabazitaxel evaluated.
and if patients exhibit signs or symptoms of Risk of cardiac arrhythmias
anaemia or blood loss. Caution is
recommended in patients with haemoglobin Cardiac arrhythmias have been reported,
<10 g/dl and appropriate measures should be most commonly tachycardia and atrial
taken as clinically indicated. fibrillation (see section 4.8).
Risk of renal failure Elderly
Renal disorders, have been reported in Elderly people (≥65 years of age) may be
association with sepsis, severe dehydration more likely to experience certain adverse
due to diarrhoea, vomiting and obstructive reactions including neutropenia and febrile
uropathy. Renal failure including cases with neutropenia (see section 4.8).
fatal outcome has been observed. Patients with liver impairment
Appropriate measures should be taken to
identify the cause and intensively treat the Treatment with CABAZITAXEL is
patients if this occurs. contraindicated in patients with severe
hepatic impairment (total bilirubin > 3 x
Adequate hydration should be ensured ULN) (See sections 4.3 and 5.2).
throughout treatment with cabazitaxel. The
patient should be advised to report any Dose should be reduced for patients with
significant change in daily urinary volume mild (total bilirubin >1 to ≤1.5 x ULN or
immediately. Serum creatinine should be AST >1.5 x ULN), hepatic impairment (see
measured at baseline, with each blood count sections 4.2 and 5.2).
and whenever the patient reports a change in
Interactions
urinary output. Cabazitaxel treatment should
be discontinued in case of any degradation
Co-administration with strong CYP3A concentrations of cabazitaxel may occur (see

inhibitors should be avoided since they may sections 4.2 and 4.4).
increase the plasma concentrations of
cabazitaxel (see sections 4.2 and 4.5). If co- Concomitant administration of aprepitant, a
administration with a strong CYP3A moderate CYP3A inhibitor, had no effect on
inhibitor cannot be avoided, close cabazitaxel clearance.
monitoring for toxicity and a cabazitaxel CYP3A inducers
dose reduction should be considered (see
sections 4.2 and 4.5). Repeated administration of rifampin (600
mg once daily), a strong CYP3A inducer,
Co-administration with strong CYP3A resulted in an increase in cabazitaxel
inducers should be avoided since they may clearance of 21% corresponding to a
decrease plasma concentrations of decrease in AUC of 17%.
cabazitaxel (see sections 4.2 and 4.5).
Therefore concomitant administration of
Excipients strong CYP3A inducers (e.g., phenytoin,
The solvent contains 573.3 mg ethanol 96% carbamazepine, rifampin, rifabutin,
(15% v/v), equivalent to 14 ml of beer or 6 rifapentin, phenobarbital) should be avoided
ml of wine. as a decrease of plasma concentrations of
cabazitaxel may occur (see sections 4.2 and
Harmful for those suffering from 4.4). In addition, patients should also refrain
alcoholism. from taking St. John's Wort.
To be taken into account in high-risk groups OATP1B1
such as patients with liver disease, or
epilepsy. In vitro, cabazitaxel has also been shown to
inhibit the transport proteins of the Organic
4.5 Interaction with other medicinal Anion Transport Polypeptides OATP1B1.
products and other forms of interaction The risk of interaction with OATP1B1
In vitro studies have shown that cabazitaxel substrates (e.g. statins, valsartan,
is mainly metabolised through CYP3A (80% repaglinide) is possible, notably during the
to 90%) (see section 5.2). infusion duration (1 hour) and up to 20
minutes after the end of the infusion. A time
CYP3A inhibitors interval of 12 hours is recommended before
Repeated administration of ketoconazole the infusion and at least 3 hours after the end
(400 mg once daily), a strong CYP3A of infusion before administering the
inhibitor, resulted in a 20% decrease in OATP1B1 substrates.
cabazitaxel clearance corresponding to a Vaccinations
25% increase in AUC. Therefore
concomitant administration of strong Administration of live or live-attenuated
CYP3A inhibitors (e.g., ketoconazole, vaccines in patients immunocompromised
itraconazole, clarithromycin, indinavir, by chemotherapeutic agents may result in
nefazodone, nelfinavir, ritonavir, saquinavir, serious or fatal infections. Vaccination with
telithromycin, voriconazole) should be a live attenuated vaccine should be avoided
avoided as an increase of plasma in patients receiving cabazitaxel. Killed or
inactivated vaccines may be administered; cabazitaxel. Due to potential exposure via

however, the response to such vaccines may seminal liquid, men treated with cabazitaxel
be diminished. should prevent contact with the ejaculate by
another person throughout treatment. Men
4.6 Fertility, pregnancy and lactation being treated with cabazitaxel are advised to
Pregnancy seek advice on conservation of sperm prior
There are no data from the use of to treatment.
cabazitaxel in pregnant women. Studies in 4.7 Effects on ability to drive and use
animals have shown reproductive toxicity at machines
maternotoxic doses (see section 5.3) and that Cabazitaxel may influence the ability to
cabazitaxel crosses the placenta barrier (see drive and use machines as it may cause
section 5.3). As with other cytotoxic fatigue and dizziness. Patients should be
medicinal products, cabazitaxel may cause advised not to drive or use machines if they
foetal harm in exposed pregnant women. experience these adverse reactions during
Cabazitaxel is not recommended during treatment.
pregnancy and in women of childbearing 4.8 Undesirable effects
potential not using contraception. Summary of safety profile
Breast-feeding The safety of CABAZITAXEL in
Available pharmacokinetics data in animals combination with prednisone or
have shown excretion of cabazitaxel and its prednisolone was evaluated in 371 patients
metabolites in milk (see section 5.3). A risk with metastatic castration resistant prostate
to the suckling child cannot be excluded. cancer who were treated with 25
mg/m2 cabazitaxel once every three weeks
Cabazitaxel should not be used during in a randomised open label, controlled phase
breast-feeding. III study. Patients received a median
Fertility duration of 6 cycles of cabazitaxel.
Animal studies showed that cabazitaxel The most commonly (≥10%) occurring
affected reproductive system in male rats adverse reactions in all grades were anaemia
and dogs without any functional effect on (97.3%), leukopenia (95.7%), neutropenia
fertility (see section 5.3). Nevertheless, (93.5%), thrombocytopenia (47.4%), and
considering the pharmacological activity of diarrhoea (46.6%). The most commonly
taxanes, their genotoxic potential and effect (≥5%) occurring grade ≥3 adverse reactions
of several compounds of this class on in the cabazitaxel group were neutropenia
fertility in animal studies, effect on male (81.7%), leukopenia (68.2%), anaemia
fertility could not be excluded in human. (10.5%), febrile neutropenia (7.5%),
diarrhoea (6.2%).
Due to potential effects on male gametes
and to potential exposure via seminal liquid, Discontinuation of treatment due to adverse
men treated with cabazitaxel should use reactions occurred in 68 patients (18.3%)
effective contraception throughout treatment receiving cabazitaxel. The most common
and are recommended to continue this for up adverse reactions leading to cabazitaxel
to 6 months after the last dose of discontinuation was neutropenia.
Tabulated list of adverse reactions tract

Adverse reactions are listed in table 2 infection
according to MedDRA system organ class Herpes 5 0
and frequency categories. Within each zoster (1.3)
frequency grouping, adverse reactions are Candidiasis 4 0
presented in order of decreasing seriousness. (1.1)
Intensity of the adverse reactions is graded
Neutropenia 347 303
according to CTCAE 4.0 (grade ≥3 = G≥3). a*
(93.5 (81.7)
Frequencies are based on all grades and
)
defined as: very common (≥1/10), common
(≥1/100 to <1/10); uncommon (≥1/1,000 to Anaemia a 361 39
<1/100); rare (≥1/10,000 to <1/1,000); very (97.3 (10.5)
rare (<1/10,000); not known (cannot be Blood and )
estimated from the available data). a
lymphatic Leukopenia 355 253
system (95.7 (68.2)
Table 2: Reported adverse reactions and
disorders )
haematological abnormalities with
cabazitaxel in combination with prednisone Thrombocyt 176 15 (4)
or prednisolone in the TROPIC study openiaa (47.4
(n=371) )
Febrile 28 28
System Adverse All grades Grad neutropenia (7.5) (7.5)
Organ reaction n (%) e>3
Class n Immune Hypersensiti 5 0
(%) system vity (1.3)
disorders
Very Com
com mon Anorexia 59 3
mon (15.9 (0.8)
)
Septic shock 4 4 Metabolis Dehydration
(1.1) (1.1) 18 8
m and (4.9) (2.2)
Sepsis 4 4 nutrition
(1.1) (1.1) disorders Hyperglycae 4 3
mia (1.1) (0.8)
Cellulitis 6 2
Infections (1.6) (0.5) Hypokalemi 4 2
and a (1.1) (0.5)
Urinary tract 27 4
infestation Psychiatri Anxiety 11 (3) 0
infection (7.3) (1.1)
s c
Influenza 11 (3) 0 Confusional 5 0
disorders state (1.3)
Cystitis 10 1
(2.7) (0.3) Dysgeusia 41 0
Nervous (11.1
Upper 10 0 system )
respiratory (2.7) disorders
Neuropathy 30 2
peripheral (8.1) (0.5) 4 0 Flushing

Peripheral 20 1 (1.1)
sensory (5.4) (0.3) Dyspnoea 44 5
neuropathy (11.9 (1.3)
Dizziness 30 0 )
Respirator
(8.1) y, thoracic Cough 40 0
Headache 28 0 and (10.8
(7.5) mediastin )
al Oropharyng 13 0
Paraesthesia 17 0
disorders eal pain (3.5)
(4.6)
Lethargy 5 1 Pneumonia 9 6
(1.3) (0.3) (2.4) (1.6)
Hypoaesthes 5 0 173 Diarrhoea 23
ia (1.3) (46.6 (6.2)
)
Sciatica 4 1
(1.1) (0.3) Nausea 127 7
(34.2 (1.9)
Conjunctivit 5 0 )
Eye is (1.3)
Vomiting 84 7
disorders Lacrimation 5 0 (22.6 (1.9)
increased (1.3) )
Tinnitus 5 0 Constipation 76 4
Ear and (1.3)
labyrinth (20.5 (1.1)
disorders Vertigo 5 0 )
(1.3)
Gastrointe Abdominal 43 7
Atrial 4 2 stinal pain (11.6 (1.9)
Cardiac fibrillation (1.1) (0.5) disorders )
disorders* Tachycardia 6 0 Dyspepsia 25 0
(1.6) (6.7)
Hypotension 20 2 Abdominal 20 0
(5.4) (0.5) pain upper (5.4)
Deep vein 8 7 Haemorrhoi 14 0
thrombosis (2.2) (1.9) ds (3.8)
Vascular Hypertensio 6 1 Gastroesoph 12 0
disorders n (1.6) (0.3) ageal reflux (3.2)
Orthostatic 5 1 disease
hypotension (1.3) (0.3) Rectal 8 2
Hot flush 5 0 haemorrhag (2.2) (0.5)
(1.3) e
Dry mouth 8 1 Pollakiuria 13 1

(2.2) (0.3) (3.5) (0.3)
Abdominal 5 1 Hydronephr 9 3
distension (1.3) (0.3) osis (2.4) (0.8)
Alopecia 37 0 Urinary 9 3
Skin and (10) retention (2.4) (0.8)
subcutane Dry skin 9 0 Urinary 9 0
ous tissue (2.4) incontinence (2.4)
disorders Erythema 5 0 Ureteric 7 5
(1.3) obstruction (1.9) (1.3)
Back pain 60 14 Reproduct Pelvic pain 7 1
(16.2 (3.8) ive system (1.9) (0.3)
) and breast
Arthralgia 39 4 disorders
(10.5 (1.1) Fatigue 136 18
) (36.7 (4.9)
Musculos Pain in 30 6 )
keletal extremity (8.1) (1.6) Asthenia 76 17
and (20.5 (4.6)
Muscle 27 0
connectiv )
spasms (7.3)
e tissue
Myalgia 14 1 Pyrexia 45 4
disorders
(3.8) (0.3) (12.1 (1.1)
)
Musculoskel 11 (3) 1
etal chest (0.3) Peripheral 34 2
General
pain oedema (9.2) (0.5)
disorders
Flank pain 7 3 and Mucosal 22 1
(1.9) (0.8) administra inflammatio (5.9) (0.3)
tion site n
Acute renal 8 6
conditions Pain 20 4
failure (2.2) (1.6)
(5.4) (1.1)
Renal 7 6
failure (1.9) (1.6) Chest pain 9 2
(2.4) (0.5)
Renal and Dysuria 25 0
urinary (6.7) Oedema 7 1
disorders Renal colic (1.9) (0.3)
5 1
(1.3) (0.3) Chills 6 0
(1.6)
Haematuria 62 7
(16.7 (1.9) Malaise 5 0
) (1.3)
Investigati Weight 32 0
ons decreased (8.6) cardiac failure. Fatal ventricular fibrillation

was reported in 1 patient (0.3%), and cardiac
Aspartate 4 0
arrest in 2 patients (0.5%). None were
aminotransf (1.1)
considered related by the investigator.
erase
increased Haematuria
Transaminas 4 0 Haematuria all grades frequency was 20.8%
es increased (1.1) at 25 mg/m2 in EFC11785 study (see section
a
based on laboratory values 5.1). Confounding causes such as disease
* see detailed section below progression, instrumentation, infection or
anticoagulation/NSAID/aspirin therapy were
Description of selected adverse reactions identified in nearly two thirds of the cases.
Neutropenia, and associated clinical events Other laboratory abnormalities
Incidence of grade ≥3 neutropenia based on The incidence of grade ≥3 anaemia,
laboratory data was 81.7%. The incidence of increased AST, ALT, and bilirubin based on
grade ≥3 clinical neutropenia and febrile laboratory abnormalities were 10.5%, 0.7%,
neutropenia adverse reactions were 21.3% 0.9%, and 0.6%, respectively.
and 7.5% respectively. Neutropenia was the
most common adverse reaction leading to Gastrointestinal disorders
medicinal product discontinuation (2.4%). Colitis, enterocolitis, gastritis, neutropenic
Neutropenic complications included enterocolitis have been observed.
neutropenic infections (0.5%), neutropenic Gastrointestinal hemorrhage and perforation,
sepsis (0.8%), and septic shock (1.1%), ileus and intestinal obstruction have also
which in some cases resulted in a fatal been reported (see section 4.4).
outcome. Respiratory disorders
The use of G-CSF has been shown to limit Cases of interstitial pneumonia/pneumonitis
the incidence and severity of neutropenia and interstitial lung disease, sometimes fatal
(see sections 4.2 and 4.4). have been reported with an unknown
Cardiac disorders and arrhythmias frequency (cannot be estimated from the
available data) (see section 4.4).
All Grade events among cardiac disorders
were more common on cabazitaxel of which Renal and urinary disorders
6 patients (1.6%) had Grade ≥3 cardiac Cystitis due to radiation recall phenomenon,
arrhythmias. The incidence of tachycardia including haemorrhagic cystitis, were
on cabazitaxel was 1.6%, none of which reported uncommonly.
were Grade ≥3. The incidence of atrial
fibrillation was 1.1% in the cabazitaxel Paediatric population
group. Cardiac failure events were more See section 4.2
common on cabazitaxel, the event term
being reported for 2 patients (0.5%). One Other special populations
patient in the cabazitaxel group died from
Elderly population
Among the 371 patients treated with There is no known antidote to cabazitaxel.
cabazitaxel in the prostate cancer study, 240 The anticipated complications of overdose
patients were 65 years or over including 70 would consist of exacerbation of adverse
patients older than 75 years. reactions as bone marrow suppression and
gastrointestinal disorders.
The following adverse reactions reported at
rates ≥5% higher in patients 65 years of age In case of overdose, the patient should be
or greater compared to younger patients kept in a specialised unit and closely
were fatigue (40.4% versus 29.8%), clinical monitored. Patients should receive
neutropenia (24.2% versus 17.6%), asthenia therapeutic G-CSF as soon as possible after
(23.8% versus 14.5%), pyrexia (14.6% discovery of overdose. Other appropriate
versus 7.6%), dizziness (10.0% versus symptomatic measures should be taken.
4.6%), urinary tract infection (9.6% versus
3.1%) and dehydration (6.7% versus 1.5%), 5. PHARMACOLOGICAL
respectively. PROPERTIES
The incidence of the following grade ≥3 5.1 Pharmacodynamic properties

adverse reactions were higher in patients Pharmacotherapeutic group: Antineoplastic
≥65 years of age compared to younger agents, taxanes.
patients; neutropenia based on laboratory Mechanism of action
abnormalities (86.3% versus 73.3%),
clinical neutropenia (23.8% versus 16.8%) Cabazitaxel is an antineoplastic agent that
and febrile neutropenia (8.3% versus 6.1%) acts by disrupting the microtubular network
(see sections 4.2 and 4.4). in cells. Cabazitaxel binds to tubulin and
promotes the assembly of tubulin into
Of the 595 patients treated with cabazitaxel microtubules while simultaneously
25 mg/m2 in the prostate cancer EFC 11785 inhibiting their disassembly. This leads to
study, 420 patients were 65 years or over. the stabilisation of microtubules, which
The adverse reactions reported at rates of at results in the inhibition of mitotic and
least 5% higher in patients 65 years of age interphase cellular functions.
or greater compared to younger patients
were diarrhoea (42.9% vs. 32.6%), fatigue Pharmacodynamic effects
(30.2% vs. 19.4%), asthenia (22.4% vs. Cabazitaxel demonstrated a broad spectrum
13.1%), constipation (20.2% vs. 12.6%), of antitumour activity against advanced
clinical neutropenia (12.9% vs. 6.3%), human tumours xenografted in mice.
febrile neutropenia (11.2% vs. 4.6%) and Cabazitaxel is active in docetaxel-sensitive
dyspnoea (9.5% vs. 3.4%). tumours. In addition, cabazitaxel
Reporting of suspected adverse reactions demonstrated activity in tumour models
insensitive to chemotherapy including
Reporting suspected adverse reactions after docetaxel.
authorisation of the medicinal product is
important. Clinical efficacy and safety
4.9 Overdose The efficacy and safety of CABAZITAXEL

in combination with prednisone or
prednisolone were evaluated in a
randomised, open-label, international, multi- lesions, and Eastern Cooperative Oncology

center, phase III study (EFC6193 study), in Group (ECOG) performance status 0 to 2.
patients with metastatic castration resistant Patients had to have neutrophils
prostate cancer previsouly treated with a >1,500/mm3, platelets >100,000/mm3,
docetaxel containing regimen. haemoglobin >10 g/dl, creatinine <1.5 x
ULN, total bilirubin <1 x ULN, AST and
Overall survival (OS) was the primary ALT <1.5 x ULN.
efficacy endpoint of the study.
Patients with a history of congestive heart
Secondary endpoints included Progression failure, or myocardial infarction within last
Free Survival [PFS (defined as time from 6 months, or patients with uncontrolled
randomization to tumour progression, cardiac arrhythmias, angina pectoris, and/or
Prostatic Specific Antigen (PSA) hypertension were not included in the study.
progression, pain progression, or death due
to any cause, whichever occurred first], Demographics, including age, race, and
Tumour Response Rate based on Response ECOG performance status (0 to 2), were
Evaluation Criteria in Solid Tumours balanced between the treatment arms. In the
(RECIST), PSA Progression (defined as a CABAZITAXEL group, the mean age was
≥25% increase or >50% in PSA non- 68 years, range (46-92) and the racial
responders or responders respectively), PSA distribution was 83.9% Caucasian, 6.9%
response (declines in serum PSA levels of at Asian/Oriental, 5.3% Black and 4% Others.
least 50%), pain progression [assessed using
the Present Pain Intensity (PPI) scale from The median number of cycles was 6 in the
the McGill-Melzack questionnaire and an CABAZITAXEL group and 4 in the
Analgesic Score (AS)] and pain response mitoxantrone group. The number of patients
(defined as 2-point greater reduction from who completed the study treatment (10
baseline median PPI with no concomitant cycles) was respectively 29.4% and 13.5%
increase in AS, or reduction of ≥50% in in the CABAZITAXEL group and in the
analgesic use from baseline mean AS with comparator group.
no concomitant increase in pain). Overall survival was significant longer with
A total of 755 patients were randomised to CABAZITAXEL compared to mitoxantrone
receive either CABAZITAXEL 25 (15.1 months versus 12.7 respectively), with
mg/m2 intravenously every 3 weeks for a a 30% reduction in the risk of death
maximum of 10 cycles with prednisone or compared to mitoxantrone (see table 3 and
prednisolone 10 mg orally daily (n=378), or figure 1).
to receive mitoxantrone 12 A sub-group of 59 patients received prior
mg/m2 intravenously every 3 weeks for a cumulative dose of docetaxel <225 mg/m²
maximum of 10 cycles with prednisone or (29 patients in CABAZITAXEL arm, 30
prednisolone 10 mg orally daily (n=377). patients in mitoxantrone arm). There was no
This study included patients over 18 years of significant difference in overall survival in
age with metastatic castration resistant this group of patients (HR (95%CI) 0.96
prostate cancer either measurable by (0.49-1.86)).
RECIST criteria or non-measurable disease
with rising PSA levels or appearance of new
Table 3 - Efficacy of CABAZITAXEL in There was an improvement in PFS in the

EFC6193 study in the treatment of patients CABAZITAXEL arm compared to
with metastatic castration resistant prostate mitoxantrone arm, 2.8 (2.4-3.0) months
cancer versus 1.4 (1.4-1.7) respectively, HR
(95%CI) 0.74 (0.64-0.86), p<0.0001.
CABAZITAXE mitoxantron
L + prednisone e+ There was a significant higher rate of
n=378 prednisone tumour response of 14.4% (95%CI: 9.6-
n=377 19.3) in patients in the CABAZITAXEL
arm compared to 4.4% (95%CI: 1.6-7.2) for
Overall
patients in the mitoxantrone arm, p=0.0005.
survival
Number of 234 (61.9%) 279 (74%) PSA secondary endpoints were positive in
patients the CABAZITAXEL arm. There was a
with deaths median PSA progression of 6.4 months
(%) (95%CI: 5.1-7.3) for patients in
CABAZITAXEL arm, compared to 3.1
Median 15.1 (14.1-16.3) 12.7 (11.6-
months (95%CI: 2.2-4.4) in the
survival 13.7)
mitoxantrone arm, HR 0.75 months (95%CI:
(months)
0.63-0.90), p=0.0010. The PSA response
(95% CI)
was 39.2% in patients on CABAZITAXEL
Hazard 0.70 (0.59-0.83) arm (95%CI: 33.9-44.5) versus 17.8% of
Ratio patients on mitoxantrone (95%CI: 13.7-
(HR)1 (95 22.0), p=0.0002.
% CI)
There was no statistical difference between
p-value <0.0001
1
both treatment arms in pain progression and
HR estimated using Cox model; a hazard pain response.
ratio of less than 1 favours CABAZITAXEL
In a non-inferiority, multicenter,
Figure 1: Kaplan Meier overall survival multinational, randomized, open label phase
curves (EFC6193) 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 a Hazard ratio is estimated using a Cox

significantly higher risk of PSA progression Proportional Hazards regression model. A
in patients with the 20 mg/m2 dose with hazard ratio < 1 indicates a lower risk of
respect to the 25 mg/m2 dose was observed cabazitaxel 20 mg/m2 with respect to 25
(HR 1.195 ; 95%CI: 1.025 to 1.393). There mg/m2.
was no statistically difference with regards
to the other secondary endpoints (PFS, The safety profile of cabazitaxel 25
tumour and pain response, tumour and pain mg/m2 observed in study EFC11785 was
progression, and four subcategories of qualitatively and quantitatively similar to
FACT-P). that observed in the study EFC6193. Study
EFC11785 demonstrated a better safety
Table 4 - Overall survival in EFC11785 profile for the cabazitaxel 20 mg/m2 dose.
study in cabazitaxel 25 mg/m2 arm versus
cabazitaxel 20 mg/m2 arm (Intent-to–treat Table 5 - Summary of safety data for
analysis) – Efficacy primary endpoint cabazitaxel 25 mg/m2 arm versus
cabazitaxel 20 mg/m2 arm in EFC11785
CBZ20+PRE CBZ25+PRE study
D D
CBZ20+PRE CBZ25+PRE
n=598 n=602
D D
Overall n=580 n=595
Survival
Median number 6/ 18 weeks 7/ 21 weeks
Number of 497 (83.1 %) 501 (83.2%) of cycles/
deaths, n (%) median duration
Median 13.4 (12.19 to 14.5 (13.47 to of treatment
survival 14.88) 15.28) Number of From 20 to From 25 to
(95% CI) patients with 15 mg/m2: 58 20 mg/m2:
(months) dose reduction (10.0%) 128 (21.5%)
Hazard Ratioa n (%) From 15 to From 20 to
versus 12 mg/m2: 9 15 mg/m2: 19
CBZ25+PRE (1.6%) (3.2%)
D 1.024 - From 15 to
12 mg/m2: 1
1-sided - (0.2%)
98.89% UCI 1.184
All grade adverse
1-sided 95% - reactions a (%)
LCI 0.922
Diarrhoea 30.7 39.8
CBZ20=Cabazitaxel 20 mg/m2,
CBZ25=Cabazitaxel 25 mg/m2, Nausea 24.5 32.1
PRED=Prednisone/Prednisolone Fatigue 24.7 27.1
CI=confidence interval, LCI=lower bound Haematuria 14.1 20.8
of the confidence interval, UCI=upper Asthenia 15.3 19.7
bound of the confidence interval Decreased 13.1 18.5
appetite The European Medicines Agency has

waived the obligation to submit the results
Vomiting 14.5 18.2
of studies with CABAZITAXEL in all
Constipation 17.6 18.0 subsets of the paediatric population in the
Back pain 11.0 13.9 indication of prostate cancer (see section 4.2
Clinical 3.1 10.9 for information on paediatric use).
neutropenia CABAZITAXEL was evaluated in an open
Urinary tract 6.9 10.8 label, multi-center Phase 1/2 study
infection conducted in a total of 39 paediatric patients
Peripheral 6.6 10.6 (aged between 4 to18 years for the phase 1
sensory part of the study and between 3 to 16 years
neuropathy for the phase 2 part of the study). The phase
2 part did not demonstrate efficacy of
Dysgeusia 7.1 10.6 cabazitaxel as single agent in paediatric
Grade ≥ 3 adverse population with recurrent or refractory
reactions b (%) diffuse intrinsic pontine glioma (DIPG) and
Clinical 2.4 9.6 high grade glioma (HGG) treated at 30
neutropenia mg/m².
Febrile 2.1 9.2 5.2 Pharmacokinetic properties
neutropenia A population pharmacokinetic analysis was
Haematological carried out in 170 patients including patients
abnormalities c (%) with advanced solid tumours (n=69),
metastatic breast cancer (n=34) and
Grade ≥ 3 73.3 metastatic prostate cancer (n=67). These
neutropenia 41.8 patients received cabazitaxel at doses of 10
Grade ≥ 3 13.7 to 30 mg/m2 weekly or every 3 weeks.
anaemia 9.9
Absorption
Grade ≥ 3 4.2
thrombocytope After 1-hour intravenous administration at
nia 2.6 25 mg/m2 cabazitaxel in patients with
CBZ20=Cabazitaxel 20 mg/m2, metastatic prostate cancer (n=67), the
CBZ25=Cabazitaxel 25 mg/m2, Cmax was 226 ng/ml (Coefficient of
PRED=Prednisone/Prednisolone Variation (CV): 107%) and was reached at
the end of the 1-hour infusion (Tmax). The
a All grade adverse reactions with an mean AUC was 991 ng.h/ml (CV: 34%).
incidence higher than 10%
No major deviation to the dose
b Grade ≥ 3 adverse reactions with an proportionality was observed from 10 to 30
incidence higher than 5% mg/m² in patients with advanced solid
c Based on laboratory values tumours (n=126).
Paediatric population Distribution

The volume of distribution (Vss) was 4870 l There is no potential risk of inhibition of
(2640 l/m² for a patient with a median BSA medicinal products that are substrates of
of 1.84 m²) at steady state. other CYP enzymes (1A2, 2B6, 2C9, 2C8,
2C19, 2E1, and 2D6) as well as no potential
In vitro, the binding of cabazitaxel to human risk of induction by cabazitaxel on
serum proteins was 89-92% and was not medicinal products that are substrates of
saturable up to 50,000 ng/ml, which covers CYP1A, CYP2C9, and CYP3A. Cabazitaxel
the maximum concentration observed in did not inhibit in vitro the major
clinical studies. Cabazitaxel is mainly bound biotransformation pathway of warfarin into
to human serum albumin (82.0%) and 7-hydroxywarfarin, which is mediated by
lipoproteins (87.9% for HDL, 69.8% for CYP2C9. Therefore, no pharmacokinetic
LDL, and 55.8% for VLDL). The in interaction of cabazitaxel on warfarin is
vitro blood-to-plasma concentration ratios in expected in vivo.
human blood ranged from 0.90 to 0.99
indicating that cabazitaxel was equally In vitro cabazitaxel did not inhibit
distributed between blood and plasma. Multidrug-Resistant Proteins (MRP): MRP1
and MRP2 or Organic Cation Transporter
Biotransformation (OCT1). Cabazitaxel inhibited the transport
Cabazitaxel is extensively metabolised in of P-glycoprotein (PgP) (digoxin,
the liver (>95%), mainly by the CYP3A vinblastin), Breast-Cancer-Resistant-
isoenzyme (80% to 90%). Cabazitaxel is the Proteins (BCRP) (methotrexate) and
main circulating compound in human Organic Anion Transporting Polypeptide
plasma. Seven metabolites were detected in OATP1B3 (CCK8) at concentrations at least
plasma (including 3 active metabolites 15 fold what is observed in clinical setting
issued form O-demethylations), with the while it inhibited the transport of OATP1B1
main one accounting for 5% of parent (estradiol-17β-glucuronide) at
exposure. Around 20 metabolites of concentrations only 5 fold what is observed
cabazitaxel are excreted into human urine in clinical setting. Therefore the risk of
and faeces. interaction with substrates of MRP, OCT1,
PgP, BCRP and OATP1B3 is unlikely in
Based on in vitro studies, the potential risk vivo at the dose of 25 mg/m2. The risk of
of inhibition by cabazitaxel at clinically interaction with OATP1B1 transporter is
relevant concentrations is possible towards possible, notably during the infusion
medicinal products that are mainly substrate duration (1 hour) and up to 20 minutes after
of CYP3A. the end of the infusion (see section 4.5).
However a clinical study has shown that Elimination
cabazitaxel (25 mg/m2 administered as a
single 1-hour infusion) did not modify the After a 1-hour intravenous infusion [14C]-
plasma levels of midazolam, a probe cabazitaxel at 25 mg/m2 in patients,
substrate of CYP3A. Therefore, at approximately 80% of the administered dose
therapeutic doses, co-administration of was eliminated within 2 weeks. Cabazitaxel
CYP3A substrates with cabazitaxel to is mainly excreted in the faeces as numerous
patients is not expected to have any clinical metabolites (76% of the dose); while renal
impact. excretion of cabazitaxel and metabolites
account for less than 4% of the dose (2.3% in patients with severe hepatic impairment
as unchanged medicinal product in urine). was not established.
Cabazitaxel had a high plasma clearance of Based on safety and tolerability data,
48.5 l/h (26.4 l/h/m² for a patient with a cabazitaxel dose should be reduced in
median BSA of 1.84 m²) and a long terminal patients with mild hepatic impairment (see
half-life of 95 hours. sections 4.2, 4.4). CABAZITAXEL is
contraindicated in patients with severe
Special populations hepatic impairment (see section 4.3).
Elderly patients Renal impairment
In the population pharmacokinetic analysis Cabazitaxel is minimally excreted via the
in 70 patients of 65 years and older (57 from kidney (2.3% of the dose). A population
65 to 75 and 13 patients above 75), no age pharmacokinetic analysis carried out in 170
effect on the pharmacokinetics of patients that included 14 patients with
cabazitaxel was observed. moderate renal impairment (creatinine
Paediatric patients clearance in the range of 30 to 50 ml/min)
and 59 patients with mild renal impairment
Safety and effectiveness of (creatinine clearance in the range of 50 to 80
CABAZITAXEL have not been established ml/min) showed that mild to moderate renal
in children and adolescents below 18 years impairment did not have meaningful effects
of age. on the pharmacokinetics of cabazitaxel. This
Hepatic impairment was confirmed by a dedicated comparative
pharmacokinetic study in solid cancer
Cabazitaxel is eliminated primarily via liver patients with normal renal function (8
metabolism. patients), moderate (8 patients) and severe
(9 patients) renal impairment, who received
A dedicated study in 43 cancer patients with
several cycles of cabazitaxel in single IV
hepatic impairment showed no influence of
infusion up to 25 mg/m2.
mild (total bilirubin >1 to ≤1.5 x ULN or
AST >1.5 x ULN) or moderate (total 5.3 Preclinical safety data
bilirubin >1.5 to ≤3.0 x ULN) hepatic Adverse reactions not observed in clinical
impairment on cabazitaxel studies, but seen in dogs after single dose, 5-
pharmacokinetics. The maximum tolerated day and weekly administation at exposure
dose (MTD) of cabazitaxel was 20 and 15 levels lower than clinical exposure levels
mg/m2, respectively. and with possible relevance to clinical use
were arteriolar/periarterolar necrosis in the
In 3 patients with severe hepatic impairment
liver, bile ductule hyperplasia and/or
(total bilirubin >3 ULN), a 39% decrease in
hepatocellular necrosis (see section 4.2).
clearance was observed when compared to
patients with mild hepatic impairment, Adverse reactions not observed in clinical
indicating some effect of severe hepatic studies, but seen in rats during repeat-dose
impairment on cabazitaxel toxicity studies at exposure levels higher
pharmacokinetics. The MTD of cabazitaxel than clinical exposure levels and with
possible relevance to clinical use were eye
disorders characterized by subcapsular lens In rats, cabazitaxel and its metabolites are
fiber swelling/degeneration. These effects excreted in maternal milk at a quantity up to
were partially reversible after 8 weeks. 1.5% of administered dose over 24 hours.
Carcinogenicity studies have not been Environmental Risk Assessment (ERA)
conducted with cabazitaxel.
Results of environmental risk assessment
Cabazitaxel did not induce mutations in the studies indicated that use of
bacterial reverse mutation (Ames) test. It CABAZITAXEL will not cause significant
was not clastogenic in an in vitro test in risk to the aquatic environment (see section
human lymphocytes (no induction of 6.6 for disposal of unused product).
structural chromosomal aberration but it
increased number of polyploid cells) and 6. PHARMACEUTICAL
induced an increase of micronuclei in the in PARTICULARS
vivo test in rats. However these genotoxicity 6.1 List of excipients
findings are inherent to the pharmacological Concentrate
activity of the compound (inhibition of
tubulin depolymerization) and have been Polysorbate 80, Citric acid
observed with medicinal products exhibiting Solvent
the same pharmacological activity.
Ethanol 96%
Cabazitaxel did not affect mating
performances or fertility of treated male rats. Water for injections
However, in repeated-dose toxicity studies,
degeneration of seminal vesicle and 6.2 Incompatibilities
seminiferous tubule atrophy in the testis This medicinal product must not be mixed
with other medicinal products except those
were observed in rats, and testicular
degeneration (minimal epithelial single cell mentioned in section 6.6.
necrosis in epididymis), was observed in PVC infusion containers or polyurethane
dogs. Exposures in animals were similar or infusion sets should not be used for the
lower than those seen in humans receiving preparation and administration of the
clinically relevant doses of cabazitaxel. infusion solution.
Cabazitaxel induced embryofoetal toxicity 6.3 Shelf life
in female rats treated intravenously once Unopened vials
daily from gestational days 6 through 17
linked with maternal toxicity and consisted 3 years.
of foetal deaths and decreased mean foetal After opening
weight associated with delay in skeletal
ossification. Exposures in animals were The concentrate and solvent vials must be
lower than those seen in humans receiving used immediately. If not used immediately,
clinically relevant doses of cabazitaxel. in-use storage times and conditions are the
Cabazitaxel crossed the placenta barrier in responsibility of the user.
rats.
After initial dilution of the concentrate with
the solvent
Chemical and physical in-use stability has cabazitaxel per 1.5 ml nominal volume (fill
been demonstrated for 1 hour at ambient volume: 73.2 mg of cabazitaxel/1.83 ml).
temperature (15°C-30°C). From a This fill volume has been established during
microbiological point of view, the the development of CABAZITAXEL to
concentrate-solvent mixture should be used compensate for liquid loss during
immediately. If not used immediately, in-use preparation of the premix. This overfill
storage times and conditions are the ensures that after dilution with
responsibility of the user and would the entire content of the accompanying
normally not be longer than 24 hour at 2°C – solvent for CABAZITAXEL, there is a
8°C, unless dilution has taken place in minimal extractable premix volume of 6 ml
controlled and validated aseptic conditions. containing 10 mg/ml CABAZITAXEL
which corresponds to the labelled amount of
After final dilution in the infusion bag/bottle 60 mg per vial.
Chemical and physical stability of the • Solvent: 4.5 ml of solvent in a 15 ml clear
infusion solution has been demonstrated for glass vial (type I) closed with a grey
8 hours at ambient temperature (including chlorobutyl rubber closure sealed by a gold
the 1-hour infusion time) and for 48 hours at colour aluminium cap covered with a
refrigerated conditions (including the 1-hour colourless plastic flip-off cap. Each vial
infusion time). contains 4.5 ml nominal volume (fill
From a microbiological point of view, the volume: 5.67 ml). This fill volume has been
infusion solution should be used established during the development and the
immediately. If not used immediately, in-use overfill ensures, after the addition of
storage times and conditions are the the entire content of the solvent vial to the
responsibility of the user and would content of CABAZITAXEL 60 mg
normally not be longer than 24 hour at 2°C – concentrate vial, a concentration of the
8°C, unless dilution has taken place in premix solution of 10 mg/ml
controlled and validated aseptic conditions. CABAZITAXEL.
6.4 Special precautions for storage 6.6 Special precautions for disposal and
Do not store above 30°C. other handling
CABAZITAXEL should only be prepared
Do not refrigerate. and administered by personnel trained in
For storage conditions after dilution of the handling cytotoxic agents. Pregnant staff
medicinal product, see section 6.3. should not handle the product. As for any
other antineoplastic agent, caution should be
6.5 Nature and contents of container exercised when handling and preparing
One pack contains one vial of concentrate CABAZITAXEL solutions, taking into
and one vial of solvent: account the use of containment devices,
personal protective equipment (e.g. gloves),
• Concentrate: 1.5 ml of concentrate in a 15
and preparation procedures. If
ml clear glass vial (type I) closed with a
CABAZITAXEL, at any step of its
grey chlorobutyl rubber closure sealed by an
handling, should come into contact with the
aluminium cap covered with a light green
skin, wash immediately and thoroughly with
plastic flip-off cap. Each vial contains 60 mg
soap and water. If it should come into
contact with mucous membranes, wash Step 1.3

immediately and thoroughly with water. Inject the entire contents into the corresponding concentrate
To limit foaming as much as possible when injecting the sol
Always dilute the concentrate for solution
direct the needle onto the inside wall of the vial of concentra
for infusion with the entire supplied solvent
solution and inject slowly.
before adding to infusion solution.
Once reconstituted, the resultant solution contains 10 mg/ml
Read this ENTIRE section carefully before cabazitaxel.
mixing and diluting. CABAZITAXEL Step 1.4
requires TWO dilutions prior to Remove the syringe and needle and mix
administration. Follow the preparation manually and gently by repeated inversions
instructions provided below. until obtaining a clear and homogeneous
Note: Both the CABAZITAXEL 60 mg/1.5 solution. It could take approximately 45
ml concentrate vial (fill volume: 73.2 mg of seconds.
cabazitaxel/1.83 ml) and the solvent vial (fill
volume: 5.67 ml) contain an overfill to
compensate for liquid loss during Step 1.5
preparation. This overfill ensures that after Let this solution stand for approximately 5
dilution with the ENTIRE contents of the minutes and check then that the solution is
accompanying solvent, there is solution homogeneous and clear.
containing 10 mg/ml cabazitaxel. It is normal for foam to persist after this time
period.
The following two-step dilution process
must be carried out in an aseptic manner for
preparing the solution for infusion. This resulting concentrate-solvent mixture
contains 10 mg/ml of cabazitaxel (at least 6
Step 1: Initial dilution of the concentrate
ml deliverable volume). The second dilution
for solution for infusion with the supplied
should be done immediately (within 1 hour)
solvent.
as detailed in Step 2.
Step 1.1 More than one vial of the concentrate-
Inspect the concentrate vial and the supplied solvent mixture may be necessary to
solvent. The concentrate solution and the administer the prescribed dose.
solvent should be clear.
Step 2: Second (final) dilution for infusion
Step 1.2 Step 2.1

Using a syringe fitted with a needle, Aseptically withdraw the required amount of
aseptically withdraw the entire contents of concentrate-solvent mixture (10 mg/ml of
the supplied solvent by partially inverting the cabazitaxel), with a graduated syringe fitted with a
vial. needle. As an example, a dose of 45 mg
CABAZITAXEL 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 ATHIYAWAD, DABHEL, DAMAN- 396210
in Step 1, it is preferable to place the needle of the (INDIA)
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.
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
CABAZITAXEL.
CABAZITAXEL 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. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,

Cabazitaxel Injection Taj Pharma-SMPC

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Cabazitaxel Injection Taj Pharma-SMPC

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Cabaz itaxel Injection 60 mg/ 1.

The solvent is a clear and colourless

Throughout the treatment, adequate despite appropriate resolution, then

Cabazitaxel is minimally excreted through CABAZITAXEL must not be mixed with

receiving cabazitaxel. Patients under of renal function to renal failure ≥CTCAE

Risk of renal failure Elderly

Co-administration with strong CYP3A concentrations of cabazitaxel may occur (see

inactivated vaccines may be administered; cabazitaxel. Due to potential exposure via

Tabulated list of adverse reactions tract

peripheral (8.1) (0.5) 4 0 Flushing

Dry mouth 8 1 Pollakiuria 13 1

ons decreased (8.6) cardiac failure. Fatal ventricular fibrillation

The incidence of the following grade ≥3 5.1 Pharmacodynamic properties

4.9 Overdose The efficacy and safety of CABAZITAXEL

randomised, open-label, international, multi- lesions, and Eastern Cooperative Oncology

Table 3 - Efficacy of CABAZITAXEL in There was an improvement in PFS in the

mg/m2 group (29.5%). A statistically a Hazard ratio is estimated using a Cox

appetite The European Medicines Agency has

Paediatric population Distribution

contact with mucous membranes, wash Step 1.3

Step 1.2 Step 2.1

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